Browsing by Author "Clark, Taane G."

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    PublicationOpen Access
    Drug resistance profiling of asymptomatic and low-density Plasmodium falciparum malaria infections on Ngodhe island, Kenya, using custom dual-indexing next-generation sequencing
    (Scientific Reports, 2023-07-14) Osborne, Ashley; Chan,Chim; Kagaya, Wataru; Kaneko,Akira; Clark, Taane G.; Campino, Susana; Gitaka, Jesse; Kita, Kiyoshi; Kongere, James; Ngara, Mtakai; Phelan,Jody E.
    Malaria control initiatives require rapid and reliable methods for the detection and monitoring of molecular markers associated with antimalarial drug resistance in Plasmodium falciparum parasites. Ngodhe island, Kenya, presents a unique malaria profile, with lower P. falciparum incidence rates than the surrounding region, and a high proportion of sub-microscopic and low-density infections. Here, using custom dual-indexing and Illumina next generation sequencing, we generate resistance profiles on seventy asymptomatic and low-density P. falciparum infections from a mass drug administration program implemented on Ngodhe island between 2015 and 2016. Our assay encompasses established molecular markers on the Pfcrt, Pfmdr1, Pfdhps, Pfdhfr, and Pfk13 genes. Resistance markers for sulfadoxine-pyrimethamine were identified at high frequencies, including a quintuple mutant haplotype (Pfdhfr/Pfdhps: N51I, C59R, S108N/A437G, K540E) identified in 62.2% of isolates. The Pfdhps K540E biomarker, used to inform decision making for intermittent preventative treatment in pregnancy, was identified in 79.2% of isolates. Several variants on Pfmdr1, associated with reduced susceptibility to quinolones and lumefantrine, were also identified (Y184F 47.1%; D1246Y 16.0%; N86 98%). Overall, we have presented a low-cost and extendable approach that can provide timely genetic profiles to inform clinical and surveillance activities, especially in settings with abundant low-density infections, seeking malaria elimination.
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    PublicationOpen Access
    Genomic Surveillance of SARS-COV-2 reveals diverse circulating variant lineages in Nairobi and Kiambu County, Kenya
    (Research Square, 2023-05-13) Kuja, Josiah O.; Waweru, Harrison; Gethii, Kimita; Mungai, Mary; Kanoi, Bernard N.; Shiluli, Clement; Mungai, Mary; Masika, Moses; Anzala, Omu; Waitumbi, John; Gitaka, Jesse; Clark, Taane G.; Mwau, Matilu
    Genomic surveillance and identification of SARS-CoV-2 outbreaks are important in understanding the genetic diversity, phylogeny, and lineages of SAR-CoV-2. Genomic surveillance provides insights into circulating infections, and insights into the robustness and design of vaccines and other infection control approaches. We sequenced 56 SARS-CoV-2 isolates from a Kenyan clinical population, of which 52 passed the Ultrafast sample Placement on the existing tRE for the phylo-genome-temporal analyses across two regions in Kenya (Nairobi and Kiambu County). B.1.1.7 (Alpha; n = 32, 61.5%) and B.1 (n = 9, 17.3%) lineages were the most predominant variant with a wide-range of Ct values (5–31) and variant mutations across the two regions. Lineages B.1.617.2, B.1.1, A.23.1, A.2.5.1, B.1.596, A, and B.1.405 were also detected across the sampling sites within the target population. The lineages and genetic isolates were traced back to China (A), Costa Rica (A.2.5.1), Europe (B.1, B.1.1, A.23.1), USA (B.1.405, B.1.596), South Africa (B.1.617.2), and United Kingdom (B.1.1.7), indicating multiple introduction events. There were, however, no genetic isolates associated with the omicron (B.1.1.529) variant of concern that is less severe than the previous variants.
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    PublicationOpen Access
    Plasmodium falciparum population dynamics in East Africa and genomic surveillance along the Kenya‑Uganda border
    (Scientific Reports, 2024-08-05) Osborne, Ashley; Mańko, Emilia; Waweru, Harrison; Kaneko, Akira; Kita, Kiyoshi; Campino, Susana; Gitaka, Jesse; Clark, Taane G.
    East African countries accounted for ~ 10% of all malaria prevalence worldwide in 2022, with an estimated 23.8 million cases and > 53,000 deaths. Despite recent increases in malaria incidence, high‑ resolution genome‑wide analyses of Plasmodium parasite populations are sparse in Kenya, Tanzania, and Uganda. The Kenyan‑Ugandan border region is a particular concern, with Uganda confirming the emergence and spread of artemisinin resistant P. falciparum parasites. To establish genomic surveillance along the Kenyan‑Ugandan border and analyse P. falciparum population dynamics within East Africa, we generated whole‑genome sequencing (WGS) data for 38 parasites from Bungoma, Western Kenya. These sequences were integrated into a genomic analysis of available East African isolate data (n = 599) and revealed parasite subpopulations with distinct genetic structure and diverse ancestral origins. Ancestral admixture analysis of these subpopulations alongside isolates from across Africa (n = 365) suggested potential independent ancestral populations from other major African populations. Within isolates from Western Kenya, the prevalence of biomarkers associated with chloroquine resistance (e.g. Pfcrt K76T) were significantly reduced compared to wider East African populations and a single isolate contained the PfK13 V568I variant, potentially linked to reduced susceptibility to artemisinin. Overall, our work provides baseline WGS data and analysis for future malaria genomic surveillance in the region