ImportanceEstimating the true burden of SARS-CoV-2 infection has been difficult in sub-Saharan Africa owing to asymptomatic infections and inadequate testing capacity. Antibody responses from serologic surveys can provide an estimate of SARS-CoV-2 exposure at the population level.ObjectiveTo estimate SARS-CoV-2 seroprevalence, attack rates, and reinfection in eastern Uganda using serologic surveillance from 2020 to early 2022.Design, Setting, and ParticipantsThis cohort study was conducted in the Tororo and Busia districts of eastern Uganda. Plasma samples from participants in the Program for Resistance, Immunology, Surveillance, and Modeling of Malaria in Uganda Border Cohort were obtained at 4 sampling intervals: October to November 2020, March to April 2021, August to September 2021, and February to March 2022. Each participant contributed up to 4 time points for SARS-CoV-2 serology, with almost half of all participants contributing at all 4 time points, and almost 90% contributing at 3 or 4 time points. Information on SARS-CoV-2 vaccination status was collected from participants, with the earliest reported vaccinations in the cohort occurring in May 2021.Main Outcomes and MeasuresThe main outcomes of this study were antibody responses to the SARS-CoV-2 spike protein as measured with a bead-based serologic assay. Individual-level outcomes were aggregated to population-level SARS-CoV-2 seroprevalence, attack rates, and boosting rates. Estimates were weighted by the local age distribution according to census data.ResultsA total of 1483 samples from 441 participants living in 76 households were tested. Of the 441 participants, 245 (55.6%) were female, and their mean (SD) age was 16.04 (16.04) years. By the end of the Delta wave and before widespread vaccination, adjusted SARS-CoV-2 seroprevalence was 67.7% (95% credible interval [CrI], 62.5%-72.6%) in the study population. During the subsequent Omicron wave, 84.8% (95% CrI, 67.9%-93.7%) of unvaccinated, previously seronegative individuals were infected for the first time, and 50.8% (95% CrI, 40.6%-59.7%) of unvaccinated, already seropositive individuals were likely reinfected, leading to an overall seropositivity of 96.0% (95% CrI, 93.4%-97.9%) in this population. These results suggest a lower probability of reinfection in individuals with higher preexisting antibody levels. There was evidence of household clustering of SARS-CoV-2 seroconversion. No significant associations were found between SARS-CoV-2 seroconversion and gender, household size, or recent Plasmodium falciparum malaria exposure.Conclusions and RelevanceIn this cohort study in a rural population in eastern Uganda, there was evidence of very high SARS-CoV-2 infection rates throughout the pandemic inconsistent with national level case data and high reinfection rates during the Omicron wave.

Indoor residual spraying (IRS) and long-lasting insecticide-treated bednets (LLINs) are common tools for reducing malaria transmission. We studied a cohort in Uganda with universal access to LLINs after 5 years of sustained IRS to explore LLIN adherence when malaria transmission has been greatly reduced. Eighty households and 526 individuals in Nagongera, Uganda were followed from October 2017 –October 2019. Every two weeks, mosquitoes were collected from sleeping rooms and LLIN adherence the prior night assessed. Episodes of malaria were diagnosed using passive surveillance. Risk factors for LLIN non-adherence were evaluated using multi-level mixed logistic regression. An age-matched case-control design was used to measure the association between LLIN non-adherence and malaria. Across all time periods, and particularly in the last 6 months, non-adherence was higher among both children <5 years (OR 3.31, 95% CI: 2.30–4.75; p<0.001) and school-aged children 5–17 years (OR 6.88, 95% CI: 5.01–9.45; p<0.001) compared to adults. In the first 18 months, collection of fewer mosquitoes was associated with non-adherence (OR 3.25, 95% CI: 2.92–3.63; p<0.001), and, in the last 6 months, residents of poorer households were less adherent (OR 5.1, 95% CI: 1.17–22.2; p = 0.03). Any reported non-adherence over the prior two months was associated with a 15-fold increase in the odds of having malaria (OR 15.0, 95% CI: 1.95 to 114.9; p = 0.009). Knowledge about LLIN use was high, and the most frequently reported barriers to use included heat and low perceived risk of malaria. Children, particularly school-aged, participants exposed to fewer mosquitoes, and those from poorer households, were less likely to use LLINs. Non-adherence to LLINs was associated with an increased risk of malaria. Strategies, such as behavior change communications, should be prioritized to ensure consistent LLIN use even when malaria transmission has been greatly reduced.

Importance: Estimating the true burden of SARS-CoV-2 infection has been difficult in sub-Saharan Africa due to asymptomatic infections and inadequate testing capacity. Antibody responses from serologic surveys can provide an estimate of SARS-CoV-2 exposure at the population level. Objective: To estimate SARS-CoV-2 seroprevalence, attack rates, and re-infection in eastern Uganda using serologic surveillance from 2020 to early 2022. Design: Plasma samples from participants in the Program for Resistance, Immunology, Surveillance, and Modeling of Malaria in Uganda (PRISM) Border Cohort were obtained at four sampling intervals: October-November 2020; March-April 2021; August-September 2021; and February-March 2022. Setting: Tororo and Busia districts, Uganda. Participants: 1,483 samples from 441 participants living in 76 households were tested. Each participant contributed up to 4 time points for SARS-CoV-2 serology, with almost half of all participants contributing at all 4 time points, and almost 90% contributing at 3 or 4 time points. Information on SARS-CoV-2 vaccination status was collected from participants, with the earliest reported vaccinations in the cohort occurring in May 2021. Main Outcome(s) and Measure(s): The main outcomes of this study were antibody responses to the SARS-CoV-2 spike protein as measured with a bead-based serologic assay. Individual-level outcomes were aggregated to population-level SARS-CoV-2 seroprevalence, attack rates, and boosting rates. Estimates were weighted by the local age distribution based on census data. Results: By the end of the Delta wave and before widespread vaccination, nearly 70% of the study population had experienced SARS-CoV-2 infection. During the subsequent Omicron wave, 85% of unvaccinated, previously seronegative individuals were infected for the first time, and ~50% or more of unvaccinated, already seropositive individuals were likely re-infected, leading to an overall 96% seropositivity in this population. Our results suggest a lower probability of re-infection in individuals with higher pre-existing antibody levels. We found evidence of household clustering of SARS-CoV-2 seroconversion. We found no significant associations between SARS-CoV-2 seroconversion and gender, household size, or recent Plasmodium falciparum malaria exposure. Conclusions and Relevance: Findings from this study are consistent with very high infection rates and re-infection rates for SARS-CoV-2 in a rural population from eastern Uganda throughout the pandemic.

Background<br />Malaria is an important cause of fever across much of sub-Saharan Africa and other places where Plasmodium falciparum infection is highly prevalent. Here, we estimate the fraction of fever that is attributable to malaria using data from two studies in Nagongera, Tororo, Uganda that followed cohorts of children and adults longitudinally from 2011-2019. The study included three years before and five years after indoor residual spraying (IRS) sharply reduced mosquito populations, malaria exposure, and the prevalence of malaria infection. We estimate the malaria attributable fraction of fever (MAFF) by directly quantifying and comparing fever before and after malaria control.<br />Methods and Findings<br />We estimated fever prevalence before and after IRS started, comparing subjective (i.e., self-reported) and objective fever during scheduled and unscheduled visits (i.e., to seek care) in young children (under 5 years old), older children (aged 5-10 years), and adults (over 18 years old). We estimated that there were 78-90 total days per person, per year (pppy) with subjective fever during the pre-IRS baseline in young children; 52-58 in older children; and 38-46 days in adults. After IRS, sub-clinical fever declined to 5-6 days pppy with fever in young children to around 3 in older children, and around 1 in adults: a 94% reduction in young children, 95% in older children, and 99% in adults. Reductions in total fever prevalence for care seeking (during unscheduled visits) declined by around 50% in young children, 65% in older children, and 80% in adults. In the before vs. after comparison, malaria accounted for 88% of objective fever during scheduled visits in young children, 75% in older children, and 91% in adults. Total fever declined by 80-85% in children and 90-93% in adults. During care seeking, malaria accounted for around 44% of objective fever in young children, but no meaningful differences were observed at other ages. These patterns were accompanied by changes in care seeking and total fever. Over the first few months of the study, care seeking rates increased in all groups, but then care seeking rates started a decline that continued until the study ended. By the end of the study, care seeking rates had declined by more than 75% overall compared with the start.<br />Conclusions<br />The fraction attributed to malaria differed by age and context. In this study population with good access to care, fever was rare at the end of the study in the absence of malaria. Based on the before vs. after comparison, malaria was directly or indirectly responsible for most subjective fever in the clinical setting, and it was also the dominant cause of objective fever. Surprisingly, a large fraction of subjective fever that occurred before IRS, during both scheduled and unscheduled visits, occurred in people who tested negative for malaria. The study draws attention to the importance of sub-clinical disease as a contributor to the burden of health in malaria endemic settings.<br />Funding The PRISM studies (U19AI089674) were funded by the National Institutes of Allergies and Infectious Diseases (NIAID) as part of the International Centers of Excellence for Malaria Research (ICEMR).