Browsing by Author "Lee, Ming-Chieh"

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    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.
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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.