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

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Gomes, Bruno ORCID: https://orcid.org/0000-0003-3877-2359, Purkait, Bidyut, Deb, Rinki, Rama, Aarti, Singh, Rudra, Foster, Geraldine ORCID: https://orcid.org/0000-0002-9769-4349, Coleman, Michael ORCID: https://orcid.org/0000-0003-4186-3526, Kumar, Vijay, Paine, Mark ORCID: https://orcid.org/0000-0003-2061-7713, Das, Pradeep and Weetman, David ORCID: https://orcid.org/0000-0002-5820-1388 (2017) 'Knockdown resistance mutations predict DDT resistance and pyrethroid tolerance in the visceral leishmaniasis vector Phlebotomus argentipes'. PLoS Neglected Tropical Diseases, Vol 11, Issue 4, e0005504.

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Abstract

Background

Indoor 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 findings

A 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/Significance

The 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.

Item Type: Article
Subjects: QU Biochemistry > Genetics > QU 500 Genetic phenomena
QU Biochemistry > Proteins. Amino Acids. Peptides > QU 58.5 DNA.
QX Parasitology > Insects. Other Parasites > QX 505 Diptera
QX Parasitology > Insects. Other Parasites > QX 600 Insect control. Tick control
WC Communicable Diseases > Tropical and Parasitic Diseases > WC 715 Visceral leishmaniasis
Faculty: Department: Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI): https://doi.org/10.1371/journal.pntd.0005504
Depositing User: Daisy Byrne
Date Deposited: 03 May 2017 14:54
Last Modified: 17 Aug 2018 08:01
URI: https://archive.lstmed.ac.uk/id/eprint/7070

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