Browsing by Author "Foy, Brian, advisor"

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Open Access
Assessment of anopheles vectorial capacity metrics and malaria transmission factors within the Rimdamal II Study
(Colorado State University. Libraries, 2021) Gray, Lyndsey Irene, author; Foy, Brian, advisor; Kading, Rebekah, committee member; Mueller, Rachel, committee member; Stenglein, Mark, committee member
To view the abstract, please see the full text of the document.
Open Access
Assessment of mosquito and animal model factors in Aedes-borne arbovirus transmission and disease
(Colorado State University. Libraries, 2021) Miller, Megan Rae, author; Foy, Brian, advisor; Wilusz, Jeffrey, committee member; Kading, Rebekah, committee member; Montgomery, Tai, committee member; Magunda, Forgivemore, committee member
To view the abstract, please see the full text of the document.
Open Access
Characterizing the target of ivermectin, the glutamate-gated chloride channel, and other insecticide targets as candidate antigens for an anti-mosquito vaccine
(Colorado State University. Libraries, 2015) Meyers, Jacob, author; Partin, Kathryn, advisor; Foy, Brian, advisor; Vigh, Jozsef, committee member; Tsunoda, Susan, committee member
The latest WHO World Malaria Report estimates that, in 2013, there were 198 million cases worldwide causing 584,000 malaria-related deaths. Current malaria control programs primarily target malaria vectors through the use of long lasting insecticide treated bed nets and indoor residual spraying of pyrethroid-based insecticides. However, pyrethroid resistance is becoming widespread in many An. gambiae populations across Africa (Ranson et al., 2011; Trape et al., 2011). Out of recent efforts to find new vector-targeting interventions with novel modes of action, the endectocide ivermectin (IVM) has arisen as a new candidate to control malaria transmission. IVM, when imbibed by vectors from host-treated blood meals, has proven to efficiently kill or disable An. gambiae s.s. both in the lab and the field (Kobylinski et al., 2010; Sylla et al., 2010). More recently, IVM mass drug administrations in multiple locations across west Africa have been shown to temporarily reduce the proportion of P. falciparum-infected An. gambiae in IVM-treated villages (Kobylinski et al., 2011; Alout et al., 2014). The primary target of IVM is the invertebrate glutamate-gated chloride channel (GluCl) (Cully et al., 1994; Cully et al., 1996; Janssen et al., 2007; McCavera et al., 2009; Janssen et al., 2010; Moreno et al., 2010). The purpose of the first chapter of this thesis was to characterize GluCl from An. gambiae in order to understand the physiological role of GluCl and how IVM may be affecting mosquito physiology. Cloning of the An. gambiae GluCl (AgGluCl) revealed unique splicing sites and products not previously predicted. We expressed AgGluCl clones in Xenopus laevis oocytes to measure its electrophysiological activity in response to glutamate and IVM. We also examined AgGluCl isoform-specific transcript levels across different tissues, ages, blood feeding status and gender and GluCl tissue expression in adult An. gambiae. Given that GluCl can be targeted by drugs found in a blood meal and that GluCl is not expressed in mammals, we wanted to test the efficacy of AgGluCl as a candidate mosquitocidal vaccine antigen. We administered a polyclonal anti-AgGluCl immunoglobulin G (anti-AgGluCl IgG) to An. gambiae mosquitoes through a blood meal or directly into the hemocoel by intrathoracic injections and found it significantly reduced An. gambiae survivorship. By co-administering anti-AgGluCl IgG with a known GluCl agonist, IVM, we discovered anti-AgGluCl IgG reverses the mosquitocidal effects of IVM. Our results describing the mosquitocidal properties of anti-AgGluCl IgG suggest that other neuronal proteins could be used as candidate antigens for a mosquitocidal vaccine. The An. gambiae GABA-gated chloride channel (resistance to dieldrin; AgRDL) is another member of the cys-loop ligand-gated ion channels with a similar structure and physiological function to AgGluCl. The An. gambiae voltage-gated sodium channel (AgVGSC) is the target of dichlorodiphenyltrichloroethane (DDT) and the pyrethroid class of insecticides (Soderlund and Bloomquist, 1989). VGSCs are also the target of multiple classes of spider, scorpion and snail toxins, demonstrating that peptides binding to VGSC extracellular residues can affect channel function (Nicholson, 2007; King et al., 2008; Stevens et al., 2011; Klint et al., 2012). Preliminary results shows that IgG targeting AgRDL or AgVGSC similarly reduce An. gambiae survivorship. Finally we tested anti-AgGluCl IgG against A. aegypti and C. tarsalis to see if this strategy has broad potential across both Anopheline and Culicine mosquitoes. However, blood meals containing anti-AgGluCl IgG had no effect on A. aegypti or C. tarsalis survivorship. We determined that this was due to a barrier in antibody translocation from the blood meal to the hemolymph. Since the IgG target, AgGluCl, is only expressed in the hemocoel, antibody translocation was required for mosquito toxicity.
Open Access
Ivermectin-treated bird feed to control West Nile virus transmission
(Colorado State University. Libraries, 2018) Nguyen, Chilinh, author; Foy, Brian, advisor; Ebel, Greg, committee member; Bowen, Richard, committee member; Huyvaert, Kathryn P., committee member
West Nile virus is the leading cause of arboviral fever and encephalitis in the United States. The highest WNV disease incidence occurs along the Great Plains region of the United States, as the ecology and land use provide a supportive habitat for the main WNV enzootic and bridge vector of the region, Culex tarsalis. However, due to the lack of dense human population, this area often does not benefit current WNV control measures as applied by conventional mosquito control districts. Based on the ecology of WNV transmission in the Great Plains region, a strategy that targets Cx. tarsalis through its ornithophilic blood feeding behavior could disrupt WNV transmission. Given that the majority of Cx. tarsalis blood meals on the northern Colorado plains may come from doves and passerine species during the WNV transmission season, effective targeting of these or other local preferred hosts with endectocide-treated bird feed could result control of WNV transmission. This study develops and characterizes the effects of IVM-treated bird feed in birds and biting Cx. tarsalis mosquitoes in both a laboratory and field setting. In Chapter 2, the effects of IVM on Cx. tarsalis survival were examined using both in vitro membrane blood meals and direct blood feeding on IVM-treated birds. Chickens and wild Eurasian Collared Doves fed solely on IVM-treated bird feed concentrations up to 200 mg IVM/kg feed exhibited no signs of toxicity, and most Cx. tarsalis that blood fed on these birds died compared to controls. Mosquito survivorship following blood feeding correlated with IVM serum concentrations at the time of blood feeding, which dropped rapidly after the withdrawal of treated feed. These results suggested IVM-treated bird feed should be further explored as a hyper-localized control strategy for WNV transmission. Chapter 3 presents the development of a method to detect and quantify IVM in individual blood meals of Anopheles gambiae and Cx. tarsalis, which will be important in measuring the coverage of this intervention in the field, and accurately assessing IVM's mosquitocidal effects in field situations. This ability to detect IVM in mosquito blood meals was similar between blood fed Cx. tarsalis and An. gambiae, and between sampling times of 0 or 12 hours post blood feed. The quantity of IVM ingested in individual mosquitoes was also compared to the venous serum concentrations of live animals. Chapter 4 presents promising results from two separate pilot field trials of IVM-treated bird feed that were conducted during the summers of 2016 and 2017. Results from 2016 showed that wild birds frequently visit the IVM-treated feeders. In addition, there was an observable trend where "far" traps that are expected to be beyond the zone of control had more WNV-positive pools compared to "near" traps at both ELC and ARDEC South sites. Results from the 2017 study continued to be promising, where birds were again visiting IVM-treated feeders and IVM could be detected in the sera of birds sampled by IVM feeders. There was also a trend of higher VI for the control sites compared to IVM sites for the 2017 season. The efficacy of IVM-treated bird feed was evaluated in two pilot trials where natural WNV transmission cycles occurred in wild birds and Cx. tarsalis, but should be followed up with field seasons with many control and IVM sites to allow for a robust analysis of IVM effects. This study introduces the novel concept of using systemic endectocides for controlling WNV transmission, and this concept could be explored for other arboviruses.
Open Access
Laboratory mouse models for bartonella bacterial infection: bacteremia, host specificity, and pathology
(Colorado State University. Libraries, 2011) Colton, Leah, author; Foy, Brian, advisor; Michael, Kosoy, advisor; Gage, Kenneth L., committee member; Bowen, Richard, committee member
Bartonella bacterial species are globally distributed in a diverse variety of mammalian reservoir hosts. Natural host infections are generally characterized by persistent bacteremias of long duration, seemingly without adverse host effect, whereas non-natural host infections can produce mild, self-limiting illnesses or more severe disease such as endocarditis. Incidental host infections seem to most closely resemble natural host infections when the taxonomic distance between the two hosts is small. The greater the taxonomic distance between the host of origin and the incidental host, the more likely it seems that the incidental host will either clear the bacteria or develop pathology following exposure. This level of bacterial host specificity has been demonstrated consistently and presents an enormous obstacle to the development of animal models, particularly murine models that reproduce characteristics of natural host infection or pathology consistent with human incidental infections. In this dissertation laboratory mouse models for bartonella infection are described following the introduction and literature review (Chapter 1). Chapter 2 reports infection of mice with bartonella strains from wild Mus species, simulating a cross-species host switch for the bacteria. Infected mice exhibited characteristics consistent with reports of natural rodent host infection. Chapter 3 reports on a mouse infection study using four rat bartonella strains, simulating a cross-genus host switch for the bacteria. Only one of the strains infected mice and alterations in bacteremia duration and magnitude were observed relative to those reported for natural host infections. Mice also displayed organ pathology following bacteremia resolution. Chapter 4 presents a mouse infection study using an Asian house shrew Bartonella elizabethae strain inoculated into three different laboratory mouse stocks. Mice of all three stocks developed bacteremia following bacterial exposures, a demonstration of cross-order host switching by the bacteria. No obvious differences in infection response were observed among the mice despite differences in their genetic backgrounds. Chapter 5 describes inoculation of aged mice with either a mouse bartonella strain or human Bartonella tamiae strains. Mice infected with the mouse strain developed bacteremia, whereas mice infected with B. tamiae did not, consistent with the idea that taxonomic distance between host of origin and incidental host can be a predictor of infection outcome. Chapter 6 details results of a study where aged mice were exposed to three different B. tamiae strains. The mice developed disease consistent with reports of human illness symptomatology. In summary (Chapter 7), these laboratory mouse models are presented as defined, scientific resources for research on Bartonella species host ecology, bacteria: host interactions, and transmission dynamics.
Open Access
Tools and techniques for the study and evaluation of malaria control measures in West Africa
(Colorado State University. Libraries, 2016) Krajacich, Benjamin, author; Foy, Brian, advisor; Ebel, Gregory, committee member; Eisen, Lars, committee member; Huyvaert, Kate, committee member; Schountz, Tony, committee member
To view the abstract, please see the full text of the document.