Day 3 parasitemia and Plasmodium falciparum Kelch 13 mutations among uncomplicated malaria patients treated with artemether-lumefantrine in Adjumani district, Uganda.

Artemisinin resistance threatens malaria control and elimination efforts globally. Recent studies have reported the emergence of Plasmodium falciparum parasites tolerant to artemisinin agents in sub-Saharan Africa, including Uganda. The current study assessed the day 3 parasite clearance and its correlation with P.

Experience of healthcare personnel on Co-payment mechanism and the implications on its use in private drug outlets in Uganda.

Background: Malaria treatment is faced with the challenge of access, affordability, availability, and quality of antimalarial medicines. Affordable medicines facility-malaria (AMFm) program and subsequently Co-payment mechanism were developed to help increase access to quality assured Artemisinin-based combination therapies (ACTs) in seven countries in sub-Saharan Africa. We explored through a qualitative study, experience of healthcare personnel on Co-payment mechanism and the implication on its use in private drug outlets in Uganda.

Day 3 parasitemia and mutations among uncomplicated malaria patients treated with artemether-lumefantrine in Adjumani district, Uganda.

Artemisinin resistance threatens malaria control and elimination efforts globally. Recent studies have reported the emergence of parasites tolerant to artemisinin agents in sub-Saharan Africa, including Uganda. The current study assessed the day 3 parasite clearance and its correlation with propeller gene () mutations in parasites isolated from patients with uncomplicated malaria under artemether-lumefantrine (AL) treatment.

Access to quality-assured artemisinin-based combination therapy and associated factors among clients of selected private drug outlets in Uganda.

Background: Malaria treatment in sub-Saharan Africa is faced with challenges including unreliable supply of efficacious agents, substandard medicines coupled with high price of artemisinin-based combinations. This affects access to effective treatment increasing risk of malaria parasite resistance development and adverse drug events. This study investigated access to quality-assured artemisinin-based combination therapy (QAACT) medicines among clients of selected private drug-outlets in Uganda.

Copayment mechanism in selected districts of Uganda: Availability, market share and price of quality assured artemisinin-based combination therapies in private drug outlets.

Background: Malaria remains one of the leading causes of morbidity, and mortality in Uganda. A large proportion of malaria symptomatic patients seek healthcare in private sector. However, availability and affordability are major barriers to access to effective treatment.

Experiences of healthcare personnel on the efficacy of artemisinin-based combination therapy and malaria diagnosis in hospitals in Uganda.

Background: The risk of widespread resistance to artemisinin-based combination therapy (ACT) remains high in Uganda following detection of Plasmodium falciparum parasites with delayed artemisinin clearance genotype and phenotype. Establishment of context specific interventions to mitigate emergence and spread of artemisinin resistance is thus key in the fight against malaria in the country. The aim of this study was to explore the experiences of healthcare personnel on malaria diagnosis and self-reported efficacy of ACT in the management of malaria symptomatic patients in hospitals in low and high malaria transmission settings in Uganda.

Pharmacopeial quality of artemether-lumefantrine anti-malarial agents in Uganda.

Background: Substandard anti-malarial agents pose a significant challenge to effective malaria control and elimination efforts especially in sub-Saharan Africa. The quality of anti-malarials in most low-and-middle income countries (LMICs) is affected by several factors including inadequate regulation and limited resources. In this study, the pharmacopeial quality of artemether-lumefantrine (AL) in low and high malaria transmission settings in Uganda was assessed.

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.

Prevalence of arps10, fd, pfmdr-2, pfcrt and pfkelch13 gene mutations in Plasmodium falciparum parasite population in Uganda.

In Uganda, Artemether-Lumefantrine and Artesunate are recommended for uncomplicated and severe malaria respectively, but are currently threatened by parasite resistance. Genetic and epigenetic factors play a role in predisposing Plasmodium falciparum parasites to acquiring Pfkelch13 (K13) mutations associated with delayed artemisinin parasite clearance as reported in Southeast Asia. In this study, we report on the prevalence of mutations in the K13, pfmdr-2 (P.

Field evaluation of the diagnostic performance of EasyScan GO: a digital malaria microscopy device based on machine-learning.

Background: Microscopic examination of Giemsa-stained blood films remains the reference standard for malaria parasite detection and quantification, but is undermined by difficulties in ensuring high-quality manual reading and inter-reader reliability. Automated parasite detection and quantification may address this issue.

Methods: A multi-centre, observational study was conducted during 2018 and 2019 at 11 sites to assess the performance of the EasyScan Go, a microscopy device employing machine-learning-based image analysis.

Efficacy and safety of artemether-lumefantrine and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria and prevalence of molecular markers associated with artemisinin and partner drug resistance in Uganda.

Background: In Uganda, artemether-lumefantrine (AL) is first-line therapy and dihydroartemisinin-piperaquine (DP) second-line therapy for the treatment of uncomplicated malaria. This study evaluated the efficacy and safety of AL and DP in the management of uncomplicated falciparum malaria and measured the prevalence of molecular markers of resistance in three sentinel sites in Uganda from 2018 to 2019.

Methods: This was a randomized, open-label, phase IV clinical trial.

Decreased Susceptibility to Dihydrofolate Reductase Inhibitors Associated With Genetic Polymorphisms in Ugandan Plasmodium falciparum Isolates.

Background: The Plasmodium falciparum dihydrofolate reductase (PfDHFR) inhibitors pyrimethamine and cycloguanil (the active metabolite of proguanil) have important roles in malaria chemoprevention, but drug resistance challenges their efficacies. A new compound, P218, was designed to overcome resistance, but drug-susceptibility data for P falciparum field isolates are limited.

Methods: We studied ex vivo PfDHFR inhibitor susceptibilities of 559 isolates from Tororo and Busia districts, Uganda, from 2016 to 2020, sequenced 383 isolates, and assessed associations between genotypes and drug-susceptibility phenotypes.

Genetic diversity and genetic relatedness in Plasmodium falciparum parasite population in individuals with uncomplicated malaria based on microsatellite typing in Eastern and Western regions of Uganda, 2019-2020.

Background: Genetic diversity and parasite relatedness are essential parameters for assessing impact of interventions and understanding transmission dynamics of malaria parasites, however data on its status in Plasmodium falciparum populations in Uganda is limited. Microsatellite markers and DNA sequencing were used to determine diversity and molecular characterization of P. falciparum parasite populations in Uganda.

Prevalence of Malaria Parasite Infections among U.S.-Bound Congolese Refugees with and without Splenomegaly.

All U.S.-bound refugees from sub-Saharan Africa receive presumptive antimalarial treatment before departing for the United States.

Deletions of pfhrp2 and pfhrp3 genes were uncommon in rapid diagnostic test-negative Plasmodium falciparum isolates from Uganda.

Background: Rapid diagnostic tests (RDTs) play a key role in malaria case management. The most widely used RDT identifies Plasmodium falciparum based on immunochromatographic recognition of P. falciparum histidine-rich protein 2 (PfHRP2).

Limitations of rapid diagnostic tests in malaria surveys in areas with varied transmission intensity in Uganda 2017-2019: Implications for selection and use of HRP2 RDTs.

Background: Plasmodium falciparum histidine-rich protein 2 (HRP2)-based rapid diagnostic tests (RDTs) are exclusively recommended for malaria diagnosis in Uganda; however, their functionality can be affected by parasite-related factors that have not been investigated in field settings.

Methods: Using a cross-sectional design, we analysed 219 RDT-/microscopy+ and 140 RDT+/microscopy+ dried blood spots obtained from symptomatic children aged 2-10 years from 48 districts in Uganda between 2017 and 2019. We aimed to investigate parasite-related factors contributing to false RDT results by molecular characterization of parasite isolates.

Changing Prevalence of Potential Mediators of Aminoquinoline, Antifolate, and Artemisinin Resistance Across Uganda.

Background: In Uganda, artemether-lumefantrine is recommended for malaria treatment and sulfadoxine-pyrimethamine for chemoprevention during pregnancy, but drug resistance may limit efficacies.

Methods: Genetic polymorphisms associated with sensitivities to key drugs were characterized in samples collected from 16 sites across Uganda in 2018 and 2019 by ligase detection reaction fluorescent microsphere, molecular inversion probe, dideoxy sequencing, and quantitative polymerase chain reaction assays.

Results: Considering transporter polymorphisms associated with resistance to aminoquinolines, the prevalence of Plasmodium falciparum chloroquine resistance transporter (PfCRT) 76T decreased, but varied markedly between sites (0-46% in 2018; 0-23% in 2019); additional PfCRT polymorphisms and plasmepsin-2/3 amplifications associated elsewhere with resistance to piperaquine were not seen.

Associations between Malaria-Preventive Regimens and Plasmodium falciparum Drug Resistance-Mediating Polymorphisms in Ugandan Pregnant Women.

Intermittent preventive treatment in pregnancy (IPTp) with monthly sulfadoxine-pyrimethamine (SP) is recommended for malaria-endemic parts of Africa, but efficacy is compromised by resistance, and, in recent trials, dihydroartemisinin-piperaquine (DP) has shown better antimalarial protective efficacy. We utilized blood samples from a recent trial to evaluate selection by IPTp with DP or SP of genetic polymorphisms that alter susceptibility to these drugs. The prevalence of known genetic polymorphisms associated with altered drug susceptibility was determined in parasitemic samples, including 375 collected before IPTp drugs were administered, 125 randomly selected from those receiving SP, and 80 from those receiving DP.

Molecular surveillance reveals the presence of pfhrp2 and pfhrp3 gene deletions in Plasmodium falciparum parasite populations in Uganda, 2017-2019.

Background: Histidine-rich protein-2 (HRP2)-based rapid diagnostic tests (RDTs) are the only RDTs recommended for malaria diagnosis in Uganda. However, the emergence of Plasmodium falciparum histidine rich protein 2 and 3 (pfhrp2 and pfhrp3) gene deletions threatens their usefulness as malaria diagnostic and surveillance tools. The pfhrp2 and pfhrp3 gene deletions surveillance was conducted in P.

Associations between Aminoquinoline Resistance Genotypes and Clinical Presentations of Plasmodium falciparum Infection in Uganda.

Mutations that mediate resistance of to aminoquinoline antimalarials are selected by prior drug use and may alter parasite fitness, but associations with clinical presentations are uncertain. We evaluated genotypes in samples from a case-control study of determinants of severe malaria in Ugandan children 4 months to 10 years of age. We studied 274 cases with severe malaria matched by age and geography to 275 uncomplicated malaria controls and 179 asymptomatic parasitemic controls.

The Diversity of the K13 Propeller Domain Did Not Increase after Implementation of Artemisinin-Based Combination Therapy in Uganda.

Artemisinin-based combination therapies (ACTs) are the standard of care to treat uncomplicated falciparum malaria. However, resistance to artemisinins, defined as delayed parasite clearance after therapy, has emerged in Southeast Asia, and the spread of resistance to sub-Saharan Africa could have devastating consequences. Artemisinin resistance has been associated in Southeast Asia with multiple nonsynonymous single nucleotide polymorphisms (NS-SNPs) in the propeller domain of the gene encoding the K13 protein (K13PD).