CHAGAS DISEASE RESEARCH

Chagas disease is a chronic parasitic infection caused by the protozoan Trypanosoma cruzi. As a WHO-recognized Neglected Tropical Disease, if receives disproportionately little attention and funding despite that fact that it infects upwards of 6 million people and causes more mortality and morbidity than any other parasitic infection in the Americas. Chagas disease is both vector-borne and zoonotic, and T. cruzi is very genetically diverse, presenting unique challenges to understand its epidemiology and pathogenesis and to develop effective control programs.

HIV Coinfection

We are currently collecting data on a cohort of HIV-infected patients who present with acute or subacute neurological syndromes at public hospitals in Santa Cruz, Bolivia and Lima and Iquitos, Peru. Prevalence of T. cruzi infection in Santa Cruz is as high as 25-30%, providing us with the opportunity to study the clinical evolution and pathogenesis of reactivation Chagas disease in HIV-infected patients. In reactivation Chagas disease, latent T. cruzi parasites begin to replicate in the bloodstream and tissues in people who are immunocompromised due to HIV, cancer, or immunosuppressive drugs. The clinical manifestations of reactivation can be quite different from the cardiomyopathy characteristic of chronic Chagas disease in immunocompetent hosts. HIV/T. cruzi-coinfected person often develop bizarre neurological lesions or acute myocarditis in the context of high-level parasitemia. This cohort will allow us to better characterize the epidemiology and clinical features of reactivation Chagas disease and develop better diagnostic tools to distinguish it from other opportunistic infections.

We do not know if this unusual syndrome is simply caused by overwhelming parasitemia that can penetrate the blood-brain barrier in the absence of immune control or if it arises from specific neurotropic strains of the parasite. Using next generation sequencing technology, we have amplified parasite DNA from the blood of HIV/T. cruzi-coinfected patients and are examining the role of multiclonality in the pathogenesis of reactivation Chagas disease.

Vector Microbiome

Vector-borne transmission by triatomine insects is still the most important way that Chagas disease is transmitted. We are studying the effect of the bacterial microbiome of the triatomine gut on Chagas disease transmission. The presence or absence of certain bacterial species in the mosquito gut has been shown to be very important for transmission of malaria, dengue, and other pathogens, but little is known about the composition and influence of the triatomine microbiome. In collaboration with Michael Levy and his site in Arequipa Peru, we have developed a method to collect hindgut contents from lab-raised and wild Triatoma infestans. We then amplify using 16S ribosomal primers and characterize the bacterial flora with next generation sequencing. In future projects we hope to evaluate the influence of specific bacterial genera on bugs’ susceptibility to infection and to probe the effects of blood meal, parasite infection, and location on insect microbiome.