| AVS 54th International Symposium | |
| Biomaterials Plenary | Sunday Sessions |
| Session BP-SuA |
| Session: | Biomaterials Plenary Session - Global Health Technologies |
| Presenter: | R.V. Durvasula, University of New Mexico School of Medicine |
| Authors: | R.V. Durvasula, University of New Mexico School of Medicine I. Hurwitz, University of New Mexico School of Medicine S. Matthews, University of New Mexico School of Medicine |
| Correspondent: | Click to Email |
The last decade saw vector-borne disease emerge as an urgent global health concern. Malaria, leishmaniasis, dengue fever, African trypanosomiasis, and Chagas disease place over sixty percent of the world’s population at risk with nearly 740 million new cases. The mainstay of vector-borne disease control has been pesticide-based vector eradication. Pesticides were responsible for dramatic reductions of malaria in India during the 1950’s and 60’s. More recently, the Southern Cone Initiative against Chagas disease achieved spectacular reductions in South America. Unfortunately, such reductions may be temporary. Progress can be retarded by twinned factors: vector resistance and cost. In addition, pesticides pose a significant hazard to human health and the environment. These limitations have inspired new strategies for prevention and control, such as genetic modification of insect vectors to reduce their competence to transmit a target pathogen. This goal has been pursued via two approaches: modification of the vector genome and paratransgenesis, which involves genetic manipulation of symbiotic bacteria resident in vectors. Although proof of concept for both of these approaches has been achieved in laboratory studies, field application remains a possibility with many attendant risks. Paratransgenesis has been proposed as a strategy for the control of Chagas disease, a parasitic illness endemic to Central and South America. The WHO estimates that 8 - 11 million people are currently infected and 25 million are at risk for the disease. Chagas disease can be chronic and debilitating, with infected persons suffering cardiac, gastrointestinal, and neurological damage. Because neither vaccine nor treatment exists for the chronic stage of the disease, controlling transmission has been a priority. Chagas disease is transmitted to humans by obligate blood-feeding insects, the triatomines (order Hemiptera, family Reduviidae). The causative agent of the disease, the parasite Trypanosoma cruzi, lives in the gut of the triatomine and is transmitted via a fecal droplet deposited by the bug after a blood meal. In the paratransgenic strategy, the symbiotic bacterium, Rhodococcus rhodnii, which lives in the Chagas disease vector, Rhodnius prolixus, has been transformed with a series of expression plasmids to export molecules that are toxic to the parasite, T. cruzi. Laboratory lines of R. prolixus carrying cecropin A-producing symbionts have been reared which are refractory to T. cruzi infection. Field use of this approach will rely on natural coprophagic spread of symbionts by R. prolixus. A fake fecal preparation termed CRUZIGARD has been made and impregnated with engineered symbionts. Under closed cage and greenhouse conditions, CRUZIGARD- mediated delivery of transgenic bacteria to target populations of R. prolixus has been demonstrated. A paratransgenic approach to another important vector-borne disease, visceral leishmaniasis, is also under development. Soil-borne bacteria isolated from the sandfly vector, P. argentipes, in Bihar, India have been transformed to export molecules to larval and adult stages of sandflies with the aim of disrupting the cycle of Leishmania donovani. The paratransgenic approach has the potential to reduce pathogen transmission. Because it involves release of engineered microbes, aspects of field release impacting the environment merit investigation. An analysis of risks versus benefits of these strategies and the role for other delivery strategies of foreign genetic material will be presented.