A marker of glutathione S-transferase-mediated resistance to insecticides is associated with higher Plasmodium infection in the African malaria vector Anopheles funestus

Abstract

Metabolic resistance to insecticides is threatening malaria control in Africa. However, the extent to which it impacts malaria transmission remains unclear. Here, we investigated the association between a marker of glutathione S-transferase mediated metabolic resistance and Plasmodium infection in field population of Anopheles funestus s.s. in comparison to the A296S-RDL target site mutation. The 119F-GSTe2 resistant allele was present in southern (Obout) (56%) and central (Mibellon) (25%) regions of Cameroon whereas the 296S-RDL resistant allele was detected at 98.5% and 15% respectively. The whole mosquito Plasmodium and sporozoite infection rates were 57% and 14.8% respectively in Obout (n = 508) and 19.7% and 5% in Mibellon (n = 360). No association was found between L119F-GSTe2 genotypes and whole mosquito infection status. However, when analyzing oocyst and sporozoite infection rates separately, the resistant homozygote 119F/F genotype was significantly more associated with Plasmodium infection in Obout than both heterozygote (OR = 2.5; P = 0.012) and homozygote susceptible (L/L119) genotypes (OR = 2.10; P = 0.013). In contrast, homozygote RDL susceptible mosquitoes (A/A296) were associated more frequently with Plasmodium infection than other genotypes (OR = 4; P = 0.03). No additive interaction was found between L119F and A296S. Sequencing of the GSTe2 gene showed no association between the polymorphism of this gene and Plasmodium infection. Glutathione S-transferase metabolic resistance is potentially increasing the vectorial capacity of resistant An . funestus mosquitoes. This could result in a possible exacerbation of malaria transmission in areas of high GSTe2-based metabolic resistance to insecticides.

Exploring the Mechanisms of Multiple Insecticide Resistance in a Highly Plasmodium-Infected Malaria Vector Anopheles funestus Sensu Stricto from Sahel of Northern Nigeria

“…These include the comprehensive work carried out at Garki [12], and the work of Leonard and Bruce-Chwatt in 1951 [13], as well as the 2005 report by Awolola on this species from southern Nigeria [17]. The transmission capability of this species has skyrocketed since then, with a P. falciparum sporozoite rate of~55% found in this study, which is comparable to the 57% obtained by Magellan and colleagues on the same species from northern Cameroon, although at the oocyst stage [39]. However, a study has described lower sporozoite rates of~8% for this species but from southern Nigeria [18].…”

“…To assess the correlation between the presence of the 119F mutation and the resistance phenotype, 12 each of DDT-alive and -dead females were genotyped using the above protocol. In addition, these 12 alive and 12 dead females were also screened, using the recently established allele-specific PCR [39].…”

An Experimental Hut Evaluation of PBO-Based and Pyrethroid-Only Nets against the Malaria Vector Anopheles funestus Reveals a Loss of Bed Nets Efficacy Associated with GSTe2 Metabolic Resistance

“…The Adamawa region is in the mountainous zone forming a transition between Cameroon's forested south and savanna north. Malaria transmission is perennial with a high transmission as shown by very high infection rate of Plasmodium infection caused by Plasmodium falciparum but also P. malariae [12]. The village was located in close proximity to permanent water bodies including a lake and swamps which provide suitable breeding sites for An.…”

“…PCR products were separated on 2% agarose gel by electrophoresis. The bands corresponding to different genotypes were interpreted as previously described [12,28].…”

“…funestus, genomic and structural analyses revealed that a leucine to phenylalanine amino acid change (L119F) in GSTe2, has enlarged the substrate-binding pocket of the enzyme, conferring DDT/pyrethroid resistance in West and Central African populations [8]. This single amino acid change was used to design a simple field applicable DNA-based diagnostic tool [12] providing the opportunity to address questions regarding the direct impact of GST-mediated metabolic resistance on insecticide-based interventions such as LLINs.…”