Our studies in tsetse and trypanosome biology have strong links with scientists in Africa. Our collaborations with National Livestock Research Institute (NaLIRRI) in Uganda focus on the population genetics of Glossina fuscipes fuscipes, the main vector of both rhodesiense and gambiense diseases. We are working to understand the role of the tsetse genetic components as well as symbiotic fauna in disease transmission (see Yale-NaLIRRI collaboration). We also have a training program in collaboration with Trypanosomiasis Research Center (TRC) in Kenya. In this program, we are working to build capacity in Africa on tsetse genomics, population genetics to understand its vectorial capacity (see Yale-East Africa Training Program).
Evolutionary genetics of tsetse and its symbionts
Human African trypanosomiasis (HAT) kills thousands of people each year in sub-Saharan Africa. The disease is caused by African trypanosomes transmitted by the tsetse fly. HAT transmission is complex; it requires mammalian and invertebrate hosts and involves domestic and wild reservoirs. No mammalian vaccines exist and therapeutic drugs have serious side effects with increasing resistance seen in patients. In contrast, reduction of tsetse populations is highly efficacious for disease control. However, the implementation of the tsetse control programs, which rely on traps and targets, have been difficult to sustain because they are not practical and require extensive community participation. A paratransgenic strategy has been developed which exploits the unique biology of tsetse and its maternally inherited bacterial symbionts. In this strategy, tsetse's mutualist symbiont Sodalis is harnessed to express trypanosome inhibitory molecules in tsetse's midgut to impair trypanosome transmission. Transgenic Sodalis bacterium conferring refractoriness may be driven into natural tsetse populations by cytoplasmic incompatibility phenomenon mediated by tsetse's symbiont, Wolbachia. We propose to investigate the biogeography of the human disease vector species, Glossina fuscipes fuscipes, its Trypanosoma parasite(s), and its Wolbachia and Sodalis symbionts. Using a combination of laboratory and field experiments, we will investigate the potential for a Wolbachia mediated gene-drive mechanism to aid in the application of paratransgenic flies. In addition, we will elucidate the basic genetic structure of this human disease vector population, for which no information exists. This information is necessary for the efficacious implementation and monitoring of either the traditional or novel control strategies. Knowledge obtained on symbiont biology, maternal linkage of tsetse's multiple symbionts, Wolbachia infection phenotype, potential strength of Wolbachia mediated drive, population genetics and epidemiological dynamics will provide the parameters needed to develop a mathematically based model framework. This model will allow us to test the predictive nature of the empirical data, design the optimal strategies for population control, and predict feasibility and robustness for the success of the replacement strategy. This interdisciplinary application will combine epidemiology, population genetics and modeling with model parameterization and verification from laboratory and field research.
Funding: R01AI068932 NIH/NIAID
Yale-East Africa Training Program
Tsetse transmitted Human African Trypanosomiasis (HAT) has re-emerged and poses a major public health crisis in Sub Sahara. There are no vaccines and efficacious drugs for control of parasite infections in the mammalian host. In contrast, control of the vector insect tsetse populations can effectively break the disease cycle. Extensive resources have been generated in the developed country laboratories with respect to tsetse genomics/genetics that can immediately improve the existing vector control tools, while promising the development of future strategies. The ability of products resulting from high-tech research to reach field implementation stages requires the presence of endemic country scientists who are well-informed in the full potential of the developed technologies, who can evaluate the pros and cons of these solutions, and who can present these perspectives to the general public and to the involved government agencies. In this training program, Yale University scientists will work with the Trypanosomiasis Research Center (TRC) in Kenya to strengthen the biomedical capacity and to acquire and implement the recent advances in applied vector genomics, genetics and bioinformatics to enhance the existing HAT control/management tools. TRC has been identified by a World Health Organization competitive initiative as the lead organization in Africa to coordinate the continent-wide capacity strengthening activities for HAT. A regional network (Eastern African Network of Trypanosomoses, EANETT) consisting of the lead institutions with governmental mandates to work on HAT in Kenya, Uganda, Tanzania, Sudan and Malawi has already made considerable progress in building south-south initiatives. The specific objectives of this application are to: 1) Develop expertise at TRC and their associates to address mechanisms of parasite transmission biology, genetics of vector competence, population biology, and bioinformatics. 2) Strengthen collaborations with the laboratories in the endemic countries in Africa to enable transfer of new technologies and tools relevant for HAT control and promote their integration into the on-going disease control programs. 3) Develop training modules (seminars, workshops and mentored research activities) to increase research capacity for HAT in Africa with a specific focus on vector biology.
Funding support: D43TW007391
GLOBAL INFECTIOUS DISEASE RESEARCH TRAINING PROGRAM AWARD, Fogarty International Center, NIH