Characteristics of patients associated with any outpatient antibiotic prescribing among Medicare Part D enrollees, 2007-2018
Kim CY , Gouin KA , Hicks LA , Kabbani S . Antimicrob Steward Healthc Epidemiol 2023 3 (1) e113 The 2007-2018 National Health Interview Survey data linked with Medicare claims were used to examine older adults' characteristics and assess their associations with receiving an antibiotic prescription. This analysis shows variation in antibiotic prescribing among adults enrolled in Medicare Part D by race and ethnicity, sex, geography, and health status. © The Society for Healthcare Epidemiology of America, 2023. |
Genetic liability for gastrointestinal inflammation disorders and association with gastrointestinal symptoms in children with and without autism
Morrill V , Benke K , Brinton J , Soke GN , Schieve LA , Fields V , Farzadegan H , Holingue C , Newschaffer CJ , Reynolds AM , Fallin MD , Ladd-Acosta C . Am J Med Genet B Neuropsychiatr Genet 2023 195 (1) e32952 Children with autism spectrum disorder (ASD) have a greater prevalence of gastrointestinal (GI) symptoms than children without ASD. We tested whether polygenic scores for each of three GI disorders (ulcerative colitis, inflammatory bowel disease, and Crohn's disease) were related to GI symptoms in children with and without ASD. Using genotyping data (564 ASD cases and 715 controls) and external genome-wide association study summary statistics, we computed GI polygenic scores for ulcerative colitis (UC-PGS), inflammatory bowel disease (IDB-PGS), and Crohn's disease (CD-PGS). Multivariable logistic regression models, adjusted for genetic ancestry, were used to estimate associations between each GI-PGS and (1) ASD case-control status, and (2) specific GI symptoms in neurotypical children and separately in ASD children. In children without ASD, polygenic scores for ulcerative colitis were significantly associated with experiencing any GI symptom (adjusted odds ratio (aOR) = 1.36, 95% confidence interval (CI) = 1.03-1.81, p = 0.03) and diarrhea specifically (aOR = 5.35, 95% CI = 1.77-26.20, p = 0.01). Among children without ASD, IBD-PGS, and Crohn's PGS were significantly associated with diarrhea (aOR = 3.55, 95% CI = 1.25-12.34, p = 0.02) and loose stools alternating with constipation (aOR = 2.57, 95% CI = 1.13-6.55, p = 0.03), respectively. However, the three PGS were not associated with GI symptoms in the ASD case group. Furthermore, polygenic scores for ulcerative colitis significantly interacted with ASD status on presentation of any GI symptom within a European ancestry subset (aOR = 0.42, 95% CI = 0.19-0.88, p = 0.02). Genetic risk factors for some GI symptoms differ between children with and without ASD. Furthermore, our finding that increased genetic risks for GI inflammatory disorders are associated with GI symptoms in children without ASD informs future work on the early detection of GI disorders. |
Improving blood pressure control in the United States: At the heart of Million Hearts 2027
Wall HK , Wright JS , Fleisher LA , Sperling LS . Am J Hypertens 2023 36 (8) 462-465 Million Hearts, a national initiative co-led by the Centers for Disease Control and Prevention (CDC) and the Centers for Medicare and Medicaid Services (CMS), was launched in 2012 to focus and drive improvement on a small set of high-impact strategies known to prevent heart attacks, strokes, and other acute cardiovascular events. Optimizing the “ABCS” of cardiovascular disease prevention (Aspirin when appropriate, Blood pressure control, Cholesterol management, and Smoking cessation) has been at the heart of the initiative. Internal analyses suggest that compared to improvements in aspirin use for secondary prevention, cholesterol management, and smoking cessation, achieving national BP control (>80%) will prevent the greatest number of cardiovascular events in a 5-year period. |
Expression-based diagnosis, treatment selection, and drug development for breast cancer
Ye Q , Wang J , Ducatman B , Raese RA , Rogers JL , Wan YW , Dong C , Padden L , Pugacheva EN , Qian Y , Guo NL . Int J Mol Sci 2023 24 (13) There is currently no gene expression assay that can assess if premalignant lesions will develop into invasive breast cancer. This study sought to identify biomarkers for selecting patients with a high potential for developing invasive carcinoma in the breast with normal histology, benign lesions, or premalignant lesions. A set of 26-gene mRNA expression profiles were used to identify invasive ductal carcinomas from histologically normal tissue and benign lesions and to select those with a higher potential for future cancer development (ADHC) in the breast associated with atypical ductal hyperplasia (ADH). The expression-defined model achieved an overall accuracy of 94.05% (AUC = 0.96) in classifying invasive ductal carcinomas from histologically normal tissue and benign lesions (n = 185). This gene signature classified cancer development in ADH tissues with an overall accuracy of 100% (n = 8). The mRNA expression patterns of these 26 genes were validated using RT-PCR analyses of independent tissue samples (n = 77) and blood samples (n = 48). The protein expression of PBX2 and RAD52 assessed with immunohistochemistry were prognostic of breast cancer survival outcomes. This signature provided significant prognostic stratification in The Cancer Genome Atlas breast cancer patients (n = 1100), as well as basal-like and luminal A subtypes, and was associated with distinct immune infiltration and activities. The mRNA and protein expression of the 26 genes was associated with sensitivity or resistance to 18 NCCN-recommended drugs for treating breast cancer. Eleven genes had significant proliferative potential in CRISPR-Cas9/RNAi screening. Based on this gene expression signature, the VEGFR inhibitor ZM-306416 was discovered as a new drug for treating breast cancer. |
State-specific prevalence of severe obesity among adults in the US using bias correction of self-reported body mass index
Zhao L , Park S , Ward ZJ , Cradock AL , Gortmaker SL , Blanck HM . Prev Chronic Dis 2023 20 E61 INTRODUCTION: Adults with severe obesity are at increased risk for poor metabolic health and may need more intensive clinical and community supports. The prevalence of severe obesity is underestimated from self-reported weight and height data. We examined severe obesity prevalence among US adults by sociodemographic characteristics and by state after adjusting for self-report bias. METHODS: Using a validated bias-correction method, we adjusted self-reported body mass index (BMI) data from the 2020 Behavioral Risk Factor Surveillance System (BRFSS) by using measured data from the National Health and Nutrition Examination Survey. We compared bias-corrected prevalence of severe obesity (BMI ≥40) with self-reported estimates by sociodemographic characteristics and state. RESULTS: Self-reported BRFSS data significantly underestimated the prevalence of severe obesity compared with bias-corrected estimates. In 2020, 8.8% of adults had severe obesity based on the bias-corrected estimates, whereas 5.3% of adults had severe obesity based on self-reported data. Women had a significantly higher prevalence of bias-corrected severe obesity (11.1%) than men (6.5%). State-level prevalence of bias-corrected severe obesity ranged from 5.5% (Massachusetts) to 13.2% (West Virginia). Based on bias-corrected estimates, 16 states had a prevalence of severe obesity greater than 10%, a level not seen in the self-reported estimates. CONCLUSION: Self-reported BRFSS data underestimated the overall prevalence of severe obesity by 40% (5.3% vs 8.8%). Accurate state-level estimates of severe obesity can help public health and health care decision makers prioritize and plan to implement effective prevention and treatment strategies for people who are at high risk for poor metabolic health. |
Trends in the diagnosed prevalence and incidence of major eye diseases in Medicare Part B fee-for-service beneficiaries aged 68 years or older
Ehrlich JR , Andes LJ , Eisenberg A , Saaddine J , Lundeen EA . Ophthalmology 2023 130 (12) 1240-1247 PURPOSE: To study contemporary trends in the diagnosed prevalence and incidence of age-related eye diseases among Medicare fee-for-service (FFS) beneficiaries. DESIGN: Analysis of Medicare administrative claims data. PARTICIPANTS: Medicare FFS beneficiaries aged 68 and older from 2005-2020. Those included were continuously enrolled in both Part A and Part B for 3 years, including the index year and 2-year lookback period. METHODS: Annual cross-sectional diagnosed prevalence and incidence rates were calculated. Age-standardization was performed using the direct standardization method to account for changes in the age-structure of the study population. Rates stratified by demographics (age, sex, race, and ethnicity) were also calculated. MAIN OUTCOME MEASURES: Annual prevalence and incidence of diagnosed age-related macular degeneration (AMD), diabetic retinopathy (DR) (among those with diabetes), and glaucoma. RESULTS: At baseline, in 2005, 60% of included beneficiaries were female, 20% were aged ≥85, 86% were non-Hispanic White, and one-quarter had diabetes. From 2005-2019, the prevalence of a diagnosis of any of the conditions studied increased from 15.0% (N=3,312,812) to 17.9% (N=3,731,281). Diagnosed incidence decreased over this period from 4.7% (N=917,846) in 2005 to 4.2% in 2019 (N=757,696). The diagnosed prevalence of AMD increased from 6.8% (N=1,504,770) to 9.4% (N=1,965,176); the diagnosed prevalence of any DR among those with diabetes decreased from 9.3% (N= 504,135) to 9.0% (N=532,859), though the diagnosed prevalence of vision-threatening DR increased from 2.0% to 3.4%; and the diagnosed prevalence of any diagnosed glaucoma decreased from 8.8% (N= 1,951,141) to 8.1% (N= 1,692,837). In 2020, the diagnosed prevalence and incidence of all diagnoses decreased. During the study period we detected demographic differences in the prevalence and incidence of diagnosis of each condition. CONCLUSIONS: This study presents updated data on the prevalence and incidence of diagnosed major chronic, age-related eye diseases among Medicare FFS beneficiaries. Compared to older epidemiological estimates, we found that the diagnosed prevalence of each condition studied was higher in more recent years. These findings may inform public health and policy planning and resource allocation to address the eye health of an increasingly older US population. |
Arthritis among children and adolescents aged <18 years - United States, 2017-2021
Lites TD , Foster AL , Boring MA , Fallon EA , Odom EL , Seth P . MMWR Morb Mortal Wkly Rep 2023 72 (29) 788-792 Arthritis affects persons of all ages, including younger adults, adolescents, and children; however, recent arthritis prevalence estimates among children and adolescents aged <18 years are not available. Previous prevalence estimates among U.S. children and adolescents aged <18 years ranged from 21 to 403 per 100,000 population depending upon the case definition used. CDC analyzed aggregated 2017-2021 National Survey of Children's Health data to estimate the national prevalence of parent-reported arthritis diagnosed among children and adolescents aged <18 years. An estimated 220,000 (95% CI = 187,000-260,000) U.S. children and adolescents aged <18 years (305 per 100,000) had diagnosed arthritis. Arthritis prevalence among non-Hispanic Black or African American children and adolescents was twice that of non-Hispanic White children and adolescents. Co-occurring conditions, including depression, anxiety, overweight, physical inactivity, and food insecurity were associated with higher prevalences of arthritis. These findings highlight that children and adolescents should be prioritized for arthritis prevention and treatments by identifying risk factors for arthritis, developing self-management interventions to improve arthritis, physical activity or weight control, and screening and linking to mental health services. Health systems and payors can take steps to ensure equitable access to therapies (e.g., physical therapies and medications). |
Hypertension among persons living with HIV - Zambia, 2021; A cross-sectional study of a national electronic health record system (preprint)
Hines JZ , Prieto JT , Itoh M , Fwoloshi S , Zyambo KD , Zachary D , Chitambala C , Minchella PA , Mulenga LB , Agolory S . medRxiv 2023 16 Background Hypertension is a major risk factor for cardiovascular disease, which is a common cause of death in Zambia. Data on hypertension prevalence in Zambia are scarce and limited to specific geographic areas and/or populations. We measured hypertension prevalence among persons living with HIV (PLHIV) in Zambia using a national electronic health record (EHR) system. Methods We did a cross-sectional study of hypertension prevalence among PLHIV aged >=18 years in Zambia during 2021. Data were extracted from the SmartCare EHR, which covers ~90% of PLHIV on treatment in Zambia. PLHIV with >=2 recorded blood pressure (BP) readings in 2021 were included. Hypertension was defined as >=2 elevated BP readings (i.e., systolic BP of >=140 mmHg or diastolic BP of >=90 mmHg) during 2021 and/or on anti-hypertensive medication recorded in their EHR in the past five years. Multivariable logistic regression was used to assess associations between hypertension and independent variables. Results Among 750,098 PLHIV aged >=18 years with >=2 visits in SmartCare during 2021, 101,363 (13.5%) had >=2 blood pressure readings recorded in their EHR. Among these PLHIV, 14.7% (95% confidence interval [CI]: 14.5-14.9) had hypertension during 2021. Only 8.9% of PLHIV with hypertension had an antihypertensive medication recorded in their EHR. The odds of hypertension were greater in older age groups compared to PLHIV aged 18-29 years (adjusted odds ratio [aOR] for 30-44 years: 2.6 [95% CI: 2.4-2.9]; aOR for 45-49 years: 6.4 [95% CI: 5.8-7.0]; aOR for >=60 years: 14.5 [95% CI: 13.1-16.1]), urban areas (aOR: 1.9 [95% CI: 1.8-2.1]), and persons prescribed ART for >=6-month at a time (aOR: 1.1 [95% CI: 1.0-1.2]). Discussion Hypertension was common among a cohort of PLHIV in Zambia, with few having documentation of being on antihypertensive treatment. Most PLHIV were excluded from the analysis because of missing BP measurements in their EHR. Strengthening integrated management of non-communicable diseases in ART clinics might help to diagnose and treat hypertension in Zambia. Data completeness needs to be improved to routinely capture cardiovascular disease risk factors, including blood pressure readings consistently for PHLIV in their EHRs. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Adult asthma prevalence and trend analysis by urban–rural status across sociodemographic characteristics—United States, 2012-20
Qin X , Pate CA , Zahran HS . J Allergy Clin Immunol Glob 2023 2 (2) 100085 Background: Asthma prevalence estimates among adults are limited for urban–rural classification across sociodemographic characteristics. Objectives: This study examined current asthma prevalence and annual trends by 6-level urban–rural categories across sociodemographic characteristics among US adults. Methods: Asthma prevalence for 2020 and annual trends for 2012-20 were estimated using Behavioral Risk Factor Surveillance System data. The 2013 National Center for Health Statistics urban and rural categories were used to define urban–rural status. Results: Current asthma prevalence was higher in medium (9.7%; prevalence ratio 1.103 [95% CI 1.037, 1.174]) and small (9.9%; 1.111 [1.031, 1.197]) metro than in large fringe metropolitan (8.6%), was higher in micropolitan (10.2%) than in both large fringe (8.6%; 1.115 [1.042, 1.194]) and large central metropolitan (8.8%; 1.080 [1.001, 1.066]) areas. Prevalence by sociodemographic characteristics varied between urban–rural scheme; the prevalence was significantly higher among adults aged 55-64 years in micropolitan (11.9%), women in small metro (12.8%), and other race non-Hispanic in noncore (most rural) (13.6%) areas, adults without a high school diploma in micropolitan areas (13.8%), household income <100% of federal poverty level in micropolitan areas (15.7%), and adults with insurance coverage in micropolitan areas (10.3%) compared to the corresponding populations in other urban–rural categories. During 2012-20, an increasing trend in prevalence was observed only in medium metro areas, with an annual percentage change of 0.81. Conclusions: Asthma prevalence differed by 6-level urban–rural categories. These findings might be helpful in establishing effective asthma control programs and targeting resource allocation at the local level. © 2023 |
Profiling and benchmarking central nervous system infections in an infectious diseases intensive care unit
Andrade HB , Rocha Ferreira da Silva I , Espinoza R , da Silva MST , Theodoro PHN , Ferreira MT , Soares J , Belay ED , Sejvar JJ , Bozza FA , Cerbino-Neto J , Japiassú AM . J Intensive Care Med 2023 39 (1) 8850666231188665 BACKGROUND: There is little information comparing the performance of community acquired central nervous system infections (CNSI) treatment by intensive care units (ICUs) specialized in infectious diseases with treatment at other ICUs. Our objective was to reduce these gaps, creating bases for benchmarking and future case-mix classification. METHODS: This is a retrospective observational cohort of 785 admissions with 82 cases of CNSI admitted to the ICU of an important Brazilian referral center for infectious diseases (INI) between January 2012 and January 2019. Comparisons were made to data retrospectively collected from the 303,500 intensive care admissions from the Brazilian state health care system included in the Epimed Monitor database. Clinical, epidemiologic, and performance indicators: the standardized mortality rate (SMR) and the standardized resource use rate per ICU surviving patient (SRU) were collected. RESULTS: Case-mix infections profile and SMR/SRU data. SUS Mixed medical/surgical ICUs: SMR = 1.26, SRU = 1.59; SUS Neurological ICUs: SMR = 1.17, SRU = 2.23; INI ICU: SMR = 1.1, SRU = 1.1; INI ICU CNSI patients: SMR = 0.95, SRU = 1.01. CONCLUSIONS: Severe patients with CNSI can be efficiently and effectively treated in an ICU specialized in infectious diseases when compared to mixed medical/surgical and neurological ICUs from the public health system. At the same time, we provided profiling and a case-mix that can help and encourage benchmarking by other institutions and other countries. |
RSV among American Indian and Alaska Native children: 2019 to 2020
Atwell JE , Hartman RM , Parker D , Taylor K , Brown LB , Sandoval M , Ritchie N , Desnoyers C , Wilson AS , Hammes M , Tiesinga J , Halasa N , Langley G , Prill MM , Bruden D , Close R , Moses J , Karron RA , Santosham M , Singleton RJ , Hammitt LL . Pediatrics 2023 152 (2) Respiratory syncytial virus (RSV) is the leading viral cause of acute lower respiratory tract infections, including bronchiolitis and pneumonia, in children under 5 years of age globally.1 Historically, RSV-associated hospitalization rates among American Indian and Alaska Native (AI/AN) children have been among the highest in the world.2,–7 Contemporary estimates of RSV-acute respiratory infection (ARI) are needed to inform RSV prevention strategies for AI/AN children. |
Updated operational guidance for implementing CDC's recommendations on testing for hepatitis C virus infection
Cartwright EJ , Patel P , Kamili S , Wester C . MMWR Morb Mortal Wkly Rep 2023 72 (28) 766-768 Current hepatitis C virus (HCV) testing guidance recommends a two-step testing sequence for diagnosis of HCV infection. Performing an HCV RNA test whenever an HCV antibody test is reactive (complete testing) is critical to achieve national HCV elimination goals. When an HCV antibody test is reactive and no HCV RNA test is performed, testing is considered incomplete. Historically, approximately one third of patients have incomplete testing. This update clarifies that all sites performing HCV screening should ensure single-visit sample collection. This approach allows for automatic HCV RNA testing when an HCV antibody test is reactive to avoid incomplete testing. Use of strategies that require multiple visits to collect HCV testing samples should be discontinued. Automatic HCV RNA testing on all HCV antibody reactive samples will increase the percentage of patients with current HCV infection who are linked to care and receive curative antiviral therapy. |
Temporal trends in hepatitis C-related hospitalizations, United States, 2000-2019
Hofmeister MG , Zhong Y , Moorman AC , Samuel CR , Teshale EH , Spradling PR . Clin Infect Dis 2023 77 (12) 1668-1675 BACKGROUND: Hospitalization burden related to hepatitis C virus (HCV) infection is substantial. We sought to describe temporal trends in hospitalization rates before and after release of direct-acting antiviral (DAA) agents. METHODS: We analyzed 2000-2019 data from adults aged ≥18 years in the National Inpatient Sample. Hospitalizations were HCV-related if 1) hepatitis C was the primary diagnosis, or 2) hepatitis C was any secondary diagnosis with a liver-related primary diagnosis. We analyzed characteristics of HCV-related hospitalizations nationally, and examined trends in age-adjusted hospitalization rates. RESULTS: During 2000-2019, there were an estimated 1,286,397 HCV-related hospitalizations in the United States. The annual age-adjusted hospitalization rate was lowest in 2019 (18.7/100,000 population) and highest in 2012 (29.6/100,000 population). Most hospitalizations occurred among persons aged 45-64 (71.8%), males (67.1%), white non-Hispanic persons (60.5%), and Medicaid/Medicare recipients (64.0%). The national age-adjusted hospitalization rate increased during 2000-2003 (annual percent change [APC] 9.4%, P<.001) and 2003-2013 (APC 1.8%, P<.001) before decreasing during 2013-2019 (APC -7.6%, P<.001). Comparing 2000 to 2019, the largest increases in hospitalization rates occurred among persons aged 55-64 years (132.9%), Medicaid recipients (41.6%), and black non-Hispanic persons (22.3%). CONCLUSIONS: Although multiple factors likely contributed, overall HCV-related hospitalization rates declined steadily after 2013, coinciding with the release of DAAs. However, the declines were not observed equally among age, race/ethnicity, or insurance categories. Expanded access to DAA treatment is needed, particularly among Medicaid and Medicare recipients, to reduce disparities and morbidity, and eliminate hepatitis C as a public health threat. |
Closing the gap in our understanding of infectious diseases
Kalinda C , Temfack E . BMC Infect Dis 2023 23 (1) 412 Systematic reviews (SR) and meta-analyses (MA) have become important in addressing specific questions of clinical importance and presenting evidence from an in-depth analysis of literature and aiding clinical decision-making. The "Systematic Reviews on infectious diseases" collection will address several important questions by summarizing large bodies of evidence in a reproducible and concise approach to advance our knowledge and understanding of infectious diseases. |
Distinct origins and transmission pathways of bla(KPC) enterobacterales across three U.S. States
Lapp Z , Octaria R , O'Malley SM , Nguyen TN , Wolford H , Crawford R , Moore C , Snippes Vagnone P , Noel D , Duffy N , Pirani A , Thomas LS , Pattee B , Pearson C , Bulens SN , Hoffman S , Kainer M , Anacker M , Meek J , See I , Gontjes KJ , Chan A , Lynfield R , Maloney M , Hayden MK , Snitkin E , Slayton RB . J Clin Microbiol 2023 61 (8) e0025923 Carbapenem-resistant Enterobacterales (CRE) are among the most concerning antibiotic resistance threats due to high rates of multidrug resistance, transmissibility in health care settings, and high mortality rates. We evaluated the potential for regional genomic surveillance to track the spread of bla(KPC)-carrying CRE (KPC-CRE) by using isolate collections from health care facilities in three U.S. states. Clinical isolates were collected from Connecticut (2017 to 2018), Minnesota (2012 to 2018), and Tennessee (2016 to 2017) through the U.S. Centers for Disease Control and Prevention's Multi-site Gram-negative Surveillance Initiative (MuGSI) and additional surveillance. KPC-CRE isolates were whole-genome sequenced, yielding 255 isolates from 214 patients across 96 facilities. Case report data on patient comorbidities, facility exposures, and interfacility patient transfer were extracted. We observed that in Connecticut, most KPC-CRE isolates showed evidence of importation from outside the state, with limited local transmission. In Minnesota, cases were mainly from sporadic importation and transmission of bla(KPC)-carrying Klebsiella pneumoniae ST258, and clonal expansion of bla(KPC)-carrying Enterobacter hormaechei ST171, primarily at a single focal facility and its satellite facilities. In Tennessee, we observed transmission of diverse strains of bla(KPC)-carrying Enterobacter and Klesbiella, with evidence that most derived from the local acquisition of bla(KPC) plasmids circulating in an interconnected regional health care network. Thus, the underlying processes driving KPC-CRE burden can differ substantially across regions and can be discerned through regional genomic surveillance. This study provides proof of concept that integrating genomic data with information on interfacility patient transfers can provide insights into locations and drivers of regional KPC-CRE burden that can enable targeted interventions. |
Population-level viremia predicts HIV incidence at the community level across the Universal Testing and Treatment Trials in eastern and southern Africa
Larmarange J , Bachanas P , Skalland T , Balzer LB , Iwuji C , Floyd S , Mills LA , Pillay D , Havlir D , Kamya MR , Ayles H , Wirth K , Dabis F , Hayes R , Petersen M . PLOS Glob Public Health 2023 3 (7) e0002157 Universal HIV testing and treatment (UTT) strategies aim to optimize population-level benefits of antiretroviral treatment. Between 2012 and 2018, four large community randomized trials were conducted in eastern and southern Africa. While their results were broadly consistent showing decreased population-level viremia reduces HIV incidence, it remains unclear how much HIV incidence can be reduced by increasing suppression among people living with HIV (PLHIV). We conducted a pooled analysis across the four UTT trials. Leveraging data from 105 communities in five countries, we evaluated the linear relationship between i) population-level viremia (prevalence of non-suppression-defined as plasma HIV RNA >500 or >400 copies/mL-among all adults, irrespective of HIV status) and HIV incidence; and ii) prevalence of non-suppression among PLHIV and HIV incidence, using parametric g-computation. HIV prevalence, measured in 257 929 persons, varied from 2 to 41% across the communities; prevalence of non-suppression among PLHIV, measured in 31 377 persons, from 3 to 70%; population-level viremia, derived from HIV prevalence and non-suppression, from < 1% to 25%; and HIV incidence, measured over 345 844 person-years (PY), from 0.03/100PY to 3.46/100PY. Decreases in population-level viremia were strongly associated with decreased HIV incidence in all trials (between 0.45/100PY and 1.88/100PY decline in HIV incidence per 10 percentage points decline in viremia). Decreases in non-suppression among PLHIV were also associated with decreased HIV incidence in all trials (between 0.06/100PY and 0.17/100PY decline in HIV incidence per 10 percentage points decline in non-suppression). Our results support both the utility of population-level viremia as a predictor of incidence, and thus a tool for targeting prevention interventions, and the ability of UTT approaches to reduce HIV incidence by increasing viral suppression. Implementation of universal HIV testing approaches, coupled with interventions to leverage linkage to treatment, adapted to local contexts, can reduce HIV acquisition at population level. |
SARS-CoV-2 outbreak among staff and evacuees at Operation Allies Welcome Safe Havens
Meeker JR , Gosdin L , Siu A , Turner L , Zusman BD , Sadigh KS , Carpenter R , Dopson S , Saindon J , Kyaw NTT , Segaloff HE , Pritchard N , Shahum A , Traboulsi R , Worrell MC , Beaucham C , Gandhi P , Winslow DL , Rotz L , Talley L , Mosites E , Boyd AT . Public Health Nurs 2023 40 (5) 758-761 We report on five SARS-CoV-2 congregate setting outbreaks at U.S. Operation Allies Welcome Safe Havens/military facilities. Outbreak data were collected, and attack rates were calculated for various populations. Even in vaccinated populations, there was rapid spread, illustrating the importance of institutional prevention and mitigation policies in congregate settings. |
A sore subject An examination of national case-based chancroid surveillance
Ogale YP , Ridpath AD , Torrone E , Quilter LAS , Grey JA . Sex Transm Dis 2023 50 (8) 467-471 BACKGROUND: Chancroid has been a nationally notifiable condition in the United States since 1944, with cases reported to Centers Disease Control and Prevention through the National Notifiable Diseases Surveillance System. Although frequently reported during the 1940s, <20 cases have been reported annually since 2011. We assessed the performance and utility of national case-based chancroid surveillance. METHODS: We reviewed the literature to contextualize chancroid surveillance through National Notifiable Diseases Surveillance System. We then assessed 4 system attributes, including data quality, sensitivity, usefulness, and representativeness: we reviewed chancroid cases reported during 2011-2020, conducted interviews with (a) sexually transmitted disease programs reporting ≥1 case in 2019 or 2020 (n = 9) and (b) Centers Disease Control and Prevention subject matter experts (n = 10), and reviewed published communicable disease reporting laws. RESULTS: Chancroid diagnostic testing is limited, which affects the surveillance case definition. National case-based surveillance has poor data quality; of the 2019 and preliminary 2020 cases (n = 14), only 3 were verified by jurisdictions as chancroid cases. Sexually transmitted disease programs report the system has low sensitivity given limited clinician knowledge and resources; experts report the system is not useful in guiding national control efforts. Review of reporting laws revealed it is not representative, as chancroid is not a reportable condition nationwide. CONCLUSIONS: Critical review of system attributes suggest that national case-based chancroid surveillance data have limited ability to help describe and monitor national trends, and chancroid's inclusion on the national notifiable list might need to be reconsidered. Alternative strategies might be needed to monitor national chancroid burden. |
Streptococcus pneumoniae nasal carriage patterns with and without common respiratory virus detections in households in Seattle, WA, USA before and during the COVID-19 pandemic
Bennett JC , Emanuels A , Heimonen J , O'Hanlon J , Hughes JP , Han PD , Chow EJ , Ogokeh CE , Rolfes MA , Lockwood CM , Pfau B , Uyeki TM , Shendure J , Hoag S , Fay K , Lee J , Sibley TR , Rogers JH , Starita LM , Englund JA , Chu HY . Front Pediatr 2023 11 1198278 BACKGROUND: Respiratory viruses might influence Streptococcus pneumoniae nasal carriage and subsequent disease risk. We estimated the association between common respiratory viruses and semiquantitative S. pneumoniae nasal carriage density in a household setting before and during the COVID-19 pandemic. METHODS: From November 2019-June 2021, we enrolled participants in a remote household surveillance study of respiratory pathogens. Participants submitted weekly reports of acute respiratory illness (ARI) symptoms. Mid-turbinate or anterior nasal swabs were self-collected at enrollment, when ARI occurred, and, in the second year of the study only, from household contacts after SARS-CoV-2 was detected in a household member. Specimens were tested using multiplex reverse-transcription PCR for respiratory pathogens, including S. pneumoniae, rhinovirus, adenovirus, common human coronavirus, influenza A/B virus, respiratory syncytial virus (RSV) A/B, human metapneumovirus, enterovirus, and human parainfluenza virus. We estimated differences in semiquantitative S. pneumoniae nasal carriage density, estimated by the inverse of S. pneumoniae relative cycle threshold (Crt) values, with and without viral detection for any virus and for specific respiratory viruses using linear generalized estimating equations of S. pneumoniae Crt values on virus detection adjusted for age and swab type and accounting for clustering of swabs within households. RESULTS: We collected 346 swabs from 239 individuals in 151 households that tested positive for S. pneumoniae (n = 157 with and 189 without ≥1 viruses co-detected). Difficulty breathing, cough, and runny nose were more commonly reported among individuals with specimens with viral co-detection compared to without (15%, 80% and 93% vs. 8%, 57%, and 51%, respectively) and ear pain and headache were less commonly reported (3% and 26% vs. 16% and 41%, respectively). For specific viruses among all ages, semiquantitative S. pneumoniae nasal carriage density was greater with viral co-detection for enterovirus, RSV A/B, adenovirus, rhinovirus, and common human coronavirus (P < 0.01 for each). When stratified by age, semiquantitative S. pneumoniae nasal carriage density was significantly greater with viral co-detection among children aged <5 (P = 0.002) and 5-17 years (P = 0.005), but not among adults aged 18-64 years (P = 0.29). CONCLUSION: Detection of common respiratory viruses was associated with greater concurrent S. pneumoniae semiquantitative nasal carriage density in a household setting among children, but not adults. |
Prevalence and determinants of hepatitis delta virus infection among HIV/hepatitis B-coinfected adults in care in the United States
Ferrante ND , Kallan MJ , Sukkestad S , Kodani M , Kitahata MM , Cachay ER , Bhattacharya D , Heath S , Napravnik S , Moore RD , Yendewa G , Mayer KH , Reddy KR , Hayden T , Kamili S , Martin JN , Kim HN , Lo Re V 3rd . J Viral Hepat 2023 30 (11) 879-888 Hepatitis delta virus (HDV) infection increases the risk of liver complications compared to hepatitis B virus (HBV) alone, particularly among persons with human immunodeficiency virus (HIV). However, no studies have evaluated the prevalence or determinants of HDV infection among people with HIV/HBV in the US. We performed a cross-sectional study among adults with HIV/HBV coinfection receiving care at eight sites within the Center for AIDS Research Network of Integrated Clinical Systems (CNICS) between 1996 and 2019. Among patients with available serum/plasma specimens, we selected the first specimen on or after their initial HBV qualifying test. All samples were tested for HDV IgG antibody and HDV RNA. Multivariable log-binomial generalized linear models were used to estimate prevalence ratios (PRs) with 95% CIs of HDV IgG antibody-positivity associated with determinants of interest (age, injection drug use [IDU], high-risk sexual behaviour). Among 597 adults with HIV/HBV coinfection in CNICS and available serum/plasma samples (median age, 43 years; 89.9% male; 52.8% Black; 42.4% White), 24/597 (4.0%; 95% CI, 2.4%-5.6%) were HDV IgG antibody-positive, and 10/596 (1.7%; 95% CI, 0.6%-2.7%) had detectable HDV RNA. In multivariable analysis, IDU was associated with exposure to HDV infection (adjusted PR = 2.50; 95% CI, 1.09-5.74). In conclusion, among a sample of adults with HIV/HBV coinfection in care in the US, 4.0% were HDV IgG antibody-positive, among whom 41.7% had detectable HDV RNA. History of IDU was associated with exposure to HDV infection. These findings emphasize the importance of HDV testing among persons with HIV/HBV coinfection, especially those with a history of IDU. |
Trends and opportunities: Hepatitis A virus infection, seroprevalence, and vaccination coverage-United States, 1976-2020
Hofmeister MG , Yin S , Nelson NP , Weng MK , Gupta N . Public Health Rep 2023 333549231184007 OBJECTIVES: The incidence of hepatitis A declined in the United States following the introduction of hepatitis A vaccines, before increasing in the setting of recent widespread outbreaks associated with person-to-person transmission. We describe the hepatitis A epidemiology in the United States, identify susceptible populations over time, and demonstrate the need for improved hepatitis A vaccination coverage, especially among adults at increased risk for hepatitis A. METHODS: We calculated the hepatitis A incidence rates for sociodemographic characteristics and percentages for risk factors and clinical outcomes for hepatitis A cases reported to the National Notifiable Diseases Surveillance System during 1990-2020. We generated nationally representative estimates and 95% CIs of hepatitis A seroprevalence during 1976-March 2020 and self-reported hepatitis A vaccination coverage during 1999-March 2020 for the noninstitutionalized civilian US population using data from the National Health and Nutrition Examination Survey. RESULTS: Overall, the rate per 100 000 population of reported cases of hepatitis A virus infection in the United States declined 17.3-fold, from 10.4 during 1990-1998 to 0.6 during 2007-2015, and then increased to 2.8 during 2016-2020. The overall hepatitis A seroprevalence in the United States increased from 38.2% (95% CI, 36.2%-40.1%) during 1976-1980 to 47.3% (95% CI, 45.4%-49.2%) during 2015-March 2020. The prevalence of self-reported hepatitis A vaccination coverage in the United States increased more than 2.5-fold, from 16.3% (95% CI, 15.0%-17.7%) during 1999-2006 to 41.9% (95% CI, 40.2%-43.7%) during 2015-March 2020. CONCLUSIONS: Hepatitis A epidemiology in the United States changed substantially during 1976-2020. Improved vaccination coverage, especially among adults recommended for vaccination by the Advisory Committee on Immunization Practices, is vital to stop current hepatitis A outbreaks associated with person-to-person transmission in the United States and prevent similar future recurrences. |
Progress toward Hepatitis B control and elimination of mother-to-child transmission of Hepatitis B virus - World Health Organization African Region, 2016-2021
Kabore HJ , Li X , Alleman MM , Manzengo CM , Mumba M , Biey J , Paluku G , Bwaka AM , Impouma B , Tohme RA . MMWR Morb Mortal Wkly Rep 2023 72 (29) 782-787 Chronic hepatitis B virus (HBV) infection is one of the leading causes of cirrhosis and liver cancer. In 2019, approximately 1.5 million persons newly acquired chronic HBV infection; among these, 990,000 (66%) were in the World Health Organization (WHO) African Region (AFR). Most chronic HBV infections are acquired through mother-to-child transmission (MTCT) or during early childhood, and approximately two thirds of these infections occur in AFR. In 2016, the World Health Assembly endorsed the goal of elimination of mother-to-child transmission (EMTCT) of HBV, documented by ≥90% coverage with both a timely hepatitis B vaccine (HepB) birth dose (HepB-BD) and 3 infant doses of HepB (HepB3), and ≤0.1% hepatitis B surface antigen (HBsAg) seroprevalence among children aged ≤5 years. In 2016, the WHO African Regional Committee endorsed targets for a 30% reduction in incidence (≤2% HBsAg seroprevalence in children aged ≤5 years) and ≥90% HepB3 coverage by 2020. By 2021, all 47 countries in the region provided HepB3 to infants beginning at age 6 weeks, and 14 countries (30%) provided HepB-BD. By December 2021, 16 (34%) countries achieved ≥90% HepB3 coverage, and only two (4%) achieved ≥90% timely HepB-BD coverage. Eight countries (17%) conducted nationwide serosurveys among children born after the introduction of HepB to assess HBsAg seroprevalence: six countries had achieved ≤2% seroprevalence, but none had achieved ≤0.1% seroprevalence among children. The development of immunization recovery plans following the COVID-19 pandemic provides an opportunity to accelerate progress toward hepatitis B control and EMTCT, including introducing HepB-BD and increasing coverage with timely HepB-BD and HepB3 vaccination. Representative HBsAg serosurveys among children and a regional verification body for EMTCT of HBV will be needed to monitor progress. |
A comparison of pathogen detection and risk factors among symptomatic children with gastroenteritis compared with asymptomatic children in the post-rotavirus vaccine era
Lee BR , Harrison CJ , Hassan F , Sasidharan A , Moffatt ME , Weltmer K , Payne DC , Wikswo ME , Parashar U , Selvarangan R . J Pediatr 2023 261 113551 OBJECTIVE: To describe demographics, pathogen distribution/seasonality, and risk factors in children seeking care for acute gastroenteritis (AGE) at a midwestern US emergency department during 5 postrotavirus vaccine years (2011-2016), and further, to compare the same data with matched healthy controls (HC). STUDY DESIGN: AGE and HC participants <11 years old enrolled in the New Vaccine Surveillance Network study between December 2011 to June 2016 were included. AGE was defined as ≥3 diarrhea episodes or ≥1 vomiting episode. Each HC's age was similar to an AGE participant's age. Pathogens were analyzed for seasonality effects. Participant risk factors for AGE illness and pathogen detections were compared between HC and a matched subset of AGE cases. RESULTS: One or more organisms was detected in 1159 of 2503 children (46.3%) with AGE compared with 99 of 537 HC (17.3%). Norovirus was detected most frequently among AGE (n = 568 [22.7%]) and second-most frequently in HC (n = 39 [6.8%]). Rotavirus was the second most frequently detected pathogen among AGE (n = 196 [7.8%]). Children with AGE were significantly more likely to have reported a sick contact compared with HC, both outside the home (15.6% vs 1.4%; P < .001) and inside the home (18.6% vs 2.1%; P < .001). Daycare attendance was higher among children with AGE (41.4%) compared with HC (29.5%; P < .001). The Clostridium difficile detection rate was slightly higher among HC (7.0%) than AGE (5.3%). CONCLUSIONS: Norovirus was the most prevalent pathogen among children with AGE. Norovirus was detected in some HC, suggesting potential asymptomatic shedding among HC. The proportion of AGE participants with a sick contact was approximately 10 times greater than that of HC. |
Meeting report: 36th international conference on antiviral research in Lyon, France, March 13-17, 2023
Spengler JR , Carter K , Delang L , Durantel D , Gowen BB , Herrero LJ , Hurst B , Janeba Z , Jordan R , Luo D , Meier C , Moffat J , Rocha-Pereira J , Seley-Radtke KL , Welch SR , Schang LM . Antiviral Res 2023 217 105678 The 36th International Conference on Antiviral Research (ICAR), sponsored by the International Society for Antiviral Research (ISAR), was held March 13-17, 2023, in Lyon, France, and concurrently through an interactive remote meeting platform. Here we provide a report summarizing the presentations at the 36th ICAR, including the ISAR speaker awards. We also detail special events, sessions, and additional awards conferred at the meeting. ICAR returned to in-person meetings in 2022, convening in Seattle, WA, USA. The 36th ICAR is the first in-person meeting of the society in Europe since the beginning of the COVID-19 pandemic, which restricted most events to virtual attendance to help mitigate the spread and subsequent public health impact of SARS-CoV-2. An exceptionally high number of registrants and record attendance at this year's ICAR, along with a vast array of demonstrable expertise in a variety of antiviral research-related fields, reflected a strong and growing antiviral research community committed to improving health outcomes from viral diseases, including SARS-CoV-2, and to future pandemic preparedness. This report highlights the breadth of expertise, quality of research, and notable advancements that were contributed by members of ISAR and other participants at the meeting. ICAR aims to continue to provide a platform for sharing information, fostering collaborations, and supporting trainees in the field of antiviral research. The 37th ICAR will be held in Gold Coast, Australia, May 20-24, 2024. |
Monitoring transmission intensity of trachoma with serology: a multi-country study (preprint)
Tedijanto C , Solomon AW , Martin DL , Nash SD , Keenan JD , Lietman TM , Lammie PJ , Aiemjoy K , Amza A , Aragie S , Arzika AM , Callahan EK , Carolan S , Dawed AA , Goodhew EB , Gwyn S , Hammou J , Kadri B , Kalua K , Maliki R , Nassirou B , Seife F , Tadesse Z , West SK , Wittberg DM , Zeru T , Arnold BF . medRxiv 2023 16 Trachoma, caused by ocular Chlamydia trachomatis infection, is targeted for global elimination as a public health problem by 2030. To provide evidence for use of antibodies to monitor C. trachomatis transmission, we collated IgG responses to Pgp3 antigen, PCR positivity, and clinical observations from 19,811 children aged 1-9 years in 14 populations. We demonstrate that age-seroprevalence curves consistently shift along a gradient of transmission intensity: rising steeply in populations with high levels of infection and active trachoma and becoming flat in populations near elimination. Seroprevalence (range: 0-54%) and seroconversion rates (range: 0-15 per 100 person-years) correlate with PCR prevalence (r: 0.88, 95% CI: 0.77, 0.93). A seroprevalence threshold of 13.5% (seroconversion rate 2.75 per 100 person-years) identifies clusters with any infection at high sensitivity (>90%) and moderate specificity (69-75%). Antibody responses in young children provide a robust, generalizable approach to monitor population progress toward and beyond trachoma elimination. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Patterns of within-host spread of Chlamydia trachomatis between vagina, endocervix and rectum revealed by comparative genomic analysis (preprint)
Joseph SJ , Bommana S , Ziklo N , Kama M , Dean D , Read TD . bioRxiv 2023 26 Chlamydia trachomatis, a gram-negative obligate intracellular bacterium, commonly causes sexually transmitted infections (STIs). Little is known about C. trachomatis transmission within the host, which is important for understanding disease epidemiology and progression. We used RNA-bait enrichment and whole-genome sequencing to compare rectal, vaginal and endocervical samples collected at the same time from 26 study participants who attended Fijian Ministry of Health and Medical Services clinics and tested positive for C. trachomatis at each anatomic site. The 78 C. trachomatis genomes from participants were from two major clades of the C. trachomatis phylogeny (the "prevalent urogenital and anorecta"l clade and "non-prevalent urogenital and anorectal" clade). For 21 participants, genome sequences were almost identical in each anatomic site. For the other five participants, two distinct C. trachomatis strains were present in different sites; in two cases, the vaginal sample was a mixture of strains. The absence of large numbers of fixed SNPs between C. trachomatis strains within many of the participants could indicate recent acquisition of infection prior to the clinic visit without sufficient time to accumulate significant variation in the different body sites. This model suggests that many C. trachomatis infections may be resolved relatively quickly in the Fijian population, possibly reflecting common prescription or over-the-counter antibiotics usage. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. |
Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa (preprint)
Sun K , Tempia S , Kleynhans J , von Gottberg A , McMorrow ML , Wolter N , Bhiman JN , Moyes J , Carrim M , Martinson NA , Kahn K , Lebina L , du Toit JD , Mkhencele T , Viboud C , Cohen C . medRxiv 2022 22 South Africa was among the first countries to detect the SARS-CoV-2 Omicron variant. Propelled by increased transmissibility and immune escape properties, Omicron displaced other globally circulating variants within 3 months of its emergence. Due to limited testing, Omicron's attenuated clinical severity, and an increased risk of reinfection, the size of the Omicron BA.1 and BA.2 subvariants (BA.1/2) wave remains poorly understood in South Africa and in many other countries. Using South African data from urban and rural cohorts closely monitored since the beginning of the pandemic, we analyzed sequential serum samples collected before, during, and after the Omicron BA.1/2 wave to infer infection rates and monitor changes in the immune histories of participants over time. Omicron BA.1/2 infection attack rates reached 65% (95% CI, 60% - 69%) in the rural cohort and 58% (95% CI, 61% - 74%) in the urban cohort, with repeat infections and vaccine breakthroughs accounting for >60% of all infections at both sites. Combined with previously collected data on pre-Omicron variant infections within the same cohorts, we identified 14 distinct categories of SARS-CoV-2 antigen exposure histories in the aftermath of the Omicron BA.1/2 wave, indicating a particularly fragmented immunologic landscape. Few individuals (<6%) remained naive to SARS-CoV-2 and no exposure history category represented over 25% of the population at either cohort site. Further, cohort participants were more than twice as likely to get infected during the Omicron BA.1/2 wave, compared to the Delta wave. Prior infection with the ancestral strain (with D614G mutation), Beta, and Delta variants provided 13% (95% CI, -21% - 37%), 34% (95% CI, 17% - 48%), and 51% (95% CI, 39% - 60%) protection against Omicron BA.1/2 infection, respectively. Hybrid immunity (prior infection and vaccination) and repeated prior infections (without vaccination) reduced the risks of Omicron BA.1/2 infection by 60% (95% CI, 42% - 72%) and 85% (95% CI, 76% - 92%) respectively. Reinfections and vaccine breakthroughs had 41% (95% CI, 26% - 53%) lower risk of onward transmission than primary infections. Our study sheds light on a rapidly shifting landscape of population immunity, along with the changing characteristics of SARS-CoV-2, and how these factors interact to shape the success of emerging variants. Our findings are especially relevant to populations similar to South Africa with low SARS-CoV-2 vaccine coverage and a dominant contribution of immunity from prior infection. Looking forward, the study provides context for anticipating the long-term circulation of SARS-CoV-2 in populations no longer naive to the virus. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Recent O-antigen diversification masks highly pathogenic STEC O104:H4 (preprint)
Lang C , Fruth A , Campbell IW , Jenkins C , Smith P , Strockbine N , Weill FX , Nubel U , Grad YH , Waldor MK , Flieger A . bioRxiv 2022 15 Background: Shiga toxin-producing E. coli (STEC) can give rise to a range of clinical outcomes from diarrhea to the life-threatening systemic condition, hemolytic uremic syndrome (HUS). A major outbreak of HUS occurred in 2011, and was caused by a rare serotype, STEC O104:H4. Prior to 2011 and since the outbreak, STEC O104:H4 were rarely associated with human infections. Method(s): From 2012 to 2020 intensified STEC surveillance was performed in Germany where subtyping of ~8,000 clinical isolates by molecular methods including whole genome sequencing was carried out. Virulence traits and phylogenetic context were investigated for a subset of strains. Result(s): A rare STEC serotype O181:H4 associated with HUS was identified, belonging to sequence type (ST) 678, like the STEC O104:H4 outbreak strain. Virulence and genomic comparisons revealed that the two strains are phylogenetically related and differ principally in the gene cluster encoding their respective lipopolysaccharide O-antigens. In addition, five other serotypes belonging to ST678 from human clinical infection were identified from diverse locations worldwide. Conclusion(s): Our data suggest the high virulence ensemble of STEC O104:H4 remains a global threat, but that horizontal exchange of O-antigen gene clusters has cloaked the pathogen with new O-antigens, confounding interpretation of their potential risk. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Respiratory Virus Circulation during the First Year of the COVID-19 Pandemic in the Household Influenza Vaccine Evaluation (HIVE) Cohort (preprint)
Fine SR , Bazzi LA , Callear AP , Petrie JG , Malosh RE , Tucker JE , Smith M , Ibiebele J , McDermott A , Rolfes MA , Monto AS , Martin ET . medRxiv 2022 09 Background The annual reappearance of respiratory viruses has been recognized for decades. The onset of the COVID-19 pandemic altered typical respiratory virus transmission patterns. COVID-19 mitigation measures taken during the pandemic were targeted at SARS-CoV-2 respiratory transmission and thus broadly impacted the burden of acute respiratory illnesses (ARIs), in general. Methods We used the longitudinal Household Influenza Vaccine Evaluation (HIVE) cohort of households in southeast Michigan to characterize mitigation strategy adherence, respiratory illness burden, and the circulation of 15 respiratory viruses during the COVID-19 pandemic determined by RT-PCR of respiratory specimens collected at illness onset. Study participants were surveyed twice during the study period (March 1, 2020, to June 30, 2021), and serologic specimens were collected for antibody measurement by electrochemiluminescence immunoassay. Incidence rates of ARI reports and virus detections were calculated and compared using incidence rate ratios for the study period and a pre-pandemic period of similar length. Results Overall, 437 participants reported a total of 772 ARIs and 329 specimens (42.6%) had respiratory viruses detected. Rhinoviruses were the most frequently detected organism, but seasonal coronaviruses-excluding SARS-CoV-2-were also common. Illness reports and percent positivity were lowest from May to August 2020, when mitigation measures were most stringent. Study participants were more adherent to mitigation measures in the first survey compared with the second survey. Supplemental serology surveillance identified 5.3% seropositivity for SARS-CoV-2 in summer 2020; 3.0% between fall 2020 and winter 2021; and 11.3% in spring 2021. Compared to a pre-pandemic period of similar length, the incidence rate of total reported ARIs for the study period was 50% lower (95% CI: 0.5, 0.6; p<0.001) than the incidence rate from March 1, 2016, to June 30, 2017. Conclusions The burden of ARI in the HIVE cohort during the COVID-19 pandemic fluctuated, with declines occurring concurrently with the widespread use of public health measures. It is notable, however, that rhinovirus and seasonal coronaviruses continued to circulate even as influenza and SARSCoV-2 circulation was low. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Risk factors for severe COVID-19 among HIV-infected and-uninfected individuals in South Africa, April 2020- March 2022 - data from sentinel surveillance (preprint)
Walaza S , Tempia S , von Gottberg A , Wolter N , Bhiman JN , Buys A , Amoako D , Moosa F , du Plessis M , Moyes J , McMorrow ML , Dawood H , Variava E , Reubenson G , Nel J , Zar HJ , Makhasi M , Meiring S , Quan V , Cohen C . medRxiv 2022 21 Background Data on risk factors for COVID-19-associated hospitalisation and mortality in high HIV prevalence settings are limited. Methods Using existing syndromic surveillance programs for influenza-like-illness and severe respiratory illness at sentinel sites in South Africa, we identified factors associated with COVID-19 hospitalisation and mortality. Results From April 2020 through March 2022, SARS-CoV-2 was detected in 24.0% (660/2746) of outpatient and 32.5% (2282/7025) of inpatient cases. Factors associated with COVID-19associated hospitalisation included: older age (25-44 [adjusted odds ratio (aOR) 1.8, 95% confidence interval (CI) 1.1-2.9], 45-64 [aOR 6.8, 95%CI 4.2-11.0] and >=65 years [aOR 26.6, 95%CI 14.4-49.1] vs 15-24 years); black race (aOR 3.3, 95%CI 2.2-5.0); obesity (aOR 2.3, 95%CI 1.4-3.9); asthma (aOR 3.5, 95%CI 1.4-8.9); diabetes mellitus (aOR 5.3, 95%CI 3.1-9.3); HIV with CD4 >=200/mm3 (aOR 1.5, 95%CI 1.1-2.2) and CD4<200/mm3 (aOR 10.5, 95%CI 5.1-21.6) or tuberculosis (aOR 12.8, 95%CI 2.8-58.5). Infection with Beta (aOR 0.5, 95%CI 0.3-0.7) vs Delta variant and being fully vaccinated (aOR 0.1, 95%CI 0.1-0.3) were less associated with COVID-19 hospitalisation. In-hospital mortality was increased in older age (45-64 years [aOR 2.2, 95%CI 1.6-3.2] and >=65 years [aOR 4.0, 95%CI 2.8-5.8] vs 25-44 years) and male sex (aOR1.3, 95%CI 1.0-1.6) and was lower in Omicron -infected (aOR 0.3, 95%CI 0.2-0.6) vs Delta-infected individuals. Conclusion Active syndromic surveillance encompassing clinical, laboratory and genomic data identified setting-specific risk factors associated with COVID-19 severity that will inform prioritization of COVID-19 vaccine distribution. Elderly, people with tuberculosis or people living with HIV, especially severely immunosuppressed should be prioritised for vaccination. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. |
SARS-CoV-2 seroprevalence in a rural and urban community household cohort in South Africa, after the third wave, April-November 2021 (preprint)
Kleynhans J , Tempia S , Wolter N , von Gottberg A , Bhiman JN , Buys A , Moyes J , McMorrow ML , Kahn K , Gomez-Olive FX , Tollman S , Martinson NA , Wafawanaka F , Lebina L , du Toit J , Jassat W , Neti M , Brauer M , Cohen C , Kgasago KP , de Gouveia L , Carrim M , du Plessis M , Kotane R , Moloantoa T . medRxiv 2022 15 By November 2021, after the third SARS-CoV-2 wave in South Africa, seroprevalence was 60% (95%CrI 56%-64%) in a rural and 70% (95%CrI 56%-64%) in an urban community; highest in individuals aged 13-18 years. High seroprevalence prior to Omicron emergence may have contributed to reduced severity observed in the 4th wave. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
SARS-CoV-2 virus dynamics in recently infected people - data from a household transmission study (preprint)
Mellis AM , Meece JK , Halasa NB , Chappell JD , McLean HQ , Grijalva CG , Hanson KE , Zhu Y , Kim A , Deyoe J , Ivacic LC , Reed C , Talbot HK , Rolfes MA . medRxiv 2022 18 (10) 1699-1703 We used daily real-time reverse-transcription polymerase chain reaction (rRT-PCR) results from 67 cases of SARS-CoV-2 infection in a household transmission study to examine the trajectory of cycle threshold (Ct) values, an inverse correlate of viral RNA concentration, from nasal specimens collected between April 2020 and May 2021. Ct values varied over the course of infection, across RT-PCR platforms, and by participant age. Specimens collected from children and adolescents showed higher Ct values and adults aged >=50 years showed lower Ct values than adults aged 18-49 years. Ct values were lower on days when participants reported experiencing symptoms. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Seasonality of Common Human Coronaviruses in the United States, 2014-2021 (preprint)
Shah MM , Winn A , Dahl RM , Kniss KL , Silk BJ , Killerby ME . medRxiv 2022 22 (10) 1970-1976 The four common human coronaviruses (HCoVs), including two alpha (HCoV-NL63 and HCoV-229E) and two beta (HCoV-HKU1 and HCoV-OC43) types, generally cause mild, upper respiratory illness. HCoVs are known to have seasonal patterns and variation in predominant types each year, but defined measures of seasonality are needed. We defined seasonality of HCoVs during July 2014 to November 2021 in the United States using a retrospective method applied to National Respiratory and Enteric Virus Surveillance System (NREVSS) data. In the six HCoV seasons prior to 2020-2021, onsets ranged from October to November, peaks from January to February, and offsets from April to June; most (>93%) HCoV detections occurred within the defined seasonal onsets and offsets. The 2020-2021 HCoV season onset was delayed by 11 weeks compared to prior seasons, likely due to COVID-19 mitigation efforts. Better defining HCoV seasonality can inform clinical preparedness and the expected patterns of emerging HCoVs. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Serial interval and incubation period estimates of monkeypox virus infection in 12 U.S. jurisdictions, May - August 2022 (preprint)
Madewell ZJ , Charniga K , Masters NB , Asher J , Fahrenwald L , Still W , Chen J , Kipperman N , Bui D , Shea M , Saathoff-Huber L , Johnson S , Harbi K , Berns AL , Perez T , Gateley E , Spicknall IH , Nakazawa Y , Gift TL . medRxiv 2022 30 Using data collected by 12 U.S. health departments, we report mean estimated serial interval for monkeypox virus infection of 8.5 (95% CrI: 7.3 - 9.9) days for symptom onset from 57 case pairs and mean estimated incubation period of 5.6 (4.3 - 7.8) days from 35 case pairs for symptom onset. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Strengthening Health System's Capacity for Linkage to HIV Care for adolescent girls and young women and adolescent boys and young men in South Africa (SheS'CapLinkage): Protocol for a mixed methods study in KwaZulu-Natal, South Africa (preprint)
Nicol E , Basera W , Lombard C , Jonas K , Ramraj T , Govindasamy D , Hlongwa M , McClinton-Appollis T , Mehlomakulu V , Naqvi N , Bedford J , Drummond J , Cheyip M , Dladla S , Pass D , Funani N , Mathews C . medRxiv 2022 12 Introduction In South Africa, HIV prevalence among adolescent girls and young women (AGYW) was 5.8% (15-19 years) and 15.6% (20-24 years) respectively in 2017. Amongst South African males, HIV prevalence in 2017 was 4.7% (15-19 years), 4.8% (20-24 years), 12.4% (25-29 years) and 18.4% (30-34 years). The National Department of Health adopted the universal test and treat (UTT) strategy in 2016, resulting in increases in same-day antiretroviral therapy initiations and linkage to care. Monitoring progress towards attainment of South Africa's 95-95-95 targets amongst AGYW and adolescent boys and young men (ABYM) relies on high quality data to identify and address gaps in linkage to care. The purpose of this study is to provide evidence to guide efforts to improve linkage to, and retention in, HIV care among AGYW and ABYM in KwaZulu-Natal, in the context of the UTT strategy. Methods and analysis This is a mixed methods study, which will be conducted in uMgungundlovu district of KwaZulu-Natal, over a 24-month period, in 22 purposively selected HIV testing and treatment service delivery points (SDPs). For the quantitative component, a sample size of 1100 participants will be recruited into the study. The qualitative component will include 30 participating patients who were successfully linked to care, 30 who were not, and 30 who have never tested for HIV. The questionnaire study population comprises of 231 healthcare providers and AGYW aged 15-24 years and ABYM aged 15-35 years old. Primary outcomes will be evaluated using a logistic regression model. A time to event analysis will also be conducted taking the study design into account. Quantitative data for outcome variables and process indicators will be summarized by domain evaluated with logistic regression to account for potential confounders. For qualitative data, manual thematic content analysis will be conducted. Ethics and dissemination The protocol was approved by the South African Medical Research Council Health Research Ethics Committee (EC052-11/2020). Findings from the study will be communicated to the study population and results will be presented to stakeholders and at appropriate local and international conferences. Outputs will also include a policy brief, peer reviewed journal articles and research capacity building through research degrees. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Systematic Review and Meta-Analysis of the Efficacy and Effectiveness of Pneumococcal Vaccines in Adults (preprint)
Farrar JL , Childs L , Ouattara M , Akhter F , Britton A , Pilishvili T , Kobayashi M . medRxiv 2022 07 The 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent pneumococcal polysaccharide vaccine (PPSV23) were previously recommended for adults in the United States. To help inform discussions on recently licensed 15- and 20-valent pneumococcal vaccine use among adults, we conducted a systematic review of PCV13 and PPSV23 efficacy or effectiveness. We conducted a search on PCV13 and PPSV23 efficacy or effectiveness (VE) studies against vaccine type (VT) invasive pneumococcal disease (IPD) and VT-pneumococcal pneumonia in adults. Nineteen studies were included: 13 on VT-IPD (four on PCV13, nine on PPSV23) and eight on VT- pneumococcal pneumonia (three on PCV13, four on PPSV23, one on PCV13 and PPSV23). One randomized-controlled trial (RCT) evaluated PCV13 and observed an efficacy of 75% and 45% against VT-IPD and VT-pneumococcal pneumonia, respectively. No RCTs reported PPSV23 efficacy. PCV13 effectiveness estimates against VTIPD ranged from 47% to 68%. Pooled PPSV23 effectiveness against VT-IPD was 45% (95% CI: 37%, 51%; I2=0%). PCV13 VE estimates against VT-pneumonia ranged from -2 to 46%. Pooled PPSV23 VE against VT-pneumococcal pneumonia was 18% (95% CI: -4%, 35%; I2=0%). Evidence suggests PCV13 and PPSV23 are effective against VT-IPD and VT-pneumococcal pneumonia in adults; this was used to inform PCV15 and PCV20 policy decisions. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Persistence of SARS-CoV-2 immunity, Omicron's footprints, and projections of epidemic resurgences in South African population cohorts (preprint)
Sun K , Tempia S , Kleynhans J , von Gottberg A , McMorrow ML , Wolter N , Bhiman JN , Moyes J , du Plessis M , Carrim M , Buys A , Martinson NA , Kahn K , Tollman S , Lebina L , Wafawanaka F , du Toit JD , Gomez-Olive FX , Mkhencele T , Viboud C , Cohen C . medRxiv 2022 13 Understanding the build-up of immunity with successive SARS-CoV-2 variants and the epidemiological conditions that favor rapidly expanding epidemics will facilitate future pandemic control. High-resolution infection and serology data from longitudinal household cohorts in South Africa reveal high cumulative infection rates and durable cross-protective immunity conferred by prior infection in the pre-Omicron era. Building on the cohort's history of past exposures to different SARS-CoV-2 variants and vaccination, we use mathematical models to explore the fitness advantage of the Omicron variant and its epidemic trajectory. Modelling suggests the Omicron wave infected a large fraction of the population, leaving a complex landscape of population immunity primed and boosted with antigenically distinct variants. Future SARS-CoV-2 resurgences are likely under a range of scenarios of viral characteristics, population contacts, and residual cross-protection. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Presence of Symptoms 6 Weeks After COVID-19 Among Vaccinated and Unvaccinated U.S. Healthcare Personnel (preprint)
Mohr NM , Plumb ID , Harland KK , Pilishvili T , Fleming-Dutra KE , Krishnadasan A , Hoth KF , Saydah SH , Mankoff Z , Haran JP , Leon ES , Talan DA , Smithline HA , Hou PC , Lee LC , Lim SC , Moran GJ , Steele MT , Beiser DG , Faine B , Nandi U , Schrading WA , Chinnock B , Chipman A , Fuentes M , LoVecchio F , Clinansmith B , Landers S , Horcher A , Wallace K , Uribe L , Pathmarajah K , Poronsky KE , Hashimoto DM , Bahamon M , Romain MSt , Kean E , Krebs E , Stubbs A , Roy S , Volturo G , Higgins A , Galbraith J , Crosby JC , Mulrow M , Gonzalez E , Gierke R , Farrar JL , Xing W , Chung Y , Yousaf A , Okaro JO , Briggs-Hagen M , Abedi GR , Nyanseor S , Watts CK . medRxiv 2022 25 Importance: Although COVID-19 vaccines protect against infection and severe disease, the role of vaccination in preventing prolonged symptoms in those with subsequent infection is unclear. Objective(s): To determine differences in symptoms stratified by prior vaccination reported by healthcare personnel (HCP) 6 weeks after onset of COVID-19, and whether there were differences in timing of return to work. Design(s): Nested cohort study within a multicenter vaccine effectiveness study. HCP with COVID-19 between December 2020 and August 2021 were followed up 6 weeks after illness onset. Setting(s): Health systems in 12 U.S. states. Participant(s): HCP participating in a vaccine effectiveness study were eligible for inclusion if they had confirmed COVID-19 with either verified mRNA vaccination (symptom onset =14 days after two doses) or no prior COVID-19 vaccination. Among 681 eligible participants, 419 (61%) completed a follow-up survey approximately 6 weeks after illness onset. Exposures: Two doses of a COVID-19 mRNA vaccine compared with no COVID-19 vaccine. Main Outcomes and Measures: Presence of symptoms 6 weeks after onset of COVID-19 illness and days to return to work after COVID-19 illness. Result(s): Among 419 HCP with confirmed COVID-19, 298 (71%) reported one or more COVID-like symptoms 6 weeks after illness onset, with a lower prevalence among vaccinated participants (60.6%) compared with unvaccinated participants (60.6% vs. 79.1%; aRR 0.70, 95% CI 0.58-0.84). Vaccinated HCP returned to work a median 2.0 days (95% CI 1.0-3.0) sooner than unvaccinated HCP (aHR 1.37; 95% CI, 1.04-1.79). Conclusion(s): A history of two doses of COVID-19 mRNA vaccine among HCP with COVID-19 illness was associated with decreased risk of COVID-like symptoms at 6 weeks and earlier to return to work. Vaccination is associated with improved recovery from COVID-19, in addition to preventing symptomatic infection. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Genomic surveillance of SARS-CoV-2 in Puerto Rico reveals emergence of an autochthonous lineage and early detection of variants (preprint)
Santiago GA , Flores B , Gonzalez GL , Charriez KN , Cora-Huertas L , Volkman HR , Van Belleghem S , Rivera-Amill V , Adams LE , Marzan M , Hernandez L , Cardona I , O'Neill E , Paz-Bailey G , Papa R , Munoz-Jordan JL . Res Sq 2022 Puerto Rico has experienced the full impact of the COVID-19 pandemic. Since SARS-CoV-2, the virus that causes COVID-19, was first detected on the island in March of 2020, it spread rapidly though the island’s population and became a critical threat to public health. We conducted a genomic surveillance study through a partnership with health agencies and academic institutions to understand the emergence and molecular epidemiology of the virus on the island. We sampled COVID-19 cases monthly over 19 months and sequenced a total of 753 SARS-CoV-2 genomes between March 2020 and September 2021 to reconstruct the local epidemic in a regional context using phylogenetic inference. Our analyses revealed that multiple importation events propelled the emergence and spread of the virus throughout the study period, including the introduction and spread of most SARS-CoV-2 variants detected world-wide. Lineage turnover cycles through various phases of the local epidemic were observed, where the predominant lineage was replaced by the next competing lineage or variant after approximately 4 months of circulation locally. We also identified the emergence of lineage B.1.588, an autochthonous lineage that predominated circulation in Puerto Rico from September to December 2020 and subsequently spread to the United States. The results of this collaborative approach highlight the importance of timely collection and analysis of SARS-CoV-2 genomic surveillance data to inform public health responses. |
Gestational SARS-CoV-2 infection is associated with placental expression of immune and trophoblast genes (preprint)
Lesseur C , Jessel RH , Ohrn S , Ma Y , Li Q , Dekio F , Brody RI , Wetmur JG , Gigase FAJ , Lieber M , Lieb W , Lynch J , Afzal O , Ibroci E , Rommel AS , Janevic T , Stone J , Howell EA , Galang RR , Dolan SM , Bergink V , De Witte LD , Chen J . medRxiv 2022 24 Introduction: Maternal SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes and can have effects on the placenta, even in the absence of severe disease or vertical transmission to the fetus. This study aimed to evaluate histopathologic and molecular effects in the placenta after SARS-CoV-2 infection during pregnancy. Method(s): We performed a study of 45 pregnant participants from the Generation C prospective cohort study at the Mount Sinai Health System in New York City. We compared histologic features and the expression of 48 immune and trophoblast genes in placentas delivered from 15 SARS-CoV-2 IgG antibody positive and 30 IgG SARS-CoV-2 antibody negative mothers. Statistical analyses were performed using Fisher's exact tests, Spearman correlations and linear regression models. Result(s): The median gestational age at the time of SARS-CoV-2 IgG serology test was 35 weeks. Two of the IgG positive participants also had a positive RT-PCR nasal swab at delivery. 82.2% of the infants were delivered at term (>=37 weeks), and gestational age at delivery did not differ between the SARSCoV-2 antibody positive and negative groups. No significant differences were detected between the groups in placental histopathology features. Differential expression analyses revealed decreased expression of two trophoblast genes (PSG3 and CGB3) and increased expression of three immune genes (CXCL10, TLR3 and DDX58) in placentas delivered from SARS-CoV-2 IgG positive participants. Discussion(s): SARS-CoV-2 infection during pregnancy is associated with gene expression changes of immune and trophoblast genes in the placenta at birth which could potentially contribute to long-term health effects in the offspring. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Hepatitis C care cascade among patients with and without tuberculosis: findings from nationwide programs in the country of Georgia, 2015-2020 (preprint)
Baliashvili D , Blumberg HM , Gandhi NR , Averhoff F , Benkeser D , Shadaker S , Gvinjilia L , Turdziladze A , Tukvadze N , Chincharauli M , Butsashvili M , Sharvadze L , Tsertsvadze T , Zarkua J , Kempker RR . medRxiv 2022 13 Background: The Eastern European country of Georgia initiated a nationwide hepatitis C virus (HCV) elimination program in 2015 to address a high burden of infection. Screening for HCV infection through antibody testing was integrated into multiple existing programs, including the National Tuberculosis Program (NTP). We sought to evaluate loss to follow-up (LTFU) from the hepatitis C care cascade among persons diagnosed with active tuberculosis (TB) disease. Method(s): Using national ID numbers, we merged databases of the HCV elimination program, NTP, and national death registry from January 1, 2015, to September 30, 2020. We estimated the proportion of patients with and without TB who were LTFU at each step of the HCV care cascade and explored temporal changes. Result(s): Among 11,985 patients with active TB, 9,065 (76%) were tested for HCV antibodies, and 1,665 (18%) had a positive result; LTFU from hepatitis C care was common, with 20% of patients with a positive antibody test not undergoing viremia testing, and 43% of patients with viremia not starting treatment for hepatitis C. Overall, among persons with confirmed viremic HCV infection, only 28% of patients with TB had a documented cure from HCV infection, compared to 55% among patients without TB. LTFU after positive antibody testing substantially decreased in the last three years, from 32% among patients diagnosed with TB in 2017 to 12% among those diagnosed in 2019. Conclusion(s): LTFU from hepatitis C care after a positive antibody or viremia test was high and more common among patients with TB than in those without TB. Better integration of TB and hepatitis C care systems can potentially reduce LTFU and improve patient outcomes. Existing large-scale programs for both TB and hepatitis C in Georgia create a unique opportunity for such integration to contribute to hepatitis C elimination efforts. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Incidence Rates of Medically Attended COVID-19 in Infants Less than 6 Months of Age (preprint)
Griffin I , Irving SA , Arriola CS , Campbell AP , Li DK , Dawood FS , Doughty-Skierski C , Ferber JR , Ferguson N , Hadden L , Henderson JT , Juergens M , Kancharla V , Naleway AL , Newes-Adeyi G , Nicholson E , Odouli R , Reichle L , Sanyang M , Woodworth K , Munoz FM . medRxiv 2022 30 Objective Studies suggest infants may be at increased risk of severe COVID-19 relative to older children, but few data exist regarding the incidence of COVID-19 episodes and associated risk factors. We estimate incidence rates and describe characteristics associated with medically attended COVID-19 episodes among infants younger than 6 months of age. Methods We analyzed electronic medical record data from a cohort of infants born March 1, 2020-February 28, 2021. Data from three health care delivery systems included demographic characteristics, maternal and infant outpatient visit and hospitalization diagnoses, and SARSCoV-2 test results. Medically attended COVID-19 episodes were defined by positive SARSCoV-2 clinical tests and/or COVID-19 diagnosis codes during medical care visits. Unadjusted and site-adjusted incidence rates by infant month of age, low and high SARS-CoV-2 circulation periods and maternal COVID-19 diagnosis were calculated. Results Among 18,192 infants aged <6 months whose mothers received prenatal care within the three systems, 173 (1.0%) had medically attended COVID-19 episodes. Incidence rates were highest among infants aged under 1 month (2.0 per 1,000 person-weeks) and 1 month (2.0 per 1,000 person-weeks) compared with older infants. Incidence rates were also higher for infants born to women with postpartum COVID-19 compared with women without known COVID-19 and women diagnosed with COVID-19 during pregnancy. Conclusion Most medically attended COVID-19 episodes in infants aged <6 months were outpatient care encounters. Infants of women with postpartum COVID-19 had a higher risk of medically attended COVID-19 than infants born to mothers who were diagnosed during pregnancy or never diagnosed underscoring the importance of COVID-19 prevention measures for their household members and caregivers to prevent infections in infants. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Reduced Odds of SARS-CoV-2 Reinfection after Vaccination among New York City Adults, June-August 2021 (preprint)
Levin-Rector A , Firestein L , McGibbon E , Sell J , Lim S , Lee EH , Weiss D , Geevarughese A , Zucker JR , Greene SK . medRxiv 2021 11 Background Belief in immunity from prior infection and concern that vaccines might not protect against new variants are contributors to vaccine hesitancy. We assessed effectiveness of full and partial COVID-19 vaccination against reinfection when Delta was the predominant variant in New York City. Methods We conducted a case-control study in which case-patients with reinfection during June 15-August 31, 2021 and control subjects with no reinfection were matched (1:3) on age, sex, timing of initial positive test in 2020, and neighborhood poverty level. Conditional logistic regression was used to calculate matched odds ratios (mOR) and 95% confidence intervals (CI). Results Of 349,598 adult residents who tested positive for SARS-CoV-2 infection in 2020, did not test positive again >90 days after initial positive test through June 15, 2021, and did not die before June 15, 2021, 1,067 were reinfected during June 15-August 31, 2021. Of 1,048 with complete matching criteria data, 499 (47.6%) were known to be symptomatic for COVID-19-like-illness, and 75 (7.2%) were hospitalized. Unvaccinated individuals, compared with fully vaccinated individuals, had elevated odds of reinfection (mOR, 2.23; 95% CI, 1.90, 2.61), of symptomatic reinfection (mOR, 2.17; 95% CI, 1.72, 2.74), and of reinfection with hospitalization (mOR, 2.59; 95% CI, 1.43, 4.69). Partially versus fully vaccinated individuals had 1.58 (95% CI: 1.22, 2.06) times the odds of reinfection. All three vaccines authorized or approved for use in the U.S. were similarly effective. Conclusion Among adults with previous SARS-CoV-2 infection, vaccination reduced odds of reinfections when the Delta variant predominated. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
SARS-CoV-2 antibody prevalence in Sierra Leone, March 2021: a cross-sectional, nationally representative, age-stratified serosurvey (preprint)
Barrie MB , Lakoh S , Kelly JD , Kanu JS , Squire J , Koroma Z , Bah S , Sankoh O , Brima A , Ansumana R , Goldberg SA , Chitre S , Osuagwu C , Maeda J , Barekye B , Numbere TW , Abdulaziz M , Mounts A , Blanton C , Singh T , Samai M , Vandi MA , Richardson ET . medRxiv 2021 Background As of 26 March 2021, the Africa CDC had reported 4,159,055 cases of COVID-19 and 111,357 deaths among the 55 African Union Member States; however, no country has published a nationally representative serosurvey as of May 2021. Such data are vital for understanding the pandemic's progression on the continent, evaluating containment measures, and policy planning. Methods We conducted a cross-sectional, nationally representative, age-stratified serosurvey in Sierra Leone in March 2021 by randomly selecting 120 Enumeration Areas throughout the country and 10 randomly selected households in each of these. One to two persons per selected household were interviewed to collect information on socio-demographics, symptoms suggestive of COVID-19, exposure history to laboratory-confirmed COVID-19 cases, and history of COVID-19 illness. Capillary blood was collected by fingerstick, and blood samples were tested using the Hangzhou Biotest Biotech RightSign COVID-19 IgG/IgM Rapid Test Cassette. Total seroprevalence was was estimated after applying sampling weights. Findings The overall weighted seroprevalence was 2.6% (95% CI 1.9-3.4). This is 43 times higher than the reported number of cases. Rural seropositivity was 1.8% (95% CI 1.0-2.5), and urban seropositivity was 4.2% (95% CI 2.6-5.7). Interpretation Although overall seroprevalence was low compared to countries in Europe and the Americas (suggesting relatively successful containment in Sierra Leone), our findings indicate enormous underreporting of active cases. This has ramifications for the country's third wave (which started in June 2021), where the average number of daily reported cases was 87 by the end of the month: this could potentially be on the order of 3,700 actual infections, calling for stronger containment measures in a country with only 0.2% of people fully vaccinated. It may also reflect significant underreporting of incidence and mortality across the continent. |
SARS-CoV-2 transmission in intercollegiate athletics not fully mitigated with daily antigen testing (preprint)
Moreno GK , Braun KM , Pray IW , Segaloff HE , Lim A , Poulson K , Meiman J , Borcher J , Westergaard RP , Moll MK , Friedrich TC , O'Connor DH . medRxiv 2021 BACKGROUND: High frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester despite mandatory directly observed daily antigen testing. METHODS: During the fall 2020 semester, athletes and staff in both programs were tested daily using Quidel's Sofia SARS Antigen Fluorescent Immunoassay (FIA), with positive antigen results requiring confirmatory testing with real-time reverse transcription polymerase chain reaction (RT-PCR). We used genomic sequencing to investigate transmission dynamics in these two outbreaks. RESULTS: In Outbreak 1, 32 confirmed cases occurred within a university athletics program after the index patient attended a meeting while infectious despite a negative antigen test on the day of the meeting. Among isolates sequenced from Outbreak 1, 24 (92%) of 26 were closely related, suggesting sustained transmission following an initial introduction event. In Outbreak 2, 12 confirmed cases occurred among athletes from two university programs that faced each other in an athletic competition despite receiving negative antigen test results on the day of the competition. Sequences from both teams were closely related and unique from strains circulating in the community, suggesting transmission during intercollegiate competition. CONCLUSIONS: These findings suggest that antigen testing alone, even when mandated and directly observed, may not be sufficient as an intervention to prevent SARS-CoV-2 outbreaks in congregate settings, and highlights the importance of supplementing serial antigen testing with appropriate mitigation strategies to prevent SARS-CoV-2 outbreak in congregate settings. SUMMARY: High frequency, rapid turnaround SARS-CoV-2 testing continues to be proposed as a way of efficiently identifying and mitigating transmission in congregate settings. However, here we describe two SARS-CoV-2 outbreaks occurred among intercollegiate university athletic programs during the fall 2020 semester. |
Surveillance and correlation of SARS-CoV-2 viral RNA, antigen, virus isolation, and self-reported symptoms in a longitudinal study with daily sampling (preprint)
Bonenfant G , Deyoe J , Wong T , Grijalva CG , Cui D , Talbot HK , Hassell N , Halasa N , Chappell J , Thornburg NJ , Rolfes MA , Wentworth D , Zhou B . medRxiv 2021 23 The novel coronavirus pandemic incited unprecedented demand for assays that detect viral nucleic acids, viral proteins, and corresponding antibodies. The 320 molecular diagnostics in receipt of FDA emergency use authorization mainly focus on viral detection; however, no currently approved test can be used to infer infectiousness, i.e., the presence of replicable virus. As the number of tests conducted increased, persistent SARS-CoV-2 RNA positivity by RT-PCR in some individuals led to concerns over quarantine guidelines. To this end, we attempted to design an assay that reduces the frequency of positive test results from individuals who do not shed culturable virus. We describe multiplex quantitative RT-PCR (qRT-PCR) assays that detect genomic RNA (gRNA) and subgenomic RNA (sgRNA) species of SARS-CoV-2, including spike (S), nucleocapsid (N), membrane (M), envelope (E), and ORF8. The absolute copy number of each RNA target was determined in longitudinal specimens from a household transmission study. Calculated viral RNA levels over the 14-day follow up period were compared with antigen testing and self-reported symptoms to characterize the clinical and molecular dynamics of infection and infer predictive values of these qRT-PCR assays relative to culture isolation. When detection of sgS RNA was added to the CDC 2019-Novel Coronavirus Real-Time RT-PCR Diagnostic Panel, we found a qRT-PCR positive result was 98% predictive of a positive culture (negative predictive value was 94%). Our findings suggest sgRNA presence correlates with active infection, may help identify individuals shedding culturable virus, and that similar multiplex assays can be adapted to current and future variants. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Mathematical modeling to inform vaccination strategies and testing approaches for COVID-19 in nursing homes (preprint)
Kahn R , Holmdahl I , Reddy S , Jernigan J , Mina MJ , Slayton RB . medRxiv 2021 BACKGROUND: Nursing home residents and staff were included in the first phase of COVID-19 vaccination in the United States. Because the primary trial endpoint was vaccine efficacy (VE) against symptomatic disease, there are limited data on the extent to which vaccines protect against SARS-CoV-2 infection and the ability to infect others (infectiousness). Assumptions about VE against infection and infectiousness have implications for possible changes to infection prevention guidance for vaccinated populations, including testing strategies. METHODS: We use a stochastic agent-based SEIR model of a nursing home to simulate SARS-CoV-2 transmission. We model three scenarios, varying VE against infection, infectiousness, and symptoms, to understand the expected impact of vaccination in nursing homes, increasing staff vaccination coverage, and different screening testing strategies under each scenario. RESULTS: Increasing vaccination coverage in staff decreases total symptomatic cases in each scenario. When there is low VE against infection and infectiousness, increasing staff coverage reduces symptomatic cases among residents. If vaccination only protects against symptoms, but asymptomatic cases remain infectious, increased staff coverage increases symptomatic cases among residents through exposure to asymptomatic but infected staff. High frequency testing is needed to reduce total symptomatic cases if the vaccine has low efficacy against infection and infectiousness, or only protects against symptoms. CONCLUSIONS: Encouraging staff vaccination is not only important for protecting staff, but might also reduce symptomatic cases in residents if a vaccine confers at least some protection against infection or infectiousness. SUMMARY: The extent of efficacy of SARS-CoV-2 vaccines against infection, infectiousness, or disease, impacts strategies for vaccination and testing in nursing homes. If vaccines confer some protection against infection or infectiousness, encouraging vaccination in staff may reduce symptomatic cases in residents. |
Novel regimens of bedaquiline-pyrazinamide combined with moxifloxacin, rifabutin, delamanid and/or OPC-167832 in murine tuberculosis models (preprint)
Tasneen R , Garcia A , Converse PJ , Zimmerman MD , Dartois V , Kurbatova E , Vernon AA , Carr W , Stout JE , Dooley KE , Nuermberger EL . bioRxiv 2021 23 A recent landmark trial showed a 4-month regimen of rifapentine, pyrazinamide, moxifloxacin and isoniazid (PZMH) to be non-inferior to the 6-month standard of care. Here, two murine models of tuberculosis were used to test whether novel regimens replacing rifapentine and isoniazid with bedaquiline and another drug would maintain or increase the sterilizing activity of the regimen. In BALB/c mice, replacing rifapentine in the PZM backbone with bedaquiline (i.e., BZM) significantly reduced both lung CFU counts after 1 month and the proportion of mice relapsing within 3 months after completing 1.5 months of treatment. Addition of rifabutin to BZM (BZMRb) further increased the sterilizing activity. In the C3HeB/FeJ mouse model characterized by caseating lung lesions, treatment with BZMRb resulted in significantly fewer relapses than PZMH after 2 months of treatment. A regimen combining the new DprE1 inhibitor OPC-167832 and delamanid (BZOD) also had superior bactericidal and sterilizing activity compared to PZM in BALB/c mice and was similar in efficacy to PZMH in C3HeB/FeJ mice. Thus, BZM represents a promising backbone for treatment-shortening regimens. Given the prohibitive drug-drug interactions between bedaquiline and rifampin or rifapentine, the BZMRb regimen represents the best opportunity to combine, in one regimen, the treatment-shortening potential of the rifamycin class with that of BZM and deserves high priority for evaluation in clinical trials. Other 4-drug BZM-based regimens and BZOD represent promising opportunities for extending the spectrum of treatment-shortening regimens to rifamycin- and fluoroquinolone-resistant tuberculosis. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. |
Early introductions and community transmission of SARS-CoV-2 variant B.1.1.7 in the United States (preprint)
Alpert T , Brito AF , Lasek-Nesselquist E , Rothman J , Valesano AL , MacKay MJ , Petrone ME , Breban MI , Watkins AE , Vogels CBF , Kalinich CC , Dellicour S , Russell A , Kelly JP , Shudt M , Plitnick J , Schneider E , Fitzsimmons WJ , Khullar G , Metti J , Dudley JT , Nash M , Beaubier N , Wang J , Liu C , Hui P , Muyombwe A , Downing R , Razeq J , Bart SM , Grills A , Morrison SM , Murphy S , Neal C , Laszlo E , Rennert H , Cushing M , Westblade L , Velu P , Craney A , Fauntleroy KA , Peaper DR , Landry ML , Cook PW , Fauver JR , Mason CE , Lauring AS , George KS , MacCannell DR , Grubaugh ND . medRxiv 2021 The emergence and spread of SARS-CoV-2 lineage B.1.1.7, first detected in the United Kingdom, has become a global public health concern because of its increased transmissibility. Over 2500 COVID-19 cases associated with this variant have been detected in the US since December 2020, but the extent of establishment is relatively unknown. Using travel, genomic, and diagnostic data, we highlight the primary ports of entry for B.1.1.7 in the US and locations of possible underreporting of B.1.1.7 cases. Furthermore, we found evidence for many independent B.1.1.7 establishments starting in early December 2020, followed by interstate spread by the end of the month. Finally, we project that B.1.1.7 will be the dominant lineage in many states by mid to late March. Thus, genomic surveillance for B.1.1.7 and other variants urgently needs to be enhanced to better inform the public health response. |
Geographic and demographic heterogeneity of SARS-CoV-2 diagnostic testing in Illinois, USA, March to December 2020 (preprint)
Holden TM , Richardson RAK , Arevalo P , Duffus WA , Runge M , Whitney E , Wise L , Ezike NO , Patrick S , Cobey S , Gerardin J . medRxiv 2021 BACKGROUND: Availability of SARS-CoV-2 testing in the United States (U.S.) has fluctuated through the course of the COVID-19 pandemic, including in the U.S. state of Illinois. Despite substantial ramp-up in test volume, access to SARS-CoV-2 testing remains limited, heterogeneous, and insufficient to control spread. METHODS: We compared SARS-CoV-2 testing rates across geographic regions, over time, and by demographic characteristics (i.e., age and racial/ethnic groups) in Illinois during March through December 2020. We compared age-matched case fatality ratios and infection fatality ratios through time to estimate the fraction of SARS-CoV-2 infections that have been detected through diagnostic testing. RESULTS: By the end of 2020, initial geographic differences in testing rates had closed substantially. Case fatality ratios were higher in non-Hispanic Black and Hispanic/Latino populations in Illinois relative to non-Hispanic White populations, suggesting that tests were insufficient to accurately capture the true burden of COVID-19 disease in the minority populations during the initial epidemic wave. While testing disparities decreased during 2020, Hispanic/Latino populations consistently remained the least tested at 1.87 tests per 1000 population per day compared with 2.58 and 2.87 for non-Hispanic Black and non-Hispanic White populations, respectively, at the end of 2020. Despite a large expansion in testing since the beginning of the first wave of the epidemic, we estimated that over half (50-80%) of all SARS-CoV-2 infections were not detected by diagnostic testing and continued to evade surveillance. CONCLUSIONS: Systematic methods for identifying relatively under-tested geographic regions and demographic groups may enable policymakers to regularly monitor and evaluate the shifting landscape of diagnostic testing, allowing officials to prioritize allocation of testing resources to reduce disparities in COVID-19 burden and eventually reduce SARS-CoV-2 transmission. |
Household Transmission and Clinical Features of SARS-CoV-2 Infections by Age in 2 US Communities (preprint)
McLean HQ , Grijalva CG , Hanson KE , Zhu YG , Deyoe JE , Meece JK , Halasa NB , Chappell JD , Mellis A , Reed C , Belongia EA , Talbot HK , Rolfes MA . medRxiv 2021 OBJECTIVES: Examine age differences in SARS-CoV-2 transmission risk from primary cases and infection risk among household contacts, and symptoms among those with SARS-CoV-2 infection. METHODS: People with SARS-CoV-2 infection in Nashville, Tennessee and central and western Wisconsin and their household contacts were followed daily for 14 days to ascertain symptoms and secondary transmission events. Households were enrolled between April 2020 and April 2021. Secondary infection risks (SIR) by age of the primary case and contacts were estimated using generalized estimating equations. RESULTS: The 226 primary cases were followed by 198 (49%) secondary SARS-CoV-2 infections among 404 household contacts. Age group-specific SIR among contacts ranged from 36% to 53%, with no differences by age. SIR was lower from primary cases aged 12-17 years than from primary cases 18-49 years (risk ratio [RR] 0.42; 95% confidence interval [CI] 0.19-0.91). SIR was 55% and 45%, respectively, among primary case-contact pairs in the same versus different age group (RR 1.47; 95% CI 0.98-2.22). SIR was highest among primary case-contacts pairs aged ≥65 years (76%) and 5-11 years (69%). Among secondary SARS-CoV-2 infections, 19% were asymptomatic; there was no difference in the frequency of asymptomatic infections by age group. CONCLUSIONS: Both children and adults can transmit and are susceptible to SARS-CoV-2 infection. SIR did not vary by age, but further research is needed to understand age-related differences in probability of transmission from primary cases by age. |
Binding and Neutralizing Antibody Responses to SARS-CoV-2 in Infants and Young Children Exceed Those in Adults (preprint)
Karron RA , Quesada MG , Schappell EA , Schmidt SD , Knoll MD , Hetrich MK , Veguilla V , Doria-Rose N , Dawood FS , Black W , Council-DiBitetto C , Ghasri T , Gormley A , Gatto M , Jordan M , Loehr K , Morsell J , Oliva J , Mateo JS , Smith K , Wanionek K , Weadon C , Woods S . medRxiv 2021 21 SARS-CoV-2 infections are frequently milder in children than adults, suggesting that immune responses may vary with age. However, information is limited regarding SARS-CoV-2 immune responses in young children. We compared Receptor Binding Domain binding antibody (RBDAb) and SARS-CoV-2 neutralizing antibody (neutAb) in children aged 0-4 years, 5-17 years, and in adults aged 18-62 years in a SARS-CoV-2 household study. Among 55 participants seropositive at enrollment, children aged 0-4 years had >10-fold higher RBDAb titers than adults (373 vs.35, P<0.0001), and the highest RBDAb titers in 11/12 households with seropositive children and adults. Children aged 0-4 years had 2-fold higher neutAb than adults, resulting in higher binding to neutralizing (B/N)Ab ratios compared to adults (1.9 vs. 0.4 for ID<inf>50</inf>, P=0.0002). Findings suggest that young children mount robust antibody responses to SARS-CoV-2 following community infections. Additionally, these results support using neutAb to measure the immunogenicity of COVID-19 vaccines in children aged 0-4 years. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines (preprint)
Wang L , Kainulainen MH , Jiang N , Di H , Bonenfant G , Mills L , Currier M , Shrivastava-Ranjan P , Calderon BM , Sheth M , Hossain J , Lin X , Lester S , Pusch E , Jones J , Cui D , Chatterjee P , Jenks HM , Morantz E , Larson G , Hatta M , Harcourt J , Tamin A , Li Y , Tao Y , Zhao K , Burroughs A , Wong T , Tong S , Barnes JR , Tenforde MW , Self WH , Shapiro NI , Exline MC , Files DC , Gibbs KW , Hager DN , Patel M , Laufer Halpin AS , Lee JS , Xie X , Shi PY , Davis CT , Spiropoulou CF , Thornburg NJ , Oberste MS , Dugan V , Wentworth DE , Zhou B , Batra D , Beck A , Caravas J , Cintron-Moret R , Cook PW , Gerhart J , Gulvik C , Hassell N , Howard D , Knipe K , Kondor RJ , Kovacs N , Lacek K , Mann BR , McMullan LK , Moser K , Paden CR , Martin BR , Schmerer M , Shepard S , Stanton R , Stark T , Sula E , Tymeckia K , Unoarumhi Y . bioRxiv 2021 30 The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of many new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccines. To ascertain and rank the risk of VOCs and VOIs, we analyzed their ability to escape from vaccine-induced antibodies. The variants showed differential reductions in neutralization and replication titers by post-vaccination sera. Although the Omicron variant showed the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retained moderate neutralizing activity against that variant. Therefore, vaccination remains the most effective strategy to combat the COVID-19 pandemic. |
Natural SARS-CoV-2 infections, including virus isolation, among serially tested cats and dogs in households with confirmed human COVID-19 cases in Texas, USA (preprint)
Hamer SA , Pauvolid-Corrêa A , Zecca IB , Davila E , Auckland LD , Roundy CM , Tang W , Torchetti M , Killian ML , Jenkins-Moore M , Mozingo K , Akpalu Y , Ghai RR , Spengler JR , Behravesh CB , Fischer RSB , Hamer GL . bioRxiv 2020 The natural infections and epidemiological roles of household pets in SARS-CoV-2 transmission are not understood. We conducted a longitudinal study of dogs and cats living with at least one SARS-CoV-2 infected human in Texas and found 47.1% of 17 cats and 15.3% of 59 dogs from 25.6% of 39 households were positive for SARS-CoV-2 via RT-PCR and genome sequencing or neutralizing antibodies. Virus was isolated from one cat. The majority (82.4%) of infected pets were asymptomatic. Re-sampling of one infected cat showed persistence of viral RNA at least 32 d-post human diagnosis (25 d-post initial test). Across 15 antibody-positive animals, titers increased (33.3%), decreased (33.3%) or were stable (33.3%) over time. A One Health approach is informative for prevention and control of SARS-CoV-2 transmission. |
A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage (preprint)
Deng X , Gu W , Federman S , du Plessis L , Pybus OG , Faria N , Wang C , Yu G , Pan CY , Guevara H , Sotomayor-Gonzalez A , Zorn K , Gopez A , Servellita V , Hsu E , Miller S , Bedford T , Greninger AL , Roychoudhury P , Starita LM , Famulare M , Chu HY , Shendure J , Jerome KR , Anderson C , Gangavarapu K , Zeller M , Spencer E , Andersen KG , MacCannell D , Paden CR , Li Y , Zhang J , Tong S , Armstrong G , Morrow S , Willis M , Matyas BT , Mase S , Kasirye O , Park M , Chan C , Yu AT , Chai SJ , Villarino E , Bonin B , Wadford DA , Chiu CY . medRxiv 2020 The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA. |
State policies relevant to disease intervention specialists in the United States
Cramer R , Ludovic JA . Sex Transm Dis 2023 50 S14-s17 BACKGROUND: The functions of disease intervention specialists (DIS) represent core infectious disease control practices and have legal foundations in the United States. Although important for state and local health departments to understand this authority, these policies have not been systematically collected and analyzed. We analyzed the authority for investigation of sexually transmitted infections (STIs) across all 50 US states and the District of Columbia. METHODS: In January 2022, we collected state policies addressing the investigation of STIs using a legal research database. We coded these policies into a database on variables of interest: (1) whether the policy authorized/required investigation, (2) what type of infection triggers an investigation, (3) and the entity who is authorized/required to perform the investigation. RESULTS: All 50 US states and District of Columbia explicitly authorize/require investigation of cases of STI. Of these jurisdictions, 62.7% require investigations, 41% authorize investigations, and 3.9% both authorize and require investigations. Sixty-seven percent authorize/require investigations for cases of communicable disease (inclusive of an STI), 45.1% authorize/require investigations for cases of STIs generally, and 3.9% authorize/require investigations for cases of a specific STI. Eighty-two percent of jurisdictions authorize/require the state to investigate, 62.7% authorize/require local governments to investigate, and 39.2% authorize/require investigations by both state and local governments. CONCLUSIONS: State laws that establish authority or duties regarding the investigation of STIs differ across states. It may be useful for state and local health departments to examine these policies relative to the morbidity of their jurisdiction and their STI prevention priorities. |
Notes from the field: Multipathogen respiratory virus testing among primary and secondary school students and staff members in a large metropolitan school district - Missouri, November 2, 2022-April 19, 2023
Goldman JL , Lee BR , Porter J , Deliu A , Tilsworth S , Almendares OM , Sleweon S , Kirking HL , Selvarangan R , Schuster JE . MMWR Morb Mortal Wkly Rep 2023 72 (28) 772-774 Respiratory virus infections are common in school-aged children (1). Although children spend most of their awake hours in the school setting, few data are available on the prevalence of respiratory viruses in schools. Surveillance for respiratory viruses other than SARS-CoV-2 has not been widely conducted in primary and secondary schools (2). | | Prospective Surveillance and Preliminary Results | To determine the prevalence of respiratory viruses in school students and staff members, prospective surveillance was implemented in a large metropolitan school district in Kansas City, Missouri with 33 pre-Kindergarten (pre-K)–grade 12 schools during the 2022–23 school year. All district students and staff members were eligible to enroll in opt-in respiratory virus testing and symptom surveys irrespective of the presence of symptoms; enrollment information was sent by the school district using existing communication channels. Self-collected anterior nasal swabs were obtained monthly and tested using multiplex viral polymerase chain reaction.* Thirty-six hours before each scheduled monthly test, an electronic survey was sent to enrolled participants (or their parent or guardian) inquiring about respiratory virus infection symptoms during the preceding 7 days.† Logistic regression models were used to compare positivity across age groups. Regression models accounted for clustering within schools when calculating cluster-robust SEs. Percentile-based bootstrapped CIs were calculated using Stata 17 software (version 17.0; StataCorp). The goal of this report is to share timely virus testing results during ongoing surveillance. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.§ |
The Role of HIV Partner Services in the Modern Biomedical HIV Prevention Era: A Network Modeling Study (preprint)
Jenness SM , Le Guillou A , Lyles C , Bernstein KT , Krupinsky K , Enns EA , Sullivan PS , Delaney KP . medRxiv 2022 21 (12) 801-807 Background HIV partner services can accelerate the use of antiretroviral-based HIV prevention tools (ART and PrEP), but its population impact on long-term HIV incidence reduction is challenging to quantify with traditional PS metrics of partner identified or HIV-screened. Understanding the role of partner services within the portfolio of HIV prevention interventions, including using it to efficiently deliver antiretrovirals, is needed to achieve HIV prevention targets. Methods We used a stochastic network model of HIV/STI transmission for men who have sex with men (MSM), calibrated to surveillance-based estimates in the Atlanta area, a jurisdiction with high HIV burden and suboptimal partner services uptake. Model scenarios varied successful delivery of partner services cascade steps (newly diagnosed "index" patient and partner identification, partner HIV screening, and linkage or reengagement of partners in PrEP or ART care) individually and jointly. Results At current levels observed in Atlanta, removal of HIV partner services had minimal impact on 10-year cumulative HIV incidence, as did improving a single partner services step while holding the others constant. These changes did not sufficiently impact overall PrEP or ART coverage to reduce HIV transmission. If all index patients and partners were identified, maximizing partner HIV screening, partner PrEP provision, partner ART linkage, and partner ART reengagement would avert 6%, 11%, 5%, and 18% of infections, respectively. Realistic improvements in partner identification and service delivery were estimated to avert 2-8% of infections, depending on the combination of improvements. Conclusions Achieving optimal HIV prevention with partner services depends on pairing improvements in index patient and partner identification with maximal delivery of HIV screening, ART, and PrEP to partners if indicated. Improving the identification steps without improvement to antiretroviral service delivery steps, or vice versa, is projected to result in negligible population HIV prevention benefit. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Modifications to student quarantine policies in K-12 schools implementing multiple COVID-19 prevention strategies restores in-person education without increasing SARS-CoV-2 transmission risk, January-March 2021 (preprint)
Dawson P , Worrell MC , Malone S , Fritz SA , McLaughlin HP , Montgomery BK , Boyle M , Gomel A , Hayes S , Maricque B , Lai AM , Neidich JA , Tinker SC , Lee JS , Tong S , Orscheln RC , Charney R , Rebmann T , Mooney J , Rains C , Yoon N , Petit M , Towns K , Goddard C , Schmidt S , Barrios LC , Neatherlin JC , Salzer JS , Newland JG . medRxiv 2022 21 Objective: To determine whether modified K-12 student quarantine policies that allow some students to continue in-person education during their quarantine period increase schoolwide SARS-CoV-2 transmission risk following the increase in cases in winter 2020-2021. Method(s): We conducted a prospective cohort study of COVID-19 cases and exposures among students and staff (n=65,621) in 103 Missouri public schools. Participants were offered free, saliva-based RT-PCR testing. An adjusted Cox regression model compared hazard rates of school-based SARS-CoV-2 infections between schools with a modified versus standard quarantine policy. Result(s): From January-March 2021, a projected 23 (1%) school-based transmission events occurred among 1,636 school close contacts. There was no difference in the adjusted hazard rates of school-based SARS-CoV-2 infections between schools with a modified versus standard quarantine policy (hazard ratio=1.00; 95% confidence interval: 0.97-1.03). Discussion(s): School-based SARS-CoV-2 transmission was rare in 103 K-12 schools implementing multiple COVID-19 prevention strategies. Modified student quarantine policies were not associated with increased school incidence of COVID-19. Modifications to student quarantine policies may be a useful strategy for K-12 schools to safely reduce disruptions to in-person education during times of increased COVID-19 community incidence. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Causes, characteristics, and patterns of prolonged unplanned school closures prior to the COVID-19 pandemic - United States, 2011 - 2019 (preprint)
Jahan FA , Zviedrite N , Gao H , Ahmed F , Uzicanin A . medRxiv 2021 08 Introduction Outside of pandemics, there is little information about occurrence of prolonged unplanned K-12 school closures (PUSC). We describe here the reasons, characteristics, and patterns of PUSC in the United States during 8 consecutive inter-pandemic academic years, 2011-2019. Methods From August 1, 2011 through June 30, 2019, daily systematic online searches were conducted to collect data on publicly announced unplanned school closures lasting >=1 school days in the United States. Closures were categorized as prolonged when schools were closed for >=5 unplanned days (approximating one full workweek), excluding weekends and scheduled days off per school calendars. Results During the eight academic years, a total of 22,112 PUSCs were identified, affecting over 800,000 teachers and 13 million students that resulted in 91.5 million student-days lost. A median of 62.9% of students in PUSC-affected schools were eligible for subsidized school meals. Most affected schools were in cities (35%) and suburban areas (33%). Natural disasters (47%), adverse weather conditions (35%), and budget/teacher strikes (15%) were the most frequently cited reasons for PUSC; illness accounted for 1%, and building/facility issues, environmental issues and violence together accounted for the remaining 2%. The highest number of PUSCs occurred in Health and Human Services Regions 2, 3, 4, and 6 encompassing areas that are frequently in the path of hurricanes and tropical storms. The majority of PUSCs in these regions were attributed to a handful of hurricanes during the fall season, including hurricanes Sandy, Irma, Harvey, Florence, and Matthew. Conclusions PUSCs occur annually in the United States due to a variety of causes and are associated with a substantive loss of student-days for in-school learning. Both these prior experiences with PUSCs and those during the current COVID-19 pandemic illustrate a need for creating sustainable solutions for high-quality distance learning and innovative supplemental feeding programs nationwide, especially in disaster-prone areas. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Public health emergency operations centres in Africa: a cross-sectional study assessing the implementation status of core components and areas for improvement, December 2021
Fekadu ST , Gebrewahid AL , Mankoula W , Eteng W , Lokossou V , Kawe Y , Abdullah A , Jian L , Kol MTM , Wilton MC , Rosenfeld E , Bemo VN , Collard E , McGinley L , Halm A , Aragaw M , Conteh IN , Braka F , Gueye AS . BMJ Open 2023 13 (6) e068934 OBJECTIVE: To assess implementation status of public health emergency operations centres (PHEOCs) in all countries in Africa. DESIGN: Cross-sectional. SETTING: Fifty-four national PHEOC focal points in Africa responded to an online survey between May and November 2021. Included variables aimed to assess capacities for each of the four PHEOC core components. To assess the PHEOCs' functionality, criteria were defined from among the collected variables by expert consensus based on PHEOC operations' prioritisation. We report results of the descriptive analysis, including frequencies of proportions. RESULTS: A total of 51 (93%) African countries responded to the survey. Among these, 41 (80%) have established a PHEOC. Twelve (29%) of these met 80% or more of the minimum requirements and were classified as fully functional. Twelve (29%) and 17 (41%) PHEOCs that met 60%-79% and below 60% the minimum requirements were classified as functional and partially functional, respectively. CONCLUSIONS: Countries in Africa made considerable progress in setting up and improving functioning of PHEOCs. One-third of the responding countries with a PHEOC have one fulfilling at least 80% of the minimum requirements to operate the critical emergency functions. There are still several African countries that either do not have a PHEOC or whose PHEOCs only partially meet these minimal requirements. This calls for significant collaboration across all stakeholders to establish functional PHEOCs in Africa. |
Efficacy of partial spraying of SumiShield, Fludora Fusion and Actellic against wild populations of Anopheles gambiae s.l. in experimental huts in Tiassal, Cte d'Ivoire
Chabi J , Seyoum A , Edi CVA , Kouassi BL , Yihdego Y , Oxborough R , Gbalegba CGN , Johns B , Desale S , Irish SR , Gimnig JE , Carlson JS , Yoshimizu M , Armistead JS , Belemvire A , Gerberg L , George K , Kirby M . Sci Rep 2023 13 (1) 11364 From August 2020 to June 2021, we assessed the efficacy of SumiShield 50WG (clothianidin), Fludora Fusion 56.25WP-SB (mixture of clothianidin and deltamethrin) and Actellic 300CS (pirimiphos-methyl) in experimental huts when partially sprayed against wild, free-flying populations of Anopheles gambiae s.l. in Tiassalé, Côte d'Ivoire. A one-month baseline period of mosquito collections was conducted to determine mosquito density and resting behavior in unsprayed huts, after which two treatments of partial indoor residual spraying (IRS) were tested: spraying only the top half of walls + ceilings or only the bottom half of walls + ceilings. These were compared to fully sprayed applications using the three IRS insecticide formulations, during twenty nights per month of collection for nine consecutive months. Mortality was assessed at the time of collection, and after a 24 h holding period (Actellic) or up to 120 h (SumiShield and Fludora Fusion). Unsprayed huts were used as a negative control. The efficacy of each partially sprayed treatment of each insecticide was compared monthly to the fully sprayed huts over the study period with a non-inferiority margin set at 10%. The residual efficacy of each insecticide sprayed was also monitored. A total of 2197 Anopheles gambiae s.l. were collected during the baseline and 17,835 during the 9-month period after spraying. During baseline, 42.6% were collected on the bottom half versus 24.3% collected on the top half of the walls, and 33.1% on the ceilings. Over the nine-month post treatment period, 73.5% were collected on the bottom half of the wall, 11.6% collected on the top half and 14.8% on the ceilings. For Actellic, the mean mortality over the nine-month period was 88.5% [87.7, 89.3] for fully sprayed huts, 88.3% [85.1, 91.4] for bottom half + ceiling sprayed walls and 80.8% [74.5, 87.1] for the top half + ceiling sprayed huts. For Fludora Fusion an overall mean mortality of 85.6% [81.5, 89.7] was recorded for fully sprayed huts, 83.7% [82.9, 84.5] for bottom half + ceiling sprayed huts and 81.3% [79.6, 83.0] for the top half + ceiling sprayed huts. For SumiShield, the overall mean mortality was 86.7% [85.3, 88.1] for fully sprayed huts, 85.6% [85.4, 85.8] for the bottom half + ceiling sprayed huts and 76.9% [76.6, 77.3] for the top half + ceiling sprayed huts. For Fludora Fusion, both iterations of partial IRS were non-inferior to full spraying. However, for SumiShield and Actellic, this was true only for the huts with the bottom half + ceiling, reflecting the resting site preference of the local vectors. The results of this study suggest that partial spraying may be a way to reduce the cost of IRS without substantially compromising IRS efficacy. |
Evaluating baits with lufenuron and nitenpyram for flea control on prairie dogs (Cynomys spp.) to mitigate plague
Eads DA , Castle KT , Wild MA , Borchert JN , Livieri TM , Matchett MR , Dobesh P , Hughes JP , Childers E . J Wildl Dis 2023 59 (4) 662-672 Plague, caused by Yersinia pestis, is a widespread threat to endangered black-footed ferrets (Mustela nigripes) and their primary prey, prairie dogs (Cynomys spp.). Wildlife biologists most commonly manage plague using insecticides to control fleas, the primary vectors of Y. pestis. We tested edible baits containing the insecticides lufenuron and/or nitenpyram in prairie dogs. During a laboratory study, we treated 26 white-tailed prairie dogs (Cynomys leucurus) with lufenuron at 300 mg/kg body mass. All animals remained clinically healthy over the 9 wk monitoring period. Although serum lufenuron concentrations were >130 ppb in two treatment groups at week 1, concentrations declined to ≤60 ppb after 3 wk in non-torpid prairie dogs and after 7 wk in torpid prairie dogs. In a field experiment, we tested baits containing a combination of 75 mg lufenuron and 6 mg nitenpyram, respectively, in black-tailed prairie dogs (Cynomys ludovicianus). We uniformly distributed baits at 125 baits/ha on two plots (treated once) and 250 baits/ha on two plots (each treated twice 4.4 wk apart). Following treatments, flea abundance increased on prairie dogs and remained stable in burrows. Our findings indicate that baits containing lufenuron and nitenpyram, at the reported treatment rates, are ineffective tools for flea control on prairie dogs. Future experiments might evaluate efficacy of higher doses of lufenuron and nitenpyram, and repetitive treatments at differing intervals over time to evaluate potentially therapeutic treatments. |
Changes in the geographic distribution of the blacklegged tick, Ixodes scapularis, in the United States
Eisen L , Eisen RJ . Ticks Tick Borne Dis 2023 14 (6) 102233 Ixodes scapularis (the blacklegged tick) was considered a species of no medical concern until the mid-1970s. By that time, the tick's geographic distribution was thought to be mainly in the southeastern United States (US), with additional localized populations along the Eastern Seaboard north to southern Massachusetts and in the Upper Midwest. Since 1975, I. scapularis has been implicated as a vector of seven human pathogens and is now widely distributed across the eastern US up to the border with Canada. Geographic expansion of tick-borne diseases associated with I. scapularis (e.g., Lyme disease, anaplasmosis, and babesiosis) is attributed to an expanding range of the tick. However, due to changes in tick surveillance efforts over time, it is difficult to differentiate between range expansion and increased recognition of already established tick populations. We provide a history of the documented occurrence of I. scapularis in the US from its description in 1821 to present, emphasizing studies that provide evidence of expansion of the geographic distribution of the tick. Deforestation and decimation of the white-tailed deer (Odocoileus virginianus), the primary reproductive host for I. scapularis adults, during the 1800s presumably led to the tick disappearing from large areas of the eastern US where it previously had been established. Subsequent reforestation and deer population recovery, together with recent climate warming, contributed to I. scapularis proliferating in and spreading from refugia where it had persisted into the early 1900s. From documented tick collection records, it appears I. scapularis was present in numerous locations in the southern part of the eastern US in the early 1900s, whereas in the north it likely was limited to a small number of refugia sites during that time period. There is clear evidence for established populations of I. scapularis in coastal New York and Massachusetts by 1950, and in northwestern Wisconsin by the late 1960s. While recognizing that surveillance for I. scapularis increased dramatically from the 1980s onward, we describe multiple instances of clearly documented expansion of the tick's geographic distribution in the Northeast, Upper Midwest, and Ohio Valley regions from the 1980s to present. Spread and local population increase of I. scapularis, together with documentation of Borrelia burgdorferi sensu stricto in host-seeking ticks, was universally followed by increases in Lyme disease cases in these areas. Southward expansion of northern populations of I. scapularis, for which the host questing behavior of the nymphal stage leads to substantially higher risk of human bites compared with southern populations, into Virginia and North Carolina also was followed by rising numbers of Lyme disease cases. Ongoing surveillance of ticks and tick-borne pathogens is essential to provide the data needed for studies that seek to evaluate the relative roles of land cover, tick hosts, and climate in explaining and predicting geographic expansion of ticks and tick-borne diseases. |
Geographic Information System Protocol for Mapping Areas Targeted for Mosquito Control in North Carolina (preprint)
Mueller A , Thomas A , Brown J , Young A , Smith K , Connelly R , Richards SL . medRxiv 2022 15 Geographic information systems (GIS) can be used to map mosquito larval and adult habitats and human populations at risk for mosquito exposure and possible arbovirus transmission. GIS can help simplify and target mosquito control efforts during routine surveillance and post-disaster (e.g., hurricane-related flooding) to protect emergency workers and public health. A practical method for prioritizing areas for emergency mosquito control has been developed and is described here. North Carolina (NC) One Map was used to identify state-level data layers of interest based on human population distribution and mosquito habitat in Brunswick, Columbus, Onslow, and Robeson Counties in eastern NC. Relevant data layers were included to create mosquito control treatment areas for targeted control and an 18-step protocol for map development is discussed. This protocol is expected to help state, territorial, tribal, and/or local public health officials and associated mosquito control programs efficiently create treatment area maps to improve strategic planning in advance of a disaster. This protocol may be applied to any NC county and beyond, thereby increasing local disaster preparedness. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Mixtures of urinary concentrations of phenols and phthalate biomarkers in relation to the ovarian reserve among women attending a fertility clinic
Génard-Walton M , McGee G , Williams PL , Souter I , Ford JB , Chavarro JE , Calafat AM , Hauser R , Mínguez-Alarcón L . Sci Total Environ 2023 898 165536 Although prior studies have found associations of the ovarian reserve with urinary concentrations of some individual phenols and phthalate metabolites, little is known about the potential associations of these chemicals as a mixture with the ovarian reserve. We investigated whether mixtures of four urinary phenols (bisphenol A, butylparaben, methylparaben, propylparaben) and eight metabolites of five phthalate diesters including di(2-ethylhexyl) phthalate were associated with markers of the ovarian reserve among 271 women attending a fertility center who enrolled in the Environment and Reproductive Health study (2004-2017). The analysis was restricted to one outcome per study participant using the earliest outcome after the last exposure assessment. Ovarian reserve markers included lower antral follicle count (AFC) defined as AFC < 7, circulating serum levels of day 3 follicle stimulating hormone (FSH) assessed by immunoassays, and diminished ovarian reserve (DOR) defined as either AFC < 7, FSH > 10 UI/L or primary infertility diagnosis of DOR. We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation to estimate the joint associations and assess the interactions between chemical exposure biomarkers on the markers of the ovarian reserve while adjusting for confounders. Among all 271 women, 738 urine samples were collected. In quantile g-computation models, a quartile increase in the exposure biomarkers mixture was not significantly associated with lower AFC (OR = 1.10, 95 % CI = 0.52, 2.30), day 3 FSH levels (Beta = 0.30, 95 % CI = -0.32, 0.93) or DOR (OR = 1.02, 95 % CI = 0.52, 2.05). Similarly, BKMR did not show any evidence of associations between the mixture and any of the studied outcomes, or interactions between chemicals. Despite the lack of associations, these results need to be explored among women in other study cohorts. |
DIRECT FROM ATSDR: APPLETREE: Building local capacity to respond to environmental exposures
Henry A , Cowins J . J Environ Health 2023 85 (10) 26-27 |
Fatal primary amebic meningoencephalitis in Nebraska: Case report and environmental investigation, August 2022
Maloney P , Mowrer C , Jansen L , Karre T , Bedrnicek J , Obaro SK , Iwen PC , McCutchen E , Wetzel C , Frederick J , Ashraf MS , Donahue M . Am J Trop Med Hyg 2023 109 (2) 322-326 Primary amebic meningoencephalitis (PAM) is a rare and lethal infection caused by Naegleria fowleri. We report an epidemiological and environmental investigation relating to a case of PAM in a previously healthy boy age 8 years. An interview of the patient's family was conducted to determine the likely exposure site and to assess risk factors. Data from the United States Geological Survey site at Waterloo, NE, on the Elkhorn River were used to estimate water temperature and streamflow at the time and site of exposure. Data from the National Weather Service were used to estimate precipitation and ambient air temperature at the time and site of exposure. Despite conventional treatment, the patient died 2 days after hospital admission. The patient participated in recreational water activities in the Elkhorn River in northeastern Nebraska 5 days before symptom onset. In the week before exposure, water and ambient air high temperatures reached annual highs, averaging 32.4°C and 35.8°C, respectively. The day before infection, 2.2 cm of precipitation was reported. Streamflow was low (407 ft3/s). Infections in several northern states, including Nebraska, suggest an expanding geographic range of N. fowleri transmission, which may lead to increased incidence of PAM in the United States. Similar environmental investigations at suspected exposure sites of future cases will allow data aggregation, enabling investigators to correlate environmental factors with infection risk accurately. |
Trends in heat related illness: Nationwide observational cohort at the US Department of Veteran Affairs
Osborne TF , Veigulis ZP , Vaidyanathan A , Arreola DM , Schramm PJ . J Clim Cha Health 2023 12 Introduction: Environmental heat can have a negative impact on health, leading to increased healthcare utilization, disability, and death. Specific clinical conditions, in combination with a global rise in temperature, may amplify the risk of heat related illnesses. Materials and Methods: We conducted a retrospective analysis of VA's national electronic health record database from January 1, 2002, through December 31, 2019. Heat related illness diagnoses were assessed for associations with patient demographics, comorbidities, and geographic residence at the time of a heat related illness diagnosis. Descriptive statistics, linear regression, and additive seasonal decomposition methods were utilized to assess risk factors and trends. Results: There were 33,114 documented cases of heat related illness, which impacted 28,039 unique patients, during our 18 year assessment period. Veterans were diagnosed with heat related illnesses in all 50 US states and there was an increase in the rate over time. The likelihood of heat related illnesses was greater for those with increased comorbidity burden. Rates increased for homeless Veterans in the first half of the assessment period, and then declined for the second half. Black, as well as American Indian/Alaska Native Veterans accounted for a greater proportion of heat related illnesses. Conclusion: There has been a statistically significant and clinically important increase in the incidence of heat related illnesses over time. There has also been an increased number of heat related diagnoses associated with existing health and demographic factors, and the increase over time did not strictly follow the expected geographic North-South climate trends. © 2023 |
A nested case-control study of serum per- and polyfluoroalkyl substances and testicular germ cell tumors among U.S. Air Force servicemen
Purdue MP , Rhee J , Denic-Roberts H , McGlynn KA , Byrne C , Sampson J , Botelho JC , Calafat AM , Rusiecki J . Environ Health Perspect 2023 131 (7) 77007 BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a component of firefighting foams used at military installations. Although high PFAS exposures have been related to cancer risks among civilian populations, the effects for military personnel are unclear. OBJECTIVES: We investigated associations between serum PFAS concentrations and testicular germ cell tumors (TGCT) among U.S. Air Force servicemen. METHODS: This nested case-control study involved active-duty Air Force servicemen with sera from the Department of Defense Serum Repository. We selected 530 cases and 530 controls individually matched on birth date, race and ethnicity, year entered the service, and year of sample collection, with prediagnostic serum samples collected between 1988 and 2017. A second prediagnostic sample, collected a median of 4 y after the first, was selected for 187 case-control pairs. Seven PFAS were quantified using isotope-dilution tandem mass spectrometry. Odds ratios (ORs) and 95% confidence intervals (CIs) from conditional logistic regression adjusting for military grade, number of deployments, and, in some models, other PFAS, estimated associations between PFAS concentrations (categorized using quartiles among controls) and TGCT. RESULTS: Elevated concentrations of some PFAS were observed for military employment in firefighting [perfluorooctanesulfonic acid (PFOS), perfluorohexanesulfonic acid (PFHxS), perfluorooctanoic acid] and service at a base with high PFAS concentrations in drinking water (PFHxS). Elevated PFOS concentrations in the second sample were positively associated with TGCT [OR for fourth vs. first quartile (ORQ4) = 2.6, 95% CI: 1.1, 6.4; ptrend = 0.02], including after adjustment for other PFAS (ORQ4 = 4.6, 95% CI: 1.4, 15.1; ptrend = 0.009). Associations with PFOS in the first/only samples were weak and not statistically significant. Elevated concentrations of perfluorononanoic acid were inversely associated with TGCT, whereas results were null for other PFAS. DISCUSSION: We identified service-related predictors of PFAS concentrations and increased TGCT relative risks with elevated PFOS concentrations among Air Force servicemen. These findings warrant further investigation in other populations and military service branches. 10.1289/EHP12603. |
Urinary glyphosate concentrations among pregnant participants in a randomized, crossover trial of organic and conventional diets
Hyland C , Spivak M , Sheppard L , Lanphear BP , Antoniou M , Ospina M , Calafat AM , Curl CL . Environ Health Perspect 2023 131 (7) 77005 BACKGROUND: Consumption of an organic diet reduces exposure to a range of agricultural pesticides. Only three studies have examined the effect of an organic diet intervention on exposure to the herbicide glyphosate, the most heavily used agricultural chemical in the world. Despite its widespread use, the primary sources of glyphosate exposure in humans are poorly understood. OBJECTIVE: Our objective was to examine the effect of an organic diet intervention on urinary glyphosate concentrations among pregnant individuals. METHODS: We conducted a 2-wk randomized crossover trial in which 39 pregnant participants living near ( ≤ 0.5 km) and far ( > 0.5 km) from agricultural fields received a 1-wk supply of conventional groceries and 1 wk of organic groceries, randomized to order. We collected daily first morning void urine samples and analyzed composite samples from each week for glyphosate. We examined differences in urinary glyphosate concentrations between the conventional week and the organic week among all participants and stratified by residential proximity to an agricultural field. RESULTS: Median specific gravity-adjusted glyphosate concentrations were 0.19 μg/L and 0.16 μg/L during the conventional and organic weeks, respectively. We observed modest decreases in urinary glyphosate concentrations from the conventional to organic week among far-field participants, but no difference among near-field participants. In secondary analyses excluding participants who did not meet a priori criteria of compliance with the intervention, we observed significant decreases in urinary glyphosate concentrations, particularly among far-field participants (p < 0.01 - 0.02, depending on exclusion criteria). DISCUSSION: This trial is the first to examine the effect of an organic diet intervention on glyphosate among people living near and far from agricultural fields. Our results suggest that diet is an important contributor to glyphosate exposure in people living > 0.5 km from agricultural fields; for people living near crops, agriculture may be a dominant exposure source during the pesticide spray season. https://doi.org/10.1289/EHP12155. |
APPLETREE: Building local capacity to respond to environmental exposures
Henry A , Cowins J . J Environ Health 2023 85 (10) 26-27 In 1987, the Agency for Toxic Substances | and Disease Registry (ATSDR) developed a | nonresearch cooperative agreement program | to help accomplish its public health mission. | That program is known as the Partnership | to Promote Local Eorts to Reduce Environmental Exposure (APPLETREE). APPLETREE funds 30 state health departments that | work closely with communities; local, state, | and federal agencies and organizations; tribal | governments; and other entities to address | site-specific issues and recommend actions to | protect public health. It is the largest cooperative agreement program within ATSDR and | builds state capacity to: | • respond to threats from human exposure to | hazardous substances in the environment, | • engage communities with site contamination and potential health eects, and | • implement activities to address local environmental health issues of concern. | APPLETREE activities are primarily focused | on protecting public health through site health | assessments, community engagement, and | capacity building and prevention activities | such as Choose Safe Places for Early Care and | Education (CSPECE; Grants.gov, 2022). |
CASCADIA: a prospective community-based study protocol for assessing SARS-CoV-2 vaccine effectiveness in children and adults using a remote nasal swab collection and web-based survey design
Babu TM , Feldstein LR , Saydah S , Acker Z , Boisvert CL , Briggs-Hagen M , Carone M , Casto A , Cox SN , Ehmen B , Englund JA , Fortmann SP , Frivold CJ , Groom H , Han PD , Kuntz JL , Lockwood T , Midgley CM , Mularski RA , Ogilvie T , Reich SL , Schmidt MA , Smith N , Starita L , Stone J , Vandermeer M , Weil AA , Wolf CR , Chu HY , Naleway AL . BMJ Open 2023 13 (7) e071446 INTRODUCTION: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the Food and Drug Administration in late 2020 for adults, authorisation for young children 6 months to <5 years of age did not occur until 2022. These authorisations were based on clinical trials, understanding real-world vaccine effectiveness (VE) in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 VE against infection among children aged >6 months and adults aged <50 years. METHODS: CASCADIA is a 4-year community-based prospective study of SARS-CoV-2 VE among 3500 adults and paediatric populations aged 6 months to 49 years in Oregon and Washington, USA. At enrolment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrolment and annually thereafter, with optional blood draws every 6 months and after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by reverse transcription-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who test positive for SARS-CoV-2 undergo serial swab collection every 3 days for 21 days. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralisation assays. ANALYSIS: The primary outcome is SARS-CoV-2 infection. Cox regression models will be used to estimate the incidence rate ratio associated with SARS-CoV-2 vaccination among the paediatric and adult population, controlling for demographic factors and other potential confounders. ETHICS AND DISSEMINATION: All study materials including the protocol, consent forms, data collection instruments, participant communication and recruitment materials, were approved by the Kaiser Permanente Interregional Institutional Review Board, the IRB of record for the study. Results will be disseminated through peer-reviewed publications, presentations, participant newsletters and appropriate general news media. |
Excess deaths directly and indirectly attributable to COVID-19 using routinely reported mortality data, Bishkek, Kyrgyzstan, 2020: a cross-sectional study
Bumburidi Y , Dzhalimbekova A , Malisheva M , Moolenaar RL , Horth R , Singer D , Otorbaeva D . BMJ Open 2023 13 (7) e069521 OBJECTIVES: Studies on excess deaths (ED) show that reported deaths from COVID-19 underestimate death. To understand mortality for improved pandemic preparedness, we estimated ED directly and indirectly attributable to COVID-19 and ED by age groups. DESIGN: Cross-sectional study using routinely reported individual deaths data. SETTINGS: The 21 health facilities in Bishkek that register all city deaths. PARTICIPANTS: Residents of Bishkek who died in the city from 2015 to 2020. OUTCOME MEASURE: We report weekly and cumulative ED by age, sex and causes of death for 2020. EDs are the difference between observed and expected deaths. Expected deaths were calculated using the historical average and the upper bound of the 95% CI from 2015 to 2019. We calculated the percentage of deaths above expected using the upper bound of the 95% CI of expected deaths. COVID-19 deaths were laboratory confirmed (U07.1) or probable (U07.2 or unspecified pneumonia). RESULTS: Of 4660 deaths in 2020, we estimated 840-1042 ED (79-98 ED per 100 000 people). Deaths were 22% greater than expected. EDs were greater for men (28%) than for women (20%). EDs were observed in all age groups, with the highest ED (43%) among people 65-74 years of age. Hospital deaths were 45% higher than expected. During peak mortality (1 July -21 July), weekly ED was 267% above expected, and ED by disease-specific cause of death were above expected: 193% for ischaemic heart diseases, 52% for cerebrovascular diseases and 421% for lower respiratory diseases. COVID-19 was directly attributable to 69% of ED. CONCLUSION: Deaths directly and indirectly associated with the COVID-19 pandemic were markedly higher than reported, especially for older populations, in hospital settings, and during peak weeks of SARS-CoV-2 transmission. These ED estimates can support efforts to prioritise support for persons at greatest risk of dying during surges. |
Poliovirus outbreak in New York State, August 2022: qualitative assessment of immediate public health responses and priorities for improving vaccine coverage
Kasstan B , Mounier-Jack S , Chantler T , Masters N , Flores SA , Stokley S , Meek H , Easton D , De Luna-Evans T , Souto M , Punjabi C , Ruppert PS , Rosenberg E , Routh J . Epidemiol Infect 2023 151 e120 In 2022, a case of paralysis was reported in an unvaccinated adult in Rockland County (RC), New York. Genetically linked detections of vaccine-derived poliovirus type 2 (VDPV2) were reported in multiple New York counties, England, Israel, and Canada. The aims of this qualitative study were to: i) review immediate public health responses in New York to assess the challenges in addressing gaps in vaccination coverage; ii) inform a longer-term strategy to improving vaccination coverage in under-vaccinated communities, and iii) collect data to support comparative evaluations of transnational poliovirus outbreaks. Twenty-three semi-structured interviews were conducted with public health professionals, healthcare professionals, and community partners. Results indicate that i) addressing suboptimal vaccination coverage in RC remains a significant challenge after recent disease outbreaks; ii) the poliovirus outbreak was not unexpected and effort should be invested to engage mothers, the key decision-makers on childhood vaccination; iii) healthcare providers (especially paediatricians) received technical support during the outbreak, and may require resources and guidance to effectively contribute to longer-term vaccine engagement strategies; vi) data systems strengthening is required to help track under-vaccinated children. Public health departments should prioritize long-term investments in appropriate communication strategies, countering misinformation, and promoting the importance of the routine immunization schedule. |
Mortality patterns over a 10-year period in Kibera, an urban informal settlement in Nairobi, Kenya, 2009-2018
Oduor C , Omwenga I , Ouma A , Mutinda R , Kiplangat S , Mogeni OD , Cosmas L , Audi A , Odongo GS , Obor D , Breiman R , Montgomery J , Agogo G , Munywoki P , Bigogo G , Verani JR . Glob Health Action 2023 16 (1) 2238428 BACKGROUND: Reliable mortality data are important for evaluating the impact of health interventions. However, data on mortality patterns among populations living in urban informal settlements are limited. OBJECTIVES: To examine the mortality patterns and trends in an urban informal settlement in Kibera, Nairobi, Kenya. METHODS: Using data from a population-based surveillance platform we estimated overall and cause-specific mortality rates for all age groups using person-year-observation (pyo) denominators and using Poisson regression tested for trends in mortality rates over time. We compared associated mortality rates across groups using incidence rate ratios (IRR). Assignment of probable cause(s) of death was done using the InterVA-4 model. RESULTS: We registered 1134 deaths from 2009 to 2018, yielding a crude mortality rate of 4.4 (95% Confidence Interval [CI]4.2-4.7) per 1,000 pyo. Males had higher overall mortality rates than females (incidence rate ratio [IRR], 1.44; 95% CI, 1.28-1.62). The highest mortality rate was observed among children aged < 12 months (41.5 per 1,000 pyo; 95% CI 36.6-46.9). All-cause mortality rates among children < 12 months were higher than that of children aged 1-4 years (IRR, 8.5; 95% CI, 6.95-10.35). The overall mortality rate significantly declined over the period, from 6.7 per 1,000 pyo (95% CI, 5.7-7.8) in 2009 to 2.7 (95% CI, 2.0-3.4) per 1,000 pyo in 2018. The most common cause of death was acute respiratory infections (ARI)/pneumonia (18.1%). Among children < 5 years, the ARI/pneumonia deaths rate declined significantly over the study period (5.06 per 1,000 pyo in 2009 to 0.61 per 1,000 pyo in 2018; p = 0.004). Similarly, death due to pulmonary tuberculosis among persons 5 years and above significantly declined (0.98 per 1,000 pyo in 2009 to 0.25 per 1,000 pyo in 2018; p = 0.006). CONCLUSIONS: Overall and some cause-specific mortality rates declined over time, representing important public health successes among this population. |
Longitudinal and Quantitative Fecal Shedding Dynamics of SARS-CoV-2, Pepper Mild Mottle Virus and CrAssphage (preprint)
Arts PJ , Kelly JD , Midgley CM , Anglin K , Lu S , Abedi GR , Andino R , Bakker KM , Banman B , Boehm AB , Briggs-Hagen M , Brouwer AF , Davidson MC , Eisenberg MC , Garcia-Knight M , Knight S , Peluso MJ , Pineda-Ramirez J , Sanchez RD , Saydah S , Tassetto M , Martin JN , Wigginton KR . medRxiv 2023 07 e0013223 Wastewater-based epidemiology (WBE) emerged during the COVID-19 pandemic as a scalable and broadly applicable method for community-level monitoring of infectious disease burden, though the lack of high-quality, longitudinal fecal shedding data of SARS-CoV-2 and other viruses limits the interpretation and applicability of wastewater measurements. In this study, we present longitudinal, quantitative fecal shedding data for SARS-CoV-2 RNA, as well as the commonly used fecal indicators Pepper Mild Mottle Virus (PMMoV) RNA and crAss-like phage (crAssphage) DNA. The shedding trajectories from 48 SARS-CoV-2 infected individuals suggest a highly individualized, dynamic course of SARS-CoV-2 RNA fecal shedding, with individual measurements varying from below limit of detection to 2.79x106 gene copies/mg - dry mass of stool (gc/mg-dw). Of individuals that contributed at least 3 samples covering a range of at least 15 of the first 30 days after initial acute symptom onset, 77.4% had at least one positive SARS-CoV-2 RNA stool sample measurement. We detected PMMoV RNA in at least one sample from all individuals and in 96% (352/367) of samples overall; and measured crAssphage DNA above detection limits in 80% (38/48) of individuals and 48% (179/371) of samples. Median shedding values for PMMoV and crAssphage nucleic acids were 1x105 gc/mg-dw and 1.86x103 gc/mgdw, respectively. These results can be used to inform and build mechanistic models to significantly broaden the potential of WBE modeling and to provide more accurate insight into SARS-CoV-2 prevalence estimates. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
CASCADIA: A prospective community-based study protocol for assessing SARS-CoV-2 vaccine effectiveness in children and adults utilizing a remote nasal swab collection and web-based survey design (preprint)
Babu TM , Feldstein LR , Saydah S , Acker Z , Boisvert CL , Briggs-Hagen M , Carone M , Casto A , Cox SN , Ehmen B , Englund JA , Fortmann SP , Frivold CJ , Groom H , Han P , Kuntz JL , Lockwood T , Midgley CM , Mularski RA , Ogilvie T , Reich S , Schmidt MA , Smith N , Starita L , Stone J , Vandermeer M , Weil AA , Wolf CR , Chu HY , Naleway AL . medRxiv 2023 07 Introduction: Although SARS-CoV-2 vaccines were first approved under Emergency Use Authorization by the FDA in late 2020 for adults, approval for young children 6 months to < 5 years of age did not occur until 2022. Understanding real world vaccine effectiveness in the setting of emerging variants is critical. The primary goal of this study is to evaluate SARS-CoV-2 vaccine effectiveness (VE) against infection among children aged >6 months and adults aged <50 years. Method(s): CASCADIA is a four-year community-based prospective study of SARS-CoV-2 VE among adult and pediatric populations aged 6 months to 49 years in Oregon and Washington. At enrollment and regular intervals, participants complete a sociodemographic questionnaire. Individuals provide a blood sample at enrollment and annually thereafter, with additional, optional blood draws after infection and vaccination. Participants complete weekly self-collection of anterior nasal swabs and symptom questionnaires. Swabs are tested for SARS-CoV-2 and other respiratory pathogens by RT-PCR, with results of selected pathogens returned to participants; nasal swabs with SARS-CoV-2 detected will undergo whole genome sequencing. Participants who report symptoms outside of their weekly swab collection and symptom survey are asked to collect an additional swab. Participants who test positive for SARS-CoV-2 undergo serial swab collection every three days for three weeks. Serum samples are tested for SARS-CoV-2 antibody by binding and neutralization assays. Analysis: Cox regression models will be used to estimate the hazard ratio associated with SARS-CoV-2 vaccination among the pediatric and adult population, controlling for demographic factors and potential confounders, including clustering within households. Ethics and dissemination: All study materials including the protocol, consent forms, participant communication and recruitment materials, and data collection instruments were approved by the Kaiser Permanente Northwest (KPNW) Institutional Review Board, the IRB of record for the study. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Sensitivity and Uncertainty Analysis for Two-Stream Capture-Recapture Methods in Disease Surveillance (preprint)
Zhang Y , Chen J , Ge L , Williamson JM , Waller LA , Lyles RH . medRxiv 2022 23 Capture-recapture methods are widely applied in estimating the number (N) of prevalent or cumulatively incident cases in disease surveillance. Here, we focus the bulk of our attention on the common case in which there are two data streams. We propose a sensitivity and uncertainty analysis framework grounded in multinomial distribution-based maximum likelihood, hinging on a key dependence parameter that is typically non-identifiable but is epidemiologically interpretable. Focusing on the epidemiologically meaningful parameter unlocks appealing data visualizations for sensitivity analysis and provides an intuitively accessible framework for uncertainty analysis designed to leverage the practicing epidemiologist's understanding of the implementation of the surveillance streams as the basis for assumptions driving estimation of N. By illustrating the proposed sensitivity analysis using publicly available HIV surveillance data, we emphasize both the need to admit the lack of information in the observed data and the appeal of incorporating expert opinion about the key dependence parameter. The proposed uncertainty analysis is an empirical Bayes-like approach designed to more realistically acknowledge variability in the estimated N associated with uncertainty in an expert's opinion about the non-identifiable parameter, together with the statistical uncertainty. We demonstrate how such an approach can also facilitate an appealing general interval estimation procedure to accompany capture-recapture methods. Simulation studies illustrate the reliable performance of the proposed approach for quantifying uncertainties in estimating N in various contexts. Finally, we demonstrate how the recommended paradigm has the potential to be directly extended for application to data from more than two surveillance streams. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
U.S. CDC support to international SARS-CoV-2 seroprevalence surveys, May 2020-February 2022 (preprint)
Hamida AB , Charles M , Murrill C , Henao O , Gallagher K . medRxiv 2022 01 (8) SARS-CoV-2 seroprevalence surveys provide critical information to assess the burden of COVID-19, describe population immunity, and guide public health strategies. Early in the pandemic, most of these surveys were conducted within high-income countries, leaving significant knowledge gaps in low-and middle-income (LMI) countries. To address this gap, the U.S. Centers for Disease Control and Prevention (CDC) is supporting serosurveys internationally. We conducted a descriptive analysis of international serosurveys supported by CDC during May 12, 2020-February 28, 2022, using an internal tracker including data on the type of assistance provided, study design, population surveyed, laboratory testing performed, and status of implementation. Since the beginning of the pandemic, CDC has supported 72 serosurveys (77 serosurvey rounds) in 35 LMI countries by providing technical assistance (TA) on epidemiologic, statistical, and laboratory methods, financial assistance (FA), or both. Among these serosurvey rounds, the majority (61%) received both TA and FA from CDC, 30% received TA only, 3% received only FA, and 5% were part of informal reviews. Fifty-four percent of these serosurveys target the general population, 13% sample pregnant women, 7% sample healthcare workers, 7% sample other special populations (internally displaced persons, patients, students, and people living with HIV), and 18% assess multiple or other populations. These studies are in different stages of implementation, ranging from protocol development to dissemination of results. They are conducted under the leadership of local governments, who have ownership over the data, in collaboration with international partners. Thirty-four surveys rounds have completed data collection. CDC TA and FA of SARS-CoV-2 seroprevalence surveys will enhance the knowledge of the COVID-19 pandemic in almost three dozen LMI countries. Support for these surveys should account for current limitations with interpreting results, focusing efforts on prospective cohorts, identifying, and forecasting disease patterns over time, and helping understand antibody kinetics and correlates of protection. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Study protocol for the Innovative Support for Patients with SARS-COV-2 Infections Registry (INSPIRE): a longitudinal study of the medium and long-term sequelae of SARS-CoV-2 infection (preprint)
O'Laughlin KN , Thompson M , Hota B , Gottlieb M , Plumb ID , Chang AM , Wisk LE , Hall AJ , Wang RC , Spatz ES , Stephens KA , Huebinger RM , McDonald SA , Venkatesh A , Gentile N , Slovis BH , Hill M , Saydah S , Idris AH , Rodriguez R , Krumholz HM , Elmore JG , Weinstein RA , Nichol G . medRxiv 2021 05 BACKGROUND: Reports on medium and long-term sequelae of SARS-CoV-2 infections largely lack quantification of incidence and relative risk. We describe the rationale and methods of the Innovative Support for Patients with SARS-CoV-2 Registry (INSPIRE) that combines patient-reported outcomes with data from digital health records to understand predictors and impacts of SARS-CoV-2 infection. METHOD(S): INSPIRE is a prospective, multicenter, longitudinal study of individuals with symptoms of SARS-CoV-2 infection in eight regions across the US. Adults are eligible for enrollment if they are fluent in English or Spanish, reported symptoms suggestive of acute SARS-CoV-2 infection, and if they are within 42 days of having a SARS-CoV-2 viral test (i.e., nucleic acid amplification test or antigen test), regardless of test results. Recruitment occurs in-person, by phone or email, and through online advertisement. A secure online platform is used to facilitate the collation of consent-related materials, digital health records, and responses to self-administered surveys. Participants are followed for up to 18 months, with patient-reported outcomes collected every three months via survey and linked to concurrent digital health data; follow-up includes no in-person involvement. Our planned enrollment is 4,800 participants, including 2,400 SARS-CoV-2 positive and 2,400 SARS-CoV-2 negative participants (as a concurrent comparison group). These data will allow assessment of longitudinal outcomes from SARS-CoV-2 infection and comparison of the relative risk of outcomes in individuals with and without infection. Patient-reported outcomes include self-reported health function and status, as well as clinical outcomes including health system encounters and new diagnoses. RESULT(S): Participating sites obtained institutional review board approval. Enrollment and follow-up are ongoing. CONCLUSION(S): This study will characterize medium and long-term sequelae of SARS-CoV-2 infection among a diverse population, predictors of sequelae, and their relative risk compared to persons with similar symptomatology but without SARS-CoV-2 infection. These data may inform clinical interventions for individuals with sequelae of SARS-CoV-2 infection. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
COVID-19 cases and hospitalizations averted by case investigation and contact tracing in the United States (preprint)
Rainisch G , Jeon S , Pappas D , Spencer KD , Fischer LS , Adhikari BB , Taylor MM , Greening B , Moonan PK , Oeltmann JE , Kahn EB , Washington ML , Meltzer MI . medRxiv 2021 21 Importance: Evidence of the impact of COVID-19 Case Investigation and Contact Tracing (CICT) programs is lacking. Policymakers need this evidence to assess its value. Objective(s): Estimate COVID-19 cases and hospitalizations averted nationwide by US states' CICT programs. Design(s): We combined data from US CICT programs (e.g., proportion of cases interviewed, contacts notified or monitored, and days to case and contact notification) with incidence data to model CICT impacts over 60 days period (November 25, 2020 to January 23, 2021) during the height of the pandemic. We estimated a range of impacts by varying assumed compliance with isolation and quarantine recommendations. Setting(s): US States and Territories Participants: Fifty-nine state and territorial health departments that received federal funding supporting COVID-19 pandemic response activities were eligible for inclusion. Of these, 22 states and 1 territory reported all measures necessary for the analysis. These 23 jurisdictions covered 42.5% of the US population (140 million persons), spanned all 4 census regions, and reported data that reflected all 59 federally funded CICT programs. Intervention(s): Public health case investigation and contact tracing Main Outcomes and Measures: Cases and hospitalizations averted; percent of cases averted among cases not prevented by vaccination and other non-pharmaceutical interventions (other NPIs). Result(s): We estimated 1.11 million cases and 27,231 hospitalizations were averted by CICT programs under a scenario where 80% of interviewed cases and monitored contacts, and 30% of notified contacts fully complied with isolation and quarantine guidance, eliminating their contributions to future transmission. As many as 1.36 million cases and 33,527 hospitalizations could have been prevented if all interviewed cases and monitored contacts had entered into and fully complied with isolation and quarantine guidelines upon being interviewed or notified. Across all scenarios and jurisdictions, CICT averted a median of 21.2% (range: 1.3% - 65.8%) of the cases not prevented by vaccination and other NPIs. Conclusions and Relevance: CICT programs likely had a substantial role in curtailing the pandemic in most jurisdictions during the winter 2020-2021 peak. Differences in impact across jurisdictions indicate an opportunity to further improve CICT effectiveness. These estimates demonstrate the potential benefits from sustaining and improving these programs. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. |
RFS proudly announces the 2022 award recipient for Foodborne Pathogens and Disease
Griffin PM . Foodborne Pathog Dis 2023 20 (7) 251 Foodborne botulism is a rapidly progressive, potentially fatal paralyzing illness caused by the consumption of botulinum neurotoxin, which is most commonly produced by Clostridium botulinum. Refrigeration is the primary barrier to botulinum neurotoxin production in many processed foods. We identified 37 cases, including four deaths, that occurred during 1994–2021 in the United States from 13 events associated with inadequate refrigeration of commercially produced products. The number of people affected per event ranged from 1 to 16. Using enhanced cost estimates for foodborne botulism cases from a published economic model, these events were estimated to cost over $79M. Potential solutions to this recurring problem include the addition of a secondary barrier, such as an acidifier, to prevent botulinum toxin production, and better labeling to convey risks of refrigerated foods that have not been processed to destroy spores of C. botulinum and to decrease the occurrence of improper storage and handling. |
Notes from the field: Multistate, multiserotype outbreak of salmonella infections linked to cashew brie United States, 2021
Lewis K , Vasser M , Garman K , Higa J , Needham M , Irving DJ , Cavallo S , Sullivan D , Marks , Kirchner M , Madad A , McCormic ZD , Dunn J . MMWR Morb Mortal Wkly Rep 2023 72 (21) 589-90 |
Evaluation of the Illumina iSeq whole genome sequencing system for enteric disease surveillance and outbreak detection
Trees E , Poates A , Sabol A , LaFon P , Truong J , Lindsey R . J Microbiol Methods 2023 211 106784 The Illumina iSeq low-capacity sequencing platform was evaluated for use in foodborne disease surveillance and outbreak detection. The platform produced high quality sequence data comparable to that of the Illumina MiSeq and was cost-effective with fast turn-around time in low sample volume environments. |
Editorial: Emerging SARS-CoV-2 variants: genomic variations, transmission, pathogenesis, clinical impact, and interventions, volume II
Yadav PD , Patil DY , Kumar S , Bergeron E , Rodriguez SE . Front Med (Lausanne) 2023 10 1215309 This Research Topic has focused on subjects such as tracking emerging SARS-CoV-2 variants, detection, isolation, and genomic characterization of emerging variants, transmission, pathogenesis, clinical effects of variants, assessment of COVID-19 vaccination and treatment effectiveness, comparative analysis of SARS-CoV-2 genomic data, and other public health intervention measures. The Research Topic featured 27 articles highlighting the emergence of Omicron variants and their sub-lineages across the globe and their clinical presentations, specifically asymptomatic infections, COVID-19-associated liver injury, and comorbidities such as hypertension, diabetes, and bronchitis. Additionally, a few studies have reported the efficacy of therapeutic drugs in reducing viral load and the significance of vaccination and a booster dose against Omicron variants. Furthermore, the studies on genomic surveillance and evolutionary analysis have demonstrated the emergence of Omicron and its sub-lineages and their characteristic mutations. All these in-depth studies have explored various elements of Omicron, resulting in a comprehensive understanding of this variant. |
Investigation of multidrug-resistant plasmids from carbapenemase-producing Klebsiella pneumoniae clinical isolates from Pakistan
Lascols C , Cherney B , Conley AB , Rishishwar L , Crawford MA , Morse SA , Fisher DJ , Anderson K , Hodge DR , Pillai SP , Hughes MA , Khan E , Sue D . Front Microbiol 2023 14 1192097 OBJECTIVES: The study aim was to investigate multidrug-resistant (MDR) plasmids from a collection of 10 carbapenemase-producing Klebsiella pneumoniae clinical isolates identified within the same healthcare institution in Pakistan. Full characterization of the MDR plasmids including structure, typing characteristics, and AMR content as well as determination of their plasmid-based antimicrobial susceptibility profiles were carried out. METHODS: Plasmids were isolated from 10 clinical isolates of Klebsiella pneumoniae, and from a corresponding set of Escherichia coli transconjugants, then sequenced using Nanopore/Illumina technology to generate plasmid hybrid assemblies. Full characterization of MDR plasmids, including determination of next generation sequencing (NGS)-based AMR profiles, plasmid incompatibility groups, and types, was carried out. The structure of MDR plasmids was analyzed using the Galileo AMR platform. For E. coli transconjugants, the NGS-based AMR profiles were compared to NGS-predicted AMR phenotypes and conventional broth microdilution (BMD) antimicrobial susceptibility testing (AST) results. RESULTS: All carbapenemase-producing K. pneumoniae isolates (carrying either bla(NDM-1), or/and bla(OXA-48)) carried multiple AMR plasmids encoding 34 antimicrobial resistance genes (ARGs) conferring resistance to antimicrobials from 6 different classes. The plasmid incompatibility groups and types identified were: IncC (types 1 and 3), IncFIA (type 26) IncFIB, IncFII (types K1, K2, K7, and K9), IncHI1B, and IncL. None of the bla(NDM-1) and bla(ESBL)-plasmids identified in this study were previously described. Most bla(NDM-1-)plasmids shared identical AMR regions suggesting potential genetic material/plasmid exchange between K. pneumoniae isolates of this collection. The majority of NGS-based AMR profiles from the E. coli transconjugants correlated well with both NGS-based predicted and conventional AST results. CONCLUSION: This study highlights the complexity and diversity of the plasmid-based genetic background of carbapenemase-producing clinical isolates from Pakistan. This study emphasizes the need for characterization of MDR plasmids to determine their complete molecular background and monitor AMR through plasmid transmission between multi-resistant bacterial pathogens. |
xenoGI 3: using the DTLOR model to reconstruct the evolution of gene families in clades of microbes
Liu N , Gonzalez TA , Fischer J , Hong C , Johnson M , Mawhorter R , Mugnatto F , Soh R , Somji S , Wirth JS , Libeskind-Hadas R , Bush EC . BMC Bioinformatics 2023 24 (1) 295 To understand genome evolution in a group of microbes, we need to know the timing of events such as duplications, deletions and horizontal transfers. A common approach is to perform a gene-tree / species-tree reconciliation. While a number of software packages perform this type of analysis, none are geared toward a complete reconstruction for all families in an entire clade. Here we describe an update to the xenoGI software package which allows users to perform such an analysis using the newly developed DTLOR (duplication-transfer-loss-origin-rearrangement) reconciliation model starting from genome sequences as input. |
SARS-CoV-2 genomic diversity in households highlights the challenges of sequence-based transmission inference (preprint)
Bendall E , Paz-Bailey G , Santiago GA , Porucznik CA , Stanford JB , Stockwell MS , Duque J , Jeddy Z , Veguilla V , Major C , Rivera-Amill V , Rolfes MA , Dawood FS , Lauring AS . medRxiv 2022 10 (6) e0040022 Background: The reliability of sequence-based inference of SARS-CoV-2 transmission is not clear. Sequence data from infections among household members can define the expected genomic diversity of a virus along a defined transmission chain. Method(s): SARS-CoV-2 cases were identified prospectively among 2,369 participants in 706 households. Specimens with an RT-PCR cycle threshold <=30 underwent whole genome sequencing. Intrahost single nucleotide variants (iSNV) were identified at >=5% frequency. Phylogenetic trees were used to evaluate the relationship of household and community sequences. Result(s): There were 178 SARS-CoV-2 cases in 706 households. Among 147 specimens sequenced, 106 yielded a whole genome consensus with coverage suitable for identifying iSNV. Twenty-six households had sequences from multiple cases within 14 days. Consensus sequences were indistinguishable among cases in 15 households, while 11 had >1 consensus that differed by 1-2 mutations. Sequences from households and the community were often interspersed on phylogenetic trees. Identification of iSNV improved inference in 2 of 15 households with indistinguishable consensus sequences and 6 of 11 with distinct ones. Conclusion(s): In multiple infection households, whole genome consensus sequences differed by 0-1 mutations. Identification of shared iSNV occasionally resolved linkage, but the low genomic diversity of SARS-CoV-2 limits the utility of "sequence-only" transmission inference. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Vibrio tarriae sp. nov., a novel member of the Cholerae clade isolated from across the United States (preprint)
Islam MT , Liang K , Orata FD , Im MS , Alam M , Lee CC , Boucher YF . bioRxiv 2022 17 A number of bacteria with close resemblance to Vibrio cholerae has been isolated over the years by the Centers for Disease Control and Prevention (CDC), which could not be assigned a proper taxonomic designation based on preliminary identification methods. Nine such isolates have been found to share 16S rRNA gene identity exceeding 99% with V. cholerae, yet DNA-DNA hybridization (60.4-62.1%) and average nucleotide identity values (94.4-95.1%) were below the species cut-off, indicating a potentially novel species. Phylogenetic analysis of core genomes places this group of isolates in a monophyletic clade, within the "Cholerae clade," but distinct from any other species. Extensive phenotypic characterization reveals unique biochemical properties that distinguish this novel species from V. cholerae. Comparative genomic analysis reveals a unique set of siderophore genes, suggesting that iron acquisition strategies could be vital for the divergence of the novel species from a common ancestor with V. cholerae. Based on genetic, phylogenetic, and phenotypic differences observed, we propose these isolates represent a novel species of the genus Vibrio, for which the name Vibrio tarriae sp. nov. is proposed. Strain 2521-89 (= DSM 112461 = CCUG 75318), isolated from lake water, is the type strain. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Inhibition of vaccinia virus L1 N-myristoylation by the host N-myristoyltransferase inhibitor IMP-1088 generates non-infectious virions defective in cell entry (preprint)
Priyamvada L , Kallemeijn WW , Faronato M , Wilkins K , Goldsmith CS , Cotter CA , Ojeda S , Solari R , Moss B , Tate EW , Satheshkumar PS . bioRxiv 2022 13 (10) e1010662 We have recently shown that the replication of rhinovirus, poliovirus and foot-and-mouth disease virus requires the co-translational N-myristoylation of viral proteins by human host cell N-myristoyltransferases (NMTs), and is inhibited by treatment with IMP-1088, an ultrapotent small molecule NMT inhibitor. Here, we reveal the role of N-myristoylation during vaccinia virus (VACV) infection in human host cells and demonstrate the anti-poxviral effects of IMP-1088. N-myristoylated proteins from VACV and the host were metabolically labelled with myristic acid alkyne during infection using quantitative chemical proteomics. We identified VACV proteins A16, G9 and L1 to be N-myristoylated. Treatment with NMT inhibitor IMP-1088 potently abrogated VACV infection, while VACV gene expression, DNA replication, morphogenesis and EV formation remained unaffected. Importantly, we observed that loss of N-myristoylation resulted in greatly reduced infectivity of assembled mature virus particles, characterized by significantly reduced host cell entry and a decline in membrane fusion activity of progeny virus. While the N-myristoylation of VACV entry proteins L1, A16 and G9 was inhibited by IMP-1088, mutational and genetic studies demonstrated that the N-myristoylation of L1 was the most critical for VACV entry. Given the significant genetic identity between VACV, monkeypox virus and variola virus L1 homologs, our data provides a basis for further investigating the role of N-myristoylation in poxviral infections as well as the potential of selective NMT inhibitors like IMP-1088 as broad-spectrum poxvirus inhibitors. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Selective whole genome amplification as a tool to enrich specimens with low Treponema pallidum genomic DNA copies for whole genome sequencing (preprint)
Thurlow CM , Joseph SJ , Ganova-Raeva L , Katz SS , Pereira L , Chen C , Debra A , Vilfort K , Workowski K , Cohen SE , Reno H , Sun Y , Burroughs M , Sheth M , Chi KH , Danavall D , Philip SS , Cao W , Kersh EN , Pillay A . bioRxiv 2021 10 Downstream next generation sequencing (NGS) of the syphilis spirochete Treponema pallidum subspecies pallidum (T. pallidum) is hindered by low bacterial loads and the overwhelming presence of background metagenomic DNA in clinical specimens. In this study, we investigated selective whole genome amplification (SWGA) utilizing multiple displacement amplification (MDA) in conjunction with custom oligonucleotides with an increased specificity for the T. pallidum genome, and the capture and removal of CpG-methylated host DNA using the NEBNext Microbiome DNA Enrichment Kit followed by MDA with the REPLI-g Single Cell Kit as enrichment methods to improve the yields of T. pallidum DNA in isolates and lesion specimens from syphilis patients. Sequencing was performed using the Illumina MiSeq v2 500 cycle or NovaSeq 6000 SP platform. These two enrichment methods led to 93-98% genome coverage at 5 reads/site in 5 clinical specimens from the United States and rabbit propagated isolates, containing >14 T. pallidum genomic copies/ul of sample for SWGA and >129 genomic copies/ul for CpG methylation capture with MDA. Variant analysis using sequencing data derived from SWGA-enriched specimens, showed that all 5 clinical strains had the A2058G mutation associated with azithromycin resistance. SWGA is a robust method that allows direct whole genome sequencing (WGS) of specimens containing very low numbers of T. pallidum, which have been challenging until now. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Early detection of SARS-CoV-2 variants using traveler-based genomic surveillance at four US airports, September 2021- January 2022 (preprint)
Wegrzyn RD , Appiah GD , Morfino R , Milford SR , Walker AT , Ernst ET , Darrow WW , Li SL , Robison K , MacCannell D , Dai D , Girinathan BP , Hicks AL , Cosca B , Woronoff G , Plocik AM , Simen BB , Moriarty L , Guagliardo SAJ , Cetron MS , Friedman CR . medRxiv 2022 22 Background Despite layered mitigation measures, international travel during the COVID-19 pandemic continues to facilitate global spread of SARS-CoV-2, including novel variants of concern (VOCs). On November 26, 2021, B.1.1.529 (Omicron) was designated as a VOC by the World Health Organization [1]. On December 6, 2021, as part of measures to reduce the introduction and spread of Omicron, the requirement for a negative SARS-CoV-2 test taken before air travel to the United States was shortened from three days to one day pre-departure [1]. Although SARS-CoV-2 genomic sequencing has increased significantly during the pandemic [2], there is still a gap in early detection of emerging variants among arriving travelers. In September 2021, the Centers for Disease Control and Prevention (CDC), in collaboration with private partners, implemented a voluntary SARS-CoV-2 genomic surveillance pilot program. Initially we enrolled arriving air travelers from India. On November 28, we expanded the program to include travelers arriving from countries with high travel volumes, including those where Omicron was first detected. Methods Design, Setting, and Participants During September 29-November 27, 2021, the surveillance program included travelers arriving on seven direct flights from India at three international airports: John F. Kennedy, New York (September 29), Newark Liberty, New Jersey (October 4), and San Francisco, California (October 12). During November 28-January 23, Hartsfield-Jackson Atlanta International Airport, Georgia was added, and participation was offered to travelers from South Africa, Nigeria, the United Kingdom, France, Germany, and Brazil, arriving on approximately 50 flights per day. Participants were 18 years or older, provided informed consent, and completed demographic, clinical, and travel history questions. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Predictors of HIV testing among youth 15-24 years in urban Ethiopia, 2017-2018 Ethiopia population-based HIV impact assessment
Ajiboye AS , Eshetu F , Lulseged S , Getaneh Y , Tademe N , Kifle T , Bray R , Eshete H , Demissie Y , Dykewicz CA , Hoos D . PLoS One 2023 18 (7) e0265710 INTRODUCTION: Youth (adolescents and young adults) aged 15-24 years comprise approximately 22% of Ethiopia's total population and make up 0.73% of HIV cases in urban Ethiopia. However, only 63% of HIV-positive youth are aware of their HIV status. We describe the HIV testing behaviors of youth 15-24 years and determined the characteristics of those who were most likely to be tested for HIV within the past year. METHODS: Using data from the 2017-2018 Ethiopia Population-based HIV Impact Assessment, we provide survey-weighted estimates and prevalence risk ratios for engagement in HIV testing in the 12 months preceding the survey. We model the likelihood of HIV testing one year or more before the survey compared to never testing, using a multinomial logistic regression model. RESULTS: Among HIV-negative and unaware HIV-positive youth 15-24 years old (N = 7,508), 21.8% [95% Confidence Interval (CI): 20.4-23.3%] reported testing for HIV in the last 12 months. Female youth [Prevalence Ratio (PR) = 1.6, 95% CI: 1.4-1.8], those aged 20-24 years (PR = 2.6, 95% CI:2.3-2.9), and those ever married (PR = 2.8, 95% CI: 2.5-3.1) were more likely to have tested for HIV within the last year. Adjusting for select demographic characteristics, sex with a non-spousal or non-live-in partner [Relative Risk (RR) = 0.3, 95% CI:0.1-0.8] among males did not increase their likelihood to test for HIV in the prior 12 months. Female youth engaged in antenatal care (RR = 3.0, 95% CI: 1.7-5.3) were more likely to test for HIV in the past year. CONCLUSION: The Ethiopian HIV case finding strategy may consider approaches for reaching untested youth, with a specific focus on adolescent males,15-19 years of age. This is critical towards achieving the UNAIDS HIV testing goal of 95% of all individuals living with HIV aware of their status by 2030. |
Self-Reported Mask Use among Persons with or without SARS CoV-2 Vaccination -United States, December 2020-August 2021 (preprint)
Calamari LE , Weintraub WS , Santos R , Gibbs M , Bertoni AG , Ward LM , Saydah S , Plumb ID , Runyon MS , Wierzba TF , Sanders JW , Herrington D , Espeland MA , Williamson J , Mongraw-Chaffin M , Bertoni A , Alexander-Miller MA , Castri P , Mathews A , Munawar I , Seals AL , Ostasiewski B , Ballard CAP , Gurcan M , Ivanov A , Zapata GM , Westcott M , Blinson K , Blinson L , Mistysyn M , Davis D , Doomy L , Henderson P , Jessup A , Lane K , Levine B , McCanless J , McDaniel S , Melius K , O'Neill C , Pack A , Rathee R , Rushing S , Sheets J , Soots S , Wall M , Wheeler S , White J , Wilkerson L , Wilson R , Wilson K , Burcombe D , Saylor G , Lunn M , Ordonez K , O'Steen A , Wagner L , McCurdy LH , Gibbs MA , Taylor YJ , Calamari L , Tapp H , Ahmed A , Brennan M , Munn L , Dantuluri KL , Hetherington T , Lu LC , Dunn C , Hogg M , Price A , Leonidas M , Manning M , Rossman W , Gohs FX , Harris A , Priem JS , Tochiki P , Wellinsky N , Silva C , Ludden T , Hernandez J , Spencer K , McAlister L , Weintraub W , Miller K , Washington C , Moses A , Dolman S , Zelaya-Portillo J , Erkus J , Blumenthal J , Romero Barrientos RE , Bennett S , Shah S , Mathur S , Boxley C , Kolm P , Franklin E , Ahmed N , Larsen M , Oberhelman R , Keating J , Kissinger P , Schieffelin J , Yukich J , Beron A , Teigen J , Kotloff K , Chen WH , Friedman-Klabanoff D , Berry AA , Powell H , Roane L , Datar R , Correa A , Navalkele B , Min YI , Castillo A , Ward L , Santos RP , Anugu P , Gao Y , Green J , Sandlin R , Moore D , Drake L , Horton D , Johnson KL , Stover M , Lagarde WH , Daniel L , Maguire PD , Hanlon CL , McFayden L , Rigo I , Hines K , Smith L , Harris M , Lissor B , Cook V , Eversole M , Herrin T , Murphy D , Kinney L , Diehl P , Abromitis N , Pierre TSt , Heckman B , Evans D , March J , Whitlock B , Moore W , Arthur S , Conway J , Gallaher TR , Johanson M , Brown S , Dixon T , Reavis M , Henderson S , Zimmer M , Oliver D , Jackson K , Menon M , Bishop B , Roeth R , King-Thiele R , Hamrick TS , Ihmeidan A , Hinkelman A , Okafor C , Bray Brown RB , Brewster A , Bouyi D , Lamont K , Yoshinaga K , Vinod P , Peela AS , Denbel G , Lo J , Mayet-Khan M , Mittal A , Motwani R , Raafat M , Schultz E , Joseph A , Parkeh A , Patel D , Afridi B , Uschner D , Edelstein SL , Santacatterina M , Strylewicz G , Burke B , Gunaratne M , Turney M , Zhou SQ , Tjaden AH , Fette L , Buahin A , Bott M , Graziani S , Soni A , Mores C , Porzucek A , Laborde R , Acharya P , Guill L , Lamphier D , Schaefer A , Satterwhite WM , McKeague A , Ward J , Naranjo DP , Darko N , Castellon K , Brink R , Shehzad H , Kuprianov D , McGlasson D , Hayes D , Edwards S , Daphnis S , Todd B , Goodwin A , Berkelman R , Hanson K , Zeger S , Hopkins J , Reilly C , Edwards K , Gayle H , Redd S . medRxiv 2022 10 Wearing a facemask can help to decrease the transmission of COVID-19. We investigated self-reported mask use among subjects aged 18 years and older participating in the COVID-19 Community Research Partnership (CRP), a prospective longitudinal COVID-19 surveillance study in the mid-Atlantic and southeastern United States. We included those participants who completed >=5 daily surveys each month from December 1, 2020 through August 31, 2021. Mask use was defined as self-reported use of a face mask or face covering on every interaction with others outside the household within a distance of less than 6 feet. Participants were considered vaccinated if they reported receiving >=1 COVID-19 vaccine dose. Participants (n=17,522) were 91% non-Hispanic White, 68% female, median age 57 years, 26% healthcare workers, with 95% self-reported receiving >=1 COVID-19 vaccine dose through August; mean daily survey response was 85%. Mask use was higher among vaccinated than unvaccinated participants across the study period, regardless of the month of the first dose. Mask use remained relatively stable from December 2020 through April (range 71-80% unvaccinated; 86-93% vaccinated) and declined in both groups beginning in mid-May 2021 to 34% and 42% respectively in June 2021; mask use has increased again since July 2021. Mask use by all was lower during weekends and on Christmas and Easter, regardless of vaccination status. Independent predictors of higher mask use were vaccination, age >=65 years, female sex, racial or ethnic minority group, and healthcare worker occupation, whereas a history of self-reported prior COVID-19 illness was associated with lower use. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Predictors of HIV Testing among Youth 15-24 Years in Urban Ethiopia, 2017-2018 Ethiopia Population-Based HIV Impact Assessment (preprint)
Ajiboye AS , Eshetu F , Lulseged S , Getaneh Y , Tademe N , Kifle T , Bray R , Eshete H , Demissie Y , Dykewicz CA , Hoos D . medRxiv 2022 20 Introduction: Youth (adolescents and young adults) aged 15-24 years comprise approximately 22% of Ethiopia's total population and make up 0.73% of HIV cases in urban Ethiopia. However, only 63% of HIV-positive youth are aware of their HIV status. We described the HIV testing behaviors of youth 15-24 years and determined the characteristics of those who were most likely to be tested for HIV within the past year. Method(s): Using data from the 2017-2018 Ethiopia Population-based HIV Impact Assessment, we provide survey-weighted estimates and prevalence risk ratios for engagement in HIV testing in the 12 months preceding the survey. We model the likelihood of HIV testing one year or more before the survey compared to never testing, using a multinomial logistic regression model. Result(s): Among HIV-negative and unaware HIV-positive youth 15-24 years old (N=7,508), 21.8% [95% Confidence Interval (CI): 20.4-23.3%] reported testing for HIV in the last 12 months. Female youth [Prevalence Ratio (PR)=1.6, 95% CI: 1.4-1.8], those aged 20-24 years (PR=2.6, 95% CI:2.3-2.9), and those ever married (PR=2.8, 95% CI: 2.5-3.1) were more likely to have tested for HIV within the last year. Adjusting for select demographic characteristics, sex with a non-spousal or non-live-in partner [Relative Risk (RR)=0.3, 95% CI:0.1-0.8] among males did not increase their likelihood to test for HIV in the prior 12 months. Female youth engaged in antenatal care (RR=3.0, 95% CI: 1.7-5.3) were more likely to test for HIV in the past year. Conclusion(s): The Ethiopian HIV case finding strategy may consider approaches for reaching untested youth, with a specific focus on adolescent males. This is critical towards achieving the UNAIDS HIV testing goal of 95% of all individuals living with HIV aware of their status by 2030. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Problems paying medical bills among adults with diagnosed HIV in the United States
Luna-Gierke RE , Tie Y , Yuan X , Luo Q , Beer L , Dasgupta S . J Assoc Nurses AIDS Care 2023 34 (5) 432-439 Problems paying medical bills may affect HIV outcomes among people with HIV (PWH), thus limiting progress toward achieving national HIV prevention goals. We analyzed nationally representative data from CDC's Medical Monitoring Project collected during 6/2018-5/2020. Among 8,108 PWH, we reported weighted percentages of characteristics and examined associations between problems paying medical bills and clinical outcomes using prevalence ratios with predicted marginal means, adjusting for potential confounding. Nineteen percent of PWH reported problems paying medical bills. Problems paying medical bills were more prevalent among persons who experienced homelessness (26.9% vs. 18.3%). People with problems paying medical bills were more likely to have adverse HIV outcomes and were more likely to have ≥1 emergency room visit (prevalence ratio [PR]: 1.59; 95% CI [1.51-1.68]) or hospitalization (PR: 1.72; 95% CI [1.55-1.91]) in the past year. Identifying PWH experiencing financial barriers and expanding access to safety net programs could improve access to care and outcomes. |
QuickStats: Percentage* of currently employed adults aged 18 years who have paid sick leave,(†) by education level - National Health Interview Survey, 2021(§)
Rosa RR , Asfaw A . MMWR Morb Mortal Wkly Rep 2023 72 (17) 473 In 2021, 72.5% of employed adults had paid sick leave. The percentage with sick leave was highest among workers with a bachelor’s degree or higher (83.6%), followed by workers with an associate degree (73.2%). The percentage of sick leave was similar for workers with some college (66.3%) and those with a high school diploma or GED (64.4%). The lowest percentage of sick leave occurred among workers with less than a high school education (48.8%). |
Productivity costs associated with reactive school closures related to influenza or influenza-like illness in the United States from 2011 to 2019 (preprint)
Park J , Joo H , Maskery BA , Zviedrite N , Uzicanin A . medRxiv 2023 07 (6) e0286734 Introduction Schools close in reaction to seasonal influenza outbreaks and, on occasion, pandemic influenza. The unintended costs of reactive school closures associated with influenza or influenza-like illness (ILI) has not been studied previously. We estimated the costs of ILI-related reactive school closures in the United States over eight academic years. Methods We used prospectively collected data on ILI-related reactive school closures from August 1, 2011 to June 30, 2019 to estimate the costs of the closures, which included productivity costs for parents, teachers, and non-teaching school staff. Productivity cost estimates were evaluated by multiplying the number of days for each closure by the state- and year-specific average hourly or daily wage rates for parents, teachers, and school staff. We subdivided total cost and cost per student estimates by school year, state, and urbanicity of school location. Results The estimated productivity cost of the closures was $476 million in total during the eight years, with most (90%) of the costs occurring between 2016-2017 and 2018-2019, and in Tennessee (55%) and Kentucky (21%). Among all U.S. public schools, the annual cost per student was much higher in Tennessee ($33) and Kentucky ($19) than any other state ($2.4 in the third highest state) or the national average ($1.2). The cost per student was higher in rural areas ($2.9) or towns ($2.5) than cities ($0.6) or suburbs ($0.5). Locations with higher costs tended to have both more closures and closures with longer durations. Conclusions In recent years, we found significant heterogeneity in year-to-year costs of ILI-associated reactive school closures. These costs have been greatest in Tennessee and Kentucky and been elevated in rural or town areas relative to cities or suburbs. Our findings might provide evidence to support efforts to reduce the burden of seasonal influenza in these disproportionately impacted states or communities. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
The economic burden of RSV-associated illness in children aged <5 years, South Africa 2011-2016 (preprint)
Moyes J , Tempia S , Walaza S , McMorrow ML , Treurnicht F , Wolter N , von Gottberg A , Kahn K , Cohen AL , Dawood H , Variava E , Cohen C . medRxiv 2022 21 Introduction Data on the economic burden of RSV-associated illness will inform decisions on the programmatic implementation of maternal vaccines and monoclonal antibodies. We estimated these costs in fine age bands to allow more accurate cost-effectiveness models to account for limited duration of protection conferred by short or long acting interventions. Methods We conducted a costing study at sentinel sites across South Africa to estimate out-of-pocket and indirect costs for RSV-associated mild and severe illness. We collected facility-specific costs for staffing, equipment, services, diagnostic tests and treatment. Using case-based data we calculated a patient day equivalent (PDE) for RSV-associated hospitalisations or clinic visits; the PDE was multiplied by the number of days of care to provide a case-cost to the healthcare system. We estimated the costs in 3-month age intervals in children aged <1 years and as a single group for children aged 1-4 years. We then applied our data to a modified version of the World Health Organization tool for estimating mean annual national cost burden, including medically and non-medically attended RSV-associated illness. Results The estimated mean annual cost of RSV-associated Illness in children aged <5 years was United States dollars ($)137 204 393, of which 81% ($111 742 713) were healthcare system incurred, 6% ($8 881 612) were out of pocket expenses and 13% ($28 225 801) were indirect costs. Thirty-three percent ($45 652 677/$137 204 393) of the total cost in children aged <5 years was in the <3-month age group, of which 52% ($71 654 002) were healthcare system incurred. The costs of non-medically attended cases increased with age from $3 307 218 in the <3-month age group to $8 603 377 in the 9-11-month age group. Conclusion Among children <5 years of age with RSV in South Africa, the highest cost burden was in young infants; therefore, interventions against RSV targeting this age group are important to reduce the health and cost burden of RSV-associated illness. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Estimating the cost-effectiveness of maternal vaccination and monoclonal antibodies for respiratory syncytial virus in Kenya and South Africa (preprint)
Koltai M , Moyes J , Nyawanda B , Nyiro J , Munywoki P , Tempia S , Li X , Antillon M , Bilcke J , Flasche S , Beutels P , Nokes DJ , Cohen C , Jit M . medRxiv 2022 10 Background Respiratory syncytial virus (RSV) causes a substantial burden of acute lower respiratory infection in children under 5 years, particularly in low- and middle-income countries (LMICs). Maternal vaccine (MV) and next-generation monoclonal antibody (mAb) candidates have been shown to reduce RSV disease in infants in phase III clinical trials. The cost-effectiveness of these biologics has been estimated using disease burden data from global meta-analyses, but these are sensitive to the detailed age breakdown of paediatric RSV disease, for which there have previously been limited data. Methods We use original hospital-based incidence data from South Africa and Kenya collected between 2010 and 2018 of RSV-associated acute respiratory infection (ARI), influenza-like illness (ILI), severe acute respiratory infection (SARI) as well as deaths with monthly age-stratification, supplemented with data on healthcare-seeking behaviour and costs to the healthcare system and households. We estimated the incremental cost per DALY averted (incremental cost-effectiveness ratio or ICER) of public health interventions by MV or mAb for a plausible range of prices (3-30 USD for vaccines and 6-60 USD for monoclonals), using an adapted version of a previously published health economic model (McMarcel) of RSV immunisation. Results Our data show higher disease incidence for infants younger than 6 months of age in the case of Kenya and South Africa than suggested by earlier projections from community incidence-based meta-analyses of LMIC data. Since MV and mAb provide protection for these youngest age groups, this leads to a substantially larger reduction of disease burden and therefore, more favourable cost-effectiveness of both interventions in both countries. Specifically, using published efficacy data, our mean estimate for reducing RSV-associated deaths in children under 5 years of age is 9% for MV and 28% for mAb in Kenya. In South Africa, the reduction is larger, with the mean estimate of 14% for MV and 48% for mAb. In the case of the lowest dose prices (3 USD for MV and 6 USD for mAb), the healthcare system perspective ICERs per DALY averted drop to 144 USD (mAb) and 397 USD (MV) in Kenya, whereas it is net cost-saving from the perspective of the South African healthcare system. At the highest assumed dose prices of 30 USD for MV and 60 USD for mAb, the median estimates for the ICER are 4528 USD for MV and 2748 USD for mAb in Kenya, while in South Africa, it is 4694 USD for MV and 2566 USD for mAb. Conclusion Interventions against RSV disease may be more cost-effective than previously estimated following the incorporation of new data indicating that the disease burden is highly concentrated in the first 6 months of life in two African settings. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. |
Estimation of the Lifetime Quality-Adjusted Life Years (QALYs) Lost Due to Syphilis acquired in the United States in 2018 (preprint)
Lee K , You S , Li Y , Chesson H , Gift TL , Berruti AA , Hsu K , Yaesoubi R , Salomon JA , Ronn M . medRxiv 2022 28 Background: The purpose of this study was to estimate the health impact of syphilis in the United States in terms of the number of quality-adjusted life years (QALYs) lost attributable to infections in 2018. Method(s): We developed a Markov model which simulates the natural history and long-term sequelae of syphilis. The model was parameterized by sex (men and women), sexual orientation (women who have sex with men, men who have sex with women [MSW], and men who have sex with men [MSM]), and by age at primary infection. We developed a separate decision tree model to account for health losses due to congenital syphilis. We estimated the average lifetime number of QALYs lost per infection, and the total expected lifetime number of QALYs lost due to syphilis acquired in 2018. We performed probabilistic sensitivity analysis to account for uncertainty in the model's estimates. Finding(s): We estimated the average number of discounted lifetime QALYs lost per infection as 0.09 [0.03-0.19 95% uncertainty interval (UI)]. The QALY loss per infection was lower among MSM (0.06) than among MSW (0.15) and women (0.10). The total expected number of QALYs lost due to syphilis acquired in 2018 was 13,349 (5,071-31,360 95%UI). MSM account for 6,373 (47.7%) of the overall burden, compared to MSW (32.1%) and women (20.2%). For each case of congenital syphilis, we estimated 1.79 (1.43-2.16 95%UI) QALYs lost for the child and 0.06 (0.01-0.14 95%UI) QALYs lost for the mother. These per-case estimates correspond to 2,332 (1,871-2,825 95%UI) and 79 (17-177 95%UI) QALYs lost for children and mothers, respectively, due to congenital syphilis in 2018. Conclusion(s): Syphilis causes substantial health losses in adults and children. Quantifying these health losses in terms of QALYs can inform cost-effectiveness analyses and can facilitate comparisons of the burden of syphilis to that of other diseases. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Diabetes prevalence and incidence inequality trends among US adults, 2008-2021
Saelee R , Hora IA , Pavkov ME , Imperatore G , Chen Y , Benoit SR , Holliday CS , Bullard KM . Am J Prev Med 2023 65 (6) 973-982 INTRODUCTION: This study examined national trends in age, sex, racial and ethnic, and socioeconomic inequalities for diagnosed diabetes prevalence and incidence among US adults from 2008-2021. METHODS: Adults (≥18 years) were from the National Health Interview Survey (2008-2021). The annual between-group variance (BGV) for sex, race, and ethnicity, and the slope index of inequality (SII) for age, education, and poverty-to-income ratio (PIR) along with the average annual percent change (AAPC) were estimated in 2023 to assess trends in inequalities over time in diabetes prevalence and incidence. For BGV and SII, a value of 0 represents no inequality while a value further from 0 represents greater inequality. RESULTS: On average over time, PIR inequalities in diabetes prevalence worsened (SII: -8.24 in 2008 and -9.80 in 2021; AAPC for SII: -1.90%, p=0.003) while inequalities in incidence for age (SII: 17.60 in 2008 and 8.85 in 2021; AAPC for SII: -6.47%, p<0.001), sex (BGV: 0.09 in 2008, 2.05 in 2009, 1.24 in 2010, and 0.27 in 2021; AAPC for BGV: -12.34%, p=0.002), racial and ethnic (BGV: 4.80 in 2008 and 2.17 in 2021; AAPC for BGV: -10.59%, p=0.010), and education (SII: -9.89 in 2008 and -2.20 in 2021; AAPC for SII: 8.27%, p=0.001) groups improved. CONCLUSIONS: From 2008-2021, age, sex, racial and ethnic, and education inequalities in the incidence of diagnosed diabetes improved but persisted. Income-related diabetes prevalence inequalities worsened over time. To close these gaps, future research could focus on identifying factors driving these trends including the contribution of morbidity and mortality. |
Retirement and cognitive aging in a racially diverse sample of older Americans
Andel R , Veal BM , Howard VJ , MacDonald LA , Judd SE , Crowe M . J Am Geriatr Soc 2023 71 (9) 2769-2778 BACKGROUND: Retirement represents a crucial transitional period for many adults with possible consequences for cognitive aging. We examined trajectories of cognitive change before and after retirement in Black and White adults. METHODS: Longitudinal examination of up to 10 years (mean = 7.1 ± 2.2 years) using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study-a national, longitudinal study of Black and White adults ≥45 years of age. Data were from 2226 members of the REGARDS study who retired around the time when an occupational ancillary survey was administered. Cognitive function was an average of z-scores for tests of verbal fluency, memory, and global function. RESULTS: Cognitive functioning was stable before retirement (Estimate = 0.05, p = 0.322), followed by a significant decline after retirement (Estimate = -0.15, p < 0.001). The decline was particularly pronounced in White (Estimate = -0.19, p < 0.001) compared with Black (Estimate = -0.07, p = 0.077) participants, twice as large in men (Estimate = -0.20, p < 0.001) compared with women (Estimate = -0.11, p < 0.001), highest among White men (Estimate = -0.22, p < 0.001) and lowest in Black women (Estimate = -0.04, p = 0.457). Greater post-retirement cognitive decline was also observed among participants who attended college (Estimate = -0.14, p = 0.016). While greater work complexity (Estimate = 0.92, p < 0.05) and higher income (Estimate = 1.03, p < 0.05) were related to better cognitive function at retirement, neither was significantly related to cognitive change after retirement. CONCLUSION: Cognitive functioning may decline at an accelerated rate immediately post-retirement, more so in White adults and men than Black adults and women. Lifelong structural inequalities including occupational segregation and other social determinants of cognitive health may obscure the role of retirement in cognitive aging. |
Community-engaged Mpox vaccination provides lessons for equitable health care in the United States
Guilamo-Ramos V , Thimm-Kaiser M , Benzekri A . Nat Med 2023 29 (9) 2160-2161 The United States is facing sizable and longstanding challenges on the path to health equity, including persistently inequitable outcomes within healthcare and national public-health initiatives. The number of voices calling for substantive reform of the increasingly expensive and, by international comparison, ineffective US healthcare system is growing. At this inflection point for health equity and health-service delivery, an examination of the current state of sexual health in the United States illustrates several failures and a notable recent success during the 2022 Mpox (formerly monkeypox) response, which highlight actionable priorities for improving the broader healthcare complex. |
Rural/urban differences in health care utilization and costs by perinatal depression status among commercial enrollees
Pollack LM , Chen J , Cox S , Luo F , Robbins CL , Tevendale H , Li R , Ko JY . J Rural Health 2023 40 (1) 26-63 PURPOSE: To understand differences in health care utilization and medical expenditures by perinatal depression (PND) status during pregnancy and 1-year postpartum overall and by rural/urban status. METHODS: We estimated differences in health care utilization and medical expenditures by PND status for individuals with an inpatient live-birth delivery in 2017, continuously enrolled in commercial insurance from 3 months before pregnancy through 1-year postpartum (study period), using MarketScan Commercial Claims data. Multivariable regression was used to examine differences by rurality. FINDINGS: Ten percent of commercially insured individuals had claims with PND. A smaller proportion of rural (8.7%) versus urban residents (10.0%) had a depression diagnosis (p < 0.0001). Of those with PND, a smaller proportion of rural (5.5%) versus urban residents (9.6%) had a depression claim 3 months before pregnancy (p < 0.0001). Compared with urban residents, rural residents had greater differences by PND status in total inpatient days (rural: 0.7, 95% confidence interval [CI]: 0.6-0.9 vs. urban: 0.5, 95% CI: 0.5-0.6) and emergency department (ED) visits (rural: 0.7, 95% CI: 0.6-0.9 vs. urban: 0.5, 95% CI: 0.4-0.5), but a smaller difference by PND status in the number of outpatient visits (rural: 9.2, 95% CI: 8.2-10.2 vs. urban: 13.1, 95% CI: 12.7-13.5). Differences in expenditures for inpatient services by PND status differed by rural/urban status (rural: $2654; 95% CI: $1823-$3485 vs. urban: $1786; 95% CI: $1445-$2127). CONCLUSIONS: Commercially insured rural residents had more utilization for inpatient and ED services and less utilization for outpatient services. Rural locations can present barriers to evidence-based care to address PND. |
Residential social vulnerability among healthcare personnel with and without severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection in Five US states, May-December 2020
Zlotorzynska M , Chea N , Eure T , Alkis Ramirez R , Blazek GT , Czaja CA , Johnston H , Barter D , Kellogg M , Emanuel C , Lynfield R , Fell A , Lim S , Lovett S , Phipps EC , Shrum Davis S , Sievers M , Dumyati G , Concannon C , Myers C , McCullough K , Woods A , Hurley C , Licherdell E , Pierce R , Ocampo VLS , Hall E , Magill SS , Grigg CT . Infect Control Hosp Epidemiol 2023 1-7 OBJECTIVE: To characterize residential social vulnerability among healthcare personnel (HCP) and evaluate its association with severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection. DESIGN: Case-control study. SETTING: This study analyzed data collected in May-December 2020 through sentinel and population-based surveillance in healthcare facilities in Colorado, Minnesota, New Mexico, New York, and Oregon. PARTICIPANTS: Data from 2,168 HCP (1,571 cases and 597 controls from the same facilities) were analyzed. METHODS: HCP residential addresses were linked to the social vulnerability index (SVI) at the census tract level, which represents a ranking of community vulnerability to emergencies based on 15 US Census variables. The primary outcome was SARS-CoV-2 infection, confirmed by positive antigen or real-time reverse-transcriptase- polymerase chain reaction (RT-PCR) test on nasopharyngeal swab. Significant differences by SVI in participant characteristics were assessed using the Fisher exact test. Adjusted odds ratios (aOR) with 95% confidence intervals (CIs) for associations between case status and SVI, controlling for HCP role and patient care activities, were estimated using logistic regression. RESULTS: Significantly higher proportions of certified nursing assistants (48.0%) and medical assistants (44.1%) resided in high SVI census tracts, compared to registered nurses (15.9%) and physicians (11.6%). HCP cases were more likely than controls to live in high SVI census tracts (aOR, 1.76; 95% CI, 1.37-2.26). CONCLUSIONS: These findings suggest that residing in more socially vulnerable census tracts may be associated with SARS-CoV-2 infection risk among HCP and that residential vulnerability differs by HCP role. Efforts to safeguard the US healthcare workforce and advance health equity should address the social determinants that drive racial, ethnic, and socioeconomic health disparities. |
Using the prevention impacts simulation model to estimate long-term impacts of multisector community partnerships' efforts to address social determinants of health
Honeycutt AA , Yarnoff B , Tayebali Z , Glasgow L , Hacker K . Prev Chronic Dis 2023 20 E62 Public health plays a key role in addressing social determinants of health (SDOH) through multisector community partnerships (MCPs), which contribute to community changes that promote healthy living; however, little is known about the longer-term impact of MCP-driven interventions. We used the Prevention Impacts Simulation Model (PRISM) in a rapid evaluation to better understand the implementation and potential impact of MCPs' SDOH initiatives. Results suggest that, if sustained, initiatives implemented by the 27 included MCPs may prevent 880 premature deaths and avert $125.7 million in medical costs over 20 years. As a validated model that estimates impact by using available implementation data, PRISM is a useful tool for evaluating SDOH initiatives. |
Previous health care experiences' influence on health care perceptions among residents of six homeless shelters in Seattle, Washington, July-October 2021
Meehan AA , Cox SN , Thuo NB , Rogers JH , Link AC , Martinez MA , Lo NK , Manns BJ , Rolfes MA , Chow EJ , Chu HY , Mosites E , Al Achkar M . J Patient Cent Res Rev 2023 10 (3) 111-120 PURPOSE: The study purpose was to learn and describe 1) where homeless shelter residents receive health care, 2) what contributes to positive or negative health care experiences among shelter residents, and 3) shelter resident perceptions toward health care. METHODS: Semi-structured interviews (SSIs) utilizing purposive sampling and focus group discussions (FGDs) utilizing convenience sampling were conducted at 6 homeless shelters in Seattle-King County, Washington, during July-October 2021. All residents (age ≥18) were eligible to participate. SSIs were conducted with 25 residents, and 8 FGDs were held. Thematic analysis was conducted using Dedoose. RESULTS: Participants received health care in settings ranging from no regular care to primary care providers. Four elements emerged as contributing positively and negatively to health care experiences: 1) ability to access health care financially, physically, and technologically; 2) clarity of communication from providers and staff about appointment logistics, diagnoses, and treatment options; 3) ease of securing timely follow-up services; and 4) respect versus stigma and discrimination from providers and staff. Participants who felt positively toward health care found low- or no-cost care to be widely available and encouraged others to seek care. However, some participants described health care in the United States as greedy, classist, discriminatory, and untrustworthy. Participants reported delaying care and self-medicating in anticipation of discrimination. CONCLUSIONS: Findings demonstrate that while people experiencing homelessness can have positive experiences with health care, many have faced negative interactions with health systems. Improving the patient experience for those experiencing homelessness can increase engagement and improve health outcomes. |
CDC-funded HIV testing services outcomes and social determinants of health in Ending the HIV Epidemic in the U.S. Jurisdictions
Patel D , Clark HA , Williams WO , Taylor-Aidoo N , Wright C . AIDS Behav 2023 We performed an ecological analysis to examine associations between CDC-funded HIV testing services outcomes and social determinants of health (SDOH) among Ending the HIV Epidemic in the U.S. jurisdictions. Using National HIV Prevention Program Monitoring & Evaluation (2020) and American Community Survey (2016-2020) data, we ran robust Poisson models (adjusted for race/ethnicity). In healthcare settings, a 10% absolute increase in percentage without health insurance was associated with a 40% lower prevalence of newly diagnosed positivity (aPR = 0.60, 95% CI: 0.43-0.83); a $5,000 increase in median household income (aPR = 1.04, 95% CI: 1.03-1.06) and a 10% absolute increase in percentage unemployed (aPR = 1.80, 95% CI: 1.31-2.46) were associated with 4% and 80%, respectively, higher prevalence of percentage linked to HIV medical care within 30 days of diagnosis (i.e., linkage). In non-healthcare settings, a 10% absolute increase in percentage with less than high school diploma (aPR = 0.53, 95% CI: 0.29-0.96) was associated with a 47% lower prevalence of newly diagnosed positivity, whereas a 10% absolute increase in percentage without health insurance (aPR = 1.92, 95% CI: 1.29-2.88) was associated with a 92% higher prevalence of newly diagnosed positivity; a 10% absolute increase in percentage with less than high school diploma was associated with a 35% lower prevalence of linkage (aPR = 0.65, 95% CI: 0.43-0.97). Addressing SDOH in HIV prevention programs will play an important role in ending the HIV epidemic. |
NHAMCS has been a trusted source of data for healthcare disparities research since 1992
Schappert SM , Santo L , Ward BW , Ashman JJ , DeFrances CJ . Public Health Nurs 2023 40 (6) 811-812 The National Center for Health Statistics (NCHS) conducts the National Hospital Ambulatory Medical Care Survey (NHAMCS), a national probability sample survey of visits to U.S. hospital emergency departments (EDs). NCHS staff recently became aware of a Brief Report published in the July 2022 issue of Public Health Nursing (Marye, 2022) which claimed that healthcare disparities research was limited with NHAMCS data; however, the report included inaccuracies about the survey and its data that should be clarified. NHAMCS has been conducted annually since 1992 and has been used for decades to understand the provision of ambulatory medical care at hospitals, as well as disparities in this care. A brief search in the PubMed® database returns hundreds of peer-reviewed research manuscripts using NHAMCS data, with at least 40 focusing on healthcare disparities. Furthermore, NHAMCS continues to be used in various U.S. government reports that focus on health care and health disparities (Agency for Healthcare Research and Quality, 2022; National Center for Health Statistics, 2023). |
Differential impact of the COVID-19 pandemic on excess mortality and life expectancy loss within the Hispanic population (preprint)
Arias E , Tejada-Vera B . medRxiv 2023 07 Background The impact of the COVID-19 pandemic on the Hispanic population resulted in the almost complete elimination of the longstanding Hispanic mortality advantage relative to the non-Hispanic White population. However, it is unknown how COVID-19 mortality affected the diverse Hispanic sub-populations. Objective We estimate life expectancy at birth in 2019 and 2020 by Hispanic sub-group and explore how changes in age-specific all-cause and COVID-19 mortality affected changes in life expectancy between 2019 and 2020 for each group. Methods We use final 2019 and 2020 mortality data from the National Center for Health Statistics and population estimates based on the 2019 and 2020 American Community Survey. We calculate life tables and apply decomposition techniques to explore the effects of changes in age- and cause-specific mortality on life expectancy. Results Patterns of age- and cause-specific excess deaths and their impact on declines in life expectancy due to the COVID-19 pandemic differed substantially by Hispanic sub-group. Life expectancy losses ranged from 0.6 to 6.7 years among males and 0.6 to 3.6 years among females. Conclusions Our findings highlight the heterogeneous impact of the COVID-19 pandemic within the Hispanic population. Contributions Our findings contribute new information that will assist future research identify the causes of the disproportionately severe impact of the COVID-19 pandemic on the Hispanic population. Our study underscores the importance of population disaggregation in endeavors to identify the multiple pathways by which the pandemic affected the Hispanic population. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Donor-derived transmission of hepatitis A virus following kidney transplantation: Clinical course of two cases from one donor
Jones JM , Agarwal A , Moorman AC , Hofmeister MG , Hulse JC , Meneveau MO , Mixon-Hayden T , Ramachandran S , Jones CM , Kellner S , Ferrell D , Sifri CD . Transplant Direct 2023 9 (8) e1506 Donor-derived transmission of infections is a rare complication of kidney transplant. Hepatitis A virus (HAV) is a common cause of acute viral hepatitis worldwide, but donor-derived transmission to organ recipients has been reported in the literature only twice previously. The timeline for HAV incubation and clearance in transplant recipients is not well understood. METHODS: In 2018, 2 kidneys and a liver were procured from a deceased donor resident of Kentucky, one of many states that was experiencing an HAV outbreak associated with person-to-person transmission through close contact, primarily among people who reported drug use. Both kidney recipients, residents of Virginia, subsequently developed acute HAV infections. We report the results of an investigation to determine the source of transmission and describe the clinical course of HAV infection in the infected kidney recipients. RESULTS: The liver recipient had evidence of immunity to HAV and did not become infected. The donor and both kidney recipients were found to have a genetically identical strain of HAV using a next-generation sequencing-based cyber molecular assay (Global Hepatitis Outbreak Surveillance Technology), confirming donor-derived HAV infections in kidney recipients. At least 1 kidney recipient experienced delayed development of detectable hepatitis A anti-IgM antibodies. By 383 and 198 d posttransplant, HAV RNA was no longer detectable in stool specimens from the left and right kidney recipients, respectively. CONCLUSIONS: Adherence to current guidance for hepatitis A vaccination may prevent future morbidity due to HAV among organ recipients. http://links.lww.com/TXD/A548. |
Treated, hospital-onset Clostridiodes difficile infection: An evaluation of predictors and feasibility of benchmarking comparing 2 risk-adjusted models among 265 hospitals
Yu KC , Ye G , Edwards JR , Dantes R , Gupta V , Ai C , Betz K , Benin AL . Infect Control Hosp Epidemiol 2023 1-9 OBJECTIVES: To evaluate the incidence of a candidate definition of healthcare facility-onset, treated Clostridioides difficile (CD) infection (cHT-CDI) and to identify variables and best model fit of a risk-adjusted cHT-CDI metric using extractable electronic heath data. METHODS: We analyzed 9,134,276 admissions from 265 hospitals during 2015-2020. The cHT-CDI events were defined based on the first positive laboratory final identification of CD after day 3 of hospitalization, accompanied by use of a CD drug. The generalized linear model method via negative binomial regression was used to identify predictors. Standardized infection ratios (SIRs) were calculated based on 2 risk-adjusted models: a simple model using descriptive variables and a complex model using descriptive variables and CD testing practices. The performance of each model was compared against cHT-CDI unadjusted rates. RESULTS: The median rate of cHT-CDI events per 100 admissions was 0.134 (interquartile range, 0.023-0.243). Hospital variables associated with cHT-CDI included the following: higher community-onset CDI (CO-CDI) prevalence; highest-quartile length of stay; bed size; percentage of male patients; teaching hospitals; increased CD testing intensity; and CD testing prevalence. The complex model demonstrated better model performance and identified the most influential predictors: hospital-onset testing intensity and prevalence, CO-CDI rate, and community-onset testing intensity (negative correlation). Moreover, 78% of the hospitals ranked in the highest quartile based on raw rate shifted to lower percentiles when we applied the SIR from the complex model. CONCLUSIONS: Hospital descriptors, aggregate patient characteristics, CO-CDI burden, and clinical testing practices significantly influence incidence of cHT-CDI. Benchmarking a cHT-CDI metric is feasible and should include facility and clinical variables. |
Constructing state and national estimates of vaccination rates from immunization information systems
Raghunathan T , Kirtland K , Li J , White K , Murthy B , Lin XM , Harris L , Gibbs-Scharf L , Zell E . J Surv Stat Methodol 2023 11 (3) 688-712 Immunization Information Systems are confidential computerized population-based systems that collect data from vaccination providers on individual vaccinations administered along with limited patient-level characteristics. Through a data use agreement, Centers for Disease Control and Prevention obtains the individual-level data and aggregates the number of vaccinations for geographical statistical areas defined by the US Census Bureau (counties or equivalent statistical entities) for each vaccine included in system. Currently, 599 counties, covering 11 states, collect and report data using a uniform protocol. We combine these data with inter-decennial population counts from the Population Estimates Program in the US Census Bureau and several covariates from a variety of sources to develop model-based estimates for each of the 3,142 counties in 50 states and the District of Columbia and then aggregate to the state and national levels. We use a hierarchical Bayesian model and Markov Chain Monte Carlo methods to obtain draws from the posterior predictive distribution of the vaccination rates. We use posterior predictive checks and cross-validation to assess the goodness of fit and to validate the models. We also compare the model-based estimates to direct estimates from the National Immunization Surveys. © 2023 The Author(s). Published by Oxford University Press on behalf of the American Association for Public Opinion Research. All rights reserved. |
A randomized controlled trial to compare immunogenicity to cell-based versus live-attenuated influenza vaccines in children
Williams KV , Li ZN , Zhai B , Alcorn JF , Nowalk MP , Levine MZ , Kim SS , Flannery B , Moehling Geffel K , Merranko AJ , Collins M , Susick M , Clarke KS , Zimmerman RK , Martin JM . J Pediatric Infect Dis Soc 2023 12 (6) 342-352 BACKGROUND: Few studies have focused on the immune response to more recent influenza vaccine formulations such as cell-cultured inactivated influenza vaccine (ccIIV4) or live-attenuated influenza vaccine (LAIV4) in older children and young adults, or differences in immunoglobulin response using newer antibody landscape technology. METHODS: Participants ages 4-21 were randomized to receive ccIIV4 (n = 112) or LAIV4 (n = 118). A novel high-throughput multiplex influenza antibody detection assay was used to provide detailed IgG, IgA, and IgM antibody isotypes, along with hemagglutination inhibition levels (HAI), measured pre- and 28 days post-vaccination. RESULTS: The HAI and immunoglobulin isotype response to ccIIV4 was greater than LAIV4, with significant increases in IgG but not IgA or IgM. The youngest participants had the highest LAIV4 response. Prior LAIV4 vaccination was associated with a higher response to current season ccIIV4. Cross-reactive A/Delaware/55/2019(H1N1)pdm09 antibodies were present pre-vaccination and increased in response to ccIIV4, but not LAIV4. Immunoglobulin assays strongly correlated with and confirmed the findings of HAI titers to measure immune response. CONCLUSIONS: Age and prior season vaccination may play a role in the immune response in children and young adults to ccIIV4 and LAIV4. While immunoglobulin isotypes provide high-level antigen-specific information, HAI titers alone can provide a meaningful representation of day 28 post-vaccination response. CLINICAL TRIALS NO: NCT03982069. |
Safety signal identification for COVID-19 bivalent booster vaccination using tree-based scan statistics in the Vaccine Safety Datalink
Katherine Yih W , Daley MF , Duffy J , Fireman B , McClure DL , Nelson JC , Qian L , Smith N , Vazquez-Benitez G , Weintraub E , Williams JTB , Xu S , Maro JC . Vaccine 2023 41 (36) 5265-5270 BACKGROUND: Traditional active vaccine safety monitoring involves pre-specifying health outcomes and biologically plausible outcome-specific time windows of concern, limiting the adverse events that can be evaluated. In this study, we used tree-based scan statistics to look broadly for >60,000 possible adverse events after bivalent COVID-19 vaccination. METHODS: Vaccine Safety Datalink enrollees aged ≥5 years receiving Moderna or Pfizer-BioNTech bivalent COVID-19 vaccine through November 2022 were followed for 56 days post-vaccination. Incident diagnoses in inpatient or emergency department settings were analyzed for clustering within the hierarchical ICD-10-CM diagnosis code "tree" and temporally within post-vaccination follow-up. The conditional self-controlled tree-temporal scan statistic was used, conditioning on total number of cases of each diagnosis and total number of cases of any diagnosis occurring during the scanning risk window across the entire tree. P = 0.01 was the pre-specified cut-off for statistical significance. RESULTS: Analysis included 352,509 doses of Moderna and 979,189 doses of Pfizer-BioNTech bivalent vaccines. After Moderna vaccination, no statistically significant clusters were found. After Pfizer-BioNTech, there were clusters of unspecified adverse events (Days 1-3, p = 0.0001-0.0007), influenza (Days 35-56, p = 0.0001), cough (Days 44-55, p = 0.0002), and COVID-19 (Days 52-56, p = 0.0004). CONCLUSIONS: For Pfizer-BioNTech only, we detected clusters of: (1) unspecified adverse effects, as have been observed in other vaccine studies using this method, and (2) respiratory disease toward the end of follow-up. The respiratory clusters were likely due to overlap of follow-up with the spread of respiratory syncytial virus, influenza, and COVID-19, i.e., confounding by seasonality. The untargeted nature of the method and its inherent adjustment for the many diagnoses and risk intervals evaluated are unique advantages. Limitations include susceptibility to time-varying confounding, lower statistical power for assessing risks of specific outcomes than in traditional studies targeting fewer outcomes, and the possibility of missing adverse events not strongly clustered in time or within the "tree." |
Estimating the future global dose demand for measles-rubella microarray patches
Ko M , Malvolti S , Cherian T , Mantel C , Biellik R , Jarrahian C , Menozzi-Arnaud M , Amorij JP , Christiansen H , Papania MJ , Meltzer MI , Masresha BG , Pastor D , Durrheim DN , Giersing B , Hasso-Agopsowicz M . Front Public Health 2022 10 1037157 BACKGROUND: Progress toward measles and rubella (MR) elimination has stagnated as countries are unable to reach the required 95% vaccine coverage. Microarray patches (MAPs) are anticipated to offer significant programmatic advantages to needle and syringe (N/S) presentation and increase MR vaccination coverage. A demand forecast analysis of the programmatic doses required (PDR) could accelerate MR-MAP development by informing the size and return of the investment required to manufacture MAPs. METHODS: Unconstrained global MR-MAP demand for 2030-2040 was estimated for three scenarios, for groups of countries with similar characteristics (archetypes), and four types of uses of MR-MAPs (use cases). The base scenario 1 assumed that MR-MAPs would replace a share of MR doses delivered by N/S, and that MAPs can reach a proportion of previously unimmunised populations. Scenario 2 assumed that MR-MAPs would be piloted in selected countries in each region of the World Health Organization (WHO); and scenario 3 explored introduction of MR-MAPs earlier in countries with the lowest measles vaccine coverage and highest MR disease burden. We conducted sensitivity analyses to measure the impact of data uncertainty. RESULTS: For the base scenario (1), the estimated global PDR for MR-MAPs was forecasted at 30 million doses in 2030 and increased to 220 million doses by 2040. Compared to scenario 1, scenario 2 resulted in an overall decrease in PDR of 18%, and scenario 3 resulted in a 21% increase in PDR between 2030 and 2040. Sensitivity analyses revealed that assumptions around the anticipated reach or coverage of MR-MAPs, particularly in the hard-to-reach and MOV populations, and the market penetration of MR-MAPs significantly impacted the estimated PDR. CONCLUSIONS: Significant demand is expected for MR-MAPs between 2030 and 2040, however, efforts are required to address remaining data quality, uncertainties and gaps that underpin the assumptions in this analysis. |
Polio vaccination activities in conflict-affected areas
Mbaeyi C . Hum Vaccin Immunother 2023 19 (2) 2237390 Conflict poses a threat to the stability of health-care systems around the world. Within the context of immunization service delivery, conflict-affected geographies are often dogged by recurrent disease outbreaks due to the inability to administer life-saving vaccines to children residing in these areas. Essential immunization coverage is often poor in conflict-affected geographies, and within the specific context of the Global Polio Eradication Initiative (GPEI), multiple rounds of supplementary immunization activities are often needed to compensate for the inability to provide adequate immunization services. In order to implement polio vaccination activities, GPEI has often resorted to innovative approaches to reach and vaccinate children in security-compromised areas. This article examines the approaches adopted by the global polio program in conducting vaccination activities in conflict-affected geographies with the aim of understanding how they have influenced the successes and setbacks of the program in its bid to eradicate all polioviruses. |
Immunogenicity of poxvirus-based vaccines against Nipah virus
Medina-Magües ES , Lopera-Madrid J , Lo MK , Spiropoulou CF , Montgomery JM , Medina-Magües LG , Salas-Quinchucua C , Jiménez-Mora AP , Osorio JE . Sci Rep 2023 13 (1) 11384 Nipah virus (NiV), an emerging zoonotic pathogen in Southeast Asia, is transmitted from Pteropus species of fruit bats to a wide range of species, including humans, pigs, horses, dogs, and cats. NiV has killed millions of animals and caused highly fatal human outbreaks since no vaccine is commercially available. This study characterized the immunogenicity and safety of poxvirus-based Nipah vaccines that can be used in humans and species responsible for NiV transmission. Mice were vaccinated with modified vaccinia Ankara (MVA) and raccoon pox (RCN) viral vectors expressing the NiV fusion (F) and glycoprotein (G) proteins subcutaneously (SC) and intranasally (IN). Importantly, both vaccines did not induce significant weight loss or clinical signs of disease while generating high circulating neutralizing antibodies and lung-specific IgG and IgA responses. The MVA vaccine saw high phenotypic expression of effector and tissue resident memory CD8ɑ(+) T cells in lungs and splenocytes along with the expression of central memory CD8ɑ(+) T cells in lungs. The RCN vaccine generated effector memory (SC) and tissue resident (IN) CD8ɑ(+) T cells in splenocytes and tissue resident (IN) CD8ɑ(+) T cells in lung cells. These findings support MVA-FG and RCN-FG viral vectors as promising vaccine candidates to protect humans, domestic animals, and wildlife from fatal disease outcomes and to reduce the global threat of NiV. |
Use of respiratory syncytial virus vaccines in older adults: Recommendations of the Advisory Committee on Immunization Practices - United States, 2023
Melgar M , Britton A , Roper LE , Talbot HK , Long SS , Kotton CN , Havers FP . MMWR Morb Mortal Wkly Rep 2023 72 (29) 793-801 Respiratory syncytial virus (RSV) is a cause of severe respiratory illness in older adults. In May 2023, the Food and Drug Administration approved the first vaccines for prevention of RSV-associated lower respiratory tract disease in adults aged ≥60 years. Since May 2022, the Advisory Committee on Immunization Practices (ACIP) Respiratory Syncytial Virus Vaccines Adult Work Group met at least monthly to review available evidence regarding the safety, immunogenicity, and efficacy of these vaccines among adults aged ≥60 years. On June 21, 2023, ACIP voted to recommend that adults aged ≥60 years may receive a single dose of an RSV vaccine, using shared clinical decision-making. This report summarizes the body of evidence considered for this recommendation and provides clinical guidance for the use of RSV vaccines in adults aged ≥60 years. RSV vaccines have demonstrated moderate to high efficacy in preventing RSV-associated lower respiratory tract disease and have the potential to prevent substantial morbidity and mortality among older adults; postmarketing surveillance will direct future guidance. |
Oral cholera vaccine coverage evaluation survey: Forcibly Displaced Myanmar Nationals and host community in Cox's Bazar, Bangladesh
Qayum MO , Billah MM , Sarker MFR , Alamgir ASM , Nurunnahar M , Khan MH , Salim Uzzaman M , Henderson A , Shirin T , Flora MS . Front Public Health 2023 11 1147563 INTRODUCTION: Cholera remains a significant public health concern in many parts of the world, particularly in areas with poor sanitation and hygiene. Bangladesh and other impoverished nations have been severely affected by cholera outbreaks, especially in areas with a high population density. In order to mitigate the spread of cholera, oral cholera vaccines (OCVs) are recommended as a prophylactic measure. In May 2018, 775,666 of the Forcibly Displaced Myanmar Nationals (FDMN) in the registered and makeshift camps and 103,605 of the residents in the host community received two doses of OCV Shanchol(TM) in Cox's Bazar, Bangladesh, because the conditions in the area favored the transmission of cholera and other waterborne diseases. This study aimed to assess the coverage of OCV among the FDMN and the host community in Cox's Bazar. METHODS: In August 2018, we enrolled 4,240 respondents for this study following the "World Health Organization (WHO) Vaccination Coverage Cluster Surveys: Reference Manual (2018)." The coverage survey was conducted with three strata of the population: the host community from the Teknaf Upazila, the registered camp, and the makeshift camp from the Ukhia Upazila. We collected information regarding OCV coverage, demographic characteristics, and knowledge and behaviors of people toward the vaccine. The data were analyzed using descriptive statistics. RESULTS: According to our study, the overall OCV coverage was 85%, with 68% in the host community, 91% in the registered camp, and 98% in the makeshift camp. The lower coverage in the host community was due to residents unaware of the vaccination campaign, the unavailability of vaccines, and unaware where to go for vaccination. DISCUSSION: Our findings demonstrate that the OCV campaign in the FDMN camps was successful, reaching over 90% coverage, while coverage in the host community was much lower. In order to make sure that OCV vaccination efforts are reaching the target population and having the desired impact, our study emphasizes the need to inform the target population of when and where to get vaccinated. |
Effectiveness of COVID-19 vaccines at preventing emergency department or urgent care encounters and hospitalizations among immunocompromised adults: An observational study of real-world data across 10 US states from August-December 2021
Embi PJ , Levy ME , Patel P , DeSilva MB , Gaglani M , Dascomb K , Dunne MM , Klein NP , Ong TC , Grannis SJ , Natarajan K , Yang DH , Stenehjem E , Zerbo O , McEvoy C , Rao S , Thompson MG , Konatham D , Irving SA , Dixon BE , Han J , Schrader KE , Grisel N , Lewis N , Kharbanda AB , Barron MA , Reynolds S , Liao IC , Fadel WF , Rowley EA , Arndorfer J , Goddard K , Murthy K , Valvi NR , Weber ZA , Fireman B , Reese SE , Ball SW , Naleway AL . Vaccine 2023 BACKGROUND: Immunocompromised (IC) persons are at increased risk for severe COVID-19 outcomes and are less protected by 1-2 COVID-19 vaccine doses than are immunocompetent (non-IC) persons. We compared vaccine effectiveness (VE) against medically attended COVID-19 of 2-3 mRNA and 1-2 viral-vector vaccine doses between IC and non-IC adults. METHODS: Using a test-negative design among eight VISION Network sites, VE against laboratory-confirmed COVID-19-associated emergency department (ED) or urgent care (UC) events and hospitalizations from 26 August-25 December 2021 was estimated separately among IC and non-IC adults and among specific IC condition subgroups. Vaccination status was defined using number and timing of doses. VE for each status (versus unvaccinated) was adjusted for age, geography, time, prior positive test result, and local SARS-CoV-2 circulation. RESULTS: We analyzed 8,848 ED/UC events and 18,843 hospitalizations among IC patients and 200,071 ED/UC events and 70,882 hospitalizations among non-IC patients. Among IC patients, 3-dose mRNA VE against ED/UC (73% [95% CI: 64-80]) and hospitalization (81% [95% CI: 76-86]) was lower than that among non-IC patients (ED/UC: 94% [95% CI: 93-94]; hospitalization: 96% [95% CI: 95-97]). Similar patterns were observed for viral-vector vaccines. Transplant recipients had lower VE than other IC subgroups. CONCLUSIONS: During B.1.617.2 (Delta) variant predominance, IC adults received moderate protection against COVID-19-associated medical events from three mRNA doses, or one viral-vector dose plus a second dose of any product. However, protection was lower in IC versus non-IC patients, especially among transplant recipients, underscoring the need for additional protection among IC adults. |
Using photovoice methodology to uncover individual-level, health systems, and contextual barriers to uptake of second dose of measles containing vaccine in Western Area Urban, Sierra Leone, 2020
Kulkarni S , Ishizumi A , Eleeza O , Patel P , Feika M , Kamara S , Bangura J , Jalloh U , Koroma M , Sankoh Z , Sandy H , Toure M , Igbu TU , Sesay T , Fayorsey RN , Abad N . Vaccine X 2023 14 100338 Background: Vaccination coverage for the second dose of the measles-containing vaccine (MCV2) among children has remained stagnant in Sierra Leone at nearly 67% since its introduction in 2015. Identifying community-specific barriers faced by caregivers in accessing MCV2 services for their children and by health workers in delivering MCV2 is key to informing strategies to improve vaccination coverage. Methods: We used Photovoice, a participatory method using photographs and narratives to understand community barriers to MCV2 uptake from March- September 2020. Six female and five male caregivers of MCV2-eligible children (15–24 months of age), and six health care workers (HCWs) in Freetown, Sierra Leone participated. After having an orientation to photovoice, they photographed barriers related to general immunization and MCV2 uptake in their community. This was followed by facilitated discussions where participants elaborated on the barriers captured in the photos. Transcripts from the six immunization-related discussions were analyzed to deduce themes through open-ended coding. A photo exhibition was held for participants to discuss the barriers and suggested solutions with decision-makers, such as the ministry of health. Results: We identified and categorized nine themes into three groups: 1) individual or caregiver level barriers (e.g., caregivers’ lack of knowledge on MCV2, concerns about vaccine side effects, and gender-related barriers); 2) health system barriers, such as HCWs’ focus on children below one year and usage of old child health cards; and 3) contextual barriers, such as poverty, poor infrastructure, and the COVID-19 pandemic. Participants suggested the decision-makers to enhance community engagement with caregivers and HCW capacity including, increasing accountability of their work using performance-based approaches, among different strategies to improve MCV2 uptake. Conclusion: Photovoice can provide nuanced understanding of community issues affecting MCV2. As a methodology, it should be integrated in broader intervention planning activities to facilitate the translation of community-suggested strategies into action. © 2023 |
Mumps vaccine effectiveness of a 3rd dose of measles, mumps, rubella vaccine in school settings during a mumps outbreak -- Arkansas, 2016-2017
Guo A , Leung J , Ayers T , Fields VS , Safi H , Waters C , Curns AT , Routh JA , Haselow DT , Marlow MA , Marin M . Public Health Pract (Oxf) 2023 6 100404 Objectives: The largest mumps outbreak in the United States since 2006 occurred in Arkansas during the 2016-17 school year. An additional dose (third dose) of measles-mumps-rubella vaccine (MMR3) was offered to school children. We evaluated the vaccine effectiveness (VE) of MMR3 compared with two doses of MMR for preventing mumps among school-aged children during the outbreak. Study design: A generalized linear mixed effects model was used to estimate the incremental vaccine effectiveness (VE) of a third dose of MMR compared with two doses of MMR for preventing mumps. Methods: We obtained school enrollment, immunization status and mumps case status from school registries, Arkansas's immunization registry, and Arkansas's mumps surveillance system, respectively. We included students who previously received 2 doses of MMR in schools with ≥1 mumps case after the MMR3 clinic. We used a generalized linear mixed model to estimate VE of MMR3 compared with two doses of MMR. Results: Sixteen schools with 9272 students were included in the analysis. Incremental VE of MMR3 versus a two-dose MMR regimen was 52.7% (95% confidence interval [CI]: -3.6%‒78.4%) overall and in 8 schools with high mumps transmission it was 64.0% (95% CI: 1.2%‒86.9%). MMR3 VE was higher among middle compared with elementary school students (68.5% [95% CI: -30.2%‒92.4%] vs 37.6% [95% CI: -62.5%‒76.1%]); these differences were not statistically significant. Conclusion: Our findings suggest MMR3 provided additional protection from mumps compared with two MMR doses in elementary and middle school settings during a mumps outbreak. © 2023 |
Prior SARS-CoV-2 Infection and COVID-19 Vaccine Effectiveness against Outpatient Illness during Widespread Circulation of SARS-CoV-2 Omicron Variant, US Flu VE Network (preprint)
Tartof SY , Xie F , Yadav R , Wernli KJ , Martin ET , Belongia EA , Gaglani M , Zimmerman RK , Talbot HK , Thornburg N , Flannery B . medRxiv 2023 11 Background: We estimated combined protection conferred by prior SARS-CoV-2 infection and COVID-19 vaccination against COVID-19-associated acute respiratory illness (ARI). Method(s): During SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variant circulation between October 2021 and April 2022, prospectively enrolled adult patients with outpatient ARI had respiratory and filter paper blood specimens collected for SARS-CoV-2 molecular testing and serology. Dried blood spots were tested for immunoglobulin-G antibodies against SARSCoV-2 nucleocapsid (NP) and spike protein receptor binding domain antigen using a validated multiplex bead assay. Evidence of prior SARS-CoV-2 infection also included documented or self-reported laboratory-confirmed COVID-19. We used documented COVID-19 vaccination status to estimate vaccine effectiveness (VE) by multivariable logistic regression by prior infection status. Result(s): 455 (29%) of 1577 participants tested positive for SARS-CoV-2 infection at enrollment; 209 (46%) case-patients and 637 (57%) test-negative patients were NP seropositive, had documented previous laboratory-confirmed COVID-19, or self-reported prior infection. Among previously uninfected patients, three-dose VE was 97% (95% confidence interval [CI], 60%-99%) against Delta, but not statistically significant against Omicron. Among previously infected patients, three-dose VE was 57% (CI, 20%-76%) against Omicron; VE against Delta could not be estimated. Conclusion(s): Three mRNA COVID-19 vaccine doses provided additional protection against SARS-CoV-2 Omicron variant-associated illness among previously infected participants. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination (preprint)
Zhou ZH , Cortese MM , Fang JL , Wood R , Hummell DS , Risma KA , Norton AE , KuKuruga M , Kirshner S , Rabin RL , Agarabi C , Staat MA , Halasa N , Ware R , Stahl A , McMahon M , Browning P , Maniatis P , Bolcen S , Edwards KM , Su JR , Dharmarajan S , Forshee R , Broder KR , Anderson S , Kozlowski S . medRxiv 2023 12 (28) 4183-4189 Background: The mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism proposed is type I hypersensitivity (i.e., IgE-mediated mast cell degranulation) to excipient polyethylene glycol (PEG). Using an assay that, uniquely, had been previously assessed in patients with anaphylaxis to PEG, our objective was to compare anti-PEG IgE in serum from mRNA COVID-19 vaccine anaphylaxis case-patients and persons vaccinated without allergic reactions. Secondarily, we compared anti-PEG IgG and IgM to assess alternative mechanisms. Method(s): Selected anaphylaxis case-patients reported to U.S. Vaccine Adverse Event Reporting System December 14, 2020 - March 25, 2021 were invited to provide a serum sample. mRNA COVID-19 vaccine study participants with residual serum and no allergic reaction post-vaccination ("controls") were frequency matched to cases 3:1 on vaccine and dose number, sex and 10-year age category. Anti-PEG IgE was measured using a dual cytometric bead assay. Anti-PEG IgG and IgM were measured using two different assays. Laboratorians were blinded to case/control status. Result(s): All 20 case-patients were women; 17 had anaphylaxis after dose 1, 3 after dose 2. Thirteen (65%) were hospitalized and 7 (35%) were intubated. Time from vaccination to serum collection was longer for case-patients vs controls (post-dose 1: median 105 vs 21 days). Among Moderna recipients, anti-PEG IgE was detected in 1 of 10 (10%) case-patients vs 8 of 30 (27%) controls (p=0.40); among Pfizer-BioNTech recipients, it was detected in 0 of 10 case-patients (0%) vs 1 of 30 (3%) controls (p>0.99). Anti-PEG IgE quantitative signals followed this same pattern. Neither anti-PEG IgG nor IgM was associated with case status with both assay formats. Conclusion(s): Our results support that anti-PEG IgE is not a predominant mechanism for anaphylaxis post-mRNA COVID-19 vaccination. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Increased vaccine sensitivity of an emerging SARS-CoV-2 variant (preprint)
Lewnard JA , Hong V , Kim JS , Shaw SF , Lewin B , Takhar H , Lipsitch M , Tartof SY . medRxiv 2023 16 (1) 3854 Host immune responses are a key source of selective pressure driving pathogen evolution. Emergence of many SARS-CoV-2 lineages has been associated with improvements in their ability to evade population immunity resulting from both vaccination and infection. Here we show diverging trends of escape from vaccine-derived and infection-derived immunity for the emerging XBB/XBB.1.5 Omicron lineage. Among 31,739 patients tested in ambulatory settings in Southern California from December, 2022 to February, 2023, adjusted odds of prior receipt of 2, 3, 4, and >=5 COVID-19 vaccine doses were 10% (95% confidence interval: 1-18%), 11% (3-19%), 13% (3-21%), and 25% (15-34%) lower, respectively, among cases infected with XBB/XBB.1.5 than among cases infected with other co-circulating lineages. Similarly, prior vaccination was associated with greater protection against progression to hospitalization among cases with XBB/XBB.1.5 than among non-XBB/XBB.1.5 cases (70% [30-87%] and 48% [7-71%], respectively, for recipients of >=4 doses). In contrast, cases infected with XBB/XBB.1.5 had 17% (11-24%) and 40% (19-65%) higher adjusted odds of having experienced 1 and >=2 prior documented infections, respectively, including with pre-Omicron variants. As immunity acquired from SARS-CoV-2 infection becomes increasingly widespread, fitness costs associated with enhanced vaccine sensitivity in XBB/XBB.1.5 may be offset by increased ability to evade infection-derived host responses. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Antiviral activities of two nucleos(t)ide analogs against vaccinia and mpox viruses in primary human fibroblasts (preprint)
Dsouza L , Pant A , Offei S , Priyamvada L , Pope B , Satheshkumar PS , Wang Z , Yang Z . bioRxiv 2023 23 Many poxviruses are significant human and animal pathogens, including viruses that cause smallpox and mpox. Identification of inhibitors of poxvirus replication is critical for drug development to manage poxvirus threats. Here we tested two compounds, nucleoside trifluridine and nucleotide adefovir dipivoxil, for antiviral activities against vaccinia virus (VACV) and mpox virus (MPXV) in physiologically relevant primary human fibroblasts. Both trifluridine and adefovir dipivoxil potently inhibited replication of VACV and MPXV (MA001 2022 isolate) in a plaque assay. Upon further characterization, they both conferred high potency in inhibiting VACV replication with half maximal effective concentrations (EC50) at low nanomolar levels in our recently developed assay based on a recombinant VACV secreted Gaussia luciferase. Our results further validated that the recombinant VACV with Gaussia luciferase secretion is a highly reliable, rapid, non-disruptive, and simple reporter tool for identification and chracterization of poxvirus inhibitors. Both compounds inhibited VACV DNA replication and downstream viral gene expression. Given that both compounds are FDA-approved drugs, and trifluridine is used to treat ocular vaccinia in medical practice due to its antiviral activity, our results suggest that it holds great promise to further test trifluridine and adefovir dipivoxil for countering poxvirus infection, including mpox. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Reported Cases of Multisystem Inflammatory Syndrome in Children (MIS-C) Aged 12-20 Years in the United States Who Received COVID-19 Vaccine, December 2020 through August 2021 (preprint)
Yousaf AR , Cortese MM , Taylor AW , Broder KR , Oster ME , Wong JM , Guh AY , McCormick DW , Kamidani S , Schlaudecker EP , Edwards K , Creech CB , Staat MA , Belay ED , Marquez P , Su JR , Salzman MB , Thompson D , Campbell AP , Museru O , Howard LM , Parise M , Finn LE , Kim M , Raman KV , Komatsu KK , Spiker BL , Burkholder CP , Lang SM , Soslow JH . medRxiv 2022 05 Background: Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory condition associated with antecedent SARS-CoV-2 infection. In the United States, reporting of MIS-C after vaccination is required under COVID-19 vaccine emergency use authorizations. This case series describes persons aged 12-20 years with MIS-C following COVID-19 vaccination reported to passive surveillance systems or through clinician outreach to CDC. Method(s): We investigated potential cases of MIS-C after COVID-19 vaccination reported to CDC's health department-based national MIS-C surveillance, the Vaccine Adverse Event Reporting System (VAERS, co-administered by CDC and the U.S. FDA), and CDC's Clinical Immunization Safety Assessment Project (CISA) from December 14, 2020, to August 31, 2021. We describe cases meeting the CDC MIS-C case definition. Any positive SARS-CoV-2 serology test satisfied the case criteria although anti-nucleocapsid antibody indicates SARS-CoV-2 infection, while anti-spike protein antibody indicates either infection or COVID-19 vaccination. Finding(s): We identified 21 persons with MIS-C after COVID-19 vaccination. Of these 21 persons, median age was 16 years (range, 12-20 years); 13 (62%) were male. All were hospitalized; 12 (57%) had intensive care unit admission, and all were discharged home. Fifteen (71%) of the 21 had laboratory evidence of past or recent SARS-CoV-2 infection, and six (29%) did not. Through August 2021, 21,335,331 persons aged 12-20 years had received >=1 dose of COVID-19 vaccine, making the overall reporting rate for MIS-C following vaccination 1.0 case per million persons receiving >=1 vaccine dose in this age group. The reporting rate for those without evidence of SARS-CoV-2 infection was 0.3 cases per million vaccinated persons. Interpretation(s): In our case series, we describe a small number of persons with MIS-C who had received >=1 COVID-19 vaccine dose before illness onset. Continued reporting of potential cases and surveillance for MIS-C illnesses after COVID-19 vaccination is warranted. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Reporting Rates for VAERS Death Reports Following COVID-19 Vaccination, December 14, 2020-November 17, 2021 (preprint)
Day B , Menschik D , Thompson D , Jankosky C , Su J , Moro P , Zinderman C , Welsh K , Nair N . medRxiv 2022 07 Background: Despite widely available safety information for the COVID-19 vaccines, vaccine hesitancy remains a challenge. In some cases, vaccine hesitancy may be related to concerns about the number of reports of death to the Vaccine Adverse Event Reporting System (VAERS). Objective(s): To provide information and context about reports of death to VAERS following COVID-19 vaccination. Design(s): Descriptive study; reporting rates for VAERS death reports. Setting(s): United States; December 14, 2020, to November 17, 2021. Participant(s): COVID-19 vaccine recipients. Measurements: Reporting rates for death events per million persons vaccinated; adverse event counts; data mining signals of disproportionate reporting. Result(s): 9,201 death events were reported for COVID-19 vaccine recipients aged five years and older (or age unknown). Reporting rates for death events increased with increasing age, and males generally had higher reporting rates than females. For death events within seven days and 42 days of vaccination, respectively, observed reporting rates were lower than the expected all-cause death rates. Reporting rates for Ad26.COV2.S vaccine were generally higher than for mRNA COVID-19 vaccines, but still lower than the expected all-cause death rates. Reported adverse events were nonspecific or reflected the known leading causes of death. Limitation(s): VAERS data are subject to several limitations such as reporting bias (underreporting and stimulated reporting), missing or inaccurate information, and lack of a control group. Reported diagnoses, including deaths, are not causally verified diagnoses. Conclusion(s): Reporting rates for death events were lower than the expected all-cause mortality rates. Trends in reporting rates reflected known trends in background mortality rates. These findings do not suggest an association between vaccination and overall increased mortality. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Serologic Responses to COVID-19 Vaccination in Children with History of Multisystem Inflammatory Syndrome (MIS-C) (preprint)
Perez MA , Hsiao HM , Chen X , Kunkel A , Baida N , Hussaini L , Lu AT , Kao CM , Laham FR , Hunstad DA , Beltran Y , Hammett TA , Godfred-Cato S , Chahroudi A , Anderson EJ , Belay E , Rostad CA . medRxiv 2022 20 Understanding the serological responses to COVID-19 vaccination in children with history of MIS-C could inform vaccination recommendations. We prospectively enrolled five children hospitalized with MIS-C and measured SARS-CoV-2 binding IgG antibodies to spike protein variants longitudinally pre- and post-Pfizer-BioNTech BNT162b2 primary series COVID-19 vaccination. We found that SARS-CoV-2 variant cross-reactive IgG antibodies waned following acute MIS-C, but were significantly boosted with vaccination and maintained for at least 3 months. We then compared post-vaccination binding, pseudovirus neutralizing, and functional antibody-dependent cell-mediated cytotoxicity (ADCC) titers to the reference strain (Wuhan-hu-1) and Omicron variant (B.1.1.529) among previously healthy children (n=6) and children with history of MIS-C (n=5) or COVID-19 (n=5). Despite the breadth of binding antibodies elicited by vaccination in all three groups, pseudovirus neutralizing and ADCC titers were reduced to the Omicron variant. Vaccination after MIS-C or COVID-19 (hybrid immunity) conferred advantage in generating pseudovirus neutralizing and functional ADCC antibodies to Omicron. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Vaccine Effectiveness against COVID-19 among Symptomatic Persons Aged >=12 Years with Reported Contact with COVID-19 Cases, February - September 2021 (preprint)
Chung JR , Kim SS , Belongia EA , McLean HQ , King JP , Nowalk MP , Zimmerman RK , Geffel KM , Martin ET , Monto AS , Lamerato LE , Gaglani M , Hoffman E , Volz M , Jackson ML , Jackson LA , Patel MM , Flannery B . medRxiv 2022 01 Individuals in contact with persons with COVID-19 are at high risk of developing COVID-19, but protection offered by COVID-19 vaccines in the context of known exposure is unknown. Symptomatic outpatients reporting acute onset of COVID-19-like illness and tested for SARSCoV-2 infection were enrolled. Among 2,229 participants, 283/451 (63%) of those reporting contact and 331/1778 (19%) without known contact tested SARS-CoV-2 positive. Using the test-negative design, adjusted vaccine effectiveness was 71% (95% confidence interval, 49%-83%) among fully vaccinated participants reporting contact versus 80% (95% CI, 72%-86%) among those without. This study supports COVID-19 vaccination and highlights the importance of efforts to increase vaccination coverage. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Vaccine effectiveness of CanSino (Adv5-nCoV) COVID-19 vaccine among childcare workers - Mexico, March-December 2021 (preprint)
Richardson VL , Franco MAC , Marquez AB , Valdez LM , Ceronio LEC , Cruz VC , Gharpure R , Lafond KE , Yau TS , Azziz-Baumgartner E , Avila MH . medRxiv 2022 17 Background: Beginning in March 2021, Mexico vaccinated childcare workers with a single-dose CanSino Biologics (Adv5-nCoV) COVID-19 vaccine. Although CanSino is currently approved for use in 10 Latin American, Asian, and European countries, little information is available about its vaccine effectiveness (VE). Method(s): We evaluated CanSino VE within a childcare worker cohort that included 1,408 childcare facilities. Participants were followed during March-December 2021 and tested through SARS-CoV-2 RT-PCR or rapid antigen test if they developed any symptom compatible with COVID-19. Vaccination status was obtained through worker registries. VE was calculated as 100% x (1-hazard ratio for SARS-CoV-2 infection in fully vaccinated vs. unvaccinated participants), using an Andersen-Gill model adjusted for age, sex, state, and local viral circulation. Result(s): The cohort included 43,925 persons who were mostly (96%) female with a median age of 32 years; 37,646 (86%) were vaccinated with CanSino. During March-December 2021, 2,250 (5%) participants had laboratory-confirmed COVID-19, of whom 25 were hospitalized and 6 died. Adjusted VE was 20% (95% CI = 10-29%) against illness, 76% (42-90%) against hospitalization, and 94% (66-99%) against death. VE against illness declined from 48% (95% CI = 33-61) after 14-60 days following full vaccination to 20% (95% CI = 9-31) after 61-120 days. Conclusion(s): CanSino vaccine was effective at preventing COVID-19 illness and highly effective at preventing hospitalization and death. It will be useful to further evaluate duration of protection and assess the value of booster doses to prevent COVID-19 and severe outcomes. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Vaccine Effectiveness of Primary Series and Booster Doses against Omicron Variant COVID-19-Associated Hospitalization in the United States (preprint)
Adams K , Rhoads JP , Surie D , Gaglani M , Ginde AA , McNeal T , Ghamande S , Huynh D , Talbot HK , Casey JD , Mohr NM , Zepeski A , Shapiro NI , Gibbs KW , Files DC , Hicks M , Hager DN , Ali H , Prekker ME , Frosch AE , Exline MC , Gong MN , Mohamed A , Johnson NJ , Srinivasan V , Steingrub JS , Peltan ID , Brown SM , Martin ET , Monto AS , Lauring AS , Khan A , Hough CL , Busse LW , ten Lohuis CC , Duggal A , Wilson JG , Gordon AJ , Qadir N , Chang SY , Mallow C , Rivas C , Babcock HM , Kwon JH , Chappell JD , Halasa N , Grijalva CG , Rice TW , Stubblefield WB , Baughman A , Lindsell CJ , Hart KW , Lester SN , Thornburg NJ , Park S , McMorrow ML , Patel MM , Tenforde MW , Self WH . medRxiv 2022 14 Objectives: To compare the effectiveness of a primary COVID-19 vaccine series plus a booster dose with a primary series alone for the prevention of Omicron variant COVID-19 hospitalization. Design(s): Multicenter observational case-control study using the test-negative design to evaluate vaccine effectiveness (VE). Setting(s): Twenty-one hospitals in the United States (US). Participant(s): 3,181 adults hospitalized with an acute respiratory illness between December 26, 2021 and April 30, 2022, a period of SARS-CoV-2 Omicron variant (BA.1, BA.2) predominance. Participants included 1,572 (49%) case-patients with laboratory confirmed COVID-19 and 1,609 (51%) control patients who tested negative for SARS-CoV-2. Median age was 64 years, 48% were female, and 21% were immunocompromised; 798 (25%) were vaccinated with a primary series plus booster, 1,326 (42%) were vaccinated with a primary series alone, and 1,057 (33%) were unvaccinated. Main Outcome Measure(s): VE against COVID-19 hospitalization was calculated for a primary series plus a booster and a primary series alone by comparing the odds of being vaccinated with each of these regimens versus being unvaccinated among cases versus controls. VE analyses were stratified by immune status (immunocompetent; immunocompromised) because the recommended vaccine schedules are different for these groups. The primary analysis evaluated all COVID-19 vaccine types combined and secondary analyses evaluated specific vaccine products. Result(s): Among immunocompetent patients, VE against Omicron COVID-19 hospitalization for a primary series plus one booster of any vaccine product dose was 77% (95% CI: 71-82%), and for a primary series alone was 44% (95% CI: 31-54%) (p<0.001). VE was higher for a boosted regimen than a primary series alone for both mRNA vaccines used in the US (BNT162b2: primary series plus booster VE 80% (95% CI: 73-85%), primary series alone VE 46% (95% CI: 30-58%) [p<0.001]; mRNA-1273: primary series plus booster VE 77% (95% CI: 67-83%), primary series alone VE 47% (95% CI: 30-60%) [p<0.001]). Among immunocompromised patients, VE for a primary series of any vaccine product against Omicron COVID-19 hospitalization was 60% (95% CI: 41-73%). Insufficient sample size has accumulated to calculate effectiveness of boosted regimens for immunocompromised patients. Conclusion(s): Among immunocompetent people, a booster dose of COVID-19 vaccine provided additional benefit beyond a primary vaccine series alone for preventing COVID-19 hospitalization due to the Omicron variant. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Longitudinal serologic and viral testing post-SARS-CoV-2 infection and post-receipt of mRNA COVID-19 vaccine in a nursing home cohort-Georgia, October 2020-April 2021 (preprint)
Tobolowsky FA , Waltenburg MA , Moritz ED , Haile M , DaSilva JC , Schuh AJ , Thornburg NJ , Westbrook A , McKay SL , LaVoie SP , Folster JM , Harcourt JL , Tamin A , Stumpf MM , Mills L , Freeman B , Lester S , Beshearse E , Lecy KD , Brown LG , Fajardo G , Negley J , McDonald LC , Kutty PK , Brown AC , Bhatnagar A , Bryant-Genevier J , Currie DW , Campbell D , Gilbert SE , Hatfield KM , Jackson DA , Jernigan JA , Dawson JL , Hudson MJ , Joseph K , Reddy SC , Wilson MM . medRxiv 2022 01 (10) e0275718 Importance: There are limited data describing SARS-CoV-2-specific immune responses and their durability following infection and vaccination in nursing home residents. Objective(s): To evaluate the quantitative titers and durability of binding antibodies detected after SARSCoV-2 infection and subsequent COVID-19 vaccination. Design(s): A prospective longitudinal evaluation included nine visits over 150 days; visits included questionnaire administration, blood collection for serology, and paired anterior nasal specimen collection for testing by BinaxNOWTM COVID-19 Ag Card (BinaxNOW), reverse transcription polymerase chain reaction (RT-PCR), and viral culture. Setting(s): A nursing home during and after a SARS-CoV-2 outbreak. Participant(s): 11 consenting SARS-CoV-2-positive nursing home residents. Main Outcomes and Measures: SARS-CoV-2 testing (BinaxNOWTM, RT-PCR, viral culture); quantitative titers of binding SARS-CoV-2 antibodies post-infection and post-vaccination (beginning after the first dose of the primary series). Result(s): Of 10 participants with post-infection serology results, 9 (90%) had detectable Pan-Ig, IgG, and IgA antibodies and 8 (80%) had detectable IgM antibodies. At first antibody detection post-infection, two-thirds (6/9, 67%) of participants were RT-PCR-positive but none were culture positive. Ten participants received vaccination; all had detectable Pan-Ig, IgG, and IgA antibodies through their final observation <=90 days post-first dose. Post-vaccination geometric means of IgG titers were 10-200-fold higher than post-infection. Conclusions and Relevance: Nursing home residents in this cohort mounted robust immune responses to SARS-CoV-2 post-infection and post-vaccination. The augmented antibody responses post-vaccination are potential indicators of enhanced protection that vaccination may confer on previously infected nursing home residents. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Mapping the distribution of zero-dose children to assess the performance of vaccine delivery strategies and their relationships with measles incidence in Nigeria (preprint)
Utazi CE , Aheto JMK , Wigley A , Tejedor-Garavito N , Bonnie A , Nnanatu CC , Wagai J , Williams C , Setayesh H , Tatem AJ , Cutts FT . medRxiv 2022 11 Geographically precise identification and targeting of populations at risk of vaccine-preventable diseases has gained renewed attention within the global health community over the last few years. District level estimates of vaccination coverage and corresponding zero-dose prevalence constitute a potentially useful evidence base to evaluate the performance of vaccination strategies. These estimates are also valuable for identifying missed communities, hence enabling targeted interventions and better resource allocation. Here, we fit Bayesian geostatistical models to map the routine coverage of the first doses of diphtheria-tetanus-pertussis vaccine (DTP1) and measles-containing vaccine (MCV1) and corresponding zero-dose estimates at 1x1 km resolution and the district level using geospatial data sets. We also map MCV1 coverage before and after the 2019 measles vaccination campaign in the northern states to further explore variations in routine vaccine coverage and to evaluate the effectiveness of both routine immunization (RI) and campaigns in reaching zero-dose children. Additionally, we map the spatial distributions of reported measles cases during 2018 to 2020 and explore their relationships with MCV zero-dose prevalence to highlight the public health implications of varying performance of vaccination strategies across the country. Our analysis revealed strong similarities between the spatial distributions of DTP and MCV zero dose prevalence, with districts with the highest prevalence concentrated mostly in the northwest and the northeast, but also in other areas such as Lagos state and the Federal Capital Territory. Although the 2019 campaign reduced MCV zero-dose prevalence substantially in the north, pockets of vulnerabilities remained in areas that had among the highest prevalence prior to the campaign. Importantly, we found strong correlations between measles case counts and MCV RI zero-dose estimates, which provides a strong indication that measles incidence in the country is mostly affected by RI coverage. Our analyses reveal an urgent and highly significant need to strengthen the country's RI program as a longer-term measure for disease control, whilst ensuring effective campaigns in the short term. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Potently neutralizing human monoclonal antibodies against the zoonotic pararubulavirus Sosuga virus (preprint)
Parrington HM , Kose N , Armstrong E , Handal L , Diaz S , Reidy J , Dong J , Stewart-Jones GBE , Shrivastava-Ranjan P , Jain S , Albarino CG , Carnahan RH , Crowe JE . bioRxiv 2022 17 Sosuga virus (SOSV) is a recently discovered paramyxovirus with a single known human case of disease. There has been little laboratory research on SOSV pathogenesis or immunity, and no approved therapeutics or vaccines are available. Here, we report the discovery of human monoclonal antibodies (mAbs) from the circulating memory B cells of the only known human case and survivor of SOSV infection. We isolated six mAbs recognizing the functional attachment protein (HN) and 18 mAbs against the fusion (F) protein. The anti-HN mAbs all target the globular head of the HN protein and can be organized into 4 competition-binding groups that exhibit epitope diversity. The anti-F mAbs can be divided into pre- or post-fusion conformation-specific categories and further into 8 competition-binding groups. Generally, pre-fusion conformation-specific anti-F mAbs showed higher potency in neutralization assays than did mAbs only recognizing the post-fusion conformation of F protein. Most of the anti-HN mAbs were more potently neutralizing than the anti-F mAbs, with mAbs in one of the HN competition-binding groups possessing ultra-potent (<1 ng/mL) half maximal inhibitory (IC50) virus neutralization values. These findings provide insight into the molecular basis for human antibody recognition of paramyxovirus surface proteins and the mechanisms of SOSV neutralization. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Programmatic Effectiveness of a Pediatric Typhoid Conjugate Vaccine Campaign in Navi Mumbai, India (preprint)
Hoffman SA , LeBoa C , Date K , Haldar P , Harvey P , Shimpi R , An Q , Zhang C , Jayaprasad N , Horng L , Fagerli K , Borhade P , Chakraborty D , Bahl S , Katkar A , Kunwar A , Yewale V , Andrews JR , Bhatnagar P , Dutta S , Luby SP . medRxiv 2022 27 Background: The WHO recommends vaccines for prevention and control of typhoid fever, especially where antimicrobial-resistant typhoid circulates. In 2018 the Navi Mumbai Municipal Corporation (NMMC), implemented a TCV campaign. The campaign targeted all children aged 9-months through 14-years within NMMC boundaries (~320,000 children) over 2 vaccination phases. The phase 1 campaign occurred from July 14-August 25, 2018 (71% coverage, ~113,420 children). We evaluated the campaign's programmatic effectiveness in reducing typhoid cases at the community level. Method(s): We established prospective, blood culture-based surveillance at 6 hospitals in Navi Mumbai, offering blood cultures to children presenting with fever for at least 3 days. We employed a cluster-randomized test-negative design to estimate the effectiveness of the vaccination campaign on pediatric typhoid cases. We matched culture-confirmed typhoid cases with up to 3 culture-negative controls by age and date of blood culture and assessed community vaccine campaign phase as an exposure using conditional logistic regression. Result(s): Between September 1, 2018-March 31, 2021, we identified 81 typhoid cases and matched these with 238 controls. Cases were 0.44 times as likely to live in vaccine campaign communities (campaign effectiveness, 56%, 95%CI: 25%-74%, p=0.002). Cases >= 5-years-old were 0.37 times as likely (95% CI: 0.19-0.70; p-value = 0.002) and cases during the first year of surveillance were 0.30 times as likely (95% CI: 0.14-0.64; p-value = 0.002) to live in vaccine campaign communities. Conclusion(s): Our findings support the use of TCV mass vaccination campaigns as effective population-based tools to combat typhoid fever. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Effectiveness of 2 and 3 mRNA COVID-19 Vaccines Doses against Omicron and Delta-Related Outpatient Illness among Adults, October 2021 - February 2022 (preprint)
Kim SS , Chung JR , Talbot HK , Grijalva CG , Wernli KJ , Martin ET , Monto AS , Belongia EA , McLean HQ , Gaglani M , Mamawala M , Nowalk MP , Geffel KM , Tartof SY , Florea A , Lee JS , Tenforde MW , Patel MM , Flannery B , Bentz ML , Burgin A , Burroughs M , Davis ML , Howard D , Lacek K , Madden JC , Nobles S , Padilla J , Sheth M , Arroliga A , Beeram M , Dunnigan K , Ettlinger J , Graves A , Hoffman E , Jatla M , McKillop A , Murthy K , Mutnal M , Priest E , Raiyani C , Rao A , Requenez L , Settele N , Smith M , Stone K , Thomas J , Volz M , Walker K , Zayed M , Annan E , Daley P , Kniss K , Merced-Morales A , Ayala E , Amundsen B , Aragones M , Calderon R , Hong V , Jimenez G , Kim J , Ku J , Lewin B , McDaniel A , Reyes A , Shaw S , Takhar H , Torres A , Burganowski R , Kiniry E , Moser KA , Nguyen M , Park S , Wellwood S , Wickersham B , Alvarado-Batres J , Benz S , Berger H , Bissonnette A , Blake J , Boese K , Botten E , Boyer J , Braun M , Breu B , Burbey G , Cravillion C , Delgadillo C , Donnerbauer A , Dziedzic T , Eddy J , Edgren H , Ermeling A , Ewert K , Fehrenbach C , Fernandez R , Frome W , Guzinski S , Heeren L , Herda D , Hertel M , Heuer G , Higdon E , Ivacic L , Jepsen L , Kaiser S , Karl J , Keffer B , King J , Koepel TK , Kohl S , Kohn S , Kohnhorst D , Kronholm E , Le T , Lemieux A , Marcis C , Maronde M , McCready I , McGreevey K , Meece J , Mehta N , Miesbauer D , Moon V , Moran J , Nikolai C , Olson B , Olstadt J , Ott L , Pan N , Pike C , Polacek D , Presson M , Price N , Rayburn C , Reardon C , Rotar M , Rottscheit C , Salzwedel J , Saucedo J , Scheffen K , Schug C , Seyfert K , Shrestha R , Slenczka A , Stefanski E , Strupp M , Tichenor M , Watkins L , Zachow A , Zimmerman B , Bauer S , Beney K , Cheng CK , Faraj N , Getz A , Grissom M , Groesbeck M , Harrison S , Henson K , Jermanus K , Johnson E , Kaniclides A , Kimberly A , Lamerato LE , Lauring A , Lehmann-Wandell R , McSpadden EJ , Nabors L , Truscon R , Balasubramani GK , Bear T , Bobeck J , Bowser E , Clarke K , Clarke LG , Dauer K , Deluca C , Dierks B , Haynes L , Hickey R , Johnson M , Jonsson A , Luosang N , McKown L , Peterson A , Phaturos D , Rectenwald A , Sax TM , Stiegler M , Susick M , Suyama J , Taylor L , Walters S , Weissman A , Williams JV , Blair M , Carter J , Chappell J , Copen E , Denney M , Graes K , Halasa N , Lindsell C , Liu Z , Longmire S , McHenry R , Short L , Tan HN , Vargas D , Wrenn J , Wyatt D , Zhu Y . medRxiv 2022 10 Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Effectiveness of Four Vaccines in Preventing SARS-CoV-2 Infection in Kazakhstan (preprint)
Nabirova D , Horth R , Smagul M , Nukenova G , Yesmagambetova A , Singer D , Henderson A , Tsoy A . medRxiv 2022 18 BACKGROUND In February 2021 Kazakhstan began offering COVID-19 vaccines to adults. Breakthrough SARS-CoV-2 infections raised concerns about real-world vaccine effectiveness. We aimed to evaluate effectiveness of four vaccines against SARS-CoV-2 infection. METHODS We conducted a retrospective cohort analysis among adults in Almaty using aggregated vaccination data and individual-level breakthrough COVID-19 cases (>=14 days from 2nd dose) using national surveillance data. We ran time-adjusted Cox-proportional-hazards model with sensitivity analysis accounting for varying entry into vaccinated cohort to assess vaccine effectiveness for each vaccine (measured as 1-adjusted hazard ratios) using the unvaccinated population as reference (N=565,390). We separately calculated daily cumulative hazards for COVID-19 breakthrough among vaccinated persons by age and vaccine month. RESULTS From February 22 to Sept 1, 2021 in Almaty, 747,558 (57%) adults were fully vaccinated (received 2 doses) and 108,324 COVID-19 cases (11,472 breakthrough) were registered. Vaccine effectiveness against infection was 78% (sensitivity estimates: 74-82%) for QazVac, 77% (72-81%) for Sputnik V, 71% (69-72%) for Hayat-Vax, and 69% (64-72%) for CoronaVac. Among vaccinated persons, the 90-day follow-up cumulative hazard for breakthrough infection was 2.2%. Cumulative hazard was 2.9% among people aged >=60 years versus 1.9% among persons aged 18-39 years (p<0.001), and 1.2% for people vaccinated in February-May versus 3.3% in June-August (p<0.001). CONCLUSION Our analysis demonstrates high effectiveness of COVID-19 vaccines against infection in Almaty similar to other observational studies. Higher cumulative hazard of breakthrough among people >60 years of age and during variant surges warrants targeted booster vaccination campaigns. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Estimating the future global dose demand for Measles-Rubella microarray patches (preprint)
Ko M , Malvoti S , Cherian T , Mantel C , Biellik R , Jarrahian C , Menozzi-Arnaud M , Amorij JP , Christiansen H , Papania M , Meltzer MI , Masresha BG , Pastor D , Durrheim DN , Giersing B , Hasso-Agopsowicz M . medRxiv 2022 12 1037157 Background: Progress towards measles and rubella (MR) elimination has stagnated as countries are unable to reach the required 95% vaccine coverage. Microarray patches (MAPs) are anticipated to offer significant programmatic advantages to needle and syringe (N/S) presentation and increase MR vaccination coverage. A demand forecast analysis of the programmatic doses required (PDR) could accelerate MR-MAP development by informing the size and return of the investment required to manufacture MAPs. Method(s): Unconstrained global MR-MAP demand for 2030-2040 was estimated for three scenarios, for groups of countries with similar characteristics (archetypes), and four types of uses of MR-MAPs (use cases). The base scenario 1 assumed that MR-MAPs would replace a share of MR doses delivered by N/S, and that MAPs can reach a proportion of previously unimmunised populations. Scenario 2 assumed that MR-MAPs would be piloted in selected countries in each region of the World Health Organization (WHO); and scenario 3 explored introduction of MR-MAPs earlier in countries with the lowest measles vaccine coverage and highest MR disease burden. Result(s): For the base scenario (1), the estimated global PDR for MR-MAPs was forecasted at 30 million doses in 2030 and increased to 220 million doses by 2040. Compared to scenario 1, scenario 2 resulted in an overall decrease in PDR of 18%, and scenario 3 resulted in a 21% increase in PDR between 2030-2040. Conclusion(s): Significant demand is expected for MR-MAPs between 2030-2040, however, efforts are required to address remaining data quality, uncertainties and gaps that underpin the assumptions in this analysis. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Impact of SARS-CoV-2 vaccination of children ages 5-11 years on COVID-19 disease burden and resilience to new variants in the United States, November 2021-March 2022: a multi-model study (preprint)
Borchering RK , Mullany LC , Howerton E , Chinazzi M , Smith CP , Qin M , Reich NG , Contamin L , Levander J , Kerr J , Espino J , Hochheiser H , Lovett K , Kinsey M , Tallaksen K , Wilson S , Shin L , Lemaitre JC , Hulse JD , Kaminsky J , Lee EC , Davis JT , Mu K , Xiong X , Pastore y Piontti A , Vespignani A , Srivastava A , Porebski P , Venkatramanan S , Adiga A , Lewis B , Klahn B , Outten J , Hurt B , Chen J , Mortveit H , Wilson A , Marathe M , Hoops S , Bhattacharya P , Machi D , Chen S , Paul R , Janies D , Thill JC , Galanti M , Yamana T , Pei S , Shaman J , Espana G , Cavany S , Moore S , Perkins A , Healy JM , Slayton RB , Johansson MA , Biggerstaff M , Shea K , Truelove SA , Runge MC , Viboud C , Lessler J . medRxiv 2022 10 Background SARS-CoV-2 vaccination of persons aged 12 years and older has reduced disease burden in the United States. The COVID-19 Scenario Modeling Hub convened multiple modeling teams in September 2021 to project the impact of expanding vaccine administration to children 5-11 years old on anticipated COVID-19 burden and resilience against variant strains. Methods Nine modeling teams contributed state- and national-level projections for weekly counts of cases, hospitalizations, and deaths in the United States for the period September 12, 2021 to March 12, 2022. Four scenarios covered all combinations of: 1) presence vs. absence of vaccination of children ages 5-11 years starting on November 1, 2021; and 2) continued dominance of the Delta variant vs. emergence of a hypothetical more transmissible variant on November 15, 2021. Individual team projections were combined using linear pooling. The effect of childhood vaccination on overall and age-specific outcomes was estimated by meta-analysis approaches. Findings Absent a new variant, COVID-19 cases, hospitalizations, and deaths among all ages were projected to decrease nationally through mid-March 2022. Under a set of specific assumptions, models projected that vaccination of children 5-11 years old was associated with reductions in all-age cumulative cases (7.2%, mean incidence ratio [IR] 0.928, 95% confidence interval [CI] 0.880-0.977), hospitalizations (8.7%, mean IR 0.913, 95% CI 0.834-0.992), and deaths (9.2%, mean IR 0.908, 95% CI 0.797-1.020) compared with scenarios where children were not vaccinated. This projected effect of vaccinating children 5-11 years old increased in the presence of a more transmissible variant, assuming no change in vaccine effectiveness by variant. Larger relative reductions in cumulative cases, hospitalizations, and deaths were observed for children than for the entire U.S. population. Substantial state-level variation was projected in epidemic trajectories, vaccine benefits, and variant impacts. Conclusions Results from this multi-model aggregation study suggest that, under a specific set of scenario assumptions, expanding vaccination to children 5-11 years old would provide measurable direct benefits to this age group and indirect benefits to the all-age U.S. population, including resilience to more transmissible variants. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. |
Impact of the COVID-19 Vaccination Program on Case Incidence, Emergency Department Visits, and Hospital Admissions among Children Aged 5-17 Years during the Delta and Omicron Periods -United States, December 2020 to April 2022 (preprint)
Topf KG , Sheppard M , Marx GE , Wiegand RE , Link-Gelles R , Binder AM , Cool AJ , Lyons BC , Park S , Fast HE , Presnetsov A , Azondekon GR , Soetebier KA , Adjemian J , Barbour KE . medRxiv 2022 10 Background: In the United States, national ecological studies suggest a positive impact of COVID-19 vaccination coverage on outcomes in adults. However, the national impact of the vaccination program on COVID-19 in children remains unknown. To determine the association of COVID-19 vaccination with U.S. case incidence, emergency department visits, and hospital admissions for pediatric populations during the Delta and Omicron periods. Method(s): We conducted an ecological analysis among children aged 5-17 and compared incidence rate ratios (RRs) of COVID-19 cases, emergency department visits, and hospital admissions by pediatric vaccine coverage, with jurisdictions in the highest vaccine coverage quartile as the reference. Result(s): RRs comparing states with lowest pediatric vaccination coverage to the highest pediatric vaccination coverage were 2.00 and 0.64 for cases, 2.96 and 1.11 for emergency department visits, and 2.76 and 1.01 for hospital admissions among all children during the Delta and Omicron periods, respectively. During the 3-week peak period of the Omicron wave, only children aged 12-15 and 16-17 years in the states with the lowest versus highest coverage, had a significantly higher rate of emergency department visits (RR=1.39 and RR=1.34, respectively). Conclusion(s): COVID-19 vaccines were associated with lower case incidence, emergency department visits and hospital admissions among children during the Delta period but the association was weaker during the Omicron period. Pediatric COVID-19 vaccination should be promoted as part of a program to decrease COVID-19 impact among children; however, vaccine effectiveness may be limited when available vaccines do not match circulating viral variants. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Infectious viral shedding of SARS-CoV-2 Delta following vaccination: a longitudinal cohort study (preprint)
Garcia-Knight M , Anglin K , Tassetto M , Lu S , Zhang A , Goldberg SA , Catching A , Davidson MC , Shak JR , Romero M , Pineda-Ramirez J , Sanchez RD , Rugart P , Donohue K , Massachi J , Sans HM , Djomaleu M , Mathur S , Servellita V , McIlwain D , Gaudiliere B , Chen J , Martinez EO , Tavs JM , Bronstone G , Weiss J , Watson JT , Briggs-Hagen M , Abedi GR , Rutherford GW , Deeks SG , Chiu C , Saydah S , Peluso MJ , Midgley CM , Martin JN , Andino R , Kelly JD . medRxiv 2022 19 (9) e1010802 The impact of vaccination on SARS-CoV-2 infectiousness is not well understood. We compared longitudinal viral shedding dynamics in unvaccinated and fully vaccinated adults. SARS-CoV-2-infected adults were enrolled within 5 days of symptom onset and nasal specimens were self-collected daily for two weeks and intermittently for an additional two weeks. SARS-CoV-2 RNA load and infectious virus were analyzed relative to symptom onset stratified by vaccination status. We tested 1080 nasal specimens from 52 unvaccinated adults enrolled in the pre-Delta period and 32 fully vaccinated adults with predominantly Delta infections. While we observed no differences by vaccination status in maximum RNA levels, maximum infectious titers and the median duration of viral RNA shedding, the rate of decay from the maximum RNA load was faster among vaccinated; maximum infectious titers and maximum RNA levels were highly correlated. Furthermore, amongst participants with infectious virus, median duration of infectious virus detection was reduced from 7.5 days (IQR: 6.0-9.0) in unvaccinated participants to 6 days (IQR: 5.0-8.0) in those vaccinated (P=0.02). Accordingly, the odds of shedding infectious virus from days 6 to 12 post-onset were lower among vaccinated participants than unvaccinated participants (OR 0.42 95% CI 0.19-0.89). These results indicate that vaccination had reduced the probability of shedding infectious virus after 5 days from symptom onset. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Influenza Vaccine Effectiveness Against Influenza A(H3N2)-Related Illness in the United States During the 2021-2022 Influenza Season (preprint)
Price AM , Flannery B , Talbot HK , Grijalva CG , Wernli KJ , Phillips CH , Monto AS , Martin ET , Belongia EA , McLean HQ , Gaglani M , Mutnal M , Geffel KM , Nowalk MP , Tartof SY , Florea A , McLean C , Kim SS , Patel MM , Chung JR . medRxiv 2022 05 Background. In the United States, influenza activity during the 2021-2022 season was modest and sufficient enough to estimate influenza vaccine effectiveness for the first time since the beginning of the COVID-19 pandemic. We estimated influenza vaccine effectiveness against lab-confirmed outpatient acute illness caused by predominant A(H3N2) viruses. Methods. Between October 2021 and April 2022, research staff across 7 sites enrolled patients aged >=6 months seeking outpatient care for acute respiratory illness with cough. Using a test-negative design, we assessed VE against influenza A(H3N2). Due to strong correlation between influenza and SARS-CoV-2 vaccination, participants who tested positive for SARS-CoV-2 were excluded from vaccine effectiveness estimations. Estimates were adjusted for site, age, month of illness, race/ethnicity and general health status. Results. Among 6,260 participants, 468 (7%) tested positive for influenza only, including 440 (94%) for A(H3N2). All 206 sequenced A(H3N2) viruses were characterized as belonging to genetic group 3C.2a1b subclade 2a.2, which has antigenic differences from the 2021-2022 season A(H3N2) vaccine component that belongs to clade 3C.2a1b subclade 2a.1. After excluding 1,948 SARS-CoV-2 positive patients, 4,312 patients were included in analyses of influenza VE; 2,463 (57%) were vaccinated against influenza. Effectiveness against A(H3N2) for all ages was 36% (95%CI, 20-49%) overall; 40% (95%CI, 24-53%) for those aged 6 months-49 years; and 10% (95%CI, -60-49%) for those aged >=50 years. Conclusion. Influenza vaccination in 2021-2022 provided protection against influenza A(H3N2)-related outpatient visits among young persons, with no measurable protection among older adults. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
SARS-CoV-2 convalescent sera binding and neutralizing antibody concentrations compared with COVID-19 vaccine efficacy estimates against symptomatic infection (preprint)
Schuh AJ , Satheshkumar PS , Dietz S , Bull-Otterson L , Charles M , Edens C , Jones JM , Bajema KL , Clarke KEN , McDonald LC , Patel S , Cuffe K , Thornburg NJ , Schiffer J , Chun K , Bastidas M , Fernando M , Petropoulos CJ , Wrin T , Cai S , Adcock D , Sesok-Pizzini D , Letovsky S , Fry AM , Hall AJ , Gundlapalli AV . medRxiv 2021 26 Previous vaccine efficacy (VE) studies have estimated neutralizing and binding antibody concentrations that correlate with protection from symptomatic infection; how these estimates compare to those generated in response to SARS-CoV-2 infection is unclear. Here, we assessed quantitative neutralizing and binding antibody concentrations using standardized SARS-CoV-2 assays on 3,067 serum specimens collected during July 27, 2020-August 27, 2020 from COVID-19 unvaccinated persons with detectable anti-SARS-CoV-2 antibodies using qualitative antibody assays. Quantitative neutralizing and binding antibody concentrations were strongly positively correlated (r=0.76, p<0.0001) and were noted to be several fold lower in the unvaccinated study population as compared to published data on concentrations noted 28 days post-vaccination. In this convenience sample, ~88% of neutralizing and ~63-86% of binding antibody concentrations met or exceeded concentrations associated with 70% COVID-19 VE against symptomatic infection from published VE studies; ~30% of neutralizing and 1-14% of binding antibody concentrations met or exceeded concentrations associated with 90% COVID-19 VE. These data support observations of infection-induced immunity and current recommendations for vaccination post infection to maximize protection against symptomatic COVID-19. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Shedding of Infectious SARS-CoV-2 Despite Vaccination (preprint)
Riemersma KK , Haddock LA , Wilson NA , Minor N , Eickhoff J , Grogan BE , Kita-Yarbro A , Halfmann PJ , Segaloff HE , Kocharian A , Florek KR , Westergaard R , Bateman A , Jeppson GE , Kawaoka Y , O'Connor DH , Friedrich TC , Grande KM . medRxiv 2021 31 The SARS-CoV-2 Delta Variant of Concern is highly transmissible and contains mutations that confer partial immune escape. The emergence of Delta in North America caused the first surge in COVID-19 cases after SARSCoV-2 vaccines became widely available. To determine whether individuals infected despite vaccination might be capable of transmitting SARS-CoV-2, we compared RT-PCR cycle threshold (Ct) data from 20,431 test-positive anterior nasal swab specimens from fully vaccinated (n = 9,347) or unvaccinated (n=11,084) individuals tested at a single commercial laboratory during the interval 28 June - 1 December 2021 when Delta variants were predominant. We observed no significant effect of vaccine status alone on Ct value, nor when controlling for vaccine product or sex. Testing a subset of low-Ct (<25) samples, we detected infectious virus at similar rates, and at similar titers, in specimens from vaccinated and unvaccinated individuals. These data indicate that vaccinated individuals infected with Delta variants are capable of shedding infectious SARS-CoV-2 and could play a role in spreading COVID-19. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. |
Transmission potential of vaccinated and unvaccinated persons infected with the SARS-CoV-2 Delta variant in a federal prison, July-August 2021 (preprint)
Salvatore PP , Lee CC , Sleweon S , McCormick DW , Nicolae L , Knipe K , Dixon T , Banta R , Ogle I , Young C , Dusseau C , Salmonson S , Ogden C , Godwin E , Ballom T , Ross T , Wynn NT , David E , Bessey TK , Kim G , Suppiah S , Tamin A , Harcourt JL , Sheth M , Lowe L , Browne H , Tate JE , Kirking HL , Hagan LM . medRxiv 2021 19 Background The extent to which vaccinated persons who become infected with SARS-CoV-2 contribute to transmission is unclear. During a SARS-CoV-2 Delta variant outbreak among incarcerated persons with high vaccination rates in a federal prison, we assessed markers of viral shedding in vaccinated and unvaccinated persons. Methods Consenting incarcerated persons with confirmed SARS-CoV-2 infection provided mid-turbinate nasal specimens daily for 10 consecutive days and reported symptom data via questionnaire. Real-time reverse transcription-polymerase chain reaction (RT-PCR), viral whole genome sequencing, and viral culture was performed on these nasal specimens. Duration of RT-PCR positivity and viral culture positivity was assessed using survival analysis. Results A total of 978 specimens were provided by 95 participants, of whom 78 (82%) were fully vaccinated and 17 (18%) were not fully vaccinated. No significant differences were detected in duration of RT-PCR positivity among fully vaccinated participants (median: 13 days) versus those not fully vaccinated (median: 13 days; p=0.50), or in duration of culture positivity (medians: 5 days and 5 days; p=0.29). Among fully vaccinated participants, overall duration of culture positivity was shorter among Moderna vaccine recipients versus Pfizer (p=0.048) or Janssen (p=0.003) vaccine recipients. Conclusions As this field continues to develop, clinicians and public health practitioners should consider vaccinated persons who become infected with SARS-CoV-2 to be no less infectious than unvaccinated persons. These findings are critically important, especially in congregate settings where viral transmission can lead to large outbreaks. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Modeling the impact of vaccination strategies for nursing homes in the context of increased SARS-CoV-2 community transmission and variants (preprint)
Holmdahl I , Kahn R , Slifka KJ , Dooling K , Slayton RB . medRxiv 2021 Nursing homes (NH) were among the first settings to receive COVID-19 vaccines in the United States, but staff vaccination coverage remains low at an average of 64%. Using an agent-based model, we examined the impact of community prevalence, the Delta variant, staff vaccination coverage, and boosters for residents on outbreak dynamics in nursing homes. We found that increased staff primary series coverage and high booster vaccine effectiveness (VE) in residents leads to fewer infections and that the cumulative incidence is highly dependent on community transmission. Despite high VE, high community transmission resulted in continued symptomatic infections in NHs. |
mRNA COVID-19 vaccine effectiveness against SARS-CoV-2 infection in a prospective community cohort, rural Wisconsin, November 2020-December 2021 (preprint)
McLean HQ , McClure DL , King JP , Meece JK , Pattinson D , Neumann G , Kawaoka Y , Rolfes MA , Belongia EA . medRxiv 2021 16 Reduced COVID-19 vaccine effectiveness (VE) has been observed with increasing predominance of the Delta variant. In a prospective rural community cohort of 1265 participants, VE against symptomatic and asymptomatic SARS-CoV-2 infection was 56% for mRNA COVID-19 vaccines. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Effectiveness of SARS-CoV-2 mRNA Vaccines for Preventing Covid-19 Hospitalizations in the United States (preprint)
Tenforde MW , Patel MM , Ginde AA , Douin DJ , Talbot HK , Casey JD , Mohr NM , Zepeski A , Gaglani M , McNeal T , Ghamande S , Shapiro NI , Gibbs KW , Files DC , Hager DN , Shehu A , Prekker ME , Erickson HL , Exline MC , Gong MN , Mohamed A , Henning DJ , Steingrub JS , Peltan ID , Brown SM , Martin ET , Monto AS , Khan A , Hough CT , Busse L , Lohuis CCT , Duggal A , Wilson JG , Gordon AJ , Qadir N , Chang SY , Mallow C , Gershengorn HB , Babcock HM , Kwon JH , Halasa N , Chappell JD , Lauring AS , Grijalva CG , Rice TW , Jones ID , Stubblefield WB , Baughman A , Womack KN , Lindsell CJ , Hart KW , Zhu Y , Olson SM , Stephenson M , Schrag SJ , Kobayashi M , Verani JR , Self WH . medRxiv 2021 BACKGROUND: As SARS-CoV-2 vaccination coverage increases in the United States (US), there is a need to understand the real-world effectiveness against severe Covid-19 and among people at increased risk for poor outcomes. METHODS: In a multicenter case-control analysis of US adults hospitalized March 11 - May 5, 2021, we evaluated vaccine effectiveness to prevent Covid-19 hospitalizations by comparing odds of prior vaccination with an mRNA vaccine (Pfizer-BioNTech or Moderna) between cases hospitalized with Covid-19 and hospital-based controls who tested negative for SARS-CoV-2. RESULTS: Among 1210 participants, median age was 58 years, 22.8% were Black, 13.8% were Hispanic, and 20.6% had immunosuppression. SARS-CoV-2 lineage B.1.1.7 was most common variant (59.7% of sequenced viruses). Full vaccination (receipt of two vaccine doses ≥14 days before illness onset) had been received by 45/590 (7.6%) cases and 215/620 (34.7%) controls. Overall vaccine effectiveness was 86.9% (95% CI: 80.4 to 91.2%). Vaccine effectiveness was similar for Pfizer-BioNTech and Moderna vaccines, and highest in adults aged 18-49 years (97.3%; 95% CI: 78.9 to 99.7%). Among 45 patients with vaccine-breakthrough Covid hospitalizations, 44 (97.8%) were ≥50 years old and 20 (44.4%) had immunosuppression. Vaccine effectiveness was lower among patients with immunosuppression (59.2%; 95% CI: 11.9 to 81.1%) than without immunosuppression (91.3%; 95% CI: 85.5 to 94.7%). CONCLUSION: During March-May 2021, SARS-CoV-2 mRNA vaccines were highly effective for preventing Covid-19 hospitalizations among US adults. SARS-CoV-2 vaccination was beneficial for patients with immunosuppression, but effectiveness was lower in the immunosuppressed population. |
Guillain-Barre Syndrome after COVID-19 Vaccination in the Vaccine Safety Datalink (preprint)
Hanson KE , Goddard K , Lewis N , Fireman B , Myers TR , Bakshi N , Weintraub E , Donahue JG , Nelson JC , Xu S , Glanz JM , Williams JTB , Alpern JD , Klein NP . medRxiv 2021 05 Importance: Post-authorization monitoring of vaccines in a large population can detect rare adverse events not identified in clinical trials including Guillain-Barre syndrome (GBS). GBS has a background rate of 1-2 per 100,000 person-years. Objective(s): To 1) describe cases and incidence of GBS following COVID-19 vaccination, and 2) assess the risk of GBS after vaccination for Ad.26.COV2.S (Janssen) and mRNA vaccines. Design(s): Interim analysis of surveillance data from the Vaccine Safety Datalink. Setting(s): Eight participating integrated healthcare systems in the United States. Participant(s): 10,158,003 individuals aged >=12 years. Exposures: Receipt of Ad.26.COV2.S, BNT162b2 (Pfizer-BioNTech), or mRNA-1273 (Moderna) COVID-19 vaccine. Main Outcomes and Measures: GBS with symptom onset in the 1-84 days after vaccination as confirmed by medical record review and adjudication. Descriptive characteristics of confirmed cases, GBS incidence rates during postvaccination risk intervals after each type of vaccine compared to the background rate, rate ratios (RRs) comparing GBS incidence in the 1-21 vs. 22-42 days postvaccination, and RRs directly comparing risk of GBS after Ad.26.COV2.S vs. mRNA vaccination, using Poisson regression adjusted for age, sex, race/ethnicity, site, and calendar day. Result(s): From December 13, 2020 through November 13, 2021, 14,723,318 doses of COVID-19 vaccines were administered, including 467,126 Ad.26.COV2.S, 8,573,823 BNT162b2, and 5,682,369 mRNA-1273 doses. Eleven cases of GBS after Ad.26.COV2.S were confirmed. The unadjusted incidence rate of confirmed cases of GBS per 100,000 person-years in the 1-21 days after Ad.26.COV2.S was 34.6 (95% confidence interval [CI]: 15.8-65.7), significantly higher than the background rate, and the adjusted RR in the 1-21 vs. 22-42 days following Ad.26.COV2.S was 6.03 (95% CI: 0.79-147.79). Thirty-four cases of GBS after mRNA vaccines were confirmed. The unadjusted incidence rate of confirmed cases per 100,000 person-years in the 1-21 days after mRNA vaccines was 1.4 (95% CI: 0.7-2.5) and the adjusted RR in the 1-21 vs. 22-42 days following mRNA vaccines was 0.56 (95% CI: 0.21-1.48). In a head-to-head comparison of Ad.26.COV2.S vs. mRNA vaccines, the adjusted RR was 20.56 (95% CI: 6.94-64.66). Conclusions and Relevance: In this interim analysis of surveillance data of COVID-19 vaccines, the incidence of GBS was elevated after Ad.26.COV2.S. Surveillance is ongoing. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Case series of thrombosis with thrombocytopenia syndrome following COVID-19 vaccination-United States, December 2020-August 2021 (preprint)
See I , Lale A , Marquez P , Streiff MB , Wheeler AP , Tepper NK , Woo EJ , Broder KR , Edwards KM , Gallego R , Geller AI , Jackson KA , Sharma S , Talaat KR , Walter EB , Akpan IJ , Ortel TL , Walker SC , Yui JC , Shimabukuro TT , Mba-Jonas A , Su JR , Shay DK . medRxiv 2021 14 Background: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. TTS presents similarly to autoimmune heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis following Janssen/Johnson & Johnson (Ad26.COV2.S) COVID-19 vaccination have been described. Objective(s): Describe surveillance data and reporting rates of TTS cases following COVID-19 vaccination. Design(s): Case series. Setting(s): United States Patients: Case-patients reported to the Vaccine Adverse Event Reporting System (VAERS) receiving COVID-19 vaccine from December 14, 2020 through August 31, 2021, with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction). If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for anti-platelet factor 4 antibody was required. Measurements: Reporting rates (cases/million vaccine doses) and descriptive epidemiology. Result(s): 52 TTS cases were confirmed following Ad26.COV2.S (n=50) or mRNA-based COVID-19 (n=2) vaccination. TTS reporting rates were 3.55 per million (Ad26.COV2.S) and 0.0057 per million (mRNA-based COVID-19 vaccines). Median age of patients with TTS following Ad26.COV2.S vaccination was 43.5 years (range: 18-70); 70% were female. Both TTS cases following mRNA-based COVID-19 vaccination occurred in males aged >50 years. All cases following Ad26.COV2.S vaccination involved hospitalization including 32 (64%) with intensive care unit admission. Outcomes of hospitalizations following Ad26.COV2.S vaccination included death (12%), discharge to post-acute care (16%), and discharge home (72%). Limitation(s): Under-reporting and incomplete case follow-up. Conclusion(s): TTS is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the two cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Predicting substantive biomedical citations without full text
Hoppe TA , Arabi S , Hutchins BI . Proc Natl Acad Sci U S A 2023 120 (30) e2213697120 Insights from biomedical citation networks can be used to identify promising avenues for accelerating research and its downstream bench-to-bedside translation. Citation analysis generally assumes that each citation documents substantive knowledge transfer that informed the conception, design, or execution of the main experiments. Citations may exist for other reasons. In this paper, we take advantage of late-stage citations added during peer review because these are less likely to represent substantive knowledge flow. Using a large, comprehensive feature set of open access data, we train a predictive model to identify late-stage citations. The model relies only on the title, abstract, and citations to previous articles but not the full-text or future citations patterns, making it suitable for publications as soon as they are released, or those behind a paywall (the vast majority). We find that high prediction scores identify late-stage citations that were likely added during the peer review process as well as those more likely to be rhetorical, such as journal self-citations added during review. Our model conversely gives low prediction scores to early-stage citations and citation classes that are known to represent substantive knowledge transfer. Using this model, we find that US federally funded biomedical research publications represent 30% of the predicted early-stage (and more likely to be substantive) knowledge transfer from basic studies to clinical research, even though these comprise only 10% of the literature. This is a threefold overrepresentation in this important type of knowledge flow. |
Scientific impact of the National Birth Defects Prevention Network multistate collaborative publications
Bascom JT , Stephens SB , Lupo PJ , Canfield MA , Kirby RS , Nestoridi E , Salemi JL , Mai CT , Nembhard WN , Forestieri NE , Romitti PA , St Louis AM , Agopian AJ . Birth Defects Res 2023 BACKGROUND: Given the lack of a national, population-based birth defects surveillance program in the United States, the National Birth Defects Prevention Network (NBDPN) has facilitated important studies on surveillance, research, and prevention of major birth defects. We sought to summarize NBDPN peer-reviewed publications and their impact. METHODS: We obtained and reviewed a curated list of 49 NBDPN multistate collaborative publications during 2000-2022, as of December 31, 2022. Each publication was reviewed and classified by type (e.g., risk factor association analysis). Key characteristics of study populations and analytic approaches used, along with publication impact (e.g., number of citations), were tabulated. RESULTS: NBDPN publications focused on prevalence estimates (N = 17), surveillance methods (N = 11), risk factor associations (N = 10), mortality and other outcomes among affected individuals (N = 6), and descriptive epidemiology of various birth defects (N = 5). The most cited publications were those that reported on prevalence estimates for a spectrum of defects and those that assessed changes in neural tube defects (NTD) prevalence following mandatory folic acid fortification in the United States. CONCLUSIONS: Results from multistate NBDPN publications have provided critical information not available through other sources, including US prevalence estimates of major birth defects, folic acid fortification and NTD prevention, and improved understanding of defect trends and surveillance efforts. Until a national birth defects surveillance program is established in the United States, NBDPN collaborative publications remain an important resource for investigating birth defects and informing decisions related to health services planning of secondary disabilities prevention and care. |
Estimating alcohol-attributable injury deaths: A comparison of epidemiological methods
Naimi TS , Sherk A , Esser MB , Zhao J . Addiction 2023 118 (12) 2466-2476 BACKGROUND AND AIMS: Injuries often involve alcohol, but determining the proportion caused by alcohol is difficult. Several approaches have been used to determine the causal role of alcohol, but these methods have not been compared directly with one another. Such a comparison would be useful for understanding the strengths and comparability of different approaches. This study compared estimates of average annual alcohol-attributable deaths in the United States from injuries during 2015-19 using a blood alcohol concentration (BAC) method compared with a population attributable fraction (PAF) approach. METHODS: For the BAC method, we used a direct method involving the proportion of decedents with a high blood alcohol concentration (BAC; e.g. ≥ 0.10%). For the PAF approach, we compared the use of unadjusted survey data with average consumption data adjusted using alcohol sales data to account for underreporting and also accounting for the underreporting of binge drinking. Survey data were from the Behavioral Risk Factor Surveillance System and mortality data were from the National Vital Statistics System. RESULTS: The number of alcohol-attributable injury deaths using the direct method (48 516 deaths annually) was similar to that using PAF methods (47 879 deaths annually), but only when alcohol use measures were adjusted using alcohol sales data. Furthermore, estimates were similar for cause-specific categories of deaths, including non-motor vehicle unintentional injuries and motor vehicle crashes. Among PAF methods, excessive drinking accounted for 38.3% of injury deaths using unadjusted survey data, but 64.8% of injury deaths using adjusted data. CONCLUSIONS: Estimates of alcohol-attributable injury deaths from a direct method and from a population attributable fraction method that adjusts for alcohol use based on alcohol sales data appear to be comparable. |
Notes from the field: Emergency department visits for nonfatal pedal cyclist injuries before and during the COVID-19 pandemic, United States, 2019-2020
Navon L , Yuan K , Beck L . MMWR Morb Mortal Wkly Rep 2023 72 (28) 769-771 During the early months of the COVID-19 pandemic, many jurisdictions implemented stay-at-home orders (1). Vehicle miles traveled (VMT)* in April 2020 declined by 40% compared with VMT in April 2019; annual VMT in 2020 declined by 13% compared with those in 2019 (2). Despite decreased VMT, pedal cyclist traffic crash fatalities increased by 10% from 859 in 2019 to 948 in 2020 (3). In 2021, pedal cyclist fatalities increased to 966, the highest number reported since 1975 (3,4). Given the increase in pedal cyclist fatalities despite the decline in VMT in 2020, emergency department (ED) visits for nonfatal pedal cyclist injuries in 2019 and 2020 were compared. |
The association between youth violence and mental health outcomes in Colombia: A cross sectional analysis
Vahedi L , Seff I , Meinhart M , Roa AH , Villaveces A , Stark L . Child Abuse Negl 2023 106336 BACKGROUND: Violence against children and youth poses public health risks regarding mental health symptoms and substance use. Less studied is the relationship between violence and mental health/substance abuse in the Latin American context. This study explored sex-stratified relationships between violence and mental health/substance use among Colombian youth. METHODS: We analyzed the 2018 Colombian Violence Against Children and Youth Survey, which collected cross-sectional data from Colombian youth (13-24 years) (n = 2706). Exposure variables were (i) binary sexual, emotional, and physical victimization and (ii) poly-victimization. The outcomes were binary suicidal thoughts, self-harm, past-month psychological distress, binge drinking, smoking, and drug use. Sex-stratified, logistic regressions were adjusted for age, primary school, parental presence, relationship status, and witnessing community violence. RESULTS: For females, (i) emotional violence (compared to being unexposed) was associated with greater odds of suicidal thoughts, self-harm, and psychological distress and (ii) sexual violence was associated with suicidal thoughts and self-harm. For males, (i) emotional violence (compared to being unexposed) was associated with greater odds of suicidal thoughts and psychological distress, but not self-harm and (ii) sexual violence exposure was associated with suicidal thoughts and self-harm. Physical violence was generally not associated with internalized mental health outcomes for females/males, when emotional and sexual violence were held constant. Poly-victimization was consistently and positively associated with internalized mental health symptoms among females, and to a lesser degree for males. Substance use outcomes for males or females were not associated with violence. CONCLUSIONS: Findings highlight the internalized mental health burden of emotional and sexual violence. |
Evaluation of factors that may influence Americans' views on when children should start playing tackle football
Waltzman D , Sarmiento K , Daugherty J . J Athl Train 2023 59 (1) 22-29 OBJECTIVE: American football is associated with the largest number of emergency department visits for pediatric sports-related traumatic brain injury, including concussions. Tackling is responsible for almost two-thirds of football concussions. Some have recommended implementing age restrictions on tackling in youth football. It is unclear whether the public would support such restrictions and what factors may drive support. DESIGN: Cross-sectional. SETTING AND PARTICIPANTS: Data were collected from 4,053 adults in the summer wave of Porter Novelli's 2020 U.S. Consumer Styles survey. MAIN MEASURES: Respondents answered questions about when is a good age to start tackle football, past football playing history, concerns about safety, and the benefits and risks of playing football. RESULTS: Most respondents believed that middle (32.8%) or high school (27.8%) was a good age to start playing tackle football. About one in five (19.8%) respondents reported children should never play tackle football. Certain groups of individuals were more likely to support having children start to play tackle football at high school age or above or to say that children should never play tackle football, including those with a bachelor's degree or more (rate ratio [RR]HS+ = 1.41, 95% confidence interval [CI]=1.14-1.76; RRNEVER = 2.70, 95% CI = 1.93-3.78), those who did not have children under 18 (RRHS+ = 1.54, 95% CI = 1.26-1.90; RRNEVER = 1.54, 95% CI = 1.14-2.07), those who were not football fans (RRNEVER = 3.07, 95% CI - 2.32-4.06), and those who were very (RRHS+ = 3.94, 95% CI = 2.87-5.42; RRNEVER = 11.52, 95% CI = 7.32-18.15) or somewhat concerned (RRHS+ = 1.88, 95% CI = 1.41-2.52) about kids' safety. CONCLUSION: Despite acknowledging benefits of playing football, many adults expressed concern about safety and endorsed high school age and older or never as a good age to start playing tackle football, highlighting a disconnect with current football program practices regarding age. |
Prevalence of adverse childhood experiences in Sub-Saharan Africa: A multicounty analysis of the Violence Against Children and Youth Surveys (VACS)
Amene EW , Annor FB , Gilbert LK , McOwen J , Augusto A , Manuel P , N'Gouanma Nobah MTV , Massetti GM . Child Abuse Negl 2023 106353 BACKGROUND: Adverse Childhood Experiences are traumatic events early in life and have been associated with significant negative health outcomes. OBJECTIVE: To estimate the prevalence of ACEs in five low- and middle-income sub-Saharan African countries. PARTICIPANTS AND SETTING: Nationally representative data from the Cote d'Ivoire (2018), Kenya (2019), Lesotho (2018), Mozambique (2019), and Namibia (2019) Violence Against Children and Youth Surveys (VACS) were used. Analyses were restricted to youth ages 18-24 years (n = 8766 females and 2732 males). METHODS: VACS data were analyzed to generate sex-stratified weighted prevalence of individual ACEs (including sexual, physical, and emotional violence; witnessing interparental violence and violence in the community; and orphanhood) and aggregate ACEs (total ACEs; 0, 1-2, and 3 or more), for each country and combined. RESULTS: The most common type of ACEs among both females and males was witnessing physical violence (males: 55.0 % [95 % CI: 51.1-58.8] and females: 37.2 % [95 % CI = 34.3-40.1]) followed by experiencing physical violence (males: 49.7 % [95 % CI = 45.5-53.9] and in females: 36.5 % [95 % CI = 33.8-39.2]). Prevalence of sexual violence was significantly higher in females than in males (16.0 % [95 % CI = 13.9-18.2] vs 8.3 % [95 % CI = 7.0-9.8]; p < 0.001). About 72 % of females and 82 % of males have experienced at least one form of ACE with 20 % of females and 24.2 % of males experiencing 3 or more ACEs. CONCLUSION: This study demonstrated that majority of the children in countries in sub-Saharan Africa have experienced multiple ACEs in their lifetime. Understanding the extent of the problem will help design early interventions to reduce childhood exposure to ACEs or mitigate against the harmful impact of ACEs. |
Associations between conflict violence, community violence, and household violence exposures among females in Colombia
Stark L , Meinhart M , Seff I , Gillespie A , Roa AH , Villaveces A . Child Abuse Negl 2023 106341 BACKGROUND: Exposure to protracted public violence is increasingly referenced as a risk factor for domestic violence, but limited quantitative evidence has demonstrated this association to date. This study analyzes associations in Colombia between lifetime experiences of external violence, including the Colombia civil conflict and community interpersonal violence, and experiences of household violence, including intimate partner and caregiver violence. METHODS AND FINDINGS: We use the 2018 Colombia Violence Against Children and Youth Survey, employing multi-variable logistic regressions to determine the association between exposure to external violence and household violence victimization for females aged 13-24 (n = 1406). Adjusted models controlled for age, ever married, currently in school, and past 12-mo work experience and standard errors were adjusted to account for the multi-stage sampling design. Females who had ever witnessed community violence (39.23 %) faced increased risks of experiencing both physical violence (aOR = 2.81; 95 % CIs: 1.54-5.14; p < 0.001) and emotional violence (aOR: 2.48; 95 % CIs: 1.29-4.75; p < 0.01) from caregivers. Females who had ever witnessed internal conflict (15.99 %) had a greater likelihood of experiencing emotional violence from caregivers (aOR: 5.24; 95 % CIs: 1.86-14.76; p < 0.01) as well as physical violence perpetrated by intimate partners (aOR: 3.31; 95 % CIs: 1.22-8.95; p < 0.05). CONCLUSIONS: This study demonstrates the connection between exposure to community violence and internal conflict and household violence victimization among adolescent and young adult females in Colombia. Findings build the evidence base for more holistic and coordinated policy and programming efforts and foreground the need to identify and support vulnerable populations across socioecological domains in contexts of chronic violence. |
Online social networks of individuals with adverse childhood experiences (preprint)
Cao Y , Rajendran S , Sundararajan P , Law R , Bacon S , Sumner SA , Masuda N . medRxiv 2022 20 Adverse childhood experiences (ACEs), which include abuse and neglect and various household challenges like exposure to intimate partner violence and substance use in the home can have negative impacts on lifelong health of affected individuals. Among various strategies for mitigating the adverse effects of ACEs is to enhance connectedness and social support for those who have experienced ACEs. However, how social networks of those who experienced ACEs differ from those who did not is poorly understood. In the present study, we use Reddit and Twitter data to investigate and compare social networks among individuals with and without ACEs exposure. We first use a neural network classifier to identify the presence or absence of public ACEs disclosures in social media posts. We then analyze egocentric social networks comparing individuals with self-reported ACEs to those with no reported history. We found that, although individuals reporting ACEs had fewer total followers in online social networks, they had higher reciprocity in following behavior (i.e., mutual following with other users), a higher tendency to follow and be followed by other individuals with ACEs, and a higher tendency to follow back individuals with ACEs rather than individuals without ACEs. These results imply that individuals with ACEs may try to actively connect to others having similar prior traumatic experiences as a positive connection and coping strategy. Supportive interpersonal connections online for individuals with ACEs appear to be a prevalent behavior and may be a way to enhance social connectedness and resilience in those who have experienced ACEs. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. |
Diagnostic accuracy of three computer-aided detection systems for detecting pulmonary tuberculosis on chest radiography when used for screening: Analysis of an international, multicenter migrants screening study
Gelaw SM , Kik SV , Ruhwald M , Ongarello S , Egzertegegne TS , Gorbacheva O , Gilpin C , Marano N , Lee S , Phares CR , Medina V , Amatya B , Denkinger CM . PLOS Glob Public Health 2023 3 (7) e0000402 The aim of this study was to independently evaluate the diagnostic accuracy of three artificial intelligence (AI)-based computer aided detection (CAD) systems for detecting pulmonary tuberculosis (TB) on global migrants screening chest x-ray (CXR) cases when compared against both microbiological and radiological reference standards (MRS and RadRS, respectively). Retrospective clinical data and CXR images were collected from the International Organization for Migration (IOM) pre-migration health assessment TB screening global database for US-bound migrants. A total of 2,812 participants were included in the dataset used for analysis against RadRS, of which 1,769 (62.9%) had accompanying microbiological test results and were included against MRS. All CXRs were interpreted by three CAD systems (CAD4TB v6, Lunit INSIGHT v4.9.0, and qXR v2) in offline setting, and re-interpreted by two expert radiologists in a blinded fashion. The performance was evaluated using receiver operating characteristics curve (ROC), estimates of sensitivity and specificity at different CAD thresholds against both microbiological and radiological reference standards (MRS and RadRS, respectively), and was compared with that of the expert radiologists. The area under the curve against MRS was highest for Lunit (0.85; 95% CI 0.83-0.87), followed by qXR (0.75; 95% CI 0.72-0.77) and then CAD4TB (0.71; 95% CI 0.68-0.73). At a set specificity of 70%, Lunit had the highest sensitivity (81.4%; 95% CI 77.9-84.6); at a set sensitivity of 90%, specificity was also highest for Lunit (54.5%; 95% CI 51.7-57.3). The CAD systems performed comparable to the sensitivity (98.3%), and except CAD4TB, to specificity (13.7%) of the expert radiologists. Similar trends were observed when using RadRS. Area under the curve against RadRS was highest for CAD4TB (0.87; 95% CI 0.86-0.89) and Lunit (0.87; 95% CI 0.85-0.88) followed by qXR (0.81; 95% CI 0.80-0.83). At a set specificity of 70%, CAD4TB had highest sensitivity (84.1%; 95% CI 82.3-85.8) followed by Lunit (80.9%; 95% CI 78.9-82.7); and at a set sensitivity of 90%, specificity was also highest for CAD4TB (54.6%; 95% CI 51.3-57.8). In conclusion, the study demonstrated that the three CAD systems had broadly similar diagnostic accuracy with regard to TB screening and comparable accuracy to an expert radiologist against MRS. Compared with different reference standards, Lunit performed better than both qXR and CAD4TB against MRS, and CAD4TB and Lunit better than qXR against RadRS. Moreover, the performance of the CADs can be impacted by characteristics of subgroup of population. The main limitation was that our study relied on retrospective data and MRS was not routinely done in individuals with a low suspicion of TB and a normal CXR. Our findings suggest that CAD systems could be a useful tool for TB screening programs in remote, high TB prevalent places where access to expert radiologists may be limited. However, further large-scale prospective studies are needed to address outstanding questions around the operational performance and technical requirements of the CAD systems. |
Practical considerations for accurate determination of free thyroxine by equilibrium dialysis
Ribera A , Zhang L , Ribeiro C , Vazquez N , Thonkulpitak J , Botelho JC , Danilenko U , van Uytfanghe K , Vesper HW . J Mass Spectrom Adv Clin Lab 2023 29 9-15 BACKGROUND: Free thyroxine (FT4) measurement is one of the most requested tests in patient care for diagnosing and treating thyroid-related illnesses. Equilibrium dialysis (ED) is considered the "gold standard" for FT4 measurement; however, several factors have a profound effect on the reliability of FT4 assays and require special consideration. METHODS: In the current study, we focused on evaluating critical factors that could contribute to reporting errors, such as adsorption of thyroxine (T4) to labware surfaces, stability of serum samples, stock solutions, and calibrator storage conditions, as well as the solvents used to prepare T4 solutions. RESULTS: The adsorption of T4 in ethanolic solutions and dialysates to labware surfaces can be reduced with the careful selection of pipette tips, test tubes, and 96-well plates. Adding pH modifiers to neat T4 solutions can improve its stability. FT4 in serum samples remains stable after exposure to four freeze-thaw cycles, 5 °C for 18-20 h, or -70 °C for a minimum of three years. CONCLUSION: The presented study has demonstrated that the loss of analyte due to pre-analytical and analytical factors during operation of the FT4 reference measurement procedure (RMP) can be minimized by careful selection of all labware for sample preparation. It was found that the accuracy and imprecision of FT4 assays can be influenced by different types of dialysis devices, but acceptable alternatives to ED membranes were identified. This study demonstrates approaches to establish a FT4 method that is independent from specific suppliers and addresses critical pre-analytical and analytical factors important for FT4 measurements. |
Novel pneumococcal capsule type 33E results from the inactivation of glycosyltransferase WciE in vaccine type 33F
Ganaie FA , Saad JS , Lo SW , McGee L , van Tonder AJ , Hawkins PA , Calix JJ , Bentley SD , Nahm MH . J Biol Chem 2023 299 (9) 105085 The polysaccharide (PS) capsule is essential for immune evasion and virulence of Streptococcus pneumoniae. Existing pneumococcal vaccines are designed to elicit anti-capsule antibodies, however, the effectiveness of these vaccines is being challenged by the emergence of new capsule types or variants. Herein, we characterize a newly discovered capsule type, 33E, that appears to have repeatedly emerged from vaccine type 33F via an inactivation mutation in the capsule glycosyltransferase gene, wciE. Structural analysis demonstrated that 33E and 33F share an identical repeat unit backbone [→5)-β-D-Galf2Ac-(1→3)-β-D-Galp-(1→3)-α-D-Galp-(1→3)-β-D-Galf-(1→3)-β-D-Glcp-(1→], except that a galactose (α-D-Galp) branch is present in 33F but not in 33E. Though the two capsule types were indistinguishable using conventional typing methods, the monoclonal antibody Hyp33FM1 selectively bound 33F but not 33E pneumococci. Further, we confirmed that wciE encodes a glycosyltransferase that catalyzes the addition of the branching α-D-Galp and that its inactivation in 33F strains results in the expression of the 33E capsule type. Though 33F and 33E share a structural and antigenic similarity, our pilot study suggested that immunization with a 23-valent pneumococcal PS vaccine containing 33F PS didn't significantly elicit cross-opsonic antibodies to 33E. New conjugate vaccines that target capsule type 33F may not necessarily protect against 33E. Therefore, studies of new conjugate vaccines require knowledge of the newly identified capsule type 33E and reliable pneumococcal typing methods capable of distinguishing it from 33F. |
Alpha and beta spillover in liquid scintillation counting analysis of urine samples
Piraner O , Eardley K , Button J . J Radioanal Nucl Chem 2023 332 (9) 3837-3844 Rapid detection and quantification of gross alpha/beta-emitting radionuclides by liquid scintillation counting (LSC) is vital in guiding response to a nuclear or radiological incidents. Liquid scintillation counters use signal pulse shape to discriminate alpha and beta events in samples but require precise optimization to minimize the spillover, or misclassification, of those events. In this study, samples at varying activity levels were analyzed by LSC to determine the effect of activity level, emitter type, and sample matrix on spillover. Analysis proved a matrix effect and a direct correlation of activity level on spillover percentage for both alpha and beta emitting-nuclides. © 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. |
Severe acute respiratory disease in American mink (Neovison vison) experimentally infected with SARS-CoV-2 (preprint)
Adney DR , Lovaglio J , Schulz JE , Yinda CK , Avanzato VA , Haddock E , Port JR , Holbrook MG , Hanley PW , Saturday G , Scott D , Spengler JR , Tansey C , Cossaboom CM , Wendling NM , Martens C , Easley J , Yap SW , Seifert SN , Munster VJ . bioRxiv 2022 24 An animal model that fully recapitulates severe COVID-19 presentation in humans has been a top priority since the discovery of SARS-CoV-2 in 2019. Although multiple animal models are available for mild to moderate clinical disease, a non-transgenic model that develops severe acute respiratory disease has not been described. Mink experimentally infected with SARS-CoV-2 developed severe acute respiratory disease, as evident by clinical respiratory disease, radiological, and histological changes. Virus was detected in nasal, oral, rectal, and fur swabs. Deep sequencing of SARS-CoV-2 from oral swabs and lung tissue samples showed repeated enrichment for a mutation in the gene encoding for nonstructural protein 6 in open reading frame 1a/1ab. Together, these data indicate that American mink develop clinical features characteristic of severe COVID19 and as such, are uniquely suited to test viral countermeasures. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission (preprint)
Karthikeyan S , Levy JI , De Hoff P , Humphrey G , Birmingham A , Jepsen K , Farmer S , Tubb HM , Valles T , Tribelhorn CE , Tsai R , Aigner S , Sathe S , Moshiri N , Henson B , Mark AM , Hakim A , Baer NA , Barber T , Belda-Ferre P , Chacón M , Cheung W , Cresini ES , Eisner ER , Lastrella AL , Lawrence ES , Marotz CA , Ngo TT , Ostrander T , Plascencia A , Salido RA , Seaver P , Smoot EW , McDonald D , Neuhard RM , Scioscia AL , Satterlund AM , Simmons EH , Abelman DB , Brenner D , Bruner JC , Buckley A , Ellison M , Gattas J , Gonias SL , Hale M , Hawkins F , Ikeda L , Jhaveri H , Johnson T , Kellen V , Kremer B , Matthews G , McLawhon RW , Ouillet P , Park D , Pradenas A , Reed S , Riggs L , Sanders A , Sollenberger B , Song A , White B , Winbush T , Aceves CM , Anderson C , Gangavarapu K , Hufbauer E , Kurzban E , Lee J , Matteson NL , Parker E , Perkins SA , Ramesh KS , Robles-Sikisaka R , Schwab MA , Spencer E , Wohl S , Nicholson L , McHardy IH , Dimmock DP , Hobbs CA , Bakhtar O , Harding A , Mendoza A , Bolze A , Becker D , Cirulli ET , Isaksson M , Barrett KMS , Washington NL , Malone JD , Schafer AM , Gurfield N , Stous S , Fielding-Miller R , Garfein RS , Gaines T , Anderson C , Martin NK , Schooley R , Austin B , MacCannell DR , Kingsmore SF , Lee W , Shah S , McDonald E , Yu AT , Zeller M , Fisch KM , Longhurst C , Maysent P , Pride D , Khosla PK , Laurent LC , Yeo GW , Andersen KG , Knight R . medRxiv 2022 As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission. |
Mucosal and systemic neutralizing antibodies to norovirus and rotavirus by oral immunization with recombinant rotavirus in infant mice (preprint)
Kawagishi T , Sanchez-Tacuba L , Feng N , Costantini VP , Tan M , Jiang X , Green KY , Vinje J , Ding S , Greenberg HB . bioRxiv 2022 02 Rotaviruses (RVs) preferentially replicate in the small intestine, frequently cause severe diarrheal disease, and following enteric infection generally induce variable levels of protective systemic and mucosal immune responses in humans and other animals. Rhesus rotavirus (RRV) is a simian RV that was previously used as a human RV vaccine and has been extensively studied in mice. Although RRV replicates poorly in the suckling mouse intestine, infection induces a robust and protective antibody response. The recent availability of plasmid-based RV reverse genetics systems has enabled the generation of recombinant RVs expressing foreign proteins. However, recombinant RVs have not yet been experimentally tested as potential vaccine vectors to immunize against other gastrointestinal pathogens in vivo. This is a missed opportunity because several live-attenuated RV vaccines are already widely administered to infants and young children worldwide. To explore the feasibility of using RV as a dual vaccine vector, we rescued a replication-competent recombinant RRV harboring bicistronic gene segment 7 that encodes both the native RV NSP3 protein and a human norovirus (HuNoV) VP1 protein from the predominant genotype GII.4 (rRRV-HuNoV-VP1). The rRRV-HuNoV-VP1 expressed HuNoV VP1 in infected cells in vitro and importantly, elicited both systemic and local antibody responses to HuNoV following oral infection of suckling mice. Serum IgG and fecal IgA from infected suckling mice bound to and neutralized both RV and HuNoV. These findings have encouraging practical implications for the design of RV-based next-generation multivalent enteric vaccines to target HuNoV and other human enteric pathogens while providing immunity to RV. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Performance Characteristics of Six Immunoglobulin M (IgM) ELISA Assays Used for Laboratory Confirmation of Measles (preprint)
Sowers SB , Anthony K , Mercader S , Colley H , Crooke SN , Rota PA , Latner DR , Hickman CJ . medRxiv 2022 04 Laboratory confirmation of infection is an essential component of measles surveillance. Detection of measles specific IgM in serum by enzyme linked immunosorbent assay (ELISA) is the most used method for confirming measles infection. ELISA formats vary as does the sensitivity and specificity of each assay. Specimens collected within 3 days of rash onset can yield a false negative result, which can delay confirmation of measles cases. Interfering substances can yield a false positive result, leading to unnecessary public health interventions. The IgM capture assay developed at the Centers for Disease Control (CDC) was compared against 5 commercially available ELISA kits for the ability to detect measles virus-specific IgM in a panel of 90 well-characterized specimens. Serum samples were tested in triplicate using each commercial kit as recommended by the manufacturer. Using the CDC measles IgM capture assay as the reference test; sensitivity and specificity for the commercial kits ranged from 50 to 83% and 86.9 to 98%, respectively. Discrepant results were observed for samples tested with all five commercial kits and ranged from 13.8 to 28.8% of the specimens tested. False positive results occurred in 2.0 to 13.1% of sera while negative results were observed in 16.7 to 50% of sera that were positive by the CDC measles IgM capture assay. Evaluation and interpretation of measles IgM serologic results can be complex, particularly in measles elimination settings. The performance characteristics of a measles IgM assay should be carefully considered when selecting an assay to achieve high quality measles surveillance. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Performance of Existing and Novel Symptom- and Antigen Testing-Based COVID-19 Case Definitions in a Community Setting (preprint)
Lee S , Almendares O , Prince-Guerra JL , Heilig CM , Tate JE , Kirking HL . medRxiv 2022 10 Point-of-care antigen tests are an important tool for SARS-CoV-2 detection, but they are less clinically sensitive than real-time reverse-transcription PCR (RT-PCR), impacting their efficacy as screening procedures. Our goal in this study was to see whether we could improve this sensitivity by considering antigen test results in combination with other relevant information, namely exposure status and reported symptoms. In November of 2020, we collected 3,419 paired upper respiratory specimens tested by RT-PCR and the Abbott BinaxNOW antigen test at two community testing sites in Pima County, Arizona. We used symptom, exposure, and antigen testing data to evaluate the sensitivity and specificity of various symptom definitions in predicting RT-PCR positivity. Our analysis yielded 6 novel multi-symptom case definitions with and without antigen test results, the best of which overall achieved a Youden's J index of 0.66, as compared with 0.52 for antigen testing alone. Using a random forest as a guide, we show that this definition, along with our others, does not lose the ability to generalize well to new data despite achieving optimal performance in our sample. Our methodology is broadly applicable, and we have made our code publicly available to aid public health practitioners in developing or fine-tuning their own screening rules. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Genital tract microbiome dynamics are associated with time of Chlamydia infection (preprint)
Zhao L , Lundy SR , Eko FO , Igietseme JU , Omosun YO . bioRxiv 2022 19 Background: We have previously shown that the time of Chlamydia infection was crucial in determining the chlamydial infectivity and pathogenesis. This study aims to determine whether the time of Chlamydia infection affects the genital tract microbiome. This study analyzed mice vaginal, uterine, and ovary/oviduct microbiome with and without Chlamydia infection. The mice were infected with Chlamydia at either 10:00 am (ZT3) or 10:00 pm (ZT15). Result(s): The results showed that mice infected at ZT3 had higher Chlamydia infectivity than those infected at ZT15. There was more variation in the compositional complexity of the vaginal microbiome (alpha diversity) of mice infected at ZT3 than those mice infected at ZT15 throughout the infection within each treatment group, with both Shannon and Simpson diversity index values decreased over time. The analysis of samples collected four weeks post-infection showed that there were significant taxonomical differences (beta diversity) between different parts of the genital tract-vagina, uterus, and ovary/oviduct-and this difference was associated with the time of infection. Firmicutes and Proteobacteria were the most abundant phyla within the microbiome in all three genital tract regions for all the samples collected during this experiment. Additionally, Firmicutes was the dominant phylum in the uterine microbiome of ZT3 Chlamydia infected mice. Conclusion(s): The results show that the time of infection is associated with the microbial dynamics in the genital tract. And this association is more robust in the upper genital tract than in the vagina. This result implies that more emphasis should be placed on understanding the changes in the microbial dynamics of the upper genital tract over the course of infection. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Intermittent systemic exposure to lipopolysaccharide-induced inflammation disrupts hippocampal long-term potentiation and impairs cognition in aging male mice (preprint)
Engler-Chiurazzi EB , Russel AE , Povroznik JM , McDonald K , Porter K , Wang DS , Billig BK , Felton CC , Hammock J , Schreurs BG , O'Callaghan JD , Zwezdaryk KJ , Simpkins JW . bioRxiv 2022 18 279-291 Age-related cognitive decline, a common component of the brain aging process, is associated with significant impairment in daily functioning and quality of life among geriatric adults. While the complexity of mechanisms underlying cognitive aging are still being elucidated, microbial exposure and the multifactorial inflammatory cascades associated with systemic infections is emerging as a potential driver of neurological senescence. The negative cognitive and neurobiological consequences of a single pathogen-associated inflammatory experience, such as that modeled through treatment with lipopolysaccharide (LPS), are well documented. Yet, the brain aging impacts of repeated, intermittent inflammatory challenges are less well studied. To extend the emerging literature assessing the impact of infection burden on cognitive function among normally aging mice, here, we repeatedly exposed adult mice to intermittent LPS challenges during the aging period. Male 10-month-old C57BL6 mice were systemically administered escalating doses of LPS once every two weeks for 2.5 months. We evaluated cognitive consequences using the non-spatial step-through inhibitory avoidance task and both spatial working and reference memory versions of the Morris water maze. We also probed several potential mechanisms, including cortical and hippocampal cytokine/chemokine gene expression as well as hippocampal neuronal function via extracellular field potential recordings. Though there was limited evidence for an ongoing inflammatory state in cortex and hippocampus, we observed impaired learning and memory and a disruption of hippocampal long-term potentiation. These data suggest that a history of intermittent exposure to LPS-induced inflammation is associated with a subtle but significantly accelerated trajectory of cognitive decline. The broader impact of these findings may have important implications for standard of care involving infections in aging individuals or populations at-risk for dementia. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Pathogens detected using a syndromic molecular diagnostic platform in patients hospitalized with severe respiratory illness in South Africa in 2017 (preprint)
Moleleki M , du Plessis M , Ndlangisa K , Reddy C , von Gottberg A , Hellferscee O , Mekgoe O , McMorrow M , Walaza S , Cohen C , Tempia S , Variava E , Wolter N . medRxiv 2021 10 Background Pneumonia continues to be a leading cause of death globally; however, in >50% of cases, an etiological agent is not identified. We describe the use of a multi-pathogen platform, TaqMan array card (TAC) real-time PCR, for the detection of pathogens in patients hospitalized with severe respiratory illness (SRI). Methods We conducted prospective hospital-based surveillance for SRI among patients at two sentinel sites in South Africa between January and December 2017. Patients were included in this study if a blood specimen and at least one respiratory specimen (naso- and oro-pharyngeal (NP/OP) swabs and/or sputum) were available for testing. We tested respiratory specimens for 21 respiratory pathogens and blood samples for nine bacteria using TAC. Pathogen detection was compared by age group and HIV status using the chi-squared test. Results During 2017, 956 patients were enrolled in SRI surveillance, and of these, 637 (67%) patients were included in this study (637 blood, 487 NP/OP and 411 sputum specimens tested). At least one pathogen was detected in 83% (527/637) of patients. Common pathogens detected included H. influenzae (225/637; 35%), S. pneumoniae (224/637; 35%), rhinovirus (144/637; 23%), S. aureus (129/637; 20%), K. pneumoniae (85/637; 13%), M. tuberculosis (75/637; 12%), and respiratory syncytial virus (57/637; 9%). Multiple pathogens (>=2) were co-detected in 57% (364/637) of patients. Conclusion While use of a multi-pathogen platform was useful in the detection of a pathogen in the majority of the patients, pathogen co-detections were common and would need clinical assessment for usefulness in individual-level treatment and management decisions. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Potential use of antibodies to provide an earlier indication of lymphatic filariasis resurgence in post-mass drug administration surveillance, American Samoa (preprint)
Cadavid Restrepo AM , Gass K , Won KY , Sheel M , Robinson K , Graves PM , Fuimaono S , Lau CL . medRxiv 2021 02 Objectives Under the Global Programme to Eliminate Lymphatic Filariasis (LF), American Samoa conducted seven rounds of mass drug administration between 2000 and 2006. The territory passed transmission assessment surveys (TAS) in 2011 (TAS-1) and 2015 (TAS-2) based on World Health Organization guidelines. In 2016, the territory failed TAS-3, indicating resurgence. This study aims to determine if antibodies (Ab) may have provided a timelier indication of LF resurgence in American Samoa. Methods We examined school-level Ag and Ab status (presence/absence of Ag- and Ab-positive children) and prevalence of single and combined Ab responses to Wb123, Bm14, Bm33 Ags at each TAS. Pearson's chi-squared tests and logistic regression were used to examine associations between school-level Ab prevalence in TAS-1 and TAS-2 and school-level Ag status in TAS-3. Results Schools with higher prevalence of Wb123 Ab in TAS-2 had higher odds of being Ag-positive in TAS-3 (odds ratio [OR] 24.5, 95% CI:1.2-512.7). Schools that were Ab-positive for WB123 plus Bm14, Bm33 or both Bm14 and Bm33 in TAS-2 had higher odds of being Ag-positive in TAS-3 (OR 16.0-24.5). Conclusion Anti-filarial Abs could provide earlier signals of resurgence and enable a timelier response. The promising role of Abs in post-MDA surveillance and decision making should be further investigated in other settings. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Equipment-free detection of SARS-CoV-2 and Variants of Concern using Cas13 (preprint)
Arizti-Sanz J , Bradley AD , Zhang YB , Boehm CK , Freije CA , Grunberg ME , Kosoko-Thoroddsen TSF , Welch NL , Pillai PP , Mantena S , Kim G , Uwanibe JN , John OG , Eromon PE , Kocher G , Gross R , Lee JS , Hensley LE , Happi CT , Johnson J , Sabeti PC , Myhrvold C . medRxiv 2021 02 The COVID-19 pandemic, and the recent rise and widespread transmission of SARS-CoV-2 Variants of Concern (VOCs), have demonstrated the need for ubiquitous nucleic acid testing outside of centralized clinical laboratories. Here, we develop SHINEv2, a Cas13-based nucleic acid diagnostic that combines quick and ambient temperature sample processing and lyophilized reagents to greatly simplify the test procedure and assay distribution. We benchmarked a SHINEv2 assay for SARS-CoV-2 detection against state-of-the-art antigen-capture tests using 96 patient samples, demonstrating 50-fold greater sensitivity and 100% specificity. We designed SHINEv2 assays for discriminating the Alpha, Beta, Gamma and Delta VOCs, which can be read out visually using lateral flow technology. We further demonstrate that our assays can be performed without any equipment in less than 90 minutes. SHINEv2 represents an important advance towards rapid nucleic acid tests that can be performed in any location. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Broad-spectrum in vitro antiviral activity of ODBG-P-RVn: an orally-available, lipid-modified monophosphate prodrug of remdesivir parent nucleoside (GS-441524) (preprint)
Lo MK , Shrivastava-Ranjan P , Chatterjee P , Flint M , Beadle JR , Valiaeva N , Schooley RT , Hostetler KY , Montgomery JM , Spiropoulou C . bioRxiv 2021 The intravenous administration of remdesivir for COVID-19 confines its utility to hospitalized patients. We evaluated the broad-spectrum antiviral activity of ODBG-P-RVn, an orally available, lipid-modified monophosphate prodrug of the remdesivir parent nucleoside (GS-441524) against viruses that cause diseases of human public health concern, including SARS-CoV-2. ODBG-P-RVn showed 20-fold greater antiviral activity than GS-441524 and had near-equivalent activity to remdesivir in primary-like human small airway epithelial cells. Our results warrant investigation of ODBG-P-RVn efficacy in vivo. |
A comparison of performance metrics for cloth face masks as source control devices for simulated cough and exhalation aerosols (preprint)
Lindsley WG , Blachere FM , Beezhold DH , Law BF , Derk RC , Hettick JM , Woodfork K , Goldsmith WT , Harris JR , Duling MG , Boutin B , Nurkiewicz T , Noti JD . medRxiv 2021 Universal mask wearing is recommended by the Centers for Disease Control and Prevention to help control the spread of COVID-19. Masks reduce the expulsion of respiratory aerosols (called source control) and offer some protection to the wearer. However, masks vary greatly in their designs and construction materials, and it is not clear which are most effective. Our study tested 15 reusable cloth masks (which included face masks, neck gaiters, and bandanas), two medical masks, and two N95 filtering facepiece respirators as source control devices for aerosols ≤ 7 µm produced during simulated coughing and exhalation. These measurements were compared with the mask filtration efficiencies, airflow resistances, and fit factors. The source control collection efficiencies for the cloth masks ranged from 17% to 71% for coughing and 35% to 66% for exhalation. The filtration efficiencies of the cloth masks ranged from 1.4% to 98%, while the fit factors were 1.3 to 7.4 on an elastomeric manikin headform and 1.0 to 4.0 on human test subjects. The correlation coefficients between the source control efficacies and the other performance metrics ranged from 0.31 to 0.66 and were significant in all but one case. However, none of the alternative metrics were strong predictors of the source control performance of cloth masks. Our results suggest that a better understanding of the relationships between source control performance and metrics like filtration efficiency, airflow resistance, and fit factor are needed to develop simple methods to estimate the effectiveness of masks as source control devices for respiratory aerosols. |
Development and validation of an enzyme immunoassay for detection and quantification of SARS-CoV-2 salivary IgA and IgG (preprint)
Costantini VP , Nguyen K , Lyski Z , Novosad S , Bardossy AC , Lyons AK , Gable P , Kutty PK , Lutgring JD , Brunton A , Thornburg NJ , Brown AC , McDonald LC , Messer W , Vinjé J . medRxiv 2021 Oral fluids offer a non-invasive sampling method for the detection of antibodies. Quantification of IgA and IgG antibodies in saliva allows studies of the mucosal and systemic immune response after natural infection or vaccination. We developed and validated an enzyme immunoassay (EIA) to detect and quantify salivary IgA and IgG antibodies against the prefusion-stabilized form of the SARS-CoV-2 spike protein. Normalization against total antibody isotype was performed to account for specimen differences, such as collection time and sample volume. Saliva samples collected from 187 SARS-CoV-2 confirmed cases enrolled in 2 cohorts and 373 pre-pandemic saliva samples were tested. The sensitivity of both EIAs was high (IgA: 95.5%; IgG: 89.7%) without compromising specificity (IgA: 99%; IgG: 97%). No cross reactivity with seasonal coronaviruses was observed. The limit of detection for SARS-CoV-2 salivary IgA and IgG assays were 1.98 ng/mL and 0.30 ng/mL, respectively. Salivary IgA and IgG antibodies were detected earlier in patients with mild COVID-19 symptoms than in severe cases. However, severe cases showed higher salivary antibody titers than those with a mild infection. Salivary IgA titers quickly decreased after 6 weeks in mild cases but remained detectable until at least week 10 in severe cases. Salivary IgG titers remained high for all patients, regardless of disease severity. In conclusion, EIAs for both IgA and IgG had high specificity and sensitivity for the confirmation of current or recent SARS-CoV-2 infections and evaluation of the IgA and IgG immune response. |
TMEM41B is a pan-flavivirus host factor (preprint)
Hoffmann HH , Schneider WM , Rozen-Gagnon K , Miles LA , Schuster F , Razooky B , Jacobson E , Wu X , Yi S , Rudin CM , MacDonald MR , McMullan LK , Poirier JT , Rice CM . bioRxiv 2020 11 11 Flaviviruses pose a constant threat to human health. These RNA viruses are transmitted by the bite of infected mosquitoes and ticks and regularly cause outbreaks. To identify host factors required for flavivirus infection we performed full-genome loss of function CRISPR-Cas9 screens. Based on these results we focused our efforts on characterizing the roles that TMEM41B and VMP1 play in the virus replication cycle. Our mechanistic studies on TMEM41B revealed that all members of the Flaviviridae family that we tested require TMEM41B. We tested 12 additional virus families and found that SARS-CoV-2 of the Coronaviridae also required TMEM41B for infection. Remarkably, single nucleotide polymorphisms (SNPs) present at nearly twenty percent in East Asian populations reduce flavivirus infection. Based on our mechanistic studies we hypothesize that TMEM41B is recruited to flavivirus RNA replication complexes to facilitate membrane curvature, which creates a protected environment for viral genome replication. | HIGHLIGHTS: TMEM41B and VMP1 are required for both autophagy and flavivirus infection, however, autophagy is not required for flavivirus infection.TMEM41B associates with viral proteins and likely facilitates membrane remodeling to establish viral RNA replication complexes.TMEM41B single nucleotide polymorphisms (SNPs) present at nearly twenty percent in East Asian populations reduce flavivirus infection.TMEM41B-deficient cells display an exaggerated innate immune response upon high multiplicity flavivirus infection. |
Short sleep duration: Children's mental, behavioral, and developmental disorders and demographic, neighborhood, and family context in a nationally representative sample, 2016-2019
Claussen AH , Dimitrov LV , Bhupalam S , Wheaton AG , Danielson ML . Prev Chronic Dis 2023 20 E58 INTRODUCTION: Many children and adolescents experience insufficient sleep, which poses risks for their short- and long-term health and development. This study examined the concurrent associations of contextual factors, including child, demographic, neighborhood, and family factors, with short sleep duration. METHODS: We combined data on children aged 3 to 17 years from the 2016-2019 National Survey of Children's Health (N = 112,925) to examine the association of parent-reported child short sleep duration (ages 3-5 y, <10 h; 6-12 y, <9 h; 13-17 y, <8 h) with mental, behavioral, and developmental disorders (MBDDs); selected physical health conditions; and demographic, neighborhood, and family factors. RESULTS: Overall, 34.7% of children experienced short sleep duration. The prevalence was highest among children aged 6 to 12 years (37.5%); children from racial and ethnic minority groups, especially non-Hispanic Black children (50.0%); children from low-income households (44.9%); children with an MBDD (39.6%); children experiencing negative neighborhood factors (poor conditions and lack of safety, support, and amenities, 36.5%); and family factors such as inconsistent bedtime (57.3%), poor parental mental (47.5%) and physical health (46.0%), and adverse childhood experiences (44.1%). The associations between sleep and demographic, neighborhood, and family factors, and MBDD remained significant after controlling for all other factors. CONCLUSION: This study identified several individual, family, and community factors that may contribute to children's short sleep duration and can be targeted to improve healthy development, particularly among children with an MBDD, from households with low socioeconomic status, or from racial and ethnic minority groups who are at increased risk for short sleep duration. |
Are individual-level risk factors for gastroschisis modified by neighborhood-level socioeconomic factors
Neo DT , Martin CL , Carmichael SL , Gucsavas-Calikoglu M , Conway KM , Evans SP , Feldkamp ML , Gilboa SM , Insaf TZ , Musfee FI , Shaw GM , Shumate C , Werler MM , Olshan AF , Desrosiers TA . Birth Defects Res 2023 115 (15) 1438-1449 BACKGROUND: Two strong risk factors for gastroschisis are young maternal age (<20 years) and low/normal pre-pregnancy body mass index (BMI), yet the reasons remain unknown. We explored whether neighborhood-level socioeconomic position (nSEP) during pregnancy modified these associations. METHODS: We analyzed data from 1269 gastroschisis cases and 10,217 controls in the National Birth Defects Prevention Study (1997-2011). To characterize nSEP, we applied the neighborhood deprivation index and used generalized estimating equations to calculate odds ratios and relative excess risk due to interaction. RESULTS: Elevated odds of gastroschisis were consistently associated with young maternal age and low/normal BMI, regardless of nSEP. High-deprivation neighborhoods modified the association with young maternal age. Infants of young mothers in high-deprivation areas had lower odds of gastroschisis (adjusted odds ratio [aOR]: 3.1, 95% confidence interval [CI]: 2.6, 3.8) than young mothers in low-deprivation areas (aOR: 6.6; 95% CI: 4.6, 9.4). Mothers of low/normal BMI had approximately twice the odds of having an infant with gastroschisis compared to mothers with overweight/obese BMI, regardless of nSEP (aOR range: 1.5-2.3). CONCLUSION: Our findings suggest nSEP modified the association between gastroschisis and maternal age, but not BMI. Further research could clarify whether the modification is due to unidentified biologic and/or non-biologic factors. |
Neurological and psychological sequelae associated with multisystem inflammatory syndrome in children
Rollins CK , Calderon J , Wypij D , Taylor AM , Davalji Kanjiker TS , Rohde JS , Maiman M , Zambrano LD , Newhams MM , Rodriguez S , Hart N , Worhach J , Kucukak S , Poussaint TY , Son MBF , Friedman ML , Gertz SJ , Hobbs CV , Kong M , Maddux AB , McGuire JL , Licht PA , Staat MA , Yonker LM , Mazumdar M , Randolph AG , Campbell AP , Newburger JW . JAMA Netw Open 2023 6 (7) e2324369 IMPORTANCE: Acute neurological involvement occurs in some patients with multisystem inflammatory syndrome in children (MIS-C), but few data report neurological and psychological sequelae, and no investigations include direct assessments of cognitive function 6 to 12 months after discharge. OBJECTIVE: To characterize neurological, psychological, and quality of life sequelae after MIS-C. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional cohort study was conducted in the US and Canada. Participants included children with MIS-C diagnosed from November 2020 through November 2021, 6 to 12 months after hospital discharge, and their sibling or community controls, when available. Data analysis was performed from August 2022 to May 2023. EXPOSURE: Diagnosis of MIS-C. MAIN OUTCOMES AND MEASURES: A central study site remotely administered a onetime neurological examination and in-depth neuropsychological assessment including measures of cognition, behavior, quality of life, and daily function. Generalized estimating equations, accounting for matching, assessed for group differences. RESULTS: Sixty-four patients with MIS-C (mean [SD] age, 11.5 [3.9] years; 20 girls [31%]) and 44 control participants (mean [SD] age, 12.6 [3.7] years; 20 girls [45%]) were enrolled. The MIS-C group exhibited abnormalities on neurological examination more frequently than controls (15 of 61 children [25%] vs 3 of 43 children [7%]; odds ratio, 4.7; 95% CI, 1.3-16.7). Although the 2 groups performed similarly on most cognitive measures, the MIS-C group scored lower on the National Institutes of Health Cognition Toolbox List Sort Working Memory Test, a measure of executive functioning (mean [SD] scores, 96.1 [14.3] vs 103.1 [10.5]). Parents reported worse psychological outcomes in cases compared with controls, particularly higher scores for depression symptoms (mean [SD] scores, 52.6 [13.1] vs 47.8 [9.4]) and somatization (mean [SD] scores, 55.5 [15.5] vs 47.0 [7.6]). Self-reported (mean [SD] scores, 79.6 [13.1] vs 85.5 [12.3]) and parent-reported (mean [SD] scores, 80.3 [15.5] vs 88.6 [13.0]) quality of life scores were also lower in cases than controls. CONCLUSIONS AND RELEVANCE: In this cohort study, compared with contemporaneous sibling or community controls, patients with MIS-C had more abnormal neurologic examinations, worse working memory scores, more somatization and depression symptoms, and lower quality of life 6 to 12 months after hospital discharge. Although these findings need to be confirmed in larger studies, enhanced monitoring may be warranted for early identification and treatment of neurological and psychological symptoms. |
Fetal sex and risk of pregnancy-associated malaria in Plasmodium falciparum-endemic regions: a meta-analysis
Unger HW , Hadiprodjo AJ , Gutman JR , Briand V , Fievet N , Valea I , Tinto H , D'Alessandro U , Landis SH , Ter Kuile F , Ouma P , Oneko M , Mwapasa V , Slutsker L , Terlouw DJ , Kariuki S , Ayisi J , Nahlen B , Desai M , Madanitsa M , Kalilani-Phiri L , Ashorn P , Maleta K , Tshefu-Kitoto A , Mueller I , Stanisic D , Cates J , Van Eijk AM , Ome-Kaius M , Aitken EH , Rogerson SJ . Sci Rep 2023 13 (1) 10310 In areas of moderate to intense Plasmodium falciparum transmission, malaria in pregnancy remains a significant cause of low birth weight, stillbirth, and severe anaemia. Previously, fetal sex has been identified to modify the risks of maternal asthma, pre-eclampsia, and gestational diabetes. One study demonstrated increased risk of placental malaria in women carrying a female fetus. We investigated the association between fetal sex and malaria in pregnancy in 11 pregnancy studies conducted in sub-Saharan African countries and Papua New Guinea through meta-analysis using log binomial regression fitted to a random-effects model. Malaria infection during pregnancy and delivery was assessed using light microscopy, polymerase chain reaction, and histology. Five studies were observational studies and six were randomised controlled trials. Studies varied in terms of gravidity, gestational age at antenatal enrolment and bed net use. Presence of a female fetus was associated with malaria infection at enrolment by light microscopy (risk ratio 1.14 [95% confidence interval 1.04, 1.24]; P = 0.003; n = 11,729). Fetal sex did not associate with malaria infection when other time points or diagnostic methods were used. There is limited evidence that fetal sex influences the risk of malaria infection in pregnancy. |
Causes of death among infants and children in the Child Health and Mortality Prevention Surveillance (CHAMPS) Network
Bassat Q , Blau DM , Ogbuanu IU , Samura S , Kaluma E , Bassey IA , Sow S , Keita AM , Tapia MD , Mehta A , Kotloff KL , Rahman A , Islam KM , Alam M , El Arifeen S , Gurley ES , Baillie V , Mutevedzi P , Mahtab S , Thwala BN , Tippett Barr BA , Onyango D , Akelo V , Rogena E , Onyango P , Omore R , Mandomando I , Ajanovic S , Varo R , Sitoe A , Duran-Frigola M , Assefa N , Scott JAG , Madrid L , Tesfaye T , Dessie Y , Madewell ZJ , Breiman RF , Whitney CG , Madhi SA . JAMA Netw Open 2023 6 (7) e2322494 IMPORTANCE: The number of deaths of children younger than 5 years has been steadily decreasing worldwide, from more than 17 million annual deaths in the 1970s to an estimated 5.3 million in 2019 (with 2.8 million deaths occurring in those aged 1-59 months [53% of all deaths in children aged <5 years]). More detailed characterization of childhood deaths could inform interventions to improve child survival. OBJECTIVE: To describe causes of postneonatal child deaths across 7 mortality surveillance sentinel sites in Africa and Asia. DESIGN, SETTING, AND PARTICIPANTS: The Child Health and Mortality Prevention Surveillance (CHAMPS) Network conducts childhood mortality surveillance in sub-Saharan Africa and South Asia using innovative postmortem minimally invasive tissue sampling (MITS). In this cross-sectional study, MITS was conducted in deceased children aged 1 to 59 months at 7 sites in sub-Saharan Africa and South Asia from December 3, 2016, to December 3, 2020. Data analysis was conducted between October and November 2021. MAIN OUTCOMES AND MEASURES: The expert panel attributed underlying, intermediate, and immediate conditions in the chain of events leading to death, based on histopathologic analysis, microbiological diagnostics, clinical data, and verbal autopsies. RESULTS: In this study, MITS was performed in 632 deceased children (mean [SD] age at death, 1.3 [0.3] years; 342 [54.1%] male). The 6 most common underlying causes of death were malnutrition (104 [16.5%]), HIV (75 [11.9%]), malaria (71 [11.2%]), congenital birth defects (64 [10.1%]), lower respiratory tract infections (LRTIs; 53 [8.4%]), and diarrheal diseases (46 [7.2%]). When considering immediate causes only, sepsis (191 [36.7%]) and LRTI (129 [24.8%]) were the 2 dominant causes. An infection was present in the causal chain in 549 of 632 deaths (86.9%); pathogens most frequently contributing to infectious deaths included Klebsiella pneumoniae (155 of 549 infectious deaths [28.2%]; 127 [81.9%] considered nosocomial), Plasmodium falciparum (122 of 549 [22.2%]), and Streptococcus pneumoniae (109 of 549 [19.9%]). Other organisms, such as cytomegalovirus (57 [10.4%]) and Acinetobacter baumannii (39 [7.1%]; 35 of 39 [89.7%] considered nosocomial), also played important roles. For the top underlying causes of death, the median number of conditions in the chain of events leading to death was 3 for malnutrition, 3 for HIV, 1 for malaria, 3 for congenital birth defects, and 1 for LRTI. Expert panels considered 494 of 632 deaths (78.2%) preventable and 26 of 632 deaths (4.1%) preventable under certain conditions. CONCLUSIONS AND RELEVANCE: In this cross-sectional study investigating causes of child mortality in the CHAMPS Network, results indicate that, in these high-mortality settings, infectious diseases continue to cause most deaths in infants and children, often in conjunction with malnutrition. These results also highlight opportunities for action to prevent deaths and reveal common interaction of various causes in the path toward death. |
Prenatal ultrasound use and risk of autism spectrum disorder: Findings from the case-control Study to Explore Early Development
Christensen D , Pazol K , Overwyk KJ , England LJ , Alexander AA , Croen LA , Dowling NF , Schieve LA , Tian LH , Tinker SC , Windham GC , Callaghan WM , Shapira SK . Paediatr Perinat Epidemiol 2023 37 (6) 527-535 BACKGROUND: Studies evaluating the association between prenatal ultrasounds and autism spectrum disorder (ASD) have largely produced negative results. Concern remains due to the rising identification of children with ASD and ultrasound use. OBJECTIVE: To evaluate the association between prenatal ultrasound use and ASD. METHODS: We used data from the Study to Explore Early Development, a multisite case-control study of preschool-aged children with ASD implemented during 2007-2012. We recruited cases from children receiving developmental disability services and randomly selected population controls from birth records. ASD case status was based on in-person standardised assessments. We stratified analyses by pre-existing maternal medical conditions and pregnancy complications associated with increased ultrasound use (ultrasound indications) and used logistic regression to model case status by increasing ultrasound counts. For pregnancies with medical record data on ultrasound timing, we conducted supplementary tests to model associations by trimester of exposure. RESULTS: Among 1524 singleton pregnancies, ultrasound indications were more common for ASD cases than controls; respectively, for each group, no indications were reported for 45.1% and 54.2% of pregnancies, while ≥2 indications were reported for 26.1% and 18.4% of pregnancies. The percentage of pregnancies with multiple ultrasounds varied by case status and the presence of ultrasound indications. However, stratified regression models showed no association between increasing ultrasound counts and case status, either for pregnancies without (aOR 1.01, 95% CI 0.92, 1.11) or with ultrasound indications (aOR 1.01, 95% CI 0.95, 1.08). Trimester-specific analyses using medical record data showed no association in any individual trimester. CONCLUSIONS: We found no evidence that prenatal ultrasound use increases ASD risk. Study strengths included gold-standard assessments for ASD case classification, comparison of cases with controls, and a stratified sample to account for conditions associated both with increased prenatal ultrasound use and ASD. |
Navigating and manipulating childbirth services in Afar, Ethiopia: A qualitative study of cultural safety in the birthing room
Hagaman A , Gonzalez Rodriguez H , Egger E , Bitewulign B , Case H , Alemayehu AK , Rhodes EC , Estifanos AS , Singh K , Woldesenbet Keraga D , Zahid M , Magge H , Barrington C . Soc Sci Med 2023 331 116073 Access to maternal health services has increased in Ethiopia during the past decades. However, increasing the demand for government birthing facility use remains challenging. In Ethiopia's Afar Region, these challenges are amplified given the poorly developed infrastructure, pastoral nature of communities, distinct cultural traditions, and the more nascent health system. This paper features semi-structured interviews with 22 women who were purposively sampled to explore their experiences giving birth in government health facilities in Afar. We used thematic analysis informed by a cultural safety framework to interpret findings. Our findings highlight how women understand, wield, and relinquish power and agency in the delivery room in government health facilities in Afar, Ethiopia. We found that Afari women are treated as 'others', that they manipulate their care as they negotiate 'cultural safety' in the health system, and that they use trust as a pathway towards more cultural safety. As the cultural safety framework calls for recognizing and navigating the diverse and fluid power dynamics of healthcare settings, the onus of negotiating power dynamics cannot be placed on Afari women, who are already multiply marginalized due to their ethnicity and gender. Health systems must adopt cultural safety in order to ensure health quality. Providers, particularly in regions with rich cultural diversity, must be trained in the cultural safety framework in order to be aware of and challenge the multidimensional power dynamics present in health encounters. |
Quickstats: Percentage* of children and adolescents aged 17 years who have experienced a specified stressful life event,(†) by type of event and family income(¶) - National Health Interview Survey,() United States, 2021
Ng AE , Arockiaraj B , Zablotsky B . MMWR Morb Mortal Wkly Rep 2023 72 (29) 807 Abbreviation: FPL = federal poverty level. | | * With 95% CIs indicated by error bars. | | † Percentages for the specified stressful life events are based on the following questions: 1) “Has child ever been the victim of violence or witnessed violence in their neighborhood?”; 2) “Has child ever been separated from a parent or guardian because the parent or guardian went to jail, prison, or a detention center?”; 3) “Did child ever live with anyone who was mentally ill or severely depressed?”; 4) Did child ever live with anyone who had a problem with alcohol or drugs?” Having any stressful event was based on having answered “yes” to any of these four questions. The four stressful life event questions come from a larger battery of questions on adverse childhood experiences. | | § As a percentage of FPL, which is based on family income and family size, using the U.S. Census Bureau’s poverty thresholds. Family income was imputed when missing. | | ¶ Estimates are based on household interviews of a sample of the civilian, noninstitutionalized U.S. population. | | In 2021, 20.2% of children and adolescents in families with incomes <200% of FPL and 12.0% of those in families with incomes ≥200% of FPL had experienced at least one specified stressful life event. Children and adolescents in families with incomes <200% of FPL were more likely than those in families with incomes ≥200% of FPL to have had the following experiences: lived with someone with alcohol or drug problems (9.1% versus 5.8%); lived with someone who was mentally ill or severely depressed (8.8% versus 6.5%); lived with someone who had been in jail (8.8% versus 2.9%); or been the victim of or witnessed violence in their neighborhood (7.2% versus 3.1%). |
Notes from the field: Autism spectrum disorder among children with laboratory evidence of prenatal Zika virus exposure - Puerto Rico, 2023
Roth NM , Delgado-López C , Wiggins LD , Muñoz NN , Mulkey SB , Nieves-Ferrer L , Woodworth KR , Rosario GM , Huertas MM , Moore CA , Tong VT , Gilboa SM , Valencia-Prado M . MMWR Morb Mortal Wkly Rep 2023 72 (29) 802-804 Infection during pregnancy with Zika virus, a mosquitoborne flavivirus, can cause birth defects and neurodevelopmental abnormalities (1). Autism spectrum disorder (ASD) is a neurodevelopmental disability characterized by social and communication impairment and restricted or repetitive patterns of behavior or interests (2); possible associations between antenatal exposure to a limited number of viruses and ASD have been observed (2). The U.S. Zika Pregnancy and Infant Registry (USZPIR)* monitors children born during January 1, 2016–March 31, 2018, to women with laboratory evidence of Zika virus infection during pregnancy. This report used data from USZPIR and the Puerto Rico Autism Registry† to estimate the prevalence of ASD diagnoses among children with possible prenatal Zika virus exposure and to describe prenatal characteristics and other outcomes by ASD diagnosis status. This activity was reviewed by CDC and was conducted consistent with applicable federal law and CDC policy.§ |
Evidence and recommendation for guanidinoacetate methyltransferase deficiency newborn screening
Ream MA , Lam WKK , Grosse SD , Ojodu J , Jones E , Prosser LA , Rose AM , Comeau AM , Tanksley S , Powell CM , Kemper AR . Pediatrics 2023 152 (2) Guanidinoacetate methyltransferase (GAMT) deficiency is an autosomal recessive disorder of creatine biosynthesis due to pathogenic variants in the GAMT gene that lead to cerebral creatine deficiency and neurotoxic levels of guanidinoacetate. Untreated, GAMT deficiency is associated with hypotonia, significant intellectual disability, limited speech development, recurrent seizures, behavior problems, and involuntary movements. The birth prevalence of GAMT deficiency is likely between 0.5 and 2 per million live births. On the basis of small case series and sibling data, presymptomatic treatment with oral supplements of creatine, ornithine, and sodium benzoate, and a protein-restricted diet to reduce arginine intake, appear to substantially improve health and developmental outcomes. Without newborn screening, diagnosis typically happens after the development of significant impairment, when treatment has limited utility. GAMT deficiency newborn screening can be incorporated into the tandem-mass spectrometry screening that is already routinely used for newborn screening, with about 1 per 100 000 newborns screening positive. After a positive screen, diagnosis is established by finding an elevated guanidinoacetate concentration and low creatine concentration in the blood. Although GAMT deficiency is significantly more rare than other conditions included in newborn screening, the feasibility of screening, the low number of positive results, the relative ease of diagnosis, and the expected benefit of presymptomatic dietary therapy led to a recommendation from the Advisory Committee on Heritable Disorders in Newborns and Children to the Secretary of Health and Human Services that GAMT deficiency be added to the Recommended Uniform Screening Panel. This recommendation was accepted in January 2023. |
Proinflammatory diets and risk of ESKD in US adults with CKD
Banerjee T , McCulloch CE , Crews DC , Burrows NR , Pavkov ME , Saran R , Morgenstern H , Bragg-Gresham J , Powe NR . Kidney360 2022 3 (11) 1852-1860 BACKGROUND: Inflammation may affect long-term kidney function. Diet may play a role in chronic inflammation. We hypothesized that proinflammatory diets increase the risk of progression to kidney failure with replacement therapy (KFRT), and systemic inflammation is a mediator of the effect of diet on progression to KFRT. METHODS: In the 1988-1994 National Health and Nutrition Examination Survey linked to the national ESKD registry, in adults with CKD (eGFR 15-59 ml/min per 1.73 m(2)), aged ≥20 years, we calculated the Adapted Dietary Inflammatory Index (ADII) at baseline from a 24-hour dietary recall and an inflammation score (IS) using average of z scores of four inflammation biomarkers. We explored the association of the ADII and IS with risk of incident KFRT using Cox proportional model, adjusting for sociodemographics, physical activity, Framingham risk score, eGFR, and urinary ACR. We evaluated whether, and to what extent, IS mediated the effect of the ADII on KFRT incidence, using causal mediation analysis. RESULTS: Of 1084 adults with CKD, 109 (10%) developed KFRT. The ADII was associated with increased risk of KFRT (relative hazard [RH] per SD increase (2.56): 1.4 [1.04-1.78]). IS was also associated with KFRT (RH: 1.12; 95% CI, 1.02 to 1.25). Approximately 36% of the association between the ADII and KFRT was explained by IS. CONCLUSIONS: Among adults with CKD, a proinflammatory diet was associated with risk of KFRT, and that association was partially explained by an increase in inflammatory markers. Dietary interventions that reduce inflammation may offer an approach for preventing KFRT. |
Automated classification of the phases relevant to work-related musculoskeletal injury risks in residential roof shingle installation operations using machine learning
Dutta A , Breloff SP , Mahmud D , Dai F , Sinsel EW , Warren CM , Wu JZ . Buildings 2023 13 (6) Awkward kneeling in sloped shingle installation operations exposes roofers to knee musculoskeletal disorder (MSD) risks. To address the varying levels of risk associated with different phases of shingle installation, this research investigated utilizing machine learning to automatically classify seven distinct phases in a typical shingle installation task. The classification process relied on analyzing knee kinematics data and roof slope information. Nine participants were recruited and performed simulated shingle installation tasks while kneeling on a sloped wooden platform. The knee kinematics data were collected using an optical motion capture system. Three supervised machine learning classification methods (i.e., k-nearest neighbors (KNNs), decision tree (DT), and random forest (RF)) were selected for evaluation. The KNN classifier provided the best performance for overall accuracy. The results substantiated the feasibility of applying machine learning in classifying shingle installation phases from workers’ knee joint rotation and roof slope angles, which may help facilitate method and tool development for automated knee MSD risk surveillance and assessment among roofers. © 2023 by the authors. |
Occupational safety and health equity impacts of artificial intelligence: A scoping review
Fisher E , Flynn MA , Pratap P , Vietas JA . Int J Environ Res Public Health 2023 20 (13) Artificial intelligence (AI) has the potential to either reduce or exacerbate occupational safety and health (OSH) inequities in the workplace, and its impact will be mediated by numerous factors. This paper anticipates challenges to ensuring that the OSH benefits of technological advances are equitably distributed among social groups, industries, job arrangements, and geographical regions. A scoping review was completed to summarize the recent literature on AI's role in promoting OSH equity. The scoping review was designed around three concepts: artificial intelligence, OSH, and health equity. Scoping results revealed 113 articles relevant for inclusion. The ways in which AI presents barriers and facilitators to OSH equity are outlined along with priority focus areas and best practices in reducing OSH disparities and knowledge gaps. The scoping review uncovered priority focus areas. In conclusion, AI's role in OSH equity is vastly understudied. An urgent need exists for multidisciplinary research that addresses where and how AI is being adopted and evaluated and how its use is affecting OSH across industries, wage categories, and sociodemographic groups. OSH professionals can play a significant role in identifying strategies that ensure the benefits of AI in promoting workforce health and wellbeing are equitably distributed. |
Using machine learning to evaluate coal geochemical data with respect to dynamic failures
Hanson DR , Lawson HE . Minerals 2023 13 (6) Dynamic failure events have occurred in the underground coal mining industry since its inception. Recent NIOSH research has identified geochemical markers that correlate with in situ reportable dynamic event occurrence, although the causes behind this correlative relationship remain unclear. In this study, NIOSH researchers conducted machine learning analysis to examine whether a model could be constructed to assess the probability of dynamic failure occurrence based on geochemical and petrographic data. Linear regression, random forest, dimensionality reduction, and cluster analyses were applied to a catalog of dynamic failure and control data from the Pennsylvania Coal Sample Databank, cross-referenced with accident data from the Mine Safety and Health Administration (MSHA). Analyses determined that 7 of the 18 geochemical parameters that were examined had the biggest impact on model performance. Classifications based on logistic regression and random forest models attained precision values of 85.7% and 96.7%, respectively. Dimensionality reduction was used to explore patterns and groupings in the data and to search for relationships between compositional parameters. Cluster analyses were performed to determine if an algorithm could find clusters with given class memberships and to what extent misclassifications of dynamic failure status occurred. Cluster analysis using a hierarchal clustering algorithm after dimensionality reduction resulted in four clusters, with one relatively distinct dynamic failure cluster, and three clusters mostly consisting of control group members but with a small number of dynamic failure members. © 2023 by the authors. |
Maternal occupational exposure to selected organic and chlorinated solvents and delivery of small-for-gestational age or preterm infants
Van Buren KW , Rocheleau CM , Chen IC , Desrosiers TA , Sanderson WT , Politis MD , Ailes EC . Am J Ind Med 2023 66 (10) 842-853 BACKGROUND: Potential reproductive effects of organic solvent exposure during pregnancy remain unclear. We investigated the association between maternal occupational exposure during pregnancy to six chlorinated solvents, three aromatic solvents, and Stoddard solvent, and delivery of preterm infants or those born small-for-gestational age (SGA). METHODS: In this case-control study of SGA and preterm birth (PTB) nested within the National Birth Defects Prevention Study (NBDPS) from 1997 to 2011, we analyzed data from 7504 singleton live births without major birth defects and their mothers. Self-reported information on jobs held in the periconceptional period was assessed for solvent exposure. Unconditional logistic regression was used to estimate the association between maternal occupational exposure (any, none) during early pregnancy to organic solvents and PTB and SGA. Linear regression was used to examine changes in mean birthweight potentially associated with maternal occupational solvent exposure. RESULTS: Maternal occupational exposure to any organic solvents overall was not associated with an increased odds of PTB (adjusted odds ratio [aOR] = 0.94; 95% confidence interval [CI] 0.67-1.33) or SGA (aOR = 0.93; 95% CI 0.65-1.34). Point estimates increased modestly for higher estimated exposure versus lower, but confidence intervals were wide and not statistically significant. Maternal exposure to solvents was not associated with a statistically significant change in term birthweight among infants. CONCLUSIONS: Occupational exposure to organic solvents at the frequency and intensity levels found in a population-based sample of pregnant workers was not associated with PTB or SGA; however, we cannot rule out any effects among pregnant workers with uncommonly high exposure to organic solvents. |
Identifying the location and size of an underground mine fire with simulated ventilation data and random forest model
Xue Y , Bahrami D , Zhou L . Min Metall Explor 2023 Underground mine fires are a threat to the safety and health of mine workers. The timely determination of the location and size of an underground fire is of great importance in developing firefighting strategies and reducing the risk of any injuries. Machine learning was used in this paper to develop a predictive model for fire location and fire size in an underground mine. The ventilation data were obtained by simulating different mine fire scenarios with MFire. The ventilation data of all airways were used as features to predict the fire location. Based on the feature importance, five airways were selected to monitor, and the airflow data of the selected airways were used to predict the fire location and fire size. An accuracy score of 0.920 was obtained for the prediction of fire location. In addition, in-depth analyses were conducted to characterize the wrong predictions with the purpose of improving the performance of the random forest model. The results show that the occurrence of fire at closely connected airways at some locations can generate misleading ventilation data for each other and the model performance can be further improved to 0.962 by grouping them. Fire size is another factor affecting the model performance and the model accuracy increases with increasing fire size. The result from this study can help mine safety personnel make informed decisions during a mine fire emergency. © 2023, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. |
Design of different shapes of drill shroud to reduce dust deposit using computational fluid dynamics method
Zheng Y , Reed WR , Potts JD . CIM J 2023 11-20 Effective dust control using drill shroud air-blocking shelves was confirmed previously through laboratory tests, field studies, and computational fluid dynamics (CFD) simulations. However, when the drilling machine moves to different locations, deposits on these shelves can produce a large dust cloud. To minimize the dust exposure hazard, this study modified the drill shroud air-blocking shelves by using the concept of angle of repose to eliminate the deposits while at the same time, confining the dust inside the drill shroud. Two types of drill shroud inner shapes were evaluated using CFD models: U-shaped and V-shaped. In addition, a drill shroud with 45 blocking shelves was built to examine its dust control capacity. The angle of repose used to minimize dust problems during mast lowering was shown to be effective in reducing the dust problems during drilling. However, care must be taken to use a properly designed shroud because the V-shaped drill shroud can potentially exacerbate dust leakage. |
Tactile gloves predict load weight during lifting with deep neural networks
Zhou G , Lu M , Yu D . IEEE Sensors J 2023 1-1 Overexertion in lifting tasks is one of the leading causes of occupational injuries. The load weight is the key information required to evaluate the risk of a lifting task. However, weight varies across different objects and is unknown in many circumstances. Existing methods of estimating the load weight without manual weighing focused on analyzing body kinematics or muscle activations, which either utilize indirect indicators or require intrusive sensors. This study proposed using tactile gloves as a new modality to predict the load weight. Hand pressure data measured by tactile gloves during each lift was formulated as a two-dimensional matrix containing spatial and temporal information. Different types of deep neural networks were adopted, and a ResNet 18 regression model achieved the best performance. Specifically, it achieved a predicted R-squared of 0.821 and a mean absolute error of 1.579 kg. In addition, to understand the model’s decision-making logic and the hand force exertion pattern during lifting, the Shapley Additive Explanations (SHAP) technique was utilized to determine the importance of each sensor at each frame. The results demonstrated that the right hand was more important than the left hand for the model to predict the load weight. Additionally, fingers were more important than palms, and the middle phase of a lifting task was more important than its beginning and ending phases. Overall, this study demonstrated the feasibility of using tactile gloves to predict the load weight and provided new scientific insights on hand force exertion patterns during lifting. IEEE |
Pneumoconiosis incidence and prevalence among US Medicare beneficiaries, 1999-2019
Kurth L , Casey ML , Mazurek JM , Blackley DJ . Am J Ind Med 2023 66 (10) 831-841 BACKGROUND: Pneumoconiosis is a group of occupational lung diseases caused by dust and fiber exposure. This study analyzes Medicare claims to estimate the burden of pneumoconiosis among fee-for-service (FFS; Medicare Parts A and B) Medicare beneficiaries during 1999-2019 in the United States. METHODS: Claim and enrollment information from 81 million continuously enrolled FFS Medicare beneficiaries were analyzed. Beneficiaries with any pneumoconiosis and cause-specific pneumoconiosis (e.g., asbestosis, silicosis) were identified using three case definitions (broad, intermediate, and narrow) with varying diagnostic criteria based on claim International Classification of Diseases, Clinical Modification (ICD-CM) diagnosis codes and Healthcare Common Procedure Coding System codes. Results are presented as ranges of values for the three case definitions. RESULTS: The 21-year prevalence range for any pneumoconiosis was 345,383-677,361 (412-833 per 100,000 beneficiaries) using the three case definitions. The highest prevalence was among those ≥75 years of age, males, Whites, and North American Natives. Most claims (70.0%-72.5%) included an ICD-CM diagnosis code for asbestosis. The broad pneumoconiosis prevalence rate increased significantly (p < 0.001) during 2002-2009 by 3%-10% annually and declined significantly by 3%-5% annually starting in 2009. The average annual broad incidence rate declined significantly by 7% annually during 2009-2019. CONCLUSIONS: Despite the decline in rate for any pneumoconiosis among Medicare beneficiaries, which is primarily attributed to a decline in asbestosis, pneumoconiosis is prevalent among FFS Medicare beneficiaries. |
Deep learning-based estimation of whole-body kinematics from multi-view images
Nguyen KX , Zheng L , Hawke AL , Carey RE , Breloff SP , Li K , Peng X . Comput Vision Image Understanding 2023 235 It is necessary to analyze the whole-body kinematics (including joint locations and joint angles) to assess risks of fatal and musculoskeletal injuries in occupational tasks. Human pose estimation has gotten more attention in recent years as a method to minimize the errors in determining joint locations. However, the joint angles are not often estimated, nor is the quality of joint angle estimation assessed. In this paper, we presented an end-to-end approach on direct joint angle estimation from multi-view images. Our method leveraged the volumetric pose representation and mapped the rotation representation to a continuous space where each rotation was uniquely represented. We also presented a new kinematic dataset in the domain of residential roofing with a data processing pipeline to generate necessary annotations for the supervised training procedure on direct joint angle estimation. We achieved a mean angle error of 7.19° on the new Roofing dataset and 8.41° on the Human3.6M dataset, paving the way for employment of on-site kinematic analysis using multi-view images. © 2023 Elsevier Inc. |
Construction industry workers' compensation injury claims due to slips, trips, and falls - Ohio, 2010-2017
Socias-Morales C , Konda S , Bell JL , Wurzelbacher SJ , Naber SJ , Earnest GS , Garza EP , Meyers AR , Scharf T . J Safety Res 2023 86 [Epub ahead of print] Problem: Compared to other industries, construction workers have higher risks for serious fall injuries. This study describes the burden and circumstances surrounding injuries related to compensable slip, trip, and fall (STF) claims from private construction industries covered by the Ohio Bureau of Workers' Compensation. Methods: STF injury claims in the Ohio construction industry from 2010-2017 were manually reviewed. Claims were classified as: slips or trips without a fall (STWOF), falls on the same level (FSL), falls to a lower level (FLL), and other. Claim narratives were categorized by work-related risk and contributing factors. Demographic, employer, and injury characteristics were examined by fall type and claim type (medical-only (MO, 0-7 days away from work, DAFW) or lost-time (LT, ≥8 DAFW)). Claim rates per 10,000 estimated full-time equivalent employees (FTEs) were calculated. Results: 9,517 Ohio construction industry STF claims occurred during the 8-year period, with an average annual rate of 75 claims per 10,000 FTEs. The rate of STFs decreased by 37% from 2010 to 2017. About half of the claims were FLL (51%), 29% were FSL, 17% were STWOF, and 3% were "other." Nearly 40% of all STF claims were LT; mostly among males (96%). The top three contributing factors for STWOF and FSL were: slip/trip hazards, floor irregularities, and ice/snow; and ladders, vehicles, and stairs/steps for FLL. FLL injury rates per 10,000 FTE were highest in these industries: Foundation, Structure, and Building Exterior Contractors (52); Building Finishing Contractors (45); and Residential Building Construction (45). The highest rate of FLL LT claims occurred in the smallest firms, and the FLL rate decreased as construction firm size increased. Discussion and Practical Applications: STF rates declined over time, yet remain common, requiring prevention activities. Safety professionals should focus on contributing factors when developing prevention strategies, especially high-risk subsectors and small firms. |
Employer Requirements and COVID-19 Vaccination and Attitudes among Healthcare Personnel in the U.S.: Findings from National Immunization Survey Adult COVID Module, August - September 2021 (preprint)
Lee JT , Hu SS , Zhou T , Bonner K , Kriss JL , Wilhelm E , Carter RJ , Holmes C , de Perio MA , Lu PJ , Nguyen KH , Brewer NT , Singleton JA . medRxiv 2022 15 Introduction Employer vaccination requirements have been used to increase vaccination uptake among healthcare personnel (HCP). In summer 2021, HCP were the group most likely to have employer requirements for COVID-19 vaccinations as healthcare facilities led the implementation of such requirements. This study examined the association between employer requirements and HCP's COVID-19 vaccination status and attitudes about the vaccine. Methods Participants were a national representative sample of United States (US) adults who completed the National Immunization Survey Adult COVID Module (NIS-ACM) during August-September 2021. Respondents were asked about COVID-19 vaccination and intent, requirements for vaccination, place of work, attitudes surrounding vaccinations, and sociodemographic variables. This analysis focused on HCP respondents. We first calculated the weighted proportion reporting COVID-19 vaccination for HCP by sociodemographic variables. Then we computed unadjusted and adjusted prevalence ratios for vaccination coverage and key indicators on vaccine attitudes, comparing HCP based on individual self-report of vaccination requirements. Results Of 12,875 HCP respondents, 41.5% reported COVID-19 vaccination employer requirements. Among HCP with vaccination requirements, 90.5% had been vaccinated against COVID-19, as compared to 73.3% of HCP without vaccination requirements-a pattern consistent across sociodemographic groups. Notably, the greatest differences in uptake between HCP with and without employee requirements were seen in sociodemographic subgroups with the lowest vaccination uptake, e.g., HCP aged 18-29 years, HCP with high school or less education, HCP living below poverty, and uninsured HCP. In every sociodemographic subgroup examined, vaccine uptake was more equitable among HCP with vaccination requirements than in HCP without. Finally, HCP with vaccination requirements were also more likely to express confidence in the vaccine's safety (68.3% vs. 60.1%) and importance (89.6% vs 79.6%). Conclusion In a large national US sample, employer requirements were associated with higher and more equitable HCP vaccination uptake across all sociodemographic groups examined. Our findings suggest that employer requirements can contribute to improving COVID-19 vaccination coverage, similar to patterns seen for other vaccines. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Using routine health data to evaluate the impact of indoor residual spraying on malaria transmission in Madagascar
Hilton ER , Rabeherisoa S , Ramandimbiarijaona H , Rajaratnam J , Belemvire A , Kapesa L , Zohdy S , Dentinger C , Gandaho T , Jacob D , Burnett S , Razafinjato C . BMJ Glob Health 2023 8 (7) INTRODUCTION: Indoor residual spraying (IRS) and insecticide-treated bed nets (ITNs) are cornerstone malaria prevention methods in Madagascar. This retrospective observational study uses routine data to evaluate the impacts of IRS overall, sustained IRS exposure over multiple years and level of spray coverage (structures sprayed/found) in nine districts where non-pyrethroid IRS was deployed to complement standard pyrethroid ITNs from 2017 to 2020. METHODS: Multilevel negative-binomial generalised linear models were fit to estimate the effects of IRS exposure overall, consecutive years of IRS exposure and spray coverage level on monthly all-ages population-adjusted malaria cases confirmed by rapid diagnostic test at the health facility level. The study period extended from July 2016 to June 2021. Facilities with missing data and non-geolocated communes were excluded. Facilities in IRS districts were matched with control facilities by propensity score analysis. Models were controlled for ITN survivorship, mass drug administration coverage, precipitation, enhanced vegetation index, seasonal effects and district. Predicted cases under a counterfactual no IRS scenario and number of cases averted by IRS were estimated using the fitted models. RESULTS: Exposure to IRS overall reduced case incidence by an estimated 30.3% from 165.8 cases per 1000 population (95% CI=139.7 to 196.7) under a counterfactual no IRS scenario, to 114.3 (95% CI=96.5 to 135.3) over 12 months post-IRS campaign in nine districts. A third year of IRS reduced malaria cases 30.9% more than a first year (incidence rate ratio (IRR)=0.578, 95% CI=0.578 to 0.825, p<0.001) and 26.7% more than a second year (IRR=0.733, 95% CI=0.611 to 0.878, p=0.001). There was no significant difference between the first and second year (p>0.05). Coverage of 86%-90% was associated with a 19.7% reduction in incidence (IRR=0.803, 95% CI=0.690 to 0.934, p=0.005) compared with coverage ≤85%, although these results were not robust to sensitivity analysis. CONCLUSION: This study demonstrates that non-pyrethroid IRS appears to substantially reduce malaria incidence in Madagascar and that sustained implementation of IRS over three years confers additional benefits. |
Plasmodium falciparum infection and disease in infancy associated with increased risk of malaria and anaemia in childhood
Andronescu LR , Buchwald AG , Sharma A , Bauleni A , Mawindo P , Liang Y , Gutman JR , Mathanga DP , Chinkhumba J , Laufer MK . Malar J 2023 22 (1) 217 BACKGROUND: Infants under 6 months of age are often excluded from malaria surveillance and observational studies. The impact of malaria during early infancy on health later in childhood remains unknown. METHODS: Infants from two birth cohorts in Malawi were monitored at quarterly intervals and whenever they were ill from birth through 24 months for Plasmodium falciparum infections and clinical malaria. Poisson regression and linear mixed effects models measured the effect of exposure to malaria in infancy on subsequent malaria incidence, weight-for-age z-scores (WAZ), and haemoglobin concentrations after 6 months. RESULTS: Infants with at least one P. falciparum infection during their first 6 months had increased incidence ratio (IRR) of P. falciparum infection (IRR = 1.27, 95% CI, 1.06-1.52) and clinical malaria (IRR = 2.37, 95% CI, 2.02-2.80) compared to infants without infection. Infants with clinical malaria had increased risk of P. falciparum infection incidence between 6 and 24 months (IRR = 1.64, 95% CI, 1.38-1.94) and clinical malaria (IRR = 1.85, 95% CI, 1.48-2.32). Exposure to malaria was associated with lower WAZ over time (p = 0.02) and lower haemoglobin levels than unexposed infants at every time interval (p = 0.02). CONCLUSIONS: Infants experiencing malaria infection or clinical malaria are at increased risk of subsequent infection and disease, have poorer growth, and lower haemoglobin concentrations. |
A zebra among the horses: Clinical implications of malaria in the United States
Huits R , Wallender E , Angelo KM , Libman M , Hamer DH . Ann Intern Med 2023 176 (9) 1269-1270 On 26 June 2023, the U.S. Centers for Disease Control and Prevention (CDC) issued a Health Alert Network report about locally acquired, mosquito-transmitted Plasmodium vivax malaria. As of 19 July 2023, 7 cases in Florida (Sarasota County) and 1 in Texas (Cameron County) had been reported. Of note, the Texas case is unrelated to the Florida cases. All of the patients received treatment and have recovered. Active surveillance for additional cases by the state health departments and mosquito control measures are ongoing (1). |
Evaluating the impact of indoor residual spraying on malaria transmission in Madagascar using routine health data (preprint)
Hilton ER , Rabeherisoa S , Ramandimbiarijaona H , Rajaratnam J , Belemvire A , Kapesa L , Zohdy S , Dentinger C , Gandaho T , Jacob D , Burnett S , Razafinjato C . medRxiv 2023 17 Introduction Indoor residual spraying (IRS) and insecticide-treated bed-nets (ITNs) are cornerstone malaria prevention methods in Madagascar. This retrospective observational study uses routine data to evaluate the impacts of IRS overall, sustained IRS exposure over multiple years, and level of spray coverage (structures sprayed/found) in nine districts where non-pyrethroid IRS was deployed to complement standard pyrethroid ITNs from 2017 to 2020. Methods Multilevel negative-binomial generalized linear models were fit to estimate the effects of IRS exposure overall; consecutive years of IRS exposure; and spray coverage level on monthly all-ages population-adjusted malaria cases confirmed by rapid diagnostic test at the health facility level. The study period extended from July 2016 to June 2017. Facilities missing data and non-geolocated communes were excluded. Facilities in IRS districts were matched with control facilities by propensity score analysis. Models controlled for ITN survivorship, mass drug administration coverage, precipitation, enhanced vegetation index, seasonal effects, and district. Predicted cases under a counterfactual no IRS scenario and number of cases averted by IRS were estimated using the fitted models. Results Exposure to IRS overall reduced case incidence by an estimated 30.3% from 165.8 cases per 1,000 population (95%CI=139.7-196.7) under a counterfactual no IRS scenario, to 114.3 (95%CI=96.5-135.3), over 12 months post-IRS campaign in 9 districts. A third year of IRS reduced malaria cases 30.9% more than a first year (IRR=0.578, 95%CI=0.578-0.825, P<0.001) and 26.7% more than a second year (IRR=0.733, 95%CI=0.611-0.878, P=0.001). There was no significant difference between a first and second year (P>0.05). Coverage of 86%-90% was associated with a 19.7% reduction in incidence (IRR= 0.803, 95%CI=0.690-0.934, P=0.005) compared to coverage <=85%, although these results were not robust to sensitivity analysis. Conclusion This study demonstrates that non-pyrethroid IRS appears to substantially reduce malaria incidence in Madagascar and that sustained implementation of IRS over 3 years confers additional benefits. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license. |
Highly multiplexed ddPCR-amplicon sequencing reveals strong Plasmodium falciparum population structure and isolated populations amenable to local elimination efforts in Zanzibar (preprint)
Holzschuh A , Lerch A , Gerlovina I , Fakih BS , Al-Mafazy AWH , Reaves EJ , Ali A , Abbas F , Ali MH , Ali MA , Hetzel MW , Yukich J , Koepfli C . bioRxiv 2023 06 Over the past 15 years, Zanzibar has made great strides towards malaria elimination; yet progress has stalled. Parasite genetic data of Plasmodium falciparum may inform strategies for malaria elimination by helping to identify contributory factors to parasite persistence. Here we elucidate fine-scale parasite population structure and infer relatedness and connectivity of infections using an identity-by-descent (IBD) approach. We sequenced 518 P. falciparum samples from 5 districts covering both main islands using a novel, highly multiplexed droplet digital PCR (ddPCR)-based amplicon deep sequencing method targeting 35 microhaplotypes and drug-resistance loci. Despite high genetic diversity, we observe strong fine-scale spatial and temporal structure of local parasite populations, including isolated populations on Pemba Island and genetically admixed populations on Unguja Island, providing evidence of ongoing local transmission. We observe a high proportion of highly related parasites in individuals living closer together, including between clinical index cases and the mostly asymptomatic cases surrounding them, consistent with isolation-by-distance. We identify a substantial fraction (2.9%) of related parasite pairs between Zanzibar, and mainland Tanzania and Kenya, consistent with recent importation. We identify haplotypes known to confer resistance to known antimalarials in all districts, including multidrug-resistant parasites, but most parasites remain sensitive to current first-line treatments. Our study provides a high-resolution view of parasite genetic structure across the Zanzibar archipelago and reveals actionable patterns, including isolated parasite populations, which may be prioritized for malaria elimination. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Spatio-temporal dynamics of malaria in Zanzibar, 2015-2020 (preprint)
Bisanzio D , Lalji S , Abbas FB , Ali MH , Hassan WS , Mkali HR , Al-Mafazy AW , Joseph JJ , Nyinondi SS , Kitojo C , Serbantez N , Reaves E , Eckert E , Ngondi J , Reithinger R . medRxiv 2022 27 Background: Despite the continued high coverage of malaria interventions, malaria elimination in Zanzibar remains elusive, with the annual number of cases increasing gradually over the last 3 years. The aims of the analyses presented here were to (i) assess the spatio-temporal dynamics of malaria in Zanzibar between 2015 and 2020, and (ii) identify malaria hotspots that would allow Zanzibar to develop an epidemiological stratification for more effective and granular intervention targeting, thereby allowing for more effective programmatic resource allocations. Method(s): Data routinely collected by Zanzibar's Malaria Case Notification (MCN) system were analyzed. The system collects detailed socio-demographic and epidemiological data from all malaria cases who are passively detected and reported at the islands' 313 public and private health facilities (defined as primary index cases), as well as through case follow-up and reactive case detection (defined as secondary cases). Using these data, spatio-temporal analyses were performed to identify the spatial heterogeneity of case reporting at shehia (ward) level during transmission seasons and its correlation with 2015-2020 rainfall. Result(s): From January 1, 2015, to April 30, 2020, 22,686 index cases were notified by health facilities and reported through the MCN system. Number of cases reported showed declining trends from 2015 to 2017, followed by an increase from 2018 to 2020. More than 40% of cases had a travel history outside Zanzibar in the month prior to testing positive for malaria. The proportion of followed-up index cases was approximately 70% for all years. Change point analysis identified 10 distinct periods of malaria transmission across the study period, and the seasonality of reported index cases was significantly correlated to the amount of precipitation that occurred during the previous rainy season. Out of Zanzibar's 388 shehias, 79 (20.3%) were identified as malaria hotspots in any given year between 2015 and 2020; these hotspots reported 52% of all index cases during the study period. Of the 79 shehias identified as hotspots, 12 (3% of all shehias) were hotspots in more than four years, i.e., considered temporally stable, reporting 14.5% of all index cases. Conclusion(s): Our findings confirm that the scale-up of malaria interventions has greatly reduced malaria transmission in Zanzibar since 2006, with mean annual shehia incidence being 3.8 cases per 1,000 over the 2015-2020 study period. Spatio-temporal analyses identified hotspots, some of which were stable across multiple years. From a programmatic perspective, malaria efforts should progress from an approach that is based on universal coverage of interventions to an approach that is more tailored and nuanced, with resources prioritized and allocated to a select number of hotspot shehias. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Residual insecticide surface treatment for preventing malaria: a systematic review protocol (preprint)
Munn Z , Stone JC , Barker TH , Price C , Pollock D , Kabaghe AN , Gimnig JE , Stevenson JC . medRxiv 2021 14 Introduction: Malaria presents a significant global public health burden, although substantial progress has been made, with vector control initiatives such as indoor residual surface spraying with insecticides and insecticide treated nets. There now exists many different approaches to apply residual insecticide to indoor and outdoor surfaces in malaria endemic settings. This review aims to synthesise the best available evidence regarding full or partial indoor or outdoor residual insecticide surface treatment for preventing malaria. Methods and Analysis: This review will comprehensively search the literature (both published and unpublished) for any studies investigating the effectiveness of residual insecticide surface treatment for malaria. Studies will be screened to meet the inclusion criteria by a minimum of two authors, followed by assessment of risk of bias (using appropriate risk of bias tools for randomised and non-randomised studies) and extraction of relevant information using structured forms by two independent authors. Meta-analysis will be carried out where possible for epidemiological outcomes such as malaria, anaemia, malaria related mortality, all-cause mortality and adverse effects. Certainty in the evidence will be established with GRADE assessments. Ethics and Dissemination: A full review report will be submitted to the Vector Control & Insecticide Resistance Unit, Global Malaria Program, WHO. A version of this report will be submitted for publication in an open access peer-reviewed journal. The report will inform the development of WHO recommendations regarding residual insecticide treatment for malaria. This systematic review does not require ethics approval as it is a review of primary studies. Registration: PROSPERO, ID 293194 (in progress as of 24th November, 2021). Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. |
Using marine cargo traffic to identify countries in Africa with greatest risk of invasion by Anopheles stephensi (preprint)
Ahn J , Sinka M , Irish S , Zohdy S . bioRxiv 2021 10 Anopheles stephensi is an efficient malaria vector commonly found in South Asia and the Arabian Peninsula, but in recent years it has established as an invasive species in the Horn of Africa (HoA). In this region, An. stephensi was first detected in a livestock quarantine station near a major seaport in Djibouti in 2012, in Ethiopia in 2016, in Sudan in 2018 and Somalia in 2019. Anopheles stephensi often uses artificial containers as larval habitats, which may facilitate introduction through maritime trade as has been seen with other invasive container breeding mosquitoes. If An. stephensi is being introduced through maritime traffic, prioritization exercises are needed to identify locations at greatest risk of An. stephensi introduction for early detection and rapid response, limiting further invasion opportunities. Here, we use UNCTAD maritime trade data to 1) identify coastal African countries which were most highly connected to select An. stephensi endemic countries in 2011, prior to initial detection in Africa, 2) develop a ranked prioritization list of countries based on likelihood of An. stephensi introduction for 2016 and 2020 based on maritime trade alone and maritime trade and habitat suitability, and 3) use network analysis to describe intracontinental maritime trade and eigenvector centrality to determine likely paths of further introduction on the continent if An. stephensi is detected in a new location. Our results show that in 2011, Sudan and Djibouti were ranked as the top two countries with likelihood of An. stephensi introduction based on maritime trade alone, and these were indeed the first two coastal countries in the HoA where An. stephensi was detected. Trade data from 2020 with Djibouti and Sudan included as source populations identify Egypt, Kenya, Mauritius, Tanzania, and Morocco as the top five countries with likelihood of An. stephensi introduction. When factoring in habitat suitability, Egypt, Kenya, Tanzania, Morocco, and Libya are ranked highest. Network analysis revealed that the countries with the highest eigenvector centrality scores, and therefore highest degrees of connectivity with other coastal African nations were South Africa (0.175), Mauritius (0.159), Ghana (0.159), Togo (0.157), and Morocco (0.044) and therefore detection of An. stephensi in any one of these locations has a higher potential to cascade further across the continent via maritime trade than those with lower eigenvector centrality scores. Taken together, these data could serve as tools to prioritize efforts for An. stephensi surveillance and control in Africa. Surveillance in seaports of countries at greatest risk of introduction may serve as an early warning system for the detection of An. stephensi, providing opportunities to limit further introduction and expansion of this invasive malaria vector in Africa. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
The potential impact of Anopheles stephensi establishment on the transmission of Plasmodium falciparum in Ethiopia and prospective control measures (preprint)
Hamlet A , Dengela D , Eric Tongren J , Tadesse FG , Bousema T , Sinka M , Seyoum A , Irish SR , Armistead JS , Churcher T . medRxiv 2021 25 Background Sub-Saharan Africa has seen substantial reductions in cases and deaths due to malaria over the past two decades. While this reduction is primarily due to an increasing expansion of interventions, urbanisation has played its part as urban areas typically experience substantially less malaria transmission than rural areas. However, this may be partially lost with the invasion and establishment of Anopheles stephensi. An. stephensi, the primary urban malaria vector in Asia, was first detected in Africa during 2012 in Djibouti and was subsequently identified in Ethiopia in 2016, and later in Sudan and Somalia. In Djibouti, malaria cases have increased 30-fold from 2012 to 2019 though the impact in the wider region remains unclear. Methods Here we have adapted an existing model of mechanistic malaria transmission to estimate the increase in vector density required to explain the trends in malaria cases seen in Djibouti. To account for the observed plasticity in An. stephensi behaviour, and the unknowns of how it will establish in a novel environment, we sample behavioural parameters in order to account for a wide range of uncertainty. This quantification is then applied to Ethiopia, considering temperature-dependent extrinsic incubation periods, pre-existing vector-control interventions and Plasmodium falciparum prevalence in order to assess the potential impact of An. stephensi establishment on P. falciparum transmission. Following this, we estimate the potential impact of scaling up ITN (insecticide treated nets)/IRS (indoor residual spraying) and implementing piperonyl butoxide (PBO) ITNs and larval source management, as well as their economic costs. Results We estimate that annual P. falciparum malaria cases could increase by 50% (95% CI 14-90) if no additional interventions are implemented. The implementation of sufficient control measures to reduce malaria transmission to pre-stephensi levels will cost hundreds of millions of USD. Conclusions Substantial heterogeneity across the country is predicted and large increases in vector control interventions could be needed to prevent a major public health emergency. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license. |
Reflecting on ACP's position paper for public health: A view from the CDC lens
Berger SA , Walensky RP . Ann Intern Med 2023 176 (8) 1124-1126 For decades, the tireless dedication of our public health agencies has saved countless lives by mitigating the spread of disease. The Centers for Disease Control and Prevention (CDC) response to COVID-19, though, highlighted both organizational and operational challenges. Informed by feedback from hundreds of internal and external interviews, CDC announced an agency-wide effort—Moving Forward—to share science faster, to translate science into practical policy, to strengthen partnerships, to communicate better, and to be a more effective public health response agency (1). As CDC’s transformation began, numerous esteemed groups similarly opined on pandemic lessons learned; the position paper from the American College of Physicians (ACP) in this issue of Annals of Internal Medicine speaks to the future of public health from the physician perspective (2), complementing other reviews. Herein, we specifically highlight budget, workforce, and data. |
Religion as a social force in health: complexities and contradictions
Idler E , Jalloh MF , Cochrane J , Blevins J . BMJ 2023 382 e076817 The relationship between religion and public health regularly makes headlines in the press, with both conflict and cooperation as themes. Recent examples include: “Battling covid when religion and public health collide,”1 “Churches and mosques educate on Ebola,”2 “Uganda: HIV-positive teens choose religion over ARV.”3 In some cases, religious institutions protect and support public health measures; in others, the opposite occurs. | | Religion is a set of spiritual beliefs and practices that manifest not only at individual level but at institutional levels through congregations of organised religions and faith based, charitable organisations. At the individual level religion may manifest as public participation in worship services of a congregation, as private practices such as prayer or meditation, or as private beliefs in the tenets of a faith or identifying as a religious person. Alongside education, income, ethnicity, and gender, religion has a quantifiable, demonstrable effect on population health.4 However, religion is different from other socioeconomic determinants of health; its unique complexities can produce both harmful and protective health effects. It therefore warrants a different conceptualisation as a social determinant of health, both to mitigate its harmful effects and to realise its protective and generative impact. |
Cannabis-involved emergency department visits among persons aged <25 years before and during the COVID-19 pandemic - United States, 2019-2022
Roehler DR , Smith Hth , Radhakrishnan L , Holland KM , Gates AL , Vivolo-Kantor AM , Hoots BE . MMWR Morb Mortal Wkly Rep 2023 72 (28) 758-765 To understand trends in U.S. cannabis-involved emergency department (ED) visits (i.e., those for which cannabis use was documented in the chief complaint or a discharge diagnosis) among young persons aged <25 years during the COVID-19 pandemic, CDC used National Syndromic Surveillance Program data to examine changes in ED visits during 2019-2022. Mean weekly cannabis-involved ED visits among all young persons were higher during the COVID-19 pandemic in 2020, 2021, and 2022, compared with corresponding periods in 2019. Large increases in cannabis-involved ED visits throughout the COVID-19 pandemic compared with prepandemic surveillance periods in 2019 were identified among persons aged ≤10 years. ED visit rates among children and adolescents aged 11-14 years did not differ by sex until the first half of the 2020-21 school year (2020, weeks 37-53), when ED visit rates among females surpassed those among males. Improving clinicians' awareness of rising cannabis-involved ED visits might aid in early diagnosis of cannabis intoxication among young persons. Further, increasing adults' knowledge regarding safe cannabis storage practices, strengthening youths' coping and problem-solving skills through evidence-based prevention programs, and modifying cannabis packaging to decrease appeal to youths might help prevent intentional and unintentional cannabis use. |
Description of kratom exposure events in Wisconsin as reported to the Wisconsin Poison Center, January 1, 2010 to September 1, 2022
DeJonge P , Gummin D , Titelbaum N , Meiman J . WMJ 2023 122 (3) 187-190 BACKGROUND: Consumption of kratom (Mitragyna speciosa), an herbal substance, can result in adverse health effects. We characterized kratom-associated adverse events in Wisconsin to provide pertinent recommendations for clinicians and public health practitioners. METHODS: Using Wisconsin Poison Center data, we searched for and summarized all records associated with exposure to "kratom," "electronic delivery device containing kratom," or "mitragyna" from January 1, 2010, to September 1, 2022. RESULTS: Kratom-associated exposure calls to the Wisconsin Poison Center increased 3.75 times during 2016 - 2020. Among all 59 calls, 26 (44.1%) reported concomitant use of another substance, agitation was the most common symptom reported (n = 23, 39%), and 7 persons required critical care. Three unintentional ingestions were reported in children aged less than 2 years old. DISCUSSION: Kratom-associated exposure calls to the Wisconsin Poison Center generally have been increasing in frequency since 2011. Wisconsinites who choose to use kratom might benefit from education regarding health risks and safe storage practices to avoid unintentional pediatric exposure. |
Characteristics and prescribing patterns of clinicians waivered to prescribe buprenorphine for opioid use disorder before and after release of new practice guidelines
Jones CM , Olsen Y , Ali MM , Sherry TB , McAninch J , Creedon T , Juliana P , Jacobus-Kantor L , Baillieu R , Diallo MM , Thomas A , Gandotra N , Sokolowska M , Ling S , Compton W . JAMA Health Forum 2023 4 (7) e231982 IMPORTANCE: In April 2021, the US Department of Health and Human Services (HHS) released practice guidelines exempting educational requirements to obtain a Drug Addiction Treatment Act (DATA) waiver to treat up to 30 patients with opioid use disorder with buprenorphine. OBJECTIVE: To compare demographic and practice characteristics of clinicians who received traditional DATA waivers before and after release of the education-exempted HHS practice guidelines and those who were approved under the guidelines. DESIGN, SETTING, AND PARTICIPANTS: This survey study was conducted electronically from February 1 to March 1, 2022. Eligible survey recipients were US clinicians who obtained an initial DATA waiver between April 2020 and November 2021. EXPOSURE: DATA waiver approval pathway. MAIN OUTCOME AND MEASURES: The outcomes were clinician demographic and practice characteristics, buprenorphine prescribing barriers, and strategies to treat patients with opioid use disorder, measured using χ2 tests and z tests to assess for differences among the waivered groups. RESULTS: Of 23 218 eligible clinicians, 4519 (19.5%) responded to the survey. This analysis was limited to 2736 respondents with a 30-patient limit at the time of survey administration who identified their DATA waiver approval pathway. Among these respondents, 1365 (49.9%; female, 831 [61.9%]; male, 512 [38.1%]) received their DATA waiver prior to the education-exempted practice guidelines (prior DATA waiver), 550 (20.1%; female, 343 [63.4%]; male, 198 [36.6%]) received their waiver after guidelines were released but met education requirements (concurrent DATA waiver), and 821 (30.0%; female, 396 [49.2%]; male, 409 [50.8%]) received the waiver under the education-exempted guidelines (practice guidelines). Among practice guidelines clinicians, 500 (60.9%) reported that traditional DATA waiver educational requirements were a reason for not previously obtaining a waiver. Demographic and practice characteristics differed by waiver approval type. Across all groups, a large minority had not prescribed buprenorphine since obtaining a waiver (prior DATA waiver, 483 [35.7%]; concurrent DATA waiver, 226 [41.2%]; practice guidelines, 359 [44.3%]; P < .001). Clinicians who prescribed buprenorphine in the past 6 months reported treating few patients in an average month: 27 practice guidelines clinicians (6.0%) prescribed to 0 patients and 338 (75.1%) to 1 to 4 patients compared with 16 (2.2%) and 435 (59.9%) for prior and 11 (3.6%) and 166 (55.0%) for concurrent DATA waiver clinicians, respectively (P < .001). Across waiver types, clinicians reported multiple challenges to buprenorphine prescribing. CONCLUSIONS AND RELEVANCE: In this survey of DATA-waivered clinicians, clinician- and systems-level challenges that limit buprenorphine prescribing were observed, even among clinicians approved under the education-exempted guidelines pathway. The findings suggest that as implementation of legislation removing the DATA waiver begins, addressing these barriers could be essential to increasing buprenorphine access. |
Hepatitis C virus-HIV coinfection in the United States among people who inject drugs: Data needed for ending dual epidemics
Moorman AC , Bixler D , Teshale EH , Hofmeister M , Roberts H , Chapin-Bardales J , Gupta N . Public Health Rep 2023 333549231181348 The overlapping epidemics of hepatitis C virus (HCV) and HIV infection stem from underlying behaviors and health disparities among disproportionately affected populations, especially people who inject drugs (PWID). Characterizing the prevalence of HCV-HIV coinfection offers improved data to address these underlying determinants of health. We performed a literature search for articles that describe US populations, were published during 2005-2021, and summarized evidence of the prevalence of HCV infection in recent HIV clusters and outbreaks among PWID. In population- and community-based studies, HCV antibody prevalence among PWID with HIV ranged from 10.7% to 71.4%, depending on the setting and study design. HCV-HIV coinfection ranged from 70% to 94% among 5 larger HIV clusters or outbreaks among PWID during 2014-2021; where characterized, HCV diagnosis preceded HIV detection by a median of 4 to 5 years. Robust modernized surveillance is needed to support and measure the progress of city, state, and national activities for ending the HIV epidemic and eliminating hepatitis C. Developing and leveraging surveillance systems can identify missed opportunities for prevention, evaluate care, and build capacity for outbreak investigation. In addition, improved data on injection drug use are crucial to inform efforts for improved HCV and HIV testing, prevention, and treatment in settings that serve PWID. By providing data in a wholistic, integrated manner, public health surveillance programs can support efforts to overcome inefficiencies of disease-specific silos, accelerate delivery of preventive and clinical services, and address the excess disease burden and health disparities associated with HCV-HIV coinfection. |
Reasons to decrease or stop nicotine and tobacco use among adults and association with MPOWER scores in twenty-one middle- and high-income countries, 2019-2020
Sharapova SR , Whitney C , Sulentic R , Pan L , Ahluwalia IB . Tob Prev Cessat 2023 9 25 INTRODUCTION: This study examined reasons why people planned to reduce or stop tobacco consumption and their relationship with MPOWER scores, adjusting for sociodemographic, cultural, and economic factors. METHODS: Data used were Euromonitor International's Voice of the Consumer: Nicotine Survey 2019-2020, World Bank's country income and WHO's MPOWER policy scores. Analytical sample included 21913 adults of legal smoking age in 21 middle- and high-income countries who used nicotine and tobacco products and planned to reduce or stop their consumption in the next 12 months. Poisson regression models with robust error variance, adjusted for sociodemographic and tobacco use covariables, generated adjusted risk ratios (ARRs) of selecting a certain reason to reduce tobacco consumption dependent on continuous MPOWER scores. RESULTS: Main reasons to reduce or stop tobacco consumption were improving health (85%), saving money (65%), pressure from family (19%), and using another substance instead (4%). Country variation was observed by MPOWER scores. Positive associations were found between some MPOWER scores and reasons to reduce or stop tobacco consumption: enforcing bans on tobacco advertising and using another substance (ARR=1.28; 95% CI: 1.11-1.47); warning about dangers of tobacco and saving money (ARR=1.25; 95% CI: 1.19-1.32); offering help to quit tobacco and using another substance (ARR=1.26; 95% CI: 1.10-1.45) or family pressure (ARR=1.11; 95% CI: 1.04-1.17); anti-tobacco campaigns and using another substance (ARR=1.15; 95% CI: 1.08-1.23); and raising taxes and saving money (ARR=1.11; 95% CI: 1.09-1.13). CONCLUSIONS: MPOWER scores are associated with reported reasons to quit tobacco including to improve health, save money, respond to family pressure or use another substance instead. |
Description of Kratom Exposure Events in Wisconsin as Reported to the Wisconsin Poison Center - January 1, 2010-September 1, 2022 (preprint)
DeJonge P , Gummin D , Titelbaum N , Meiman J . medRxiv 2023 05 Background: Consumption of kratom (Mitragyna speciosa), an herbal substance, can result in adverse health effects. We characterized kratom-associated adverse events in Wisconsin to provide pertinent recommendations for clinicians and public health practitioners. Method(s): Using Wisconsin Poison Center (WPC) data, we searched for and summarized all records associated with exposure to "kratom", "electronic delivery device containing kratom", or "mitragyna" during January 1, 2010-September 1, 2022. Result(s): Kratom-associated exposure calls to WPC increased 3.75 times during 2016-2020. Among all 59 calls, 26 (44.1%) reported concomitant use of another substance, agitation was the most common symptom reported (23, 39%), and 7 persons required critical care. Three unintentional ingestions were reported in infants aged <2 years. Discussion(s): Kratom-associated exposure calls to WPC have been generally increasing in frequency since 2011. Wisconsinites who choose to use kratom might benefit from education regarding health risks and safe storage practices to avoid unintentional pediatric exposure. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Isolating the effect of COVID-19 related disruptions on HIV diagnoses in the United States in 2020 (preprint)
Viguerie A , Song R , Johnson AS , Lyles CM , Hernandez A , Farnham PG . medRxiv 2022 01 Background: Diagnoses of HIV in the US decreased by 17% in 2020 due to COVID-related disruptions. The extent to which this decrease is attributable to changes in HIV testing versus HIV transmission is unclear. We seek to better understand this issue by analyzing the discrepancy in expected versus observed HIV diagnoses in 2020 among persons who acquired HIV between 2010-2019, as changes in diagnosis patterns in this cohort cannot be attributed to changes in transmission. Method(s): We developed three methods based on the CD4-depletion model to estimate excess missed diagnoses in 2020 among persons with HIV (PWH) infected from 2010-2019. We stratified the results by transmission group, sex assigned at birth, race/ethnicity, and region to examine differences by group and confirm the reliability of our estimates. We performed similar analyses projecting diagnoses in 2019 among PWH infected from 2010-2018 to evaluate the accuracy of our methods against surveillance data. Result(s): There were approximately 3100-3300 (approximately 18%) fewer diagnoses than expected in 2020 among PWH infected from 2010-2019. Females (at birth), heterosexuals, persons who inject drugs, and Hispanic/Latino PWH missed diagnoses at higher levels than the overall population. Validation and stratification analyses confirmed the accuracy and reliability of our estimates. Conclusion(s): The substantial drop in number of previously infected PWH diagnosed in 2020, suggests that changes in testing played a substantial role in the observed decrease. Levels of missed diagnoses differed substantially across population subgroups. Increasing testing efforts and innovative strategies to reach undiagnosed PWH are needed to offset this diagnosis gap. These analyses may be used to inform future estimates of HIV transmission during the COVID-19 pandemic. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
QuickStats: Life expectancy at birth, by sex - National Vital Statistics System, United States, 2019-2021
Xu J , Minino A . MMWR Morb Mortal Wkly Rep 2023 72 (28) 775 Life expectancy at birth for the total population declined 2.4 years from 78.8 in 2019 to 76.4 years in 2021. Life expectancy declined for both males and females during this period. For males, life expectancy declined from 76.3 to 73.5 years and for females from 81.4 to 79.3 years. Life expectancy was higher for females than males by 5.1 years in 2019, and that difference increased to 5.8 years in 2021. |
Soft tick relapsing fever - United States, 2012-2021
Beeson AM , Kjemtrup A , Oltean H , Schnitzler H , Venkat H , Ruberto I , Marzec N , Cozart D , Tengelsen L , Ladd-Wilson S , Rettler H , Mayes B , Broussard K , Garcia A , Drake LL , Dietrich EA , Petersen J , Hinckley AF , Kugeler KJ , Marx GE . MMWR Morb Mortal Wkly Rep 2023 72 (29) 777-781 Soft tick relapsing fever (STRF) (also known as tickborne relapsing fever) is a rare infection caused by certain Borrelia spirochetes and transmitted to humans by soft-bodied Ornithodoros ticks. In the United States, acquisition of STRF is commonly associated with exposure to rustic cabins, camping, and caves. Antibiotic treatment is highly effective for STRF, but without timely treatment, STRF can result in severe complications, including death. No nationally standardized case definition for STRF exists; however, the disease is reportable in 12 states. This report summarizes demographic and clinical information for STRF cases reported during 2012-2021 from states where STRF is reportable. During this period, 251 cases were identified in 11 states. The median annual case count was 24. Most patients with STRF (55%) were hospitalized; no fatalities were reported. The geographic distribution and seasonal pattern of STRF have remained relatively constant since the 1990s. Persons should avoid rodent-infested structures and rodent habitats, such as caves, in areas where STRF is endemic. STRF surveillance, prevention, and control efforts would benefit from a standardized case definition and increased awareness of the disease among the public and clinicians. |
Quail rearing practices and potential for avian influenza virus transmission, Bangladesh
Hasan SMM , Sturm-Ramirez K , Kamal AM , Islam MA , Rahman M , Kile JC , Kennedy ED , Gurley ES , Islam MS . Ecohealth 2023 20 (2) 167-177 In 2015, human influenza surveillance identified a human infection with A/H9N2 in Dhaka, Bangladesh with evidence of exposure to a sick quail. We conducted in-depth interviews with household quail caregivers, pet bird retail shop owners, and mobile vendors, key informant interviews with pet bird wholesale shop owners, one group discussion with pet bird retail shop workers and unstructured observations in households, pet bird wholesale and retail markets, and mobile bird vendor's travelling areas to explore quail rearing and selling practices among households, mobile vendors, and retail pet bird and wholesale bird markets in Dhaka. Every day, quail were supplied from 23 districts to two wholesale markets, and then sold to households and restaurants directly, or through bird shops and mobile vendors. All respondents (67) reported keeping quail with other birds in cages, feeding quail, cleaning feeding pots, removing quail faeces, slaughtering sick quail, and discarding dead quail. Children played with quail and assisted in slaughtering of quail. Most respondents (94%) reported rinsing hands with water only after slaughtering and disposing of wastes and dead quail. No personal protective equipment was used during any activities. Frequent unprotected contact with quail and their by-products potentially increased the risk of cross-species avian influenza virus transmission. Avian influenza surveillance in retail pet bird and wholesale bird markets, mobile vendors, and households may identify cases promptly and reduce the risk of virus transmission. |
Antiviral susceptibility of clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses isolated from birds and mammals in the United States, 2022
Nguyen HT , Chesnokov A , De La Cruz J , Pascua PNQ , Mishin VP , Jang Y , Jones J , Di H , Ivashchenko AA , Killian ML , Torchetti MK , Lantz K , Wentworth DE , Davis CT , Ivachtchenko AV , Gubareva LV . Antiviral Res 2023 217 105679 Clade 2.3.4.4 b highly pathogenic avian influenza (HPAI) A (H5N1) viruses that are responsible for devastating outbreaks in birds and mammals pose a potential threat to public health. Here, we evaluated their susceptibility to influenza antivirals. Of 1015 sequences of HPAI A (H5N1) viruses collected in the United States during 2022, eight viruses (∼0.8%) had a molecular marker of drug resistance to an FDA-approved antiviral: three adamantane-resistant (M2-V27A), four oseltamivir-resistant (NA-H275Y), and one baloxavir-resistant (PA-I38T). Additionally, 31 viruses contained mutations that may reduce susceptibility to inhibitors of neuraminidase (NA) (n = 20) or cap-dependent endonuclease (CEN) (n = 11). A panel of 22 representative viruses was tested phenotypically. Overall, clade 2.3.4.4 b A (H5N1) viruses lacking recognized resistance mutations were susceptible to FDA-approved antivirals. Oseltamivir was least potent at inhibiting NA activity, while the investigational NA inhibitor AV5080 was most potent, including against NA mutants. A novel NA substitution T438N conferred 12-fold reduced inhibition by zanamivir, and in combination with the known marker N295S, synergistically affected susceptibility to all five NA inhibitors. In cell culture-based assays HINT and IRINA, the PA-I38T virus displayed 75- to 108-fold and 37- to 78-fold reduced susceptibility to CEN inhibitors baloxavir and investigational AV5116, respectively. Viruses with PA-I38M or PA-A37T showed 5- to 10-fold reduced susceptibilities. As HPAI A (H5N1) viruses continue to circulate and evolve, close monitoring of drug susceptibility is needed for risk assessment and to inform decisions regarding antiviral stockpiling. |
Tick salivary gland components dampen Kasokero virus infection and shedding in its vertebrate reservoir, the Egyptian rousette bat (Rousettus aegyptiacus)
Schuh AJ , Amman BR , Guito JC , Graziano JC , Sealy TK , Towner JS . Parasit Vectors 2023 16 (1) 249 BACKGROUND: The human-pathogenic Kasokero virus (KASV) circulates in an enzootic transmission cycle between Egyptian rousette bats (ERBs; Rousettus aegyptiacus) and their argasid tick ectoparasites, Ornithodoros (Reticulinasus) faini. Although tick salivary gland components have been shown to potentiate virus infection in vertebrate non-reservoirs (i.e. incidental hosts or small animal models of disease), there is a lack of information on the effect of tick salivary gland components on viral infection and shedding in vertebrate reservoirs. METHODS: To determine the impact of tick salivary gland components on KASV infection and shedding in ERBs, KASV loads were quantified in blood, oral swab, rectal swab, and urine specimens collected daily through 18 days post inoculation from groups of ERBs intradermally inoculated with KASV or KASV + O. (R.) faini tick salivary gland extract (SGE). RESULTS: Bats inoculated with KASV + tick SGE had significantly lower peak and cumulative KASV viremias and rectal shedding loads compared to bats inoculated with KASV only. CONCLUSIONS: We report for the first time to our knowledge that tick salivary gland components dampen arbovirus infection and shedding in a vertebrate reservoir. This study advances our understanding of biological factors underlying arbovirus maintenance in nature. |
On skunk rabies and its prevention in North America
Velasco-Villa A . Equine Vet Educ 2023 The case report by Navarro-López et al. (2023) in this issue describes a thorough differential diagnosis in a horse with acute neurological disease. Rabies was confirmed by direct fluorescent antibody (DFA) test. Rabies virus (RABV) was isolated from brain tissue of the ill mare by intracerebral inoculation in sucking mice. Sequencing and phylogenetic inference allowed the identification of the rabies virus variant (RVV) associated with this case. Thus, Navarro-López et al. reported that the rabid mare got infected with a RVV associated with skunks. This clinical commentary elaborates on the seemingly rare skunk rabies across North America (NA), highlighting its relevance in human and animal health that have remained somehow neglected. |
Probable transmission of SARS-CoV-2 from an African lion to zoo employees (preprint)
Siegrist AA , Richardson KL , Ghai RR , Pope B , Yeadon J , Culp B , Behravesh CB , Liu L , Brown JA , Boyer LV . medRxiv 2023 31 (6) 1102-1108 Animal to human transmission of SARS-CoV-2 has not previously been reported in a zoo setting. A vaccinated African lion with physical limitations requiring hand feeding tested positive for SARS-CoV-2 after development of respiratory signs. Zoo employees were screened, monitored prospectively for development of symptoms, then re-screened as indicated, with confirmation by RT-PCR and whole-genome virus sequencing when possible. Trace-back investigation narrowed the source of infection to one of five people. Three exposed employees subsequently developed symptoms, two with viral genomes identical to the lion's. Forward contact tracing investigation confirmed probable lion-to-human transmission. Close contact with large cats is a risk factor for bidirectional zoonotic SARS-CoV-2 transmission that should be considered when occupational health and biosecurity practices at zoos are designed and implemented. SARS-CoV-2 rapid testing and detection methods in big cats and other susceptible animals should be developed and validated to facilitate timely implementation of One Health investigations. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Intracellular diversity of WNV within circulating avian peripheral blood mononuclear cells reveals host-dependent patterns of polyinfection (preprint)
Frank DT , Byas AD , Murrieta R , Weger-Lucarelli J , Ruckert C , Gallichotte E , Yoshimoto JA , Allen C , Bosco-Lauth AM , Graham B , Felix TA , Brault A , Ebel GD . bioRxiv 2023 29 Error-prone replication of RNA viruses generates the genetic diversity required for adaptation within rapidly changing environments. Thus, arthropod-borne virus (arbovirus) populations exist in nature as mutant swarms that are maintained between arthropods and vertebrates. Previous studies have demonstrated that West Nile virus (WNV) population dynamics are host dependent: In American crows, which experience extremely high viremia, purifying selection is weak and population diversity is high compared to American robins, which have 100 to 1000-fold lower viremia. WNV passed in robins experiences fitness gains, whereas that passed in crows does not. Therefore, we tested the hypothesis that high crow viremia allows higher genetic diversity within individual avian peripheral-blood mononuclear cells (PBMCs), reasoning that this could have produced the previously observed host-specific differences in genetic diversity and fitness. Specifically, we infected cells and birds with a novel, barcoded version of WNV and sequenced viral RNA from single cells to quantify the number of WNV barcodes that each contained. Our results demonstrate that the richness of WNV populations within crows far exceeds that in robins. Similarly, rare WNV variants were maintained by crows more frequently than by robins. Our results suggest that increased viremia in crows relative to robins leads to maintenance of defective genomes and less prevalent variants, presumably through complementation. Our findings further suggest that weaker purifying selection in highly susceptible crows is attributable to this higher viremia, polyinfections and complementation. These studies further document the role of particular, ecologically relevant hosts in shaping virus population structure. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Spatiotemporal Distribution of Vector Mosquito Species and Areas at Risk for Arbovirus Transmission in Maricopa County, Arizona (preprint)
Wilke ABB , Damian D , Litvinova M , Byrne T , Zardini A , Poletti P , Merler S , Mutebi JP , Townsend J , Ajelli M . bioRxiv 2022 28 Mosquito-borne diseases are a major global public health concern and mosquito surveillance systems are essential for the implementation of effective mosquito control strategies. The objective of our study is to determine the spatiotemporal distribution of vector mosquito species in Maricopa County, AZ from 2011 to 2021, and to identify the hotspot areas for West Nile virus (WNV) and St. Louis Encephalitis virus (SLEV) transmission in 2021. The Maricopa County Mosquito Control surveillance system utilizes BG-Sentinel and EVS-CDC traps throughout the entire urban and suburban areas of the county. We estimated specific mosquito species relative abundance per unit area using the Kernel density estimator in ArcGIS 10.2. We calculated the distance between all traps in the surveillance system and created a 4 km buffer radius around each trap to calculate the extent to which each trap deviated from the mean number of Cx. quinquefasciatus and Cx. tarsalis collected in 2021. Our results show that vector mosquito species are widely distributed and abundant in the urban areas of Maricopa County. A total of 691,170 Culex quinquefasciatus, 542,733 Culex tarsalis, and 292,305 Aedes aegypti were collected from 2011 to 2022. The relative abundance of Ae. aegypti was highly seasonal peaking in the third and fourth quarters of the year. Culex quinquefasciatus, on the other hand, was abundant throughout the year with several regions consistently yielding high numbers of mosquitoes. Culex tarsalis was abundant but it only reached high numbers in well-defined areas bordering natural and rural areas. We also detected high levels of heterogeneity in the risk of WNV and SLEV transmission to humans disregarding traps geographical proximity. The well-defined species-specific spatiotemporal and geographical patterns found in this study can be used to inform vector control operations. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. |
Structural Elucidation of a Protective B cell Epitope on Outer Surface Protein C (OspC) of the Lyme disease spirochete, Borreliella burgdorferi (preprint)
Rudolph MJ , Davis SA , Emranul Haque HM , Weis DD , Vance DJ , Piazza CL , Ejemel M , Cavacini L , Wang Y , Lamine Mbow M , Gilmore RD , Mantis NJ . bioRxiv 2022 29 Outer surface protein C (OspC) plays a pivotal role in mediating tick-to-host transmission and infectivity of the Lyme disease spirochete, Borreliella burgdorferi. OspC is a helical-rich homodimer that interacts with tick salivary proteins, as well as components of the mammalian immune system. Several decades ago, it was shown that the OspC-specific monoclonal antibody, B5, was able to passively protect mice from experimental tick-transmitted infection by B. burgdorferi strain B31. However, B5's epitope has never been elucidated, despite widespread interest in OspC as a possible Lyme disease vaccine antigen. Here we report the crystal structure of B5 antigen-binding fragments (Fabs) in complex with recombinant OspC type A (OspCA). Each OspC monomer within the homodimer was bound by a single B5 Fab in a side-on orientation, with contact points along OspC's a-helix 1 and a-helix 6, as well as interactions with the loop between a-helices 5 and 6. In addition, B5's complementarity-determining region (CDR) H3 bridged the OspC-OspC' homodimer interface, revealing the quaternary nature of the protective epitope. To provide insight into the molecular basis of B5 serotype specificity, we solved the crystal structures of recombinant OspC types B and K and compared them to OspCA. This study represents the first structure of a protective B cell epitope on OspC and will aid in the rational design of OspC-based vaccines and therapeutics for Lyme disease. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Multiple lineages of Monkeypox virus detected in the United States, 2021-2022 (preprint)
Gigante CM , Korber B , Seabolt MH , Wilkins K , Davidson W , Rao AK , Zhao H , Hughes CM , Minhaj F , Waltenburg MA , Theiler J , Smole S , Gallagher GR , Blythe D , Myers R , Schulte J , Stringer J , Lee P , Mendoza RM , Griffin-Thomas LA , Crain J , Murray J , Atkinson A , Gonzalez AH , Nash J , Batra D , Damon I , McQuiston J , Hutson CL , McCollum AM , Li Y . bioRxiv 2022 11 (6619) 560-565 Monkeypox is a viral zoonotic disease endemic in Central and West Africa. In May 2022, dozens of non-endemic countries reported hundreds of monkeypox cases, most with no epidemiological link to Africa. We identified two lineages of Monkeypox virus (MPXV) among nine 2021 and 2022 U.S. monkeypox cases. A 2021 case was highly similar to the 2022 MPXV outbreak variant, suggesting a common ancestor. Analysis of mutations among these two lineages revealed an extreme preference for GA-to-AA mutations indicative of APOBEC3 cytosine deaminase activity that was shared among West African MPXV since 2017 but absent from Congo Basin lineages. Poxviruses are not thought to be subject to APOBEC3 editing; however, these findings suggest APOBEC3 activity has been recurrent and dominant in recent West African MPXV evolution. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Interspecies transmission from pigs to ferrets of antigenically distinct swine H1 influenza A viruses with loss in reactivity to human vaccine virus antisera as measures of relative zoonotic risk (preprint)
Brian Kimble J , Souza CK , Anderson TK , Arendsee ZW , Hufnagel DE , Young KM , Lewis NS , Todd Davis C , Vincent Baker AL . bioRxiv 2022 13 During the last decade, endemic swine H1 influenza A viruses (IAV) from six different genetic clades of the hemagglutinin gene caused zoonotic infections in humans. The majority of zoonotic events with swine IAV were restricted to a single case with no subsequent transmission. However, repeated introduction of human-seasonal H1N1, continual reassortment between endemic swine IAV, and subsequent drift in the swine host resulted in highly diverse swine IAV with human-origin genes that may become a risk to the human population. To prepare for the potential of a future swine-origin IAV pandemic in humans, public health laboratories selected candidate vaccine viruses (CVV) for use as vaccine seed strains. To assess the pandemic risk of contemporary US swine H1N1 or H1N2 strains, we quantified the genetic diversity of swine H1 HA genes, and identified representative strains from each circulating clade. We then characterized the representative swine IAV against human seasonal vaccine and CVV strains using ferret antisera in hemagglutination inhibition assays (HI). HI assays revealed that 1A.3.3.2 (pdm) and 1B.2.1 (delta-2) demonstrated strong cross reactivity to human seasonal vaccines or CVVs. However, swine IAV from three clades that represent more than 50% of the detected swine IAVs in the USA showed significant reduction in cross-reactivity compared to the closest CVV virus: 1A.1.1.3 (alpha-deletion), 1A.3.3.3-clade 3 (gamma), and 1B.2.2.1 (delta-1a). Representative viruses from these three clades were further characterized in a pig-to-ferret transmission model and shown to exhibit variable transmission efficiency. Our data prioritize specific genotypes of swine H1N1 and H1N2 to further investigate in the risk they pose to the human population. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Divergent lineages of pathogenic Leptospira species are widespread and persisting in the environment in Puerto Rico, USA (preprint)
Stone NE , Hall CM , Ortiz M , Hutton S , Santana-Propper E , Celona KR , Williamson CHD , Bratsch N , Fernandes LGV , Busch JD , Pearson T , Rivera-Garcia S , Soltero F , Galloway R , Sahl JW , Nally JE , Wagner DM . medRxiv 2021 11 Background: Leptospirosis, caused by Leptospira bacteria, is a common zoonosis worldwide more prevalent in the tropics. Reservoir species and risk factors have been identified but surveys for environmental sources of leptospirosis are rare. Furthermore, understanding of environmental Leptospira containing pathogenic genes and possibly capable of causing disease is incomplete and could result in some pathogenic strains evading detection, thereby convoluting diagnosis, prevention, and epidemiology. Methodology/Principal Findings: We collected environmental samples from 22 sites in Puerto Rico during three sampling periods over 14-months (Dec 2018-Feb 2020); 10 water and 10 soil samples were collected at each site. Samples were screened for pathogenic Leptospira DNA using the lipL32 PCR assay and positive samples were sequenced to assess genetic diversity. One urban site in San Juan was sampled three times over 14 months to assess persistence in soil; live leptospires were obtained during the last sampling period. Isolates were whole genome sequenced and LipL32 expression was assessed in vitro. We detected pathogenic Leptospira DNA at 15/22 sites; both soil and water were positive at 5/15 sites. We recovered lipL32 sequences from 83/86 positive samples (15/15 positive sites) and secY sequences from 32/86 (10/15 sites); multiple genotypes were identified at 12 sites. These sequences revealed significant diversity across samples, including four novel lipL32 phylogenetic clades. Most samples from the serially sampled site were lipL32 positive at each time point. We sequenced the genomes of six saprophytic and two pathogenic Leptospira isolates; the latter represent a novel pathogenic Leptospira species likely belonging to a new serogroup. Conclusions/Significance: Diverse and novel pathogenic Leptospira are widespread in the environment in Puerto Rico. The disease potential of the novel lineages is unknown but several persisted for >1 year in soil, which could contaminate water. This work increases understanding of environmental Leptospira and should improve leptospirosis surveillance and diagnostics. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Content Index (Achived Edition)
- Antimicrobial Resistance and Antibiotic Stewardship
- Chronic Diseases and Conditions
- Communicable Diseases
- Community Health Services
- Disaster Preparedness and Emergency Services
- Disease Reservoirs and Vectors
- Environmental Health
- Epidemiology and Surveillance
- Food Safety
- Genetics and Genomics
- Global Health
- Health Behavior and Risk
- Health Economics
- Health Equity and Health Disparities
- Healthcare Associated Infections
- Immunity and Immunization
- Informatics
- Injury and Violence
- Laboratory Sciences
- Maternal and Child Health
- Nutritional Sciences
- Occupational Safety and Health
- Parasitic Diseases
- Public Health Leadership and Management
- Social and Behavioral Sciences
- Substance Use and Abuse
- Vital Statistics
- Zoonotic and Vectorborne Diseases
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