Insecticide Resistance Profiles and Synergism of Field Aedes aegypti from Indonesia

Abstract

Information on the insecticide resistance profiles of Aedes aegypti in Indonesia is fragmentary because of the lack of wide-area insecticide resistance surveillance. We collected Ae. aegypti from 32 districts and regencies in 27 Indonesian provinces and used WHO bioassays to evaluate their resistance to deltamethrin, permethrin, bendiocarb, and pirimiphos-methyl. To determine the possible resistance mechanisms of Ae. aegypti, synergism tests were conducted using piperonyl butoxide (PBO) and S,S,S-tributylphosphorotrithioates (DEF). The Ae. aegypti from all locations exhibited various levels of resistance to pyrethroids. Their resistance ratio (RR ₅₀) to permethrin and deltamethrin ranged from 4.08× to 127× and from 4.37× to 72.20×, respectively. In contrast with the findings of other studies, most strains from the highly urbanized cities on the island of Java (i.e., Banten, Jakarta, Bandung, Semarang, Yogyakarta, and Surabaya) exhibited low to moderate resistance to pyrethroids. By contrast, the strains collected from the less populated Kalimantan region exhibited very high resistance to pyrethroids. The possible reasons are discussed herein. Low levels of resistance to bendiocarb (RR ₅₀, 1.24–6.46×) and pirimiphos-methyl (RR ₅₀, 1.01–2.70×) were observed in all tested strains, regardless of locality. PBO and DEF synergists significantly increased the susceptibility of Ae. aegypti to permethrin and deltamethrin and reduced their resistance ratio to less than 16×. The synergism tests suggested the major involvement of cytochrome P450 monooxygenases and esterases in conferring pyrethroid resistance. On the basis of our results, we proposed a 6-month rotation of insecticides (deltamethrin + synergists ➝ bendiocarb ➝ permethrin + synergists ➝ pirimiphos-methyl) and the use of an insecticide mixture containing pyrethroid and pyrimiphos-methyl to control Ae. aegypti populations and overcome the challenge of widespread Ae. aegypti resistance to pyrethroid in Indonesia.

Author summary

Insecticide resistance is a major impediment to the successful management of vector-transmitted diseases because it increases the vector’s chances of surviving under insecticide treatment. In Indonesia, the implementation of insecticide resistance management at the national level is particularly challenging due to the vast area and regional disparities in terms of population, health, and socioeconomic status. Previous studies on determining insecticide resistance of Aedes mosquito only focused on several cities in some provinces of Indonesia, making resistance monitoring results difficult to interpret and arguably reflect the generality in Indonesia. To complicate the matter, data released by the Ministry of Agriculture of Indonesia in 2022 showed that approximately 82% of insecticides registered to control Ae. aegypti in Indonesia are pyrethroid-based products. Principally, we found that the synergists PBO and DEF significantly reduce the resistance of field Ae. aegypti from Indonesia toward permethrin and deltamethrin. Bendiocarb and pirimiphos-methyl remain highly toxic to the field strains of Ae. aegypti. We suggest the feasible choice of insecticide group for Ae. aegypti vector management based on the currently registered insecticide inventory. The finding also underscores the urgent need to approve other non-pyrethroid-based insecticides as alternative tools for reducing the risk of resistance development during an outbreak.