Chagas disease in Texas: From diagnosis to clinical epidemiology
Chagas disease (Trypanosoma cruzi infection) is one of the most significant neglected tropical diseases affecting the Americas. There are an estimated 8–9 million prevalent cases worldwide with approximately 300,000 infected people in the United States. Chagas disease is often referred to as the ‘silent killer’ because of a prolonged asymptomatic period lasting up to 3 decades. In up to one-third of individuals undetected progressive cardiac damage develops during this latent period that manifest suddenly as cardiac complications, including cardiac arrest. The transmission dynamic of this parasite is a complicated process that involves 130 vector species and over 100 known mammalian reservoirs including domestic, peri-domestic, and wildlife species. Understanding the complex relationship between vector species and mammalian hosts is important for preventing transmission to humans. We performed a historical literature review and meta-analysis to assess the disease burden in the Texas wildlife and domestic animal populations. Reports of sylvatic transmission in Texas date back to the 1940’s. We found that 23 species can serve as reservoirs for T. cruzi including wood rats, raccoons, and canines, which were most frequently reported as reservoirs. These findings have important implications for autochthonous transmission in the United States as it has been documented that the majority of autochthonous cases arise form the interruption of the sylvatic transmission cycle. To better understand how transmission is occurring and what cardiac symptoms manifest in infected individuals in Texas we conducted a study of Chagas positive blood donors in San Antonio, Texas. In 2007 national blood donation screening became mandatory in the United States out of concern for transmission from blood transfusion. Since screening started, 47 seropositive donors were identified in the greater San Antonio area. Our case investigation found 71% (12 out of 17) of enrolled donors had evidence of T. cruzi infection that was locally acquired. High-risk behaviors for disease acquisition in those with autochthonous transmission included rural residence, outdoor occupations, and hobbies. Of most concern, 50% (6 out of 12) had evidence of Chagas cardiac disease based on electrocardiogram analysis. This study identified the largest percentage of autochthonous cases to date in the United States and has important implications for public health officials and clinicians as our understanding of the global epidemiology of this disease changes. Finally, to gain a better understanding of how T. cruzi successfully evades the immune system we characterized the immune evasion properties of Tc24, a B-cell superantigen. Preliminary data suggested that the Tc24 protein that localizes to the T. cruzi membrane during all life stages possesses B-cell superantigenic properties. These antigens facilitate immune escape by interfering with antibody-mediated responses, particularly the avoidance of catalytic antibodies. These antibodies are an innate host defense mechanism present in the naive antibody repertoire, and catalytic antibody-antigen binding results in hydrolysis of the target. We tested the B-cell superantigenic properties of Tc24 by comparing the degree of Tc24 hydrolysis by IgM purified from either Tc24 unexposed or exposed mice and humans. Data presented in this report suggest that the T. cruzi Tc24 is a B-cell superantigen based on the observations that 1) Tc24 was hydrolyzed by IgM present in serum of unexposed mice and humans, and 2) exposure to Tc24 eliminated catalytic activity as early as 4 days after T. cruzi infection.
Gunter, Sarah M, "Chagas disease in Texas: From diagnosis to clinical epidemiology" (2016). Texas Medical Center Dissertations (via ProQuest). AAI10131760.