Efficacy and safety of fexinidazole for treatment of chronic indeterminate Chagas disease (FEXI-12): a multicentre, randomised, double-blind, phase 2 trial.

BACKGROUND: More than six million people worldwide, particularly in vulnerable communities in Latin America, are infected with Trypanosoma cruzi, the causative agent of Chagas disease. Only a small portion have access to diagnosis and treatment. Both drugs used to treat this chronic, neglected infection, benznidazole and nifurtimox, were developed more than 50 years ago, and adverse drug reactions during treatment pose a major barrier, causing 20% of patients to discontinue therapy. Fexinidazole proved efficacious in an earlier, interrupted clinical trial, but the doses evaluated were not well tolerated. The present study evaluated fexinidazole at lower doses and for shorter treatment durations. METHODS: In this randomised, double-blind, phase 2 trial, we included adult patients (18-60 years old) with confirmed T cruzi infection by serology and PCR and without signs of organ involvement. We evaluated three regimens of fexinidazole-600 mg once daily for 10 days (6·0 g total dose), 1200 mg daily for 3 days (3·6 g), and 600 mg daily for 3 days followed by 1200 mg daily for 4 days (6·6 g)-and compared them with a historical placebo control group (n=47). The primary endpoint was sustained negative results by PCR at end of treatment and on each visit up to four months of follow-up. This study is registered with ClinicalTrials.gov, NCT03587766, and EudraCT, 2016-004905-15. FINDINGS: Between Oct 16, 2017, and Aug 7, 2018, we enrolled 45 patients (n=15 for each group), of whom 43 completed the study. Eight (19%) of 43 fexinidazole-treated patients reached the primary endpoint, compared with six (13%) of 46 in the historical control group. Mean parasite load decreased sharply following treatment but rebounded beginning 10 weeks after treatment. Five participants had seven grade 3 adverse events: carpal tunnel, sciatica, device infection, pneumonia, staphylococcal infection, and joint and device dislocation. Two participants discontinued treatment due to adverse events unrelated to fexinidazole. INTERPRETATION: The fexinidazole regimens in this study had an acceptable safety profile but did not prove effective against T cruzi infection. Development of fexinidazole monotherapy for treating T cruzi infection has been stopped. FUNDING: The Drugs for Neglected Diseases initiative.

A standardized clinical database for research in Chagas disease: The NHEPACHA network.

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.

Efficacy of three benznidazole dosing strategies for adults living with chronic Chagas disease (MULTIBENZ): an international, randomised, double-blind, phase 2b trial.

BACKGROUND: Treatment with benznidazole for chronic Chagas disease is associated with low cure rates and substantial toxicity. We aimed to compare the parasitological efficacy and safety of 3 different benznidazole regimens in adult patients with chronic Chagas disease. METHODS: The MULTIBENZ trial was an international, randomised, double-blind, phase 2b trial performed in Argentina, Brazil, Colombia, and Spain. We included participants aged 18 years and older diagnosed with Chagas disease with two different serological tests and detectable T cruzi DNA by qPCR in blood. Previously treated people, pregnant women, and people with severe cardiac forms were excluded. Participants were randomly assigned 1:1:1, using a balanced block randomisation scheme stratified by country, to receive benznidazole at three different doses: 300 mg/day for 60 days (control group), 150 mg/day for 60 days (low dose group), or 400 mg/day for 15 days (short treatment group). The primary outcome was the proportion of patients with a sustained parasitological negativity by qPCR during a follow-up period of 12 months. The primary safety outcome was the proportion of people who permanently discontinued the treatment. Both primary efficacy analysis and primary safety analysis were done in the intention-to-treat population. The trial is registered with EudraCT, 2016-003789-21, and ClinicalTrials.gov, NCT03191162, and is completed. FINDINGS: From April 20, 2017, to Sept 20, 2020, 245 people were enrolled, and 234 were randomly assigned: 78 to the control group, 77 to the low dose group, and 79 to the short treatment group. Sustained parasitological negativity was observed in 42 (54%) of 78 participants in the control group, 47 (61%) of 77 in the low dose group, and 46 (58%) of 79 in the short treatment group. Odds ratios were 1·41 (95% CI 0·69-2·88; p=0·34) when comparing the low dose and control groups and 1·23 (0·61-2·50; p=0·55) when comparing short treatment and control groups. 177 participants (76%) had an adverse event: 62 (79%) in the control group, 56 (73%) in the low dose group, and 59 (77%) in the short treatment group. However, discontinuations were less frequent in the short treatment group compared with the control group (2 [2%] vs 11 [14%]; OR 0·20, 95% CI 0·04-0·95; p=0·044). INTERPRETATION: Participants had a similar parasitological responses. However, reducing the usual treatment from 8 weeks to 2 weeks might maintain the same response while facilitating adherence and increasing treatment coverage. These findings should be confirmed in a phase 3 clinical trial. FUNDING: European Community's 7th Framework Programme.

Chagas disease control-surveillance in the Americas: the multinational initiatives and the practical impossibility of interrupting vector-borne Trypanosoma cruzi transmission

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.

Critical analysis of Chagas disease treatment in different countries

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.

The translational challenge in Chagas disease drug development

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.

Higher congenital transmission rate of Trypanosoma cruzi associated with family history of congenital transmission

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.

Transmisión congénita de Trypanosoma cruzi: Argentina 2002-2014 / Congenital transmission of Trypanosoma cruzi. Argentina 2002-2014

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.

Effects of trypanocidal treatment on echocardiographic parameters in chagas cardiomyopathy and prognostic value of wall motion score index: A BENEFIT trial echocardiographic substudy

Serial echocardiographic studies in chronic Chagas cardiomyopathy are scarce. The aims of this study were to evaluate whether therapy with benznidazole modifies the progression of cardiac impairment and to identify baseline echocardiographic parameters related to prognosis. METHODS: A prospective sub study was conducted in 1,508 patients with chronic Chagas cardiomyopathy randomized to benznidazole or placebo, who underwent two-dimensional echocardiography at enrollment, 2 years, and final follow-up (5.4 years). Left ventricular (LV) ejection fraction, LV wall motion score index (WMSI), indexed left atrial volume, and chamber dimensions were collected and correlated to all-cause death and a composite hard outcome using univariate and multivariate analyses. RESULTS: At enrollment, most patients had normal chamber dimensions, and 70.5% had preserved LV ejection fractions. During follow-up, all chamber dimensions increased similarly in both treatment arms. LV ejection fraction was comparably reduced (55.7 ± 12.7% to 52.1 ± 14.6% vs 56.3 ± 12.7% to 52.8 ± 14.1%) and LV WMSI similarly increased (1.31 ± 0.41 to 1.49 ± 0.03 and 1.27 ± 0.38 to 1.51 ± 0.03) for the benznidazole and placebo groups, respectively (P > .05). A higher baseline LV WMSI was identified in subjects who died compared with those alive at final echocardiography (1.76 ± 0.517 vs 1.271 ± 0.393, P < .0001). There was a significant (P < .0001) graded increase in the risk for the composite outcome with worsening LV WMSI (hazard ratios, 2.27 [95% CI, 1.69-3.06] and 6.42 [95% CI, 4.94-8.33]) and also of death (hazard ratios, 2.45 [95% CI, 1.62-3.71] and 8.99 [95% CI, 6.3-12.82]) for 1 < LV WMSI < 1.5 and LV WMSI > 1.5, respectively. Both LV WMSI and indexed left atrial volume remained independent predictors in multivariate analysis. CONCLUSIONS: Trypanocidal treatment had no effect on echocardiographic progression of chronic Chagas cardiomyopathy over 5.4 years. Despite normal global LV systolic function, regional wall motion abnormalities and indexed left atrial volume identified patients at higher risk for hard adverse clinical outcomes. Copyright © 2018 American Society of Echocardiography. Published by Elsevier Inc. All rights reserved. KEYWORDS: Chagas cardiomyopathy; Echocardiography; Prognosis; Trypanocidal therapy. (AU)

Inmunoserología y métodos moleculares para el diagnóstico de Chagas: revisión sistemática rápida / Immunoserology and molecular techniques for diagnosis of Chagas´ disease: rapid systematic review / Imunoserologia e métodos moleculares para o diagnóstico de Chagas: revisão sistemática rápida

Con el objetivo de incrementar la precisión diagnóstica, la Organización Mundial de la Salud recomienda la realización de dos o más pruebas inmunoserológicas para el diagnóstico de la enfermedad de Chagas en etapa crónica. El objetivo de este trabajo fue realizar una revisión sistemática rápida acerca del desempeño de las técnicas inmunoserológicas y métodos moleculares en la población general. Se identificaron 178 estudios de los cuales fueron incluidos nueve. Las técnicas de ELISA mostraron la mayor sensibilidad (82-98%) y especificidad (96-100%). Los métodos rápidos mostraron valores de sensibilidad entre 88-93% y especificidad 97- 100%, mientras que los métodos moleculares (PCR) presentaron niveles muy variables de sensibilidad (22-92%) y especificidad (70-100%). Estos resultados muestran que las técnicas de ELISA cuentan con una sensibilidad y especificidad adecuadas. La PCR, al igual que los métodos rápidos, mostró una gran variabilidad en los resultados, debido principalmente a la heterogeneidad de la técnicas y profusión de métodos elaborados de manera in house.

In order to increase diagnostic accuracy, the World Health Organization recommends performing two or more immunoserological tests for the diagnosis of Chagas disease in chronic stage. The aim of this work was to make a rapid systematic review of the performance of immunoserological techniques and molecular methods in the general population. A total of 178 studies were identified, nine ofwhich were included. ELISA techniques showed the highest sensitivity (82-98%) and specificity (96-100%). Rapid methods presented values of sensitivity between 88-93% and 97-100% of specificity, while the molecular methods (PCR) showed highly variable levels of sensitivity (22-92%) and specificity (70-100%). These results indicate that ELISA techniques have adequate sensitivity and specificity. PCR, as well as rapid methods, showed great variability in the results, mainly due to the heterogeneity of the techniques and abundance of "in-house" methods.

Visando a aumentar a precisão do diagnóstico, a Organização Mundial da Saúde recomenda executar dois ou mais testes imunoserológicos para o diagnóstico na fase crônica da doença de Chagas. O objetivo deste trabalho foi fazer uma revisão sistemática rápida sobre o desempenho de técnicas imunoserológicas e métodos moleculares na população em geral. Foram identificados 178 estudos dos quais se incluíram nove. Técnicas de ELISA mostraram a maior sensibilidade (82-98%) e especificidade (96-100%). Métodos rápidos apresentaram valores de sensibilidade e especificidade de 88-93% e 97-100%, respectivamente enquanto que os métodos moleculares (PCR) tinham níveis extremamente variáveis de sensibilidade (22-92%) e especificidade (70-100%). Estes resultados mostram que as técnicas de ELISA possuem sensibilidade e especificidade adequadas. A PCR, bem como os métodos rápidos, mostrou grande variabilidade nos resultados, principalmente devido à heterogeneidade das técnicas e profusão de métodos desenvolvidos de modo in house.

Estrategia para mejorar el acceso al tratamiento etiológico para la enfermedad de Chagas en el primer nivel de atención en Argentina / Strategy to improve access to etiological treatment of Chagas disease at the first level of care in Argentina

Objetivo. Mejorar la distribución del tratamiento etiológico para la enfermedad de Chagas mediante la identificación de barreras para su descentralización al primer nivel de atención en Argentina. Métodos. Se llevó a cabo un estudio cualitativo, de carácter exploratorio y descriptivo, en base a entrevistas semiestructuradas a actores clave pertenecientes al Programa Nacional de Chagas y miembros de los equipos de salud del primer nivel de atención con el objetivo de identificar barreras para el diagnóstico y tratamiento de la enfermedad de Chagas en diferentes niveles (administrativo, efectores de salud y comunidad) que podrían afectar una estrategia descentralizada de distribución. Además, se implementó un piloto de descentralización en diez centros de atención primaria en una provincia argentina. Resultados. Se realizaron 22 entrevistas semiestructuradas con responsables de programas y profesionales de la salud. Los principales obstáculos hallados fueron la falta de búsqueda sistemática de casos, la poca articulación entre los niveles de atención y los actores del sistema de salud, la falta de capacitación del equipo de salud respecto al tratamiento, el seguimiento de los pacientes y las barreras asociadas a los pacientes. Se llevó a cabo un programa piloto de descentralización y se evaluaron estrategias para optimizar la intervención a gran escala. Conclusiones. Los resultados permitieron mejorar la implementación del plan de descentralización del tratamiento a través de una mejor articulación interprogramática, la capitalización de herramientas de monitoreo y de comunicación ya existentes, y la sensibilización de los equipos de salud. Además, se formularon recomendaciones tendientes a mejorar el diagnóstico y el tratamiento de la enfermedad de Chagas.

Objective. Improve distribution of etiological treatment of Chagas disease by identifying barriers to the decentralization of treatment to the first level of care in Argentina. Methods. A qualitative, exploratory, and descriptive study was conducted using semi-structured interviews of key actors belonging to the National Chagas Program and members of health teams at the first level of care, for the purpose of identifying barriers to diagnosis and treatment of Chagas disease at different levels (administrative, health agents, and community) that could affect a decentralized distribution strategy. Additionally, pilot decentralization was instituted in 10 primary health care centers in an Argentine province. Results. Semi-structured interviews were conducted with 22 program heads and health professionals. Principal obstacles found were lack of systematic case-finding, poor coordination among levels of care and health system actors, lack of health team training on treatment, patient monitoring, and patient-related barriers. A pilot decentralization program was carried out and strategies were evaluated to optimize large-scale intervention. Conclusions. The results made it possible to improve implementation of the plan to decentralize treatment through better inter-program coordination, capitalization on existing monitoring and communication tools, and sensitization of health teams. Furthermore, recommendations were developed to improve diagnosis and treatment of Chagas disease.

First Colombian consensus on congenital Chagas and clinical approach for women of child-bearing age diagnosed with Chagas / Primer consenso colombiano sobre Chagas congénito y orientación clínica a mujeres en edad fértil con diagnóstico de Chagas

Congenital transmission of Chagas disease has not been extensively studied in Colombia, and there are no standardized processes in the health system regarding the specific diagnosis, treatment and follow-up of this disease. To generate recommendations on congenital Chagas disease and Chagas in women of childbearing age in Colombia, a consensus of experts was developed. An extensive literature search through the Medline database was carried out using the MeSH terms: «Chagas disease/congenital¼, «prevention and control¼, «diagnosis¼, «therapeutics¼ and «pregnancy¼. Appropriate abstracts were selected and the full texts were analyzed. The relevant information was synthesized, classified, and organized into tables and figures and was presented to a panel of experts, which was composed of 30 professionals from various fields. Based on the Delphi methodology, three rounds of consultation were conducted. The first and second rounds were based on electronic questionnaires that measured the level of consensus of each question among the participants. The third round was based on a face-to-face discussion focusing on those questions without consensus in the previous consultations. The evidence was adapted to national circumstances on a case-by-case basis, and the content the final document was approved. These recommendations are proposed for use in routine medical practice by health professionals in Colombia.

La transmisión congénita de la enfermedad de Chagas ha sido poco estudiada en Colombia y existen pocos procedimientos rutinarios en el sistema de salud para el manejo de esta enfermedad. Por ello se desarrolló un consenso de expertos dirigido a generar recomendaciones de diagnóstico y tratamiento de Chagas con- génito y orientación a mujeres en edad fértil. Con ese propósito se realizó una búsqueda extensiva de la literatura, empleando una combinación de términos Mes (Chagas, Chagas congénito, prevención, control, diagnóstico, tratamiento y embarazo) para reflejar el estado del arte en cada tema de interés. Después de ello, se leyeron los resúmenes y aquellos seleccionados para análisis del texto completo. La literatura relevante se sintetizo, clasifico y organizo en tablas y se presentó al panel de expertos, el cual estaba constituido por 30 profesionales en diferentes áreas. Mediante la metodología Delphi se realizaron 2 rondas de cuestionarios virtuales y una reunión presencial en los cuales se evaluaron los niveles de acuerdo entre los participantes. Los puntos con falta de consenso durante las 2 rondas virtuales se expusieron durante las mesas de discusión en la ronda presencial. La evidencia utilizada se adaptó a las particularidades nacionales según el caso y se aprobó el contenido del documento final. Se propone que estas recomendaciones sean usadas por profesionales de la salud en Colombia.

Integrated control of Chagas disease for its elimination as public health problem - A Review

Chagas disease or American trypanosomiasis is, together with geohelminths, the neglected disease that causes more loss of years of healthy life due to disability in Latin America. Chagas disease, as determined by the factors and determinants, shows that different contexts require different actions, preventing new cases or reducing the burden of disease. Control strategies must combine two general courses of action including prevention of transmission to prevent the occurrence of new cases (these measures are cost effective), as well as opportune diagnosis and treatment of infected individuals in order to prevent the clinical evolution of the disease and to allow them to recuperate their health. All actions should be implemented as fully as possible and with an integrated way, to maximise the impact. Chagas disease cannot be eradicated due because of the demonstrated existence of infected wild triatomines in permanent contact with domestic cycles and it contributes to the occurrence of at least few new cases. However, it is possible to interrupt the transmission of Trypanosoma cruzi in a large territory and to eliminate Chagas disease as a public health problem with a dramatic reduction of burden of the disease.

Congenital Chagas disease: an update

Congenital infection with Trypanosoma cruzi is a global problem, occurring on average in 5% of children born from chronically infected mothers in endemic areas, with variations depending on the region. This presentation aims to focus on and update epidemiological data, research methods, involved factors, control strategy and possible prevention of congenital infection with T. cruzi. Considering that etiological treatment of the child is always effective if performed before one year of age, the diagnosis of infection in pregnant women and their newborns has to become the standard of care and integrated into the surveillance programs of syphilis and human immunodeficiency virus. In addition to the standard tests, polymerase chain reaction performed on blood of neonates of infected mothers one month after birth might improve the diagnosis of congenital infection. Recent data bring out that its transmission can be prevented through treatment of infected women before they become pregnant. The role of parasite genotypes and host genetic factors in parasite transmission and development of infection in foetuses/neonates has to be more investigated in order to better estimate the risk factors and impact on health of congenital infection with T. cruzi.

Primer consenso colombiano sobre Chagas congénito y orientación clínica a mujeres en edad fértil con diagnóstico de Chagas / First Colombian consensus on congenital Chagas and clinical approach to women of fertile age diagnosed with Chagas

La transmisión congénita de la enfermedad de Chagas ha sido poco estudiada en Colombia y existen pocos procedimientos rutinarios en el sistema de salud para el manejo de esta enfermedad. Por ello se desarrolló un consenso de expertos dirigido a generar recomendaciones de diagnóstico y tratamiento de Chagas congénito y orientación a mujeres en edad fértil. Con ese propósito se realizó una búsqueda extensiva de la literatura, empleando una combinación de términos MeSH (Chagas, Chagas congénito, prevención, control, diagnóstico, tratamiento y embarazo) para reflejar el estado del arte en cada tema de interés. Después de ello, se leyeron los resúmenes y aquellos seleccionados para análisis del texto completo. La literatura relevante se sintetizó, clasificó y organizó en tablas y se presentó al panel de expertos, el cual estaba constituido por 30 profesionales en diferentes áreas. Mediante la metodología Delphi se realizaron 2 rondas de cuestionarios virtuales y una reunión presencial en los cuales se evaluaron los niveles de acuerdo entre los participantes. Los puntos con falta de consenso durante las 2 rondas virtuales se expusieron durante las mesas de discusión en la ronda presencial. La evidencia utilizada se adaptó a las particularidades nacionales según el caso y se aprobó el contenido del documento final. Se propone que estas recomendaciones sean usadas por profesionales de la salud en Colombia.

Congenital transmission of Chagas disease has not been extensively studied in Colombia, and there are no standardized processes in the health system regarding the specific diagnosis, treatment and follow-up of this disease. In order to generate recommendations on congenital Chagas disease and Chagas in women of childbearing age in Colombia, a consensus of experts was developed. An extensive literature search through the Medline database was carried out using the MeSH terms: " Chagas disease/congenital " , " prevention and control " , " diagnosis " , " therapeutics " and " pregnancy " . Appropriate abstracts were selected and the full texts were analyzed. The relevant information was synthesized, classified, and organized into tables and figures and was presented to a panel of experts, which was composed of 30 professionals from various fields. Based on the Delphi methodology, three rounds of consultation were conducted. The first and second rounds were based on electronic questionnaires that measured the level of consensus of each question among the participants. The third round was based on a face-toface discussion focusing on those questions without consensus in the previous consultations. The evidence was adapted to national circumstances on a case-by-case basis, and the content the final document was approved. These recommendations are proposed for use in routine medical practice by health professionals in Colombia.

Therapy, diagnosis and prognosis of chronic Chagas disease: insight gained in Argentina

The purpose of this review is to describe research findings regarding chronic Chagas disease in Argentina that have changed the standards of care for patients with Trypanosoma cruzi infection. Indirect techniques (serological tests) are still the main tools for the primary diagnosis of infection in the chronic phase, but polymerase chain reaction has been shown to be promising. The prognosis of patients with heart failure or advanced stages of chagasic cardiomyopathy is poor, but a timely diagnosis during the initial stages of the disease would allow for prescription of appropriate therapies to offer a better quality of life. Treatment of T. cruzi infection is beneficial as secondary prevention to successfully cure the infection or to delay, reduce or prevent the progression to disease and as primary disease prevention by breaking the chain of transmission. Current recommendations have placed the bulk of the diagnostic and treatment responsibility on the Primary Health Care System. Overall, the current research priorities with respect to Chagas disease should be targeted towards (i) the production of new drugs that would provide a shorter treatment course with fewer side effects; (ii) the development of new tools to confirm cure after a full course of treatment during the chronic phase and (iii) biomarkers to identify patients with a high risk of developing diseases.

Etiological treatment of young women infected with Trypanosoma cruzi, and prevention of congenital transmission / Tratamento etiológico de mulheres jovens infectadas com Trypanosoma cruzi e prevenção da transmissão congênita

The objective was to detect Trypanosoma cruzi infection in 32 children in Salta, Argentina, born to 16 chronically infected young women who were treated with benznidazole. Tests were performed to assess the efficacy of treatment after 14 years. At the end of the follow up, 87.5 percent of the women were non-reactive to EIA tests, 62.5 percent to IHA and 43.8 percent to IFA. 62.5 percent of the women were non-reactive according to two or three serological tests. No infected children were detected among the newborns of mothers treated before their pregnancy.

O objetivo foi detectar a infecção do Trypanosoma cruzi em 32 crianças nacidas de 16 jovens mulheres cronicamente infectadas e tratadas com benzinadol, em Salta, Argentina. Testes foram feitos para avaliar a eficácia após 14 anos do tratamento. Ao final do seguimento 87.5 por cento das mulheres foram não reativas ao EIA, 62.5 por cento ao IHA e 43.8 por cento ao IFA. 62.5 por cento das mulheres foram não reativas de acordo a 3 ou 2 testes serológicos. Nenhuma criança infectada foi detectada entre os recém-nascidos de mães tratadas antes da gravidez.

Transmisión vectorial y congénita del Trypanosoma cruzi en Las Lomitas, Formosa / Vectorial and congenital transmission of Trypanosoma cruzi in Las Lomitas, Formosa

La enfermedad de Chagas causada por el Trypanosoma cruzi es una causa importante de morbimortalidad en Latino América. El objetivo de este estudio fue describir las tasas de infestación en las viviendas de cuatro comunidades aborígenes de Las Lomitas (Región del Gran Chaco), Formosa, Argentina; la tasa de infección en la población infantil residente en las mismas, en donantes de sangre y en mujeres embarazadas que asistieron al Hospital de Las Lomitas y la tasa de infección congénita de niños nacidos de mujeres infectadas durante el período de estudio. La tasa de infestación en 172 viviendas evaluadas en 2006 alcanzó el 32%. La prevalencia de infección en 445 personas fue de 17.5% y en menores de 5 años de edad fue 8.6%. La tasa de infección en donantes de sangre alcanzó a 18.6% y en mujeres embarazadas fue 29.1%. La tasa de infección considerada congénita en 47 niños nacidos de mujeres infectadas residentes en viviendas bajo vigilancia fue de 17.0%. El estudio mostró, al momento de su inicio, índices compatibles con transmisión vectorial activa. Después del control vectorial con insecticidas, la tasa de infestación se redujo a 3.3%. El sistema de salud local incorporó procedimientos de prevención primaria y secundaria para evitar nuevos casos e instaurar el tratamiento de la población infectada.

Chagas disease, caused by Trypanosoma cruzi, is a major cause of morbidity and mortality in Latin America. The objective of this study was to describe the rate of infestation in four aboriginal communities in Las Lomitas (Great Chaco Region), Formosa, Argentina; the rate of infection in children residing in these communities, in blood donors and in pregnant women who received care at the Hospital Las Lomitas, as well as the rate of congenital infection in children born to women infected during the study period. The rate of infestation of 172 households evaluated in 2006 reached 32%. Prevalence of infection among 445 people was 17.5% and in children under 5 years old it was 8.6%. The rate of infection reached 18.6% in blood donors and 29.1% in pregnant women. The rate of infection among 47 children born to infected women, and living in residences under vectorial surveillance was 17.0%. These infections were considered as congenital. This study showed indexes compatible with active vectorial transmission at the beginning. After vectorial control with insecticides the infestation rate has been reduced to 3.3%. The local health system has introduced high impact procedures of primary and secondary prevention in order to prevent new cases and to treat infected people.