A5114859414- Malaria Research and Control
- Computational Drug Discovery Methods
- HIV/AIDS drug development and treatment
- Pharmacological Effects and Toxicity Studies
- Infectious Encephalopathies and Encephalitis
- Mosquito-borne diseases and control
- Epilepsy research and treatment
- Trypanosoma species research and implications
- Drug Transport and Resistance Mechanisms
- Drug-Induced Hepatotoxicity and Protection
- Traumatic Brain Injury and Neurovascular Disturbances
- Drug-Induced Ocular Toxicity
- Hemoglobinopathies and Related Disorders
- Neonatal and fetal brain pathology
- Research on Leishmaniasis Studies
- Asthma and respiratory diseases
- Emergency and Acute Care Studies
- Media Studies and Communication
- Neuroscience and Neuropharmacology Research
- Global Maternal and Child Health
- Parasites and Host Interactions
- Diverse Scientific Research Studies
- Discourse Analysis in Language Studies
- Family and Patient Care in Intensive Care Units
- Disaster Response and Management
Kenyatta University
2024
African Conservation Centre
2021
Kenya Medical Research Institute
2006-2018
Translational Therapeutics (United States)
2017-2018
Family Research Institute
2017-2018
University of British Columbia
2013-2018
Child and Family Research Institute
2017-2018
International Development Research Centre
2017-2018
British Columbia Children's Hospital
2017-2018
Wellcome Trust
2014
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...
Abstract Background The spread of resistance to chloroquine (CQ) led its withdrawal from use in most countries sub-Saharan Africa the 1990s. In Malawi, this was followed by a rapid reduction frequency point where drug is now considered be effective once again, just nine years after withdrawal. report, polymorphisms markers associated with CQ-resistance against Plasmodium falciparum isolates coastal Kenya (Kilifi) were investigated, 1993, prior CQ, 2006, seven Changes those that occurred...
ABSTRACT We have analyzed the in vitro chemosensitivity profiles of 115 Kenyan isolates for chloroquine (CQ), piperaquine, lumefantrine (LM), and dihydroartemisinin association with polymorphisms pfcrt at codon 76 pfmdr 1 86, as well variations copy number . The median drug concentrations that inhibit 50% parasite growth (IC 50 s) were 41 nM (interquartile range [IQR], 18 to 73 nM), (IQR, 29 96 32 17 46 2 3 nM) CQ, LM, dihydroartemisinin, respectively. activity CQ correlated inversely LM ( r...
Background The emergence of artemisinin-resistant P. falciparum malaria in South-East Asia highlights the need for continued global surveillance efficacy artemisinin-based combination therapies. Methods On Kenyan coast we studied treatment responses 474 children 6–59 months old with uncomplicated a randomized controlled trial dihydroartemisinin-piperaquine vs. artemether-lumefantrine from 2005 to 2008. (ISRCTN88705995) Results proportion patients residual parasitemia on day 1 rose 55%...
Early identification of causal genetic variants underlying antimalarial drug resistance could provide robust epidemiological tools for timely public health interventions. Using a novel natural genetics strategy mapping candidate genes we analyzed >75,000 high quality single nucleotide polymorphisms selected from high-resolution whole-genome sequencing data in 27 isolates Plasmodium falciparum. We identified associated with susceptibility to dihydroartemisinin that implicate one region on...
An emergency triage, assessment and treatment plus admission care (ETAT+) intervention was implemented in Rwandan district hospitals to improve hospital for severely ill infants children. Many interventions are rarely with perfect fidelity under real-world conditions. Thus, evaluations of the experiences implementing ETAT+ important terms identifying potential barriers successful implementation. This study explored perspectives healthcare workers (HCWs) on relevance documented its HCWs...
ABSTRACT We have analyzed the activities of antifolates pyrimethamine (PM), chlorcycloguanil (CCG), WR99210, trimethoprim (TMP), methotrexate (MTX), and trimetrexate (TMX) against Kenyan Plasmodium falciparum isolates adapted in vitro for long-term culture. also assessed relationship between these drug mutations dihydrofolate reductase ( dhfr ), a domain gene associated with antifolate resistance. As expected, WR99210 was most potent drug, median 50% inhibitory concentration (IC 50 )...
Resistance to the amino alcohol quinine has been associated with polymorphisms in pfnhe, a sodium hydrogen exchanger. We investigated role of this gene resistance vitro isolates from Kenya. analyzed pfnhe whole-gene polymorphisms, using capillary sequencing, and pfcrt at codon 76 (pfcrt-76) pfmdr1 86 (pfmdr1-86), PCR-enzyme restriction methodology, 29 Kilifi, Kenya, for association activities 2 alcohols, mefloquine halofantrine. In activity was assessed as drug concentration that inhibits...
The folate derivatives folic acid (FA) and folinic (FNA) decrease the in vivo vitro activities of antifolate drugs Plasmodium falciparum. However, effects 5-methyl-tetrahydrofolate (5-Me-THF) tetrahydrofolate (THF), two dominant circulating forms humans, have not been explored yet. We investigated FA, FNA, 5-Me-THF, THF on activity antimalarial antifolates pyrimethamine chlorcycloguanil anticancer methotrexate (MTX), aminopterin, trimetrexate (TMX), against P. results indicate that these...
Background Drug resistance remains a chief concern for malaria control. In order to determine the genetic markers of drug resistant parasites, we tested genome-wide associations (GWA) sequence-based genotypes from 35 Kenyan P. falciparum parasites with activities 22 antimalarial drugs. Methods and Principal Findings Parasites isolated children acute febrile were adapted culture, sensitivity was determined by in vitro growth presence anti-malarial genotyped using whole genome sequencing...
The combination therapy of the Artemisinin-derivative Artemether (ART) with Lumefantrine (LM) (Coartem®) is an important malaria treatment regimen in many endemic countries. Resistance to Artemisinin has already been reported, and it feared that LM resistance (LMR) could also evolve quickly. Therefore molecular markers which can be used track Coartem® efficacy are urgently needed. Often, stable arises from initial, unstable phenotypes identified vitro. Here we have Plasmodium falciparum...
We have analyzed the in vitro activities of pyronaridine and methylene blue against 59 Plasmodium falciparum isolates from Kenya association with polymorphisms Pfcrt (codon 76), Pfmdr1 86), Pfnhe (full sequence). The median inhibitory concentrations that kill 50% parasites were 13.5 3.3 nM for blue, respectively. Their not associated these genes. drugs' high indicate they would be efficacious Kenyan vivo.
In light of reports increasing resistance parasites to amodiaquine in African countries which Plasmodium falciparum is endemic as well the paucity recent vitro sensitivity data, we assessed vivo and P. isolates from 128 pediatric outpatients (0.5-10 years old) Pingilikani, Kilifi District, Kenya, who were treated with (10 mg/kg/day for 3 days). The polymerase chain reaction-corrected parasitological cure rate on day 28 (by Kaplan-Meier analysis) was 82% (95% confidence interval [CI],...
The Plasmodium falciparum genome is rich in regions of low amino acid complexity which evolve with few constraints on size. To explore the extent diversity these loci, we sequenced repeat pfmdr1, pfmdr5, pfmdr6, pfmrp2, and antigenic locus pfmsp8 laboratory cultured-adapted clinical isolates. We further assessed associations between repeats parasite vitro responses to 7 antimalarials determine possible adaptive roles drug tolerance. Our results show extensive variations reference isolates...
Administration of oral corticosteroids at the onset an upper respiratory tract infection (URTI) can be effective in management acute asthma exacerbations children. This study was designed to identify barriers parent-initiated implementation clinical practice guideline-recommended use for prophylaxis against severe Twenty-seven children who presented BC Children’s Hospital with URTI-induced were recruited. Parents received a filled prescription course used earliest their child’s next URTI....
ABSTRACT The mechanisms of drug resistance development in the Plasmodium falciparum parasite to lumefantrine (LUM), commonly used combination with artemisinin, are still unclear. We assessed polymorphisms Pfmspdbl2 for associations LUM activity a Kenyan population. MSPDBL2 codon 591S was associated reduced susceptibility ( P = 0.04). high frequency Kenya may be driven by widespread use artemisinin therapy (Coartem).
The argumentative talk on radio and TV has become a popular feature of media discourse in Kenya. Question-answer sequences as the unfolds through joint participation co-participants have emerged means to put into effect. Yet, nature questions their categorization remain little understood. Given recursive question-answer sequences, this paper investigates question typology that sets apart shows from other types talk. data consists transcripts two Kenyan shows: Checkpoint KTN Opinion Court...