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.Fil: Sosa-Estani, Sergio Alejandro. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Segura, Elsa Leonor. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

El tratamiento etiológico de la enfermedad de Chagas como estrategia de salud pública

El tratamiento etiológico de la infección por Trypanosoma cruzi (enfermedad de Chagas) forma parte de las actividades centrales del Programa Nacional de Chagas. La producción nacional de benznidazol optimizará el acceso y estimulará la práctica de la indicación terapéutica.Fil: Sosa-Estani, Sergio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; 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"; Argentin

Electrocardiographic Abnormalities and Treatment with Benznidazole among Children with Chronic Infection by Trypanosoma cruzi: A Retrospective Cohort Study

Background: Chronic infection by Trypanosoma cruzi could cause heart conduction disturbances. We sought to analyze electrocardiographic abnormalities among children with chronic T. cruzi infection with and without trypanocidal treatment with benznidazole. Methodology/Principal Findings: We studied 111 children 6–16 years of age with asymptomatic chronic T. cruzi infection who were recruited in 1991–1992 in Salta, Argentina. Most children were randomly assigned to benznidazole 5 mg/Kg/day (n = 47) or matching placebo (n = 48) for 60 days. Remaining children (n = 16) received treatment with benznidazole 5 mg/Kg/day open-label. Electrocardiograms were obtained at baseline and in 1995–1996, 1998, 2000 and 2005, and were analyzed using the Buenos Aires method. Among the 94 children with an electrocardiogram at baseline, 8 (8.5%) had electrocardiographic abnormalities, including 4 (4.7%) children with right bundle branch block. Proportion of abnormal electrocardiograms in the full population (n = 111) remained constant over time (media follow-up 8.6 years). Multivariable adjusted prevalence ratios (95% confidence interval [95%CI]) for electrocardiographic abnormalities in 1995–1996, 1998, 2000 and 2005 comparing children treated with benznidazole versus those not treated were 2.76 (0.66, 11.60), 2.33 (0.44, 12.31), 3.06 (0.48, 19.56), and 1.94 (0.33, 11.25), respectively. Among the 86 children with a normal electrocardiogram at baseline, 16 (18.6%) developed electrocardiographic abnormalities during follow-up. The multivariable adjusted hazard ratio for incident electrocardiographic abnormalities comparing children treated with benznidazole versus those not treated was 0.68 (95%CI: 0.25, 1.88). Conclusions/Significance: Electrocardiographic abnormalities are frequent among children with chronic T. cruzi infection. Treatment with benznidazole for 60 days may not be associated with less electrocardiographic abnormalities.Fil: Colantonio, Lisandro Damián. University of Alabama at Birmingahm; Estados Unidos. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Prado, Nilda. 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”; ArgentinaFil: Segura, Elsa Leonor. 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; ArgentinaFil: Sosa-Estani, Sergio Alejandro. 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; Argentin

Frequency of the Congenital Transmission of Trypanosoma cruzi: A Systematic Review and Meta-Analysis

BACKGROUND: Chagas disease is caused by the parasite Trypanosoma cruzi and is endemic in much of Latin America. With increased globalisation and immigration, it is a risk in any country, partly through congenital transmission. The frequency of congenital transmission is unclear. OBJECTIVE: To assess the frequency of congenital transmission of T. cruzi. SEARCH STRATEGY: PubMed, Journals@Ovid Full Text, EMBASE, CINAHL, Fuente Academica and BIREME databases were searched using seven search terms related to Chagas disease or T. cruzi and congenital transmission. SELECTION CRITERIA: The inclusion criteria were the following: Dutch, English, French, Portuguese or Spanish language; case report, case series or observational study; original data on congenital T. cruzi infection in humans; congenital infection rate reported or it could be derived. This systematic review included 13 case reports/series and 51 observational studies. DATA COLLECTION AND ANALYSIS: Two investigators independently collected data on study characteristics, diagnosis and congenital infection rate. The principal summary measure - the congenital transmission rate - is defined as the number of congenitally infected infants divided by the number of infants born to infected mothers. A random effects model was used. MAIN RESULTS: The pooled congenital transmission rate was 4.7% (95% confidence interval: 3.9-5.6%). Countries where T. cruzi is endemic had a higher rate of congenital transmission compared with countries where it is not endemic (5.0% versus 2.7%). CONCLUSIONS: Congenital transmission of Chagas disease is a global problem. Overall risk of congenital infection in infants born to infected mothers is about 5%. The congenital mode of transmission requires targeted screening to prevent future cases of Chagas disease.Fil: Howard, Elizabeth J.. University of Tulane; Estados UnidosFil: Xiong, Xu. University of Tulane; Estados UnidosFil: Carlier, Yves. Université Libre de Bruxelles; BélgicaFil: Sosa-estani, Sergio Alejandro. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud. Instituto Nacional de Parasitología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Buekens, Pierre. University of Tulane; Estados Unido

Therapy of Chagas Disease: Implications for Levels of Prevention

This paper reviews the evidence supporting the use of etiological treatment for Chagas disease that has changed the standard of care for patients with Trypanosoma cruzi infection in the last decades. Implications of this evidence on different levels of prevention as well as gaps in current knowledge are also discussed. In this regard, etiological treatment has shown to be beneficial as an intervention for 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. Timely diagnosis during initial stages would allow for the prescription of appropriate therapies mainly in the primary health care system thus improving chances for a better quality of life. Based on current evidence, etiological treatment has to be considered as an essential public health strategy useful to reduce disease burden and to eliminate Chagas disease altogether

Epidemic outbreak of tegumentary leishmaniasis in Puerto Esperanza, Misiones, 1998

La provincia de Misiones en 1998 notificó 205 casos de leishmaniosis, 98% en la localidad de Puerto Esperanza. El análisis de las fichas clínicas (n:129) de los casos atendidos en Hospital Puerto Esperanza (enero a septiembre 1998) mostró una mayor proporción de lesión cutánea simple (97,2%), localizada en miembros inferiores (72,5%), sin casos de lesión mucosa. Los resultados fueron coherentes con los de la literatura de otros focos epidémicos en Argentina debidos a Leishmania (V.) Braziliensis. No hubo diferencia significativa de incidencia entre sexos, se registró en todos los grupos etarios, y fue susceptible al tratamiento convencional. El foco principal se registró en el Barrio Km1 con un máximo de transmisión en abril de 1998. La intradermoreacción de Montenegro en población general (n:205) no mostró reactividad en asintomáticos. Se capturaron 577 Phlebotominae pertenecientes a 8 especies, las más abundantes fueron Lutzomyia intermedia (79,7%) y Lu. whitmani (10,9%), presentes en peridomicilios de Km1 asociados a selva paranaense residual y vegetación secundaria. Los resultados se discuten en el marco de estrategias posibles de vigilancia y control.The province of Misiones reported 205 leishmaniasis cases during 1998, 98% of them from the locality of Puerto Esperanza. The resports of Puerto Esperanza Hospital (January to September 1998) for leishmanuasis were analysed (n:129). The mainly reported lesion was the single cutaneous ulcer (97,2%), localized in the inferior limbs (72,5%), without any mucosa involvement. The reults are consistent with the knowledge from other Argentinean leishmaniasis foci due to Leishmania (V.) braziliensis. The difference in incidence among sexes was not significant, leishmaniasis was reported in all age groups, and it was suceptible to the convenctional treatment. The main focus was located in Km1 neighbourhood, the transmission peak was during April 1998. The Montenegro skin test among general population (m:205) did not show reactivity among asymptomatic people. The prevalent Phlebotominae species was Lutzomyia intermedia (79,7%) and Lu. whitmani (10,9%), among the 577 individuals belonging to 8 species collected. The Phlebotominae were abundant in periodomestic habitats of Km1 neighbourhoood, close to human dwellings, in places associated with residual primary forest and secondary vegetation. The results are discussed in the fram of surveillance and possible control stategies.Fil: Salomón, Oscar Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Centro Nacional de Diagnóstico e Investigaciones Endemo-epidémicas; ArgentinaFil: Sosa-estani, Sergio Alejandro. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Centro Nacional de Diagnóstico e Investigaciones Endemo-epidémicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Monzani, Ángel S.. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Centro Nacional de Diagnóstico e Investigaciones Endemo-epidémicas; ArgentinaFil: Studer, Catalina. Dirección Nacional de Institutos de Investigación. Administración Nacional de Laboratorios e Institutos de Salud. Centro Nacional de Diagnóstico e Investigaciones Endemo-epidémicas; Argentin

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

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.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; ArgentinaFil: Fabbro, Diana Lucrecia. Universidad Nacional del Litoral; ArgentinaFil: Segura, Elsa Leonor. 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; ArgentinaFil: 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; Argentin

Congenital transmission of Trypanosoma cruzi. Argentina 2002-2014

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

Cultural barriers to effective communication between Indigenous communities and health care providers in Northern Argentina: an anthropological contribution to Chagas disease prevention and control

INTRODUCTION: Ninety percent of the aboriginal communities of Argentina are located in areas of endemic vectorial transmission of Chagas disease. Control activities in these communities have not been effective. The goal of this research was to explore the role played by beliefs, habits, and practices of Pilaga and Wichi indigenous communities in their interaction with the local health system in the province of Formosa. This article contributes to the understanding of the cultural barriers that affect the communication process between indigenous peoples and their health care providers. METHODS: Twenty-nine open ended interviews were carried out with members of four indigenous communities (Pilaga and Wichi) located in central Formosa. These interviews were used to describe and compare these communities' approach to health and disease as they pertain to Chagas as well as their perceptions of Western medicine and its incarnation in local health practice. RESULTS: Five key findings are presented: 1) members of these communities tend to see disease as caused by other people or by the person's violation of taboos instead of as a biological process; 2) while the Pilaga are more inclined to accept Western medicine, the Wichi often favour the indigenous approach to health care over the Western approach; 3) members of these communities do not associate the vector with the transmission of the disease and they have little awareness of the need for vector control activities; 4) indigenous individuals who undergo diagnostic tests and accept treatment often do so without full information and knowledge; 5) the clinical encounter is rife with conflict between the expectations of health care providers and those of members of these communities. CONCLUSION: Our analysis suggests that there is a need to consider the role of the cultural patterning of health and disease when developing interventions to prevent and control Chagas disease among indigenous communities in Northern Argentina. This is especially important when communicating with these communities about prevention and control. These research findings might also be of value to national and provincial agencies in charge of decreasing the rates of Chagas disease among indigenous populations.Fil: Dell Arciprete, Paula. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Braunstein, Jose Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Touris, María Cecilia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C.G. Malbrán”. Instituto Nacional de Parasitología “Dr. M. Fatala Chabén”; ArgentinaFil: Dinardi, Matias Andres. Universidad Nacional de Tres de Febrero; ArgentinaFil: Llovet, Ignacio Diego. Universidad Nacional de Luján. Departamento de Ciencias Sociales; ArgentinaFil: Sosa-Estani, Sergio Alejandro. Instituto de Efectividad Clínica y Sanitaria; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C.G. Malbrán”. Instituto Nacional de Parasitología “Dr. M. Fatala Chabén”; Argentin

Clinical and pharmacological profile of benznidazole for treatment of Chagas disease

Introduction: Chagas disease (CD) is one of the most neglected public health problems in the Americas, where <1% of the estimated 6 million people with the infection have been diagnosed and treated. The goal of treatment is to eliminate the parasite, decrease the probability of cardiomyopathy and other complications during the chronic stage of infection, and interrupt the cycle of disease transmission by preventing congenital infection. Currently, only benznidazole (BZN) and nifurtimox are recognized by the World Health Organization as effective drugs for treatment of CD. In this paper, we provide an overview of the clinical pharmacology of BZN. Areas covered: This review covers the historical background, chemistry, mechanism of action, pharmacokinetics, preclinical research, resistance, clinical research, toxicology, adverse effects, and current regulatory status of BZN. Expert commentary: Ongoing investigations aim to optimize BZN therapy by adjusting the current standard regimen or by combining BZN with new chemical entities. These studies are assessing alternatives that improve safety while maintaining or increasing the efficacy of BZN. Timely diagnosis and antitrypanosomal treatment are critical components of programs to eliminate CD as a public health problem, and can dramatically reduce the heavy burden of morbidity and mortality caused by the disease.Fil: Müller Kratz, Jadel. No especifíca;Fil: García Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Forsyth, Colin J.. No especifíca;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; Argentin