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. 2021 Apr 1;10(4):415.
doi: 10.3390/pathogens10040415.

Pyrethroid Resistance Aggravation in Ugandan Malaria Vectors Is Reducing Bednet Efficacy

Magellan Tchouakui  1 , Leon M J Mugenzi  1   2 , Benjamin D Menze  1 , Jude N T Khaukha  3 , Williams Tchapga  1 , Micareme Tchoupo  1 , Murielle J Wondji  1   4 , Charles S Wondji  1   4
Affiliations

Pyrethroid Resistance Aggravation in Ugandan Malaria Vectors Is Reducing Bednet Efficacy

Magellan Tchouakui et al. Pathogens. .

Abstract

Monitoring cases of insecticide resistance aggravation and the effect on the efficacy of control tools is crucial for successful malaria control. In this study, the resistance intensity of major malaria vectors from Uganda was characterised and its impact on the performance of various insecticide-treated nets elucidated. High intensity of resistance to the discriminating concentration (DC), 5× DC, and 10× DC of pyrethroids was observed in both Anopheles funestus and Anopheles gambiae in Mayuge and Busia leading to significant reduced performance of long-lasting insecticidal nets (LLINs) including the piperonyl butoxide (PBO)-based nets (Olyset Plus). Molecular analysis revealed significant over-expression of cytochrome P450 genes (CYP9K1 and CYP6P9a/b). However, the expression of these genes was not associated with resistance escalation as no difference was observed in the level of expression in mosquitoes resistant to 5× DC and 10× DC compared to 1× DC suggesting that other resistance mechanisms are involved. Such high intensity of pyrethroid resistance in Uganda could have terrible consequences on the effectiveness of insecticide-based interventions and urgent action should be taken to prevent the spread of super-resistance in malaria vectors.

Keywords: An. funestus; CYP9K1; Uganda; cytochrome P450; malaria; metabolic resistance; resistance escalation; vector control.

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Conflict of interest statement

All the authors declare that there is no conflict of interest concerning the research conducted and the publication of the results obtained.

Figures

Figure 1
Figure 1
Susceptibility profile to main insecticides of An. funestus and An. gambiae s.l populations from Busia and Mayuge: (A) susceptibility profile of An. funestus; (B) Susceptibility profile and intensity of An. gambiae s.l. Error bars represent standard error of the mean (SEM).
Figure 2
Figure 2
Resistance intensity and synergist assay of An. funestus populations from Busia and Mayuge: (A) Determination of resistance intensity with 5× and 10× the diagnostic concentrations of permethrin and deltamethrin. Results are average of percentage mortalities ± SEM; (B) Effect of pre-exposure to synergist PBO against permethrin and deltamethrin. Results are average of percentage mortalities from four replicates each ± SEM.
Figure 3
Figure 3
Bio-efficacy of different commercial LLINs against An. funestus in Busia and Mayuge. Results of cone bioassays with PermaNet®3.0 (side and roof), PermaNet®2.0, Olyset®Plus and Olyset®Net. Results are average of percentage mortalities ± SEM of five replicates. NM = no mortality.
Figure 4
Figure 4
Analysis of the molecular basis of the escalation of pyrethroid resistance in An. funestus: Distribution of the genotypes for key resistance markers in F0 female An. funestus from Eastern Uganda including CYP6P9a, CYP6P9b, L119F-GSTe2, and A296S-RDL showing low frequency of resistant genotypes (A) and Distribution of the genotypes at the L119F-GSTe2 locus between mosquitoes alive and dead after exposition to deltamethrin 1×, 5× and 10× (B). Differential gene expression of the P450 genes CYP6P9a, CYP6P9b, CYP9K1, and CYP6P5 and the Gluthatione S-tranferase GSTe2 in An. funestus from Mayuge (C) and Busia (D), error bars represent standard error of the mean.
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