Decline in frequency of the 2La chromosomal inversion in Anopheles gambiae (s.s.) in Western Kenya: correlation with increase in ownership of insecticide-treated bed nets

Abstract

BackgroundThe 2La chromosomal inversion, a genetic polymorphism in An. gambiae (sensu stricto) (s.s.), is associated with adaptation to microclimatic differences in humidity and desiccation resistance and mosquito behaviors. Ownership of insecticide-treated bed nets (ITNs) for malaria control has increased markedly in western Kenya in the last 20 years. An increase in the frequency of ITNs indoors could select against house entering or indoor resting of Anopheles mosquitoes. Thus, the frequency of the 2La inversion is postulated to change in An. gambiae (s.s.) with the increase of ITN ownership over time.MethodsAnopheles gambiae mosquitoes were sampled between 1994 and 2011 using pyrethrum knockdown, bednet traps and human landing catches (HLC) from Asembo and Seme, western Kenya. The 2La inversion was detected by a PCR assay with primers designed for proximal breakpoints of the 2La/a and 2L+a/+a chromosomal conformation. Mosquitoes were tested for malaria parasite infection by sporozoite ELISA.ResultsThe frequency of the 2La chromosomal inversion declined from 100 % of all chromosomes in 1994 to 17 % in 2005 and remained low through 2011 (21 %). ITN ownership increased from 0 to > 90 % of houses in the study area during this interval. The decline in the frequency of the 2La chromosomal inversion was significantly, negatively correlated with year (r = -0.93) and with increase in ITN ownership (r = -0.96). The frequency of the homo- and heterokaryotypes departed significantly from Hardy-Weinberg equilibrium, suggesting that 2La/a karyotype was under selection, earlier in its favor and later, against it. Precipitation and maximum monthly temperature did not vary over time, therefore there was no trend in climate that could account for the decline. There was no significant difference in frequency of the 2La inversion in An. gambiae (s.s.) females sampled indoors or outdoors in HCL in 2011, nor was there an association between the 2La inversion and infection with Plasmodium falciparum sporozoites.ConclusionsThe increase in ITN ownership in the study area was negatively correlated with the frequency of 2La inversion. The decline in 2La frequency in western Kenya is postulated to be due to differential impacts of ITNs on mosquitoes with different 2La karyotypes, possibly mediated by differences in behavior associated with the 2La karyotypes. Further research is required to determine if this is a widespread phenomenon, to further determine the association of the 2La karyotypes with mosquito behavior, and to assess whether ITNs are exerting selection mediated by differences in behavior on the different karyotypes.

Candidate-gene based GWAS identifies reproducible DNA markers for metabolic pyrethroid resistance from standing genetic variation in East African Anopheles gambiae

“…In A. gambiae s.s. samples from a 17-year time series collected in Western Kenya, Matoke-Muhia et al . 45 detected a sharp decline in frequency of the previously numerically-dominant 2La karyotype in favour of the 2L+ a karyotype, which correlated strongly (r = −0.96) with the changing coverage of pyrethroid-treated bednets in the area. To our knowledge our study is the first to provide direct association data directly linking pyrethroid resistance with 2La inversion polymorphism, adding corroborative evidence to the field survey results from Western Kenya.…”

The Anopheles gambiae 2La chromosome inversion is associated with susceptibility to Plasmodium falciparum in Africa

“…It is this behavioral tendency of 2L+ a /2L+ a mosquitoes that makes them a potential concern, because under the pressure of indoor-based vector control such as ITNs and IRS, the relative population frequencies of the 2L+ a allele would be expected to increase, and the resulting population could become more exophilic. In the only examination of 2La genotypes under indoor selection pressure to our knowledge, the 2L+ a /2L+ a frequency increased from 0% detectable in 1994 before ITN rollout in western Kenya to 66% by 2011 after rollout ( Matoke-Muhia et al, 2016 ). The 2La inversion is not genetically associated with resistance to the pyrethroid insecticides used on ITNs ( Brooke et al, 2002 ), so the underlying mechanism is more likely to be behavioral avoidance rather than chemical selection.…”

“…However, as observed in that work, the intraspecific differences in infection rate required confirmation at other geographic sites to generalize the findings and could potentially be due to many interacting factors, including differential longevity, physiological susceptibility to Plasmodium , and feeding behavior. To our knowledge, association of the 2La inversion with Plasmodium infection has only been examined once since the initial cytogenetic study, and no significant effect was detected ( Matoke-Muhia et al, 2016 ), but the small sample size of infected mosquitoes in the study (n = 15) would yield low statistical power to detect an effect among three genotypes, even if one existed.…”

Genetic heterogeneity in Anopheles darlingi related to biting behavior in western Amazon

“…Besides temperature, indoor residual spraying could be an important drive in the selection of mosquito females. Different reports already showed fast selection of mosquito resistance genes correlated to insecticide usage, either by insecticide-treated bed nets (ITNs) and indoors residual spraying [42][43][44][45]. Both rural settlement studied (Granada and Remansinho) have no long history in use of ITNs, but both places usually use indoors residual spraying.…”