Distribution of Anopheles gambiae thioester-containing protein 1 alleles along malaria transmission gradients in The Gambia.

BACKGROUND: Thioester-containing protein 1 (TEP1) is a highly polymorphic gene playing an important role in mosquito immunity to parasite development and associated with Anopheles gambiae vectorial competence. Allelic variations in TEP1 could render mosquito either susceptible or resistant to parasite infection. Despite reports of TEP1 genetic variations in An. gambiae, the correlation between TEP1 allelic variants and transmission patterns in malaria endemic settings remains unclear. METHODS: TEP1 allelic variants were characterized by PCR from archived genomic DNA of > 1000 An. gambiae mosquitoes collected at 3 time points between 2009 and 2019 from eastern Gambia, where malaria transmission remains moderately high, and western regions with low transmission. RESULTS: Eight common TEP1 allelic variants were identified at varying frequencies in An. gambiae from both transmission settings. These comprised the wild type TEP1, homozygous susceptible genotype, TEP1s; homozygous resistance genotypes: TEP1rA and TEP1rB, and the heterozygous resistance genotypes: TEP1srA, TEP1srB, TEP1rArB and TEP1srArB. There was no significant disproportionate distribution of the TEP1 alleles by transmission setting and the temporal distribution of alleles was also consistent across the transmission settings. TEP1s was the most common in all vector species in both settings (allele frequencies: East = 21.4-68.4%. West = 23.5-67.2%). In Anopheles arabiensis, the frequency of wild type TEP1 and susceptible TEP1s was significantly higher in low transmission setting than in high transmission setting (TEP1: Z = - 4.831, P < 0.0001; TEP1s: Z = - 2.073, P = 0.038). CONCLUSIONS: The distribution of TEP1 allele variants does not distinctly correlate with malaria endemicity pattern in The Gambia. Further studies are needed to understand the link between genetic variations in vector population and transmission pattern in the study settings. Future studies on the implication for targeting TEP1 gene for vector control strategy such as gene drive systems in this settings is also recommended.

Does insecticide resistance contribute to heterogeneities in malaria transmission in The Gambia?

BACKGROUND: Malaria hotspots, areas with consistently higher than average transmission, may become increasingly common as malaria declines. This phenomenon, currently observed in The Gambia, may be caused by several factors, including some related to the local vectors, whose contribution is poorly understood. METHODS: Using WHO susceptibility bioassays, insecticide resistance status was determined in vector populations sampled from six pairs of villages across The Gambia, each pair contained a low and high prevalence village. RESULTS: Three vector species were observed (23.5% Anopheles arabiensis, 31.2% Anopheles gambiae, 43.3% Anopheles coluzzii and 2.0% An. coluzzii × An. gambiae hybrids). Even at a fine scale, significant differences in species composition were detected within village pairs. Resistance to both DDT and deltamethrin was more common in An. gambiae, most markedly in the eastern part of The Gambia and partly attributable to differing frequencies of resistance mutations. The Vgsc-1014F target site mutation was strongly associated with both DDT (OR = 256.7, (95% CI 48.6-6374.3, p < 0.001) and deltamethrin survival (OR = 9.14, (95% CI 4.24-21.4, p < 0.001). A second target site mutation, Vgsc-1575Y, which co-occurs with Vgsc-1014F, and a metabolic marker of resistance, Gste2-114T, conferred additional survival benefits to both insecticides. DDT resistance occurred significantly more frequently in villages with high malaria prevalence (p = 0.025) though this did not apply to deltamethrin resistance. CONCLUSION: Whilst causality of relationships requires further investigation, variation in vector species and insecticide resistance in The Gambia is associated with malaria endemicity; with a notably higher prevalence of infection and insecticide resistance in the east of the country. In areas with heterogeneous malaria transmission, the role of the vector should be investigated to guide malaria control interventions.

Status of insecticide resistance in Anopheles gambiae (s.l.) of The Gambia.

BACKGROUND: Vector control activities, namely long-lasting insecticidal nets (LLIN) and indoor residual spraying (IRS), have contributed significantly to the decreasing malaria burden observed in The Gambia since 2008. Nevertheless, insecticide resistance may threaten such success; it is important to regularly assess the susceptibility of local malaria vectors to available insecticides. METHODS: In the transmission seasons of 2016 and 2017, Anopheles gambiae (s.l.) larvae were sampled in or around the nine vector surveillance sentinel sites of the Gambia National Malaria Control Programme (GNMCP) and in a few additional sampling points. Using WHO susceptibility bioassays, female adult mosquitoes were exposed to insecticide-impregnated papers. Molecular identification of sibling species and insecticide resistance molecular markers was done on a subset of 2000 female mosquitoes. RESULTS: A total of 4666 wild-caught female adult mosquitoes were exposed to either permethrin (n = 665), deltamethrin (n = 744), DDT (n = 1021), bendiocarb (n = 990) or pirimiphos-methyl (n = 630) insecticide-impregnated papers and control papers (n = 616). Among the 2000 anophelines, 1511 (80.7%) were Anopheles arabiensis, 204 (10.9%) Anopheles coluzzii, 75 (4%) Anopheles gambiae (s.s.), and 83 (4.4%) An. gambiae (s.s.) and An. coluzzii hybrids. There was a significant variation in the composition and species distribution by regions and year, P = 0.009. Deltamethrin, permethrin and DDT resistance was found in An. arabiensis, especially in the coastal region, and was mediated by Vgsc-1014F/S mutations (odds ratio = 34, P = 0.014). There was suspected resistance to pirimiphos-methyl (actellic 300CS) in the North Bank Region although only one survivor had the Ace-1-119S mutation. CONCLUSIONS: As no confirmed resistance to bendiocarb and actellic 300CS was detected, the national malaria control programme can continue using these insecticides for IRS. Nevertheless, the detection of Ace-1 119S mutation warrants extensive monitoring. The source of insecticide pressure driving insecticide resistance to pyrethroids and DDT detected at the coastal region should be further investigated in order to properly manage the spread of resistance in The Gambia.