T. cruzi has been divided into two main lineages: T. cruzi I (TcI) and T. cruzi II (TcII). TcI is predominant in Mexico and Central America, while TcII is predominant in most of South America, including Argentina. In recent studies from Argentina, the risk of congenital transmission has been estimated to vary between 2.6 percent and 7.9 percent. By contrast, we know very little about the congenital transmission of TcI. It has been suggested that congenital transmission of T. cruzi is strain related, and there is an urgent need to know if TcI transmits differently than TcII. Our primary hypothesis is that congenital transmission rates are different for TcI versus TcII. Our secondary hypothesis is that the characteristics of T. cruzi infected mothers (e.g., age, parity, transmission in previous pregnancies) and their exposure to vectors are different in regions where TcI is predominant versus regions where TcII is predominant. To test these hypotheses, we propose to conduct a prospective study to enroll at delivery 10,000 women in Mexico, 5,000 women in Honduras, and 5,000 women in Argentina. We will measure transmitted maternal T. cruzi antibodies in cord blood, and, if the results are positive, we will identify infants who are congenitally infected by performing parasitological examinations on cord blood and at 4-8 weeks, and serological follow-up at 10 months. We will also perform standard PCR, real-time quantitative PCR, and T. cruzi genotyping on maternal blood, standard PCR and T. cruzi genotyping on the cord blood of congenitally infected newborns, and serological examinations on siblings. We will estimate the exposure to vectors in the household. In addition, we will measure prenatal outcomes among infected and uninfected infants with seropositive mothers, and the birth weight of their siblings.
The specific aims of this study are: 1) To determine the rate of congenital transmission of TcI compared to TcII;2) To compare the T. cruzi infected mothers'characteristics and exposure to vectors in regions where TcI is predominant and regions where TcII is predominant;and 3) To describe the birth outcomes of infected and uninfected infants born to TcI and TcII seropositive women.
A better understanding of the epidemiology of TcI congenital infection is a crucial step toward the potential development of screening and early treatment programs in Mexico and Central America, as well as in the United States, where large immigrant populations come from countries where TcI predominates. Thus, the proposed research project is highly relevant to public health.
|Howard, E J; Xiong, X; Carlier, Y et al. (2014) Frequency of the congenital transmission of Trypanosoma cruzi: a systematic review and meta-analysis. BJOG 121:22-33|
|Buekens, Pierre; Cafferata, Maria-Luisa; Alger, Jackeline et al. (2013) Congenital transmission of Trypanosoma cruzi in Argentina, Honduras, and Mexico: study protocol. Reprod Health 10:55|