The public health and economic burden imposed by mosquito-borne diseases on the developing world, and especially Africa, is enormous. Malaria accounts for the largest portion of global mosquito-borne disease morbidity and mortality. There is an urgent need for novel vector control tools that reduce malaria transmission by mosquitoes in distinct ways from traditional insecticides, including tools that have new molecular targets in mosquitoes, new modes of delivery to the mosquito, and tools that can target transmission by vectors not well- controlled by insecticide-treated nets or indoor residual spraying. To be maximally effective in resource- constrained environments of the developing world, such tools must also be able to integrate with existing malaria control interventions and existing human health infrastructures. Our broad hypothesis is that ivermectin used in human de-worming campaigns in African villages, and which we have shown can disrupt malaria parasite transmission in Senegalese villages, could serve as one of these promising new tools. Ivermectin is an oral drug, already given by mass administration to humans in the developing world for onchocerciasis control, and malaria vectors can ingest and be killed by this drug when they bite humans after these mass drug administrations. Our data suggests that more frequent administrations of ivermectin in malaria-endemic communities would result in sustained reductions in malaria parasite transmission. To get to this goal, a thorough examination of the ivermectin effects against malaria vectors in the field and laboratory is necessary. We propose two specific aims:
Aim 1 : Perform field population studies in Senegal on the effects of ivermectin ingested by wild malaria vectors.
Aim 2 : Perform laboratory and modeling studies on the effects ivermectin may have on mosquitoes and malaria parasite transmission.

Public Health Relevance

This project proposes to understand how the drug ivermectin can affect the survival of African malaria vectors and interrupt malaria parasite transmission in Africa. The project is intended to lay the scientific foundation for using ivermectin as a new malaria control tool.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI094349-04
Application #
8843336
Study Section
Vector Biology Study Section (VB)
Program Officer
Costero-Saint Denis, Adriana
Project Start
2012-02-15
Project End
2016-01-31
Budget Start
2015-02-01
Budget End
2016-01-31
Support Year
4
Fiscal Year
2015
Total Cost
$502,622
Indirect Cost
$151,418
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
Alout, Haoues; Foy, Brian D (2017) Ivermectin: a complimentary weapon against the spread of malaria? Expert Rev Anti Infect Ther 15:231-240
Fauver, Joseph R; Grubaugh, Nathan D; Krajacich, Benjamin J et al. (2016) West African Anopheles gambiae mosquitoes harbor a taxonomically diverse virome including new insect-specific flaviviruses, mononegaviruses, and totiviruses. Virology 498:288-299
Meyers, Jacob I; Gray, Meg; Kuklinski, Wojtek et al. (2015) Characterization of the target of ivermectin, the glutamate-gated chloride channel, from Anopheles gambiae. J Exp Biol 218:1478-86
Meyers, Jacob I; Gray, Meg; Foy, Brian D (2015) Mosquitocidal properties of IgG targeting the glutamate-gated chloride channel in three mosquito disease vectors (Diptera: Culicidae). J Exp Biol 218:1487-95
Chaccour, Carlos J; Rabinovich, N Regina; Slater, Hannah et al. (2015) Establishment of the Ivermectin Research for Malaria Elimination Network: updating the research agenda. Malar J 14:243
Grubaugh, Nathan D; Sharma, Supriya; Krajacich, Benjamin J et al. (2015) Xenosurveillance: a novel mosquito-based approach for examining the human-pathogen landscape. PLoS Negl Trop Dis 9:e0003628
Krajacich, Benjamin J; Slade, Jeremiah R; Mulligan, Robert F et al. (2015) Sampling host-seeking anthropophilic mosquito vectors in west Africa: comparisons of an active human-baited tent-trap against gold standard methods. Am J Trop Med Hyg 92:415-21
Seaman, Jonathan A; Alout, Haoues; Meyers, Jacob I et al. (2015) Age and prior blood feeding of Anopheles gambiae influences their susceptibility and gene expression patterns to ivermectin-containing blood meals. BMC Genomics 16:797
Hoxmeier, J Charles; Thompson, Brice D; Broeckling, Corey D et al. (2015) Analysis of the metabolome of Anopheles gambiae mosquito after exposure to Mycobacterium ulcerans. Sci Rep 5:9242
Kobylinski, Kevin C; Alout, Haoues; Foy, Brian D et al. (2014) Rationale for the coadministration of albendazole and ivermectin to humans for malaria parasite transmission control. Am J Trop Med Hyg 91:655-62

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