Inactive Total Small Business Set-Aside (FAR 19.5)

Vector borne diseases can reduce mission readiness for U.S. service members supporting global contingency operations. The yellow fever mosquito, Aedes aegypti, poses one of the greatest vector borne d... Vector borne diseases can reduce mission readiness for U.S. service members supporting global contingency operations. The yellow fever mosquito, Aedes aegypti, poses one of the greatest vector borne disease threats to U.S. military operations due its widespread geographic distribution combined with its ability to transmit a number of pathogenic viruses, which include the viruses that cause dengue, chikungunya, Zika, and yellow fever. Pyrethroid resistance has been reported in Ae. aegypti from numerous geographic locations, which decreases the efficacy of products currently used to protect service members. Although multiple mechanisms underlie pyrethroid resistance in Ae. aegypti, two single nucleotide polymorphisms (SNPs) that change the sodium channels have shown to be reliable indicators of knock down resistance (kdr) in field populations. A growing number of studies identify the presence of these mutations, which occur at codons 1016 and 1534, as a less expensive and labor-intensive alternative to bottle bioassays. To date, the majority of studies have used descriptive approaches to examine the distribution of kdr alleles in Ae. aegypti. There have only been a few attempts to model the distribution of kdr alleles using regression analysis. For example, the proportion of mosquitoes having homozygous mutant variants at both the 1016 and 1534 sites, was previously modeled using beta regression analysis. One of the limitations of beta regression is that only a single allele combination can be modeled at a given time, while nine different allele combinations are possible with each representing a different level of kdr resistance. One potential solution is to use an ordinal distribution model, which allows data with multiple discrete categories that also follow a natural order to be represented as response variables. In the case of kdr alleles, the relative level of resistance conferred by each allele combination could be represented as a discrete variable, and is known to follow a natural order based on the number of dilocus mutant alleles present, with 0, 1 or 2 copies resulting in pyrethroid resistance of 5-fold, 20-fold or 60-fold, respectively. Therefore, kdr allele combinations could be categorized as low (0 copies), moderate (1 copy) and high (2 copies) pyrethroid resistance. This categorization would also overcome the challenges of analyzing allele combinations that are rarely observed in field collections such as IIFF, IIFC, and VIFF. We propose a proof of concept study to evaluate a new method for analyzing the distribution of kdr alleles. Firstly, we will use ovitraps to conduct systematic sampling of Ae. aegypti in Iquitos, Peru, and the nearby city of Tegucigalpa in Honduras. These sites were chosen due to our knowledge of dengue transmission and insecticide use along with established surveillance networks. Secondly, we will perform adult collections in order to compare kdr frequencies between life stages and collection methods. Thirdly, kdr alleles will be identified using established NAMRU-6 protocols. Finally, the frequency of specific kdr alleles will be modeled using an ordinal distribution model, which can accommodate data with multiple discrete categories. The overall objective of NAMRU-6 Spatially targeted vector surveillance is to conduct surveillance of arthropod vector of pathogens of military importance such as malaria and leishmania parasites across SOUTHCOM to better understand the full transmission cycle and provide robust FVBI risk assessments. Accomplishing this activity requires in-depth surveillance and on-site expertise in endemic sites to ensure accurate and reliable information to generate arthropod vector geographical distribution data and identify vector-borne parasites pathogens. Honduras is a key country in Central America, has a strategic location in the SOUTHCOM, and is an endemic region for tropical infectious diseases such as malaria, leishmaniasis, dengue, zika and re-emerging or emerging pathogens, for which vector species remain to be identified in highly endemic areas. Robust mosquito collections are required to inform such a model. Accomplishing this activity in Honduras requires in-depth surveillance, on-site expertise, and coordination with local Ministry of Health to ensure accurate and reliable information to generate distribution data for kdr frequencies in Aedes aegypti. More specifically, robust collections require the services of a research institution that can collect entomological samples and identify mosquito specimens. Establishing malaria and leishmania vector surveillance capacity for NAMRU-6 in Honduras requires the services of a research institution that can support laboratory experiments for pathogen detection on mosquitoes and sand flies to generate actionable data that can be used for the benefit of the war-fighter.