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.

Author Summary

Malaria and lymphatic filariasis are two of the most important mosquito-borne parasitic diseases worldwide, which can occur as concomitant human infections. The Anopheles sinensis mosquito is the most common malaria and lymphatic filariasis vector in Southeast Asia. Disease-vector control is an important part of the global malaria and filariasis control strategies. Pyrethroid insecticides are the major vector control agents, and rotational or combinational use with other classes of insecticides has been proposed to mitigate the problem of pyrethroid resistance. Therefore, assessing resistance to multiple classes of insecticides is important because vector control programs may not be effective, or even fail, if mosquito vectors are already resistant to the insecticides being used in rotation or combination. The field populations of An. sinensis mosquito from central China (Anhui) and southern China (Yunnan) developed high resistance to four classes of insecticides tested, including pyrethroids (deltamethrin and permethrin), organochlorine (DDT), organophosphate (malathion), and carbamate (bendiocarb). This study examined two questions: 1) the consequences of long-term insecticide rotation use on insecticide resistance, and 2) the role of metabolic detoxification and target site insensitivity in resistance to chemical insecticides. The information obtained from this investigation is valuable in informing current and future vector control strategies.