BEYOND VECTOR CONTROL: CONGENITAL AND IMPORTED CHAGAS DISEASE

Globalization has made Chagas disease an important public health problem in non-endemic areas with high numbers of Latin American immigrants. The U.S. has the highest number of imported cases among all non-endemic countries and is second highest in terms of the economic impact due to Chagas disease-related costs. Congenital transmission represents more than 22% of new cases of Chagas disease worldwide. Although early detection provides an opportunity for effective and safe treatment, diagnostic tests for early detection suffer from low sensitivity. This dissertation aims to: 1) Determine the burden of Trypanosoma cruzi infection and cardiac abnormalities in Latin American individuals living in the Washington Metropolitan area, 2) Evaluate the accuracy of current FDA-approved diagnostic tests of Chagas disease in this immigrant population, and 3) Evaluate a newly developed test “IgM Shed Acute Phase Antigen (SAPA) ELISA” for the early diagnosis of congenital Chagas disease in an endemic population, Santa Cruz, Bolivia. We found a high prevalence of Chagas disease in a community-based study of 1571 Latin American immigrants living in the Washington Metropolitan (WMA) area (4.3%). Having seen the vector in an endemic area was an important risk factor for infection in individuals from different geographic areas. Other factors previously described in endemic areas (having ever lived in a rural area, heard of Chagas disease, or had a family member with the disease) were mainly important among southern South American immigrants. Infected participants from Mexico and Central America where T. cruzi Discrete Typing Unit I (TcI) is prevalent have a higher percentage of cardiac conduction system abnormalities than do participants from southern South America where TcII/TcV/TcVI are prevalent (Chapter 4). In a subset of 1093 samples from Latin American immigrants in the WMA, an evaluation of current FDA-approved tests to diagnose Chagas disease in the U.S. was conducted. Low sensitivity of the recombinant-based ELISA test (Chagatest recombinant v.3.0, Wiener Laboratories, Argentina) was observed, and a large percentage of indeterminate results were obtained using the lysate-based ELISA (Hemagen Chagas EIA, Hemagen, U.S.). Low levels of antibodies to recombinant and lysate antigens was noted in infected participants from TcI areas compared to participants from TcII/TcV/TcVI areas (Chapter 5). In the third study (chapter 6), we found that socioeconomic factors were determinants of low maternal adherence to the 9-month follow-up screening program for detection of congenital infection. The IgM SAPA ELISA test was validated in two prospective cohort studies of infants born from mothers with T. cruzi infection in Santa Cruz, Bolivia. The IgM SAPA ELISA provided similar sensitivity and specificity to the more sophisticated qPCR assay in samples obtained at birth. In conclusion, Chagas disease and associated cardiac abnormalities are important public health problems in Latin American immigrants living in the WMA. Access to more sensitive and robust diagnostic tests is required to provide accurate diagnosis in this highly diverse group of immigrants at-risk of infection. Finally, the IgM SAPA ELISA is a high accurate and simple platform that can be implemented in endemic countries to improve early detection of congenital Chagas disease