7. Project Summary/Abstract Chagas disease, or American trypanosomiasis, is caused by the parasite Trypanosoma cruzi. It is a major cause of cardiac disease in the Americas. An estimated six million persons are currently infected, including one million women of reproductive age. Mothers can transmit T. cruzi to their babies during pregnancy, and infected babies are at risk of developing chronic Chagas disease later in life. Retrospective observational studies suggest that women treated at a young age do not transmit T. cruzi when pregnant later in life. The level of parasitic load is a known risk factor for congenital transmission. Benznidazole (BZN) is the drug of choice for preconceptional treatment to reduce parasitic load. The fear of treatment-related side effects limits the implementation of the standard 60-day treatment with BZN 300 mg/day of T. cruzi seropositive women during the postpartum period to prevent transmission in a future pregnancy. A short and low dose BZN treatment might reduce major side effects and increase compliance, but its efficacy to reduce T. cruzi parasitic load compared to the standard 60-day course is not yet established. We are proposing to perform a double-blinded, non-inferiority randomized controlled trial comparing a short 30- day treatment with BZN 150mg/day (30d/150mg) vs. a 60-day treatment with BZN 300 mg/day (60d/300mg). We will recruit not previously treated T. cruzi seropositive women with a live birth during the postpartum period in Argentina, randomize them at six months postpartum, and follow them up with the following specific aims: Specific Aim 1: To measure the effect of BZN 30d/150mg compared to 60d/300mg preconceptional treatment on parasitic load measured by the frequency of positive PCR (primary outcome) and by real-time quantitative PCR (qPCR), immediately (Specific Aim 1a) and 10 months (Specific Aim 1b) after treatment. Hypothesis 1a: The frequency of positive PCR and the parasitic load measured by qPCR immediately after BZN 30d/150mg will be non-inferior (Non Inferiority [NI] margin for PCR: 10% absolute difference) to BZN 60d/300mg. Hypothesis 1b: The frequency of positive PCR and the parasitic load measured by qPCR 10 months after BZN 30d/150mg will be non-inferior (NI margin for PCR: 9% absolute difference) to BZN 60d/300mg. Specific Aim 2: To measure the frequency of serious adverse events leading to treatment interruption of BZN 30d/150mg compared to 60d/300mg. Hypothesis 2: The frequency of serious adverse events leading to treatment interruption will be 50% lower with BZN 30d/150mg than with BZN 60d/300mg. A 24-month recruitment period is planned in four hospitals with 23,436 deliveries in 2015 and frequencies of T. cruzi seropositive women varying from 1.5% to 4.8%. We are planning to enroll 600 T. cruzi seropositive women.