With the control of the vectorial and transfusional routes of infection with Trypanosoma cruzi, congenital transmission has become an important source of new cases. This study evaluated the efficacy of trypanocidal therapy to prevent congenital Chagas disease and compared the clinical and serological evolution between treated and untreated infected mothers. We conducted a multicenter, observational study on a cohort of mothers infected with T. cruzi, with and without trypanocidal treatment before pregnancy. Their children were studied to detect congenital infection. Among 354 “chronically infected mother-biological child” pairs, 132 were treated women and 222 were untreated women. Among the children born to untreated women, we detected 34 infected with T. cruzi (15.3%), whose only antecedent was maternal infection. Among the 132 children of previously treated women, no infection with T. cruzi was found (0.0%) (p<0.05). Among 117 mothers with clinical and serological follow up, 71 had been treated and 46 were untreated. The women were grouped into three groups. Group A: 25 treated before 15 years of age; Group B: 46 treated at 15 or more years of age; Group C: untreated, average age of 29.2±6.2 years at study entry. Follow-up for Groups A, B and C was 16.3±5.8, 17.5±9.2 and 18.6±8.6 years respectively. Negative seroconversion: Group A, 64.0% (16/25); Group B, 32.6% (15/46); Group C, no seronegativity was observed. Clinical electrocardiographic alterations compatible with chagasic cardiomyopathy: Group A 0.0% (0/25); B 2.2% (1/46) and C 15.2% (7/46). The trypanocidal treatment of women with chronic Chagas infection was effective in preventing the congenital transmission of Trypanosoma cruzi to their children; it had also a protective effect on the women's clinical evolution and deparasitation could be demonstrated in many treated women after over 10 years of follow up.

Background: Current algorithm for Congenital Chagas Disease (cCD) diagnosis is unsatisfactory due to low sensitivity of the parasitological methods. Moreover, loss to follow-up precludes final serodiagnosis after nine months of life in many cases. A duplex TaqMan qPCR kit for Trypanosoma cruzi DNA amplification was prospectively evaluated in umbilical cord (UCB) and peripheral venous blood (PVB) of infants born to CD mothers at endemic and non-endemic sites of Argentina.Methods: We enrolled and followed-up 370 infants; qPCR was compared to gold-standard cCD diagnosis following studies of diagnostic accuracy guidelines.Findings: Fourteen infants (3 •78%) had cCD. The qPCR sensitivity and specificity were higher in PVB (72 •73%, 99 •15% respectively) than in UCB (66 •67%, 96 •3%). Positive and negative predictive values were 80 and 98 •73% and 50 and 98 •11% for PVB and UCB, respectively. The Areas under the Curve (AUC) of ROC analysis for qPCR and micromethod (MM) were 0 •81 and 0 •67 in UCB and 0 •86 and 0 •68 in PVB, respectively. Parasitic loads ranged from 37 •5 to 23,709 parasite equivalents/mL. Discrete typing Unit Tc V was identified in five cCD patients and in six other cCD cases no distinction among Tc II, Tc V or Tc VI was achieved.Interpretation: This first prospective field study demonstrated that qPCR was more sensitive than MM for early cCD detection and more accurate in PVB than in UCB. Its use, as an auxiliary diagnostic tool to MM will provide more accurate records on cCD incidence.

HighlightsThis is the first meta-analysis of individual data in chronic Trypanosoma cruzi infection after treatment.The probability of seroreversion is variable along the course of follow-up.An interaction was found between age at treatment and country setting.The course of parasitological/molecular tests after treatment needs to be assessed.

Infection by Trypanosoma cruzi or Chagas Disease (ChD) affects around 7 million people in the Americas, most of which are unaware of their status due to lack of clinical manifestations and poor access to diagnosis. Rapid diagnostic tests (RDTs) are widely used for screening different infections (HIV, Hepatitis B, Syphilis), and their application for ChD would facilitate access to diagnosis, especially in remote areas where health services have scarce resources. We conducted a prospective intervention study during 2018 to evaluate in field two RDTs for ChD, authorized by the National Administration of Medicaments, Aliments, and Medical Technologies of Argentina (ANMAT), to in vitro diagnostic reactive; in endemic and non-endemic areas of Argentina. We recruited 607 volunteers older than 18 years in Salta province and City of Buenos Aires. The RDTs Ab Standard Diagnostics SD Bioline® (SD) and Check Chagas Wiener Lab® (WL) were performed in situ with whole blood sample, and confirmatory serology was done at a reference center. The rate of infection with T. cruzi was 17.8% (108/607). SD test showed a performance of 97.2% sensitivity (95%CI 93.5-100), 91.7% specificity (95%CI 96.2-99.2%), and WL test 93.4% sensitivity (95%CI 88.2-98.6%), 99.1% specificity (95%CI 91.9-100%). The sensitivity and specificity for the two RDTs tested were higher than previously reported. These results encourage the use of the tested RDTs in Salta province and to perform further field studies for the implementation of these RDTs in other epidemiological scenarios. This will be very important to improve access to diagnosis of Chagas and its clinical manage as a neglected disease, especially in remote areas with health access barriers.

Background: Retrospective observational studies suggest that transmission of Trypanosoma cruzi does not occur in treated women when pregnant later in life. The level of parasitemia 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 Argentine guideline recommending BZN 60d/300 mg (or equivalent) treatment 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 60d/300 mg course is not yet established. Clinical trials testing alternative BZN courses among women of reproductive age are urgently needed. Methods and design: We are proposing to perform a double-blinded, non-inferiority randomized controlled trial comparing a short low dose 30-day treatment with BZN 150 mg/day (30d/150 mg) vs. BZN 60d/300 mg. We will recruit not previously treated T. cruzi seropositive women with a live birth during the postpartum period in Argentina, randomize them at 6 months postpartum, and follow them up with the following specific aims: Specific aim 1: to measure the effect of BZN 30d/150 mg compared to 60d/300 mg preconceptional treatment on parasitic load measured by the frequency of positive Polymerase Chain Reaction (PCR) (primary outcome) and by real-time quantitative PCR (qPCR), immediately and 10 months after treatment. Specific aim 2: to measure the frequency of serious adverse events and/or any adverse event leading to treatment

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Funding:The program is funded by Fundacio ´n Mundo Sano and Asociacio ´n para Desarrollo Sanitario Regional (ADESAR), both of which played a role in the program design and implementation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background Retrospective observational studies suggest that transmission of Trypanosoma cruzi does not occur in treated women when pregnant later in life. The level of parasitemia 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 Argentine guideline recommending BZN 60d/300mg (or equivalent) treatment 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 60d/300mg course is not yet established. Clinical trials testing alternative BZN courses among women of reproductive age are urgently needed.Methods and design We are proposing to perform a double-blinded, non-inferiority randomized controlled trial comparing a short low dose 30-day treatment with BZN 150mg/day (30d/150mg) vs. BZN 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 Polymerase Chain Reaction (PCR) (primary outcome) and by real-time quantitative PCR (qPCR), immediately and 10 months after treatment.Specific aim 2: to measure the frequency of serious adverse events and/or any adverse event leading to treatment interruption.Trial registration: ClinicalTrials.gov. Identifier: NCT03672487. Registered 14 September 2018, https://clinicaltrials.gov/ct2/show/NCT03672487?recrs=a&cond=Chagas+Disease&cntry=AR&draw=2&rank=3