Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
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Outbreak of invasive Serratia marcescens among persons incarcerated in a state prison, California, USA, March 2020-December 2022
Kamali A , Ferguson D , Dowless H , Ortiz N , Mukhopadhyay R , Schember C , Lunsford R , Hutchinson J , Scherer M , Crandall J , Bauer H , Yu A , Kimura A . Emerg Infect Dis 2024 30 (13) S41-s48 Serratia marcescens is an environmental gram-negative bacterium that causes invasive disease in rare cases. During 2020-2022, an outbreak of 21 invasive Serratia infections occurred in a prison in California, USA. Most (95%) patients had a history of recent injection drug use (IDU). We performed whole-genome sequencing and found isolates from 8 patients and 2 pieces of IDU equipment were closely related. We also identified social interactions among patients. We recovered S. marcescens from multiple environmental samples throughout the prison, including personal containers storing Cell Block 64 (CB64), a quaternary ammonium disinfectant solution. CB64 preparation and storage conditions were suboptimal for S. marcescens disinfection. The outbreak was likely caused by contaminated CB64 and propagated by shared IDU equipment and social connections. Ensuring appropriate preparation, storage, and availability of disinfectants and enacting interventions to counteract disease spread through IDU can reduce risks for invasive Serratia infections in California prisons. |
Contribution of individual support components to roof stability in a longwall gateroad
Khademian Z . Min Metall Explor 2024 According to the 2010–2019 Mine Safety and Health Administration (MSHA) accident report database, 91% of reported ground control accidents in US longwall mines were caused by roof instability. Gateroads are subjected to significant changes in loading conditions from the development to the longwall abutment loading phases. When combined with thinly bedded shale roof, found in many US longwall coal mines, the design of efficient roof support becomes challenging. In previous work, the bonded block modeling (BBM) of roof by UDEC was validated against field extensometer measurements in a longwall entry roof at a 180-m depth of cover. The BBM was shown capable of capturing delamination and buckling of shale roof, one of the main roof instability mechanisms in longwall mines. This paper presents the recent findings on the roof-support interaction using BBM models of the same longwall entry. The effects of cable bolts, roof bolt density, and strap support on potential roof instability are studied. Results demonstrate the potential for BBM numerical models to help understand the complex roof and support system interactions and to assist with optimizing gateroad support systems. © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024. |
Association between SARS-CoV-2 infection and select symptoms and conditions 31 to 150 days after testing among children and adults
Zhang Y , Romieu-Hernandez A , Boehmer TK , Azziz-Baumgartner E , Carton TW , Gundlapalli AV , Fearrington J , Nagavedu K , Dea K , Moyneur E , Cowell LG , Kaushal R , Mayer KH , Puro J , Rasmussen SA , Thacker D , Weiner MG , Saydah S , Block JP . BMC Infect Dis 2024 24 (1) 181 BACKGROUND: An increasing number of studies have described new and persistent symptoms and conditions as potential post-acute sequelae of SARS-CoV-2 infection (PASC). However, it remains unclear whether certain symptoms or conditions occur more frequently among persons with SARS-CoV-2 infection compared with those never infected with SARS-CoV-2. We compared the occurrence of specific COVID-associated symptoms and conditions as potential PASC 31- to 150-day following a SARS-CoV-2 test among adults and children with positive and negative test results. METHODS: We conducted a retrospective cohort study using electronic health record (EHR) data from 43 PCORnet sites participating in a national COVID-19 surveillance program. This study included 3,091,580 adults (316,249 SARS-CoV-2 positive; 2,775,331 negative) and 675,643 children (62,131 positive; 613,512 negative) who had a SARS-CoV-2 laboratory test during March 1, 2020-May 31, 2021 documented in their EHR. We used logistic regression to calculate the odds of having a symptom and Cox models to calculate the risk of having a newly diagnosed condition associated with a SARS-CoV-2 positive test. RESULTS: After adjustment for baseline covariates, hospitalized adults and children with a positive test had increased odds of being diagnosed with ≥ 1 symptom (adults: adjusted odds ratio[aOR], 1.17[95% CI, 1.11-1.23]; children: aOR, 1.18[95% CI, 1.08-1.28]) or shortness of breath (adults: aOR, 1.50[95% CI, 1.38-1.63]; children: aOR, 1.40[95% CI, 1.15-1.70]) 31-150 days following a SARS-CoV-2 test compared with hospitalized individuals with a negative test. Hospitalized adults with a positive test also had increased odds of being diagnosed with ≥ 3 symptoms or fatigue compared with those testing negative. The risks of being newly diagnosed with type 1 or type 2 diabetes (adjusted hazard ratio[aHR], 1.25[95% CI, 1.17-1.33]), hematologic disorders (aHR, 1.19[95% CI, 1.11-1.28]), or respiratory disease (aHR, 1.44[95% CI, 1.30-1.60]) were higher among hospitalized adults with a positive test compared with those with a negative test. Non-hospitalized adults with a positive test also had higher odds or increased risk of being diagnosed with certain symptoms or conditions. CONCLUSIONS: Patients with SARS-CoV-2 infection, especially those who were hospitalized, were at higher risk of being diagnosed with certain symptoms and conditions after acute infection. |
Chemoprevention for malaria with monthly intermittent preventive treatment with dihydroartemisinin-piperaquine in pregnant women living with HIV on daily co-trimoxazole in Kenya and Malawi: a randomised, double-blind, placebo-controlled trial
Barsosio HC , Madanitsa M , Ondieki ED , Dodd J , Onyango ED , Otieno K , Wang D , Hill J , Mwapasa V , Phiri KS , Maleta K , Taegtmeyer M , Kariuki S , Schmiegelow C , Gutman JR , Ter Kuile FO . Lancet 2024 403 (10424) 365-378 BACKGROUND: The efficacy of daily co-trimoxazole, an antifolate used for malaria chemoprevention in pregnant women living with HIV, is threatened by cross-resistance of Plasmodium falciparum to the antifolate sulfadoxine-pyrimethamine. We assessed whether addition of monthly dihydroartemisinin-piperaquine to daily co-trimoxazole is more effective at preventing malaria infection than monthly placebo plus daily co-trimoxazole in pregnant women living with HIV. METHODS: We did an individually randomised, two-arm, placebo-controlled trial in areas with high-grade sulfadoxine-pyrimethamine resistance in Kenya and Malawi. Pregnant women living with HIV on dolutegravir-based combination antiretroviral therapy (cART) who had singleton pregnancies between 16 weeks' and 28 weeks' gestation were randomly assigned (1:1) by computer-generated block randomisation, stratified by site and HIV status (known positive vs newly diagnosed), to daily co-trimoxazole plus monthly dihydroartemisinin-piperaquine (three tablets of 40 mg dihydroartemisinin and 320 mg piperaquine given daily for 3 days) or daily co-trimoxazole plus monthly placebo. Daily co-trimoxazole consisted of one tablet of 160 mg sulfamethoxazole and 800 mg trimethoprim. The primary endpoint was the incidence of Plasmodium infection detected in the peripheral (maternal) or placental (maternal) blood or tissue by PCR, microscopy, rapid diagnostic test, or placental histology (active infection) from 2 weeks after the first dose of dihydroartemisinin-piperaquine or placebo to delivery. Log-binomial regression was used for binary outcomes, and Poisson regression for count outcomes. The primary analysis was by modified intention to treat, consisting of all randomised eligible participants with primary endpoint data. The safety analysis included all women who received at least one dose of study drug. All investigators, laboratory staff, data analysts, and participants were masked to treatment assignment. This trial is registered with ClinicalTrials.gov, NCT04158713. FINDINGS: From Nov 11, 2019, to Aug 3, 2021, 904 women were enrolled and randomly assigned to co-trimoxazole plus dihydroartemisinin-piperaquine (n=448) or co-trimoxazole plus placebo (n=456), of whom 895 (99%) contributed to the primary analysis (co-trimoxazole plus dihydroartemisinin-piperaquine, n=443; co-trimoxazole plus placebo, n=452). The cumulative risk of any malaria infection during pregnancy or delivery was lower in the co-trimoxazole plus dihydroartemisinin-piperaquine group than in the co-trimoxazole plus placebo group (31 [7%] of 443 women vs 70 [15%] of 452 women, risk ratio 0·45, 95% CI 0·30-0·67; p=0·0001). The incidence of any malaria infection during pregnancy or delivery was 25·4 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 77·3 per 100 person-years in the co-trimoxazole plus placebo group (incidence rate ratio 0·32, 95% CI 0·22-0·47, p<0·0001). The number needed to treat to avert one malaria infection per pregnancy was 7 (95% CI 5-10). The incidence of serious adverse events was similar between groups in mothers (17·7 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group [23 events] vs 17·8 per 100 person-years in the co-trimoxazole group [25 events]) and infants (45·4 per 100 person-years [23 events] vs 40·2 per 100 person-years [21 events]). Nausea within the first 4 days after the start of treatment was reported by 29 (7%) of 446 women in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 12 (3%) of 445 women in the co-trimoxazole plus placebo group. The risk of adverse pregnancy outcomes did not differ between groups. INTERPRETATION: Addition of monthly intermittent preventive treatment with dihydroartemisinin-piperaquine to the standard of care with daily unsupervised co-trimoxazole in areas of high antifolate resistance substantially improves malaria chemoprevention in pregnant women living with HIV on dolutegravir-based cART and should be considered for policy. FUNDING: European and Developing Countries Clinical Trials Partnership 2; UK Joint Global Health Trials Scheme (UK Foreign, Commonwealth and Development Office; Medical Research Council; National Institute for Health Research; Wellcome); and Swedish International Development Cooperation Agency. |
P16 expression and recurrent cervical intraepithelial neoplasia after cryotherapy among women living with HIV
Maina D , Chung MH , Temmerman M , Moloo Z , Wawire J , Greene SA , Unger ER , Mugo N , Sakr S , Sayed S , McGrath CJ . Front Med (Lausanne) 2023 10 1277480 BACKGROUND: The expression of p16 protein, a surrogate marker for high-risk human papillomavirus (hrHPV), is associated with cervical dysplasia. We evaluated correlates of p16 expression at treatment for high-grade cervical lesions and its utility in predicting the recurrence of cervical intraepithelial lesions grade 2 or higher (CIN2+) following cryotherapy among women with HIV. METHODS: This is a subgroup analysis of women with HIV in Kenya with baseline cervical biopsy-confirmed CIN2+ who were randomized to receive cryotherapy and followed every six-months for two-years for biopsy-confirmed recurrence of CIN2+. P16 immunohistochemistry was performed on the baseline cervical biopsy with a positive result defined as strong abnormal nuclear expression in a continuous block segment of cells (at least 10-20 cells). RESULTS: Among the 200 women with CIN2+ randomized to cryotherapy, 160 (80%) had a baseline cervical biopsy specimen available, of whom 94 (59%) were p16-positive. p16 expression at baseline was associated with presence of any one of 14 hrHPV genotypes [Odds Ratio (OR) = 3.2; 95% Confidence Interval (CI), 1.03-9.78], multiple lifetime sexual partners (OR = 1.6; 95% CI, 1.03-2.54) and detectable plasma HIV viral load (>1,000 copies/mL; OR = 1.43; 95% CI, 1.01-2.03). Longer antiretroviral therapy duration (≥2 years) at baseline had lower odds of p16 expression (OR = 0.46; 95% CI, 0.24-0.87) than <2 years of antiretroviral therapy. Fifty-one women had CIN2+ recurrence over 2-years, of whom 33 (65%) were p16-positive at baseline. p16 was not associated with CIN2+ recurrence (Hazard Ratio = 1.35; 95% CI, 0.76-2.40). CONCLUSION: In this population of women with HIV and CIN2+, 41% of lesions were p16 negative and baseline p16 expression did not predict recurrence of cervical neoplasia during two-year follow up. |
Association between hypertension and diabetes control and COVID-19 severity: National Patient-Centered Clinical Research Network, United States, March 2020 to February 2022
Jackson SL , Woodruff RC , Nagavedu K , Fearrington J , Rolka DB , Twentyman E , Carton TW , Puro J , Denson JL , Kappelman MD , Paranjape A , Thacker D , Weiner MG , Goodman AB , Lekiachvili A , Boehmer TK , Block JP . J Am Heart Assoc 2023 12 (21) e030240 Background Hypertension and diabetes are associated with increased COVID-19 severity. The association between level of control of these conditions and COVID-19 severity is less well understood. Methods and Results This retrospective cohort study identified adults with COVID-19, March 2020 to February 2022, in 43 US health systems in the National Patient-Centered Clinical Research Network. Hypertension control was categorized as blood pressure (BP) <130/80, 130 to 139/80 to 89, 140 to 159/90 to 99, or ≥160/100 mm Hg, and diabetes control as glycated hemoglobin <7%, 7% to <9%, ≥9%. Adjusted, pooled logistic regression assessed associations between hypertension and diabetes control and severe COVID-19 outcomes. Among 1 494 837 adults with COVID-19, 43% had hypertension and 12% had diabetes. Among patients with hypertension, the highest baseline BP was associated with greater odds of hospitalization (adjusted odds ratio [aOR], 1.30 [95% CI, 1.23-1.37] for BP ≥160/100 versus BP <130/80), critical care (aOR, 1.30 [95% CI, 1.21-1.40]), and mechanical ventilation (aOR, 1.32 [95% CI, 1.17-1.50]) but not mortality (aOR, 1.08 [95% CI, 0.98-1.12]). Among patients with diabetes, the highest glycated hemoglobin was associated with greater odds of hospitalization (aOR, 1.61 [95% CI, 1.47-1.76] for glycated hemoglobin ≥9% versus <7%), critical care (aOR, 1.42 [95% CI, 1.31-1.54]), mechanical ventilation (aOR, 1.12 [95% CI, 1.02-1.23]), and mortality (aOR, 1.18 [95% CI, 1.09-1.27]). Black and Hispanic adults were more likely than White adults to experience severe COVID-19 outcomes, independent of comorbidity score and control of hypertension or diabetes. Conclusions Among 1.5 million patients with COVID-19, higher BP and glycated hemoglobin were associated with more severe COVID-19 outcomes. Findings suggest that adults with poorest control of hypertension or diabetes might benefit from efforts to prevent and initiate early treatment of COVID-19. |
Poliovirus type 1 systemic humoral and intestinal mucosal immunity induced by monovalent oral poliovirus vaccine, fractional inactivated poliovirus vaccine, and bivalent oral poliovirus vaccine: A randomized controlled trial
Snider CJ , Zaman K , Wilkinson AL , Binte Aziz A , Yunus M , Haque W , Jones KAV , Wei L , Estivariz CF , Konopka-Anstadt JL , Mainou BA , Patel JC , Lickness JS , Pallansch MA , Wassilak SGF , Steven Oberste M , Anand A . Vaccine 2023 41 (41) 6083-6092 BACKGROUND: To inform response strategies, we examined type 1 humoral and intestinal immunity induced by 1) one fractional inactivated poliovirus vaccine (fIPV) dose given with monovalent oral poliovirus vaccine (mOPV1), and 2) mOPV1 versus bivalent OPV (bOPV). METHODS: We conducted a randomized, controlled, open-label trial in Dhaka, Bangladesh. Healthy infants aged 5 weeks were block randomized to one of four arms: mOPV1 at age 6-10-14 weeks/fIPV at 6 weeks (A); mOPV1 at 6-10-14 weeks/fIPV at 10 weeks (B); mOPV1 at 6-10-14 weeks (C); and bOPV at 6-10-14 weeks (D). Immune response at 10 weeks and cumulative response at 14 weeks was assessed among the modified intention-to-treat population, defined as seroconversion from seronegative (<1:8 titers) to seropositive (≥1:8) or a four-fold titer rise among seropositive participants sustained to age 18 weeks. We examined virus shedding after two doses of mOPV1 with and without fIPV, and after the first mOPV1 or bOPV dose. The trial is registered at ClinicalTrials.gov (NCT03722004). FINDINGS: During 18 December 2018 - 23 November 2019, 1,192 infants were enrolled (arms A:301; B:295; C:298; D:298). Immune responses at 14 weeks did not differ after two mOPV1 doses alone (94% [95% CI: 91-97%]) versus two mOPV1 doses with fIPV at 6 weeks (96% [93-98%]) or 10 weeks (96% [93-98%]). Participants who received mOPV1 and fIPV at 10 weeks had significantly lower shedding (p < 0·001) one- and two-weeks later compared with mOPV1 alone. Response to one mOPV1 dose was significantly higher than one bOPV dose (79% versus 67%; p < 0·001) and shedding two-weeks later was significantly higher after mOPV1 (76% versus 56%; p < 0·001) indicating improved vaccine replication. Ninety-nine adverse events were reported, 29 serious including two deaths; none were attributed to study vaccines. INTERPRETATION: Given with the second mOPV1 dose, fIPV improved intestinal immunity but not humoral immunity. One mOPV1 dose induced higher humoral and intestinal immunity than bOPV. FUNDING: U.S. Centers for Disease Control and Prevention. |
Physical activity-friendly policies and community design features in the US, 2014 and 2021
Webber BJ , Whitfield GP , Moore LV , Stowe E , Omura JD , Pejavara A , Galuska DA , Fulton JE . Prev Chronic Dis 2023 20 E72 INTRODUCTION: The 2014 Community-Based Survey of Supports for Healthy Eating and Active Living documented the prevalence of US municipal policy and community design supports for physical activity. The survey was repeated in 2021. Our study examined change in the prevalence of supports from 2014 to 2021, overall and by municipality characteristic. METHODS: Municipalities were sampled independently each survey year. We calculated prevalence in 2014 and 2021 and the prevalence ratio (PR) for 15 supports covering zoning codes, park policies and budgets, design standards, Complete Streets policies, and shared use agreements. We used a Bonferroni-corrected Breslow-Day test to test for interaction by municipality characteristic. RESULTS: In 2014 (2,009 municipalities) compared with 2021 (1,882 municipalities), prevalence increased for several zoning codes: block sizes of walkable distances (PR = 1.46), minimum sidewalk width (PR = 1.19), pedestrian amenities along streets (PR = 1.15), continuous sidewalk coverage (PR = 1.14), and building orientation to pedestrian scale (PR = 1.08). Prevalence also increased for design standards requiring dedicated bicycle infrastructure for roadway expansion projects or street retrofits (PR = 1.19). Prevalence declined for shared use agreements (PR = 0.87). The prevalence gap widened between the most and least populous municipalities for Complete Streets policies (from a gap of 33.6 percentage points [PP] in 2014 to 54.0 PP in 2021) and for zoning codes requiring block sizes that were walkable distances (from 11.8 PP to 41.4 PP). CONCLUSION: To continue progress, more communities could consider adopting physical activity-friendly policies and design features. |
Sporozoite immunization: Innovative Translational Science to Support the Fight against malaria
Richie TL , Church LWP , Murshedkar T , Billingsley PF , James ER , Chen MC , Abebe Y , Natasha Kc , Chakravarty S , Dolberg D , Healy SA , Diawara H , Sissoko MS , Sagara I , Cook DM , Epstein JE , Mordmüller B , Kapulu M , Kreidenweiss A , Franke-Fayard B , Agnandji ST , López Mikue MA , McCall MBB , Steinhardt L , Oneko M , Olotu A , Vaughan AM , Kublin JG , Murphy SC , Jongo S , Tanner M , Sirima SB , Laurens MB , Daubenberger C , Silva JC , Lyke KE , Janse CJ , Roestenberg M , Sauerwein RW , Abdulla S , Dicko A , Kappe SHI , Sim BKL , Duffy PE , Kremsner PG , Hoffman SL . Expert Rev Vaccines 2023 22 (1) 964-1007 INTRODUCTION: Malaria, a devastating febrile illness caused by protozoan parasites, sickened 247,000,000 people in 2021 and killed 619,000, mostly children and pregnant women in sub-Saharan Africa. A highly effective vaccine is urgently needed, especially for Plasmodium falciparum (Pf), the deadliest human malaria parasite. AREAS COVERED: Sporozoites (SPZ), the parasite stage transmitted by Anopheles mosquitoes to humans, are the only vaccine immunogen achieving > 90% efficacy against Pf infection. This review describes > 30 clinical trials of PfSPZ vaccines in the U.S.A., Europe, Africa, and Asia, based on first-hand knowledge of the trials and PubMed searches of 'sporozoites,' 'malaria,' and 'vaccines.' EXPERT OPINION: First generation (radiation-attenuated) PfSPZ vaccines are safe, well tolerated, 80-100% efficacious against homologous controlled human malaria infection (CHMI) and provide 18-19 months protection without boosting in Africa. Second generation chemo-attenuated PfSPZ are more potent, 100% efficacious against stringent heterologous (variant strain) CHMI, but require a co-administered drug, raising safety concerns. Third generation, late liver stage-arresting, replication competent (LARC), genetically-attenuated PfSPZ are expected to be both safe and highly efficacious. Overall, PfSPZ vaccines meet safety, tolerability, and efficacy requirements for protecting pregnant women and travelers, with licensure for these populations possible within five years. Protecting children and mass vaccination programs to block transmission and eliminate malaria are long-term objectives. |
Investigation and public health response to a COVID-19 outbreak in a rural resort community — Blaine County, Idaho, 2020 (preprint)
Dunne EM , Maxwell T , Dawson-Skuza C , Burns M , Ball C , Turner K , Hahn CG , Bowyer M , Carter KK , Hudson L . medRxiv 2021 2021.02.09.21251216 Blaine County, Idaho, a rural area with a renowned resort, experienced an outbreak of novel coronavirus disease (COVID-19). We undertook an epidemiologic investigation to describe the outbreak and guide public health action. Confirmed cases of COVID-19 were identified from reports of SARS-CoV-2-positive laboratory test results to South Central Public Health District.Information on symptoms, hospitalization, recent travel, healthcare worker status, and close contacts was obtained by medical record review and patient interviews. Viral sequence analysis was conducted on a subset of available specimens. During March 13–April 10, 2020, a total of 451 COVID-19 cases occurred among Blaine County residents (1,959 cases per 100,000 population). An additional 37 cases occurred in out-of-state residents. Among the 451 COVID-19 patients, the median age was 51 years (Interquartile range [IQR]: 37–63), 52 (11.5%) were hospitalized, and 5 (1.1%) died. The median duration between specimen collection and a positive laboratory result was 9 days (IQR: 4–10). Forty-four (9.8%) patients reported recent travel. Healthcare workers comprised 56 (12.4%) cases; 33 of whom worked at the only hospital in the county, leading to a 15-day disruption of hospital services. Of 562 close contacts monitored by public health authorities, 22 (3.9%) had laboratory-confirmed COVID-19 and an additional 29 (5.2%) experienced compatible symptoms. Sequencing results from 34 Idaho specimens supported epidemiologic findings indicating travel as a source of SARS-CoV-2, and identified multiple lineages among hospital workers. Community mitigation strategies included school and resort closure, stay-at-home orders, and restrictions on incoming travelers. COVID-19 outbreaks in rural communities can disrupt health services. Lack of local laboratory capacity led to long turnaround times for COVID-19 test results. Rural communities frequented by tourists should consider implementing restrictions on incoming travelers among other mitigation strategies to reduce COVID-19 transmission.Competing Interest StatementThe authors have declared no competing interest.Funding StatementNo external funding was received.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:COVID-19 is a reportable disease under Idaho Department of Health and Welfare Rules, IDAPA 16.02.10. Case investigation, data collection, and analysis were conducted for public health purposes. This project was reviewed by the Center for Surveillance, Epidemiology, and Laboratory Services Human Subjects Contact at the Centers for Disease Control and Prevention (CDC). The project was determined to meet the requirements of public health surveillance covered by the U.S. Department of Health and Human Services Policy for the Protection of Human Research Subjects as defined in 45 CFR 46.102, and the decision was made that this project was nonresearch and did not require ethical review by the CDC Human Research Protection Office. Ethical approval was waived and informed consent was not required.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesSARS-CoV-2 sequence data have be n uploaded to the GISAID database, with accession numbers provided in S1 Table. Data on the estimated proportion of Blaine County residents staying at home are available at https://docs.safegraph.com/docs/social-distancing-metrics. Census block group data are available at https://data.census.gov/cedsci/. De-identified patient data are not publicly available for legal and ethical reasons. These data were collected as part of reportable disease surveillance under Idaho law, and not for research purposes. Due to the rural setting and relatively small population, there is a risk of reidentification of some patients included in the data set. De-identified data can be requested from the Idaho Division of Public Health by contacting the Bureau of Communicable Diseases Epidemiology Section at Epimail{at}dhw.Idaho.gov. https://www.gisaid.org/ |
Demographic and co-morbidity characteristics of patients tested for SARS-CoV-2 from March 2020 to January 2022 in a national clinical research network: results from PCORnet (preprint)
Block JP , Marsolo KA , Nagavedu K , Bailey LC , Boehmer TK , Fearrington J , Harris AM , Garrett N , Goodman AB , Gundlapalli AV , Kaushal R , Kho A , McTigue KM , Nair VP , Puro J , Shenkman E , Weiner MG , Williams N , Carton TW . medRxiv 2023 18 Background: Prior studies have documented differences in the age, racial, and ethnic characteristics among patients with SARS-CoV-2 infection. However, little is known about how these characteristics changed over time during the pandemic and whether racial, ethnic, and age disparities evident early in the pandemic were persistent over time. This study reports on trends in SARS-CoV-2 infections among U.S. adults from March 1, 2020 to January, 31 2022, using data from electronic health records. Methods and Findings: We captured repeated cross-sectional information from 43 large healthcare systems in 52 U.S. States and territories, participating in PCORnet, the National Patient-Centered Clinical Research Network. Using distributed queries executed at each participating institution, we acquired information for all patients >= 20 years of age who were tested for SARS-CoV-2 (both positive and negative results), including care setting, age, sex, race, and ethnicity by month as well as comorbidities (assessed with diagnostic codes). During this time period, 1,325,563 patients had positive (13% inpatient) and 6,705,868 patients had negative (25% inpatient) viral tests for SARS-CoV-2. Disparities in testing positive were present across racial and ethnic groups, especially in the inpatient setting. Compared to White patients, Black or African American and other race patients had relative risks for testing positive of 1.5 or greater in the inpatient setting for 12 of the 23-month study period. Compared to non-Hispanic patients, Hispanic patients had relative risks for testing positive in the inpatient setting of 1.5 or greater for 16 of 23. Ethnic and racial differences were present in emergency department and ambulatory settings but were less common across time than in inpatient settings. Trends in infections by age group demonstrated higher test positivity for older patients in the inpatient setting only for most months, except for June and July of 2020, April to August 2021, and January 2022. Comorbidities were common, with much higher rates among those hospitalized; hypertension (38% of patients SARS-CoV-2 positive vs. 29% for those negative) and type 2 diabetes mellitus (22% vs. 13%) were the most common. Conclusion and Relevance: Racial and ethnic disparities changed over time among persons infected with SARS-CoV-2. These trends highlight potential underlying mechanisms, such as poor access to care and differential vaccination rates, that may have contributed to greater disparities, especially early in the pandemic. Monitoring data on characteristics of patients testing positive in real time could allow public health officials and policymakers to tailor interventions to ensure that patients and communities most in need are receiving adequate testing, mitigation strategies, and treatment. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
A global genomic analysis of Salmonella Concord reveals lineages with high antimicrobial resistance in Ethiopia
Cuypers WL , Meysman P , Weill FX , Hendriksen RS , Beyene G , Wain J , Nair S , Chattaway MA , Perez-Sepulveda BM , Ceyssens PJ , de Block T , Lee WWY , Pardos de la Gandara M , Kornschober C , Moran-Gilad J , Veldman KT , Cormican M , Torpdahl M , Fields PI , ÄŒerný T , Hardy L , Tack B , Mellor KC , Thomson N , Dougan G , Deborggraeve S , Jacobs J , Laukens K , Van Puyvelde S . Nat Commun 2023 14 (1) 3517 Antimicrobial resistant Salmonella enterica serovar Concord (S. Concord) is known to cause severe gastrointestinal and bloodstream infections in patients from Ethiopia and Ethiopian adoptees, and occasional records exist of S. Concord linked to other countries. The evolution and geographical distribution of S. Concord remained unclear. Here, we provide a genomic overview of the population structure and antimicrobial resistance (AMR) of S. Concord by analysing genomes from 284 historical and contemporary isolates obtained between 1944 and 2022 across the globe. We demonstrate that S. Concord is a polyphyletic serovar distributed among three Salmonella super-lineages. Super-lineage A is composed of eight S. Concord lineages, of which four are associated with multiple countries and low levels of AMR. Other lineages are restricted to Ethiopia and horizontally acquired resistance to most antimicrobials used for treating invasive Salmonella infections in low- and middle-income countries. By reconstructing complete genomes for 10 representative strains, we demonstrate the presence of AMR markers integrated in structurally diverse IncHI2 and IncA/C2 plasmids, and/or the chromosome. Molecular surveillance of pathogens such as S. Concord supports the understanding of AMR and the multi-sector response to the global AMR threat. This study provides a comprehensive baseline data set essential for future molecular surveillance. |
Immunogenicity of novel oral poliovirus vaccine type 2 administered concomitantly with bivalent oral poliovirus vaccine: an open-label, non-inferiority, randomised, controlled trial
Wilkinson AL , Zaman K , Hoque M , Estivariz CF , Burns CC , Konopka-Anstadt JL , Mainou BA , Kovacs SD , An Q , Lickness JS , Yunus M , Snider CJ , Zhang Y , Coffee E , Abid T , Wassilak SGF , Pallansch MA , Oberste MS , Vertefeuille JF , Anand A . Lancet Infect Dis 2023 23 (9) 1062-1071 BACKGROUND: Novel oral poliovirus vaccine type 2 (nOPV2) was developed by modifying the Sabin strain to increase genetic stability and reduce risk of seeding new circulating vaccine-derived poliovirus type 2 outbreaks. Bivalent oral poliovirus vaccine (bOPV; containing Sabin types 1 and 3) is the vaccine of choice for type 1 and type 3 outbreak responses. We aimed to assess immunological interference between nOPV2 and bOPV when administered concomitantly. METHODS: We conducted an open-label, non-inferiority, randomised, controlled trial at two clinical trial sites in Dhaka, Bangladesh. Healthy infants aged 6 weeks were randomly assigned (1:1:1) using block randomisation, stratified by site, to receive nOPV2 only, nOPV2 plus bOPV, or bOPV only, at the ages of 6 weeks, 10 weeks, and 14 weeks. Eligibility criteria included singleton and full term (≥37 weeks' gestation) birth and parents intending to remain in the study area for the duration of study follow-up activities. Poliovirus neutralising antibody titres were measured at the ages of 6 weeks, 10 weeks, 14 weeks, and 18 weeks. The primary outcome was cumulative immune response for all three poliovirus types at the age of 14 weeks (after two doses) and was assessed in the modified intention-to-treat population, which was restricted to participants with adequate blood specimens from all study visits. Safety was assessed in all participants who received at least one dose of study product. A non-inferiority margin of 10% was used to compare single and concomitant administration. This trial is registered with ClinicalTrials.gov, NCT04579510. FINDINGS: Between Feb 8 and Sept 26, 2021, 736 participants (244 in the nOPV2 only group, 246 in the nOPV2 plus bOPV group, and 246 in the bOPV only group) were enrolled and included in the modified intention-to-treat analysis. After two doses, 209 (86%; 95% CI 81-90) participants in the nOPV2 only group and 159 (65%; 58-70) participants in the nOPV2 plus bOPV group had a type 2 poliovirus immune response; 227 (92%; 88-95) participants in the nOPV2 plus bOPV group and 229 (93%; 89-96) participants in the bOPV only group had a type 1 response; and 216 (88%; 83-91) participants in the nOPV2 plus bOPV group and 212 (86%; 81-90) participants in the bOPV only group had a type 3 response. Co-administration was non-inferior to single administration for types 1 and 3, but not for type 2. There were 15 serious adverse events (including three deaths, one in each group, all attributable to sudden infant death syndrome); none were attributed to vaccination. INTERPRETATION: Co-administration of nOPV2 and bOPV interfered with immunogenicity for poliovirus type 2, but not for types 1 and 3. The blunted nOPV2 immunogenicity we observed would be a major drawback of using co-administration as a vaccination strategy. FUNDING: The US Centers for Disease Control and Prevention. |
Constant vs. cyclic flow when testing face masks and respirators as source control devices for simulated respiratory aerosols
Lindsley WG , Blachere FM , Derk RC , Boots T , Duling MG , Boutin B , Beezhold DH , Noti JD . Aerosol Sci Technol 2023 57 (3) 215-232 SARS-CoV-2 spreads by infectious aerosols and droplets from the respiratory tract. Masks and respirators can reduce the transmission of infectious respiratory diseases by collecting these aerosols at the source. The ability of source control devices to block aerosols can be tested by expelling an aerosol through a headform using constant airflows, which are simpler, or cyclic airflows, which are more realistic but require more complex methods. Experiments with respirators found that using cyclic vs. constant flows affected the amount of aerosol inhaled, but similar comparisons have not been made for source control devices with exhaled aerosols. We measured the collection efficiencies for exhaled aerosols for two cloth masks, two medical masks with and without an elastic mask brace, a neck gaiter, and an N95 filtering facepiece respirator using 15 L/min and 85 L/min constant and cyclic flows and a headform with pliable skin. The collection efficiencies for the 15 L/min cyclic flow, 15 L/min constant flow, and 85 L/min constant flow were not significantly different in most cases. The apparent collection efficiencies for the 85 L/min cyclic flow were artificially increased by rebreathing and refiltration of the aerosol from the collection chamber. The collection efficiencies correlated well with the fit factors (rho > 0.95) but not the filtration efficiencies (rho < 0.54). Our results suggest that the aerosol collection efficiency measurements of source control devices are comparable when testing the devices using either constant or cyclic airflows and that the potential for aerosol rebreathing must be considered when conducting experiments.Copyright © This work was authored as part of the Contributor's official duties as an Employee of the United States Government and is therefore a work of the United States Government. In accordance with 17 USC. 105, no copyright protection is available for such works under US Law. |
Visualizing Cancer Incidence and Mortality Estimates by Congressional Districts, United States 2012-2016
Senkomago V , Thompson TD , Scott LC , Singh SD , O'Neil ME , Wilson R , King JB , Jim MM , Lu H , Wu M , Benard VB , Richardson LC . J Registry Manag 2020 47 (2) 67-79 BACKGROUND: Cancer incidence and death rates in the United States are often published at the county or statelevels; examining cancer statistics at the congressional district (CD) level allows decision makers to better understand how cancer is impacting the specific populations they represent. METHODS: Cancer incidence data were obtained from the Centers for Disease Control and Prevention's National Program of Cancer Registries and the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Mortality data were obtained from the National Center for Health Statistics. CD rates were estimated by assigning the county-level age-adjusted rates to the census block and weighting those by the block population proportion of the CD. Those weighted rates were then aggregated over the blocks within the CD to estimate the district rate. Incidence rate estimates for 406 CDs and death rate estimates for 436 CDs were reported according to the boundaries for the 115th Congress of the United States. Maps showing rate estimates for all cancers combined, lung/bronchus, colorectal, female breast, cervical, and prostate cancer are presented by sex and race/ethnicity. RESULTS: The distribution of cancer incidence and death rates by CDs show similar patterns to those that have been observed at the county and state levels, with the highest cancer incidence and death rates observed in CDs in the South and Eastern regions. CONCLUSION: This examination of cancer rates at the CD-level provides data that can be used to inform cancer control strategies at the local and national levels. Displaying the data with the Data Visualizations tool makes it easily accessible to the public and decision makers. |
Structural elucidation of a protective B cell epitope on outer surface protein C (OspC) of the Lyme disease spirochete, borreliella Burgdorferi
Rudolph MJ , Davis SA , Haque HME , Weis DD , Vance DJ , Piazza CL , Ejemel M , Cavacini L , Wang Y , Mbow ML , Gilmore RD , Mantis NJ . mBio 2023 14 (2) e0298122 Outer surface protein C (OspC) plays a pivotal role in mediating tick-to-host transmission and infectivity of the Lyme disease spirochete, Borreliella burgdorferi. OspC is a helical-rich homodimer that interacts with tick salivary proteins, as well as components of the mammalian immune system. Several decades ago, it was shown that the OspC-specific monoclonal antibody, B5, was able to passively protect mice from experimental tick-transmitted infection by B. burgdorferi strain B31. However, B5's epitope has never been elucidated, despite widespread interest in OspC as a possible Lyme disease vaccine antigen. Here, we report the crystal structure of B5 antigen-binding fragments (Fabs) in complex with recombinant OspC type A (OspC(A)). Each OspC monomer within the homodimer was bound by a single B5 Fab in a side-on orientation, with contact points along OspC's α-helix 1 and α-helix 6, as well as interactions with the loop between α-helices 5 and 6. In addition, B5's complementarity-determining region (CDR) H3 bridged the OspC-OspC' homodimer interface, revealing the quaternary nature of the protective epitope. To provide insight into the molecular basis of B5 serotype specificity, we solved the crystal structures of recombinant OspC types B and K and compared them to OspC(A). This study represents the first structure of a protective B cell epitope on OspC and will aid in the rational design of OspC-based vaccines and therapeutics for Lyme disease. IMPORTANCE The spirochete Borreliella burgdorferi is a causative agent of Lyme disease, the most common tickborne disease in the United States. The spirochete is transmitted to humans during the course of a tick taking a bloodmeal. After B. burgdorferi is deposited into the skin of a human host, it replicates locally and spreads systemically, often resulting in clinical manifestations involving the central nervous system, joints, and/or heart. Antibodies directed against B. burgdorferi's outer surface protein C (OspC) are known to block tick-to-host transmission, as well as dissemination of the spirochete within a mammalian host. In this report, we reveal the first atomic structure of one such antibody in complex with OspC. Our results have implications for the design of a Lyme disease vaccine capable of interfering with multiple stages in B. burgdorferi infection. |
COVID-19 outcomes stratified by control status of hypertension and diabetes: Preliminary findings from PCORnet, U.S
Jackson SL , Block JP , Rolka DB , Pavkov ME , Chevinsky JR , Lekiachvili A , Carton TW , Thacker D , Denson JL , Paranjape A , Kappelman MD , Boehmer TK , Twentyman E . AJPM Focus 2022 1 (1) 100012 INTRODUCTION: Hypertension and diabetes are associated with increased COVID-19 severity, yet less is known about COVID-19 outcomes across levels of disease control for these conditions. METHODS: All adults aged 20 years with COVID-19 between March 1, 2020 and March 15, 2021 in 42 healthcare systems in National Patient-Centered Clinical Research Network were identified. RESULTS: Among 656,049 adults with COVID-19, 41% had hypertension, and 13% had diabetes. Of patients with classifiable hypertension, 35% had blood pressure <130/80 mmHg, 40% had blood pressure of 130139/8089 mmHg, 21% had blood pressure of 140159/9099 mmHg, and 6% had blood pressure 160/100 mmHg. Severe COVID-19 outcomes were more prevalent among those with blood pressure of 160/100 than among those with blood pressure of 130-139/80-89, including hospitalization (23.7% [95% CI=23.0, 24.4] vs 11.7% [95% CI=11.5, 11.9]), receipt of critical care (5.5% [95% CI=5.0, 5.8] vs 2.4% [95% CI=2.3, 2.5]), receipt of mechanical ventilation (3.0% [95% CI=2.7, 3.3] vs 1.2% [95% CI=1.1, 1.3]), and 60-day mortality (4.6% [95% CI=4.2, 4.9] vs 1.8% [95% CI=1.7, 1.9]). Of patients with classifiable diabetes, 44% had HbA1c <7%, 35% had HbA1c 7% to <9%, and 21% had HbA1c 9%. Hospitalization prevalence was 31.3% (95% CI=30.7, 31.9) among those with HbA1c <7% vs 40.2% (95% CI=39.4, 41.1) among those with HbA1c 9%; other outcomes did not differ substantially by HbA1c. CONCLUSIONS: These findings highlight the importance of appropriate management of hypertension and diabetes, including during public health emergencies such as the COVID-19 pandemic. |
Effect of monthly intermittent preventive treatment with dihydroartemisinin-piperaquine with and without azithromycin versus monthly sulfadoxine-pyrimethamine on adverse pregnancy outcomes in Africa: a double-blind randomised, partly placebo-controlled trial
Madanitsa M , Barsosio HC , Minja DTR , Mtove G , Kavishe RA , Dodd J , Saidi Q , Onyango ED , Otieno K , Wang D , Ashorn U , Hill J , Mukerebe C , Gesase S , Msemo OA , Mwapasa V , Phiri KS , Maleta K , Klein N , Magnussen P , Lusingu JPA , Kariuki S , Mosha JF , Alifrangis M , Hansson H , Schmiegelow C , Gutman JR , Chico RM , Ter Kuile FO . Lancet 2023 401 (10381) 1020-1036 BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin-piperaquine is more effective than IPTp with sulfadoxine-pyrimethamine at reducing malaria infection during pregnancy in areas with high-grade resistance to sulfadoxine-pyrimethamine by Plasmodium falciparum in east Africa. We aimed to assess whether IPTp with dihydroartemisinin-piperaquine, alone or combined with azithromycin, can reduce adverse pregnancy outcomes compared with IPTp with sulfadoxine-pyrimethamine. METHODS: We did an individually randomised, double-blind, three-arm, partly placebo-controlled trial in areas of high sulfadoxine-pyrimethamine resistance in Kenya, Malawi, and Tanzania. HIV-negative women with a viable singleton pregnancy were randomly assigned (1:1:1) by computer-generated block randomisation, stratified by site and gravidity, to receive monthly IPTp with sulfadoxine-pyrimethamine (500 mg of sulfadoxine and 25 mg of pyrimethamine for 1 day), monthly IPTp with dihydroartemisinin-piperaquine (dosed by weight; three to five tablets containing 40 mg of dihydroartemisinin and 320 mg of piperaquine once daily for 3 consecutive days) plus a single treatment course of placebo, or monthly IPTp with dihydroartemisinin-piperaquine plus a single treatment course of azithromycin (two tablets containing 500 mg once daily for 2 consecutive days). Outcome assessors in the delivery units were masked to treatment group. The composite primary endpoint was adverse pregnancy outcome, defined as fetal loss, adverse newborn baby outcomes (small for gestational age, low birthweight, or preterm), or neonatal death. The primary analysis was by modified intention to treat, consisting of all randomised participants with primary endpoint data. Women who received at least one dose of study drug were included in the safety analyses. This trial is registered with ClinicalTrials.gov, NCT03208179. FINDINGS: From March-29, 2018, to July 5, 2019, 4680 women (mean age 25·0 years [SD 6·0]) were enrolled and randomly assigned: 1561 (33%; mean age 24·9 years [SD 6·1]) to the sulfadoxine-pyrimethamine group, 1561 (33%; mean age 25·1 years [6·1]) to the dihydroartemisinin-piperaquine group, and 1558 (33%; mean age 24·9 years [6.0]) to the dihydroartemisinin-piperaquine plus azithromycin group. Compared with 335 (23·3%) of 1435 women in the sulfadoxine-pyrimethamine group, the primary composite endpoint of adverse pregnancy outcomes was reported more frequently in the dihydroartemisinin-piperaquine group (403 [27·9%] of 1442; risk ratio 1·20, 95% CI 1·06-1·36; p=0·0040) and in the dihydroartemisinin-piperaquine plus azithromycin group (396 [27·6%] of 1433; 1·16, 1·03-1·32; p=0·017). The incidence of serious adverse events was similar in mothers (sulfadoxine-pyrimethamine group 17·7 per 100 person-years, dihydroartemisinin-piperaquine group 14·8 per 100 person-years, and dihydroartemisinin-piperaquine plus azithromycin group 16·9 per 100 person-years) and infants (sulfadoxine-pyrimethamine group 49·2 per 100 person-years, dihydroartemisinin-piperaquine group 42·4 per 100 person-years, and dihydroartemisinin-piperaquine plus azithromycin group 47·8 per 100 person-years) across treatment groups. 12 (0·2%) of 6685 sulfadoxine-pyrimethamine, 19 (0·3%) of 7014 dihydroartemisinin-piperaquine, and 23 (0·3%) of 6849 dihydroartemisinin-piperaquine plus azithromycin treatment courses were vomited within 30 min. INTERPRETATION: Monthly IPTp with dihydroartemisinin-piperaquine did not improve pregnancy outcomes, and the addition of a single course of azithromycin did not enhance the effect of monthly IPTp with dihydroartemisinin-piperaquine. Trials that combine sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine for IPTp should be considered. FUNDING: European & Developing Countries Clinical Trials Partnership 2, supported by the EU, and the UK Joint-Global-Health-Trials-Scheme of the Foreign, Commonwealth and Development Office, Medical Research Council, Department of Health and Social Care, Wellcome, and the Bill-&-Melinda-Gates-Foundation. |
Safety, tolerability, and immunogenicity of inactivated poliovirus vaccine with or without E.coli double mutant heat-labile toxin (dmLT) adjuvant in healthy adults; a phase 1 randomized study
Erdem R , De Coster I , Withanage K , Mercer LD , Marchant A , Taton M , Cools N , Lion E , Cassels F , Higgins D , Ivinson K , Locke E , Mahmood K , Wright PF , Gast C , White JA , Ackerman ME , Konopka-Anstadt JL , Mainou BA , Van Damme P . Vaccine 2023 41 (10) 1657-1667 BACKGROUND: Inactivated trivalent poliovirus vaccine (IPV) induces humoral immunity, which protects against paralytic poliomyelitis but does not induce sufficient mucosal immunity to block intestinal infection. We assessed the intestinal immunity in healthy adults in Belgium conferred by a co-formulation of IPV with the mucosal adjuvant double mutant Labile Toxin (dmLT) derived from Escherichia coli. METHODS: Healthy fully IPV-vaccinated 18-45-year-olds were randomly allocated to three groups: on Day 1 two groups received one full dose of IPV (n = 30) or IPV + dmLT (n = 30) in a blinded manner, and the third received an open-label dose of bivalent live oral polio vaccine (bOPV types 1 and 3, n = 20). All groups received a challenge dose of bOPV on Day 29. Participants reported solicited and unsolicited adverse events (AE) using study diaries. Mucosal immune responses were measured by fecal neutralization and IgA on Days 29 and 43, with fecal shedding of challenge viruses measured for 28 days. Humoral responses were measured by serum neutralizing antibody (NAb). RESULTS: Solicited and unsolicited AEs were mainly mild-to-moderate and transient in all groups, with no meaningful differences in rates between groups. Fecal shedding of challenge viruses in both IPV groups exceeded that of the bOPV group but was not different between IPV and IPV + dmLT groups. High serum NAb responses were observed in both IPV groups, alongside modest levels of fecal neutralization and IgA. CONCLUSIONS: Addition of dmLT to IPV administered intramuscularly neither affected humoral nor intestinal immunity nor decreased fecal virus shedding following bOPV challenge. The tolerability of the dose of dmLT used in this study may allow higher doses to be investigated for impact on mucosal immunity. Registered on ClinicalTrials.gov - NCT04232943. |
Achieving the UNAIDS 90-90-90 targets: a comparative analysis of four large community randomised trials delivering universal testing and treatment to reduce HIV transmission in sub-Saharan Africa
Sabapathy K , Balzer L , Larmarange J , Block L , Floyd S , Iwuji C , Wirth K , Ayles H , Fidler S , Kamya M , Petersen M , Havlir D , Dabis F , Moore J , Hayes R . BMC Public Health 2022 22 (1) 2333 BACKGROUND: Four large community-randomized trials examining universal testing and treatment (UTT) to reduce HIV transmission were conducted between 2012-2018 in Botswana, Kenya, Uganda, Zambia and South Africa. In 2014, the UNAIDS 90-90-90 targets were adopted as a useful metric to monitor coverage. We systematically review the approaches used by the trials to measure intervention delivery, and estimate coverage against the 90-90-90 targets. We aim to provide in-depth understanding of the background contexts and complexities that affect estimation of population-level coverage related to the 90-90-90 targets. METHODS: Estimates were based predominantly on "process" data obtained during delivery of the interventions which included a combination of home-based and community-based services. Cascade coverage data included routine electronic health records, self-reported data, survey data, and active ascertainment of HIV viral load measurements in the field. RESULTS: The estimated total adult populations of trial intervention communities included in this study ranged from 4,290 (TasP) to 142,250 (Zambian PopART Arm-B). The estimated total numbers of PLHIV ranged from 1,283 (TasP) to 20,541 (Zambian PopART Arm-B). By the end of intervention delivery, the first-90 target (knowledge of HIV status among all PLHIV) was met by all the trials (89.2%-94.0%). Three of the four trials also achieved the second- and third-90 targets, and viral suppression in BCPP and SEARCH exceeded the UNAIDS target of 73%, while viral suppression in the Zambian PopART Arm-A and B communities was within a small margin (~3%) of the target. CONCLUSIONS: All four UTT trials aimed to implement wide-scale testing and treatment for HIV prevention at population level and showed substantial increases in testing and treatment for HIV in the intervention communities. This study has not uncovered any one estimation approach which is superior, rather that several approaches are available and researchers or policy makers seeking to measure coverage should reflect on background contexts and complexities that affect estimation of population-level coverage in their specific settings. All four trials surpassed UNAIDS targets for universal testing in their intervention communities ahead of the 2020 milestone. All but one of the trials also achieved the 90-90 targets for treatment and viral suppression. UTT is a realistic option to achieve 95-95-95 by 2030 and fast-track the end of the HIV epidemic. |
Evaluating size effects for a porous, weak, homogeneous limestone
Sinha S , Walton G , Chaurasia A , Diederichs M , Batchler T . Rock Mech Rock Eng 2022 [Epub ahead of print] In rock engineering, size effects have been a topic of extensive research since the early 1960s, and despite many advances over the years, our understanding of size effect remains incomplete, especially for weak, porous, homogeneous rocks. Indeed, the vast majority of studies related to size effect have specifically considered low porosity rocks (generally crystalline). To bridge this gap in knowledge, we conducted unconfined compression tests on cubic limestone blocks ranging in size from 0.1 to 0.9 m. Texas Cream Limestone, which is a porous, homogeneous, weak rock, was chosen for this study. As this rock has not previously been studied in the literature, conventional compression tests and indirect tensile strength tests on cylindrical specimens were completed prior to testing the cube specimens. For the largest specimens, 3D digital image correlation (3D-DIC) was employed to track the surficial displacements as a function of the applied load. The tests revealed a lack of size effect for the entire range of block sizes considered. To evaluate size effects more broadly, data from prior studies on sedimentary rocks were compiled, and a tendency for the magnitude of the size effect on strength to decline with increasing porosity was noted. Some hypotheses regarding this trend are presented and evaluated based on strain-field heterogeneity metrics obtained from the 3D-DIC analysis. |
Cleaning of anthropometric data from PCORnet electronic health records using automated algorithms.
Lin PD , Rifas-Shiman SL , Aris IM , Daley MF , Janicke DM , Heerman WJ , Chudnov DL , Freedman DS , Block JP . JAMIA Open 2022 5 (4) ooac089 OBJECTIVE: To demonstrate the utility of growthcleanr, an anthropometric data cleaning method designed for electronic health records (EHR). MATERIALS AND METHODS: We used all available pediatric and adult height and weight data from an ongoing observational study that includes EHR data from 15 healthcare systems and applied growthcleanr to identify outliers and errors and compared its performance in pediatric data with 2 other pediatric data cleaning methods: (1) conditional percentile (cp) and (2) PaEdiatric ANthropometric measurement Outlier Flagging pipeline (peanof). RESULTS: 687226 children (<20 years) and 3267293 adults contributed 71246369 weight and 51525487 height measurements. growthcleanr flagged 18% of pediatric and 12% of adult measurements for exclusion, mostly as carried-forward measures for pediatric data and duplicates for adult and pediatric data. After removing the flagged measurements, 0.5% and 0.6% of the pediatric heights and weights and 0.3% and 1.4% of the adult heights and weights, respectively, were biologically implausible according to the CDC and other established cut points. Compared with other pediatric cleaning methods, growthcleanr flagged the most measurements for exclusion; however, it did not flag some more extreme measurements. The prevalence of severe pediatric obesity was 9.0%, 9.2%, and 8.0% after cleaning by growthcleanr, cp, and peanof, respectively. CONCLUSION: growthcleanr is useful for cleaning pediatric and adult height and weight data. It is the only method with the ability to clean adult data and identify carried-forward and duplicates, which are prevalent in EHR. Findings of this study can be used to improve the growthcleanr algorithm. |
Seroprevalence of AAV neutralizing antibodies in males with Duchenne muscular dystrophy.
Verma S , Nwosu SN , Razdan R , Upadhyayula SR , Phan HC , Koroma AA , Leguizamo I , Correa NS , Kuipa M , Lee D , Vanderford TH , Gardner MR . Hum Gene Ther 2022 34 430-438 Adeno-associated virus (AAV) based gene therapies are emerging strategies in Duchenne muscular dystrophy (DMD) treatment. Exposure to wild-type AAV can lead to development of neutralizing antibodies (NAb) and block AAV transduction, thereby limiting the delivery of AAV vector-based gene therapy. Therefore, it is imperative to check for the presence of AAV NAbs in a patient who is a candidate for gene therapy. We prospectively enrolled 101 genetically confirmed males with DMD (median age 11 years, 48% ambulatory, 59% on steroids) and performed AAV neutralization assays against AAV2, AAV8, AAV9, and AAVrh74 serotypes. Serotype analysis showed AAV9 (36%) and AAVrh74 (32%) seroprevalence was lower compared to AAV2 (56%) and AAV8 (47%). Interestingly, age was not correlated with NAb titer for any of the capsids. NAb responses were observed at a higher frequency in African American participants and at a lower frequency for Caucasian participants for all four serotypes. Further analysis showed no significant differences in NAb titers depending, regardless of serotype, on whether participants were taking steroids. Finally, we observed higher AAV8, AAV9, and AAVrh74 seroprevalence and significantly higher AAV2 and AAV8 NAb titers in participants that were ambulatory compared to the non-ambulatory participants. Overall, these data identify AAV9 and AAVrh74 as the two serotypes with lower preexisting NAbs in this study's cohort of 101 males with DMD, possibly showing their utility for future gene therapy applications to treat this cohort men with DMD. |
Racial and Ethnic Disparities in Outpatient Treatment of COVID-19 - United States, January-July 2022.
Boehmer TK , Koumans EH , Skillen EL , Kappelman MD , Carton TW , Patel A , August EM , Bernstein R , Denson JL , Draper C , Gundlapalli AV , Paranjape A , Puro J , Rao P , Siegel DA , Trick WE , Walker CL , Block JP . MMWR Morb Mortal Wkly Rep 2022 71 (43) 1359-1365 In December 2021 and early 2022, four medications received emergency use authorization (EUA) by the Food and Drug Administration for outpatient treatment of mild-to-moderate COVID-19 in patients who are at high risk for progressing to severe disease; these included nirmatrelvir/ritonavir (Paxlovid) and molnupiravir (Lagevrio) (both oral antivirals), expanded use of remdesivir (Veklury; an intraveneous antiviral), and bebtelovimab (a monoclonal antibody [mAb]).* Reports have documented disparities in mAb treatment by race and ethnicity (1) and in oral antiviral treatment by zip code-level social vulnerability (2); however, limited data are available on racial and ethnic disparities in oral antiviral treatment.(†) Using electronic health record (EHR) data from 692,570 COVID-19 patients aged ≥20 years who sought medical care during January-July 2022, treatment with Paxlovid, Lagevrio, Veklury, and mAbs was assessed by race and ethnicity, overall and among high-risk patient groups. During 2022, the percentage of COVID-19 patients seeking medical care who were treated with Paxlovid increased from 0.6% in January to 20.2% in April and 34.3% in July; the other three medications were used less frequently (0.7%-5.0% in July). During April-July 2022, when Paxlovid use was highest, compared with White patients, Black or African American (Black) patients were prescribed Paxlovid 35.8% less often, multiple or other race patients 24.9% less often, American Indian or Alaska Native and Native Hawaiian or other Pacific Islander (AIAN/NHOPI) patients 23.1% less often, and Asian patients 19.4% less often; Hispanic patients were prescribed Paxlovid 29.9% less often than non-Hispanic patients. Racial and ethnic disparities in Paxlovid treatment were generally somewhat higher among patients at high risk for severe COVID-19, including those aged ≥50 years and those who were immunocompromised. The expansion of programs focused on equitable awareness of and access to outpatient COVID-19 treatments, as well as COVID-19 vaccination, including updated bivalent booster doses, can help protect persons most at risk for severe illness and facilitate equitable health outcomes. |
Pre- and postlicensure animal efficacy studies comparing anthrax antitoxins
Slay RM , Cook R , Hendricks K , Boucher D , Merchlinsky M . Clin Infect Dis 2022 75 S441-s450 BACKGROUND: The deliberate use of Bacillus anthracis spores is believed by the US government to be a high bioweapons threat. The first line of defense following potential exposure to B. anthracis spores would be postexposure prophylaxis with antimicrobials that have activity against B. anthracis. Additional therapies to address the effects of toxins may be needed in systemically ill individuals. Over the last 2 decades, the United States government (USG) collaborated with the private sector to develop, test, and stockpile 3 antitoxins: anthrax immunoglobulin intravenous (AIGIV), raxibacumab, and obiltoxaximab. All 3 products target protective antigen, a protein factor common to the 2 exotoxins released by B. anthracis, and hamper or block the toxins' effects and prevent or reduce pathogenesis. These antitoxins were approved for licensure by the United States Food and Drug Administration based on animal efficacy studies compared to placebo. METHODS: We describe USG-sponsored pre- and postlicensure studies that compared efficacy of 3 antitoxins in a New Zealand White rabbit model of inhalation anthrax; survival following a lethal aerosolized dose of B. anthracis spores was the key measure of effectiveness. To model therapeutic intervention, intravenous treatments were started following onset of antigenemia. RESULTS: In pre- and postlicensure studies, all 3 antitoxins were superior to placebo; in the postlicensure study, raxibacumab and obiltoxaximab were superior to AIGIV, but neither was superior to the other. CONCLUSIONS: These data illustrate the relative therapeutic benefit of the 3 antitoxins and provide a rationale to prioritize their deployment. |
A recombinant rabies vaccine that prevents viral shedding in rabid common vampire bats (Desmodus rotundus).
Cárdenas-Canales EM , Velasco-Villa A , Ellison JA , Satheshkumar PS , Osorio JE , Rocke TE . PLoS Negl Trop Dis 2022 16 (8) e0010699 Vampire bat transmitted rabies (VBR) is a continuing burden to public health and agricultural sectors in Latin America, despite decades-long efforts to control the disease by culling bat populations. Culling has been shown to disperse bats, leading to an increased spread of rabies. Thus, non-lethal strategies to control VBR, such as vaccination, are desired. Here, we evaluated the safety and efficacy of a viral-vectored recombinant mosaic glycoprotein rabies vaccine candidate (RCN-MoG) in vampire bats (Desmodus rotundus) of unknown history of rabies exposure captured in México and transported to the United States. Vaccination with RCN-MoG was demonstrated to be safe, even in pregnant females, as no evidence of lesions or adverse effects were observed. We detected rabies neutralizing antibodies in 28% (8/29) of seronegative bats post-vaccination. Survival proportions of adult bats after rabies virus (RABV) challenge ranged from 55-100% and were not significantly different among treatments, pre- or post-vaccination serostatus, and route of vaccination, while eight pups (1-2.5 months of age) used as naïve controls all succumbed to challenge (P<0.0001). Importantly, we found that vaccination with RCN-MoG appeared to block viral shedding, even when infection proved lethal. Using real-time PCR, we did not detect RABV nucleic acid in the saliva samples of 9/10 vaccinated bats that succumbed to rabies after challenge (one was inconclusive). In contrast, RABV nucleic acid was detected in saliva samples from 71% of unvaccinated bats (10/14 sampled, plus one inconclusive) that died of the disease, including pups. Low seroconversion rates post-vaccination and high survival of non-vaccinated bats, perhaps due to earlier natural exposure, limited our conclusions regarding vaccine efficacy. However, our findings suggest a potential transmission-blocking effect of vaccination with RCN-MoG that could provide a promising strategy for controlling VBR in Latin America beyond longstanding culling programs. |
Head-to-head comparison of the immunogenicity of RotaTeq and Rotarix rotavirus vaccines and factors associated with seroresponse in infants in Bangladesh: a randomised, controlled, open-label, parallel, phase 4 trial
Velasquez-Portocarrero DE , Wang X , Cortese MM , Snider CJ , Anand A , Costantini VP , Yunus M , Aziz AB , Haque W , Parashar U , Sisay Z , Soeters HM , Hyde TB , Jiang B , Zaman K . Lancet Infect Dis 2022 22 (11) 1606-1616 BACKGROUND: A head-to-head comparison of the most widely used oral rotavirus vaccines has not previously been done, particularly in a high child mortality setting. We therefore aimed to compare the immunogenicity of RotaTeq (Merck, Kenilworth, NJ, USA) and Rotarix (GlaxoSmithKline, Rixensart, Belgium) rotavirus vaccines in the same population and examined risk factors for low seroresponse. METHODS: We did a randomised, controlled, open-label, parallel, phase 4 trial in urban slums within Mirpur and Mohakahli (Dhaka, Bangladesh). We enrolled eligible participants who were healthy infants aged 6 weeks and full-term (ie, >37 weeks' gestation). We randomly assigned participants (1:1), using block randomisation via a computer-generated electronic allocation with block sizes of 8, 16, 24, and 32, to receive either three RotaTeq vaccine doses at ages 6, 10, and 14 weeks or two Rotarix doses at ages 6 and 10 weeks without oral poliovirus vaccine. Coprimary outcomes were the rotavirus-specific IgA seroconversion in both vaccines, and the comparison of the rotavirus IgA seroconversion by salivary secretor phenotype in each vaccine arm. Seroconversion at age 18 weeks in the RotaTeq arm and age of 14 weeks in the Rotarix arm was used to compare the complete series of each vaccine. Seroconversion at age 14 weeks was used to compare two RotaTeq doses versus two Rotarix doses. Seroconversion at age 22 weeks was used to compare the immunogenicity at the same age after receiving the full vaccine series. Safety was assessed for the duration of study participation. This study is registered with ClinicalTrials.gov, NCT02847026. FINDINGS: Between Sept 1 and Dec 8, 2016, a total of 1144 infants were randomly assigned to either the RotaTeq arm (n=571) or Rotarix arm (n=573); 1080 infants (531 in the RotaTeq arm and 549 in the Rotarix arm) completed the study. Rotavirus IgA seroconversion 4 weeks after the full series occurred in 390 (73%) of 531 infants age 18 weeks in the RotaTeq arm and 354 (64%) of 549 infants age 14 weeks in the Rotarix arm (p=0·01). At age 14 weeks, 4 weeks after two doses, RotaTeq recipients had lower seroconversion than Rotarix recipients (268 [50%] of 531 vs 354 [64%] of 549; p<0·0001). However, at age 22 weeks, RotaTeq recipients had higher seroconversion than Rotarix recipients (394 [74%] of 531 vs 278 [51%] of 549; p<0·0001). Among RotaTeq recipients, seroconversion 4 weeks after the third dose was higher than after the second dose (390 [73%] of 531 vs 268 [50%] of 531; p<0·0001]. In the RotaTeq arm, rotavirus IgA seroconversion was lower in non-secretors than in secretors at ages 14 weeks (p=0·08), 18 weeks (p=0·01), and 22 weeks (p=0·02). Similarly, in the Rotarix arm, rotavirus IgA seroconversion was lower in non-secretors than in secretors at ages 14 weeks (p=0·02) and 22 weeks (p=0·01). 65 (11%) of 571 infants had adverse events in the RotaTeq arm compared with 63 (11%) of 573 infants in the Rotarix arm; no adverse events were attributed to the use of either vaccine. One death due to aspiration occurred in the RotaTeq arm, which was not related to the vaccine. INTERPRETATION: RotaTeq induced a higher magnitude and longer duration of rotavirus IgA response than Rotarix in this high child mortality setting. Additional vaccination strategies should be evaluated to overcome the suboptimal performance of current oral rotavirus vaccines in these settings. FUNDING: US Centers for Disease Control and Prevention. |
Male circumcision uptake during the Botswana Combination Prevention Project
Marukutira T , Ussery F , Kadima E , Mills LA , Moore J , Block L , Bachanas P , Davis S , Schissler T , Mosha R , Komotere O , Diswai T , Ntsuape C , Lebelonyane R , Bock N . PLoS One 2022 17 (6) e0269178 INTRODUCTION: Voluntary medical male circumcision (VMMC) uptake has been slow in some countries, including Botswana. To inform demand creation efforts, we examined sociodemographic characteristics and referral procedures associated with VMMC uptake in the Botswana Combination Prevention Project (BCPP) and examined the effectiveness of referral of men to MC services from HIV testing venues. DESIGN: BCPP was a community-randomized trial evaluating the impact of a combination HIV prevention package which included VMMC on community HIV incidence. We conducted a sub-analysis of VMMC uptake in intervention communities. METHODS: During the initial VMMC campaign in 15 intervention communities, baseline male circumcision (MC) status was assessed among men eligible for HIV testing. Uncircumcised male community residents aged 16-49 years with negative/unknown HIV status were mobilized and linked to study VMMC services. Outcomes included MC baseline status and uptake through study services. Univariate and multivariate logistic regressions were performed to identify factors associated with MC uptake. RESULTS: Of 12,864 men eligible for testing, 50% (n = 6,448) were already circumcised. Among the uncircumcised men (n = 6,416), 10% (n = 635) underwent MC. Of the 5,071 men identified as eligible for MC through HIV testing services, 78% declined referral and less than 1% of those were circumcised. Of those accepting referral (n = 1,107), 16% were circumcised. Younger (16-24 years) (aOR: 1.51; 95%CI:1.22,1.85), unemployed men (aOR:1.34; 95%CI: 1.06,1.69), and those undergoing HIV testing at mobile venues (aOR: 1.88; 95%CI: 1.53,2.31) were more likely to get circumcised. Fear of pain was the most prevalent (27%) reason given for not being circumcised. CONCLUSION: Younger, unemployed men seeking HIV testing at mobile sites in Botswana were more likely to get VMMC. Addressing unique barriers for employed and older men may be necessary. Given the simplicity of VMMC as an intervention, the HIV testing programs offer a platform for identifying uncircumcised men and offering information and encouragement to access services. |
Simplified Cas13-based assays for the fast identification of SARS-CoV-2 and its variants.
Arizti-Sanz J , Bradley A , Zhang YB , Boehm CK , Freije CA , Grunberg ME , Kosoko-Thoroddsen TF , Welch NL , Pillai PP , Mantena S , Kim G , Uwanibe JN , John OG , Eromon PE , Kocher G , Gross R , Lee JS , Hensley LE , MacInnis BL , Johnson J , Springer M , Happi CT , Sabeti PC , Myhrvold C . Nat Biomed Eng 2022 6 (8) 932-943 The widespread transmission and evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) call for rapid nucleic acid diagnostics that are easy to use outside of centralized clinical laboratories. Here we report the development and performance benchmarking of Cas13-based nucleic acid assays leveraging lyophilised reagents and fast sample inactivation at ambient temperature. The assays, which we named SHINEv.2 (for 'streamlined highlighting of infections to navigate epidemics, version 2'), simplify the previously reported RNA-extraction-free SHINEv.1 technology by eliminating heating steps and the need for cold storage of the reagents. SHINEv.2 detected SARS-CoV-2 in nasopharyngeal samples with 90.5% sensitivity and 100% specificity (benchmarked against the reverse transcription quantitative polymerase chain reaction) in less than 90 min, using lateral-flow technology and incubation in a heat block at 37 °C. SHINEv.2 also allows for the visual discrimination of the Alpha, Beta, Gamma, Delta and Omicron SARS-CoV-2 variants, and can be run without performance losses by using body heat. Accurate, easy-to-use and equipment-free nucleic acid assays could facilitate wider testing for SARS-CoV-2 and other pathogens in point-of-care and at-home settings. |
HIV incidence in Botswana rural communities with high antiretroviral treatment coverage: Results from the Botswana Combination Prevention Project, 2013-2017
Ussery F , Bachanas P , Alwano MG , Lebelonyane R , Block L , Wirth K , Ussery G , Sento B , Gaolathe T , Kadima E , Abrams W , Segolodi T , Hader S , Lockman S , Moore J . J Acquir Immune Defic Syndr 2022 91 (1) 9-16 BACKGROUND: and Setting: The Botswana Combination Prevention Project (BCPP) demonstrated a 30% reduction in community HIV incidence through expanded HIV testing, enhanced linkage to care, and universal antiretroviral treatment and exceeded the Joint United Nations Programme on HIV/AIDS 90-90-90 targets. We report rates and characteristics of incident HIV infections. METHODS: BCPP was a community-randomized controlled trial conducted in 30 rural/peri-urban Botswana communities from 2013 to 2017. Home-based and mobile HIV-testing campaigns were conducted in 15 intervention communities, with 39% of participants testing at least twice. We assessed the HIV incidence rate (IR; number of new HIV infections per 100 person-years (py) at risk) among repeat testers and risk factors with a Cox proportional hazards regression model. RESULTS: During 27,517py, 195 (women,79%) of 18,597 became HIV-infected (0.71/100py). Women had a higher IR (1.01/100py; 95% CI, 0.99 to 1.02) than men (0.34/100py; 95% CI, 0.33 to 0.35). The highest IRs were among women aged 16-24 years (1.87/100py) and men aged 25-34 years (0.56/100py). The lowest IRs were among those aged 35-64 years (women,0.41/100py; men,0.20/100py). Hazard of incident infection was highest among women aged 16-24 (HR=7.05). Sex and age were significantly associated with incidence (both P<0.0001). CONCLUSIONS: Despite an overall reduction in HIV incidence and approaching the UNAIDS 95-95-95 targets, high HIV incidence was observed in adolescent girls and young women. These findings highlight the need for additional prevention services [pre-exposure prophylaxis (PrEP), DREAMS] to achieve epidemic control in this subpopulation and increased efforts with men with undiagnosed HIV. |
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