Updating breakpoints in the United States: a summary from the ASM Clinical Microbiology Open 2022
Patel JB , Alby K , Humphries R , Weinstein M , Lutgring JD , Naccache SN , Simner PJ . J Clin Microbiol 2023 61 (10) e0115422 Accurate antimicrobial susceptibility testing (AST) and reporting are essential for guiding appropriate therapy for patients and direction for public health prevention and control actions. A critical feature of AST reporting is the interpretation of AST results using clinical breakpoints for reporting as susceptible, susceptible-dose dependent, intermediate, or resistant. Breakpoints are subject to continuous adjustment and updating to best reflect current clinical data. These breakpoint changes can benefit patients and public health only if adopted in a timely manner. A recent survey identified that up to 70% of College of American Pathologists (CAP)-accredited U.S. laboratories and 45% of CAP-accredited laboratories outside the U.S. use various obsolete clinical breakpoints to interpret AST results to guide patient care. The reason for the ongoing use of obsolete breakpoints is multifactorial, including barriers encountered by laboratories, commercial AST device manufacturers, standards development organizations, and regulatory bodies alike. To begin to address this important patient safety issue, CAP implemented checklist requirements for CAP-accredited laboratories to ensure up-to-date clinical breakpoint use. Furthermore, the topic was discussed at the June 2022 American Society for Microbiology Clinical Microbiology Open (CMO) with various stakeholders to identify potential solutions. This minireview summarizes the breakpoint setting process in the U.S. and highlights solutions to close the gap between breakpoint revisions and implementation in clinical and public health laboratories. Solutions discussed include clarification of data requirements and minimum inhibitory concentration only reporting for regulatory clearance of AST devices, clinical data generation to close breakpoints gaps, advocacy, education, and greater dialogue between stakeholders. |
Antifungal therapeutic drug monitoring practices: Results of an Emerging Infections Network Survey
Benedict K , Gold JAW , Beekmann SE , Polgreen PM , Toda M , Smith DJ . Open Forum Infect Dis 2023 10 (9) ofad468 In a survey of 523 infectious disease specialists, a moderate to high percentage reported using any antifungal therapeutic drug monitoring (TDM) during itraconazole (72%), posaconazole (72%), and voriconazole (90%) treatment, and a low to moderate percentage reported using any antifungal TDM during prophylaxis (32%, 55%, and 65%, respectively). Long turnaround times for send-out TDM testing and logistical difficulties were frequent barriers. |
A brief report on juvenile amyotrophic lateral sclerosis cases in the United States National ALS Registry: 2010-2018
Raymond J , Berry J , Kasarskis EJ , Larson T , Horton DK , Mehta P . Amyotroph Lateral Scler Frontotemporal Degener 2023 1-3 Juvenile ALS (jALS) is a rare form of ALS, defined as symptom onset before age 25. This report describes the demographic characteristics of confirmed and likely jALS cases in a large cohort of ALS patients ascertained in the National ALS Registry (Registry) from 2010 to 2018. Patients in the Registry must be at least 18 years of age. Of the 44 identified patients, 37.8% were diagnosed at age 24, were more likely to be nonwhite (54.5%), male (79.5%), and live in the Midwest or Northeast regions (54.5%) of the US. Some 68.9% of the jALS cases were received from federal administrative databases, and 16% came from the web portal only. Demographic characteristics for jALS cases in the Registry differed from previous publications examining ALS cases for all adults. More research is needed to better understand risk factors contributing to jALS, which could lead to earlier diagnosis and therapeutic interventions. |
Use of cancer survivorship care guidelines by primary care providers in the United States
Townsend JS , Rohan EA , Sabatino SA , Puckett M . J Am Board Fam Med 2023 36 (5) 789-802 BACKGROUND: National organizations have issued comprehensive cancer survivorship care guidelines to improve care of cancer survivors, many of whom receive care from primary care providers (PCPs). METHODS: We analyzed Porter Novelli's 2019 fall DocStyles survey to assess use of cancer survivorship care guidelines, receipt of survivorship training, types of survivorship services provided, and confidence providing care among PCPs in the United States. We grouped PCPs by use of any guideline ("users") versus no guideline use ("nonusers"). We calculated descriptive statistics and conducted multivariable logistic regression analyses to examine guideline use, having received training on providing survivorship care services, and confidence in providing care. Within the panel, sampling quotas were set so that 1000 primary care physicians, 250 OB/GYNs, 250 pediatricians, and 250 nurse practitioners/physician assistants were recruited. RESULTS: To reach selected quotas, 2696 health professionals were initially contacted to participate, resulting in a response rate of 64.9%. Sixty-two percent of PCPs reported using guidelines and 17% reported receiving survivorship care training. Use of any guidelines or receiving training was associated with reporting providing a range of survivorship services and confidence in providing care. After adjusting for demographic characteristics, guideline users were more likely than nonusers to report assessing genetic cancer risk (OR = 2.65 95% confidence interval (CI) (1.68, 4.17)), screening for cancer recurrence (OR = 2.32 95% CI (1.70, 3.18)) or a new cancer (OR = 1.63, 95% CI (1.20, 2.22)), and treating depression (OR = 1.64, 95% CI (1.20, 2.25)). Receipt of training was also positively associated with providing genetic risk assessment, surveillance for recurrence, as well as assessing late/long-term effects, and treating pain, fatigue, and sexual side effects. CONCLUSION: Survivorship care guidelines and training support PCPs in providing a range of survivorship care services. |
Improving anemia assessment in clinical and public health settings
Williams AM , Brown KH , Allen LH , Dary O , Moorthy D , Suchdev PS . J Nutr 2023 153 Suppl 1 S29-S41 We aim to provide a practical approach to assess anemia and its primary causes, both in clinical settings and in the context of public health programs. Anemia remains a global challenge; thus, to achieve goals for anemia reduction and assess progress, standardized approaches are required for the assessment of anemia and its causes. We first provide a brief review of how to assess anemia, based on hemoglobin concentrations and cutoffs that correspond to age, sex, and physiologic status. Next, we discuss how to assess the likely causes of anemia in different settings. The causes of anemia are classified as non-nutritional (for example, because of infection, inflammation, blood loss, or genetic disorders) or nutrition-specific (for example, because of deficiencies of iron, vitamin A, riboflavin, vitamin B(12), or folate). There is an important overlap between these 2 categories, such as the increased likelihood of iron deficiency in the context of inflammation. Given the multifaceted nature of anemia etiology, we introduce a framework for anemia assessment based on the "ecology of anemia," which recognizes its many overlapping causes. This conceptual framework is meant to inform what data on anemia causes may need to be collected in population surveys. The framework has a supporting table with information on the diagnostic tests, biomarkers and proposed cutoffs, characteristics, and feasibility of collecting the myriad information that can help elucidate the anemia etiology. We also provide examples of how this framework can be applied to interpret the anemia risk factor data from population-based surveys that can inform decisions about context-specific interventions. Finally, we present research gaps and priorities related to anemia assessment. |
Invasive pneumococcal disease and potential impact of pneumococcal conjugate vaccines among adults, including persons experiencing homelessness - Alaska, 2011-2020
Steinberg J , Bressler SS , Orell L , Thompson GC , Kretz A , Reasonover AL , Bruden D , Bruce MG , Fischer M . Clin Infect Dis 2023 BACKGROUND: Adults aged ≥65 years, adults with certain underlying medical conditions, and persons experiencing homelessness are at increased risk for invasive pneumococcal disease (IPD). Two new pneumococcal conjugate vaccines, 15-valent pneumococcal conjugate vaccine (PCV15) and 20-valent pneumococcal conjugate vaccine (PCV20), were recently approved for use in U.S. adults. We described the epidemiology of IPD among Alaska adults and estimated the proportion of IPD cases potentially preventable by new vaccines. METHODS: We used statewide, laboratory-based surveillance data to calculate and compare IPD incidence rates and 95% confidence intervals (CI) among Alaska adults aged ≥18 years during 2011-2020 and estimate the proportion of IPD cases that were caused by serotypes in PCV15 and PCV20. RESULTS: During 2011-2020, 1,164 IPD cases were reported among Alaska adults for an average annual incidence of 21.3 cases per 100,000 adults per year (95% CI: 20.1-22.5). Incidence increased significantly during the study period (p<0.01). IPD incidence among Alaska Native adults was 4.7 times higher than among non-Alaska Native adults (95% CI: 4.2-5.2). Among adults experiencing homelessness in Anchorage, IPD incidence was 72 times higher than the general adult population (95% CI: 59-89). Overall, 1,032 (89%) Alaska adults with IPD had an indication for pneumococcal vaccine according to updated vaccination guidelines; 456 (39%) and 700 (60%) cases were caused by serotypes in PCV15 and PCV20, respectively. CONCLUSIONS: Use of PCV15 and PCV20 could substantially reduce IPD among adults in Alaska, including Alaska Native adults and adults experiencing homelessness. |
Recombinant Sudan virus and evaluation of humoral cross-reactivity between Ebola and Sudan virus glycoproteins after infection or rVSV-ΔG-ZEBOV-GP vaccination
Kainulainen MH , Harmon JR , Whitesell AN , Bergeron E , Karaaslan E , Cossaboom CM , Malenfant JH , Kofman A , Montgomery JM , Choi MJ , Albariño CG , Spiropoulou CF . Emerg Microbes Infect 2023 12 (2) 2265660 Ebola disease outbreaks are major public health events because of human-to-human transmission and high mortality. These outbreaks are most often caused by Ebola virus, but at least three related viruses can also cause the disease. In 2022, Sudan virus re-emerged causing more than 160 confirmed and probable cases. This report describes generation of a recombinant Sudan virus and demonstrates its utility by quantifying antibody cross-reactivity between Ebola and Sudan virus glycoproteins after human infection or vaccination with a licensed Ebola virus vaccine. |
The elimination of hepatitis D as a public health problem: Needs and challenges
Vanwolleghem T , Armstrong PA , Buti M , FitzSimons D , Valckx S , Hendrickx G , Van Damme P . J Viral Hepat 2023 31 (1) 47-50 Infection with hepatitis D virus leads to liver disease and cancer most rapidly of all hepatitis viruses. However, knowledge about hepatitis D remains poor and the burden and impact are underestimated, even though some 12-15 million people mainly in low- and middle-income countries may be affected. Its epidemiology is changing, with increasing migration leading to increased risks of infection and disease. A recent Viral Hepatitis Prevention Board meeting reviewed the current epidemiological status, improvements in diagnostic testing, advances in the development of novel antiviral agents in phase III trials and the need for a greater public health response, such as new guidelines and recommended testing of all people newly identified as infected with hepatitis B virus for hepatitis D virus infection. It identified issues and needs for attention with regard to prevention, diagnosis and treatment. |
Paediatric acute hepatitis of unknown aetiology: a national surveillance investigation in the USA during 2021 and 2022
Cates J , Baker JM , Almendares O , Balachandran N , McKeever ER , Kambhampati AK , Cubenas C , Vinjé J , Cannon JL , Chhabra P , Freeman B , Reagan-Steiner S , Bhatnagar J , Gastañaduy PA , Kirking HL , Sugerman D , Parashar UD , Tate JE . Lancet Child Adolesc Health 2023 7 (11) 773-785 BACKGROUND: Adenovirus is a known cause of hepatitis in immunocompromised children, but not in immunocompetent children. In April, 2022, following multiple reports of hepatitis of unknown aetiology and adenovirus viraemia in immunocompetent children in the USA and UK, the US Centers for Disease Control and Prevention (CDC) and jurisdictional health departments initiated national surveillance of paediatric acute hepatitis of unknown aetiology. We aimed to describe the clinical and epidemiological characteristics of children identified with hepatitis of unknown aetiology between Oct 1, 2021, and Sept 30, 2022, in the USA and to compare characteristics of those who tested positive for adenovirus with those who tested negative. METHODS: In this national surveillance investigation in the USA, children were identified for investigation if they were younger than 10 years with elevated liver transaminases (>500 U/L) who had an unknown cause for their hepatitis and onset on or after Oct 1, 2021. We reviewed medical chart abstractions, which included data on demographics, underlying health conditions, signs and symptoms of illness, laboratory results, vaccination history, radiological and liver pathology findings, diagnoses and treatment received, and outcomes. Caregiver interviews were done to obtain information on symptoms and health-care utilisation for the hepatitis illness, medical history, illness in close contacts or at school or daycare, diet, travel, and other potential exposures. Blood, stool, respiratory, and tissue specimens were evaluated according to clinician discretion and available specimens were submitted to CDC for additional laboratory testing or pathology evaluation. FINDINGS: Surveillance identified 377 patients from 45 US jurisdictions with hepatitis of unknown aetiology with onset from Oct 1, 2021, to Sept 30, 2022. The median age of patients was 2·8 years (IQR 1·2-5·0) and 192 (51%) were male, 184 (49%) were female, and one patient had sex unknown. Only 22 (6%) patients had a notable predisposing underlying condition. 347 patients (92%) were admitted to hospital, 21 (6%) subsequently received a liver transplant, and nine (2%) died. Among the 318 patients without notable underlying conditions, 275 were tested for adenovirus. Of these 116 (42%) had at least one positive specimen, and species F type 41 was the most frequent type identified (19 [73%] of 26 typed specimens were HAdV-41). Proportions of patients who had acute liver failure, received a liver transplant, and died were similar between those who tested positive for adenovirus compared with those who tested negative. Adenovirus species F was detected by polymerase chain reaction in nine pathology liver evaluations, but not by immunohistochemistry in seven of the nine with adequate liver tissue available. Interviews with caregivers yielded no common exposures. INTERPRETATION: Adenovirus, alone or in combination with other factors, might play a potential role in acute hepatitis among immunocompetent children identified in this investigation, but the pathophysiologic mechanism of liver injury is unclear. To inform both prevention and intervention measures, more research is warranted to determine if and how adenovirus might contribute to hepatitis risk and the potential roles of other pathogens and host factors. FUNDING: None. |
Severity of influenza-associated hospitalisations by influenza virus type and subtype in the USA, 2010-19: a repeated cross-sectional study
Sumner KM , Masalovich S , O'Halloran A , Holstein R , Reingold A , Kirley PD , Alden NB , Herlihy RK , Meek J , Yousey-Hindes K , Anderson EJ , Openo KP , Monroe ML , Leegwater L , Henderson J , Lynfield R , McMahon M , McMullen C , Angeles KM , Spina NL , Engesser K , Bennett NM , Felsen CB , Lung K , Shiltz E , Thomas A , Talbot HK , Schaffner W , Swain A , George A , Rolfes MA , Reed C , Garg S . Lancet Microbe 2023 4 (11) e903-e912 BACKGROUND: Influenza burden varies across seasons, partly due to differences in circulating influenza virus types or subtypes. Using data from the US population-based surveillance system, Influenza Hospitalization Surveillance Network (FluSurv-NET), we aimed to assess the severity of influenza-associated outcomes in individuals hospitalised with laboratory-confirmed influenza virus infections during the 2010-11 to 2018-19 influenza seasons. METHODS: To evaluate the association between influenza virus type or subtype causing the infection (influenza A H3N2, A H1N1pdm09, and B viruses) and in-hospital severity outcomes (intensive care unit [ICU] admission, use of mechanical ventilation or extracorporeal membrane oxygenation [ECMO], and death), we used FluSurv-NET to capture data for laboratory-confirmed influenza-associated hospitalisations from the 2010-11 to 2018-19 influenza seasons for individuals of all ages living in select counties in 13 US states. All individuals had to have an influenza virus test within 14 days before or during their hospital stay and an admission date between Oct 1 and April 30 of an influenza season. Exclusion criteria were individuals who did not have a complete chart review; cases from sites that contributed data for three or fewer seasons; hospital-onset cases; cases with unidentified influenza type; cases of multiple influenza virus type or subtype co-infection; or individuals younger than 6 months and ineligible for the influenza vaccine. Logistic regression models adjusted for influenza season, influenza vaccination status, age, and FluSurv-NET site compared odds of in-hospital severity by virus type or subtype. When missing, influenza A subtypes were imputed using chained equations of known subtypes by season. FINDINGS: Data for 122 941 individuals hospitalised with influenza were captured in FluSurv-NET from the 2010-11 to 2018-19 seasons; after exclusions were applied, 107 941 individuals remained and underwent influenza A virus imputation when missing A subtype (43·4%). After imputation, data for 104 969 remained and were included in the final analytic sample. Averaging across imputed datasets, 57·7% (weighted percentage) had influenza A H3N2, 24·6% had influenza A H1N1pdm09, and 17·7% had influenza B virus infections; 16·7% required ICU admission, 6·5% received mechanical ventilation or ECMO, and 3·0% died (95% CIs had a range of less than 0·1% and are not displayed). Individuals with A H1N1pdm09 had higher odds of in-hospital severe outcomes than those with A H3N2: adjusted odds ratios (ORs) for A H1N1pdm09 versus A H3N2 were 1·42 (95% CI 1·32-1·52) for ICU admission; 1·79 (1·60-2·00) for mechanical ventilation or ECMO use; and 1·25 (1·07-1·46) for death. The adjusted ORs for individuals infected with influenza B versus influenza A H3N2 were 1·06 (95% CI 1·01-1·12) for ICU admission, 1·14 (1·05-1·24) for mechanical ventilation or ECMO use, and 1·18 (1·07-1·31) for death. INTERPRETATION: Despite a higher burden of hospitalisations with influenza A H3N2, we found an increased likelihood of in-hospital severe outcomes in individuals hospitalised with influenza A H1N1pdm09 or influenza B virus. Thus, it is important for individuals to receive an annual influenza vaccine and for health-care providers to provide early antiviral treatment for patients with suspected influenza who are at increased risk of severe outcomes, not only when there is high influenza A H3N2 virus circulation but also when influenza A H1N1pdm09 and influenza B viruses are circulating. FUNDING: The US Centers for Disease Control and Prevention. |
Proteomic and genetic analyses of influenza A viruses identify pan-viral host targets
Haas KM , McGregor MJ , Bouhaddou M , Polacco BJ , Kim EY , Nguyen TT , Newton BW , Urbanowski M , Kim H , Williams MAP , Rezelj VV , Hardy A , Fossati A , Stevenson EJ , Sukerman E , Kim T , Penugonda S , Moreno E , Braberg H , Zhou Y , Metreveli G , Harjai B , Tummino TA , Melnyk JE , Soucheray M , Batra J , Pache L , Martin-Sancho L , Carlson-Stevermer J , Jureka AS , Basler CF , Shokat KM , Shoichet BK , Shriver LP , Johnson JR , Shaw ML , Chanda SK , Roden DM , Carter TC , Kottyan LC , Chisholm RL , Pacheco JA , Smith ME , Schrodi SJ , Albrecht RA , Vignuzzi M , Zuliani-Alvarez L , Swaney DL , Eckhardt M , Wolinsky SM , White KM , Hultquist JF , Kaake RM , García-Sastre A , Krogan NJ . Nat Commun 2023 14 (1) 6030 Influenza A Virus (IAV) is a recurring respiratory virus with limited availability of antiviral therapies. Understanding host proteins essential for IAV infection can identify targets for alternative host-directed therapies (HDTs). Using affinity purification-mass spectrometry and global phosphoproteomic and protein abundance analyses using three IAV strains (pH1N1, H3N2, H5N1) in three human cell types (A549, NHBE, THP-1), we map 332 IAV-human protein-protein interactions and identify 13 IAV-modulated kinases. Whole exome sequencing of patients who experienced severe influenza reveals several genes, including scaffold protein AHNAK, with predicted loss-of-function variants that are also identified in our proteomic analyses. Of our identified host factors, 54 significantly alter IAV infection upon siRNA knockdown, and two factors, AHNAK and coatomer subunit COPB1, are also essential for productive infection by SARS-CoV-2. Finally, 16 compounds targeting our identified host factors suppress IAV replication, with two targeting CDK2 and FLT3 showing pan-antiviral activity across influenza and coronavirus families. This study provides a comprehensive network model of IAV infection in human cells, identifying functional host targets for pan-viral HDT. |
Monkeypox virus-infected individuals mount comparable humoral immune responses as Smallpox-vaccinated individuals
Otter AD , Jones S , Hicks B , Bailey D , Callaby H , Houlihan C , Rampling T , Gordon NC , Selman H , Satheshkumar PS , Townsend M , Mehta R , Pond M , Jones R , Wright D , Oeser C , Tonge S , Linley E , Hemingway G , Coleman T , Millward S , Lloyd A , Damon I , Brooks T , Vipond R , Rowe C , Hallis B . Nat Commun 2023 14 (1) 5948 In early 2022, a cluster of monkeypox virus (MPXV) infection (mpox) cases were identified within the UK with no prior travel history to MPXV-endemic regions. Subsequently, case numbers exceeding 80,000 were reported worldwide, primarily affecting gay, bisexual, and other men who have sex with men (GBMSM). Public health agencies worldwide have offered the IMVANEX Smallpox vaccination to these individuals at high-risk to provide protection and limit the spread of MPXV. We have developed a comprehensive array of ELISAs to study poxvirus-induced antibodies, utilising 24 MPXV and 3 Vaccinia virus (VACV) recombinant antigens. Panels of serum samples from individuals with differing Smallpox-vaccine doses and those with prior MPXV infection were tested on these assays, where we observed that one dose of Smallpox vaccination induces a low number of antibodies to a limited number of MPXV antigens but increasing with further vaccination doses. MPXV infection induced similar antibody responses to diverse poxvirus antigens observed in Smallpox-vaccinated individuals. We identify MPXV A27 as a serological marker of MPXV-infection, whilst MPXV M1 (VACV L1) is likely IMVANEX-specific. Here, we demonstrate analogous humoral antigen recognition between both MPXV-infected or Smallpox-vaccinated individuals, with binding to diverse yet core set of poxvirus antigens, providing opportunities for future vaccine (e.g., mRNA) and therapeutic (e.g., mAbs) design. |
Therapies for people hospitalized with COVID-19 and alignment with national clinical guidelines in a large hospital, Almaty, Kazakhstan, 2020-2021
Gazezova S , Nabirova D , Detmar A , Smagul M , Kasabekova L , Zikriyarova S , Horth R . Front Med (Lausanne) 2023 10 1248959 Background: Clinical practice guidelines were continually changing during the COVID-19 pandemic to reflect the best available evidence for a novel virus. In Kazakhstan, the national clinical guidelines for COVID-19 patient care were regularly modified and it was not known if and to what extent these guidelines were being followed in practice. | | Methods: We conducted a sub-analysis of data collected from an observational study among people hospitalized with COVID-19 in a large infectious disease hospital in Almaty in four cross-sections of increased COVID-19 incidence: T1 (1 June–30 August 2020); T2 (1 October–31 December 2020); T3 (1 April–31 May 2021); and T4 (1 July–26 October 2021). Modifications to the national COVID-19 treatment guidelines were identified and clinical data were abstracted from electronic medical records. We assessed frequency of antibiotic, glucocorticoid, anticoagulant, and antiviral administered in each period and determined if these aligned with national clinical guidelines. We used multivariable logistic regression to compare practices across periods. | | Results: Six modifications were made to national COVID-19 treatment guidelines during this study. Of 1,146 people hospitalized with COVID-19, 14% were in T1, 14% in T2, 22% in T3, and 50% in T4. Anticoagulant treatment was administered to 87% (range: 56%–95%), antibiotic treatment to 60% (range: 58%–64%), glucocorticoid to 55% (range: 43%–64%) and antiviral therapy 15% (range: 7%–22%). Majority of treatments were not aligned with national guidelines, including 98% of anticoagulant use, 95% of antibiotic use, 56% of glucocorticoid use, and 56% of antiviral use. There were no significant changes in practice following changes in guidelines for antibiotic use (64% in T1 to 58% in T2, p = 0.30). There was significant increase in use of anticoagulant (84% in T2 vs. 95% in T3, p < 0.01), glucocorticoid (43% in T2 vs. 64% in T3, p < 0.01), and antiviral treatment (7% in T3 vs. 15% in T4, p < 0.01) after guidelines updates. | | Conclusion: The majority of treatments administered to people hospitalized with COVID-19 in four periods of high incidence in Almaty were not aligned with updated clinical guidelines. Antibiotic misuse was markedly high throughout. Increased awareness and training on clinical practice guidelines as updates are released may help improve adoption of evidence-based practices. |
Implementing quality management strategies improves clinical quality as a voluntary medical male circumcision program in Namibia matures: a process analysis
O'Bryan G , Ensminger A , Billah I , Sithole E , Nghatanga M , Brandt L , Shepard M , Aupokolo M , Mengistu AT , Forster N , Zemburuka B , Mutandi G , Barnhart S , O'Malley G , Feldacker C . BMC Health Serv Res 2023 23 (1) 1044 BACKGROUND: Surgical voluntary medical male circumcision (VMMC) is a safe procedure; however, maintaining quality standards at scale, particularly during scale-up, is a challenge making ongoing quality management (QM) efforts essential. This study describes program quality measured by rates of adverse events (AEs) over four years of VMMC implementation in Namibia, compares AE rates over time, and discusses QM processes that contextualize AE trends and illustrate improvements in quality as the program matured. The International Training and Education Center for Health (I-TECH) assisted the Namibian Ministry of Health and Social Services (MoHSS) in expanding VMMC in three regions among boys and men over 10 years of age between January 2015 and September 2019. METHODS: A comprehensive package of QM strategies was implemented by multi-disciplinary onsite teams with support from national and international technical advisors. Retrospective routine MoHSS data from the VMMC register, client forms, and monthly AE reports were collected during implementation in the three regions to assess the impact of QM interventions on AEs and to calculate the proportion of clients who experienced AEs over time. The proportion of clients who experienced an AE over time was compared using a Cochran-Armitage test for trend. RESULTS: Between January 2015 and September 2019, 40,336 clients underwent VMMC and 593 (1.5%) clients experienced a post-operative AE in the three supported regions. The AE rate was highest in the first quarter of clinical service delivery in each region (January-March 2015 in Oshana and Zambezi, October-December 2017 in //Kharas) but declined over the implementation period as the program matured. This observed trend between program maturity and declining AE rates over time was significant (p < 0.001) when compared using a Cochran-Armitage test for trend. CONCLUSIONS: As the I-TECH-supported VMMC program matured, QM measures were introduced and routinized, and clinical quality improved over time with the rate of AEs decreasing significantly over the implementation period. Applying systematic and continuous QM processes and approaches across the continuum of VMMC services and considering local context can contribute to increased clinical safety. QM measures that are established in more mature program sites can be quickly adopted to respond to quality issues in program expansion sites. |
Does prior exposure to larvicides influence dengue virus susceptibility in Aedes aegypti (Diptera: Culicidae)?
Aldridge RL , Alto BW , Roxanne Connelly C , Okech B , Siegfried B , Eastmond BH , Alomar AA , Linthicum KJ . J Med Entomol 2023 Control of mosquito vector populations is primarily intended to reduce the transmission of pathogens they transmit. Use of chemical controls, such as larvicides, can have unforeseen consequences on adult traits if not applied properly. The consequences of under application of larvicides are little studied, specifically the impacts on pathogen infection and transmission by the vectors that survive exposure to larvicides. We compared vector susceptibility of Aedes aegypti (L.) for dengue virus, serotype 1 (DENV-1) previously exposed as larvae to an LC50 of different classes of insecticides as formulated larvicides. Larval exposure to insect growth regulators (methoprene and pyriproxyfen) significantly increased susceptibility to infection of DENV-1 in Ae. aegypti adults but did not alter disseminated infection or transmission. Larval exposure to temephos, spinosad, and Bti did not increase infection, disseminated infection, or transmission of DENV-1. Our findings describe a previously under observed phenomenon, the latent effects of select larvicides on mosquito vector susceptibility for arboviruses. These data suggest that there are unintended consequences of sublethal exposure to select larvicides that can influence susceptibility of Ae. aegypti to DENV infection, and indicates the need for further investigation of sublethal effects of insecticides on other aspects of mosquito biology, especially those parameters relevant to a mosquitoes ability to transmit arboviruses (life span, biting behavior, extrinsic incubation period). |
Securing the supply of benzathine benzylpenicillin: a global perspective on risks and mitigation strategies to prevent future shortages
Seghers F , Taylor MM , Storey A , Dong J , Wi TC , Wyber R , Ralston K , Nguimfack BD . Int Health 2023 Benzathine benzylpenicillin is a globally indispensable medicine. As a long-lasting injectable penicillin, it serves as the primary treatment for syphilis, group A streptococcal infections, rheumatic fever and rheumatic heart disease. A competitive market and low profit margins, compounded by limited visibility of demand, have resulted in a decreased number of active pharmaceutical ingredient (API) manufacturers. By 2016, only three Chinese API manufacturers remained, continuing to supply to the global market today. Recurring global shortages, a consequence of supply and demand imbalances, indicate underlying market risks. Therefore, the need for mitigation strategies is imperative. |
Is gastroschisis associated with county-level socio-environmental quality during pregnancy?
Krajewski AK , Patel A , Gray CL , Messer LC , Keeler CY , Langlois PH , Reefhuis J , Gilboa SM , Werler MM , Shaw GM , Carmichael SL , Nembhard WN , Insaf TZ , Feldkamp ML , Conway KM , Lobdell DT , Desrosiers TA . Birth Defects Res 2023 115 (18) 1758-1769 BACKGROUND: Gastroschisis prevalence more than doubled between 1995 and 2012. While there are individual-level risk factors (e.g., young maternal age, low body mass index), the impact of environmental exposures is not well understood. METHODS: We used the U.S. Environmental Protection Agency's Environmental Quality Index (EQI) as a county-level estimate of cumulative environmental exposures for five domains (air, water, land, sociodemographic, and built) and overall from 2006 to 2010. Adjusted odds ratios (aOR) and 95% confidence interval (CI) were estimated from logistic regression models between EQI tertiles (better environmental quality (reference); mid; poorer) and gastroschisis in the National Birth Defects Prevention Study from births delivered between 2006 and 2011. Our analysis included 594 cases with gastroschisis and 4105 infants without a birth defect (controls). RESULTS: Overall EQI was modestly associated with gastroschisis (aOR [95% CI]: 1.29 [0.98, 1.71]) for maternal residence in counties with poorer environmental quality, compared to the reference (better environmental quality). Within domain-specific indices, only the sociodemographic domain (aOR: 1.51 [0.99, 2.29]) was modestly associated with gastroschisis, when comparing poorer to better environmental quality. CONCLUSIONS: Future work could elucidate pathway(s) by which components of the sociodemographic domain or possibly related psychosocial factors like chronic stress potentially contribute to risk of gastroschisis. |
U. S. federal perspective on critical research issues in nanoEHS
Carter J , Bjorkland R , Boyes WK , Geraci C , Hackley VA , Howard J , Kennedy A , Linkov I , Matheson J , Mortensen H , Muianga C , Petersen EJ , Savage N , Schulte P , Standridge S , Thomas T , Trump B , Nadadur S . Environ Sci Nano 2023 This article discusses critical issues and opportunities going forward in nanotechnology environmental, health, and safety (nanoEHS) research from the perspective of Federal Government Agency participants in the United States (U.S.) National Nanotechnology Initiative (NNI) interagency Nanotechnology Environmental and Health Implications Working Group (NEHI). NEHI is responsible for coordination of Federal Science Agency nanoEHS research. As participants in NEHI, we examine these critical issues from an integrated, transdisciplinary perspective, noting examples of impactful research efforts that are advancing knowledge in these areas. Major themes identified include detection, measurement, and characterization of real-world nanomaterial exposures, understanding the biological transformation of nanomaterials and their potential (eco) toxicological implications, understanding the landscape of nanotechnology-enabled products in commerce, and advancing the EHS knowledge infrastructure related to nanomaterials and nanotechnology. Significant investments in nanoEHS research over two decades have led to establishment of a unique and diverse multidisciplinary, multisector community of practice. These investments must be leveraged and adapted not only to future nanotechnology, but also to use as a model for accelerating acquisition of safe and reliable risk information for tomorrow's emerging technologies for a more sustainable and competitive world. © 2023 The Royal Society of Chemistry. |
Equipping educators to empower students with a tracking education kit
Curtiss C . J Environ Health 2023 86 (1) 34-36 Recent findings reveal serious recruitment needs within the environmental health workforce. In addition, the public health landscape continues to evolve, with technological improvements in data collection, analysis, visualization, and dissemination. New environmental public health professionals must be equipped with the most current and best resources to help them succeed in their jobs. | | The Environmental Public Health Tracking Program (Tracking Program) within the Centers for Disease Control and Prevention aims to connect environmental and health information into one place, making it accessible to anyone and easy to share. Tools are only effective, however, when they are known and used. Student education on how to use the Tracking Program tools is a step toward empowering and readying the future workforce. This month’s column highlights a new Tracking Education Kit for educators—a collection of instructor lessons featuring PowerPoint slides, an assignment bank, a questions bank, an assignment bank navigator, and an instructor guide. |
Patterns of urinary organophosphate ester metabolite trajectories in children: the HOME Study
Yang W , Braun JM , Vuong AM , Percy Z , Xu Y , Xie C , Deka R , Calafat AM , Ospina M , Yolton K , Cecil KM , Lanphear BP , Chen A . J Expo Sci Environ Epidemiol 2023 BACKGROUND: Organophosphate esters (OPEs) have replaced flame retardant polybrominated diphenyl ethers as flame retardants in consumer products, but few longitudinal studies have characterized childhood OPE exposure. OBJECTIVE: We aimed to examine the exposure pattern of urinary OPE metabolites in children. METHODS: We quantified three urinary OPE metabolites five times in children (1, 2, 3, 5, 8 years) from 312 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study, a prospective pregnancy and birth cohort in Cincinnati, Ohio, USA. We examined the associations of average maternal OPE metabolite concentrations with OPE metabolite concentrations in childhood, characterized childhood OPE trajectories with latent class growth analysis (LCGA), and examined factors related to trajectory membership. RESULTS: Bis(2-chloroethyl) phosphate (BCEP) had the lowest median concentrations over time (0.66-0.97 mg/L) while the median concentrations of bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) increased with age (1.44-3.80 mg/L). The median concentrations of diphenyl phosphate (DPHP) fluctuated between 1.96 and 2.69 mg/L. Intraclass correlation coefficients for urinary metabolites measured at five time points indicated high variability within individuals (0.13-0.24). Average maternal urinary BCEP and BDCIPP were associated with concentrations in early childhood. Maternal education, the birth year of the child, and having a carpet in the main activity room were associated with BCEP and BDCIPP trajectory while none of the factors were associated with DPHP trajectory. SIGNIFICANCE: The trajectory analysis showed different patterns of urinary OPE metabolite concentrations, suggesting the need to collect multiple samples to adequately reflect OPE exposure. IMPACT STATEMENT: In this well-established cohort, we evaluated the patterns of urinary OPE metabolites in children ages 1-8 years. The number of repeated measures over childhood has not been achieved in prior studies. Our results suggested the high variability of urinary OPE metabolites within individuals. Maternal metabolite concentrations during pregnancy were related to child concentrations at ages 1-3 years. BCEP, BDCIPP, and DPHP demonstrated different trajectories in children, which suggests that multiple samples may be required to capture OPE exposure patterns in childhood. |
Analysis of interview breakoff in the Behavioral Risk Factor Surveillance System, 2018 and 2019
Hsia J , Gilbert M , Zhao G , Town M , Inusah S , Garvin W . AJPM Focus 2023 2 (2) 100076 INTRODUCTION: Survey breakoff is an important source of total survey error. Most studies of breakoff have been of web surveys-less is known about telephone surveys. In the past decade, the breakoff rate has increased in the Behavioral Risk Factor Surveillance System, the world's largest annual telephone survey. Analysis of breakoff in Behavioral Risk Factor Surveillance System can improve the quality of Behavioral Risk Factor Surveillance System. It will also provide evidence in research of total survey error on telephone surveys. METHODS: We used data recorded as breakoff in the 2018 and 2019 Behavioral Risk Factor Surveillance System. We converted questions and modules to a time variable and applied Kaplan-Meier method and a proportional hazard model to estimate the conditional and cumulative probabilities of breakoff and study the potential risk factors associated with breakoff. RESULTS: Cumulative probability of breakoffs up to the end of the core questionnaire was 7.03% in 2018 and 9.56% in 2019. The highest conditional probability of breakoffs in the core was 2.85% for the physical activity section. Cumulative probability of breakoffs up to the end of the core was higher among those states that inserted their own questions or optional modules than among those that did not in both years. The median risk ratio of breakoff among all states was 5.70 in 2018 and 3.01 in 2019. Survey breakoff was associated with the length of the questionnaire, the extent of expected recollection, and the location of questions. CONCLUSIONS: Breakoff is not an ignorable component of total survey error and should be considered in Behavioral Risk Factor Surveillance System data analyses when variables have higher breakoff rates. |
Estimating the burden of influenza hospitalizations across multiple seasons using capture-recapture
Howa AC , Zhu Y , Wyatt D , Markus T , Chappell JD , Halasa N , Trabue CH , Olson S , Ferdinands J , Garg S , Schaffner W , Grijalva CG , Talbot HK . J Infect Dis 2023 INTRODUCTION: Influenza remains an important cause of hospitalizations in the United States. Estimating the number of influenza hospitalizations is vital for public health decision making. Combining existing surveillance systems through capture-recapture methods allows for more comprehensive burden estimations. METHODS: Data from independent surveillance systems were combined using capture-recapture methods to estimate influenza hospitalization rates for children and adults in Middle Tennessee during consecutive influenza seasons from 2016-17 through 2019-20. EIP identified cases through surveillance of laboratory results for hospitalized children and adults. HAIVEN and NVSN recruited hospitalized patients with respiratory symptoms or fever. Population-based influenza rates and the proportion of cases detected by each surveillance system were calculated. RESULTS: Estimated overall influenza hospitalization rates ranged from 23 influenza-related hospitalizations per 10,000 persons in 2016-17 to 40 per 10,000 persons in 2017-18. Adults age ≥65 years had the highest hospitalization rates across seasons and experienced a rate of 170 hospitalizations per 10,000 persons during the 2017-18 season. EIP consistently identified a higher proportion of influenza cases for adults and children compared with HAIVEN and NVSN, respectively. CONCLUSION: Current surveillance systems underestimate the influenza burden. Capture-recapture provides an alternative approach to use data from independent surveillance systems and complement population-based burden estimates. |
Quickstats: Rate of emergency department visits*(,)(†) for substance use disorders(§) among adults aged ≥18 years, by age group - National Hospital Ambulatory Medical Care Survey, United States, 2018-2019 and 2020-2021
O’Jiaku-Okorie A , Yin X , Lucas C . MMWR Morb Mortal Wkly Rep 2023 72 (39) 1073 The rate of emergency department visits with a primary diagnosis of a substance use disorder among adults increased from 74.4 per 10,000 population during 2018–2019 to 103.8 during 2020–2021. Between these two periods, this rate increased 42% among patients aged 18–34 years (from 86.1 to 122.5) and 38% among patients aged ≥35 years (from 69.5 to 96.1). During both 2018–2019 and 2020–2021, adults aged 18–34 years were more likely to visit an emergency department for substance abuse, use, or dependence than were those aged ≥35 years. |
Strengthening surveillance, disease detection, and outbreak response through Guinea-Bissau's Frontline Field Epidemiology Training Program: a cross-sectional descriptive study
Camará M , da Costa FP , Chambe G , Betunde A , Cardoso P , Johnson K , Rullan-Oliver P , Lopez A . Pan Afr Med J 2023 45 133 INTRODUCTION: the goal of the Field Epidemiology Training Program (FETP) - Frontline is to strengthen the country's surveillance capacity at the district level to prepare and respond to health emergencies, including outbreaks, by training a skilled frontline public health workforce. We describe the FETP - Frontline program, including implementation, structure, achievements, impact, and its role in improving the epidemiological workforce capacity of Guinea-Bissau. METHODS: this cross-sectional descriptive study uses 2015-2019 program data collected through record reviews and historical narratives from FETP students and graduates. We generated descriptive summary statistics using the Guinea-Bissau's FETP-Frontline program database, student assignments, and investigation reports, after reviewing the FETP standardized curriculum and program guidelines. RESULTS: since its inception in 2016, FETP Frontline has implemented 14 cohorts and trained 198 frontline surveillance officers. Program participants improved surveillance data quality, investigated 51 outbreaks at national and regional levels, and contributed to disease research and surveillance in 227 separate field investigations. Participants frequently responded to priority health emergencies, including clusters or outbreaks of Zika, microencephalies, dengue, yellow fever, anthrax, malaria, and tuberculosis. CONCLUSION: Guinea-Bissau's FETP - Frontline program provides a practical example of an effective strategy to strengthen health systems through a well-prepared workforce trained to quickly detect and respond to health threats. |
Establishing vaccine pregnancy registries and active surveillance studies in low-and middle-income countries: Experience from an observational cohort surveillance project in The Gambia
Kochhar S , Okomo U , Nkereuwem O , Shaum A , Gidudu JF , Bittaye M , Fofana S , Marena M , Kaira MJ , Kampmann B , Longley AT . Vaccine 2023 41 (44) 6453-6455 Despite significant advances in child survival, infectious diseases continue to be among the leading causes of neonatal deaths [1]. Maternal immunization is a well-recognized public health intervention to reduce vaccine-preventable disease-related morbidity and mortality in the pregnant woman, her foetus, and infant from tetanus, pertussis, seasonal influenza, and COVID-19 [2]. The development of new maternal vaccines against respiratory syncytial virus (RSV) and group B streptococcus (GBS) may significantly decrease the morbidity and mortality from these diseases in neonates and infants [2], with the U.S. Food and Drug Administration (FDA) approval for licensure of an RSV vaccine to be administered in pregnancy occurring in August 2023 [3]. | | Ongoing safety assessment of novel vaccines administered during pregnancy requires well-functioning passive and active surveillance systems to collect and assess adverse maternal and neonatal outcomes [4]. In high-income countries (HICs), regulatory authorities, such as the European Medicines Agency (EMA) and the U.S. FDA, require extensive post-authorization safety monitoring activities for products used during pregnancy, including active surveillance for safety-related events through pregnancy registries and observational cohort studies [4], [5], [6]. However, safety surveillance for vaccines used in pregnancy in many low- and middle-income countries (LMICs) currently relies on passive surveillance systems whose output cannot be interpreted appropriately due to lack of information on background rates of adverse events in pregnancy in general and lack of data on the number of pregnant women vaccinated as the relevant specific comparator [4], [5], [6]. |
Draft genome sequences of a historical collection of Listeria monocytogenes from humans and other sources, 1926-1964
Brown P , Murray RGE , Galsworthy S , Ivanova M , Leekitcharoenphon P , Ward T , Kucerova Z , Chen Y , Elhanafi D , Siletzky R , Kathariou S . Microbiol Resour Announc 2023 12 (10) e0062523 Listeria monocytogenes can persistently contaminate food processing environments and tolerate sanitizers. Most sequenced strains are from clinical and environmental sources in the contemporary era, with relatively few prior to extensive food processing and sanitizer use. We report the genome sequences of a diverse panel of 83 strains from 1926 to 1964. |
Development of reverse genetic tools to study Chapare and Machupo viruses
Jain S , Shrivastava-Ranjan P , Flint M , Montgomery JM , Spiropoulou CF , Albariño CG . Virology 2023 588 109888 Arenaviruses are highly pathogenic viruses that pose a serious public health threat. Chapare virus (CHAV) and Machupo virus (MACV), two New World arenaviruses, cause hemorrhagic fevers with case fatality rates of up to 45%. Research on therapeutic drug targets and vaccines for these viruses is limited because biosafety level 4 containment is required for handling them. In this study, we developed reverse genetics systems, including minigenomes and recombinant viruses, that will facilitate the study of these pathogens. The minigenome system is based on the S segment of CHAV or MACV genomes expressing the fluorescent reporter gene ZsGreen (ZsG). We also generated recombinant CHAV and MACV with and without the ZsG reporter gene. As a proof-of-concept study, we used both minigenomes and recombinant viruses to test the inhibitory effects of previously reported antiviral compounds. The new reverse genetics system described here will facilitate future therapeutic studies for these two life-threatening arenaviruses. |
Developing One Health surveillance systems
Hayman DTS , Adisasmito WB , Almuhairi S , Behravesh CB , Bilivogui P , Bukachi SA , Casas N , Becerra NC , Charron DF , Chaudhary A , Ciacci Zanella JR , Cunningham AA , Dar O , Debnath N , Dungu B , Farag E , Gao GF , Khaitsa M , Machalaba C , Mackenzie JS , Markotter W , Mettenleiter TC , Morand S , Smolenskiy V , Zhou L , Koopmans M . One Health 2023 17 100617 The health of humans, domestic and wild animals, plants, and the environment are inter-dependent. Global anthropogenic change is a key driver of disease emergence and spread and leads to biodiversity loss and ecosystem function degradation, which are themselves drivers of disease emergence. Pathogen spill-over events and subsequent disease outbreaks, including pandemics, in humans, animals and plants may arise when factors driving disease emergence and spread converge. One Health is an integrated approach that aims to sustainably balance and optimize human, animal and ecosystem health. Conventional disease surveillance has been siloed by sectors, with separate systems addressing the health of humans, domestic animals, cultivated plants, wildlife and the environment. One Health surveillance should include integrated surveillance for known and unknown pathogens, but combined with this more traditional disease-based surveillance, it also must include surveillance of drivers of disease emergence to improve prevention and mitigation of spill-over events. Here, we outline such an approach, including the characteristics and components required to overcome barriers and to optimize an integrated One Health surveillance system. © 2023 The Authors |
Associations between sexual behavior stigma and HIV risk behaviors, testing, treatment, and infection among men who have sex with men in Ukraine
Alvey B , Stone J , Salyuk T , Barzilay EJ , Doan I , Vickerman P , Trickey A . AIDS Behav 2023 Stigma toward same-sex behaviors may be a structural driver of HIV epidemics among men who have sex with men (MSM) in Eastern Europe and has been linked to adverse HIV-outcomes elsewhere. We explored associations between sexual behavior stigma with HIV risk behaviors, testing, treatment, and infection. From November 2017 to February 2018, MSM across 27 Ukrainian cities were recruited to cross-sectional surveys using respondent driven sampling. Eligible participants were cisgender males aged ≥ 14 years residing in participating cities that reported ≥ 1 sexual contact with another man in the prior 6 months. Participants self-reported experience of stigma (ever) and various HIV-outcomes and were tested for HIV antibodies. Regression models were used to explore associations between three sexual behavior stigma variables with demographic and HIV-related variables. Of 5812 recruited cisgender MSM, 5544 (95.4%) were included. 1663 (30.0%) MSM reported having experienced stigma due to being MSM from family and friends, 698 (12.6%) reported anticipated healthcare stigma, and 1805 (32.6%) reported general public/social stigma due to being MSM (enacted). All forms of stigma were associated with heightened HIV risk behaviors; those experiencing stigma (vs not) had more anal sex partners in the prior month and were less likely to have used condoms during their last anal intercourse. Stigma was not associated with HIV infection, testing, or treatment variables. A sizeable proportion of Ukrainian MSM reported ever experiencing stigma due to being MSM. MSM that had experienced stigma had higher odds of HIV sexual risk behaviors. Further study using longitudinal designs is required to determine causality. |
Engagement with traditional healers for early detection of plague in Uganda
Apangu T , Candini G , Abaru J , Candia B , Okoth FJ , Atiku LA , Griffith KS , Hayden MH , Zielinski-Gutiérrez E , Schwartz AM , McCormick DW , Mead PS , Kugeler KJ . Am J Trop Med Hyg 2023 109 (5) 1129-1136 In rural Uganda, many people who are ill consult traditional healers prior to visiting the formal healthcare system. Traditional healers provide supportive care for common illnesses, but their care may delay diagnosis and management of illnesses that can increase morbidity and mortality, hinder early detection of epidemic-prone diseases, and increase occupational risk to traditional healers. We conducted open-ended, semi-structured interviews with a convenience sample of 11 traditional healers in the plague-endemic West Nile region of northwestern Uganda to assess their knowledge, practices, and attitudes regarding plague and the local healthcare system. Most were generally knowledgeable about plague transmission and its clinical presentation and expressed willingness to refer patients to the formal healthcare system. We initiated a public health outreach program to further improve engagement between traditional healers and local health centers to foster trust in the formal healthcare system and improve early identification and referral of patients with plaguelike symptoms, which can reflect numerous other infectious and noninfectious conditions. During 2010-2019, 65 traditional healers were involved in the outreach program; 52 traditional healers referred 788 patients to area health centers. The diagnosis was available for 775 patients; malaria (37%) and respiratory tract infections (23%) were the most common diagnoses. One patient had confirmed bubonic plague. Outreach to improve communication and trust between traditional healers and local healthcare settings may result in improved early case detection and intervention not only for plague but also for other serious conditions. |
Tetanus, diphtheria, and acellular pertussis vaccination coverage among publicly insured pregnant women, U.S., 2016-2019
Isenhour CJ , Skoff TH , Lindley MC , Zhou F , Hariri S . AJPM Focus 2023 2 (1) 100060 INTRODUCTION: Vaccination with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine during pregnancy is highly effective against Bordetella pertussis in young infants. We aimed to evaluate the uptake of maternal tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccination during the recommended gestation period of 27 through 36 weeks among women enrolled in a public medical insurance plan in the U.S. METHODS: In this analysis using Centers for Medicare and Medicaid Services insurance claims data, we identified women aged 15 through 49 years who delivered a live-born infant from 2016 through 2019. We identified claims for tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccination to calculate the proportion of women who were vaccinated during Weeks 27 through 36 of gestation in each calendar year. We also assessed the average annual maternal tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis coverage by age group, race and ethnicity, U.S. Census region of residence, and plan type. Data were analyzed in 2021. RESULTS: Among 4,318,823 deliveries, the 4-year national average for tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccination was 26%, improving from 22% in 2016 to 31% in 2019 (p<0.001). Within subgroups, the lowest 4-year average coverage was among women aged 15 through 18 years (22%); Black, non-Hispanic (23%) and Hispanic women (24%); those residing in the South (18%); those enrolled in a Children's Health Insurance Program plan (22%); and those covered by a fee-for-service plan (19%). Coverage increased across all subgroups from 2016 through 2019. CONCLUSIONS: Although maternal tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis coverage among publicly insured women in the U.S. increased from 2016 through 2019, it remained considerably lower than estimated national coverage, with notable differences by race and ethnicity. |
Incremental burden on health-related quality of life, health service utilization and direct medical expenditures associated with cognitive impairment among non-institutionalized people with diabetes aged 65 years and older
Guan D , Lewis MO , Li P , Zhang Y , Zhang P , Tang S , Brown J , Guo J , Zhang Y , Shao H . Diabetes Obes Metab 2023 26 (1) 275-282 AIMS: To quantify the incremental health and economic burden associated with cognitive impairment (CI) among non-institutionalized people with diabetes ≥65 years in the United States. MATERIALS AND METHODS: Using 2016-2019 Medical Expenditure Panel Surveys data, we identified participants ≥65 years with diabetes. We used propensity score weighting to quantify the CI-associated incremental burden on health-related quality of life measured by the 12-item Short Form Survey (SF-12), including the mental component summary score, physical component summary score and health utility. We also compared the annual health service utilization and expenditures on ambulatory visits, prescriptions, home care, emergency room (ER), hospitalizations and total annual direct medical expenditures. RESULTS: We included 5094 adults aged ≥65 with diabetes, of whom 804 had CI. After propensity score weighting, CI was associated with a lower mental component summary score (-8.4, p < .001), physical component summary score (-5.2, p < .001) and health utility (-0.12, p < .001). The CI group had more ambulatory visits (+4.4, p = .004) and prescriptions (+9.9, p < .001), with higher probabilities of having home care (+11.3%, p < .001) and ER visits (+8.2%, p = .001). People with CI spent $5441 (p < .001) more annually, $2039 (p = .002) more on prescriptions, $2695 (p < .001) more on home care and $118 (p < .001) more on ER visits. There is no statistically significant difference in the utilization and expenditure of hospitalizations. CONCLUSION: CI was associated with worse health-related quality of life, higher health service utilization and expenditures. Our findings can be used to monitor the health and economic burden of CI in non-institutionalized older persons with diabetes. |
Comparison of demographic characteristics and social determinants of health between adults with diagnosed HIV and all adults in the US
Dasgupta S , McManus T , Tie Y , Lin CY , Yuan X , Sharpe JD , Fletcher KM , Beer L . AJPM Focus 2023 2 (3) 100115 INTRODUCTION: Quantifying disparities in social determinants of health between people with HIV and the total population could help address health inequities, and ensure health and well-being among people with HIV in the U.S., but estimates are lacking. METHODS: Several representative data sources were used to assess differences in social determinants of health between adults with diagnosed HIV (Centers for Disease Control and Prevention Medical Monitoring Project) and the total adult population (U.S. Census Bureau's decennial census, American Community Survey, Household Pulse Survey, the Current Population Survey Annual Social and Economic Supplements; the Department of Housing and Urban Development's point-in-time estimates of homelessness; and the Bureau of Justice Statistics). The differences were quantified using standardized prevalence differences and standardized prevalence ratios, adjusting for differences in age, race/ethnicity, and birth sex between people with HIV and the total U.S. population. RESULTS: Overall, 35.6% of people with HIV were living in a household with an income at or below the federal poverty level, and 8.1% recently experienced homelessness. Additionally, 42.9% had Medicaid and 27.6% had Medicare; 39.7% were living with a disability. Over half (52.3%) lived in large central metropolitan counties and 20.6% spoke English less than very well based on survey responses. After adjustment, poverty (standardized prevalence difference=25.1%, standardized prevalence ratio=3.5), homelessness (standardized prevalence difference=8.5%, standardized prevalence ratio=43.5), coverage through Medicaid (standardized prevalence difference=29.5%, standardized prevalence ratio=3.0) or Medicare (standardized prevalence difference=7.8%), and disability (standardized prevalence difference=30.3%, standardized prevalence ratio=3.0) were higher among people with HIV than the total U.S. population. The percentage of people with HIV living in large central metropolitan counties (standardized prevalence difference=13.4%) or who were recently incarcerated (standardized prevalence ratio=5.9) was higher than the total U.S. population. CONCLUSIONS: These findings provide a baseline for assessing national-level disparities in social determinants of health between people with HIV and the total U.S. population, and it can be used as a model to assess local disparities. Addressing social determinants of health is essential for achieving health equity, requiring a multipronged approach with interventions at the provider, facility, and policy levels. |
Social determinants of health-related Z codes and health care among patients with hypertension
Lee JS , MacLeod KE , Kuklina EV , Tong X , Jackson SL . AJPM Focus 2023 2 (2) 100089 INTRODUCTION: Tracking social needs can provide information on barriers to controlling hypertension and the need for wraparound services. No recent studies have examined ICD-10-CM social determinants of health-related Z codes (Z55-Z65) to indicate social needs with a focus on patients with hypertension. METHODS: Three cohorts were identified with a diagnosis of hypertension during 2016-2017 and continuously enrolled in fee-for-service insurance through June 2021: (1) commercial, age 18-64 years (n=1,024,012); (2) private insurance to supplement Medicare (Medicare Supplement), age ≥65 years (n=296,340); and (3) Medicaid, age ≥18 years (n=146,484). Both the proportion of patients and healthcare encounters or visits with social determinants of health-related Z code were summarized annually. Patient and visit characteristics were summarized for 2019. RESULTS: In 2020, the highest annual documentation of social determinants of health-related Z codes was among Medicaid beneficiaries (3.02%, 0.46% commercial, 0.42% Medicare Supplement); documentation was higher among inpatient than among outpatient visits for all insurance types. Z63 (related to primary support group) was more common among commercial and Medicare Supplement beneficiaries, and Z59 (housing and economic circumstances) was more common among Medicaid beneficiaries. The 2019 total unadjusted medical expenditures were 1.85, 1.78, and 1.61 times higher for those with social determinants of health-related Z code than for those without commercial, Medicare Supplement, and Medicaid, respectively. Patients with social determinants of health-related Z code also had higher proportions of diagnosed chronic conditions. Among Medicaid beneficiaries, differences in the presence of social determinants of health-related Z code by race or ethnicity were observed. CONCLUSIONS: Although currently underreported, social determinants of health-related Z codes provide an opportunity to integrate social and medical data and may help decision makers understand the need for additional services among individuals with hypertension. |
Rural and urban differences in hypertension management through telehealth before and during the COVID-19 pandemic among commercially insured patients
Lee JS , Bhatt A , Jackson SL , Pollack LM , Omeaku N , Lowe K , Wilson C , Luo F , Roy K . Am J Hypertens 2023 BACKGROUND: The COVID-19 pandemic prompted a rapid increase in telehealth use. However, limited evidence exists on how rural and urban residents used telehealth and in-person outpatient services to manage hypertension during the pandemic. METHODS: This longitudinal study analyzed 701,410 US adults (18-64 years) in the MarketScan Commercial Claims Database, who were continuously enrolled from January 2017 through March 2022. We documented monthly numbers of hypertension-related telehealth and in-person outpatient visits (per 100 individuals), and the proportion of telehealth visits among all hypertension-related outpatient visits, from January 2019 through March 2022. We used Welch's 2-tail t-test to differentiate monthly estimates by rural-urban status and month-to-month changes. RESULTS: From February through April 2020, the monthly number of hypertension-related telehealth visits per 100 individuals increased from 0.01 to 6.05 (P<0.001) for urban residents and from 0.01 to 4.56 (P<0.001) for rural residents. Hypertension-related in-person visits decreased from 20.12 to 8.30 (P<0.001) for urban residents and from 20.48 to 10.15 (P<0.001) for rural residents. The proportion of hypertension-related telehealth visits increased from 0.04% to 42.15% (P<0.001) for urban residents and from 0.06% to 30.98% (P<0.001) for rural residents. From March 2020 to March 2022, the monthly average of the proportions of hypertension-related telehealth visits was higher for urban residents than for rural residents (10.19% vs. 6.96%; P<0.001). CONCLUSIONS: Data show that rural residents were less likely to use telehealth for hypertension management. Understanding trends in hypertension-related telehealth utilization can highlight disparities in the sustained use of telehealth to advance accessible health care. |
State insurance mandates and racial and ethnic inequities in assisted reproductive technology utilization
Korkidakis A , DeSantis CE , Kissin DM , Hacker MR , Koniares K , Yartel A , Adashi EY , Penzias AS . Fertil Steril 2023 121 (1) 54-62 OBJECTIVE: To examine whether the (1) scope of state-mandated insurance coverage for assisted reproductive technology (ART), and (2) proportion of the population eligible for this coverage, are associated with reductions in racial/ethnic inequities in ART utilization. DESIGN: National cross-sectional, ecologic study. SUBJECTS: We employed estimates from the U.S. Census Bureau of all women 20-44 years of age living in the U.S. in 2018. The number of women who initiated an ART cycle during that year that was reported to the U.S. Centers for Disease Control and Prevention (CDC) was obtained from the National ART Surveillance System (NASS). EXPOSURE: State mandates were classified by scope of required coverage for fertility services: Comprehensive, Limited, and No Mandate. MAIN OUTCOMES MEASURES: Race and ethnic-specific ART utilization rates, defined as number of women undergoing ≥1 ART cycles per 10,000 women, were the primary outcome. As state mandates do not apply to all insurance plans, Comprehensive Mandate utilization rates were recalculated using denominators corrected for the estimated proportions of populations eligible for coverage. RESULTS: Across all mandate categories, Non-Hispanic (NH) Asian and NH White populations had the highest ART utilization rates, whereas the lowest rates were among Hispanic, NH Black, and NH Other/Multiple Races populations. As compared to the NH Asian reference group, the NH Black population had smaller inequities in the Comprehensive Mandate group than the No Mandate group (Rate Ratio [RR 0.33 [0.28-0.38] versus RR 0.23 [0.22-0.24]). Using the Comprehensive Mandate group for each race/ethnicity as reference, the NH Black and NH Other/Multiple Races populations had the largest relative differences in utilization between the No Mandate and Comprehensive Mandate groups (RR 0.39 [0.37-0.41] and 0.33 [0.28-0.38], respectively). Within the Comprehensive Mandate group, the disparities in the Hispanic and NH Black populations moved towards the null after correcting for state-mandated insurance eligibility. CONCLUSIONS: Racial/ethnic inequities in ART utilization were reduced in states with comprehensive infertility coverage mandates. Inequities were further attenuated after correcting for mandate eligibility. Mandates alone, however, were not sufficient to eliminate disparities. These findings can inform future strategies aimed at improving ART access under a social justice framework. |
Inequities in COVID-19 vaccination coverage among pregnant persons, by disaggregated race and ethnicity - Massachusetts, May 2021-October 2022
Shephard HM , Manning SE , Nestoridi E , Darling AM , Brown CM , Hatch M , Ahnger-Pier K , Pagnano S , Mather D , Yazdy MM . MMWR Morb Mortal Wkly Rep 2023 72 (39) 1052-1056 National estimates suggest that COVID-19 vaccination coverage among pregnant persons is lower among those identifying as Hispanic or Latino (Hispanic) and non-Hispanic Black or African American. When examining COVID-19 vaccination coverage during pregnancy by race and ethnicity, however, data are typically limited to large, aggregate categories that might obscure within-group inequities. To address this, Massachusetts examined COVID-19 vaccination coverage among pregnant persons by combinations of 12 racial and 34 ethnic groupings. Among 102,275 persons with a live birth in Massachusetts during May 1, 2021-October 31, 2022, receipt of ≥1 dose of a COVID-19 vaccine before or during pregnancy was 41.6% overall and was highest among persons who identified as Asian (55.0%) and lowest among those who identified as Hispanic (26.7%). However, within all broad racial and ethnic groupings, disparities in COVID-19 vaccination coverage were identified when the data were disaggregated into more granular categories; for example, COVID-19 vaccination coverage ranged from 10.8%-61.1% among pregnant persons who identified as Hispanic. Disaggregated analyses reveal diverse experiences within broad racial and ethnic groupings. This information can be used to guide outreach to pregnant persons in communities with lower rates of COVID-19 vaccination coverage during pregnancy. |
Examining bias from differential depletion of susceptibles in vaccine effectiveness estimates in settings of waning
Kahn R , Feikin DR , Wiegand RE , Lipsitch M . Am J Epidemiol 2023 193 (1) 232-234 Waning of the effectiveness of COVID-19 vaccines against SARS-CoV-2 infection and | symptomatic disease has been observed in many settings (1-3). The documented ability of | booster doses to restore vaccine effectiveness (VE) to higher levels suggests at least some of | the observed waning is real (3-4). However, differential depletion of susceptibles through | infection-induced immunity related to individuals’ vaccination status can create bias that induces | spurious waning, complicating interpretation of vaccine effectiveness estimates (5-8). | In previous work (5), we showed that spurious waning was detectable but modest in settings | without true waning where true VE was very high (0.95) and constant over time (i.e., no true | waning), and more notable in settings where true VE was lower (0.70) and constant over time. | This led us to the natural question: Is spurious waning modest or more notable in situations | where true effectiveness wanes over time? Here we examine bias that can arise in settings in | which true waning occurs. |
Persistence of immunity following a single dose of inactivated poliovirus vaccine: a phase 4, open label, non-randomised clinical trial
Sharma AK , Verma H , Estivariz CF , Bajracharaya L , Rai G , Shah G , Sherchand J , Jones KAV , Mainou BA , Chavan S , Jeyaseelan V , Sutter RW , Shrestha LP . Lancet Microbe 2023 4 (11) e923-e930 BACKGROUND: The polio eradication endgame required the withdrawal of Sabin type 2 from the oral poliovirus vaccine and introduction of one or more dose of inactivated poliovirus vaccine (IPV) into routine immunisation schedules. However, the duration of single-dose IPV immunity is unknown. We aimed to address this deficiency. METHODS: In this phase 4, open-label, non-randomised clinical trial, we assessed single-dose IPV immunity. Two groups of infants or children were screened: the first group had previously received IPV at 14 weeks of age or older (previous IPV group; age >2 years); the second had not previously received IPV (no previous IPV group; age 7-12 months). At enrolment, all participants received an IPV dose. Children in the no previous IPV group received a second IPV dose at day 30. Blood was collected three times in each group: on days 0, 7, and 30 in the previous IPV group and on days 0, 30, and 37 in the no previous IPV group. Poliovirus antibody was measured by microneutralisation assay. Immunity was defined as the presence of a detectable antibody or a rapid anamnestic response (ie, priming). We used the χ(2) to compare proportions and the Mann-Whitney U test to assess continuous variables. To assess safety, vaccinees were observed for 30 min, caregivers for each participating child reported adverse events after each follow-up visit and were questioned during each follow-up visit regarding any adverse events during the intervening period. Adverse events were recorded and graded according to the severity of clinical symptoms. The study is registered with ClinicalTrials.gov, NCT03723837. FINDINGS: From Nov 18, 2018, to July 31, 2019, 502 participants enrolled in the study, 458 (255 [65%] boys and 203 [44%] girls) were included in the per protocol analysis: 234 (93%) in the previous IPV group and 224 (90%) in the no previous IPV group. In the previous IPV group, 28 months after one IPV dose 233 (>99%) of 234 children had persistence of poliovirus type 2 immunity (100 [43%] of 234 children were seropositive; 133 [99%] of 134 were seronegative and primed). In the no previous IPV group, 30 days after one IPV dose all 224 (100%) children who were type 2 poliovirus naive had seroconverted (223 [>99%] children) or were primed (one [<1%]). No adverse events were deemed attributable to study interventions. INTERPRETATION: A single IPV dose administered at 14 weeks of age or older is highly immunogenic and induces nearly universal type 2 immunity (seroconversion and priming), with immunity persisting for at least 28 months. The polio eradication initiative should prioritise first IPV dose administration to mitigate the paralytic burden caused by poliovirus type 2. FUNDING: WHO and Rotary International. |
COVID-19 vaccination recommendations and practices for women of reproductive age by health care providers - Fall DocStyles Survey, United States, 2022
Meghani M , Salvesen Von Essen B , Zapata LB , Polen K , Galang RR , Razzaghi H , Meaney-Delman D , Waits G , Ellington S . MMWR Morb Mortal Wkly Rep 2023 72 (39) 1045-1051 Pregnant and postpartum women are at increased risk for severe illness from COVID-19 compared with nonpregnant women of reproductive age. COVID-19 vaccination is recommended for all persons ≥6 months of age. Health care providers (HCPs) have a unique opportunity to counsel women of reproductive age, including pregnant and postpartum patients, about the importance of receiving COVID-19, influenza, and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines. Data from the Fall 2022 DocStyles survey were analyzed to examine the prevalence of COVID-19 vaccination attitudes and practices among HCPs caring for women of reproductive age, and to determine whether providers recommended and offered or administered COVID-19 vaccines to women of reproductive age, including their pregnant patients. Overall, 82.9% of providers reported recommending COVID-19 vaccination to women of reproductive age, and 54.7% offered or administered the vaccine in their practice. Among HCPs who cared for pregnant patients, obstetrician-gynecologists were more likely to recommend COVID-19 vaccination to pregnant patients (94.2%) than were family practitioners or internists (82.1%) (adjusted prevalence ratio [aPR] = 1.1). HCPs were more likely to offer or administer COVID-19 vaccination on-site to pregnant patients if they also offered or administered influenza (aPR = 5.5) and Tdap vaccines (aPR = 2.3). Encouraging HCPs to recommend, offer, and administer the COVID-19 vaccines along with influenza or Tdap vaccines might help reinforce vaccine confidence and increase coverage among women of reproductive age, including pregnant women. |
Influenza, tdap, and COVID-19 vaccination coverage and hesitancy among pregnant women - United States, April 2023
Razzaghi H , Kahn KE , Calhoun K , Garacci E , Skoff TH , Ellington SR , Jatlaoui TC , Black CL . MMWR Morb Mortal Wkly Rep 2023 72 (39) 1065-1071 Influenza, tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap), and COVID-19 vaccines can reduce the risk for influenza, pertussis, and COVID-19 among pregnant women and their infants. To assess influenza, Tdap, and COVID-19 vaccination coverage among women pregnant during the 2022-23 influenza season, CDC analyzed data from an Internet panel survey conducted during March 28-April 16, 2023. Among 1,814 survey respondents who were pregnant at any time during October 2022-January 2023, 47.2% reported receiving influenza vaccine before or during their pregnancy. Among 776 respondents with a live birth by their survey date, 55.4% reported receiving Tdap vaccine during pregnancy. Among 1,252 women pregnant at the time of the survey, 27.3% reported receipt of a COVID-19 bivalent booster dose before or during the current pregnancy. Data from the same questions included in surveys conducted during influenza seasons 2019-20 through 2022-23 show that the proportion of pregnant women who reported being very hesitant about influenza and Tdap vaccinations during pregnancy increased from 2019-20 to 2022-23. Pregnant women who received a provider recommendation for vaccination were less hesitant about influenza and Tdap vaccines. Promotion of efforts to improve vaccination coverage among pregnant women, such as provider recommendation for vaccination and informative conversations with patients to address vaccine hesitancy, might reduce vaccine hesitancy and increase coverage with these important vaccines to protect mothers and their infants against severe respiratory diseases. |
Consensus pregnancy-related criteria for suicide and unintentional overdoses using a Delphi process
Smid MC , Vaughn P , Nowicki CC , Goodman DA , Zaharatos J , Campbell KA . Arch Womens Ment Health 2023 Suicide and unintentional overdose are leading manners of preventable death during and within a year of pregnancy. Recently, the Utah Maternal Mortality Review Committee (MMRC) developed 10 criteria to guide pregnancy-related classification of these deaths. Our objective was to (1) evaluate if consensus could be reached across experts in maternal mortality review when applying criteria to the determination of pregnancy-relatedness in mock MMRC case evaluation and (2) assess how additional case information shifted participants' determination of pregnancy-relatedness in these mock cases. We used a modified Delphi process to evaluate criteria for pregnancy-related suicides and unintentional overdose. The study team developed base case scenarios to reflect the 10 proposed criteria. Base scenarios varied in timing of death (prenatal or delivery, early postpartum (<6 months), late postpartum (6-12 months)) and level of additional information available (e.g., informant interviews, social media posts). Consensus in favor of a criterion was met when ≥75% of participants identified a case as pregnancy-related in at least 1 scenario. Fifty-eight participants, representing 48 MMRCs, reviewed scenarios. Of 10 proposed criteria, 8 reached consensus. Overall, participants classified 19.4% of base case scenarios as pregnancy-related, which increased to 56.8% with additional information. Pregnancy-related classification changed across timing of death and with availability of additional information (prenatal or delivery 27.7% versus 84.6%; early postpartum 30.0% versus 58.3%; late postpartum 0.0% versus 25.0%, respectively). We identified consensus supporting the application of 8 standardized criteria in MMRC determinations of pregnancy-relatedness among suicide and unintentional overdose deaths. |
Associations between verbal and physical abuse in the home and mental health indicators among heterosexual and lesbian, gay, bisexual, and questioning high school students in the US-Adolescent Behaviors and Experiences Survey, 2021
Ethier KA , Jones SE , Shear EK , Dittus PJ . J Adolesc Health 2023 74 (1) 198-201 PURPOSE: A number of factors may contribute to disparities in mental health and suicidality for lesbian, gay, bisexual, and questioning (LGBQ) students, including parental abuse. METHODS: The Centers for Disease Control and Prevention's (CDC) Adolescent Behaviors and Experiences Survey included a nationally representative sample of US high school students during the COVID-19 pandemic. The current analyses examined experiences of verbal and physical abuse in the home with mental health and suicidality among LGBQ students compared to heterosexual students. RESULTS: The relationship between abuse and mental health and suicidality was significant for all students; however, LGBQ students experienced substantially more abuse and had significantly poorer mental health and greater suicidality than heterosexual students. DISCUSSION: Experiencing verbal or physical abuse in the home is strongly associated with poor mental health and suicidality among youth, regardless of sexual identity; however, among LGBQ students who experienced abuse, the prevalence of poor mental health and suicidality reached crisis levels. |
Serologic immunity to tetanus in the United States, National Health and Nutrition Examination Survey, 2015-2016
Bampoe VD , Brown N , Deng L , Schiffer J , Jia LT , Epperson M , Gorantla Y , Park SH , Ao J , Acosta AM , Hariri S . Clin Infect Dis 2023 BACKGROUND: Tetanus, a life-threatening infection, has become rare in the United States since introduction of tetanus toxoid-containing vaccines (TTCVs), recommended as a childhood series followed by decennial boosters beginning at age 11-12 years; vaccination uptake is high in children but suboptimal in adults. The objective of this study was to estimate the prevalence of sero-immunity to tetanus among persons aged ≥6 years in the United States and to identify factors associated with tetanus sero-immunity. Understanding population protection against tetanus informs current and future vaccine recommendations. METHODS: Anti-tetanus toxoid antibody concentrations were measured for participants of the 2015-2016 National Health and Nutrition Examination Survey (NHANES) aged ≥6 years for whom surplus serum samples were available using a microsphere-based multiplex antibody capture assay. Prevalence of sero-immunity, defined as ≥0.10 IU/mL, was estimated overall and by demographic characteristics. Factors associated with tetanus sero-immunity were examined using multivariable regression. RESULTS: Overall, 93.8% of the U.S. population aged ≥6 years had sero-protection against tetanus. Prevalence of sero-immunity was above 90% across racial/ethnic categories, sex, and poverty levels. By age, ≥90% had protective sero-immunity through age 69 years but prevalence of sero-immunity declined thereafter, with 75.8% of those aged ≥80 years having protective sero-immunity. Older age (adjusted prevalence ratio (aPR): 0.89, 95% CI: 0.85-0.92) and being born outside the United States (aPR: 0.96, 95% CI: 0.93-0.98) were significantly associated with lower prevalence of sero-immunity. CONCLUSION: The majority of the U.S. population has vaccine-induced sero-immunity to tetanus, demonstrating the success of the vaccination program. |
Artificial intelligence in the prediction of venous thromboembolism: A systematic review and pooled analysis
Chiasakul T , Lam BD , McNichol M , Robertson W , Rosovsky RP , Lake L , Vlachos IS , Adamski A , Reyes N , Abe K , Zwicker JI , Patell R . Eur J Haematol 2023 111 (6) 951-962 BACKGROUND: Accurate diagnostic and prognostic predictions of venous thromboembolism (VTE) are crucial for VTE management. Artificial intelligence (AI) enables autonomous identification of the most predictive patterns from large complex data. Although evidence regarding its performance in VTE prediction is emerging, a comprehensive analysis of performance is lacking. AIMS: To systematically review the performance of AI in the diagnosis and prediction of VTE and compare it to clinical risk assessment models (RAMs) or logistic regression models. METHODS: A systematic literature search was performed using PubMed, MEDLINE, EMBASE, and Web of Science from inception to April 20, 2021. Search terms included "artificial intelligence" and "venous thromboembolism." Eligible criteria were original studies evaluating AI in the prediction of VTE in adults and reporting one of the following outcomes: sensitivity, specificity, positive predictive value, negative predictive value, or area under receiver operating curve (AUC). Risks of bias were assessed using the PROBAST tool. Unpaired t-test was performed to compare the mean AUC from AI versus conventional methods (RAMs or logistic regression models). RESULTS: A total of 20 studies were included. Number of participants ranged from 31 to 111 888. The AI-based models included artificial neural network (six studies), support vector machines (four studies), Bayesian methods (one study), super learner ensemble (one study), genetic programming (one study), unspecified machine learning models (two studies), and multiple machine learning models (five studies). Twelve studies (60%) had both training and testing cohorts. Among 14 studies (70%) where AUCs were reported, the mean AUC for AI versus conventional methods were 0.79 (95% CI: 0.74-0.85) versus 0.61 (95% CI: 0.54-0.68), respectively (p < .001). However, the good to excellent discriminative performance of AI methods is unlikely to be replicated when used in clinical practice, because most studies had high risk of bias due to missing data handling and outcome determination. CONCLUSION: The use of AI appears to improve the accuracy of diagnostic and prognostic prediction of VTE over conventional risk models; however, there was a high risk of bias observed across studies. Future studies should focus on transparent reporting, external validation, and clinical application of these models. |
Dynamic evolution of bacterial ligand recognition by formyl peptide receptors
Paterson NM , Al-Zubieri H , Ragona J , Kohler KM , Tirado J , Geisbrecht BV , Barber MF . Genome Biol Evol 2023 15 (10) The detection of invasive pathogens is critical for host immune defense. Cell surface receptors play a key role in the recognition of diverse microbe-associated molecules, triggering leukocyte recruitment, phagocytosis, release of antimicrobial compounds, and cytokine production. The intense evolutionary forces acting on innate immune receptor genes have contributed to their rapid diversification across plants and animals. However, the functional consequences of immune receptor divergence are often unclear. Formyl peptide receptors (FPRs) comprise a family of animal G-protein coupled receptors which are activated in response to a variety of ligands including formylated bacterial peptides, pathogen virulence factors, and host-derived antimicrobial peptides. FPR activation in turn promotes inflammatory signaling and leukocyte migration to sites of infection. Here we investigate patterns of gene loss, diversification, and ligand recognition among FPRs in primates and carnivores. We find that FPR1, which plays a critical role in innate immune defense in humans, has been lost in New World primates. Amino acid variation in FPR1 and FPR2 among primates and carnivores is consistent with a history of repeated positive selection acting on extracellular domains involved in ligand recognition. To assess the consequences of FPR divergence on bacterial ligand interactions, we measured binding between primate FPRs and the FPR agonist Staphylococcus aureus enterotoxin B, as well as S. aureus FLIPr-like, an FPR inhibitor. We found that few rapidly evolving sites in primate FPRs are sufficient to modulate recognition of bacterial proteins, demonstrating how natural selection may serve to tune FPR activation in response to diverse microbial ligands. |
Lab on a chip for detecting Clara cell protein 16 (CC16) for potential screening of the workers exposed to respirable silica aerosol
Ahn C , Lee T , Shin JH , Lee JS , Thiyagarajan Upaassana V , Ghosh S , Ku BK . Microfluid Nanofluidics 2023 27 (11) 1-10 Early detection of pulmonary responses to silica aerosol exposure, such as lung inflammation as well as early identification of silicosis initiation, is of great importance in disease prevention of workers. In this study, to early screen the health condition of the workers who are exposed to respirable silica dusts, an immunoassay lab on a chip (LOC) was designed, developed and fully characterized for analyzing Clara cell protein 16 (CC16) in serum which has been considered as one of the potential biomarkers of lung inflammation or lung damage due to the respirable silica dusts. Sandwich immunoassay of CC16 was performed on the LOC developed with a custom-designed portable analyzer using artificial serums spiked with CC16 protein first and then human serums obtained from the coal mine workers exposed to the respirable silica-containing dusts. The dynamic range of CC16 assay performed on the LOC was in a range of 0.625–20 ng/mL, and the achieved limit of detection (LOD) was around 0.35 ng/mL. The assay results of CC16 achieved from both the developed LOC and the conventional 96 well plate showed a reasonable corelation. The correlation between the conventional reader and the developed portable analyzer was found to be reasonable, resulting in R 2 ~ 0.93. This study shows that the LOC developed for the early detection of CC16 can be potentially applied for the development of a field-deployable point-of-care testing (POCT) for the early monitoring of the field workers who are exposed to silica aerosol. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. |
An approach to determining the most common causes of stillbirth in low and middle-income countries: A commentary
Goldenberg RL , Ordi J , Blau DM , Rakislova N , Kulkarni V , Ghanchi NK , Saleem S , Goudar SS , Goco N , Paganelli C , McClure EM . Gates Open Res 2023 7 102 Stillbirth, one of the most common adverse pregnancy outcomes, is especially prevalent in low and middle-income countries (LMICs). Understanding the causes of stillbirth is crucial to developing effective interventions. In this commentary, investigators working across several LMICs discuss the most useful investigations to determine causes of stillbirths in LMICs. Useful data were defined as 1) feasible to obtain accurately and 2) informative to determine or help eliminate a cause of death. Recently, new tools for LMIC settings to determine cause of death in stillbirths, including minimally invasive tissue sampling (MITS) - a method using needle biopsies to obtain internal organ tissue from deceased fetuses for histology and pathogen identification in those tissues have become available. While placental histology has been available for some time, the development of the Amsterdam Criteria in 2016 has provided a useful framework to categorize placental lesions. The authors recommend focusing on the clinical history, the placental evaluation, the external examination of the fetus, and, when available, fetal tissue obtained by MITS, especially of the lung (focused on histology and microbiology) and brain/cerebral spinal fluid (CSF) and fetal blood (focused on microbiological analysis). The authors recognize that this approach may not identify some causes of stillbirth, including some genetic abnormalities and internal organ anomalies, but believe it will identify the most common causes of stillbirth, and most of the preventable causes. |
Impact of anthropometry training and feasibility of 3D imaging on anthropometry data quality among children under five years in a postmortem setting
Gupta PM , Sivalogan K , Oliech R , Alexander E , Klein J , Addo OY , Gethi D , Akelo V , Blau DM , Suchdev PS . PLoS One 2023 18 (9) e0292046 BACKGROUND: The Child Health and Mortality Prevention Surveillance Network (CHAMPS) identifies causes of under-5 mortality in high mortality countries. OBJECTIVE: To address challenges in postmortem nutritional assessment, we evaluated the impact of anthropometry training and the feasibility of 3D imaging on data quality within the CHAMPS Kenya site. DESIGN: Staff were trained using World Health Organization (WHO)-recommended manual anthropometry equipment and novel 3D imaging methods to collect postmortem measurements. Following training, 76 deceased children were measured in duplicate and were compared to measurements of 75 pre-training deceased children. Outcomes included measures of data quality (standard deviations of anthropometric indices and digit preference scores (DPS)), precision (absolute and relative technical errors of measurement, TEMs or rTEMs), and accuracy (Bland-Altman plots). WHO growth standards were used to produce anthropometric indices. Post-training surveys and in-depth interviews collected qualitative feedback on measurer experience with performing manual anthropometry and ease of using 3D imaging software. RESULTS: Manual anthropometry data quality improved after training, as indicated by DPS. Standard deviations of anthropometric indices exceeded limits for high data quality when using the WHO growth standards. Reliability of measurements post-training was high as indicated by rTEMs below 1.5%. 3D imaging was highly correlated with manual measurements; however, on average 3D scans overestimated length and head circumference by 1.61 cm and 2.27 cm, respectively. Site staff preferred manual anthropometry to 3D imaging, as the imaging technology required adequate lighting and additional considerations when performing the measurements. CONCLUSIONS: Manual anthropometry was feasible and reliable postmortem in the presence of rigor mortis. 3D imaging may be an accurate alternative to manual anthropometry, but technology adjustments are needed to ensure accuracy and usability. |
Inferring school district learning modalities during the COVID-19 pandemic with a hidden Markov model
Panaggio MJ , Fang M , Bang H , Armstrong PA , Binder AM , Grass JE , Magid J , Papazian M , Shapiro-Mendoza CK , Parks SE . PLoS One 2023 18 (10) e0292354 During the COVID-19 pandemic, many public schools across the United States shifted from fully in-person learning to alternative learning modalities such as hybrid and fully remote learning. In this study, data from 14,688 unique school districts from August 2020 to June 2021 were collected to track changes in the proportion of schools offering fully in-person, hybrid and fully remote learning over time. These data were provided by Burbio, MCH Strategic Data, the American Enterprise Institute's Return to Learn Tracker and individual state dashboards. Because the modalities reported by these sources were incomplete and occasionally misaligned, a model was needed to combine and deconflict these data to provide a more comprehensive description of modalities nationwide. A hidden Markov model (HMM) was used to infer the most likely learning modality for each district on a weekly basis. This method yielded higher spatiotemporal coverage than any individual data source and higher agreement with three of the four data sources than any other single source. The model output revealed that the percentage of districts offering fully in-person learning rose from 40.3% in September 2020 to 54.7% in June of 2021 with increases across 45 states and in both urban and rural districts. This type of probabilistic model can serve as a tool for fusion of incomplete and contradictory data sources in order to obtain more reliable data in support of public health surveillance and research efforts. |
Sex differences in COVID-19 deaths in the by industry and occupation, 2021
Syamlal G , Kurth LM , Blackley DJ , Dodd KE , Mazurek JM . Am J Prev Med 2023 INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) pandemic has disproportionately impacted workers in certain industries and occupations. The infection risk for SARS-CoV-2 and future respiratory viruses in the workplace is a significant concern for workers, employers, and policymakers. The current study describes the differences in COVID-19 mortality by sex and industry/occupation among working-age U.S. residents in 49 states and New York City. METHODS: The 2021 National Vital Statistics System (NVSS) public use multiple-cause-of-death data for U.S. decedents aged 15‒64 years (working-age) with information on usual industry and occupation were analyzed in 2022. Age-standardized COVID-19 death rates for selected demographic characteristics and adjusted proportional mortality ratios (PMRs) were estimated by sex and by usual industry and occupation. RESULTS: In 2021, 133,596 (14.3%) U.S. decedents aged 15‒64 years had COVID-19 listed as the underlying cause of death; the highest COVID-19 death rate was among persons aged 55‒64 years (172.4/100,000 population) and males (65.5/100,000 population). Among males, American Indian or Alaskan Native and among females, Black or African American had the highest death rates. Hispanic males had higher age-adjusted death rates than Hispanic females. Working-age male decedents in the public administration (PMR=1.39) and management of companies & enterprises industries (PMR=1.39) and community and social services occupations (PMR=1.68) and female decedents in the utilities industry (PMR=1.20) and protective services occupation (PMR=1.18) had the highest PMRs. CONCLUSIONS: COVID-19 death rates and PMRs varied by sex, industry, and occupation groups. These findings underscore the importance of workplace public health interventions, which could protect workers and their communities. |
Peripheral and placental prevalence of sulfadoxine-pyrimethamine resistance markers in plasmodium falciparum among pregnant women in Southern Province, Rwanda
Alruwaili M , Uwimana A , Sethi R , Murindahabi M , Piercefield E , Umulisa N , Abram A , Eckert E , Munguti K , Mbituyumuremyi A , Gutman JR , Sullivan DJ . Am J Trop Med Hyg 2023 109 (5) 1057-1062 Intermittent preventive therapy during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended in areas of moderate to high malaria transmission intensity. As a result of the increasing prevalence of SP resistance markers, IPTp-SP was withdrawn from Rwanda in 2008. Nonetheless, more recent findings suggest that SP may improve birthweight even in the face of parasite resistance, through alternative mechanisms that are independent of antimalarial effects. The prevalence of single nucleotide polymorphisms in Plasmodium falciparum dihydropteroate synthase (pfdhps) and dihydrofolate reductase (pfdhfr) genes associated with SP resistance among 148 pregnant women from 2016 to 2018 within Rwanda's Southern Province (Huye and Kamonyi districts) was measured using a ligase detection reaction-fluorescent microsphere assay. The frequency of pfdhps K540E, A581G, and the quintuple (pfdhfr N51I + C59R + S108N/pfdhps A437G + K540E) and sextuple (pfdhfr N51I + C59R + S108N/pfdhps A437G + K540E + A581G) mutant genotypes was 90%, 38%, 75%, and 28%, respectively. No significant genotype difference was seen between the two districts, which are approximately 50 km apart. Observed agreements for matched peripheral to placental blood were reported and found to be 207 of 208 (99%) for pfdhfr and 239 of 260 (92%) for pfdhps. The peripheral blood sample did not miss any pfdhfr drug-resistant mutants or pfdhps except at the S436 loci. At this level of the sextuple mutant, the antimalarial efficacy of SP for preventing low birthweight is reduced, although overall SP still exerts a nonmalarial benefit during pregnancy. This study further reveals the need to intensify preventive measures to sustain malaria control in Rwanda to keep the overall incidence of malaria during pregnancy low. |
A safety net tobacco use cessation resource: Quitline service usage, 2019
Tetlow SM , Zhang L , Borowiecki M , Kim Y , Gentzke AS , Wang TW , Cornelius ME , Hawkins NA . Prev Chronic Dis 2023 20 E84 INTRODUCTION: Quitlines are free, accessible evidence-based services that may provide an important resource for people facing barriers to clinical treatment for cessation of tobacco use. METHODS: Using 2019 intake data from the National Quitline Data Warehouse, we examined quitline service usage, stratified by sociodemographic characteristics. Only US quitlines reporting service type data were included (n = 40 [of 51]). Callers (aged ≥12 years) who registered with a quitline, reported current use of a tobacco product, and received at least 1 service comprised the analytic data. Chi-square tests examined differences in quitline services received by participant characteristics. RESULTS: In 2019, 182,544 people reporting current use of a tobacco product received at least 1 service from a quitline in 39 states and the District of Columbia. Among them, 80.4% had attained less than a college or university degree and 70.4% were uninsured or enrolled in Medicaid or in Medicare (aged <65 years). By educational attainment (aged ≥25 years), receipt of cessation medications ranged from 59.4% of callers with a college or university degree to 65.0% of callers with a high school diploma (P < .001). The range by insurance coverage was 59.3% of callers with private insurance to 74.7% of callers with Medicare (aged <65 years) (P < .001). CONCLUSION: Quitlines served as a resource for low-SES populations in 2019, providing cessation services to many people who may face barriers to clinical cessation treatment. Strengthening and expanding quitlines may help to increase cessation among populations with a disproportionately high prevalence of tobacco product use and improve the health and well-being of people in the US. |
Detection of SARS-CoV-2 neutralizing antibodies in retropharyngeal lymph node exudates of white-tailed deer (odocoileus virginianus) from Nebraska, USA
Poonsuk K , Loy D , Birn R , Buss B , Donahue M , Nordeen T , Sinclair K , Meduna L , Brodersen B , Loy JD . J Wildl Dis 2023 59 (4) 702-708 Disease surveillance testing for emerging zoonotic pathogens in wildlife is a key component in understanding the epidemiology of these agents and potential risk to human populations. Recent emergence of SARS-CoV-2 in humans, and subsequent detection of this virus in wildlife, highlights the need for developing new One Health surveillance strategies. We used lymph node exudate, a sample type that is routinely collected in hunter-harvested white-tailed deer (WTD, Odocoileus virginianus) for surveillance of chronic wasting disease, to assess anti-SARS-CoV-2 neutralizing antibodies. A total of 132 pairs of retropharyngeal lymph nodes collected from Nebraska WTD harvested in Nebraska, US, in 2019 (pre-SARS-CoV-2 pandemic) and 2021 (post-SARS-CoV-2 pandemic) were tested for SARS-CoV-2 with reverse transcription PCR. Thereafter, exudates obtained from these same lymph nodes were tested for SARS-CoV-2 neutralizing antibodies using a surrogate virus neutralization test. Neutralizing antibodies were detected in the exudates with high diagnostic specificity (100% at proposed cutoff of 40% inhibition). Application of this testing approach to samples collected for use in other disease surveillance activities may provide additional epidemiological data on SARS-CoV-2 exposure, and there is further potential to apply this sample type to detection of other pathogens of interest. |
Multistate outbreak of turtle-associated salmonellosis highlights ongoing challenges with the illegal sale and distribution of small turtles
Nemechek K , Stapleton GS , Waltenburg MA , Low MSF , Gollarza L , Adams J , Peralta V , Lopez K , Morrison A , Schnitzler H , Kline KE , McGinnis S , Nichols M . Zoonoses Public Health 2023 70 (8) 684-691 The sale and distribution of small turtles (shell length <4 inches) as pets has been banned in the United States since 1975 because of the risk of Salmonella transmission, especially to children. Despite this 48-year-old ban, salmonellosis outbreaks continue to be linked to contact with small turtles. During investigations of turtle-associated outbreaks, information regarding the turtle farm of origin is difficult to obtain because turtles are commonly sold by transient vendors. During 2020-2021, public health officials investigated a multistate illness outbreak caused by Salmonella enterica serotype Typhimurium linked to pet small turtles. Cases were defined as a laboratory-confirmed Salmonella Typhimurium infection highly related (within 0-6 allele differences) to the outbreak strain based on whole-genome sequencing analysis by core-genome multilocus sequence typing with illness onset occurring during 27 August 2020-14 May 2021. Forty-three patients were identified from 12 states; of these, 35% (15/43) were children <5 years old. Among patients with available information, 37% (14/38) were hospitalized, and one death was reported. Seventy-four percent (25/34) of patients reported turtle exposure in the week before illness onset, and 84% (16/19) specified exposure to small turtles. The outbreak strain was isolated from samples collected from a Pennsylvania patient's small turtle tank. Two patients reported purchasing their small turtles from pet stores. Salmonella Braenderup was isolated from samples collected from small turtles and their habitat at one of these stores; however, at that time, this strain was not associated with any human illnesses. This investigation was notable because of the documented sale of small turtles from several pet stores combined with the identification of a single small turtle supplier to these pet stores. The high proportion of children involved in this outbreak highlights the continued need to educate the pet industry as well as parents and caregivers about the risk of turtle-associated salmonellosis especially in children. Understanding and addressing the persisting challenges related to the illegal sale and distribution of small turtles could reduce the burden of turtle-associated salmonellosis. |
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