Remoscope: a label-free imaging cytometer for malaria diagnostics.

Malaria diagnostic testing in high transmission settings remains a burden on healthcare systems. Here we present Remoscope, a portable automated imaging cytometer that scans fresh, unstained whole blood using a custom neural network on low-cost hardware. By screening up to two million red blood cells, Remoscope performs label-free quantitative stage-specific detection of () in 1-12 minutes without sample fixation, staining, or slide scanning.

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.

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.

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.

Targeted newborn metabolomics: prediction of gestational age from cord blood.

Objective: Our study sought to determine whether metabolites from a retrospective collection of banked cord blood specimens could accurately estimate gestational age and to validate these findings in cord blood samples from Busia, Uganda.

Study Design: Forty-seven metabolites were measured by tandem mass spectrometry or enzymatic assays from 942 banked cord blood samples. Multiple linear regression was performed, and the best model was used to predict gestational age, in weeks, for 150 newborns from Busia, Uganda.

A Novel Malaria Lateral Flow Assay for Detecting Plasmodium falciparum Lactate Dehydrogenase in Busia, Uganda.

Rapid diagnostic tests (RDTs) for Plasmodium falciparum commonly detect histidine-rich protein 2 (HRP-2), but HRP-2 deletions are increasingly recognized. We evaluated a prototype test detecting parasite lactate dehydrogenase (pLDH) and compared it to commercially available RDTs at a health facility in Uganda, using quantitative polymerase chain reaction as a gold standard. The prototype pLDH test had a high sensitivity for infections with at least 100 parasites/µL (98%), comparable to HRP-2, and greater than an existing pLDH RDT (89%).

Sources of persistent malaria transmission in a setting with effective malaria control in eastern Uganda: a longitudinal, observational cohort study.

Background: Symptomatic malaria cases reflect only a small proportion of all Plasmodium spp infections. Many infected individuals are asymptomatic, and persistent asymptomatic Plasmodium falciparum infections are common in endemic settings. We aimed to quantify the contribution of symptomatic and asymptomatic infections to P falciparum transmission in Tororo, Uganda.

Peripheral Plasmodium falciparum Infection in Early Pregnancy Is Associated With Increased Maternal Microchimerism in the Offspring.

Background: Placental malaria has been associated with increased cord blood maternal microchimerism (MMc), which in turn may affect susceptibility to malaria in the offspring. We sought to determine the impact of maternal peripheral Plasmodium falciparum parasitemia during pregnancy on MMc and to determine whether maternal cells expand during primary parasitemia in the offspring.

Methods: We conducted a nested cohort study of maternal-infant pairs from a prior pregnancy malaria chemoprevention study.

Intermittent preventive treatment with dihydroartemisinin-piperaquine and risk of malaria following cessation in young Ugandan children: a double-blind, randomised, controlled trial.

Background: Intermittent preventive treatment (IPT) of malaria with dihydroartemisinin-piperaquine is a promising strategy for malaria prevention in young African children. However, the optimal dosing strategy is unclear and conflicting evidence exists regarding the risk of malaria after cessation of chemoprevention. We aimed to compare two dosing strategies of IPT with dihydroartemisinin-piperaquine in young Ugandan children, and to evaluate the risk of malaria after cessation of IPT.

Systemic inflammation is associated with malaria and preterm birth in women living with HIV on antiretrovirals and co-trimoxazole.

Women living with HIV (WLHIV) have an increased risk of malaria in pregnancy (MiP). It is unclear if MiP in WLHIV causes a systemic inflammatory response and increases the risk of adverse birth outcomes, especially for women receiving antiretroviral therapy (ART) and daily trimethoprim-sulfamethoxazole (TMP/SXT). We analyzed repeated plasma samples in a cohort of malaria-exposed Ugandan WLHIV receiving ART and daily TMP/SXT to examine changes in inflammatory markers across pregnancy and their association with birth outcomes.

Household and maternal risk factors for malaria in pregnancy in a highly endemic area of Uganda: a prospective cohort study.

Background: Malaria in pregnancy is a major public health challenge, but its risk factors remain poorly understood in some settings. This study assessed the association between household and maternal characteristics and malaria among pregnant women in a high transmission area of Uganda.

Methods: A nested prospective study was conducted between 6th September 2016 and 5th December 2017 in Busia district.

The prevalence of histologic acute chorioamnionitis among HIV infected pregnant women in Uganda and its association with adverse birth outcomes.

Background: Preterm birth (PTB) is a leading cause of neonatal mortality and longer-term morbidity. Acute chorioamnionitis (ACA) is a common cause of PTB, however, there are limited data on the prevalence of ACA and its association with PTB in resource limited settings.

Methods: Data and samples came from a clinical trial evaluating novel strategies for the prevention of malaria in HIV infected pregnant women in Uganda.

Dihydroartemisinin-piperaquine for intermittent preventive treatment of malaria during pregnancy and risk of malaria in early childhood: A randomized controlled trial.

Background: Intermittent preventive treatment of malaria in pregnancy (IPTp) with dihydroartemisinin-piperaquine (IPTp-DP) has been shown to reduce the burden of malaria during pregnancy compared to sulfadoxine-pyrimethamine (IPTp-SP). However, limited data exist on how IPTp regimens impact malaria risk during infancy. We conducted a double-blinded randomized controlled trial (RCT) to test the hypothesis that children born to mothers given IPTp-DP would have a lower incidence of malaria during infancy compared to children born to mothers who received IPTp-SP.

Estradiol Levels Are Altered in Human Immunodeficiency Virus-Infected Pregnant Women Randomized to Efavirenz-Versus Lopinavir/Ritonavir-Based Antiretroviral Therapy.

Background: Combination antiretroviral therapy (cART) use in pregnancy has been associated with hormonal dysregulation. We performed a secondary retrospective analysis of longitudinal progesterone and estradiol levels in pregnancy using specimens from the Protease Inhibitors to Reduce Malaria Morbidity in HIV-infected Pregnant Women study, which randomized Ugandan human immunodeficiency virus (HIV)-infected ART-naive women to initiate either lopinavir/ritonavir (LPV/r)-based or efavirenz (EFV)-based cART.

Methods: Three hundred twenty-six women (160 randomized to the EFV arm and 166 women to the LPV/r arm) with at least 1 plasma sample collected during pregnancy were included.

Altered angiogenesis as a common mechanism underlying preterm birth, small for gestational age, and stillbirth in women living with HIV.

Background: Angiogenic processes in the placenta are critical regulators of fetal growth and impact birth outcomes, but there are limited data documenting these processes in HIV-infected women or women from low-resource settings.

Objective: We sought to determine whether angiogenic factors are associated with adverse birth outcomes in HIV-infected pregnant women started on antiretroviral therapy.

Study Design: This is a secondary analysis of samples collected as part of a clinical trial randomizing pregnant women and adolescents infected with HIV to lopinavir/ritonavir-based (n = 166) or efavirenz-based (n = 160) antiretroviral therapy in Tororo, Uganda.

Relationships between infection with Plasmodium falciparum during pregnancy, measures of placental malaria, and adverse birth outcomes.

Background: Malaria in pregnancy has been associated with maternal morbidity, placental malaria, and adverse birth outcomes. However, data are limited on the relationships between longitudinal measures of malaria during pregnancy, measures of placental malaria, and birth outcomes.

Methods: This is a nested observational study of data from a randomized controlled trial of intermittent preventive therapy during pregnancy among 282 participants with assessment of placental malaria and delivery outcomes.

Viral Suppression and Retention in Care up to 5 Years After Initiation of Lifelong ART During Pregnancy (Option B+) in Rural Uganda.

Background: Lifelong antiretroviral therapy (ART) is recommended for all HIV-infected pregnant women, but early studies suggest that women often drop out of care postpartum and data are limited on virologic outcomes.

Methods: We evaluated viral suppression (primary outcome) and retention in care up to 5 years after ART initiation among HIV-infected women who started lifelong ART during pregnancy, irrespective of CD4 count, in a study in rural Uganda (NCT00993031). Participants were followed in the study for up to 1 year postpartum, then referred to clinics in surrounding communities.

Reductions in malaria in pregnancy and adverse birth outcomes following indoor residual spraying of insecticide in Uganda.

Background: Indoor residual spraying of insecticide (IRS) is a key intervention for reducing the burden of malaria in Africa. However, data on the impact of IRS on malaria in pregnancy and birth outcomes is limited.

Methods: An observational study was conducted within a trial of intermittent preventive therapy during pregnancy in Tororo, Uganda.

Dihydroartemisinin-Piperaquine for the Prevention of Malaria in Pregnancy.

Background: Intermittent treatment with sulfadoxine-pyrimethamine is widely recommended for the prevention of malaria in pregnant women in Africa. However, with the spread of resistance to sulfadoxine-pyrimethamine, new interventions are needed.

Methods: We conducted a double-blind, randomized, controlled trial involving 300 human immunodeficiency virus (HIV)-uninfected pregnant adolescents or women in Uganda, where sulfadoxine-pyrimethamine resistance is widespread.