Multiple insecticide resistance and first evidence of V410L kdr mutation in Aedes (Stegomyia) aegypti (Linnaeus) from Burkina Faso.

The response to recent dengue outbreaks in Burkina Faso was insecticide-based, despite poor knowledge of the vector population's susceptibility to the insecticides used. Here, we report on the susceptibility to the main insecticide classes and identify important underlying mechanisms in Aedes aegypti populations in Ouagadougou and Banfora, in 2019 and 2020. Wild Ae. aegypti were tested as adults in WHO bioassays and then screened in real time melting curve qPCR analyses to genotype the F1534C, V1016I, and V410L Aedes kdr mutations. Ae. aegypti showed moderate resistance to 0.1% bendiocarb (80-95% survival post-exposure), 0.8% Malathion (60-100%), 0.21% pirimiphos-methyl (75% - 97%), and high resistance to 0.03% deltamethrin (20-70%). PBO pre-exposure partially restored pyrethroid susceptibility. Genotyping detected high frequency of 1534C allele (0.92) and moderate 1016I (0.1-0.32). The V410L mutation was detected in Burkina Faso for the first time (frequency 0.1-0.36). Mosquitoes surviving 4 h exposure to 0.03% deltamethrin had significantly higher frequencies of the F1534C mutation than dead mosquitoes (0.70 vs. 0.96, p < 0.0001) and mosquitoes surviving 2 - 4 h exposure had a significantly reduced life span. Ae. aegypti from Burkina Faso are resistant to multiple insecticide classes with multiple mechanisms involved, demonstrating the essential role of insecticide resistance monitoring within national dengue control programmes.

Anti-malarial efficacy and resistance monitoring of artemether-lumefantrine and dihydroartemisinin-piperaquine shows inadequate efficacy in children in Burkina Faso, 2017-2018.

BACKGROUND: The World Health Organization recommends regularly assessing the efficacy of artemisinin-based combination therapy (ACT), which is a critical tool in the fight against malaria. This study evaluated the efficacy of two artemisinin-based combinations recommended to treat uncomplicated Plasmodium falciparum malaria in Burkina Faso in three sites: Niangoloko, Nanoro, and Gourcy. METHODS: This was a two-arm randomized control trial of the efficacy of artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP). Children aged 6-59 months old were monitored for 42 days. The primary outcomes of the study were uncorrected and PCR-corrected efficacies to day 28 for AL and 42 for DP. Molecular markers of resistance to artemisinin derivatives and partner drugs were also analysed. RESULTS: Of 720 children enrolled, 672 reached study endpoints at day 28, 333 in the AL arm and 339 in the DP arm. PCR-corrected 28-day per protocol efficacy in the AL arm was 74% (64-83%) in Nanoro, 76% (66-83%) in Gourcy, and 92% (84-96%) in Niangoloko. The PCR-corrected 42-day per protocol efficacy in the DP arm was 84% (75-89%) in Gourcy, 89% (81-94%) in Nanoro, and 97% (92-99%) in Niangoloko. No Pfk13 mutation previously associated with artemisinin-resistance was observed. No statistically significant association was found between treatment outcome and presence of the 86Y mutation in the Pfmdr1 gene. There was also no association observed between treatment outcome and Pfpm2 or Pfmdr1 copy number variation. CONCLUSION: The results of this study indicate evidence of inadequate efficacy of AL at day 28 and DP at day 42 in the same two sites. A change of first-line ACT may be warranted in Burkina Faso. Trial Registry Pan African Clinical Trial Registry Identifier: PACTR201708002499311. Date of registration: 8/3/2017 https://pactr.samrc.ac.za/Search.aspx.

Insecticide resistance and behavioural adaptation as a response to long-lasting insecticidal net deployment in malaria vectors in the Cascades region of Burkina Faso.

The decline in malaria across Africa has been largely attributed to vector control using long-lasting insecticidal nets (LLINs). However, this intervention has prompted widespread insecticide resistance (IR) and been associated with changes in mosquito behaviour that reduce their contact with LLINs. The relative importance and rate at which IR and behavioural adaptations emerge are poorly understood. We conducted surveillance of mosquito behaviour and IR at 12 sites in Burkina Faso to assess the magnitude and temporal dynamics of insecticide, biting and resting behaviours in vectors in the 2-year period following mass LLIN distribution. Insecticide resistance was present in all vector populations and increased rapidly over the study period. In contrast, no longitudinal shifts in LLIN-avoidance behaviours (earlier or outdoor biting and resting) were detected. There was a moderate but statistically significant shift in vector species composition from Anopheles coluzzii to Anopheles gambiae which coincided with a reduction in the proportion of bites preventable by LLINs; possibly driven by between-species variation in behaviour. These findings indicate that adaptations based on insecticide resistance arise and intensify more rapidly than behavioural shifts within mosquito vectors. However, longitudinal shifts in mosquito vector species composition were evident within 2 years following a mass LLIN distribution. This ecological shift was characterized by a significant increase in the exophagic species (An. gambiae) and coincided with a predicted decline in the degree of protection expected from LLINs. Although human exposure fell through the study period due to reducing vector densities and infection rates, such ecological shifts in vector species along with insecticide resistance were likely to have eroded the efficacy of LLINs. While both adaptations impact malaria control, the rapid increase of the former indicates this strategy develops more quickly in response to selection from LLINS. However, interventions targeting both resistance strategies will be needed.