Patrick Kelly, MD - US grants

Project summary/abstract Mosquito control remains the primary tool for combating many mosquito-vectored diseases, such as Dengue, Chikungunya, Zika, and West Nile, because no approved vaccine, therapeutant or prophylaxis is currently available for use. Key deficiencies of existing vector control methods include resistance to existing insecticides and the inability to find and treat cryptic breeding sites, which provide refuge to immature mosquitoes and allow for the rapid recovery of mosquito populations following conventional control efforts. The self-delivering method known as `auto-dissemination' addresses this deficiency by using mosquitoes as the vehicle to deliver a potent mosquito growth regulator to cryptic breeding sites. The Phase 1 results have included pilot laboratory and field work, as a proof-of-principle against both Aedes aegypti and Aedes albopictus. The epidemiology of Zika has led to an urgent need for preemptive vector control approaches. Specifically, a majority of Zika virus infections in humans are not detected quickly. Delayed detection can undermine a public health protection plan that is based on reactive approaches, i.e., a strategy of initiating intensive vector control only after the detection of an epidemic, because by the time of detection, a large proportion of the human population can be infected already. The approach being developed in the proposed work is ideal as a preemptive approach, because (1) it requires small amounts of chemical, i.e., less environmental impact and (2) the artificially-reared mosquito carriers can be delivered at any time, e.g., before an indigenous vector population reaches dangerous levels. The ?Auto-Dissemination Augmented by Males? (ADAM) is based on mass-producing male mosquitoes, which do not bite or transmit pathogens. The ADAM method can utilize wild type mosquitoes, Wolbachia- infected mosquitoes or Genetically Modified mosquitoes. Integration with existing mosquito mass rearing programs can speed the uptake of the ADAM technology. Adult ADAM males are treated with an Insect Growth Regulator (IGR) and then released to deliver lethal doses of the IGR to oviposition sites. Phase I work included: 1) laboratory development, 2) regulatory work, e.g., approval of a Research Authorization from the California Department of Pesticide Regulation, 3) field trials in KY against Ae. albopictus, and 4) field trials in collaboration with the Consolidated Mosquito Abatement District (CMAD) to test the ADAM approach against Ae. aegypti. The laboratory results show that Ae. albopictus, Ae. aegypti, and Culex pipiens males can: 1) tolerate the IGR with negligible cost to the male carriers, 2) directly deliver larvicide to breeding sites, and 3) cross-contaminate females with IGR doses that are subsequently lethal to larvae. Field trials with both Ae. aegypti and Ae. albopictus show the ADAM method to cause significant larval mortality and significant reductions in the adult population, when compared to the non-treated sites. Phase 1 work also included an improvement of methods for the mass manufacturing of adult male mosquitoes. In the proposed Phase II work, we will conduct work to replicate and expand field trials against Ae. aegypti and Ae. albopictus, from proof-of-principle trials to a scale that is adequate for operational use by mosquito abatement districts. By performing field trials with multiple abatement districts from different states, our proposed Phase II work will satisfy an EPA requirement for commercial registration, i.e., that efficacy and safety be demonstrated in multiple ecological contexts. In addition to the EPA, the data will be submitted to the World Health Organization (WHO) Vector Control Advisory Group (VCAG), which serves as an advisory body on new forms of vector control. WHO approval is anticipated to increase international uptake of the ADAM technology. Additional Phase II work will extend Phase I work with Cx. pipiens, an important vector of West Nile Virus. Specifically, one or more field trials will provide efficacy data for use against this additional, important mosquito species, which is another focus of abatement districts' vector control efforts.  

Project Summary/ Abstract African tick-bite fever caused by Rickettsia africae is probably the most common human spotted fever group rickettsiosis. It occurs throughout Africa, wherever its major vector, Amblyomma variegatum, is found. Other Amblyomma species can also transmit R. africae and the organism has spread in Amblyomma loculosum on migratory birds through the Indian and Pacific Ocean islands. Rickettsia africae also occurs in Central America in A. ovale, and in the Caribbean islands in A. variegatum which were imported on cattle from Africa in the 1800s. Infected ticks were spread widely around the Caribbean islands on cattle egrets, which are migratory birds that move readily between the islands and as far as the Florida Keys. The presence of R. africae in the nearby Caribbean islands and Central America, and Africa, the expanding tourism and trade between these areas and the USA, the travelers entering the USA from Africa, the Caribbean, and Central America that are infected with R. africae, and the presence of migratory birds raises the risks of A. variegatum and/or R. africae being introduced into the USA and becoming established. If Amblyomma species endemic in the USA could then become infected with and maintain and transmit R. africae, African tick-bite fever could become established in the USA causing widespread morbidity as it does in Africa. Additionally, this would further complicate the already difficult diagnosis of American spotted fever group Rickettsia infections, in particular Rocky Mountain spotted fever. The effects of R. africae on American wildlife are unknown. To establish the reservoir and vector capacity of the most relevant US Amblyomma species, A. americanum and A. maculatum, we intend to conduct transmission experiments with guinea pigs and calves as hosts. Amblyomma variegatum larvae/ nymphs and adults infected with R. africae will be fed on guinea pigs or calves, respectively, at the same time as uninfected immature and adult US Amblyomma species to determine if infections can be transferred horizontally. If infections can be demonstrated in the US Amblyomma species, further experiments will be performed to establish if R. africae can be transmitted vertically between feeding stages (transtadially), transovarially through the eggs, and from each feeding stage to the host. Data generated from these experiments will enable American health workers to more precisely determine the risk of African tick-bite fever becoming established in the USA and for appropriate prevention and response strategies to be developed.

The merger of a pair of black holes or neutron stars creates gravitational waves. Mergers that lead to explosions also emit light, which conveys information about the heavy elements that are created. Since 2015, astronomers have recorded the gravitational waves from fifty mergers. However, visible light from only a single merger has been clearly pinpointed. This project will develop telescopes in New Mexico and Greece that can image a large region of the sky within just two seconds of an alert. By searching more quickly than existing facilities can do, the telescopes will identify new, brightening sources on the sky and obtain early data. The project will also monitor nearby galaxies for very young supernovae. Undergraduates from Minnesota and New Mexico as well as citizen scientists will participate. The inclusion of underrepresented minorities, notably Native Americans and Hispanics, is planned in various aspects of the work that will provide broad training suitable for future academic or private industry careers.

At each site, the Total-Coverage Ultra-Fast Response to Binary Mergers Observatory (TURBO) will consist of large-format CMOS detectors mounted on sixteen 0.20-meter diameter optical telescopes. Within two seconds of a trigger alert, TURBO will begin obtaining continuous, multi-band images of up to 240 square degrees. A prototype telescope in St. Paul, Minnesota has been implemented that can acquire images within two seconds of an alert. Counterparts to gravitational-wave detections of mergers will multiply the information available from just the gravitational waves alone by revealing the mergers’ distances, environments, and nucleosynthetic products. Given its unique sensitivity to prompt emission, TURBO may detect novel types of counterparts, yielding potential insights, for example, into the poorly understood observed population of binary black-hole mergers. Observations of supernovae in nearby galaxies at the time of explosion (4-6 events each year) can be expected to provide new understanding of their stellar progenitor populations and explosion mechanisms. The opportunity to included numerous undergraduate students in research projects and the use of Zooinverse in analysis of the data is planned.


This project advances the goals of the Windows on the Universe Big Idea.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.