Estimation of cause-specific mortality in Rakai, Uganda, using verbal autopsy 1999-2019.

BACKGROUND: There are scant data on the causes of adult deaths in sub-Saharan Africa. We estimated the level and trends in adult mortality, overall and by different causes, in rural Rakai, Uganda, by age, sex, and HIV status. OBJECTIVES: To estimate and analyse adult cause-specific mortality trends in Rakai, Uganda. METHODOLOGY: Mortality information by cause, age, sex, and HIV status was recorded in the Rakai Community Cohort study using verbal autopsy interviews, HIV serosurveys, and residency data. We estimated the average number of years lived in adulthood. Using demographic decomposition methods, we estimated the contribution of each cause of death to adult mortality based on the average number of years lived in adulthood. RESULTS: Between 1999 and 2019, 63082 adults (15-60 years) were censused, with 1670 deaths registered. Of these, 1656 (99.2%) had completed cause of death data from verbal autopsy. The crude adult death rate was 5.60 (95% confidence interval (CI): 5.33-5.87) per 1000 person-years of observation (pyo). The crude death rate decreased from 11.41 (95% CI: 10.61-12.28) to 3.27 (95% CI: 2.89-3.68) per 1000 pyo between 1999-2004 and 2015-2019. The average number of years lived in adulthood increased in people living with HIV and decreased in HIV-negative individuals between 2000 and 2019. Communicable diseases, primarily HIV and Malaria, had the biggest decreases, which improved the average number of years lived by approximately extra 12 years of life in females and 6 years in males. There were increases in deaths due to non-communicable diseases and external causes, which reduced the average number of years lived in adulthood by 2.0 years and 1.5 years in females and males, respectively. CONCLUSION: There has been a significant decline in overall mortality from 1999 to 2019, with the greatest decline seen in people living with HIV since the availability of antiretroviral therapy in 2004. By 2020, the predominant causes of death among females were non-communicable diseases, with external causes of death dominating in males.

Main findings: There are significant declines in mortality in people living with HIV. However, mortality in HIV-negative people increased due to non-communicable diseases in females, and injuries and external causes of death among males.Added knowledge: In this HIV-endemic area, decreasing adult mortality has been documented over the last 20 years. This paper benchmarks the changes in cause-specific mortality in this area.Global health impact for policy action: As in many African countries, more effort is needed to reduce mortality for non-communicable diseases, injuries, and external causes of death as these seem to have been neglected.

The intersection between migration, HIV, and contraceptive use in Uganda: a cross-sectional population-based study.

BACKGROUND: Low use of modern methods of contraception has been linked to HIV seropositivity and to migration, but few studies have evaluated the intersection of both risk factors with contraceptive use. METHODS: We analyzed cross-sectional data from sexually active female participants aged 15 to 49 years in the Rakai Community Cohort Study (RCCS) between 2011 and 2013. The RCCS is an open population-based census and individual survey in south-central Uganda. Recent in-migrants (arrival within approximately 1.5 years) into RCCS communities were identified at time of household census. The primary outcome was unsatisfied demand for a modern contraceptive method (injectable, oral pill, implant, or condom), which was defined as non-use of a modern contraceptive method among female participants who did not want to become pregnant in the next 12 months. Poisson regression models with robust variance estimators were used to identify associations and interactions between recent migration and HIV serostatus on unsatisfied contraceptive demand. RESULTS: There were 3,417 sexually active participants with no intention of becoming pregnant in the next year. The mean age was 30 (± 8) years, and 17.3% (n = 591) were living with HIV. Overall, 43.9% (n = 1,500) were not using any modern contraceptive method. Recent in-migrants were somewhat more likely to have unsatisfied contraceptive demand as compared to long-term residents (adjusted prevalence risk ratio [adjPRR] = 1.14; 95% confidence interval [95%CI]: 1.02-1.27), whereas participants living with HIV were less likely to have unsatisfied contraceptive demand relative to HIV-seronegative participants (adjPRR = 0.80; 95%CI = 0.70-0.90). When stratifying on migration and HIV serostatus, we observed the highest levels of unsatisfied contraceptive demand among in-migrants living with HIV (48.7%); however, in regression analyses, interaction terms between migration and HIV serostatus were not statistically significant. CONCLUSIONS: Unsatisfied contraceptive demand was high in this rural Ugandan setting. Being an in-migrant, particularly among those living with HIV, was associated with higher unsatisfied contraceptive demand.

Through a cross-sectional study, we explored the relationship between HIV status, migration, and contraceptive use among sexually active women of reproductive age in rural south-central Uganda. People who had moved into the study area within the last 1.5 years were considered in-migrants, compared to long-term residents i.e. people who had not moved. We examined unsatisfied demand for a modern contraceptive method, which is to say female participants who did not want to become pregnant in the next 12 months and were not using at least one of the following contraceptive methods: injectable, oral pill, implant, or condom. We included 3,417 sexually active female participants with no intention of becoming pregnant in the next year. The average age of these women was 30 years, less than 20% were living with HIV, and almost half were not using any modern contraceptive methods. Recent in-migrants were somewhat more likely to have unsatisfied contraceptive demand as compared to long-term residents, whereas participants living with HIV were less likely to have unsatisfied contraceptive demand relative to HIV-negative participants. Being an in-migrant, particularly among those living with HIV, was associated with higher unsatisfied contraceptive demand. This study shows the need for integrating contraceptive and HIV services for mobile populations in East Africa.

HIV epidemiologic trends among occupational groups in Rakai, Uganda: A population-based longitudinal study, 1999-2016.

Certain occupations have been associated with heightened risk of HIV acquisition and spread in sub-Saharan Africa, including female bar and restaurant work and male transportation work. However, data on changes in population prevalence of HIV infection and HIV incidence within occupations following mass scale-up of African HIV treatment and prevention programs is very limited. We evaluated prospective data collected between 1999 and 2016 from the Rakai Community Cohort Study, a longitudinal population-based study of 15- to 49-year-old persons in Uganda. Adjusted prevalence risk ratios for overall, treated, and untreated, prevalent HIV infection, and incidence rate ratios for HIV incidence with 95% confidence intervals were estimated using Poisson regression to assess changes in HIV outcomes by occupation. Analyses were stratified by gender. There were 33,866 participants, including 19,113 (56%) women. Overall, HIV seroprevalence declined in most occupational subgroups among men, but increased or remained mostly stable among women. In contrast, prevalence of untreated HIV substantially declined between 1999 and 2016 in most occupations, irrespective of gender, including by 70% among men (12.3 to 4.2%; adjPRR = 0.30; 95%CI:0.23-0.41) and by 78% among women (14.7 to 4.0%; adjPRR = 0.22; 95%CI:0.18-0.27) working in agriculture, the most common self-reported primary occupation. Exceptions included men working in transportation. HIV incidence similarly declined in most occupations, but there were no reductions in incidence among female bar and restaurant workers, women working in local crafts, or men working in transportation. In summary, untreated HIV infection and HIV incidence have declined within most occupational groups in Uganda. However, women working in bars/restaurants and local crafts and men working in transportation continue to have a relatively high burden of untreated HIV and HIV incidence, and as such, should be considered priority populations for HIV programming.

Mortality Among HIV-Infected Adults on Antiretroviral Therapy in Southern Uganda.

BACKGROUND: Monitoring and evaluation of clinical programs requires assessing patient outcomes. Numerous challenges complicate these efforts, the most insidious of which is loss to follow-up (LTFU). LTFU is a composite outcome, including individuals out of care, undocumented transfers, and unreported deaths. Incorporation of vital status information from routine patient outreach may improve the mortality estimates for those LTFU. SETTINGS: We analyzed routinely collected clinical and patient tracing data for individuals (15 years or older) initiating antiretroviral treatment between January 2014 and December 2018 at 2 public HIV care clinics in greater Rakai, Uganda. METHODS: We derived unadjusted mortality estimates using Kaplan-Meier methods. Estimates, adjusted for unreported deaths, applied weighting through the Frangakis and Rubin method to represent outcomes among LTFU patients who were successfully traced and for whom vital status was ascertained. Confidence intervals were determined through bootstrap methods. RESULTS: Of 1969 patients with median age at antiretroviral treatment initiation of 31 years (interquartile range: 25-38), 1126 (57.2%) were female patients and 808 (41%) were lost. Of the lost patients, 640 patient files (79.2%) were found and reviewed, of which 204 (31.8%) had a tracing attempt. Within the electronic health records of the program, 28 deaths were identified with an estimated unadjusted mortality 1 year after antiretroviral treatment initiation of 2.5% (95% CI: 1.8% to 3.3%). Using chart review and patient tracing data, an additional 24 deaths (total 52) were discovered with an adjusted 1-year mortality of 3.8% (95% CI: 2.6% to 5.0%). CONCLUSIONS: Data from routine outreach efforts by HIV care and treatment programs can be used to support plausible adjustments to estimates of client mortality. Mortality estimates without active ascertainment of vital status of LTFU patients may significantly underestimate program mortality.

Spike protein is a key target for stronger and more persistent T-cell responses-a study of mild and asymptomatic SARS-CoV-2 infection.

OBJECTIVES: Understanding the immune response in very mild and asymptomatic COVID-19 is crucial for developing effective vaccines and immunotherapies, yet remains poorly characterized. This longitudinal study examined the evolution of interferon (IFN)-γ responses to SARS-CoV-2 peptides in 109 asymptomatic or mildly symptomatic Ugandan COVID-19 patients across 365 days and explored their association with antibody generation. METHODS: T-cell responses to spike-containing clusters of differentiation (CD4)-S and CD8 nCoV-A (CD8-A) megapools, and the non-spike CD4-R and CD8 nCoV-B (CD8-B) megapools, were assessed and correlated with demographic and temporal variables. RESULTS: SARS-CoV-2-specific IFN-γ responses were consistently detected in all peptide pools and time points, with the spike-targeted response exhibiting higher potency and durability than the non-spike responses. Throughout the entire 365-day infection timeline, a robust positive correlation was observed between CD4 T-cell responses to the spike-derived peptides and anti-spike immunoglobulin G antibody levels, underscoring their interdependent dynamics in the immune response against SARS-CoV-2; in contrast, CD8 T-cell responses exhibited no such correlation, highlighting their distinctive, autonomous role in defense. No meaningful variations in complete blood count parameters were observed between individuals with COVID-19 infection and those without, indicating clinical insignificance. CONCLUSIONS: This study highlights the dominant role of spike-directed T-cell responses in mild and asymptomatic disease and provides crucial longitudinal data from Sub-Saharan African settings. The findings provide valuable insights into the dynamics of T-cell responses and their potential significance in developing effective strategies for combating COVID-19.

The intersection between migration, HIV, and family planning in Uganda: a cross-sectional population-based study.

Background: Low use of modern methods of contraception has been linked to HIV seropositivity and to migration, but few studies have evaluated the intersection of both risk factors with contraceptive use. Methods: We analyzed cross-sectional data from sexually active female participants aged 15 to 49 years in the Rakai Community Cohort Study (RCCS) between 2011 and 2013. The RCCS is an open population-based census and individual survey in south-central Uganda. Recent in-migrants (arrival within approximately 1.5 years) into RCCS communities were identified at time of household census. The primary outcome was unsatisfied demand for a modern contraceptive method (injectable, oral pill, implant, or condom), which was defined as non-use of a modern contraceptive method among female participants who did not want to become pregnant in the next 12 months. Poisson regression models with robust variance estimators were used to identify associations and interactions between recent migration and HIV serostatus on unsatisfied contraceptive demand. Results: There were 3,417 sexually active participants with no intention of becoming pregnant in the next year. The mean age was 30 (±8) years, and 17.3% (n=591) were living with HIV. Overall, 43.9% (n=1,500) were not using any modern contraceptive method. Recent in-migrants were somewhat more likely to have unsatisfied contraceptive demand as compared to long-term residents (adjusted prevalence risk ratio [adjPRR]=1.14; 95% confidence interval [95%CI]: 1.02-1.27), whereas participants living with HIV were less likely to have unsatisfied contraceptive demand relative to HIV-seronegative participants (adjPRR=0.80; 95%CI=0.70-0.90). When stratifying on migration and HIV serostatus, we observed the highest levels of unsatisfied contraceptive demand among in-migrants living with HIV (48.7%); however, in regression analyses, interaction terms between migration and HIV serostatus were not statistically significant. Conclusions: Unsatisfied contraceptive demand was high in this rural Ugandan setting. Being an in-migrant, particularly among those living with HIV, was associated with higher unsatisfied contraceptive demand.

Implications of rapid population growth on survey design and HIV estimates in the Rakai Community Cohort Study (RCCS), Uganda.

OBJECTIVE: Since rapid population growth challenges longitudinal population-based HIV cohorts in Africa to maintain coverage of their target populations, this study evaluated whether the exclusion of some residents due to growing population size biases key HIV metrics like prevalence and population-level viremia. DESIGN, SETTING AND PARTICIPANTS: Data 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. The study includes adults aged 15-49 years who were censused from 2019 to 2020. MEASURES: We fit ensemble machine learning models to RCCS census and survey data to predict HIV seroprevalence and viremia (prevalence of those with viral load >1000 copies/mL) in the excluded population and evaluated whether their inclusion would change overall estimates. RESULTS: Of the 24 729 census-eligible residents, 2920 (12%) residents were excluded from the RCCS because they were living in new households. The predicted seroprevalence for these excluded residents was 10.8% (95% CI: 9.6% to 11.8%)-somewhat lower than 11.7% (95% CI: 11.2% to 12.3%) in the observed sample. Predicted seroprevalence for younger excluded residents aged 15-24 years was 4.9% (95% CI: 3.6% to 6.1%)-significantly higher than that in the observed sample for the same age group (2.6% (95% CI: 2.2% to 3.1%)), while predicted seroprevalence for older excluded residents aged 25-49 years was 15.0% (95% CI: 13.3% to 16.4%)-significantly lower than their counterparts in the observed sample (17.2% (95% CI: 16.4% to 18.1%)). Over all ages, the predicted prevalence of viremia in excluded residents (3.7% (95% CI: 3.0% to 4.5%)) was significantly higher than that in the observed sample (1.7% (95% CI: 1.5% to 1.9%)), resulting in a higher overall population-level viremia estimate of 2.1% (95% CI: 1.8% to 2.4%). CONCLUSIONS: Exclusion 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.

Rapid, early, and potent Spike-directed IgG, IgM, and IgA distinguish asymptomatic from mildly symptomatic COVID-19 in Uganda, with IgG persisting for 28 months.

Introduction: Understanding how spike (S)-, nucleoprotein (N)-, and RBD-directed antibody responses evolved in mild and asymptomatic COVID-19 in Africa and their interactions with SARS-CoV-2 might inform development of targeted treatments and vaccines. Methods: Here, we used a validated indirect in-house ELISA to characterise development and persistence of S- and N-directed IgG, IgM, and IgA antibody responses for 2430 SARS-CoV-2 rt-PCR-diagnosed Ugandan specimens from 320 mild and asymptomatic COVID-19 cases, 50 uninfected contacts, and 54 uninfected non-contacts collected weekly for one month, then monthly for 28 months. Results: During acute infection, asymptomatic patients mounted a faster and more robust spike-directed IgG, IgM, and IgA response than those with mild symptoms (Wilcoxon rank test, p-values 0.046, 0.053, and 0.057); this was more pronounced in males than females. Spike IgG antibodies peaked between 25 and 37 days (86.46; IQR 29.47-242.56 BAU/ml), were significantly higher and more durable than N- and RBD IgG antibodies and lasted for 28 months. Anti-spike seroconversion rates consistently exceeded RBD and nucleoprotein rates. Spike- and RBD-directed IgG antibodies were positively correlated until 14 months (Spearman's rank correlation test, p-values 0.0001 to 0.05), although RBD diminished faster. Significant anti-spike immunity persisted without RBD. 64% and 59% of PCR-negative, non-infected non-contacts and suspects, exhibited baseline SARS-CoV-2 N-IgM serological cross-reactivity, suggesting undetected exposure or abortive infection. N-IgG levels waned after 787 days, while N-IgM levels remained undetectable throughout. Discussion: Lower N-IgG seroconversion rates and the absence of N-IgM indicate that these markers substantially underestimate the prior exposure rates. Our findings provide insights into the development of S-directed antibody responses in mild and asymptomatic infections, with varying degrees of symptoms eliciting distinct immune responses, suggesting distinct pathogenic pathways. These longer-lasting data inform vaccine design, boosting strategies, and surveillance efforts in this and comparable settings.

Capacity to Consent to Research Among Adolescent-Parent Dyads in Rakai, Uganda.

OBJECTIVES: To assess the cognitive capacity of early, middle, and late adolescents and their parents or guardians to provide informed consent to a population-based cohort study. STUDY DESIGN: Adolescent-parent/guardian dyads including 40 early (n = 80; 10-14 years), 20 middle (15-17 years), and 20 late (18-19 years) adolescents were recruited from the Rakai Community Cohort Study, an open demographic cohort in Uganda. Participants were administered the MacArthur Competence Assessment Tool for Clinical Research, a structured open-ended assessment; interviews were recorded and transcribed. Twenty transcripts were scored independently by two coders; the intraclass correlation coefficient was 0.89. The remaining interviews were scored individually. We compared mean scores for early and middle/late adolescents using a one-sided t test and score differences between parent/guardian and adolescent dyads using two-sided paired t tests. RESULTS: Early adolescents (mean score, 28.8; 95% CI, 27.1-30.5) scored significantly lower (P < .01) than middle/late adolescents (32.4; 31.6-33.1). In paired dyad comparisons, we observed no statistically significant difference in scores between parents/guardians and middle/late adolescents (difference, -0.2; 95% CI, -1.0-0.6). We found a statistically significant difference in scores between parents/guardians and early adolescents (difference, 3.0; 95% CI, 1.2-4.8). CONCLUSIONS: The capacity of adolescents-of different ages and in diverse settings-to comprehend risks, benefits, and other elements of informed consent is a critical but understudied area in research ethics. Our findings support the practice of having middle and late adolescents provide independent informed consent for sexual and reproductive health studies. Early adolescents may benefit from supported decision-making approaches.

Makerere's contribution to the development of a high impact HIV research population-based cohort in the Rakai Region, Uganda.

Longitudinal population-based cohort studies can provide critical insights on temporal, spatial and sociodemographic changes in health status and health determinants that are not obtained by other study designs. However, establishing and maintaining such a cohort study can be challenging and expensive. Here, we describe the role of Makerere University in the development and conduct of such a cohort. We chronicle the first academia-led reports of HIV in East Africa; how this led to initiation of the Rakai Community Cohort Study in 1988, the first and oldest HIV cohort in sub-Saharan Africa; its impact on HIV prevention, care and treatment; how the cohort has been maintained; and opportunities, challenges, and future directions including non-communicable diseases.

Field evaluation of the performance of seven Antigen Rapid diagnostic tests for the diagnosis of SARs-CoV-2 virus infection in Uganda.

OBJECTIVE: The objective of this study was to evaluate the performance of seven antigen rapid diagnostic tests (Ag RDTs) in a clinical setting to identify those that could be recommended for use in the diagnosis of SARS-CoV-2 infection in Uganda. METHODS: This was a cross-sectional prospective study. Nasopharyngeal swabs were collected consecutively from COVID-19 PCR positive and COVID-19 PCR negative participants at isolation centers and points of entry, and tested with the SARS-CoV-2 Ag RDTs. Test sensitivity and specificity were generated by comparing results against qRT-PCR results (Berlin Protocol) at a cycle threshold (Ct) cut-off of ≤39. Sensitivity was also calculated at Ct cut-offs ≤29 and ≤33. RESULTS: None of the Ag RDTs had a sensitivity of ≥80% at Ct cut-off values ≤33 and ≤39. Two kits, Panbio™ COVID-19 Ag and VivaDiag™ SARS-CoV-2 Ag had a sensitivity of ≥80% at a Ct cut-off value of ≤29. Four kits: BIOCREDIT COVID -19 Ag, COVID-19 Ag Respi-Strip, MEDsan® SARS-CoV-2 Antigen Rapid Test and Panbio™ COVID-19 Ag Rapid Test had a specificity of ≥97%. CONCLUSIONS: This evaluation identified one Ag RDT, Panbio™ COVID-19 Ag with a performance at high viral load (Ct value ≤29) reaching that recommended by WHO. This kit was recommended for screening of patients with COVID -19-like symptoms presenting at health facilities.

Rapid Replacement of SARS-CoV-2 Variants by Delta and Subsequent Arrival of Omicron, Uganda, 2021.

Genomic surveillance in Uganda showed rapid replacement of severe acute respiratory syndrome coronavirus 2 over time by variants, dominated by Delta. However, detection of the more transmissible Omicron variant among travelers and increasing community transmission highlight the need for near-real-time genomic surveillance and adherence to infection control measures to prevent future pandemic waves.

Incident HIV Infection Among Young Men Associated With Female Sexual Partner Types Identified Through Latent Class Analysis, Rakai, Uganda.

BACKGROUND: Sexual partner characteristics are important determinants of HIV acquisition, but little is known about partner types of young men in sub-Saharan Africa. METHODS: Sexually active men aged 15-24 years from 5 rounds (2005-2013) of the Rakai Community Cohort Study in Uganda reported characteristics of up to 4 past-year female partners. Partner types were identified using latent class analysis. HIV incidence rates (IRs) were calculated by partner-type combinations, and individual-level risk adjusted IR ratios (aIRRs) relative to the lowest incidence type were estimated using the Poisson regression with generalized estimating equations. RESULTS: Young men (N = 1771) reported 4539 past-year female sexual partners. Three partner types were identified: type A: noncohabiting, student, medium duration partnerships; type B: cohabiting, nonstudent, longer duration partnerships; and type C: noncohabiting, nonstudent shorter duration partnerships. Type C partners engaged in the most HIV-related risk behaviors. Many men (29%) had more than 1 partner type/round. IR overall was 9.8/1000 person-years [95% confidence interval (CI): 4.7 to 20.6]. IR was 4.0 (95% CI: 1.2 to 12.7) for men with type A partners alone (41% of men). Relative to them, IR for those with type B partners alone (25%) was not significantly different. Men with type C partners alone (5%) had higher risk (aIRR = 3.2; 95% CI: 1.0 to 9.9), as did men with >1 partner type, including men with both type A and type B partners (12%; aIRR = 6.3; 95% CI: 2.5 to 15.9) and men with type C and other partner types (17%; aIRR = 4.3; 95% CI: 1.7 to 10.8). CONCLUSIONS: Partner-type combination was strongly associated with HIV incidence; type C partners and having more than 1 partner type were the riskiest patterns.

Severe Acute Respiratory Syndrome Coronavirus-2 seroprevalence in South-Central Uganda, during 2019-2021.

BACKGROUND: Globally, key subpopulations such as healthcare workers (HCW) may have a higher risk of contracting SARS-CoV-2. In Uganda, limited access to Personal Protective Equipment and lack of clarity on the extent/pattern of community spread may exacerbate this situation. The country established infection prevention/control measures such as lockdowns and proper hand hygiene. However, due to resource limitations and fatigue, compliance is low, posing continued onward transmission risk. This study aimed to describe extent of SARS-CoV-2 seroprevalence in selected populations within the Rakai region of Uganda. METHODS: From 30th November 2020 to 8th January 2021, we collected venous blood from 753 HCW at twenty-six health facilities in South-Central Uganda and from 227 population-cohort participants who reported specific COVID-19 like symptoms (fever, cough, loss of taste and appetite) in a prior phone-based survey conducted (between May and August 2020) during the first national lockdown. 636 plasma specimens collected from individuals considered high risk for SARS-CoV-2 infection, prior to the first confirmed COVID-19 case in Uganda were also retrieved. Specimens were tested for antibodies to SARS-CoV-2 using the CoronaChek™ rapid COVID-19 IgM/IgG lateral flow test assay. IgM only positive samples were confirmed using a chemiluminescent microparticle immunoassay (CMIA) (Architect AdviseDx SARS-CoV-2 IgM) which targets the spike protein. SARS-CoV-2 exposure was defined as either confirmed IgM, both IgM and IgG or sole IgG positivity. Overall seroprevalence in each participant group was estimated, adjusting for test performance. RESULTS: The seroprevalence of antibodies to SARS-CoV-2 in HCW was 26.7% [95%CI: 23.5, 29.8] with no difference by sex, age, or cadre. We observed no association between PPE use and seropositivity among exposed healthcare workers. Of the phone-based survey participants, 15.6% [95%CI: 10.9, 20.3] had antibodies to SARS-CoV-2, with no difference by HIV status, sex, age, or occupation. Among 636 plasma specimens collected prior to the first confirmed COVID-19 case, 2.3% [95%CI: 1.2, 3.5] were reactive. CONCLUSIONS: Findings suggest high seroprevalence of antibodies to SARS-CoV-2 among HCW and substantial exposure in persons presenting with specific COVID-19 like symptoms in the general population of South-Central Uganda. Based on current limitations in serological test confirmation, it remains unclear whether seroprevalence among plasma specimens collected prior to confirmation of the first COVID-19 case implies prior SARS-CoV-2 exposure in Uganda.

Brief Report: Mobile Phones, Sexual Behaviors, and HIV Incidence in Rakai, Uganda, From 2010 to 2018.

BACKGROUND: Sub-Saharan Africa has the highest HIV incidence and prevalence in the world. In the past decade, mobile phone ownership has doubled, affecting social and sexual practices. Using longitudinal follow-up data, this study examined whether mobile phone ownership was associated with sexual behaviors and HIV incidence for youth and adults. METHODS: The Rakai Community Cohort Study gathers demographic and sexual health information and conducts HIV testing among an open cohort in southcentral Uganda every 12-18 months. RESULTS: Of the 10,618 participants, 58% owned a mobile phone, 69% lived in rural locations, and 77% were sexually active. Analyses were adjusted for time, location, religion, and socioeconomic status. Phone ownership was associated with increased odds of ever having had sex act for 15- to 19-year-olds [men adjusted odds ratio (AOR): 2.12, 95% confidence interval (CI): 1.78 to 2.52; women AOR: 3.20, 95% CI: 2.45 to 4.17]. Among sexually active participants, owning a phone was associated with increased odds of having 2 or more concurrent sex partners (15- to 24-year-old men AOR: 1.76, 95% CI: 1.34 to 2.32; 25 to 49-year-old men: AOR 1.81, 95% CI: 1.54 to 2.13; 25- to 49-year-old women AOR: 1.81, 95% CI: 1.32 to 2.49). For men, phone ownership was associated with increased odds of circumcision (15- to 24-year-old men AOR: 1.24, 95% CI: 1.08 to 1.41; 25- to 49-year-old men AOR: 1.12, 95% CI: 1.01 to 1.24). Phone ownership was not associated with HIV incidence. CONCLUSION: Although mobile phone ownership was associated with sexual risk behaviors, it was not associated with increased risk of HIV acquisition. Research should continue exploring how phones can be used for reducing sexual health risk.

HIV combination prevention and declining orphanhood among adolescents, Rakai, Uganda, 2001-18: an observational community cohort study.

BACKGROUND: Orphanhood increased markedly in the 1980s and 1990s in sub-Saharan Africa because of HIV-related mortality. Little is known about the contribution of HIV interventions, such as antiretroviral therapy (ART) and male medical circumcision, to more recent trends in orphanhood. In this study, we examined trends over time in maternal-only, paternal-only, and double orphanhood among adolescents before and after ART and male medical circumcision became widely available in the Rakai region of south-central Uganda. We sought to understand the association between adolescent orphanhood and HIV combination prevention (community-level ART use and prevalence of male medical circumcision). We hypothesised that increasing combination prevention, including greater use of ART and higher prevalence of male medical circumcision, would be associated with a lower probability of orphanhood. METHODS: We examined the prevalence of orphanhood among adolescents aged 15-19 years, before and after roll-out of ART in mid-2004 and male medical circumcision in 2007, using data from 28 continuously followed communities within the Rakai Community Cohort Study. We used multinomial logistic regression with clustered SEs to estimate adjusted relative risk ratios (RRs) for maternal-only, paternal-only, and double orphanhood compared with non-orphanhood over 11 survey rounds between 2001 and 2018. Controlling for community HIV prevalence, household socioeconomic status, and adolescent age, we examined the association between community prevalence of ART use among people living with HIV and prevalence of male circumcision, including traditional circumcision. The primary outcome was orphanhood among adolescents aged 15-19 years. FINDINGS: Orphanhood declined from 52% (920 of 1768 participants) in 2001-02 to 23% (592 of 2609 participants) by 2016-18 (p<0·0001), while double orphanhood declined from 20% (346 of 1768 participants) to 3% (86 of 2609 participants) (p<0·0001). Community prevalence of ART use among people living with HIV increased from 11% (105 of 945 participants) in 2005-06 to 78% (1163 of 1485 participants) in 2016-18. Male circumcision rates rose from 19% (147 of 790 participants) in 2005-06 to 65% (3535 of 5433 participants) in 2016-18. In the multinomial logistic regression model, a 10% increase in community prevalence of ART use was associated with a decrease in maternal orphanhood (adjusted relative RR 0·90, 95% CI 0·85-0·95) and double orphanhood (0·80, 0·75-0·85). In the post-ART era, a 10% increase in the community prevalence of male circumcision was associated with a decrease in paternal orphanhood (2005-18, adjusted relative RR 0·92, 0·87-0·97) and double orphanhood (0·91, 0·85-0·98). INTERPRETATION: Widespread availability and uptake of HIV combination prevention was associated with marked reductions in orphanhood among adolescents. Reductions in orphanhood promise improved health and social outcomes for young people. FUNDING: Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, and the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases.

Establishing a centralized data mart from the Rakai community cohort study to improve HIV research in Rakai, Uganda.

To improve timely access to quality HIV research data, the Rakai Health Sciences Program (RHSP) Data Mart was developed to store cohort study data from a legacy database platform in a modernized system using standard data management processes. The RHSP Data Mart was developed on a Microsoft SQL Server platform using Microsoft SQL Server Integration Services with custom data mappings and queries. The data mart stores 20+ years of longitudinal HIV research data and includes standard processes for managing data, data dictionary, training materials, and a library of queries to fulfill data requests and load new data from completed survey rounds. The RHSP Data Mart enables efficient querying and analysis of multidimensional research data by simplifying data integration and processing. A sustainable database platform with well-defined data management processes promotes data accessibility and reproducibility, enabling researchers to advance their understanding and management of infectious diseases.

Severe Acute Respiratory Syndrome Coronavirus-2 Seropositivity in South-Central Uganda, During 2019 - 2021.

Background: Globally, key subpopulations such as healthcare workers (HCWs) have a higher risk of contracting SARS-CoV-2. In Uganda, limited access to personal protective equipment amidst lack of clarity on the extent and pattern of the community disease burden may exacerbate this situation. We assessed SARS-CoV-2 antibody seroprevalence among high-risk sub-populations in South-central Uganda, including HCWs, persons within the general population previously reporting experiencing key COVID-19 like symptoms (fever, cough, loss of taste and smell) and archived plasma specimens collected between October 2019 â€" 18 th March 2020, prior to confirmation of COVID-19 in Uganda. Methods: From November 2020 - January 2021, we collected venous blood from HCWs at selected health facilities in South-Central Uganda and from population-cohort participants who reported specific COVID-19 like symptoms in a prior phone-based survey conducted (between May to August 2020) during the first national lockdown. Pre-lockdown plasma collected (between October 2019 and March 18 th , 2020) from individuals considered high risk for SARS-CoV-2 infection was retrieved. Specimens were tested for antibodies to SARS-CoV-2 using the CoronaChek TM rapid COVID-19 IgM/IgG lateral flow test assay. IgM only positive samples were confirmed using a chemiluminescent microparticle immunoassay (CMIA) (Architect AdviseDx SARS-CoV-2 IgM) which targets the spike protein. SARS-CoV-2 exposure was defined as either confirmed IgM, both IgM and IgG or sole IgG positivity. Results: The seroprevalence of antibodies to SARS-CoV-2 in HCWs was 21.1% [95%CI: 18.2-24.2]. Of the phone-based survey participants, 11.9% [95%CI: 8.0-16.8] had antibodies to SARS-CoV-2. Among 636 pre-lockdown plasma specimens, 1.7% [95%CI: 0.9-3.1] were reactive. Conclusions: Findings suggest a high seroprevalence of antibodies to SARS-CoV-2 among HCWs and substantial exposure in persons presenting with specific COVID-19 like symptoms in the general population of South-central Uganda. Based on current limitations in serological test confirmation, it remains unclear whether pre-lockdown seropositivity implies prior SARS-CoV-2 exposure in Uganda.

Evaluation of the performance of 25 SARS-CoV-2 serological rapid diagnostic tests using a reference panel of plasma specimens at the Uganda Virus Research Institute.

INTRODUCTION: Serological testing is needed to better understand the epidemiology of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Rapid diagnostic tests (RDTs) have been developed to detect specific antibodies, IgM and IgG, to the virus. The performance of 25 of these RDTs was evaluated. METHODS: A serological reference panel of 50 positive and 100 negative plasma specimens was developed from SARS-CoV-2 PCR and antibody positive patients and pre-pandemic SARS-CoV-2-negative specimens collected in 2016. Test performance of the 25 RDTs was evaluated against this panel. RESULTS: A total of 10 RDTs had a sensitivity ≥98%, while 13 RDTs had a specificity ≥98% to anti-SARS-CoV-2 IgG antibodies. Four RDTs (Boson, MultiG, Standard Q, and VivaDiag) had both sensitivity and specificity ≥98% to anti-SARS-CoV-2 IgG antibodies. Only three RDTs had a sensitivity ≥98%, while 10 RDTs had a specificity ≥98% to anti-SARS-CoV-2 IgM antibodies. Three RDTs (Autobio, MultiG, and Standard Q) had sensitivity and specificity ≥98% to combined IgG/IgM. The RDTs that performed well also had perfect or almost perfect inter-reader agreement. CONCLUSIONS: This evaluation identified three RDTs with a sensitivity and specificity to IgM/IgG antibodies of ≥98% with the potential for widespread antibody testing in Uganda.

Alcohol use during pregnancy in Rakai, Uganda.

INTRODUCTION: Antenatal alcohol use is linked to adverse maternal and neonatal outcomes. Uganda has one of the highest rates of alcohol use in sub-Saharan Africa, but the prevalence of antenatal alcohol use has not been reported in the Rakai region. METHODS: We used cross-sectional data from pregnant women in the Rakai Community Cohort Study between March 2017 and September 2018. Using bivariate and multivariable analyses, we assessed associations between self-reported antenatal alcohol use and sociodemographic characteristics, intimate partner violence (IPV), and HIV status. RESULTS: Among 960 pregnant women, the median age was 26 years, 35% experienced IPV in the past 12 months, 13% were living with HIV, and 33% reported alcohol use during their current pregnancy. After adjusting for marital status, education, smoking, and HIV status; Catholic religion (AOR: 3.54; 95% CI: 1.89-6.64; compared to other), bar/restaurant work (AOR: 2.40; 95% CI: 1.17-4.92; compared to agriculture), >one sex partner in past year (AOR: 1.92; 95% CI: 1.17-3.16), a partner that drank before sex in past year (AOR: 2.01; 95% CI: 1.48-2.74), and past year IPV (AOR: 1.55; 95% CI: 1.14-2.11) were associated with antenatal alcohol use. CONCLUSION: We found that alcohol use during pregnancy was common and associated with religion, occupation, higher numbers of past year sex partners, having a partner who drank before sex in the past 12 months, and IPV experience. More research is needed to understand the quantity, frequency, and timing of antenatal alcohol use; and potential impacts on neonates; and to identify services that are acceptable and effective among pregnant women.