The mosquito Aedes aegypti is the primary urban vector of the viruses causing dengue and chikungunya fever for which vaccines and effective pharmaceuticals are lacking. Epidemic dengue is emerging in the Americas: Mexico has reported >750,000 clinical dengue cases since 2009. Endemic chikungunya fever was reported in the Americas for the first time in 2013 and is now spreading into the Caribbean and Mexico. The only available strategy to suppress dengue or chikungunya fever outbreaks is to reduce vector populations through insecticide applications. However, Ae. aegypti suppression is compromised through a recent rapid rise across Latin America of knockdown resistance (kdr) to pyrethroid insecticides. Widespread, heavy use of pyrethroid space sprays ? due to their strong human safety profile ? has created immense selection pressure for resistance. This resistance is primarily under the control of the voltage gated sodium channel gene (para). Our preliminary data show that high frequencies (>80%) of kdr-conferring alleles occur commonly in Ae. aegypti in Mexico, and that state-of-the-art netting treated with a synergized pyrethroid effectively kills susceptible Ae. aegypti but has unacceptably low (~20%) killing efficacy for Mexican Ae. aegypti strains with high frequencies of kdr-conferring alleles. Our preliminary studies also show that: a) even in the absence of gene flow barriers, local insecticide pressure, rather than migration of mosquitoes with kdr-conferring mutations, is the primary determinant of the local kdr profile for Ae. aegypti; and b) the frequency of kdr-conferring mutations in a highly resistant strain reverted from near fixation to lower levels within 14 generations when pyrethroid pressure was removed. These findings provide hope that the current, disastrous kdr situation can be reversed through insecticide resistance management (IRM) schemes to restore and protect the invaluable pyrethroid susceptibility resource in Ae. aegypti. The goals for this proposal are to demonstrate that pyrethroid susceptibility can be restored and protected in Ae. aegypti and Ae. albopictus through insecticide rotation and focused indoor spraying. We also will identify genes other than para that confer pyrethroid resistance in Ae. aegypti through RNAseq and deep sequencing of exon enriched libraries. Our partnering Mexican institution is Instituto Nacional de Salud Pblica ? Centro Regional de Investigacin en Salud Pblica (INSP-CRISP) in Tapachula.

Public Health Relevance

The mosquito Aedes aegypti transmits the viruses that cause dengue and chikungunya fever for which no vaccines or effective drugs exist. The only available strategy to suppress outbreaks of these diseases is to reduce vector populations through insecticides. But insecticide use has recently become compromised due to the recent rapid rise of knockdown resistance (kdr) to pyrethroid insecticides. This is a proposal to determine whether pyrethroid susceptibility in Ae. aegypti can be restored and protected through insecticide rotation and indoor spraying. We will also identify other genes that control pyrethroid resistance. Our partnering Mexican institution is Instituto Nacional de Salud Pblica ? Centro Regional de Investigacin en Salud Pblica (INSP- CRISP) in Tapachula.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI121211-01A1
Application #
9157808
Study Section
Vector Biology Study Section (VB)
Program Officer
Costero-Saint Denis, Adriana
Project Start
2016-07-01
Project End
2021-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
1
Fiscal Year
2016
Total Cost
$338,586
Indirect Cost
$88,586
Name
Colorado State University-Fort Collins
Department
Microbiology/Immun/Virology
Type
Schools of Veterinary Medicine
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
Saavedra-Rodriguez, Karla; Maloof, Farah Vera; Campbell, Corey L et al. (2018) Parallel evolution of vgsc mutations at domains IS6, IIS6 and IIIS6 in pyrethroid resistant Aedes aegypti from Mexico. Sci Rep 8:6747
Loroño-Pino, Maria A; Uitz-Mena, Ana; Carrillo-Solís, Claudia M et al. (2018) The Use of Insecticide-Treated Curtains for Control of Aedes aegypti and Dengue Virus Transmission in ""Fraccionamiento"" Style Houses in México. J Trop Med 2018:4054501