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The NHEPACHA Iberoamerican Network, founded on the initiative of a group of researchers from Latin American countries and Spain, aims to establish a research framework for Chagas disease that encompasses diagnosis and treatment. For this purpose, the network has created a questionnaire to gather relevant data on epidemiological, clinical, diagnostic, and therapeutic aspects of the disease. This questionnaire was developed based on a consensus of expert members of the network, with the intention of collecting high-quality standardized data, which can be used interchangeably by the different research centers that make up the NHEPACHA network. Furthermore, the network intends to offer a clinical protocol that can be embraced by other researchers, facilitating comparability among published studies, as well as the development of therapeutic response and progression markers.

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OBJECTIVES: To determine the comparative efficacy and safety of a fixed dose of benznidazole (BZN) with an adjusted-dose for Trypanosoma cruzi-seropositive adults without cardiomyopathy. METHODS: We conducted a systematic review and individual participant data (IPD) meta-analysis following Cochrane methods, and the PRISMA-IPD statement for reporting. Randomised controlled trials (RCTs) allocating participants to fixed or adjusted doses of BZN for T. cruzi-seropositive adults without cardiomyopathy were included. We searched (December 2021) Cochrane, MEDLINE, EMBASE, LILACS and trial registries and contacted Chagas experts. Selection, data extraction, risk of bias assessment using the Cochrane tool, and a GRADE summary of finding tables were performed independently by pairs of reviewers. We conducted a random-effects IPD meta-analysis using the one-stage strategy, or, if that was impossible, the two-stage strategy. RESULTS: Five RCTs (1198 patients) were included, none directly comparing fixed with adjusted doses of BZN. Compared to placebo, BZN therapy was strongly associated with negative qPCR and sustainable parasitological clearance regardless of the type of dose and subgroup analysed. For negative qPCR, the fixed/adjusted rate of odds ratios (RORF/A ) was 8.83 (95% CI 1.02-76.48); for sustained parasitological clearance, it was 4.60 (95% CI 0.40-52.51), probably indicating at least non-inferior effect of fixed doses, with no statistically significant interactions by scheme for global and most subgroup estimations. The RORF/A for treatment interruption due to adverse events was 0.44 (95% CI 0.14-1.38), probably indicating no worse tolerance of fixed doses. CONCLUSIONS: We found no direct comparison between fixed and adjusted doses of BZN. However, fixed doses versus placebo are probably not inferior to weight-adjusted doses of BZN versus placebo in terms of parasitological efficacy and safety. Network IPD meta-analysis, through indirect comparisons, may well provide the best possible answers in the near future. REGISTRATION: The study protocol was registered in PROSPERO (CRD42019120905).

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As a result of globalization and constant migratory flows, Chagas disease is now present in almost all continents. The management and treatment of the disease is often influenced by the economic and social context of the societies that host patients. In this manuscript, we aim to provide a comparative review of approaches to patients with Chagas disease in the Americas and Europe.

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Chagas disease (CD) still imposes a heavy burden on most Latin American countries. Vector-borne and mother-to-child transmission cause several thousand new infections per year, and at least 5 million people carry Trypanosoma cruzi. Access to diagnosis and medical care, however, is far from universal. Starting in the 1990s, CD-endemic countries and the Pan American Health Organization-World Health Organization (PAHO-WHO) launched a series of multinational initiatives for CD control-surveillance. An overview of the initiatives' aims, achievements, and challenges reveals some key common themes that we discuss here in the context of the WHO 2030 goals for CD. Transmission of T. cruzi via blood transfusion and organ transplantation is effectively under control. T. cruzi, however, is a zoonotic pathogen with 100+ vector species widely spread across the Americas; interrupting vector-borne transmission seems therefore unfeasible. Stronger surveillance systems are, and will continue to be, needed to monitor and control CD. Prevention of vertical transmission demands boosting current efforts to screen pregnant and childbearing-aged women. Finally, integral patient care is a critical unmet need in most countries. The decades-long experience of the initiatives, in sum, hints at the practical impossibility of interrupting vector-borne T. cruzi transmission in the Americas. The concept of disease control seems to provide a more realistic description of what can in effect be achieved by 2030.

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Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. There is an urgent need for safe, effective, and accessible new treatments since the currently approved drugs have serious limitations. Drug development for Chagas disease has historically been hampered by the complexity of the disease, critical knowledge gaps, and lack of coordinated R&D efforts. This review covers some of the translational challenges associated with the progression of new chemical entities from preclinical to clinical phases of development, and discusses how recent technological advances might allow the research community to answer key questions relevant to the disease and to overcome hurdles in R&D for Chagas disease.

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Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi. There is an urgent need for safe, effective, and accessible new treatments since the currently approved drugs have serious limitations. Drug development for Chagas disease has historically been hampered by the complexity of the disease, critical knowledge gaps, and lack of coordinated R&D efforts. This review covers some of the translational challenges associated with the progression of new chemical entities from preclinical to clinical phases of development, and discusses how recent technological advances might allow the research community to answer key questions relevant to the disease and to overcome hurdles in R&D for Chagas disease.

RESUMO

As a result of globalization and constant migratory flows, Chagas disease is now present in almost all continents. The management and treatment of the disease is often influenced by the economic and social context of the societies that host patients. In this manuscript, we aim to provide a comparative review of approaches to patients with Chagas disease in the Americas and Europe.

RESUMO

Chagas disease (CD) still imposes a heavy burden on most Latin American countries. Vector-borne and mother-to-child transmission cause several thousand new infections per year, and at least 5 million people carry Trypanosoma cruzi. Access to diagnosis and medical care, however, is far from universal. Starting in the 1990s, CD-endemic countries and the Pan American Health Organization-World Health Organization (PAHO-WHO) launched a series of multinational initiatives for CD control-surveillance. An overview of the initiatives' aims, achievements, and challenges reveals some key common themes that we discuss here in the context of the WHO 2030 goals for CD. Transmission of T. cruzi via blood transfusion and organ transplantation is effectively under control. T. cruzi, however, is a zoonotic pathogen with 100+ vector species widely spread across the Americas; interrupting vector-borne transmission seems therefore unfeasible. Stronger surveillance systems are, and will continue to be, needed to monitor and control CD. Prevention of vertical transmission demands boosting current efforts to screen pregnant and childbearing-aged women. Finally, integral patient care is a critical unmet need in most countries. The decades-long experience of the initiatives, in sum, hints at the practical impossibility of interrupting vector-borne T. cruzi transmission in the Americas. The concept of disease control seems to provide a more realistic description of what can in effect be achieved by 2030.

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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.

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BACKGROUND: Current treatment for Chagas disease with the only available drugs, benznidazole or nifurtimox, has substantial limitations, including long treatment duration and safety and tolerability concerns. We aimed to evaluate the efficacy and safety of new benznidazole monotherapy regimens and combinations with fosravuconazole, in the treatment of Chagas disease. METHODS: We did a double-blind, double-dummy, phase 2, multicentre, randomised trial in three outpatient units in Bolivia. Adults aged 18-50 years with chronic indeterminate Chagas disease, confirmed by serological testing and positive qualitative PCR results, were randomly assigned (1:1:1:1:1:1:1) to one of seven treatment groups using a balanced block randomisation scheme with an interactive response system. Participants were assigned to benznidazole 300 mg daily for 8 weeks, 4 weeks, or 2 weeks, benznidazole 150 mg daily for 4 weeks, benznidazole 150 mg daily for 4 weeks plus fosravuconazole, benznidazole 300 mg once per week for 8 weeks plus fosravuconazole, or placebo, with a 12-month follow-up period. The primary endpoints were sustained parasitological clearance at 6 months, defined as persistent negative qualitative PCR results from end of treatment, and incidence and severity of treatment-emergent adverse events, serious adverse events, and adverse events leading to treatment discontinuation. Primary efficacy analysis was based on the intention-to-treat and per-protocol populations and secondary efficacy analyses on the per-protocol population. Safety analyses were based on the as-treated population. Recruitment is now closed. This trial is registered with ClinicalTrials.gov, NCT03378661. FINDINGS: Between Nov 30, 2016, and July 27, 2017, we screened 518 patients, and 210 were enrolled and randomised. 30 patients (14%) were assigned to each treatment group. All 210 randomised patients were included in the intention-to-treat population, and 190 (90%) were included in the per-protocol population. In the intention-to-treat analysis, only one (3%) of 30 patients in the placebo group had sustained parasitological clearance at 6 months of follow-up. Sustained parasitological clearance at 6 months was observed in 25 (89%) of 28 patients receiving benznidazole 300 mg daily for 8 weeks (rate difference vs placebo 86% [95% CI 73-99]), 25 (89%) of 28 receiving benznidazole 300 mg daily for 4 weeks (86% [73-99]), 24 (83%) of 29 receiving benznidazole 300 mg daily for 2 weeks (79% [64-95]), 25 (83%) of 30 receiving benznidazole 150 mg daily for 4 weeks (80% [65-95]), 23 (85%) of 28 receiving benznidazole 150 mg daily for 4 weeks plus fosravuconazole (82% [67-97]), and 24 (83%) of 29 receiving benznidazole 300 mg weekly for 8 weeks plus fosravuconazole (79% [64-95]; p<0·0001 for all group comparisons with placebo). Six patients (3%) had ten serious adverse events (leukopenia [n=3], neutropenia [n=2], pyrexia, maculopapular rash, acute cholecystitis, biliary polyp, and breast cancer), eight had 12 severe adverse events (defined as interfering substantially with the patient's usual functions; elevated alanine aminotransferase [n=4], elevated gamma-glutamyltransferase [n=2], elevated aspartate aminotransferase [n=1], neutropenia [n=3], leukopenia [n=1], and breast cancer [n=1]), and 15 (7%) had adverse events that led to treatment discontinuation (most of these were in the groups who received benznidazole 300 mg daily for 8 weeks, benznidazole 300 mg once per week for 8 weeks plus fosravuconazole, and benznidazole 150 mg daily for 4 weeks plus fosravuconazole). No adverse events leading to treatment discontinuation were observed in patients treated with benznidazole 300 mg daily for 2 weeks or placebo. There were no treatment-related deaths. INTERPRETATION: Benznidazole induced effective antiparasitic response, regardless of treatment duration, dose, or combination with fosravuconazole, and was well tolerated in adult patients with chronic Chagas disease. Shorter or reduced regimens of benznidazole could substantially improve treatment tolerability and accessibility, but further studies are needed to confirm these results. FUNDING: Drugs for Neglected Diseases initiative (DNDi). TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

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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.

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A Trypanosoma cruzi Loopamp kit was recently developed as a ready-to-use diagnostic method requiring minimal laboratory facilities. We evaluated its diagnostic accuracy for detection of acute Chagas disease (CD) in different epidemiological and clinical scenarios. In this retrospective study, a convenience series of clinical samples (venous blood treated with EDTA or different stabilizer agents, heel-prick blood in filter paper or cerebrospinal fluid samples (CSF)) from 30 infants born to seropositive mothers (13 with congenital CD and 17 noninfected), four recipients of organs from CD donors, six orally-infected cases after consumption of contaminated guava juice and six CD patients coinfected with HIV at risk of CD reactivation (N = 46 patients, 46 blood samples and 1 CSF sample) were tested by T. cruzi Loopamp kit (Tc LAMP) and standardized quantitative real-time PCR (qPCR). T. cruzi Loopamp accuracy was estimated using the case definition in the different groups as a reference. Cohen's kappa coefficient (κ) was applied to measure the agreement between Tc LAMP (index test) and qPCR (reference test). Sensitivity and specificity of T. cruzi Loopamp kit in blood samples from the pooled clinical groups was 93% (95% CI: 77-99) and 100% (95% CI: 80-100) respectively. The agreement between Tc LAMP and qPCR was almost perfect (κ = 0.92, 95% CI: 0.62-1.00). The T. cruzi Loopamp kit was sensitive and specific for detection of T. cruzi infection. It was carried out from DNA extracted from peripheral blood samples (via frozen EDTA blood, guanidine hydrochloride-EDTA blood, DNAgard blood and dried blood spots), as well as in CSF specimens infected with TcI or TcII/V/VI parasite populations. The T. cruzi Loopamp kit appears potentially useful for rapid detection of T. cruzi infection in congenital, acute and CD reactivation due to HIV infection.

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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.

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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 interruption. TRIAL REGISTRATION: ClinicalTrials.gov . Identifier: NCT03672487 . Registered 14 September 2018.

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In a pilot study, we showed that the intermittent administration of benznidazole in chronic Chagas disease patients resulted in a low rate of treatment suspension and therapeutic failure, as assessed by quantitative PCR (qPCR) at the end of treatment. Here, a 3-year posttreatment follow-up study of the same cohort of patients is presented. The treatment scheme consisted of 12 doses of benznidazole at 5 mg/kg of body weight/day in two daily doses every 5 days. Parasite load, Trypanosoma cruzi-specific antibodies, and serum chemokine levels were measured prior to treatment and after a median follow-up of 36 months posttreatment by DNA minicircle kinetoplastid and nuclear DNA satellite sequence qPCR methods, conventional serological techniques, a Luminex-based assay with recombinant T. cruzi proteins, and a cytometric bead array. At the end of follow-up, 14 of 17 (82%) patients had negative qPCR findings, whereas three of 17 (18%) had detectable nonquantifiable findings by at least one of the qPCR techniques. A decline in parasite-specific antibodies at 12 months posttreatment was confirmed by conventional serological tests and the Luminex assays. Monocyte chemoattractant protein 1 levels increased after treatment, whereas monokine induced by gamma interferon levels decreased. New posttreatment electrocardiographic abnormalities were observed in only one patient who had cardiomyopathy prior to treatment. Together, these data strengthen our previous findings by showing that the intermittent administration of benznidazole results in a low rate of treatment suspension, with treatment efficacy comparable to that of a daily dose of 5 mg/kg for 60 days.

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Background: Chagas Disease is a neglected tropical disease caused by the protozoan Trypanosoma cruzi, with some of the most serious manifestations affecting the cardiovascular system. It is a chronic, stigmatizing condition, closely associated with poverty and affecting close to 6 million people globally. Although historically the disease was limited to endemic areas of Latin America recent years have seen an increasing global spread. In addition to the morbidity and mortality associated with the disease, the social and economic burdens on individuals and society are substantial. Often called the 'silent killer', Chagas disease is characterized by a long, asymptomatic phase in affected individuals. Approximately 30% then go on develop chronic Chagas cardiomyopathy and other serious cardiac complications such as stroke, rhythm disturbances and severe heart failure. Methods: In a collaboration of the World Hearth Federation (WHF) and the Inter-American Society of Cardiology (IASC) a writing group consisting of 20 diverse experts on Chagas disease (CD) was convened. The group provided up to date expert knowledge based on their area of expertise. An extensive review of the literature describing obstacles to diagnosis and treatment of CD along with proposed solutions was conducted. A survey was sent to all WHF Members and, using snowball sampling to widen the consultation, to a variety of health care professionals working in the CD global health community. The results were analyzed, open comments were reviewed and consolidated, and the findings were incorporated into this document, thus ensuring a consensus representation. Results: The WHF IASC Roadmap on Chagas Disease offers a comprehensive summary of current knowledge on prevention, diagnosis and management of the disease. In providing an analysis of 'roadblocks' in access to comprehensive care for Chagas disease patients, the document serves as a framework from which strategies for implementation such as national plans can be formulated. Several dimensions are considered in the analysis: healthcare system capabilities, governance, financing, community awareness and advocacy. Conclusion: The WHF IASC Roadmap proposes strategies and evidence-based solutions for healthcare professionals, health authorities and governments to help overcome the barriers to comprehensive care for Chagas disease patients. This roadmap describes an ideal patient care pathway, and explores the roadblocks along the way, offering potential solutions based on available research and examples in practice. It represents a call to action to decision-makers and health care professionals to step up efforts to eradicate Chagas disease.

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INTRODUCTION: Congenital transmission (CT) of Trypanosoma cruzi has led to globalization of Chagas disease and its growing relevance as a public health problem. Although the occurrence of CT has been associated with several factors, its mechanisms are still unknown. This study aimed to analyze the geographical and familiar variables of mothers and their association with CT of Chagas disease in a population living in non-endemic areas of Argentina for the last decades. METHODS: We developed a retrospective cohort study in a sample of 2120 mother-child pairs who attended three reference centers in the cities of Buenos Aires, Santa Fe, and Salta between 2002 and 2015. RESULTS: The highest CT rates were observed in children born to Argentinean mothers (10.7%) and in children born to mothers from Buenos Aires (11.7%). Considering the areas of origin of the mothers, those from areas of null-low risk for vector-borne infection had higher CT rates than those from areas of medium-high risk (11.1% vs 8.2%). We also observed a significant intra-familiar "cluster effect," with CT rates of 35.9% in children with an infected sibling, compared to 8.2% in children without infected siblings (RR=4.4 95% CI 2.3-8.4). CONCLUSIONS: The associations observed suggest a higher CT rate in children born to mothers who acquired the infection congenitally, with familiar antecedents, and from areas without the presence of vectors. These observations are considered new epidemiological evidence about Chagas disease in a contemporary urban population, which may contribute to the study of CT and may also be an interesting finding for healthcare professionals.

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Abstract INTRODUCTION: Congenital transmission (CT) of Trypanosoma cruzi has led to globalization of Chagas disease and its growing relevance as a public health problem. Although the occurrence of CT has been associated with several factors, its mechanisms are still unknown. This study aimed to analyze the geographical and familiar variables of mothers and their association with CT of Chagas disease in a population living in non-endemic areas of Argentina for the last decades. METHODS: We developed a retrospective cohort study in a sample of 2120 mother-child pairs who attended three reference centers in the cities of Buenos Aires, Santa Fe, and Salta between 2002 and 2015. RESULTS: The highest CT rates were observed in children born to Argentinean mothers (10.7%) and in children born to mothers from Buenos Aires (11.7%). Considering the areas of origin of the mothers, those from areas of null-low risk for vector-borne infection had higher CT rates than those from areas of medium-high risk (11.1% vs 8.2%). We also observed a significant intra-familiar "cluster effect," with CT rates of 35.9% in children with an infected sibling, compared to 8.2% in children without infected siblings (RR=4.4 95% CI 2.3-8.4). CONCLUSIONS: The associations observed suggest a higher CT rate in children born to mothers who acquired the infection congenitally, with familiar antecedents, and from areas without the presence of vectors. These observations are considered new epidemiological evidence about Chagas disease in a contemporary urban population, which may contribute to the study of CT and may also be an interesting finding for healthcare professionals.

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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.

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