Rapid selection of a pyrethroid metabolic enzyme CYP9K1 by operational malaria control activities

• Published in: Proceedings of the National Academy of Sciences - PNAS 2018-05, Vol.115 (18), p.4619-4624
• Main Authors: Vontas, John, Grigoraki, Linda, Morgan, John, Tsakireli, Dimitra, Fuseini, Godwin, Segura, Luis, de Carvalho, Julie Niemczura, Nguema, Raul, Weetman, David, Slotman, Michel A., Hemingway, Janet
• Format: Article
• Language: English
• Subjects: Animals; Anopheles - drug effects; Anopheles - parasitology; Bednets; Biological Sciences; Children; Cytochrome; Cytochrome P-450 Enzyme System - metabolism; Cytochrome P450; Cytochromes P450; Deltamethrin; Disease control; Disease transmission; Equatorial Guinea - epidemiology; Female; Humans; Insecticide Resistance; Insecticides; Insecticides - pharmacokinetics; Islands - epidemiology; M form; Malaria; Malaria - epidemiology; Malaria - genetics; Malaria - metabolism; Malaria - prevention & control; Mass distribution; Metabolism; Mosquito Control - methods; Mosquitoes; Prevalence; Pyrethrins - pharmacokinetics; Reversion; Spraying; Vector-borne diseases
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.1719663115

Since 2004, indoor residual spraying (IRS) and long-lasting insecticide-impregnated bednets (LLINs) have reduced the malaria parasite prevalence in children on Bioko Island, Equatorial Guinea, from 45% to 12%. After target site-based (knockdown resistance; kdr) pyrethroid resistance was detected in 2004 in Anopheles coluzzii (formerly known as the M form of the Anopheles gambiae complex), the carbamate bendiocarb was introduced. Subsequent analysis showed that kdr alone was not operationally significant, so pyrethroid-based IRS was successfully reintroduced in 2012. In 2007 and 2014–2015, mass distribution of new pyrethroid LLINs was undertaken to increase the net coverage levels. The combined selection pressure of IRS and LLINs resulted in an increase in the frequency of pyrethroid resistance in 2015. In addition to a significant increase in kdr frequency, an additional metabolic pyrethroid resistance mechanism had been selected. Increased metabolism of the pyrethroid deltamethrin was linked with up-regulation of the cytochrome P450 CYP9K1. The increase in resistance prompted a reversion to bendiocarb IRS in 2016 to avoid a resurgence of malaria, in line with the national Malaria Control Program plan.