Multiple Resistances and Complex Mechanisms of Anopheles sinensis Mosquito: A Major Obstacle to Mosquito-Borne Diseases Control and Elimination in China

Abstract

Malaria, dengue fever, and filariasis are three of the most common mosquito-borne diseases worldwide. Malaria and lymphatic filariasis can occur as concomitant human infections while also sharing common mosquito vectors. The overall prevalence and health significance of malaria and filariasis have made them top priorities for global elimination and control programmes. Pyrethroid resistance in anopheline mosquito vectors represents a highly significant problem to malaria control worldwide. Several methods have been proposed to mitigate insecticide resistance, including rotational use of insecticides with different modes of action. Anopheles sinensis, an important malaria and filariasis vector in Southeast Asia, represents an interesting mosquito species for examining the consequences of long-term insecticide rotation use on resistance. We examined insecticide resistance in two An. Sinensis populations from central and southern China against pyrethroids, organochlorines, organophosphates, and carbamates, which are the major classes of insecticides recommended for indoor residual spray. We found that the mosquito populations were highly resistant to the four classes of insecticides. High frequency of kdr mutation was revealed in the central population, whereas no kdr mutation was detected in the southern population. The frequency of G119S mutation in the ace-1 gene was moderate in both populations. The classification and regression trees (CART) statistical analysis found that metabolic detoxification was the most important resistance mechanism, whereas target site insensitivity of L1014 kdr mutation played a less important role. Our results indicate that metabolic detoxification was the dominant mechanism of resistance compared to target site insensitivity, and suggests that long-term rotational use of various insecticides has led An. sinensis to evolve a high insecticide resistance. This study highlights the complex network of mechanisms conferring multiple resistances to chemical insecticides in mosquito vectors and it has important implication for designing and implementing vector resistance management strategies.

Genome‐wide and expression‐profiling analyses suggest the main cytochrome P450 genes related to pyrethroid resistance in the malaria vector, Anopheles sinensis (Diptera Culicidae)

“…Two sets of transcriptome assembly sequences of An. sinensis were downloaded from GenBank as EST databases . P450 amino acid sequences of An.…”

“…Because of extensive and continued application, pyrethroid resistance in An. sinensis is now widespread in many regions of China . However, the molecular mechanisms of pyrethroid resistance in An.…”

“…Previous studies have shown that higher P450 activity might provide pyrethroid resistance in An. sinensis . CYP6Z2 , CYP4G16 , CYP4G17 and CYP4H15 have been reported to be upregulated in pyrethroid‐resistant An.…”

Estimated resistance of the malaria mosquito Anopheles messeae s.l . to the insecticide malathion

“…The triplet GGC codes for glycine at the 119 th position of ACE‐1 in mosquitoes from Anopheles gambiae , An. sinensis , Anopheles albimanus, and Culex pipiens natural populations (Weill et al , Chang et al ). This triplet is replaced by the AGC triplet in resistant mutants via a single mononucleotide substitution.…”

“…The triplet GGC codes for glycine at the 119 th position of ACE-1 in mosquitoes from Anopheles gambiae, An. sinensis, Anopheles albimanus, and Culex pipiens natural populations (Weill et al 2004, Chang et al 2014 (Selvi et al 2005), minimal and maximal values from ten groups under selection are provided. a GGG glycine triplet at the position.…”