Knockdown resistance mutations predict DDT resistance and pyrethroid tolerance in the visceral leishmaniasis vector Phlebotomus argentipes

Abstract

BackgroundIndoor residual spraying (IRS) with DDT has been the primary strategy for control of the visceral leishmaniasis (VL) vector Phlebotomus argentipes in India but efficacy may be compromised by resistance. Synthetic pyrethroids are now being introduced for IRS, but with a shared target site, the para voltage-gated sodium channel (VGSC), mutations affecting both insecticide classes could provide cross-resistance and represent a threat to sustainable IRS-based disease control.Methodology/Principal findingsA region of the Vgsc gene was sequenced in P. argentipes from the VL hotspot of Bihar, India. Two knockdown resistance (kdr) mutations were detected at codon 1014 (L1014F and L1014S), each common in mosquitoes, but previously unknown in phlebotomines. Both kdr mutations appear largely recessive, but as homozygotes (especially 1014F/F) or as 1014F/S heterozygotes exert a strong effect on DDT resistance, and significantly predict survivorship to class II pyrethroids in short-duration bioassays. The mutations are present at high frequency in wild P. argentipes populations from Bihar, with 1014F significantly more common in higher VL areas.Conclusions/SignificanceThe Vgsc mutations detected appear to be a primary mechanism underlying DDT resistance in P. argentipes and a contributory factor in reduced pyrethroid susceptibility, suggesting a potential impact if P. argentipes are subjected to suboptimal levels of pyrethroid exposure, or additional resistance mechanisms evolve. The assays to detect kdr frequency changes provide a sensitive, high-throughput monitoring tool to detecting spatial and temporal variation in resistance in P. argentipes.

Understanding Behavioural Temperament of Phlebotomus argentipes Under the Influence of DDT-IRS Versus SP-IRS for Scoping New Approaches for Maximum Control Over the VL-Vector Population in Bihar

“…After getting the satisfactory results in terms of sand fly collection just within a week of IRS, the comparison based exophilic versus endophilic sand fly density was extended at the villages lying within the regime of Saran along with Vaishali i.e., highly endemic for Kala-azar. The data exhibited a major chunk of P. argentipes collected from the outdoor sites as compared with the indoor habitat validating our hypothesis of gradual shifting of habitat of VL vectors from endophilic to exophilic which is undoubtedly followed due to the fact of developed resistance among them [14,17,26] against chemical constituent of IRS. Under the influence of developed resistance against insecticide, insects instead of getting killed, they duly modify their behavior to cope the toxicity of that insecticide that further rewards them with survival [17].…”

“…Also, DDT constituted IRS probed a serious impact over the sand fly density [15,18,23] and accordingly upon year-toyear VL cases too, that remained sessile with DDT-IRS activation got flared-up each time with cessation of DDT-IRS [11] and its continuous perusal furthermore overruled its effect very soon ultimately leading to surging-up of sand fly density at sprayed sites. Hence, it became very difficult to conclude whether the sand fly resurgence was a single effect of DDT withdrawal [11] or the combo effect along with developed resistance among sand flies against DDT insecticide [8,14,15,25,26].…”

Occurrence of pyrethroid resistance mutation in Cydia pomonella (Lepidoptera: Tortricidae) throughout Argentina

“…The discontinuation for many years of pyrethroid applications, and the immigration of susceptible individuals from surrounding abandoned and organic orchards could explain the low of kdr frequency in this region. Since the kdr-type resistance allele is partially or completely recessive (Bouvier et al, 2001;Gomes et al, 2017), results from this study suggest that kdr mutation in populations from Río Negro and Neuquén valley may not explain by itself the lambdacyhalothrin resistance levels. The present and previous studies (Soleño et al, 2008;Cichón et al, 2013) would indicate that lambda-cyhalothrin resistance in C. pomonella from CSA, GUE, and VRG3 is conferred by multiple-resistance mechanisms including kdr mutation in the sodium channel and increased activities of CYP450 and esterases.…”

Population dynamics, pathogen detection and insecticide resistance of mosquito and sand fly in refugee camps, Greece

“…albopictus samples were amplified, purified and sequenced (primers in Table 1). In sand flies, a DNA fragment of the VGSC gene (flanking the codons 1011, 1014, 1016, and 1020) was amplified, purified (Macherey Nagel, Dueren, Germany commercial kit) and sequenced (primers in Table 1) as described in reference [27].…”