Fine scale spatial investigation of multiple insecticide resistance and underlying target-site and metabolic mechanisms in Anopheles gambiae in central Côte d’Ivoire

Routine monitoring of occurrence, levels and mechanisms of insecticide resistance informs effective management strategies, and should be used to assess the effect of new tools on resistance. As part of a cluster randomised controlled trial evaluating a novel insecticide-based intervention in central Côte d’Ivoire, we assessed resistance and its underlying mechanisms in Anopheles gambiae populations from a subset of trial villages. Resistance to multiple insecticides in An. gambiae s.s. and An. coluzzii was detected across villages, with dose–response assays demonstrating extremely high resistance intensity to the pyrethroid deltamethrin (> 1,500-fold), and mortality following exposure to pyrethroid-treated bednets was low (< 30% mortality in cone bioassays). The 1014F kdr mutation was almost fixed (≥ 90%) in all villages but the 1575Y kdr-amplifying mutation was relatively rare (< 15%). The carbamate and organophosphate resistance-associated Ace-1 G119S mutation was also detected at moderate frequencies (22–43%). Transcriptome analysis identified overexpression of P450 genes known to confer pyrethroid resistance (Cyp9K1, Cyp6P3, and Cyp6M2), and also a carboxylesterase (COEAE1F) as major candidates. Cyp6P3 expression was high but variable (up to 33-fold) and correlated positively with deltamethrin resistance intensity across villages (r2 = 0.78, P = 0.02). Tools and strategies to mitigate the extreme and multiple resistance provided by these mechanisms are required in this area to avoid future control failures

Transcriptomic analysis of insecticide resistance in the lymphatic filariasis vector Culex quinquefasciatus

Culex quinquefasciatus plays an important role in transmission of vector-borne diseases of public health importance, including lymphatic filariasis (LF), as well as many arboviral diseases. Currently, efforts to tackle C. quinquefasciatus vectored diseases are based on either mass drug administration (MDA) for LF, or insecticide-based interventions. Widespread and intensive insecticide usage has resulted in increased resistance in mosquito vectors, including C. quinquefasciatus. Herein, the transcriptome profile of Ugandan bendiocarb-resistant C. quinquefasciatus was explored to identify candidate genes associated with insecticide resistance. High levels of insecticide resistance were observed for five out of six insecticides tested, with the lowest mortality (0.97%) reported to permethrin, while for DDT, lambdacyhalothrin, bendiocarb and deltamethrin the mortality rate ranged from 1.63–3.29%. Resistance to bendiocarb in exposed mosquitoes was marked, with 2.04% mortality following 1 h exposure and 58.02% after 4 h. Genotyping of the G119S Ace-1 target site mutation detected a highly significant association (p 8-fold increase vs unexposed controls). These results provide evidence that bendiocarb resistance in Ugandan C. quinquefasciatus is mediated by both target-site mechanisms and over-expression of detoxification enzymes

The evidence for improving housing to reduce malaria: a systematic review and meta-analysis

Background The global malaria burden has fallen since 2000, sometimes before large-scale vector control programmes were initiated. While long-lasting insecticide-treated nets and indoor residual spraying are highly effective interventions, this study tests the hypothesis that improved housing can reduce malaria by decreasing house entry by malaria mosquitoes. Methods A systematic review and meta-analysis was conducted to assess whether modern housing is associated with a lower risk of malaria than traditional housing, across all age groups and malaria-endemic settings. Six electronic databases were searched to identify intervention and observational studies published from 1 January, 1900 to 13 December, 2013, measuring the association between house design and malaria. The primary outcome measures were parasite prevalence and incidence of clinical malaria. Crude and adjusted effects were combined in fixed- and random-effects meta-analyses, with sub-group analyses for: overall house type (traditional versus modern housing); screening; main wall, roof and floor materials; eave type; ceilings and elevation. Results Of 15,526 studies screened, 90 were included in a qualitative synthesis and 53 reported epidemiological outcomes, included in a meta-analysis. Of these, 39 (74 %) showed trends towards a lower risk of epidemiological outcomes associated with improved house features. Of studies assessing the relationship between modern housing and malaria infection (n = 11) and clinical malaria (n = 5), all were observational, with very low to low quality evidence. Residents of modern houses had 47 % lower odds of malaria infection compared to traditional houses (adjusted odds ratio (OR) 0°53, 95 % confidence intervals (CI) 0°42–0°67, p < 0°001, five studies) and a 45–65 % lower odds of clinical malaria (case–control studies: adjusted OR 0°35, 95 % CI 0°20–0°62, p <0°001, one study; cohort studies: adjusted rate ratio 0°55, 95 % CI 0°36–0°84, p = 0°005, three studies). Evidence of a high risk of bias was found within studies. Conclusions Despite low quality evidence, the direction and consistency of effects indicate that housing is an important risk factor for malaria. Future research should evaluate the protective effect of specific house features and incremental housing improvements associated with socio-economic development