Browsing by Author "Afrane, Yaw A."

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    Genetic diversity and population structure of the human malaria parasite Plasmodium falciparum surface protein Pfs47 in isolates from the lowlands in Western Kenya
    (PLOS ONE, 2021-11-29) Onyango, Shirley A.; Ochwedo, Kevin O.; Machani, Maxwell G.; Omondi, Collince J.; Debrah, Isaiah; Ogolla, Sidney O.; Ming-Chieh, Lee; Guofa, Zhou; Kokwaro, Elizabeth; Kazura, James W.; Afrane, Yaw A.; Githeko, Andrew K.; Daibin, Zhong; Guiyun, Yan
    Plasmodium falciparum parasites have evolved genetic adaptations to overcome immune responses mounted by diverse Anopheles vectors hindering malaria control efforts. Plasmo dium falciparum surface protein Pfs47 is critical in the parasite’s survival by manipulating the vector’s immune system hence a promising target for blocking transmission in the mos quito. This study aimed to examine the genetic diversity, haplotype distribution, and popula tion structure of Pfs47 and its implications on malaria infections in endemic lowlands in Western Kenya. Cross-sectional mass blood screening was conducted in malaria endemic regions in the lowlands of Western Kenya: Homa Bay, Kombewa, and Chulaimbo. Dried blood spots and slide smears were simultaneously collected in 2018 and 2019. DNA was extracted using Chelex method from microscopic Plasmodium falciparum positive samples and used to genotype Pfs47 using polymerase chain reaction (PCR) and DNA sequencing. Thirteen observed haplotypes of the Pfs47 gene were circulating in Western Kenya. Popula tion-wise, haplotype diversity ranged from 0.69 to 0.77 and the nucleotide diversity 0.10 to 0.12 across all sites. All the study sites displayed negative Tajima’s D values although not significant. However, the negative and significant Fu’s Fs statistical values were observed across all the study sites, suggesting population expansion or positive selection. Overall genetic differentiation index was not significant (FST = -0.00891, P > 0.05) among parasite populations. All Nm values revealed a considerable gene flow in these populations. These results could have important implications for the persistence of high levels of malaria trans mission and should be considered when designing potential targeted control interventions.
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    Molecular characterization and genotype distribution of thioester-containing protein 1 gene in Anopheles gambiae mosquitoes in western Kenya
    (Malaria Journal, 2022) Onyango, Shirley A.; Ochwedo, Kevin O.; Machani, Maxwell G.; Olumeh, Julius O.; Debrah, Isaiah; Omondi, Collince J.; Ogolla, Sidney O.; Ming Chieh, Lee; Guofa, Zhou; Kokwaro, Elizabeth; Kazura, James W.; Afrane, Yaw A.; Githeko, Andrew K.; Zhong, Daibin; Yan, Guiyun
    Background: Evolutionary pressures lead to the selection of efcient malaria vectors either resistant or susceptible to Plasmodium parasites. These forces may favour the introduction of species genotypes that adapt to new breeding habitats, potentially having an impact on malaria transmission. Thioester-containing protein 1 (TEP1) of Anopheles gambiae complex plays an important role in innate immune defenses against parasites. This study aims to character ize the distribution pattern of TEP1 polymorphisms among populations of An. gambiae sensu lato (s.l.) in western Kenya. Methods: Anopheles gambiae adult and larvae were collected using pyrethrum spray catches (PSC) and plastic dippers respectively from Homa Bay, Kakamega, Bungoma, and Kisumu counties between 2017 and 2020. Collected adults and larvae reared to the adult stage were morphologically identifed and then identifed to sibling species by PCR. TEP1 alleles were determined in 627 anopheles mosquitoes using restriction fragment length polymorphisms polymerase chain reaction (RFLP-PCR) and to validate the TEP1 genotyping results, a representative sample of the alleles was sequenced. Results: Two TEP1 alleles (TEP1*S1 and TEP1*R2) and three corresponding genotypes (*S1/S1, *R2/S1, and *R2/R2) were identifed. TEP1*S1 and TEP1*R2 with their corresponding genotypes, homozygous *S1/S1 and heterozygous *R2/S1 were widely distributed across all sites with allele frequencies of approximately 80% and 20%, respectively both in Anopheles gambiae and Anopheles arabiensis. There was no signifcant diference detected among the popula tions and between the two mosquito species in TEP1 allele frequency and genotype frequency. The overall low levels in population structure (FST=0.019) across all sites corresponded to an efective migration index (Nm=12.571) and low Nei’s genetic distance values (<0.500) among the subpopulation. The comparative fxation index values revealed minimal genetic diferentiation between species and high levels of gene fow among populations. Conclusion: Genotyping TEP1 has identifed two common TEP1 alleles (TEP1*S1 and TEP1*R2) and three corre sponding genotypes (*S1/S1, *R2/S1, and *R2/R2) in An. gambiae s.l. The TEP1 allele genetic diversity and population structure are low in western Kenya.
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    Plasmodium Falciparum Pfs47 Haplotype Compatibility to Anopheles Gambiae in Kisumu, a Malaria-Endemic Region of Kenya
    (Scientific Reports, 2025-02) Onyango, Shirley A.; Machani, Maxwell G.; Ochwedo, Kevin O.; Oriango, Robin M.; Lee, Ming-Chieh; Kokwaro, Elizabeth; Afrane, Yaw A.; Githeko, Andrew K.; Zhong, Daibin; Yan, Guiyun
    Insecticide resistance and outdoor transmission have reduced the effectiveness of existing malaria transmission prevention strategies. As a result, targeted approaches to support continuing malaria control, such as transmission-blocking vaccines, are required. Cross-sectional mass blood screening in children between 5 and 15 years was conducted in Chulaimbo, Kisumu, during the dry and wet seasons in 2018 and 2019. Plasmodium falciparum gametocyte carriers were identified by Microscopy. Subsequently, carriers were used to feed colony bred Anopheles gambiae females in serum replacement and whole blood membrane feeding experiments. The infection prevalence was 19.7% (95% Cl 0.003–0.007) with 95% of the infections being caused by P. falciparum. Of all confirmed P. falciparum infections, 16.9% were gametocytes. Thirty-seven paired experiments showed infection rates of 0.9% and 0.5% in the serum replacement and whole blood experiments, respectively, with no significant difference (P=0.738). Six Pfs47 haplotypes were identified from 24 sequenced infectious blood samples: Hap_1 (E27D and L240I), Hap_2 (S98T); Hap_3 (E27D); Hap_4 (L240I); Hap_5 (E188D); and Hap_6 without mutations. Haplotype 4 had the highest frequency of 29.2% followed by Hap_3 and Hap_6 at 20.8% each then Hap_1 with a frequency of 16.7%, whereas Hap_5 and Hap_2 had frequencies of 8.3% and 4.2% respectively. Varying frequencies of Pfs47 haplotypes observed from genetically heterogeneous parasite populations in endemic regions illuminates vector compatibility to refracting P. falciparum using the hypothesized lock and key analogy. This acts as a bottleneck that increases the frequency of P. falciparum haplotypes that escape elimination by vector immune responses. The interaction can be used as a potential target for transmission blocking through a refractory host.