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

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

doi:10.1016/j.crpvbd.2022.100106

Cited by 13 publications

(5 citation statements)

References 72 publications

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“…Moreover, 1014F/1014S double mutants seem to express a resistance phenotype almost comparable to that of 1014F homozygotes (71).…”

Section: Discussionmentioning

confidence: 93%

Longitudinal survey of insecticide resistance in a village of Central Region of Burkina Faso reveals co-occurrence of 1014F, 1014S and 402L mutations in Anopheles coluzzii and Anopheles arabiensis

Perugini,

Pichler,

Guelbeogo

et al. 2024

Preprint

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Introduction. Pyrethroid resistance is one of the major threats for effectiveness of insecticide-treated bed nets (ITNs) in malaria vector control. Genotyping of mutations in the voltage gated sodium channel (VGSC) gene is widely used to easily assess the evolution and spread of pyrethroid target-site resistance among malaria vectors. L1014F and L1014S substitutions are the most common and best characterized VGSC mutations in major African malaria vector species of the Anopheles gambiae complex. Recently, an additional substitution involved in pyrethroid resistance i.e. V402L, has been detected in Anopheles coluzzii from West Africa lacking any other resistance alleles at locus 1014. We here monitored the evolution of target-site resistance mutations L1014F/S and V402L in A. coluzzii and A. arabiensis specimens from a Burkina Faso village over a 10-year range after the massive ITN scale-up started in 2010. Methods. A. coluzzii (N = 300) and A. arabiensis (N = 362) specimens collected in 2011, 2015 and 2020 at Goden village were genotyped by TaqMan assays and sequencing for the three target site resistance mutations; allele frequencies were statistically investigated over the years. Results. A divergent trend in resistant allele frequencies was observed in the two species: 1014F decreased in A. coluzzii (from 0.76 to 0.52) but increased in A. arabiensis (from 0.18 to 0.70); 1014S occurred only in A. arabiensis and slightly decreased over time (from 0.33 to 0.23); 402L increased in A. coluzzii (from 0.15 to 0.48) and was found for the first time in one A. arabiensis specimen. In 2020 the co-occurrence of different resistance alleles reached 43% in A. coluzzii (alleles 410L and 1014F) and 32% in A. arabiensis (alleles 1014F and 1014S). Conclusions. Overall, an increasing level of target-site resistance was observed among the populations with only 1% of the two malaria vector species being wild type at both loci, 1014 and 402, in 2020. This, together with the co-occurrence of different mutations in the same specimens, calls for future investigations on the possible synergism between resistance alleles and their phenotype to implement local tailored intervention strategies.

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“…Moreover, 1014F/1014S double mutants seem to express a resistance phenotype almost comparable to that of 1014F homozygotes (71).…”

Section: Discussionmentioning

confidence: 93%

Longitudinal survey of insecticide resistance in a village of Central Region of Burkina Faso reveals co-occurrence of 1014F, 1014S and 402L mutations in Anopheles coluzzii and Anopheles arabiensis

Perugini,

Pichler,

Guelbeogo

et al. 2024

Preprint

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“…gambiae s.l. from different countries, and even different ecological zones within a country, respond contrastingly to deltamethrin and permethrin, with PBO exposure restoring varying levels of partial susceptibility [82][83][84][85][86] . Analogous to SULF, PBO speci cally binds and inhibits CYP450s and thus restores mortality in mosquitoes through blocking phase I detoxi cation 87 and is currently incorporated on pyrethroid-PBO bed nets being used in Africa 1, 4 .…”

Section: Discussionmentioning

confidence: 99%

Uridine diphosphate (UDP)- glycosyltransferases (UGTs) confer insecticide resistance in the major malaria vectors Anopheles gambiae s.l and Anopheles funestus

Logan,

Mäurer,

Wapler

et al. 2024

Preprint

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Malaria remains one of the highest causes of morbidity and mortality, with 249 million cases and over 608,000 deaths in 2022. Insecticides, which target the Anopheles mosquito vector, are the primary method to control malaria. The widespread nature of resistance to the most important insecticide class, the pyrethroids, threatens the control of this disease. To reverse the stall in malaria control there is urgent need for new vector control tools, which necessitates understanding the molecular basis of pyrethroid resistance. In this study we utilised multi-omics data to identify uridine-diphosphate (UDP)- glycosyltransferases (UGTs) potentially involved in resistance across multiple Anopheles species. Phylogenetic analysis identifies sequence similarities between Anopheline UGTs and those involved in agricultural pesticide resistance to pyrethroids, pyrroles and spinosyns. Expression of five UGTs was characterised in An. gambiae and An. coluzzii to determine constitutive over- expression, induction, and tissue specificity. Furthermore, a UGT inhibitor, sulfinpyrazone, restored susceptibility to pyrethroids and DDT in An. gambiae, An. coluzzii, An. arabiensis and An. funestus, the major African malaria vectors. Taken together, this study provides clear evidence of the role of UGTs in pyrethroid resistance as well as highlighting the potential use of sulfinpyrazone as a novel synergist for vector control.

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“…However, pyrethroid-PBO LLINs have several potential limitations. Widespread pyrethroid resistance has been reported in Uganda [23,24], and across Africa, with both knock-down and metabolic resistance described across several settings [11]. PBO is a synergist, not an insecticide, and can only restore sensitivity to pyrethroid insecticides if resistance is due to specific metabolic mechanisms.…”

Section: Discussionmentioning

confidence: 99%

LLIN Evaluation in Uganda Project (LLINEUP2) – Effect of long-lasting insecticidal nets (LLINs) treated with pyrethroid plus pyriproxyfen vs LLINs treated with pyrethroid plus piperonyl butoxide in Uganda: a cluster-randomised trial

Gonahasa,

Namuganga,

Nassali

et al. 2024

Preprint

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BackgroundWe embedded a pragmatic, cluster-randomised trial into Uganda’s national campaign to distribute long-lasting insecticidal nets (LLINs) in 2020–2021, comparing LLINs treated with pyrethroids plus the synergist piperonyl butoxide (PBO), to LLINs treated with pyrethroids plus pyriproxyfen, an insect growth regulator.MethodsTarget communities surrounding public health facilities (clusters, n=64), covering 32 high-burden districts not receiving indoor residual spraying, were included. Clusters were randomised 1:1 in blocks of two by district to receive: (1) pyrethroid-PBO LLINs (PermaNet 3.0, n=32) or (2) pyrethroid-pyriproxyfen LLINs (Royal Guard, n=32). LLINs were delivered from 7 November 2020 to 26 March 2021 and malaria outcome data were collected until 31 March 2023. Estimates of malaria incidence in residents of all ages (the primary outcome) were generated for each cluster from enhanced health facility surveillance data. At 12- (24 November 2021 to 1 April 2022) and 24-months (23 November 2022 to 21 March 2023) post-LLIN distribution, cross-sectional community surveys were conducted in randomly selected households (at least 50 per cluster, 3,200 per survey).FindingsIn the two years following LLIN distribution, 186,364 episodes of malaria were diagnosed in cluster residents during 398,931 person-years of follow-up. Malaria incidence after 24-months was lower than at baseline in both arms (pyrethroid-PBO: 465 vs 676 episodes per 1000 person-years; pyrethroid-pyriproxyfen: 469 vs 674 episodes per 1000 person-years); but the difference between the arms was not statistically significant (incidence rate ratio 1.06, 95% confidence interval [CI] 0.91– 1.22, p=0.47). Two years post-distribution, ownership of at least one LLIN for every two household residents was low in both arms (41.1% pyrethroid-PBO vs 38.6% pyrethroid-pyriproxyfen). Parasite prevalence in children aged 2-10 years was no different between the arms in either survey and similar results were observed for prevalence of anaemia in children aged 2-4 years.InterpretationThe effectiveness of pyrethroid-PBO LLINs and pyrethroid-pyriproxyfen LLINs was no different in Uganda, but two years after mass distribution, LLIN coverage was inadequate.FundingUS National Institutes for Health, Bill and Melinda Gates FoundationTrial registrationNCT04566510. Registered 28 September 2020,https://clinicaltrials.gov/ct2/show/NCT04566510

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

Cited by 13 publications

References 72 publications

Longitudinal survey of insecticide resistance in a village of Central Region of Burkina Faso reveals co-occurrence of 1014F, 1014S and 402L mutations in Anopheles coluzzii and Anopheles arabiensis

Longitudinal survey of insecticide resistance in a village of Central Region of Burkina Faso reveals co-occurrence of 1014F, 1014S and 402L mutations in Anopheles coluzzii and Anopheles arabiensis

Uridine diphosphate (UDP)- glycosyltransferases (UGTs) confer insecticide resistance in the major malaria vectors Anopheles gambiae s.l and Anopheles funestus

LLIN Evaluation in Uganda Project (LLINEUP2) – Effect of long-lasting insecticidal nets (LLINs) treated with pyrethroid plus pyriproxyfen vs LLINs treated with pyrethroid plus piperonyl butoxide in Uganda: a cluster-randomised trial

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