Sub-lethal aquatic doses of pyriproxyfen may increase pyrethroid resistance in malaria mosquitoes

Opiyo, M. A., Ngowo, H. S. , Mapua, S. A., Mpingwa, M., Nchimbi, N., Matowo, N. S., Majambere, S. and Okumu, F. O. (2021) Sub-lethal aquatic doses of pyriproxyfen may increase pyrethroid resistance in malaria mosquitoes. PLoS ONE, 16(3), e0248538. (doi: 10.1371/journal.pone.0248538) (PMID:33735241) (PMCID:PMC7971891)

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Background: Pyriproxyfen (PPF), an insect growth hormone mimic is widely used as a larvicide and in some second-generation bed nets, where it is combined with pyrethroids to improve impact. It has also been evaluated as a candidate for auto-dissemination by adult mosquitoes to control Aedes and Anopheles species. We examined whether PPF added to larval habitats of pyrethroid-resistant malaria vectors can modulate levels of resistance among emergent adult mosquitoes. Methodology: Third-instar larvae of pyrethroid-resistant Anopheles arabiensis (both laboratory-reared and field-collected) were reared in different PPF concentrations, between 1×10−9 milligrams active ingredient per litre of water (mgAI/L) and 1×10−4 mgAI/L, or no PPF at all. Emergent adults escaping these sub-lethal exposures were tested using WHO-standard susceptibility assays on pyrethroids (0.75% permethrin and 0.05% deltamethrin), carbamates (0.1% bendiocarb) and organochlorides (4% DDT). Biochemical basis of pyrethroid resistance was investigated by pre-exposure to 4% PBO. Bio-efficacies of long-lasting insecticide-treated nets, Olyset® and PermaNet 2.0 were also examined against adult mosquitoes with or without previous aquatic exposure to PPF. Results: Addition of sub-lethal doses of PPF to larval habitats of pyrethroid-resistant An. arabiensis, consistently resulted in significantly reduced mortalities of emergent adults when exposed to pyrethroids, but not to bendiocarb or DDT. Mortality rates after exposure to Olyset® nets, but not PermaNet 2.0 were also reduced following aquatic exposures to PPF. Pre-exposure to PBO followed by permethrin or deltamethrin resulted in significant increases in mortality, compared to either insecticide alone. Conclusions: Partially-resistant mosquitoes exposed to sub-lethal aquatic concentrations of PPF may become more resistant to pyrethroids than they already are without such pre-exposures. Studies should be conducted to examine whether field applications of PPF, either by larviciding or other means actually exacerbates pyrethroid-resistance in areas where signs of such resistance already exist in wild the vector populations. The studies should also investigate mechanisms underlying such magnification of resistance, and how this may impact the potential of PPF-based interventions in areas with pyrethroid resistance.

Item Type:Articles
Additional Information:This work was funded by the Bill and Melinda Gates Foundation (Grant Numbers: OPP52644) awarded to Dr. Fredros Okumu. N.S.M received financial support from Wellcome Trust and the Association of Physicians of Great Britain and Ireland (Grant number: WT104029/Z/14/Z), while H.S.N, and F.O.O were supported by a Wellcome Trust Intermediate Research Fellowship (Grant number: WT102350/Z/13/Z) and a grant from World Health Organization, Special Program for Research and Training in Tropical Diseases (Grant No. B40445). We acknowledge the support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and support from the Generalitat de Catalunya through the CERCA Program. CISM is supported by the Government of Mozambique and the Spanish Agency for International Development (AECID).
Glasgow Author(s) Enlighten ID:Ngowo, Halfan and Okumu, Dr Fredros
Creator Roles:
Ngowo, H. S.Data curation, Formal analysis, Validation, Visualization, Writing – review and editing
Okumu, F. O.Conceptualization, Funding acquisition, Methodology, Project administration, Resources, Supervision, Validation, Visualization, Writing – review and editing
Authors: Opiyo, M. A., Ngowo, H. S., Mapua, S. A., Mpingwa, M., Nchimbi, N., Matowo, N. S., Majambere, S., and Okumu, F. O.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN (Online):1932-6203
Copyright Holders:Copyright © 2021 Opiyo et al.
First Published:First published in PLoS ONE 16(3): e0248538
Publisher Policy:Reproduced under a Creative Commons License

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