Trypanosoma cruzi, the causative agent of Chagas disease, exhibits a high genetic variability and has been classified into six discrete typing units (DTUs) named TcI through TcVI. This genetic diversity is believed to be associated with clinical characteristics and outcomes, but evidence supporting such associations has been limited. Herein, we performed a phylogenetic analysis of T. cruzi sequences of the mini-exon intergenic region obtained from a large cohort of pregnant women and newborns from Argentina, Honduras, and Mexico, to assess parasite genetic diversity and possible associations with congenital transmission. Analysis of 105 samples (including five paired samples) from maternal and umbilical cord blood indicated that T. cruzi DTU distribution was similar among pregnant women and newborns from these three countries, with a high frequency of TcII-TcV-TcVI DTUs, including mixed infections with TcI. However, phylogenetic analysis revealed that although the same parasite haplotypes circulated in these three countries, they were present at different frequencies, leading to significant geographic differences. Of importance, a strong association was observed between parasite haplotypes and congenital infection of newborns. Thus, the identification of parasite haplotypes in pregnant women, but not of parasite DTUs, may help predict congenital transmission of T. cruzi.

BackgroundAlthough there is increasing evidence for a relationship between symptomatic Zika virus (ZIKV) maternal infection, and microcephaly, a firm causal relation has yet to be established by epidemiologic studies. Studies also need to be conducted in recently infected settings. Our objectives are to assess the frequency of ZIKV infection during pregnancy in Honduras and the association of microcephaly with ZIKV infection.Methods/DesignWe will perform a prospective study enrolling pregnant women at their first antenatal visit and following them up until delivery. At the time of enrollment, women will be interviewed to collect socio-demographic data, data needed to locate them for potential additional follow-up, and data about ZIKV symptoms during pregnancy. We will also collect maternal blood as soon as possible after enrollment. A probable maternal ZIKV infection will be defined as positive for maternal ZIKV IgM. A confirmed maternal ZIKV infection will be defined as positive for ZIKV IgM confirmed by plaque reduction neutralization test. Microcephaly at birth will be defined as an occipito-frontal circumference <2SD for sex and gestational age. Our objective is to enroll 2000 pregnant women. In a first step, we will follow a case cohort design and only analyze blood samples for cases and a sub-cohort of 200 women randomly selected. Blood samples for the entire population will be analyzed at a later stage if funds are available.DiscussionThis protocol was designed to be implemented with minimal resources. It allows a cohort to be built, which could be a foundation for future in-depth and follow-up studies.

BackgroundTrypanosoma cruzi has been divided into Discrete Typing Units I and non-I (II-VI). T. cruzi I is predominant in Mexico and Central America, while non-I is predominant in most of South America, including Argentina. Little is known about congenital transmission of T. cruzi I. The specific aim of this study is to determine the rate of congenital transmission of T. cruzi I compared to non-I.Methods/designWe are conducting a prospective study to enroll at delivery, 10,000 women in Argentina, 7,500 women in Honduras, and 13,000 women in Mexico. We are measuring transmitted maternal T. cruzi antibodies by performing two rapid tests in cord blood (Stat-Pak, Chembio, Medford, New York, and Trypanosoma Detect, InBios, Seattle, Washington). If at least one of the results is positive, we are identifying infants who are congenitally infected by performing parasitological examinations on cord blood and at 4–8 weeks, and serological follow-up at 10 months. Serological confirmation by ELISA (Wiener, Rosario, Argentina) is performed in cord and maternal blood, and at 10 months. We also are performing T. cruzi standard PCR, real-time quantitative PCR and genotyping on maternal venous blood and on cord blood, and serological examinations on siblings. Data are managed by a Data Center in Montevideo, Uruguay. Data are entered online at the sites in an OpenClinica data management system, and digital pictures of data forms are sent to the Data Center for quality control. Weekly reports allow for rapid feedback to the sites.Trial registrationObservational study with ClinicalTrials.gov Identifier NCT01787968

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