A5083020309- Malaria Research and Control
- Computational Drug Discovery Methods
- Mosquito-borne diseases and control
- Parasites and Host Interactions
- vaccines and immunoinformatics approaches
- Enzyme Structure and Function
- Cancer therapeutics and mechanisms
- Protein Structure and Dynamics
- HIV/AIDS drug development and treatment
- Biochemical and Molecular Research
- Hepatitis C virus research
- Aquaculture disease management and microbiota
- Agriculture, Plant Science, Crop Management
- Plant Pathogens and Fungal Diseases
- Lipid Membrane Structure and Behavior
- Drug Transport and Resistance Mechanisms
- Traditional and Medicinal Uses of Annonaceae
- Plant Pathogens and Resistance
- Tuberculosis Research and Epidemiology
Kenya Medical Research Institute
2014-2022
United States Army Medical Research Directorate - Africa
2014-2022
Rhodes University
2021
Jomo Kenyatta University of Agriculture and Technology
2016
The development of artemisinin (ART)-resistant parasites in Southeast Asia (SEA) threatens malaria control globally. Mutations the Kelch 13 (K13)-propeller domain have been useful identifying ART resistance SEA. combination therapy (ACT) remains highly efficacious treatment uncomplicated Sub-Saharan Africa (SSA). However, it is crucial that efficacy ACT closely monitored. Toward this effort, study profiled prevalence K13 nonsynonymous mutations different ecological zones Kenya and time...
Abstract Genetic analysis of molecular markers is critical in tracking the emergence and/or spread artemisinin resistant parasites. Clinical isolates collected western Kenya pre- and post- introduction combination therapies (ACTs) were genotyped at SNP positions regions strong selection signatures on chromosome 13 14, as described Southeast Asia (SEA). Twenty five SNPs using Sequenom MassArray pfmdr 1 gene copy number by real-time PCR. Parasite clearance half-life vitro drug sensitivity...
ABSTRACT In combination with antibiotics, quinine is recommended as the second-line treatment for uncomplicated malaria, an alternative first-line severe and of malaria in first trimester pregnancy. Quinine has been shown to have frequent clinical failures, yet mechanisms action resistance not fully elucidated. However, linked polymorphisms multiple genes, including multidrug 1 (Pf mdr1 ), chloroquine transporter crt sodium/hydrogen exchanger gene nhe1 ). Here, we investigated association...
Sulphadoxine-pyrimethamine (SP), an antifolate, was replaced by artemether-lumefantrine as the first-line malaria drug treatment in Kenya 2004 due to wide spread of resistance. However, SP still remains recommended for intermittent preventive pregnant women and infants (IPTP/I) owing its safety profile. This study assessed prevalence mutations dihydrofolate reductase (Pfdhfr) dihydropteroate synthase (Pfdhps) genes associated with resistance samples collected between 2008 2012. Field...
The Plasmodium falciparum in vitro culture system is critical for genotypic and phenotypic analyses of the parasites. For analysis, genomic DNA can be obtained directly from patient blood sample or adapted parasites whereas immediate ex vivo are used. However, parasite biology studies have not investigated whether adaptation process affects and/or characteristics short- long-term cultures. Here, we set out to study dynamics stability genetic profiles as field isolate were continuous...
There are concerns that resistance to artemisinin-based combination therapy might emerge in Kenya and sub-Saharan Africa (SSA) the same pattern as was with chloroquine sulfadoxine–pyrimethamine. Single nucleotide polymorphisms (SNPs) critical alleles of pfmdr1 gene have been associated artemisinin its partner drugs. Microsatellite analysis loci flanking genes anti-malarial drug has used defining geographic origins, dissemination resistant parasites identifying regions genome under selection....
Atovaquone (ATQ) is a drug used to prevent and treat malaria that functions by targeting the Plasmodium falciparum cytochrome b (PfCytb) protein. PfCytb catalyzes transmembrane electron transfer (ET) pathway which maintains mitochondrial membrane potential. The ubiquinol substrate binding site of protein has heme bL, bH iron-sulphur [2FE-2S] cluster cofactors act as redox centers aid in ET. Recent studies investigating ATQ resistance mechanisms have shown point mutations confer resistance....
Genetically determined artemisinin resistance in Plasmodium falciparum has been described Southeast Asia. The relevance of recently Kelch 13-propeller mutations for Sub-Saharan Africa parasites is still unknown. Asia have low genetic diversity compared to Africa, where are highly genetically diverse. This study attempted elucidate whether genetics provides a basis discovering molecular markers response drug treatment P. Kenya. collected pre- and post- introduction combination therapy (ACT)...
The impact of pre-existing immunity on the efficacy artemisinin combination therapy is largely unknown. We performed in-depth profiling serological responses in a therapeutic study [comparing artesunate-mefloquine (ASMQ) and artemether-lumefantrine (AL)] using proteomic microarray. Responses to over 200 Plasmodium antigens were significantly associated with ASMQ treatment outcome but not AL. used machine learning develop predictive models based immunoprofile data. predict for high (72-85%)...
The dimeric dihydropyrimidine dehydrogenase (DPD), metalloenzyme, an adjunct anti-cancer drug target, contains highly specialized 4 × Fe2+4S2−4 clusters per chain. These facilitate the catalysis of rate-limiting step in pyrimidine degradation pathway through a harmonized electron transfer cascade that triggers redox catabolic reaction. In process, bulk administered 5-fluorouracil (5-FU) cancer is inactivated, while small proportion activated to nucleic acid antimetabolites. occurrence...
Background: Microscopic parasite detection during the course of treatment or follow-up suggests that a proportion ACT treated children in Kenya do not completely clear Plasmodium falciparum parasitemia. mutation chloroquine resistance transporter gene (Pfcrt76), multidrug gene1 (Pfmdr1), deubiquitinating enzyme (Pfcubp-1) and clathrin vesicle associated adapter 2, u subunit encoding (Pfap2mu) resistant protein 1 (Pfmrp1) have been with subsequent patent recrudescence after treatment. As...
Abstract The role of humoral immunity on the efficacy artemisinin combination therapy (ACT) has not been investigated, yet naturally acquired is key determinant antimalarial therapeutic response. We conducted a study in high transmission settings western Kenya, which showed artesunate-mefloquine (ASMQ) and dihydroartemisinin-piperaquine (DP) were more efficacious than artemether-lumefantrine (AL). To investigate underlying prophylactic mechanism, we compared broad range immune responses...
Abstract The dimeric dihydropyrimidine dehydrogenase (DPD) metalloenzyme, an adjunct anti-cancer drug target contains highly specialized 4 × Fe 2+ S 2- clusters per chain. These facilitate the catalysis of rate-limiting step in pyrimidine degradation pathway through a harmonized electron transfer cascade that triggers redox catabolic reaction. In process, majority administered 5-fluorouracil (5-FU) cancer is inactivated while small proportion activated to nucleic acid antimetabolites....