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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. Funding: FITS SALUD 001-CHAGAS (FONARSEC, MINCyT, Argentina) to the Public-Private Consortium (INGEBI-CONICET, INP-ANLIS MALBRAN and Wiener Laboratories); ERANET-LAC-HD 328 to AGS and PICT 2015-0074 (FONCYT, MinCyT) to AGS and FA. Fil: Benatar, Alejandro Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Danesi, Emmaría. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina Fil: Besuschio, Susana Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Bortolotti, Santiago. Wiener Laboratorios SAIC; Argentina Fil: Cafferata, María Luisa. Instituto de Efectividad Clínica y Sanitaria; Argentina Fil: Ramirez Gomez, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Lopez Albizu, Maria Constanza. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina Fil: Scollo, Karenina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina Fil: Baleani, María. Wiener Laboratorios SAIC; Argentina Fil: Lara, Laura. Instituto de Maternidad y Ginecología ''Nuestra Señora de las Mercedes''; Argentina Fil: Agolti, Gustavo. Gobierno de la Provincia de Chaco. Hospital Julio César Perrando; Argentina Fil: Seu, Sandra. Gobierno de la Provincia de Santiago del Estero. Hospital Regional Dr. Ramón Carrillo; Argentina Fil: Adamo, Elsa. Provincia de Santiago del Estero. Centro Integral de Salud La Banda; Argentina Fil: Lucero, Raul Horacio. Universidad Nacional del Nordeste. Instituto de Medicina Regional; Argentina Fil: Irazu, Lucía. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina Fil: Rodriguez, Marcelo. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina Fil: Poeylaut Palena, Andrés Alberto. Wiener Laboratorios SAIC; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Longhi, Silvia Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Esteva, Mónica Inés. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina Fil: Althabe, Fernando. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Rojkin, Federico. Wiener Laboratorios SAIC; Argentina Fil: Bua, Jacqueline Elena. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Sosa-Estani, Sergio Alejandro. Instituto de Efectividad Clínica y Sanitaria; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Schijman, Alejandro Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina Fil: Congenital Chagas Disease Study Group. No especifíca

© 2020 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See http://creativecommons.org/licenses/by/4.0/, As the global COVID-19 pandemic advances, it increasingly impacts those vulnerable populations who already bear a heavy burden of neglected tropical disease. Chagas disease (CD), a neglected parasitic infection, is of particular concern because of its potential to cause cardiac, gastrointestinal, and other complications which could increase susceptibility to COVID-19. The over one million people worldwide with chronic Chagas cardiomyopathy require special consideration because of COVID-19's potential impact on the heart, yet the pandemic also affects treatment provision to people with acute or chronic indeterminate CD. In this document, a follow-up to the WHF-IASC Roadmap on CD, we assess the implications of coinfection with SARS-CoV-2 and Trypanosoma cruzi, the etiological agent of CD. Based on the limited evidence available, we provide preliminary guidance for testing, treatment, and management of patients affected by both diseases, while highlighting emerging healthcare access challenges and future research needs., The authors would like to thank Marina Certo, DNDi Platforms Coordination Officer, for invaluable support of the writing group. DNDi is grateful to its donors, public and private, who have provided funding to DNDi since its inception in 2003. A full list of DNDi donors can be found at http://www.dndi.org/donors/donors. MASY is grateful for financial support from FAPESP 2012/50273-0. ALPR is grateful for support from CNPq (310679/2016-8 and 465518/2014-1) and FAPEMIG (PPM-00428-17).

Chagas disease is a neglected disease that remains a public health threat, particularly in Latin America. The most important treatment options are nitroimidazole derivatives, such as nifurtimox and benznidazole (BZN). Some studies suggest that for adults seropositive to T. cruzi but without clinically evident chronic Chagas cardiomyopathy (CCC), a simple fixed-dose scheme of BZN could be equivalent to a weight-adjusted dose. We compared the efficacy and safety of a fixed dose of BZN with an adjusted dose for T. cruzi seropositive adults without CCC. We used the Cochrane methods, and reported according to the PRISMA statement. We included randomized controlled trials (RCTs) allocating participants to fixed and/or adjusted doses of BZN for T. cruzi seropositive adults without CCC. We searched (December 2019) Cochrane, MEDLINE, EMBASE, LILACS, Clinicaltrials.gov, and International Clinical Trials Registry Platform (ICTRP), and contacted Chagas experts. Selection, data extraction, and risk of bias assessment, using the Cochrane tool, were performed independently by pairs of reviewers. Discrepancies were solved by consensus within the team. Primary outcomes were parasite‐related outcomes and efficacy or patient‐related safety outcomes. We conducted a meta-analysis using RevMan 5.3 software and used GRADE summary of finding tables to present the certainty of evidence by outcome. We identified 655 records through our search strategy and 10 studies (four of them ongoing) met our inclusion criteria. We did not find any study directly comparing fixed vs adjusted doses of BZN, however, some outcomes allowed subgroup comparisons between fixed and adjusted doses of BZN against placebo. Moderate-certainty evidence suggests no important subgroup differences for positive PCR at one year and for three safety outcomes (drug discontinuation, peripheral neuropathy, and mild rash). The same effect was observed for any serious adverse events (low-certainty evidence). All subgroups showed similar effects (I2 0% for all these subgroup comparisons but 32% for peripheral neuropathy), supporting the equivalence of BZN schemes. We conclude that there is no direct evidence comparing fixed and adjusted doses of BZN. Based on low to very low certainty of evidence for critical clinical outcomes and moderate certainty of evidence for important outcomes, fixed and adjusted doses may be equivalent in terms of safety and efficacy. An individual patient data network meta-analysis could better address this issue., Author summary Chagas disease is a major public health problem that requires, among other control interventions, an optimal trypanocidal therapy that achieves the best possible compliance to cure active infection, mainly in children and young populations, women before they become pregnant to prevent congenital transmission, and chronic populations who are currently not being treated and with a risk of progression to cardiomyopathy. Some studies suggest that a simple fixed-dose scheme of benznidazole could be equivalent to the dose adjusted by weight for the treatment of adults seropositive to T. cruzi without clinically evident chronic Chagas cardiomyopathy. To confirm or reject this potential equivalence of schemes, we conducted a rigorous systematic review and meta-analysis of randomized controlled trials by reviewing and analyzing the totality of available literature on the subject. Although we did not find direct evidence addressing this question, it appears that an adjusted dose is probably equivalent in terms of important safety and efficacy outcomes, while the effect on critical outcomes is uncertain. Since we did not find any ongoing study comparing fixed versus adjusted doses of benznidazole, we are conducting an individual patient data network meta-analysis to address this question.

En Argentina nacen alrededor de 1500 niños por año con infección por Trypanosoma cruzi. Latransmisión vertical es la principal vía de generación de nuevos casos de Chagas, y de su presencia en zonas no endémicas. Nuestro objetivo fue relevar datos disponibles sobre infección congénita por T. cruzi,analizar su evolución y relación con indicadores de prevalencia materna y riesgo vectorial por regiones de Argentina.Se investigaron fuentes oficiales y bibliografía científica. Se obtuvieron datos nacionales y provinciales del período 1997-2014 del subsector público de salud. Se observó un aumento de embarazadas controladas, que alcanzó una cobertura del 60.3% en 2014. La prevalencia de infección materna descendió de 9.0% a 2.6%.El control en hijos de mujeres infectadas fue variable (entre 23.3% y 93.6% de los niños en riesgo) y la calidad del dato fue deficiente según provincia y año. La tasa de transmisión congénita tuvo una evolución irregular y, según un indicador corregido, la tasa media nacional fluctuó entre 1.9 y 8.2%. Se observó asociación entre la prevalencia materna y el riesgo vectorial en las provincias (test Wilcoxon p = 0.017). La tasa de transmisión congénita provincial no mostró relación con la tasa de infección materna (regresión lineal p = 0.686) ni con elnivel de riesgo vectorial (test Kruskal-Wallis p = 0.3154). Los datos isponibles muestran una deficiencia en los controles de hijos de madres infectadas y de su notificación en el período analizado. Deben mejorar ambos aspectos para obtener información epidemiológica fiable y permitir el acceso oportuno de los niños infectados al tratamiento. . In Argentina, around 1500 children are born each year with Trypanosoma cruzi infection. Mother-to-child transmission is the main source of new cases of Chagas disease and of its occurrence in non-endemic areas. Our objective was to survey the information available on congenital T. cruzi infection, to analyze its evolution and its relation with the index of maternal infection and the risk for vector-borne infection by province of Argentina. Data concerning the public health sector for the period 1997-2014 were retrieved from national and local records. An increase in the number and proportion of pregnant women examined for Chagas was observed, reaching 60.3% coverage in 2014. The prevalence of maternal infection dropped from 9.0% to 2.6%. The control of newborns from infected women was highly variable (23.3%-93.6%), and data quality was deficient, varying amply by province and year. The rate of congenital infection had an irregular evolution and its national average fluctuated between 1.9 and 8.2%. An association was observed between the risk for vector-borne infection and the prevalence of maternal infection by province (Wilcoxon test p = 0.017). The rate of congenital transmission by province was neither associated with the rate of maternal infection (linear regression p = 0.686) nor with the risk for vectorial infection (Kruskal-Wallis test p = 0.3154). The available data show insufficient control of children born from infected mothers, as well as deficient recording of these procedures. Both aspects must be improved to achieve better epidemiological information and to enable timely access of infected children to treatment. Fil: Danesi, Emmaría. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Centro Nacional de Diagnóstico e Investigaciones Endemo-epidémicas; Argentina Fil: Codebó, María Olenka. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina Fil: Sosa-Estani, Sergio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Centro Nacional de Diagnóstico e Investigaciones Endemo-epidémicas; Argentina

En Argentina nacen alrededor de 1500 niños por año con infección por Trypanosoma cruzi. La transmisión vertical es la principal vía de generación de nuevos casos de Chagas, y de su presencia en zonas no endémicas. Nuestro objetivo fue relevar datos disponibles sobre infección congénita por T. cruzi, analizar su evolución y relación con indicadores de prevalencia materna y riesgo vectorial por regiones de Argentina. Se investigaron fuentes oficiales y bibliografía científica. Se obtuvieron datos nacionales y provinciales del período 1997-2014 del subsector público de salud. Se observó un aumento de embarazadas controladas, que alcanzó una cobertura del 60.3% en 2014. La prevalencia de infección materna descendió de 9.0% a 2.6%. El control en hijos de mujeres infectadas fue variable (entre 23.3% y 93.6% de los niños en riesgo) y la calidad del dato fue deficiente según provincia y año. La tasa de transmisión congénita tuvo una evolución irregular y, según un indicador corregido, la tasa media nacional fluctuó entre 1.9 y 8.2%. Se observó asociación entre la prevalencia materna y el riesgo vectorial en las provincias (test Wilcoxon p = 0.017). La tasa de transmisión congénita provincial no mostró relación con la tasa de infección materna (regresión lineal p = 0.686) ni con el nivel de riesgo vectorial (test Kruskal-Wallis p = 0.3154). Los datos disponibles muestran una deficiencia en los controles de hijos de madres infectadas y de su notificación en el período analizado. Deben mejorar ambos aspectos para obtener información epidemiológica fiable y permitir el acceso oportuno de los niños infectados al tratamiento. In Argentina, around 1500 children are born each year with Trypanosoma cruzi infection. Mother-to-child transmission is the main source of new cases of Chagas disease and of its occurrence in non-endemic areas. Our objective was to survey the information available on congenital T. cruzi infection, to analyze its evolution and its relation with the index of maternal infection and the risk for vector-borne infection by province of Argentina. Data concerning the public health sector for the period 1997-2014 were retrieved from national and local records. An increase in the number and proportion of pregnant women examined for Chagas was observed, reaching 60.3% coverage in 2014. The prevalence of maternal infection dropped from 9.0% to 2.6%. The control of newborns from infected women was highly variable (23.3%-93.6%), and data quality was deficient, varying amply by province and year. The rate of congenital infection had an irregular evolution and its national average fluctuated between 1.9 and 8.2%. An association was observed between the risk for vector-borne infection and the prevalence of maternal infection by province (Wilcoxon test p = 0.017). The rate of congenital transmission by province was neither associated with the rate of maternal infection (linear regression p = 0.686) nor with the risk for vectorial infection (Kruskal-Wallis test p = 0.3154). The available data show insufficient control of children born from infected mothers, as well as deficient recording of these procedures. Both aspects must be improved to achieve better epidemiological information and to enable timely access of infected children to treatment.