Search

Combination HIV prevention and treatment interventions (CHIs) have led to substantial declines in HIV incidence in sub-Saharan Africa; however, population-level data on non-HIV sexually transmitted infections (STIs) in the context of CHIs are rare. We aimed to assess STI burden following scale-up of CHIs in Uganda.The Sexually Transmitted Infection Prevalence Study (STIPS) was a cross-sectional study nested within a population-based cohort among inland agrarian and Lake Victoria fishing populations in southern Uganda. STIPS enrolled consenting residents aged 18-49 years in two communities (one inland and one fishing) between May and October, 2019, and measured the prevalence of chlamydia, gonorrhoea, trichomonas, syphilis, and herpes simplex virus 2 (HSV-2).Between May 27, 2019 and Oct 25, 2019, STIPS enrolled 1825 participants. HIV prevalence was 14·0% among the inland population and 39·8% among the fishing population, with about 90% HIV viral load suppression in both communities. Among inland and fishing populations, chlamydia prevalence was 9·6% (95% CI 7·9-11·7) and 9·9% (8·1-12·0), gonorrhoea prevalence 5·0% (3·8-6·7) and 8·4% (6·8-10·5), trichomonas prevalence 9·4% (7·7-11·5) and 12·2% (10·2-14·5), and HSV-2 prevalence 43·0% (39·9-46·3) and 64·4% (61·3-67·6), respectively. In the fishing population, syphilis seropositivity was 24·2% (21·5-27·2) with 9·4% (7·7-11·5) having high-titre (rapid plasma reagin ≥1:8) infection, including 16·9% (11·9-24·0%) of men living with HIV. Prevalence of at least one curable STI (chlamydia, gonorrhoea, trichomonas, or high-titre syphilis) was 51% higher among people living with HIV (vs HIV negative; adjusted prevalence risk ratio [PRR] 1·51; 95% CI 1·27-1·78), including among pregnant women (adjusted PRR 1·87, 1·11-3·17), with no differences by HIV suppression status.Despite near universal HIV treatment, STI burden remains extremely high in southern Uganda, particularly among people living with HIV. There is an urgent need to integrate STI care with HIV services in African settings.National Institutes of Health.

Background Herpes simplex virus type 2 (HSV-2) is an incurable STI associated with increased risk of acquiring and transmitting HIV. HSV-2 prevalence is extremely high in sub-Saharan Africa, but population-level estimates of HSV-2 incidence are sparse. We quantified HSV-2 prevalence, risk-factors for infection, and age-patterns of incidence in south-central Uganda. Methods We measured HSV-2 prevalence from cross-sectional serological data among men and women aged 18-49 in two communities (fishing/inland). We identified risk-factors for seropositivity, and inferred age-patterns of HSV-2 with a Bayesian catalytic model. Results HSV-2 prevalence was 53.6% (n = 975/1819, 95%CI 51.3%-55.9%). Prevalence increased with age, was higher in the fishing community, and among women, reaching 93.6% (95%CrI 90.2%-96.6%) by age 49. Factors associated with HSV-2 seropositivity included more lifetime sexual partners, HIV positive status, and lower education. HSV-2 incidence increased steeply in late adolescence, peaking at age 18 for women and 19-20 for men. HIV prevalence was up to ten-fold higher in HSV-2-positive individuals. Conclusions HSV-2 prevalence and incidence were extremely high, with most infections occurring in late adolescence. Interventions against HSV-2, such as future vaccines or therapeutics, must reach young target populations. Remarkably higher HIV prevalence among HSV-2-positive individuals underscores this population as a priority for HIV prevention.

BackgroundHuman papillomavirus (HPV) vaccination coverage remains suboptimal in the United States, underscoring the importance of monitoring trends in vaccine hesitancy.MethodsCross-sectional data from the 2011–2020 National Immunization Survey–Teen were used to assess trends in HPV vaccination initiation among 13–17-year-olds, parental intent to initiate vaccination, and primary reasons for parental hesitancy.ResultsAmong all sex and race and ethnicity groups, the prevalence of HPV vaccination initiation increased over time, but parental intent to vaccinate against HPV for unvaccinated teens remained consistently low (≤45%). Among hesitant parents, “safety concerns” increased in nearly all demographic groups, with the greatest increases observed for non-Hispanic white female and male teens and no change for non-Hispanic black female teens. In 2019–2020, parents of unvaccinated non-Hispanic white teens were least likely to intend on vaccinating their teens, and the most common reason for hesitancy varied by sex and race and ethnicity (eg, “safety concerns” for white teens and “not necessary” for black female teens).ConclusionsAlthough HPV vaccination initiation increased over time, a substantial fraction of parents remain hesitant, and trends in their reason varied by sex and race and ethnicity. Health campaigns and clinicians should address vaccine safety and necessity.

SummaryRedefining viral load suppression (VLS) using lower cutpoints could impact progress towards the UNAIDS 95-95-95 targets. We assessed impacts of lowering the VLS cutpoint on achieving the 95-95-95 VLS target in the Rakai Community Cohort Study. Population VLS fell from 86% to 84% and 76%, respectively, after lowering VLS cutpoints from

The public health crisis created by the COVID-19 pandemic has spurred a deluge of scientific research aimed at informing the public health and medical response to the pandemic. However, early in the pandemic, those working in frontline public health and clinical care had insufficient time to parse the rapidly evolving evidence and use it for decision-making. Academics in public health and medicine were well-placed to translate the evidence for use by frontline clinicians and public health practitioners. The Novel Coronavirus Research Compendium (NCRC), a group of >60 faculty and trainees across the United States, formed in March 2020 with the goal to quickly triage and review the large volume of preprints and peer-reviewed publications on SARS-CoV-2 and COVID-19 and summarize the most important, novel evidence to inform pandemic response. From April 6 through December 31, 2020, NCRC teams screened 54 192 peer-reviewed articles and preprints, of which 527 were selected for review and uploaded to the NCRC website for public consumption. Most articles were peer-reviewed publications (n = 395, 75.0%), published in 102 journals; 25.1% (n = 132) of articles reviewed were preprints. The NCRC is a successful model of how academics translate scientific knowledge for practitioners and help build capacity for this work among students. This approach could be used for health problems beyond COVID-19, but the effort is resource intensive and may not be sustainable in the long term.

Background Lyme disease (LD) and babesiosis are increasing in the United States. We sought to characterize and compare their epidemiology and health burden using a nationally representative sample of hospitalizations. Methods Data were extracted from the National Inpatient Sample (NIS) pertaining to LD and babesiosis for 2018 and 2019. The NIS is a comprehensive database of all-payer inpatient hospitalizations, representing a stratified systematic random sample of discharges from US hospitals. Patient demographics, clinical outcomes, and admission costs were evaluated, in addition to hospital-level variables (eg, location/teaching status and census division). Annual incidence of hospitalizations was calculated using US Census Bureau data. Results The annual incidence of hospitalizations of LD-related and babesiosis-related hospitalizations were 6.98 and 2.03 per 1 000 000 persons/year. Of the 4585 LD hospitalizations in 2018–2019, 60.9% were among male patients, 85.3% were White, and 39.0% were ≥60 years. Of the 1330 babesiosis hospitalizations in 2018–2019, 72.2% were among male patients, 78.9% were White, and 74.1% were ≥60 years; 70.0% of LD and 91.7% of babesiosis hospitalizations occurred in Middle Atlantic or New England. Lower disease severity was noted in 81.8% of LD hospitalizations compared with 49.3% of babesiosis hospitalizations, whereas those suffering from high severity were 2.3% and 6.0%, respectively. The mean hospital charges for LD and babesiosis hospitalizations were $33 440.8 and $40 689.8, respectively. Conclusions Despite overlap between the 2 diseases, LD has a broader geographic range and a greater number of hospital admissions, whereas babesiosis is more severe, incurring longer hospital stays, higher inpatient costs, and deaths.

BackgroundLongitudinal population-based cohorts are critical in HIV surveillance programs in Africa but continued rapid population growth poses serious challenges to maintaining cohort representativeness with limited resources. In one such cohort, we evaluated if systematic exclusion of some residents due to growing population size biases key HIV metrics like prevalence and viremia.MethodsData were obtained from the Rakai Community Cohort study (RCCS) in south central Uganda, an open population-based cohort which began excluding some residents of newly constructed household structures within its surveillance boundaries in 2008. We evaluated the extent to which changing inclusion criteria may bias recent population HIV seroprevalence and viremia estimates from the RCCS using ensemble machine learning models fit to 2019-2020 RCCS census and survey data.ResultsOf the 24,729 census-eligible residents, 2,920 (12%) were living within new household structures and excluded. Predicted seroprevalence for excluded residents was 11.4% (95% Confidence Interval: 10.2, 12.3) compared to 11.8% in the observed sample. However, predicted seroprevalence for younger excluded residents 15-24 years was 5.1% (3.6, 6.1), which was significantly higher than that in the observed sample for the same age group (2.6%). Over all ages, predicted prevalence of viremia in excluded residents (2.8% [2.2, 3.3]) was higher than that in the observed sample (1.7%), resulting in a somewhat higher overall population viremia estimate of 1.9% [1.8, 2.0]).ConclusionsExclusion of residents in new households may modestly bias HIV viremia estimates and some age-specific seroprevalence estimates in the RCCS. Overall HIV seroprevalence estimates were not significantly affected.Key messages (3-5)In-migrants in the observed sample in the RCCS surveillance area differ from currently excluded in-migrants on various demographic characteristics.Machine learning methods may be useful tools in estimating biases introduced by the systematic exclusion of populations for which we have some data.In the context of rapid population growth, population-based open cohorts in sub-Saharan Africa must prioritize limited resources while ensuring HIV estimates are representative of the population.FundingFunding for this project was supported by the National Institute of Allergy and Infectious Diseases (R01AI143333 and R01AI155080) and the National Institute of Mental Health (R01MH115799). The findings and conclusions in this article are those of the authors and do not necessarily represent the official position of the funding agencies.Research by Aleya Khalifa reported in this publication was supported by the National Institute of Allergy And Infectious Diseases (T32AI114398). Larry Chang was supported by the National Heart, Lung, and Blood Institute (R01HL152813), Fogarty International Center (D43TW010557) and the Johns Hopkins University Center for AIDS Research (P30AI094189). Susie Hoffman and John Santelli were supported by the U.S. National Institute of Child Health and Human Development (NICHD) (R01HD091003; Santelli, PI). Susie Hoffman was also supported by the National Institute of Mental Health (P30-MH43520; Remien, PI). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Ethics approvalThis study was approved by the Uganda National Council for Science and Technology (approval number HS 540), the Uganda Virus Research Institution Research and Ethics Committee (approval number GC/127/08/12/137), Johns Hopkins Institutional Review Board (approval number IRB-00217467), and the Columbia University Institutional Review Board (approval number IRB-AAAR5428).

In-person schooling has proved contentious and difficult to study throughout the SARS-CoV-2 pandemic. Data from a massive online survey in the United States indicates an increased risk of COVID-19-related outcomes among respondents living with a child attending school in-person. School-based mitigation measures are associated with significant reductions in risk, particularly daily symptoms screens, teacher masking, and closure of extra-curricular activities. With seven or more mitigation measures, the association between in-person schooling and COVID-19-related outcomes all but disappears. Teachers working outside the home were more likely to report COVID-19-related outcomes, but this association is similar to other occupations (e.g., healthcare, office work). In-person schooling is associated with household COVID-19 risk, but this risk can likely be controlled with properly implemented school-based mitigation measures.One sentence summaryLiving with children attending in-person school is linked to a higher risk of COVID-19 outcomes, which school-based interventions can mitigate.

Because of the importance of schools to childhood development, the relationship between in-person schooling and COVID-19 risk has been one of the most important questions of this pandemic. Previous work in the United States during winter 2020–2021 showed that in-person schooling carried some risk for household members and that mitigation measures reduced this risk. Schooling and the COVID-19 landscape changed radically over spring semester 2021. Here, we use data from a massive online survey to characterize changes in in-person schooling behavior and associated risks over that period. We find increases in in-person schooling and reductions in mitigations over time. In-person schooling is associated with increased reporting of COVID-19 outcomes even among vaccinated individuals (although the absolute risk among the vaccinated is greatly reduced). Vaccinated teachers working outside the home were less likely to report COVID-19–related outcomes than unvaccinated teachers working exclusively from home. Adequate mitigation measures appear to eliminate the excess risk associated with in-person schooling.

BackgroundCombination HIV interventions (CHIs) have led to significant declines in HIV incidence in sub-Saharan Africa; however, population-level data on non-HIV sexually transmitted infection (STI) burden in the context of CHIs are rare. We aimed to assess STI burden in Uganda following mass scale-up of CHIs, including universal HIV treatment.MethodsThe Sexually Transmitted Infection Prevalence Study (STIPS) was a cross-sectional study nested within the Rakai Community Cohort Study (RCCS), a population-based cohort among inland agrarian and Lake Victoria fishing populations in southern Uganda. STIPS enrolled consenting participants, 18-49 years, between May and October 2019 and measured prevalence of Chlamydia trachomatis (chlamydia), Neisseria gonorrhoeae (gonorrhea), Trichomonas vaginalis (trichomonas), syphilis, and herpes simplex virus type 2 (HSV-2).FindingsSTIPS enrolled 1,825 participants, including 965 women (53%), of whom 9% (n=107) were pregnant. Overall, there was 9.8% prevalence of chlamydia (95%CI:8.5-11%), 6.7% gonorrhea (95%CI:5.7-8.0%), and 11% trichomonas (95%CI:9.5-12%). In the fishing population, syphilis reactivity was 24% (95%CI:22-27%), with 9.4% (95%CI:7.7-11%) having high titer (RPR ≥ 1:8) infection, including 17% (95%CI:12-24%) of HIV-positive men. Prevalence of ≥ 1 curable STI (chlamydia, gonorrhea, trichomonas, or high titer syphilis) was 44% higher among HIV-positive persons (adjusted prevalence risk ratio [adjPRR]=1.44,95%CI:1.22-1.71), with no differences by HIV treatment status. HIV-positive pregnant women were more likely than HIV-negative pregnant women to have a curable STI (adjPRR=1.87, 95%CI: 1.08-3.23).InterpretationSTI burden remains extremely high in Uganda, particularly among HIV-positive persons. There is an urgent need to integrate STI diagnostic testing and treatment with HIV services in African settings.FundingNational Institutes of Health

Background Chlamydia trachomatis is the most common nationally notifiable sexually transmitted infection in the United States; however, the seroprevalence of C. trachomatis infection is unknown. Methods This cross-sectional study was conducted among 1725 females aged 18 to 39 years who provided serum and urine samples in the 2013 through 2016 National Health and Nutrition Examination Surveys. Presence of anti-C. trachomatis Pgp3 immunoglobulin G (IgG) was determined using both an enzyme-linked immunosorbent assay (ELISA) and multiplex bead array (MBA). Weighted seroprevalence estimates were calculated. Correlates of seroprevalence were examined by multivariable Poisson regression. Results In 2013 through 2016, overall seroprevalence of C. trachomatis Pgp3 IgG was 30.0% (95% confidence interval [CI], 25.5-35.0) as measured by ELISA and 29.4% (95% CI, 25.8-33.0) as measured by the MBA assay. Overall agreement between tests was 87.1% (1503/1725). There was a high positive agreement by the MBA assay with current detection of chlamydia in urine (86% [36/42]), a past-year diagnosis of chlamydia (81.8% [27/33]), and a history of treatment for pelvic inflammatory disease (60.7% [37/61]). Seroprevalence of C. trachomatis Pgp3 IgG, as measured by MBA, was significantly higher among non-Hispanic Blacks (68.0%; adjusted prevalence ratio (aPR) = 2.7 [95% CI, 2.3-3.3]), Mexican Americans (30.9%; aPR = 1.5 [95% CI, 1.2-1.9]), and other Hispanics (35.0%; aPR = 1.9 [95% CI, 1.4-2.5]) compared with non-Hispanic Whites (21.4%). A higher lifetime number of sexual partners and a younger age at sexual debut was also associated with higher seroprevalence. Conclusion Both the ELISA and MBA serologic assays revealed a high prevalence of antibodies to C. trachomatis Pgp3 in young adult females in the US household population. There were major racial/ethnic disparities in exposure to C. trachomatis, with increased vulnerability among non-Hispanic Black females.

The Rakai Community Cohort Study in south central Uganda has surveyed people aged 15–49 since 1994. Antiretroviral therapy (ART) was introduced in 2004. HIV p24 and gp41 subtype distribution and viral diversity were studied from blood samples collected at three surveys in 1994–1995, 2002–2003, and 2008–2009, which were compared with a new survey round from 2011 to 2012. These included 1364 HIV+ individuals. For both p24 and gp41 domains, the genetic diversity within subtypes A and D was significantly increasing in the pre-ART era and decreased between the last two survey rounds in the ART era (p

Because of the importance of schools to childhood development, the relationship between in-person schooling and COVID-19 risk has been one of the most important questions of the COVID-19 pandemic. Previous work using data from the United States in winter 2020-21 showed that in-person schooling carried some risk for household members, and that mitigation measures reduced this risk. However, in-person schooling behavior and the COVID-19 landscape changed radically over the 2021 spring semester. Here we use data from a massive online survey to characterize changes in in-person schooling behavior and associated risks over that period. We find a significant increase in the frequency of in-person schooling and a reduction in mitigation, and that in-person schooling is associated with increased reporting of COVID-19 outcomes, even among vaccinated individuals (though the absolute risk among the vaccinated is greatly reduced). Moreover, vaccinated teachers working outside the home were less likely to report COVID-19-related outcomes than unvaccinated teachers reporting no work outside the home. Adequate mitigation measures appear to eliminate the excess risk associated with in person schooling.

This national survey demonstrates age-disparate (≥5 years; AD-5) sexual partnerships remain common among males and females aged 20 to 29 years in the United States (2005-2016). Females reported more older AD-5 partners, and males reported more younger AD-5 partners. Having AD-5 partners was associated with greater lifetime and recent number of sexual partners.

Data from the National Inpatient Sample indicate that Clostridioides difficile prevalence decreased from 10.1 (95% confidence interval [CI] = 9.9–10.3) to 8.6 (95% CI = 8.5–8.8) per 1000 hospital discharges between 2016 and 2018, after accounting for age, sex, and race. There was heterogeneity in the prevalence and decrease in prevalence by geographic region in the United States.

We combined behavioral survey data from the human immunodeficiency virus (HIV) Prevention Trials Network 068 study with phylogenetic information to determine if cluster membership was associated with characteristics of young women and their partners. Clusters were more likely to involve young women from specific villages and schools, indicating some localized transmission.Supplemental digital content is available in the text.

Background Antibiotic resistance has been identified as a public health threat both in the United States and globally. The United States published the National Strategy for Combating Antibiotic Resistance in 2014, which included goals to reduce inappropriate outpatient antibiotic use. Methods This cross-sectional study was conducted using National Health and Nutrition Examination Surveys (NHANES) years 1999–2018. Weighted prevalence of past 30-day nontopical outpatient antibiotic use was calculated, as well as the change in prevalence from 1999–2002 to 2015–2018 and 2007–2010 to 2015–2018, both overall and for subgroups. Associations with past 30-day nontopical outpatient antibiotic use in 2015–2018 were examined using predictive margins calculated by multivariable logistic regression. Results The overall prevalence of past 30-day nontopical outpatient antibiotic use adjusted for age, sex, race/ethnicity, poverty status, time of year of the interview, and insurance status from 1999–2002 to 2015–2018 changed significantly from 4.9% (95% CI, 3.9% to 5.0%) to 3.0% (95% CI, 2.6% to 3.0%), with the largest decrease among children age 0–1 years. From 2007–2010 to 2015–2018, there was no significant change (adjusted prevalence ratio [adjPR], 1.0; 95% CI, 0.8 to 1.2). Age was significantly associated with antibiotic use, with children age 0–1 years having significantly higher antibiotic use than all other age categories >6 years. Being non-Hispanic Black was negatively associated with antibiotic use as compared with being non-Hispanic White (adjPR, 0.6; 95% CI, 0.4 to 0.8). Conclusions While there were declines in antibiotic use from 1999–2002 to 2015–2018, there were no observed declines during the last decade.

BackgroundWe assessed the performance of CoronaCHEK lateral flow assay on samples from Uganda and Baltimore to determine the impact of geographic origin on assay performance.MethodsSerum samples from SARS-CoV-2 PCR+ individuals (Uganda: 78 samples from 78 individuals and Baltimore: 266 samples from 38 individuals) and from pre-pandemic individuals (Uganda 1077 and Baltimore 532) were evaluated. Prevalence ratios (PR) were calculated to identify factors associated with a false-positive test.ResultsAfter first positive PCR in Ugandan samples the sensitivity was: 45% (95% CI 24,68) at 0-7 days; 79% (95%CI 64,91) 8-14 days; and 76% (95%CI 50,93) >15 days. In samples from Baltimore, sensitivity was: 39% (95% CI 30, 49) 0-7 days; 86% (95% CI 79,92) 8-14 days; and 100% (95% CI 89,100) 15 days post positive PCR. The specificity of 96.5% (95% CI 97.5,95.2) in Ugandan samples was significantly lower than samples from Baltimore 99.3% (95% CI 98.1,99.8), pConclusionsSensitivity of the CoronaCHEK was similar in samples from Uganda and Baltimore. The specificity was significantly lower in Ugandan samples than in Baltimore samples. False positive results in Ugandan samples appear to correlate with a recent history of a febrile illness, potentially indicative of a cross-reactive immune response in individuals from East Africa.

Introduction UNAIDS models suggest HIV incidence is declining in sub‐Saharan Africa. The objective of this study was to assess whether modelled trends are supported by empirical evidence. Methods We conducted a systematic review and meta‐analysis of adult HIV incidence data from sub‐Saharan Africa by searching Embase, Scopus, PubMed and OVID databases and technical reports published between 1 January 2010 and 23 July 2019. We included prospective and cross‐sectional studies that directly measured incidence from blood samples. Incidence data were abstracted according to population risk group, geographic location, sex, intervention arm and calendar period. Weighted regression models were used to assess incidence trends across general population studies by sex. We also identified studies reporting greater than or equal to three incidence measurements since 2010 and assessed trends within them. Results Total 291 studies, including 22 sub‐Saharan African countries, met inclusion criteria. Most studies were conducted in South Africa (n = 102), Uganda (n = 46) and Kenya (n = 41); there were 26 countries with no published incidence data, most in western and central Africa. Data were most commonly derived from prospective observational studies (n = 163; 56%) and from geographically defined populations with limited demographic or risk‐based enrolment criteria other than age (i.e., general population studies; n = 151; 52%). Across general population studies, average annual incidence declines since 2010 were 0.12/100 person‐years (95% CI: 0.06–0.18; p = 0.001) among men and 0.10/100 person‐years (95% CI: −0.02–0.22; p = 0.093) among women in eastern Africa, and 0.25/100 person‐years (95% CI: 0.17–034; p

BackgroundUNAIDS models suggest HIV incidence is declining in sub-Saharan Africa; however, it is unclear whether modeled trends are supported by empirical evidence.MethodsWe conducted a systematic review and meta-analysis of adult HIV incidence data from sub-Saharan Africa by searching Embase, Scopus, PubMed, and OVID databases and technical reports published between January 1, 2010 and July 23, 2019. We included studies that directly measured incidence from blood samples. Incidence data were abstracted according to population risk group, geographic location, sex, intervention arm, and calendar period. Weighted regression models were used to assess incidence trends across general population studies by sex. We also identified studies reporting ≥3 incidence measurements since 2010 and assessed trends within them.Findings292 studies met inclusion criteria. Most studies were conducted in South Africa (n=102), Uganda (n=46), and Kenya (n=41); there were 27 countries with no published incidence data, most in western and central Africa. Across general population studies, average annual incidence declines since 2010 were 0.16/1000 person-years (95%CI:0.06-0.26;p=0.004) among men and 0.16/1000 person-years (95%CI: −0.01-0.33;p=0.060) among women in eastern Africa, and 0.25/1000 person-years (95%CI:0.17-034;pInterpretationEmpirical incidence data show the rate of new HIV infections is declining in eastern and southern Africa. However, recent incidence data are non-existent or very limited for many countries, particularly in western and central Africa.FundingNational Institute of Allergy and Infectious Diseases

Background The efficacy of coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) is primarily ascribed as a source of neutralizing anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. However, the composition of other immune components in CCP and their potential roles remain largely unexplored. This study aimed to describe the composition and concentrations of plasma cytokines and chemokines in eligible CCP donors. Methods A cross-sectional study was conducted among 20 prepandemic healthy blood donors without SARS-CoV-2 infection and 140 eligible CCP donors with confirmed SARS-CoV-2 infection. Electrochemiluminescence detection-based multiplexed sandwich immunoassays were used to quantify plasma cytokine and chemokine concentrations (n = 35 analytes). A SARS-CoV-2 microneutralization assay was also performed. Differences in the percentage of detection and distribution of cytokine and chemokine concentrations were examined by categorical groups using Fisher’s exact and Wilcoxon rank-sum tests, respectively. Results Among CCP donors (n = 140), the median time since molecular diagnosis of SARS-CoV-2 was 44 days (interquartile range = 38–50) and 9% (n = 12) were hospitalized due to COVID-19. Compared with healthy blood donor controls, CCP donors had significantly higher plasma levels of interferon (IFN)-γ, interleukin (IL)-10, IL-15, IL-21, and macrophage-inflammatory protein-1, but lower levels of IL-1RA, IL-8, IL-16, and vascular endothelial growth factor-A (P Conclusions Heterogeneity in cytokine and chemokine composition of CCP suggests there is a different inflammatory state among the CCP donors compared with SARS-CoV-2 naive, healthy blood donors.

Background There are limited data on individual human immunodeficiency virus (HIV) viral load (VL) trajectories at the population-level after the introduction of universal test and treat (UTT) in sub-Saharan Africa. Methods Human immunodeficiency virus VLs were assessed among HIV-positive participants through 3 population-based surveys in 4 Ugandan fishing communities surveyed between November 2011 and August 2017. The unit of analysis was a visit-pair (2 consecutive person-visits), which were categorized as exhibiting durable VL suppression, new/renewed VL suppression, viral rebound, or persistent viremia. Adjusted relative risks (adjRRs) and 95% confidence intervals (CIs) of persistent viremia were estimated using multivariate Poisson regression. Results There were 1346 HIV-positive participants (n = 1883 visit-pairs). The population-level prevalence of durable VL suppression increased from 29.7% to 67.9% during UTT rollout, viral rebound declined from 4.4% to 2.7%, and persistent viremia declined from 20.8% to 13.3%. Younger age (15–29 vs 40–49 years; adjRR = 1.80; 95% CI = 1.19–2.71), male sex (adjRR = 2.09, 95% CI = 1.47–2.95), never being married (vs currently married; adjRR = 1.88, 95% CI = 1.34–2.62), and recent migration to the community (vs long-term resident; adjRR = 1.91, 95% CI = 1.34–2.73) were factors associated with persistent viremia. Conclusions Despite increases in durable VL suppression during roll out of UTT in hyperendemic communities, a substantial fraction of the population, whose risk profile tended to be younger, male, and mobile, remained persistently viremic.

Introduction WHO/UNAIDS recommended Voluntary Medical Male Circumcision in 2007 based on systematic review of observational studies prior to 1999 and three randomized controlled trials (RCTs). To inform updated WHO guidance, we conducted a systematic review and meta‐analysis of impact of circumcision on the risk of HIV infection among heterosexual men. Methods Studies in PubMed of HIV incidence and changes in prevalence in heterosexual men by circumcision status were identified. Pooled incidence rate ratios were computed using fixed‐ and random‐effects meta‐analysis and risk of bias was assessed using the ROBINS‐I tool. Results and Discussion In three RCTs, the pooled incidence ratio was 0.41 (95% CI 0.30 to 0.56), with risk difference 10 (8 to 12) fewer infections per 1000 person‐years (py). Pooled incidence ratios were 0.34 (0.24 to 0.49) in two post‐RCT follow‐up studies, 0.29 (0.19 to 0.43) in men at high HIV risk (five cohorts), 0.48 (0.33 to 0.70) in four community‐based cohorts before circumcision scale‐up, and 0.56 (0.49 to 0.64) (7 [6 to 8] fewer per 1000 py) in six community‐based cohorts during circumcision and antiretroviral treatment scale‐up. Heterogeneity between studies was low except in men at high HIV risk. We estimated 520,000 (425,000 to 605,000) fewer infections occurred in men by end of 2018 from 22.7 million circumcisions performed since 2008 and increasing by 155,000 (125,000 to 180,000) annually if epidemic conditions remain similar. After exclusion of studies with high risk of bias and those conducted outside Africa, pooled incidence ratios were similar. There was no evidence of confounding nor changes in risk behaviour following circumcision. In post‐hoc exploratory analyses we observed a trend of decreasing effectiveness of circumcision in cohorts with lower HIV incidence. Conclusions Efficacy of medical male circumcision on HIV incidence from randomized controlled trials was supported by effectiveness from observational studies in populations with diverse HIV risk and changing epidemic contexts. Voluntary Medical Male Circumcision remains an important evidence‐based intervention for control of generalized HIV epidemics.

In the United States, human papillomavirus (HPV) vaccination has been recommended for females since 2006 and males since 2011. We assessed temporal trends in HPV vaccine coverage (defined as receipt of ≥1 dose) among 9-26-year-old participants in the 2011-2016 National Health and Nutrition Examination Surveys. While coverage increased overall, from 37.7% to 45.7%, among females (adjusted prevalence difference [aPD], 7.1%; 95% confidence interval [CI], .1%-13.7%), there was no change among female adolescents aged 9-17 years. For males, coverage increased overall, from 7.8% to 27.4% (aPD, 18.8%; 95% CI, 14.1%-23.5%), and among every stratum of age, race/ethnicity, health insurance status, poverty level, and immigration status (P ≤ .05). The increase in HPV vaccine coverage observed among males is encouraging, but coverage remains below national targets for both males and females.

BackgroundTo assess the effect of a combination strategy for prevention of human immunodeficiency virus (HIV) on the incidence of HIV infection, we analyzed the association between the incidence of HIV and the scale-up of antiretroviral therapy (ART) and medical male circumcision in Rakai, Uganda. Changes in population-level viral-load suppression and sexual behaviors were also examined. MethodsBetween 1999 and 2016, data were collected from 30 communities with the use of 12 surveys in the Rakai Community Cohort Study, an open, population-based cohort of persons 15 to 49 years of age. We assessed trends in the incidence of HIV on the basis of observed seroconversion data, participant-reported use of ART, participant-reported male circumcision, viral-load suppression, and sexual behaviors. ResultsIn total, 33,937 study participants contributed 103,011 person-visits. A total of 17,870 persons who were initially HIV-negative were followed for 94,427 person-years; among these persons, 931 seroconversions were...

International audience; Background: International and global organisations advocate targeting interventions to areas of high HIV prevalence (ie, hotspots). To better understand the potential benefits of geo-targeted control, we assessed the extent to which HIV hotspots along Lake Victoria sustain transmission in neighbouring populations in south-central Uganda.Methods: We did a population-based survey in Rakai, Uganda, using data from the Rakai Community Cohort Study. The study surveyed all individuals aged 15-49 years in four high-prevalence Lake Victoria fishing communities and 36 neighbouring inland communities. Viral RNA was deep sequenced from participants infected with HIV who were antiretroviral therapy-naive during the observation period. Phylogenetic analysis was used to infer partial HIV transmission networks, including direction of transmission. Reconstructed networks were interpreted through data for current residence and migration history. HIV transmission flows within and between high-prevalence and low-prevalence areas were quantified adjusting for incomplete sampling of the population.Findings: Between Aug 10, 2011, and Jan 30, 2015, data were collected for the Rakai Community Cohort Study. 25 882 individuals participated, including an estimated 75·7% of the lakeside population and 16·2% of the inland population in the Rakai region of Uganda. 5142 participants were HIV-positive (2703 [13·7%] in inland and 2439 [40·1%] in fishing communities). 3878 (75·4%) people who were HIV-positive did not report antiretroviral therapy use, of whom 2652 (68·4%) had virus deep-sequenced at sufficient quality for phylogenetic analysis. 446 transmission networks were reconstructed, including 293 linked pairs with inferred direction of transmission. Adjusting for incomplete sampling, an estimated 5·7% (95% credibility interval 4·4-7·3) of transmissions occurred within lakeside areas, 89·2% (86·0-91·8) within inland areas, 1·3% (0·6-2·6) from lakeside to inland areas, and 3·7% (2·3-5·8) from inland to lakeside areas.Interpretation: Cross-community HIV transmissions between Lake Victoria hotspots and surrounding inland populations are infrequent and when they occur, virus more commonly flows into rather than out of hotspots. This result suggests that targeted interventions to these hotspots will not alone control the epidemic in inland populations, where most transmissions occur. Thus, geographical targeting of high prevalence areas might not be effective for broader epidemic control depending on underlying epidemic dynamics.Funding: The Bill & Melinda Gates Foundation, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, the National Institute of Child Health and Development, the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases, the World Bank, the Doris Duke Charitable Foundation, the Johns Hopkins University Center for AIDS Research, and the President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention.

The limiting-antigen avidity (LAg-Avidity) assay with viral load (VL) >1,000 copies/mL is being used to estimate population-level HIV incidence in Africa. However, this has not been validated in East Africa where HIV-1 subtypes A and D circulate. Sera from persons seen in two surveys (2008–2009 and 2012–2013) limited to those who attended the previous round of the Rakai Community Cohort in Uganda were analyzed. The performance of the current LAg-Avidity protocol, with a mean duration of recent infection (MDRI) of 130 days and false recent rate (FRR) of 0%, was compared with subtype-specific MDRI and FRR, adjusted to subtype distributions. The observed incidence was 1.05/100 person years (py) [95% confidence interval (CI) 0.90–1.23] in 2008–2009 and 0.66/100 py (95% CI 0.52–0.83) in 2012–2013. In contrast, the per-protocol LAg-Avidity incidence estimates were 1.63/100 py (95% CI 0.97–2.30) in 2008–2009 and 2.55/100 py (95% CI 1.51–3.59) in 2012–2013 (a significant increase, p

BACKGROUND: Combination antiretroviral therapy (ART) improves HIV-associated neurocognitive disorder (HAND) stage in the US where subtype B predominates, but the effect of ART and subtype on HAND stage in individuals in Uganda with subtypes D and A is largely unknown. SETTING: A community-based cohort of participants residing in Rakai, Uganda. METHODS: 399 initially ART-naive HIV-seropositive (HIV+) individuals were followed over two years. Neurological, neuropsychological test and functional assessments were used to determine HAND stage. Frequency and predictors of HAND and HIV-associated dementia (HAD) were assessed at baseline and at follow-up after ART initiation in 312 HIV+ individuals. HIV subtype was determined from gag and env sequences. RESULTS: At two year follow-up, HAD frequency among HIV+ individuals on ART (n=312) decreased from 13% to 5% (p 100,000 copies/mL. At follow-up, age and depression remained significantly associated with HAD. CONCLUSION: HIV+ individuals on ART in rural Uganda had a significant decrease in the frequency of HAD, but HAND persists after two years on ART. The current guideline of immediate ART initiation after HIV diagnosis is likely to greatly reduce HAD in Sub-Saharan Africa. Further studies of the effect of HIV subtype and neurocognitive performance are warranted.

Background: Targeting combination HIV interventions to locations and populations with high HIV burden is a global priority, but the impact of these strategies on HIV incidence is unclear. We assessed the impact of combination HIV interventions on HIV incidence in four HIV-hyperendemic communities in Uganda. Methods: We did an open population-based cohort study of people aged 15–49 years residing in four fishing communities on Lake Victoria. The communities were surveyed five times to collect self-reported demographic, behavioural, and service-uptake data. Free HIV testing was provided at each interview, with referral to combination HIV intervention services as appropriate. From November, 2011, combination HIV intervention services were rapidly expanded in these geographical areas. We evaluated trends in HIV testing coverage among all participants, circumcision coverage among male participants, antiretroviral therapy (ART) coverage and HIV viral load among HIV-positive participants, and sexual behaviours and HIV incidence among HIV-negative participants. Findings: From Nov 4, 2011, to Aug 16, 2017, data were collected from five surveys. Overall, 8942 participants contributed 20 721 person-visits; 4619 (52%) of 8942 participants were male. HIV prevalence was 41% (1598 of 3870) in the 2011–12 baseline survey and declined to 37% (1740 of 4738) at the final survey (p

The dynamics of infectious disease epidemics are driven by interactions between individuals with differing disease status (e.g., susceptible, infected, immune). Mechanistic models that capture the dynamics of such "dependent happenings" are a fundamental tool of infectious disease epidemiology. Recent methodological advances combined with access to new data sources and computational power have resulted in an explosion in the use of dynamic models in the analysis of emerging and established infectious diseases. Increasing use of models to inform practical public health decision making has challenged the field to develop new methods to exploit available data and appropriately characterize the uncertainty in the results. Here, we discuss recent advances and areas of active research in the mechanistic and dynamic modeling of infectious disease. We highlight how a growing emphasis on data and inference, novel forecasting methods, and increasing access to "big data" are changing the field of infectious disease dynamics. We showcase the application of these methods in phylodynamic research, which combines mechanistic models with rich sources of molecular data to tie genetic data to population-level disease dynamics. As dynamics and mechanistic modeling methods mature and are increasingly tied to principled statistical approaches, the historic separation between the infectious disease dynamics and "traditional" epidemiologic methods is beginning to erode; this presents new opportunities for cross pollination between fields and novel applications.

HIV-1 subtype and viral load set point have been implicated as strong predictors of HIV-1 disease progression; however, the relationship between these two variables has not been investigated. We used data from the Rakai Community Cohort Study to investigate whether the association between viral load set point and disease progression is modified by HIV subtype. Time to AIDS or AIDS-related death was estimated by Kaplan–Meier survival analysis stratified by subtype and viral set point, and Cox proportional hazards regression with an interaction term between viral load set point and HIV subtype. The interaction term did not indicate effect measure modification between viral load set point and progression to AIDS by HIV-1 subtype [adjusted hazard ratio (aHR), 0.99; 95% confidence interval (CI) 0.61–1.61; p = .968]. Stratifed analysis by subtype was also not indicative of a difference in relationship between viral load set point and time to AIDS with overlapping 95% CIs between subtypes A and D (subtype A aHR: 2.40, 95% CI 1.45–3.99, subtype D aHR: 1.96, 95% CI 1.60–2.40). These results indicate that the higher mortality in subtype D-infected individuals is independent of viral load set point.

Phylogenetic analysis of pathogens is an increasingly powerful way to reduce the spread of epidemics, including HIV. As a result, phylogenetic approaches are becoming embedded in public health and research programmes, as well as outbreak responses, presenting unique ethical, legal, and social issues that are not adequately addressed by existing bioethics literature. We formed a multidisciplinary working group to explore the ethical issues arising from the design of, conduct in, and use of results from HIV phylogenetic studies, and to propose recommendations to minimise the associated risks to both individuals and groups. We identified eight key ethical domains, within which we highlighted factors that make HIV phylogenetic research unique. In this Review, we endeavoured to provide a framework to assist researchers, public health practitioners, and funding institutions to ensure that HIV phylogenetic studies are designed, done, and disseminated in an ethical manner. Our conclusions also have broader relevance for pathogen phylogenetics. ispartof: LANCET HIV vol:5 issue:11 pages:E656-E666 ispartof: location:Netherlands status: published

HIV-1 set-point viral load—the approximately stable value of viraemia in the first years of chronic infection—is a strong predictor of clinical outcome and is highly variable across infected individuals. To better understand HIV-1 pathogenesis and the evolution of the viral population, we must quantify the heritability of set-point viral load, which is the fraction of variation in this phenotype attributable to viral genetic variation. However, current estimates of heritability vary widely, from 6% to 59%. Here we used a dataset of 2,028 seroconverters infected between 1985 and 2013 from 5 European countries (Belgium, Switzerland, France, the Netherlands and the United Kingdom) and estimated the heritability of set-point viral load at 31% (CI 15%–43%). Specifically, heritability was measured using models of character evolution describing how viral load evolves on the phylogeny of whole-genome viral sequences. In contrast to previous studies, (i) we measured viral loads using standardized assays on a sample collected in a strict time window of 6 to 24 months after infection, from which the viral genome was also sequenced; (ii) we compared 2 models of character evolution, the classical “Brownian motion” model and another model (“Ornstein–Uhlenbeck”) that includes stabilising selection on viral load; (iii) we controlled for covariates, including age and sex, which may inflate estimates of heritability; and (iv) we developed a goodness of fit test based on the correlation of viral loads in cherries of the phylogenetic tree, showing that both models of character evolution fit the data well. An overall heritability of 31% (CI 15%–43%) is consistent with other studies based on regression of viral load in donor–recipient pairs. Thus, about a third of variation in HIV-1 virulence is attributable to viral genetic variation., Author summary The severity of the outcome of infection by a pathogen depends on many distinct factors. These include the environment and the genetic sequences of both the host and the pathogen, among others. The fraction of variability in disease outcome explained by pathogen genetic factors is termed “heritability”, because these factors are “inherited” by the new host upon infection. Quantifying heritability is key to understanding the development of the disease and the evolution of the virus. Here, we determined heritability of set-point viral load (SPVL) in HIV-1. SPVL is the stable value of viraemia in asymptomatic infection and it is a strong predictor of disease severity. While heritability of SPVL has been estimated using comparisons of viral genome sequences, this has resulted in widely variable estimates of heritability. Using a large dataset of patients living in Europe, standardised viral loads measures, and new methods, we obtain a more definitive estimate of HIV-1 SPVL heritability in Europe at about 30%. Thus, a significant amount of the variation in disease outcome is explained by the genetics of the virus.

A growing number of government agencies, funding organizations, and publishers are endorsing the call for increased data sharing, especially in biomedical research, many with an ultimate goal of open data. Open data is among the least restrictive forms of data sharing, in contrast to managed access mechanisms, which typically have terms of use and in some cases oversight by the data generators themselves. But despite an ethically sound rationale and growing support for open data sharing in many parts of the world, concerns remain, particularly among researchers in low- and middle-income countries (LMICs) in Africa, Latin America, and parts of Asia and the Middle East that comprise the Global South. Drawing on our perspective as researchers and ethicists working in the Global South, we see opportunities to improve community engagement, raise awareness, and build capacity, all toward improving research and data sharing involving researchers in LMICs.

Next-generation sequencing has yet to be widely adopted for HIV. The difficulty of accurately reconstructing the consensus sequence of a quasispecies from reads (short fragments of DNA) in the presence of rapid between- and within-host evolution may have presented a barrier. In particular, mapping (aligning) reads to a reference sequence leads to biased loss of information; this bias can distort epidemiological and evolutionary conclusions.De novoassembly avoids this bias by effectively aligning the reads to themselves, producing a set of sequences called contigs. However contigs provide only a partial summary of the reads, misassembly may result in their having an incorrect structure, and no information is available at parts of the genome where contigs could not be assembled. To address these problems we developed the toolshiverto preprocess reads for quality and contamination, then map them to a reference tailored to the sample using corrected contigs supplemented with existing reference sequences. Run with two commands per sample, it can easily be used for large heterogeneous data sets. We useshiverto reconstruct the consensus sequence and minority variant information from paired-end short-read data produced with the Illumina platform, for 65 existing publicly available samples and 50 new samples. We show the systematic superiority of mapping toshiver’s constructed reference over mapping the same reads to the standard reference HXB2: an average of 29 bases per sample are called differently, of which 98.5% are supported by higher coverage. We also provide a practical guide to working with imperfect contigs.