A5051310567- Malaria Research and Control
- Mosquito-borne diseases and control
- Computational Drug Discovery Methods
- Parasites and Host Interactions
- Drug-Induced Hepatotoxicity and Protection
- Hemoglobinopathies and Related Disorders
- Research on Leishmaniasis Studies
- Pharmaceutical Economics and Policy
- Hepatitis C virus research
- Drug Transport and Resistance Mechanisms
- Pharmaceutical Quality and Counterfeiting
- Pharmacological Effects and Toxicity Studies
- Digital Imaging for Blood Diseases
- vaccines and immunoinformatics approaches
- Invertebrate Immune Response Mechanisms
- Immune Cell Function and Interaction
- Cell Image Analysis Techniques
- Genetics, Bioinformatics, and Biomedical Research
- Global Maternal and Child Health
- Iron Metabolism and Disorders
- Ubiquitin and proteasome pathways
- Diverse Scientific Research Studies
- Viral Infections and Vectors
- Trypanosoma species research and implications
- Identification and Quantification in Food
Makerere University
2016-2025
Infectious Diseases Research Collaboration
2016-2025
Kampala University
2022
Mulago Hospital
2010-2016
University of London
2014
Ministry of Health
2005
San Francisco General Hospital
2005
University of California, San Francisco
2005
Adequate clinical and parasitologic cure by artemisinin combination therapies relies on the component partner drug. Polymorphisms in Plasmodium falciparum chloroquine resistance transporter ( pfcrt ) P. multidrug 1 pfmdr1 genes are associated with decreased sensitivity to amodiaquine lumefantrine, but effects of these polymorphisms therapeutic responses artesunate-amodiaquine (ASAQ) artemether-lumefantrine (AL) have not been clearly defined. Individual patient data from 31 trials were...
In Uganda, artemether-lumefantrine is recommended for malaria treatment and sulfadoxine-pyrimethamine chemoprevention during pregnancy, but drug resistance may limit efficacies. Genetic polymorphisms associated with sensitivities to key drugs were characterized in samples collected from 16 sites across Uganda 2018 2019 by ligase detection reaction fluorescent microsphere, molecular inversion probe, dideoxy sequencing, quantitative polymerase chain assays. Considering transporter...
Partial resistance of Plasmodium falciparum to the artemisinin component artemisinin-based combination therapies, most important malaria drugs, emerged in Southeast Asia and now threatens East Africa. resistance, which manifests as delayed clearance after therapy, is mediated principally by mutations kelch protein K13 (PfK13). Limited longitudinal data are available on emergence spread We performed annual surveillance among patients who presented with uncomplicated at 10 16 sites across...
Artemisinin partial resistance may facilitate selection of Plasmodium falciparum resistant to combination therapy partner drugs. We evaluated 99 P. isolates collected in 2021 from northern Uganda, where resistance-associated PfK13 C469Y and A675V mutations have emerged, eastern these are uncommon. With the ex vivo ring survival assay, with 469Y mutation (median 7.3% for mutant, 2.5% mixed, 1.4% wild type) and/or Pfcoronin or falcipain-2a, had significantly greater survival; all >5% at least...
Human immunodeficiency virus (HIV) infection may increase the burden of malaria by increasing susceptibility to or decreasing response antimalarial treatment. We investigated seroprevalence rate HIV-1 and its effect on treatment outcomes in adults children with uncomplicated falciparum Uganda.This retrospective study included 1965 patients > =18 months old who were randomized receive 1 3 regimens at 7 sites Uganda. testing was performed using 2 enzyme-linked immunosorbent assays Western blot...
ABSTRACT Polymorphisms in the Plasmodium falciparum pfmdr1 gene were assayed pretreatment samples and from patients reinfected following therapy with artemether-lumefantrine. The alleles 86N, 184F, 1246D significantly increased prevalence after treatment. All had a single copy. Treatment artemether-lumefantrine selects for polymorphisms that may alter antimalarial drug response.
Significance Tropical rainforest hunter-gatherer populations worldwide share the pygmy phenotype, or small human body size. The evolutionary history of this phenotype is largely unknown. Here we studied DNA from Batwa, a population east central Africa, to identify regions Batwa genome that underlie phenotype. We then performed genomic analyses study evolution these regions, including comparisons with Baka, west African population. conclude likely arose due positive natural selection and it...
Abstract Background The treatment and control of malaria in Africa is challenged by drug resistance, including Plasmodium falciparum transporter, folate pathway, PfK13 mutations that mediate resistance to aminoquinolines, antifolates, artemisinins, respectively. Characterization susceptibility informs optimal strategies. Methods We characterized ex vivo susceptibilities nine drugs isolates collected from individuals presenting with uncomplicated eastern (2019-2024) northern (2021-2024)...
Background Drug resistance in Plasmodium falciparum poses a major threat to malaria control. Combination antimalarial therapy including artemisinins has been advocated recently improve efficacy and limit the spread of resistance, but are expensive relatively untested highly endemic areas. We compared artemisinin-based other combination therapies four districts Uganda with varying transmission intensity. Methods Findings enrolled 2,160 patients aged 6 mo or greater uncomplicated malaria....
The control of malaria is challenged by resistance Plasmodium falciparum to multiple drugs. New combination regimens are now advocated for the treatment uncomplicated malaria, but extent newer agents incompletely understood. We measured in vitro sensitivity P. parasites cultured from children enrolled a drug efficacy trial Kampala, Uganda, 2006 2008. Sensitivities were comparing levels histidine-rich protein-2 incubated with different concentrations drugs those untreated controls. exhibited...
ABSTRACT We evaluated markers of artemisinin resistance in Plasmodium falciparum isolated Kampala 2014. By standard vitro assays, all isolates were highly sensitive to dihydroartemisinin (DHA). the ring-stage survival assay, after a 6-h DHA pulse, parasitemia was undetectable 40 43 cultures at 72 h. Two 53 had nonsynonymous K13-propeller gene polymorphisms but did not have mutations associated with Asia. Thus, we see evidence for Uganda.
Standard therapy for malaria in Uganda changed from chloroquine to + sulfadoxine-pyrimethamine 2000, and artemether-lumefantrine 2004, although implementation of each change was slow. Plasmodium falciparum genetic polymorphisms are associated with alterations drug sensitivity. We followed the prevalence resistance-mediating P. 982 samples Tororo, a region high transmission intensity, collected three successive treatment trials conducted during 2003-2012, excluding known recent prior...
The potential spread of antimalarial drug resistance to Africa, in particular for artemisinins and key partner drugs, is a major concern. We surveyed Plasmodium falciparum genetic markers associated with sensitivity on 3 occasions at ∼6-month intervals 2016 2017 10 sites representing range epidemiological settings Uganda. For putative transporters, we found continued evolution toward wild-type sequences increased chloroquine. pfcrt K76T, by the prevalence wild type was >60% all >90% 6 sites....
Treatment and control of malaria depends on artemisinin-based combination therapies (ACTs) is challenged by drug resistance, but thus far resistance to artemisinins partner drugs has primarily occurred in southeast Asia. The aim this study was characterise antimalarial susceptibility Plasmodium falciparum isolates from Tororo Busia districts Uganda. In prospective longitudinal study, P were collected patients aged 6 months or older presenting at the District Hospital (Tororo district, a site...
Abstract 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 inter-reader reliability. Automated quantification may address this issue. Methods A multi-centre, observational study was conducted during 2018 2019 at 11 sites to assess performance EasyScan Go, a microscopy device employing machine-learning-based image analysis....
ABSTRACT Changing treatment practices may be selecting for changes in the drug sensitivity of malaria parasites. We characterized ex vivo and parasite polymorphisms associated with 459 Plasmodium falciparum samples obtained from subjects enrolled two clinical trials Tororo, Uganda, 2010 to 2013. Sensitivities chloroquine monodesethylamodiaquine varied widely; sensitivities quinine, dihydroartemisinin, lumefantrine, piperaquine were generally good. Associations between included decreased...
We assessed Plasmodium falciparum drug resistance markers in parasites collected 2012, 2013, and 2015 at 3 sites Uganda. The prevalence frequency of with mutations putative transporters previously associated to aminoquinolines, but increased sensitivity lumefantrine (pfcrt 76T; pfmdr1 86Y 1246Y), decreased markedly all sites. Antifolate were common, apparent emergence (pfdhfr 164L; pfdhps 581G) high-level resistance. K13 linked artemisinin uncommon did not increase over time. Changing...
ABSTRACT Dihydroartemisinin-piperaquine (DP) has demonstrated excellent efficacy for the treatment and prevention of malaria in Uganda. However, resistance to both components this regimen emerged Southeast Asia. The artemether-lumefantrine, first-line treat Uganda, also been excellent, but continued pressure may select parasites with decreased sensitivity lumefantrine. To gain insight into current drug patterns, ex vivo sensitivities were assessed genotypes previously associated altered...