Malaria vectors in the Democratic Republic of the Congo: the mechanisms that confer insecticide resistance in Anopheles gambiae and Anopheles funestus

Abstract

BackgroundThe Democratic Republic of the Congo (DRC) is characterized as a holoendemic malaria area with the main vectors being Anopheles funestus and members of the Anopheles gambiae complex. Due to political instability and socio-economic challenges in the region, knowledge of insecticide resistance status and resistance mechanisms in these vectors is limited. Mosquitoes were collected from a mining site in the north-eastern part of the country and, following identification, were subjected to extensive testing for the target-site and biochemical basis of resistance. Quantitative real-time PCR was used to assess a suite of 10 genes frequently involved in pyrethroid and dichlorodiphenyltrichloroethane (DDT) resistance in An. gambiae females and males. In An. funestus, gene expression microarray analysis was carried out on female mosquitoes.ResultsIn both species, deltamethrin resistance was recorded along with high resistance and suspected resistance to DDT in An. gambiae and An. funestus, respectively. A total of 85% of An. gambiae carried the kdr mutations as either homozygous resistant (RR) (L1014S, L1014F or both) or heterozygous (RS), however only 3% carried the rdl mutant allele (RS) and no ace-1 mutations were recorded. Synergist assays indicated a strong role for P450s in deltamethrin resistance in both species. In An. gambiae, analysis of transcription levels showed that the glutathione-S-transferase, GSTS1-2, produced the highest fold change in expression (7.6-fold in females and 31-fold in males) followed by GSTE2, thioredoxin peroxidase (TPX2), and cytochrome oxidases (CYP6M2 and CYP6P1). All other genes tested produced fold change values below 2. Microarray analysis revealed significant over-transcription of cuticular proteins as well as CYP6M7, CYP6P9a and CYP6P9b in insecticide resistant An. funestus.ConclusionsThese data show that high levels of deltamethrin resistance in the main malaria vector species, conferred by enzymatic detoxification, are present in the DRC.Electronic supplementary materialThe online version of this article (10.1186/s12936-017-2099-y) contains supplementary material, which is available to authorized users.

Proteomic Investigation on Anopheles gambiae in Burkina Faso Related to Insecticide Pressures from Different Climatic Regions

“…Previous studies have shown that GSH S‐transferase, carboxylesterases and peroxidases were involved in the resistance to DDT and malathion, [ 38,40 ] while GSH S‐transferases and cytochromes were associated with resistance to DDT, permethrin, deltamethrin, λ ‐cyhalothrin, and malathion. [ 41,42,43 ] Thioredoxin peroxidase was associated with resistance to deltamethrin [ 44 ] and acetyl‐CoA acyltransferase, enoyl‐CoA isomerase, and glutathione S‐transferase with resistance to organophosphate. [ 39 ] GSH S‐transferase and cytochromes were the most impacted by insecticide pressures in both climate regions.…”

Insecticide resistance in Anopheles gambiae from the northern Democratic Republic of Congo, with extreme knockdown resistance (kdr) mutation frequencies revealed by a new diagnostic assay

“…gambiae s.s. in the North East were found to be resistant to deltamethrin, DDT and bendiocarb. Pre-exposure to PBO (piperonyl butoxide), a synergist that inhibits the activity of cytochrome P450 enzymes and some esterases which may be involved in the detoxification of pyrethroids, significantly increased mortality in bioassays suggesting that metabolic enzymes were at least partly responsible for the resistance phenotype [ 7 ]. A study in 2013 of two sites near Kinshasa found that An.…”

Malaria Rapid Diagnostic Test (HRP2/pLDH) Positivity, Incidence, Care Accessibility and Impact of Community WASH Action in DR Congo: Mixed Method Study involving 625 Households

“…Mixed method research comprising three distinct studies was conducted in two semi-rural towns of Kongo Central province, DRC, from January 2017 through March 2018. The main study involved 3,712 individuals from 625 households and included: (1) a cross-sectional design (baseline survey) using Malaria Indicator Questionnaire [13,21] from the World Bank and WHO Malaria Program in Africa and Madagascar; (2) an action research (a 6-month prospective study) consisting of two interventions: community participatory WASH action and malaria education campaign. The latter intervention was implemented in both study sites (Fig.…”