Characterizing pyrethroid resistance and mechanisms in Anopheles gambiae (s.s.) and Anopheles arabiensis from 11 districts in Uganda

Henry Ddumba Mawejje; David Weetman; Adrienne Epstein; Amy Lynd; Jimmy Opigo; Catherine Maiteki-Sebuguzi; Jo Lines; Moses R Kamya; Philip J Rosenthal; Martin J Donnelly; Grant Dorsey; Sarah G Staedke

doi:10.1016/j.crpvbd.2022.100106

Characterizing pyrethroid resistance and mechanisms in Anopheles gambiae (s.s.) and Anopheles arabiensis from 11 districts in Uganda

Curr Res Parasitol Vector Borne Dis. 2022 Dec 10:3:100106. doi: 10.1016/j.crpvbd.2022.100106. eCollection 2023.

Authors

Henry Ddumba Mawejje^{1

2}, David Weetman³, Adrienne Epstein³, Amy Lynd³, Jimmy Opigo⁴, Catherine Maiteki-Sebuguzi^{1

4}, Jo Lines², Moses R Kamya^{1

5}, Philip J Rosenthal⁶, Martin J Donnelly³, Grant Dorsey⁶, Sarah G Staedke²

Affiliations

¹ Infectious Diseases Research Collaboration, Kampala, Uganda.
² London School of Hygiene and Tropical Medicine, London, UK.
³ Department of Vector Biology, Liverpool School of Tropical Medicine, Liverpool, UK.
⁴ National Malaria Control Division, Uganda Ministry of Health, Kampala, Uganda.
⁵ Department of Medicine, Makerere University College of Health Sciences, Kampala, Uganda.
⁶ Department of Medicine, University of California, San Francisco, USA.

Abstract

Insecticide resistance threatens recent progress on malaria control in Africa. To characterize pyrethroid resistance in Uganda, Anopheles gambiae (s.s.) and Anopheles arabiensis were analyzed from 11 sites with varied vector control strategies. Mosquito larvae were collected between May 2018 and December 2020. Sites were categorized as receiving no indoor-residual spraying ('no IRS', n = 3); where IRS was delivered from 2009 to 2014 and in 2017 and then discontinued ('IRS stopped', n = 4); and where IRS had been sustained since 2014 ('IRS active', n = 4). IRS included bendiocarb, pirimiphos methyl and clothianidin. All sites received long-lasting insecticidal nets (LLINs) in 2017. Adult mosquitoes were exposed to pyrethroids; with or without piperonyl butoxide (PBO). Anopheles gambiae (s.s.) and An. arabiensis were identified using PCR. Anopheles gambiae (s.s.) were genotyped for Vgsc-995S/F, Cyp6aa1, Cyp6p4-I236M, ZZB-TE, Cyp4j5-L43F and Coeae1d, while An. arabiensis were examined for Vgsc-1014S/F. Overall, 2753 An. gambiae (s.l.), including 1105 An. gambiae (s.s.) and 1648 An. arabiensis were evaluated. Species composition varied by site; only nine An. gambiae (s.s.) were collected from 'IRS active' sites, precluding species-specific comparisons. Overall, mortality following exposure to permethrin and deltamethrin was 18.8% (148/788) in An. gambiae (s.s.) and 74.6% (912/1222) in An. arabiensis. Mortality was significantly lower in An. gambiae (s.s.) than in An. arabiensis in 'no IRS' sites (permethrin: 16.1 vs 67.7%, P < 0.001; deltamethrin: 24.6 vs 83.7%, P < 0.001) and in 'IRS stopped' sites (permethrin: 11.3 vs 63.6%, P < 0.001; deltamethrin: 25.6 vs 88.9%, P < 0.001). When PBO was added, mortality increased for An. gambiae (s.s.) and An. arabiensis. Most An. gambiae (s.s.) had the Vgsc-995S/F mutation (95% frequency) and the Cyp6p4-I236M resistance allele (87%), while the frequency of Cyp4j5 and Coeae1d were lower (52% and 55%, respectively). Resistance to pyrethroids was widespread and higher in An. gambiae (s.s.). Where IRS was active, An. arabiensis dominated. Addition of PBO to pyrethroids increased mortality, supporting deployment of PBO LLINs. Further surveillance of insecticide resistance and assessment of associations between genotypic markers and phenotypic outcomes are needed to better understand mechanisms of pyrethroid resistance and to guide vector control.

Keywords: Anopheles arabiensis; Anopheles gambiae; Piperonyl butoxide (PBO); Pyrethroid resistance; Triple mutation.

Abstract

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