Malaria continues to sicken and kill millions of people around the world every year, and is an especially intractable problem in sub-Saharan Africa. Mosquito adulticides are the bedrock of effective malaria control because they are relatively cost-effective, they can be applied to walls or bednets, and they target the most critical variable in malaria transmission models, adult mosquito survivor rates. However, widespread insecticide resistance and continued malaria transmission require the development of novel adulticides and novel ways to apply them. Endectocides are broad spectrum, low toxicity drugs with combined anti-helminthic and anti-ectoparasitic properties and are currently given to human populations for onchocerciasis and lymphatic filariasis control. Current endectocides that act as agonists to glutamate and GABA-gated chloride ion channels in mosquito myoneural junctions, could also be effectively used for malaria control in sub- Saharan Africa and would have certain major advantages over other adulticides due to their molecular targets, how they would be administered to the human population, and the bionomics of African malaria vectors. This research is intended to determine the effective doses of glutamate and GABA-gated chloride ion channel agonist endectocides (macrocyclic lactones, milbemycins, nodulasporamides) for killing adult Anopheles spp. when administered via an artificial bloodmeal. Secondly, mass-ivermectin administration for onchocerciasis control in Southeastern Senegal will be tested for mosquitocidal effects on bloodfeeding adult Anopheles spp. in the field, and that this effect will transiently interrupt malaria transmission in the local community.

Public Health Relevance

This project seeks to develop novel methods to control malaria in sub-Saharan Africa by evaluating current anti-helminth drugs for activity against African malaria vectors and testing their effects in a natural field experiment. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AI079528-01
Application #
7512454
Study Section
Vector Biology Study Section (VB)
Program Officer
Costero, Adriana
Project Start
2008-07-01
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2009-06-30
Support Year
1
Fiscal Year
2008
Total Cost
$147,000
Indirect Cost
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; Krajacich, Benjamin J; Meyers, Jacob I et al. (2014) Evaluation of ivermectin mass drug administration for malaria transmission control across different West African environments. Malar J 13:417
Sylla, Massamba; Kobylinski, Kevin C; Foy, Brian D (2013) Gates Grand Challenges Explorations award: Endectocides for Controlling Transmission of Mosquito-borne Diseases. Malariaworld J 4:
Deus, K M; Saavedra-Rodriguez, K; Butters, M P et al. (2012) The effect of ivermectin in seven strains of Aedes aegypti (Diptera: Culicidae) including a genetically diverse laboratory strain and three permethrin resistant strains. J Med Entomol 49:356-63
Butters, Matthew P; Kobylinski, Kevin C; Deus, Kelsey M et al. (2012) Comparative evaluation of systemic drugs for their effects against Anopheles gambiae. Acta Trop 121:34-43
Kobylinski, Kevin C; Sylla, Massamba; Black 4th, William et al. (2012) Mermithid nematodes found in adult Anopheles from southeastern Senegal. Parasit Vectors 5:131
Kobylinski, Kevin C; Sylla, Massamba; Chapman, Phillip L et al. (2011) Ivermectin mass drug administration to humans disrupts malaria parasite transmission in Senegalese villages. Am J Trop Med Hyg 85:3-5
Foy, Brian D; Kobylinski, Kevin C; Chilson Foy, Joy L et al. (2011) Probable non-vector-borne transmission of Zika virus, Colorado, USA. Emerg Infect Dis 17:880-2
Foy, Brian D; Kobylinski, Kevin C; da Silva, Ines Marques et al. (2011) Endectocides for malaria control. Trends Parasitol 27:423-8
Campbell, C L; Lehmann, C J; Gill, S S et al. (2011) A role for endosomal proteins in alphavirus dissemination in mosquitoes. Insect Mol Biol 20:429-36
Kobylinski, Kevin C; Deus, Kelsey M; Butters, Matthew P et al. (2010) The effect of oral anthelmintics on the survivorship and re-feeding frequency of anthropophilic mosquito disease vectors. Acta Trop 116:119-26

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