Autor: |
Osoti V; KEMRI-Wellcome Trust Collaborative Programme, Kilifi, Kenya., Akinyi M; KEMRI-Wellcome Trust Collaborative Programme, Kilifi, Kenya.; Institute of Primate Research, National Museums of Kenya, Nairobi, Kenya., Wamae K; KEMRI-Wellcome Trust Collaborative Programme, Kilifi, Kenya., Kimenyi KM; KEMRI-Wellcome Trust Collaborative Programme, Kilifi, Kenya.; Department of Biochemistry, University of Nairobi, Nairobi, Kenya., de Laurent Z; KEMRI-Wellcome Trust Collaborative Programme, Kilifi, Kenya., Ndwiga L; KEMRI-Wellcome Trust Collaborative Programme, Kilifi, Kenya., Gichuki P; Eastern and Southern Africa Centre of International Parasite Control, Kenya Medical Research Institutegrid.33058.3d, Nairobi, Kenya., Okoyo C; Eastern and Southern Africa Centre of International Parasite Control, Kenya Medical Research Institutegrid.33058.3d, Nairobi, Kenya., Kepha S; Eastern and Southern Africa Centre of International Parasite Control, Kenya Medical Research Institutegrid.33058.3d, Nairobi, Kenya., Mwandawiro C; Eastern and Southern Africa Centre of International Parasite Control, Kenya Medical Research Institutegrid.33058.3d, Nairobi, Kenya., Kandie R; Division of National Malaria Programme, Ministry of Health, Nairobi, Kenya., Bejon P; KEMRI-Wellcome Trust Collaborative Programme, Kilifi, Kenya.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Snow RW; KEMRI-Wellcome Trust Collaborative Programme, Kilifi, Kenya.; Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom., Ochola-Oyier LI; KEMRI-Wellcome Trust Collaborative Programme, Kilifi, Kenya. |
Abstrakt: |
Molecular surveillance of Plasmodium falciparum parasites is important to track emerging and new mutations and trends in established mutations and should serve as an early warning system for antimalarial resistance. Dried blood spots were obtained from a Plasmodium falciparum malaria survey in school children conducted across eight counties in western Kenya in 2019. Real-time PCR identified 500 P. falciparum-positive samples that were amplified at five drug resistance loci for targeted amplicon deep sequencing (TADS). The absence of important kelch 13 mutations was similar to previous findings in Kenya pre-2019, and low-frequency mutations were observed in codons 569 and 578. The chloroquine resistance transporter gene codons 76 and 145 were wild type, indicating that the parasites were chloroquine and piperaquine sensitive, respectively. The multidrug resistance gene 1 haplotypes based on codons 86, 184, and 199 were predominantly present in mixed infections with haplotypes NYT and NFT, driven by the absence of chloroquine pressure and the use of lumefantrine, respectively. The sulfadoxine-pyrimethamine resistance profile was a "superresistant" combination of triple mutations in both Pfdhfr (51I 59R 108N) and Pfdhps (436H 437G 540E), rendering sulfadoxine-pyrimethamine ineffective. TADS highlighted the low-frequency variants, allowing the early identification of new mutations, Pfmdr1 codon 199S and Pfdhfr codon 85I and emerging 164L mutations. The added value of TADS is its accuracy in identifying mixed-genotype infections and for high-throughput monitoring of antimalarial resistance markers. |