Pugh, Gregory Scott, authorFoy, Brian D., advisorKading, Rebekah, committee memberHemming-Schroeder, Elizabeth, committee memberNachappa, Punya, committee member2025-09-012025-09-012025https://hdl.handle.net/10217/241894https://doi.org/10.25675/3.02214Approximately 80% of the world's population is at risk of at least one vector-borne disease. Most of these diseases are preventable through protective measures such as insecticide treated bed nets or indoor residual spraying of insecticides along the walls of a domicile. However, these measures can be cost prohibitive and due to these costs, disproportionate infection rates are found within the communities which have lower incomes. Additionally, invasive species are overtaking ecological niches where endemic vectors once thrived. Because of this, novel diseases are being introduced into naïve human populations, which could have deleterious results. While disease prevention methods, such as vaccinations, are becoming more common, these methods often leave out the populations which need them the most, due to vaccinations typically require a solid cold-chain infrastructure. Furthermore, these prevention methods do not exist for some of these diseases, therefore controlling the mosquito populations with insecticides are the "gold standard" for preventing disease outbreak. However, mosquito vectors are exhibiting resistance, both biological and behavioral, to commonly used insecticide classes, resulting in cross-resistance to new products, before they come to market. Novel approaches to mosquito control are necessary to circumvent the rising insecticide resistance issues, such as the development of new control methods and identifying mosquito population dynamics. Endectocides, such as ivermectin and isoxazolines, could be of assistance in regions where resistant mosquitoes are feeding on human and livestock hosts when insecticides are commonly used. Ivermectin is a gluatamate-gate chloride channel agonist causing death by flaccid paralysis in arthropods which feed on treated individuals and is extremely efficacious on anopheline mosquitoes. Additionally, ivermectin is known to cause a reduction in fecundity and refeeding frequency of mosquitoes which imbibe a sublethal dose. This class of drug has been used for the last 30 years as an antihelminth drug in rural Africa and is accepted as a beneficial drug for community health. While ivermectin has a short half-life in human plasma, new models suggest that a change in dosing regimen may retain the mosquitocidal effects up to 28 days post-intervention. Prior studies have conducted clinical trials using this dosing regimen, observing the effects on the mosquito populations. However, these studies have paired ivermectin with malaria treatment methods, which could alter the mosquitocidal effects of ivermectin. The Repeat Ivermectin Mass Drug Administration for the control of MALaria II (RIMDAMAL II) clinical trial sought to control this by only administering ivermectin once a month to select villages in mass drug administration campaigns in Burkina Faso. In addition to observing the mosquitocidal effects of ivermectin on wild mosquitoes, plasma was obtained from participants to elucidate the pharmacokinetics and pharmacodynamics of human processed ivermectin. The goal of this clinical trial was to reduce the malaria burden within children, by controlling the older, possibly infectious mosquitoes. The extrinsic incubation period (EIP), or the time it takes a mosquito to become infectious after consuming an infected blood meal, is dependent on both the mosquito species, the pathogen, and external factures such as climate. Understanding the EIP is essential to determine if a mosquito population has higher risk of transmitting a pathogen to the human population, the older a mosquito population is, the greater the risk. For instance, the EIP for Plasmodium development for mosquitoes in the Anopheles gambiae complex is between 9 and 16 days before the parasite can disseminate throughout the mosquitoes, eventually arriving to the salivary glands, making her infectious when she imbibes her next bloodmeal. While the EIP of West Nile virus in Culex tarsalis is between 8 and 18 days, there are some instances where the virus can escape the midgut and reach the salivary glands within a few days, causing mosquitoes to become infectious before the established EIP. This makes time crucial when assessing the age of the mosquito population. However, the current methods to age mosquito populations are slow, expensive, and require a high degree of technical knowledge. Additionally, the current "gold standard" of mosquito age-grading is qualitative, observing the populations parity rate, which requires an exorbitant amount of time, especially when mosquito control experts are in the conducting control operations. Furthermore, these parity methods are difficult to conduct on certain species of mosquitoes due to their ability to be autogenous, or lay eggs without the need for a prior blood meal, causing an inappropriate classification of population age. Thus, a new age-grading method is needed for mosquito control experts and researchers to identify mosquito populations which contain the greatest risk for pathogen transmission. However, a novel technique is being researched. As a mosquito ages, she loses her wing scales, eventually becoming threadbare. Qualitative methods in the past placed mosquitoes into prescribed bins based on the look of their wings. We have previously identified a novel, high-throughput, and quantitative method to age mosquito populations using machine vison algorithms to determine the pixel intensity of wing photos. This dissertation has investigated the pharmacodynamics of human processed ivermectin on Anopheles gambiae mosquitoes and observing a possible feeding aversion to participants which contain a high venous concentration of ivermectin. Furthermore, we have further refined our pixel intensity method and developed a known age model of An. gambiae G3 strain. We then applied the known age model to the pixel intensities of wing photos collected from wild An. gambiae sensu lato (s.l.) mosquitoes captured during the RIMDAMAL II clinical trial, interpolating their ages. Additionally, using this novel method, we observed a significant decrease in pixel intensities once new dual-chemistry bed nets were issued halfway through our clinical trial, suggesting the pixel intensity method was sensitive enough to examine mosquito control interventions. We have also applied the pixel intensity method to wild Cx. tarsalis around the Greater Salt Lake and Northern Colorado during mosquito control interventions to elucidate if the observations in An. gambiae pixel intensity could be seen Cx. tarsalis. These age-grading techniques lay the foundation for an inexpensive and high throughput measurement for public health, mosquito control experts, and researchers to identify if a mosquito vector population has the capacity to transmit pathogens to the community.born digitaldoctoral dissertationsengCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.AnophelesCulicidaevector controlCulexage gradingmosquitoText