Cholera outbreak associated with drinking contaminated lake shore water, Namayingo District, Uganda, July-August 2023.

Background: Cholera is endemic in Uganda with periodic outbreaks occurring annually. On July 24, 2023, Uganda's Ministry of Health confirmed a cholera outbreak in Sigulu Island, Namayingo District. We investigated to determine its magnitude, identify possible exposures, and recommend evidence-based control interventions.

Malaria epidemics and its drivers in Uganda in 2022.

Background: In Uganda, malaria is a year-round health threat, with transmission intensity varying across regions. Despite ongoing intensified interventions, an unprecedented malaria resurgence in early 2022 affected several districts, prompting a swift response from the National Malaria Control Division (NMCD). This study aims to assess the scale and underlying causes of the epidemics, quantify the excess cases and deaths, and propose targeted prevention and response strategies.

Significant variations in tolerance to clothianidin and pirimiphos-methyl in Anopheles gambiae and Anopheles funestus populations during a dramatic malaria resurgence despite sustained indoor residual spraying in Uganda.

Background: A dramatic malaria resurgence occurred in areas of Uganda between 2020 and 2022, coinciding with the switch to clothianidin-based formulations for indoor residual spraying. During the resurgence, Anopheles funestus sensu lato (s.l.

"After a long day of play, I get tired and forget to unfurl my bednet": a qualitative study exploring factors affecting insecticide-treated bednet use among school-aged children in eastern.

Background: Despite widespread access to long-lasting insecticidal nets, infection with malaria parasites remains prevalent among African school-aged children. Though this group contributes significantly to malaria transmission, few studies have explored why their bednet use is inconsistent especially from the perspective of the children themselves. This qualitative study sought to understand the behavioral and contextual factors influencing bednet use among school-aged children in Eastern Uganda.

Significant variations in tolerance to clothianidin and pirimiphos-methyl in and populations during a dramatic malaria resurgence despite sustained indoor residual spraying in Uganda.

A dramatic malaria resurgence occurred in areas of Uganda between 2020 and 2022 coincident with the switch to clothianidin-based formulations for indoor residual spraying. During the resurgence, numbers increased but when an alternative insecticide, pirimiphos methyl, was reintroduced in 2023, both malaria cases and mosquito density fell. In this study, we investigated possible causes of the resurgence by assessing; 1) whether sufficient quantities of insecticide were sprayed; 2) the residual insecticide bioefficacy against wild mosquitoes and; 3) the insecticide susceptibility of vector populations using standard test tube assays and wall cone assays.

Liver stage P. falciparum antigens highly targeted by CD4+ T cells in malaria-exposed Ugandan children.

T cell responses against liver stage Plasmodium help protect against reinfection, but the antigens and epitopes targeted by these T cells are largely unknown. This knowledge gap has impeded mechanistic studies to identify the effector functions most critical for protection. We performed a bioinformatic analysis of gene expression datasets to identify plasmodial genes that are highly and selectively expressed during liver stage infection and predict epitopes within them likely to bind MHC-II molecules prevalent in Uganda.

Analytical Sensitivity Analysis and Clinical Impact Modeling of Rapigen Rapid Diagnostic Tests for Malaria.

Laboratory benchmarking allows objective analysis of the analytical performance of malaria rapid diagnostic tests (RDTs). We present the analytical detection limits of the Rapigen BIOCREDIT Malaria Ag Pf/Pv (pLDH/pLDH), the Rapigen BIOCREDIT Malaria Ag Pf (pLDH/HRPII), and two best-in-class WHO-prequalified comparator RDTs, generated using standardized panels containing recombinant antigen, in vitro cultured parasites, international standards, and clinical samples. Detection limit antigen concentrations of HRP2, PfLDH, and PvLDH were determined for the Rapigen and comparator RDTs.

Clinical immunity to malaria involves epigenetic reprogramming of innate immune cells.

The regulation of inflammation is a critical aspect of disease tolerance and naturally acquired clinical immunity to malaria. Here, we demonstrate using RNA sequencing and epigenetic landscape profiling by cytometry by time-of-flight, that the regulation of inflammatory pathways during asymptomatic parasitemia occurs downstream of pathogen sensing-at the epigenetic level. The abundance of certain epigenetic markers (methylation of H3K27 and dimethylation of arginine residues) and decreased prevalence of histone variant H3.

Dramatic resurgence of malaria after 7 years of intensive vector control interventions in Eastern Uganda.

Background: Tororo District, Uganda experienced a dramatic decrease in malaria burden from 2015-19 following 5 years of indoor residual spraying (IRS) with carbamate (Bendiocarb) and then organophosphate (Actellic) insecticides. However, a marked resurgence occurred in 2020, which coincided with a change to a clothianidin-based IRS formulations (Fludora Fusion/SumiShield). To quantify the magnitude of the resurgence, investigate causes, and evaluate the impact of a shift back to IRS with Actellic in 2023, we assessed changes in malaria metrics in regions within and near Tororo District.

Susceptibility of Anopheles gambiae to Natural Plasmodium falciparum Infection: A Comparison between the Well-Established Anopheles gambiae s.s Line and a Newly Established Ugandan Anopheles gambiae s.s. Line.

Much of our understanding of malaria transmission comes from mosquito feeding assays using Anopheles mosquitoes from colonies that are well adapted to membrane feeding. This raises the question whether results from colony mosquitoes lead to overestimates of outcomes in wild Anopheles mosquitoes. We successfully established an Anopheles colony using progeny of wild Anopheles gambiae s.

Metagenomic next-generation sequencing to characterize potential etiologies of non-malarial fever in a cohort living in a high malaria burden area of Uganda.

Causes of non-malarial fevers in sub-Saharan Africa remain understudied. We hypothesized that metagenomic next-generation sequencing (mNGS), which allows for broad genomic-level detection of infectious agents in a biological sample, can systematically identify potential causes of non-malarial fevers. The 212 participants in this study were of all ages and were enrolled in a longitudinal malaria cohort in eastern Uganda.

House design and risk of malaria, acute respiratory infection and gastrointestinal illness in Uganda: A cohort study.

House construction is rapidly modernizing across Africa but the potential benefits for human health are poorly understood. We hypothesised that improvements to housing would be associated with reductions in malaria, acute respiratory infection (ARI) and gastrointestinal illness in an area of low malaria endemicity in Uganda. Data were analysed from a cohort study of male and female child and adult residents (n = 531) of 80 randomly-selected households in Nagongera sub-county, followed for 24 months (October 4, 2017 to October 31, 2019).

Seroprevalence of Antibodies to SARS-CoV-2 in Rural Households in Eastern Uganda, 2020-2022.

Importance: Estimating 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.

Objective: To estimate SARS-CoV-2 seroprevalence, attack rates, and reinfection in eastern Uganda using serologic surveillance from 2020 to early 2022.

Antibodies to repeat-containing antigens in are exposure-dependent and short-lived in children in natural malaria infections.

Protection against , which is primarily antibody-mediated, requires recurrent exposure to develop. The study of both naturally acquired limited immunity and vaccine induced protection against malaria remains critical for ongoing eradication efforts. Towards this goal, we deployed a customized PhIP-seq T7 phage display library containing 238,068 tiled 62-amino acid peptides, covering all known coding regions, including antigenic variants, to systematically profile antibody targets in 198 Ugandan children and adults from high and moderate transmission settings.

Malaria-driven expansion of adaptive-like functional CD56-negative NK cells correlates with clinical immunity to malaria.

Natural killer (NK) cells likely play an important role in immunity to malaria, but the effect of repeated malaria on NK cell responses remains unclear. Here, we comprehensively profiled the NK cell response in a cohort of 264 Ugandan children. Repeated malaria exposure was associated with expansion of an atypical, CD56 population of NK cells that differed transcriptionally, epigenetically, and phenotypically from CD56 NK cells, including decreased expression of PLZF and the Fc receptor γ-chain, increased histone methylation, and increased protein expression of LAG-3, KIR, and LILRB1.

Measures of malaria transmission, infection, and disease in an area bordering two districts with and without sustained indoor residual spraying of insecticide in Uganda.

Tororo District, in Eastern Uganda, experienced a dramatic decline in malaria burden starting in 2014 following the implementation of indoor residual spraying of insecticide (IRS) in the setting of repeated long-lasting insecticide treated nets (LLINs) distribution campaigns. However, in 2020 malaria began to resurge in Tororo following a change in the active ingredient used for IRS. In this study, epidemiological measures of malaria were compared shortly after the resurgence between two parishes in Tororo District (Kayoro and Osukuru) and one contiguous parish in Busia District (Buteba), where IRS has never been implemented.

East Africa International Center of Excellence for Malaria Research: Summary of Key Research Findings.

The Program for Resistance, Immunology, Surveillance, and Modeling of Malaria (PRISM) has been conducting malaria research in Uganda since 2010 to improve the understanding of the disease and measure the impact of population-level control interventions in the country. Here, we will summarize key research findings from a series of studies addressing routine health facility-based surveillance, comprehensive cohort studies, studies of the molecular epidemiology, and transmission of malaria, evaluation of antimalarial drug efficacy, and resistance across the country, and assessments of insecticide resistance. Among our key findings are the following.

Simulating the Impacts of Augmenting Intensive Vector Control with Mass Drug Administration or Test-and-Treat Strategies on the Malaria Infectious Reservoir.

Highly effective vector control can reduce malaria burden significantly, but individuals with parasitemia provide a potential reservoir for onward transmission. We performed an empirical, non-parametric simulation based on cohort data from Tororo District, Uganda-an area with historically high but recently reduced malaria transmission-to estimate the effects of mass drug administration (MDA) and test-and-treat on parasite prevalence. We estimate that a single round of MDA would have accelerated declines in parasite prevalence dramatically over 2 years (cumulative parasite prevalence ratio [PPR], 0.

Reconstructing the SARS-CoV-2 epidemic in eastern Uganda through longitudinal serosurveillance in a malaria cohort.

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.

Age-dependent changes in circulating Tfh cells influence development of functional malaria antibodies in children.

T-follicular helper (Tfh) cells are key drivers of antibodies that protect from malaria. However, little is known regarding the host and parasite factors that influence Tfh and functional antibody development. Here, we use samples from a large cross-sectional study of children residing in an area of high malaria transmission in Uganda to characterize Tfh cells and functional antibodies to multiple parasites stages.

The influence of the environment and indoor residual spraying on malaria risk in a cohort of children in Uganda.

Studies have estimated the impact of the environment on malaria incidence although few have explored the differential impact due to malaria control interventions. Therefore, the objective of the study was to evaluate the effect of indoor residual spraying (IRS) on the relationship between malaria and environment (i.e.

Asymptomatic School-Aged Children Are Important Drivers of Malaria Transmission in a High Endemicity Setting in Uganda.

Achieving malaria elimination requires a better understanding of the transmissibility of human infections in different transmission settings. This study aimed to characterize the human infectious reservoir in a high endemicity setting in eastern Uganda, using gametocyte quantification and mosquito feeding assays. In asymptomatic infections, gametocyte densities were positively associated with the proportion of infected mosquitoes (β = 1.