Browsing by Author "Githeko, Andrew K."
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Item Age‑specific Plasmodium parasite profile in pre and post ITN intervention period at a highland site in western Kenya(BioMed Central, 2017) Ototo, Ednah N.; Zhou, Guofa; Kamau, Lucy; Mbugi, Jenard P.; Wanjala, Christine L.; Machani, Maxwell; Atieli, Harrysone; Githeko, Andrew K.; Yan, GuiyunBackground: Monitoring and evaluation of entomological, parasitological and clinical data is an important component of malaria control as it is a measure of the success of the interventions. In many studies, clinical data has been used to monitor trends in malaria morbidity and mortality. This study was conducted to demonstrate age dependent prevalence of malaria in the pre- and post-interventions period. Methods: A series of cross-sectional malaria parasitological surveys were conducted in Iguhu, western Kenya. Participants were randomly selected school-aged children between 6 and 13 years. The study was conducted between June 2002–December 2003 and January 2012–February 2015. Sexual and asexual parasite prevalence and densities were determined using microscopy. Age-dependence in parasite infections was compared between 2002–2003 and 2012–2015. Results: Plasmodium falciparum had the highest prevalence of 43.5 and 11.5% in the pre- and post-intervention periods. Plasmodium malariae had a prevalence of 2.3 and 0.2%, while Plasmodium ovale had a prevalence of 0.3 and 0.1% during the pre- and post-intervention period, respectively. There was a 73.7% reduction in prevalence of P. falciparum in the post-intervention compared to the pre-intervention period. Plasmodium falciparum parasite density increased by 71.2% between pre- and post-intervention period from (geometric mean of ) 554.4–949.2 parasites/μl. Geometric mean gametocytaemia in Iguhu was higher in the post-intervention period (106.4 parasites/μl), when compared to the pre-intervention period (54.1 parasites/μl). Prevalence and density of P. falciparum showed a lower age-dependency during post-intervention period when compared to pre-intervention period. Conclusion: The study provides evidence for reduction of malaria prevalence following the introduction of LLINs and ACT in western Kenya. Fewer people become infected but the few infected may be more infectious as suggested by higher gametocyte densities. The high parasite densities, which were not dependent on age, observed in the post intervention period imply that a more comprehensive integrated malaria management may be required to sustain the current interventions and hence reduce malaria transmission.Item Evaluation of universal coverage of insecticide-treated nets in western Kenya: field surveys(BioMed Central, 2014) Zhou, Guofa; Li, Jessica S.; Ototo, Ednah N.; Atieli, Harrysone E.; Githeko, Andrew K.; Yan, GuiyunBackground: Mass distribution of insecticide-treated nets (ITNs) is a cost-effective way to achieve universal coverage, but maintaining this coverage is more difficult. In addition to commonly used indicators, evaluation of universal coverage should include coverage of effective nets and changes in coverage over time. Methods: Longitudinal and cross-sectional household ITN surveys were carried out from 2010 to 2013 in six locations representing a variety of settings across western Kenya. Five indicators were used to evaluate the current status of universal coverage: 1) ITN ownership – proportion of households that own at least one ITN, 2) access index – ratio of the number of family members over the number of ITNs owned by that household, 3) operational coverage – proportion of the at-risk population potentially covered by ITNs, assuming one ITN for every two people, 4) effective coverage – population coverage of effective ITNs, and 5) usage – proportion of the population that used ITNs the previous night. Results: ITN ownership and operational coverage increased substantially from 2010 to 2013, but this increase was mostly due to the 2011 mass distribution campaign. In 2013, household ITN ownership was on average 84.4% (95% CI [78.4, 90.5]) across the six study areas, and operational coverage was 83.2% (95% CI [72.5, 93.8]). The ITN access rate was 59.1% (95% CI [56.6, 61.7]), and 40.8% (95% CI [38.3, 43.4]) of the people at risk needed more nets to achieve universal coverage. About 88.5% (95% CI [86.1, 90.9]) of the ITNs were below three years old and 16.5% (95% CI [12.1, 20.9]) of the ITNs had hole(s). The estimated effective long-lasting insecticide-treated net (LLIN) coverage was 70.5% (95 CI [58.7, 82.3]). Approximately 18.4% (95% CI [15.5, 21.4]) of the ITNs were shared by more than three persons, and the population ITN usage rate was about 75-87%. The reason for not using ITNs was almost exclusively “net not available”. Conclusion: Current methods of delivering ITNs, i.e., one mass campaign every five years and regular distribution of ITNs from health center can barely maintain the current effective coverage. Inaccessibility and loss of physical integrity of ITNs are major hindrances to achieving and maintaining universal coverage.Item 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, YanPlasmodium 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.Item Insecticide Resistance and Its Intensity in Urban Anopheles Arabiensis in Kisumu City, Western Kenya: Implications for Malaria Control in Urban Areas(PLoS ONE, 2024-11) MachaniI, Maxwell G.; Nzioki, Irene; Onyango, Shirley A.; Onyango, Brenda; Githure, John; Atieli, Harrysone; Wang, Chloe; Lee, Ming-Chieh; Githeko, Andrew K.Background The rise of insecticide resistance poses a growing challenge to the effectiveness of vector control tools, particularly in rural areas. However, the urban setting has received comparatively less focus despite its significance in attracting rural to urban migration. Unplanned urbanization, often overlooked, exacerbates insecticide resistance as Anopheles mosquitoes adapt to the polluted environments of rapidly expanding cities. This study aimed to assess the insecticide susceptibility status of malaria vectors and identify potential underlying mechanisms across three distinct ecological settings characterized by differing levels of urbanization in Kisumu County, Kenya. Methods The study was conducted in 2022–2023 in Kisumu County, western Kenya. Field-derived An. gambiae (s.l.) larvae collected from a long stretch of urban-to-rural continuum were phenotyped as either resistant or susceptible to six different insecticides using the World Health Organization (WHO) susceptibility test. Polymerase chain reaction (PCR) techniques were used to identify the species of the An. gambiae complex and screened for mutations at voltage-gated sodium channels (Vgsc-1014F, Vgsc-1014S, Vgsc-1575Y) and acetylcholinesterase (Ace1) target site mutation 119S. Metabolic enzyme activities (non-specific β-esterases and monooxygenases) were evaluated in mosquitoes not exposed to insecticides using microplate assays. Additionally, during larval sampling, a retrospective questionnaire survey was conducted to determine pesticide usage by the local inhabitants. Results Anopheles arabiensis dominated in urban (96.2%) and peri-urban (96.8%) areas, while An. gambiae (s.s.) was abundant in rural settings (82.7%). Urban mosquito populations showed high resistance intensity to deltamethrin (Mortality rate: 85.2% at 10x) and suspected resistance to Pirimiphos-methyl and bendiocarb while peri-urban and rural populations exhibited moderate resistance intensity to deltamethrin (mortality rate >98% at 10x). Preexposure of mosquitoes to a synergist piperonyl butoxide (PBO) significantly increased mortality rates: from 40.7% to 88.5% in urban, 51.9% to 90.3% in peri-urban, and 55.4% to 87.6% in rural populations for deltamethrin, and from 41.4% to 78.8% in urban, 43.7% to 90.7% in peri-urban, and 35% to 84.2% in rural populations for permethrin. In contrast, 100% mortality to chlorfenapyr and clothianidin was observed in all the populations tested. The prevalence of L1014F mutation was notably higher in urban An. arabiensis (0.22) unlike the peri-urban (0.11) and rural (0.14) populations while the L1014S mutation was more prevalent in rural An. gambiae (0.93). Additionally, urban An. arabiensis exhibited elevated levels of mixed function oxidases (0.8/mg protein) and non-specific esterases (2.12/mg protein) compared to peri-urban (0.57/mg protein and 1.5/mg protein, respectively) and rural populations (0.6/mg protein and 1.8/mg protein, respectively). Pyrethroids, apart from their use in public health through LLINs, were being highly used for agricultural purposes across all ecological settings (urban 38%, peri-urban 36% and rural 37%) followed by amidine group, with organophosphates, neonicotinoids and carbamates being of secondary importance. Conclusion These findings show high resistance of An. arabiensis to insecticides commonly used for vector control, linked with increased levels of detoxification enzymes. The observed intensity of resistance underscores the pressing issue of insecticide resistance in urban areas, potentially compromising the effectiveness of vector control measures, especially pyrethroid-treated LLINs. Given the species’ unique behavior and ecology compared to An. gambiae, tailored vector control strategies are needed to address this concern in urban settings.Item 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, GuiyunBackground: 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.Item 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, GuiyunInsecticide 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.Item Surveillance of malaria vector population density and biting behaviour in western Kenya(BioMed Central, 2015) Ototo, Ednah N; Mbugi, Jenard P.; Wanjala, Christine L.; Zhou, Guofa; Githeko, Andrew K.; Yan, GuiyunBackground: Malaria is a great public health burden and Africa suffers the largest share of malaria-attributed deaths. Despite control efforts targeting indoor malaria transmission, such as insecticide-treated bed nets (ITNs) and deployment of indoor residual spraying, transmission of the parasite in western Kenya is still maintained. This study was carried out to determine the impact of ITNs on indoor vector densities and biting behaviour in western Kenya. Methods: Indoor collection of adult mosquitoes was done monthly in six study sites in western Kenya using pyrethrum spray collections from 2012 to 2014. The rotator trap collections were done in July–August in 2013 and May–June in 2014. Mosquitoes were collected every 2 h between 18.00 and 08.00 h. Human behaviour study was conducted via questionnaire surveys. Species within Anopheles gambiae complex was differentiated by PCR and sporozoite infectivity was determined by ELISA. Species distribution was determined and bed net coverage in the study sites was recorded. Results: During the study a total of 5,469 mosquito vectors were collected from both PSC and Rotator traps comprising 3,181 (58.2%) Anopheles gambiae and 2,288 (41.8%) Anopheles funestus. Compared to all the study sites, Rae had the highest density of An. gambiae with a mean of 1.2 (P < 0.001) while Kombewa had the highest density of An. funestus with a mean of 1.08 (P < 0.001). Marani had the lowest density of vectors with 0.06 An. gambiae and 0.17 An. funestus (P < 0.001). Among the 700 PCR confirmed An. gambiae s.l. individuals, An. gambiae s.s. accounted for 49% and An. arabiensis 51%. Over 50% of the study population stayed outdoors between 18.00 and 20.00 and 06.00 and 08.00 which was the time when highest densities of blood fed vectors were collected. Anopheles gambie s.s. was the main malaria parasite vector in the highland sites and An. arabiensis in the lowland sites. Bed net ownership in 2012 averaged 87% across the study sites. Conclusions: This study suggests that mass distribution of ITNs has had a significant impact on vector densities, species distribution and sporozoite rate. However, shift of biting time poses significant threats to the current malaria vector control strategies which heavily rely on indoor controls