Treatment and seroconversion in a cohort of children suffering from recent chronic Chagas infection in Yoro, Honduras.

Between 1999-2002, Médécins Sans Frontières-Spain implemented a project seeking to determine the efficacy and safety of benznidazole in the treatment of recent chronic Chagas disease in a cohort of seropositive children in the Yoro Department, Honduras. A total of 24,471 children were screened for Trypanosoma cruzi IgG antibodies through conventional enzyme-linked immunosorbent assays (ELISA) on filter paper. Recombinant ELISA (0.93% seroprevalence) showed 256 initially reactive cases, including 232 confirmed positive cases. Of these, 231 individuals were treated with benznidazole (7.5 mg/kg/day) for 60 days and were followed with a strict weekly medical control and follow-up protocol. At the end of the project, 229 patients were examined by the Honduras Secretariat of Health for post-treatment serological assessments; 88.2% seroconverted after 18 months and 93.9% seroconverted after three years. No differences were found in the seroconversion rates according to age or sex. Most of the side effects of the treatment were minor. These results support the argument that in areas where T. cruzi I is predominant and in areas affected by T. cruzi II, when vector transmission has been interrupted, Chagas disease diagnosis and treatment are feasible, necessary and ethically indisputable.

Treatment and seroconversion in a cohort of children suffering from recent chronic Chagas infection in Yoro, Honduras

Between 1999-2002, Médécins Sans Frontières-Spain implemented a project seeking to determine the efficacy and safety of benznidazole in the treatment of recent chronic Chagas disease in a cohort of seropositive children in the Yoro Department, Honduras. A total of 24,471 children were screened for Trypanosoma cruzi IgG antibodies through conventional enzyme-linked immunosorbent assays (ELISA) on filter paper. Recombinant ELISA (0.93 percent seroprevalence) showed 256 initially reactive cases, including 232 confirmed positive cases. Of these, 231 individuals were treated with benznidazole (7.5 mg/kg/day) for 60 days and were followed with a strict weekly medical control and follow-up protocol. At the end of the project, 229 patients were examined by the Honduras Secretariat of Health for post-treatment serological assessments; 88.2 percent seroconverted after 18 months and 93.9 percent seroconverted after three years. No differences were found in the seroconversion rates according to age or sex. Most of the side effects of the treatment were minor. These results support the argument that in areas where T. cruzi I is predominant and in areas affected by T. cruzi II, when vector transmission has been interrupted, Chagas disease diagnosis and treatment are feasible, necessary and ethically indisputable.

Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Médecins Sans Frontières.

BACKGROUND: Chagas disease (American trypanosomiasis) is a zoonotic or anthropozoonotic disease caused by the parasite Trypanosoma cruzi. Predominantly affecting populations in poor areas of Latin America, medical care for this neglected disease is often lacking. Médecins Sans Frontières/Doctors Without Borders (MSF) has provided diagnostic and treatment services for Chagas disease since 1999. This report describes 10 years of field experience in four MSF programs in Honduras, Guatemala, and Bolivia, focusing on feasibility protocols, safety of drug therapy, and treatment effectiveness. METHODOLOGY: From 1999 to 2008, MSF provided free diagnosis, etiological treatment, and follow-up care for patients <18 years of age seropositive for T. cruzi in Yoro, Honduras (1999-2002); Olopa, Guatemala (2003-2006); Entre Ríos, Bolivia (2002-2006); and Sucre, Bolivia (2005-2008). Essential program components guaranteeing feasibility of implementation were information, education, and communication (IEC) at the community and family level; vector control; health staff training; screening and diagnosis; treatment and compliance, including family-based strategies for early detection of adverse events; and logistics. Chagas disease diagnosis was confirmed by testing blood samples using two different diagnostic tests. T. cruzi-positive patients were treated with benznidazole as first-line treatment, with appropriate counseling, consent, and active participation from parents or guardians for daily administration of the drug, early detection of adverse events, and treatment withdrawal, when necessary. Weekly follow-up was conducted, with adverse events recorded to assess drug safety. Evaluations of serological conversion were carried out to measure treatment effectiveness. Vector control, entomological surveillance, and health education activities were carried out in all projects with close interaction with national and regional programs. RESULTS: Total numbers of children and adolescents tested for T. cruzi in Yoro, Olopa, Entre Ríos, and Sucre were 24,471, 8,927, 7,613, and 19,400, respectively. Of these, 232 (0.9%), 124 (1.4%), 1,475 (19.4%), and 1,145 (5.9%) patients, respectively, were diagnosed as seropositive. Patients were treated with benznidazole, and early findings of seroconversion varied widely between the Central and South American programs: 87.1% and 58.1% at 18 months post-treatment in Yoro and Olopa, respectively; 5.4% by up to 60 months in Entre Ríos; and 0% at an average of 18 months in Sucre. Benznidazole-related adverse events were observed in 50.2% and 50.8% of all patients treated in Yoro and Olopa, respectively, and 25.6% and 37.9% of patients in Entre Ríos and Sucre, respectively. Most adverse events were mild and manageable. No deaths occurred in the treatment population. CONCLUSIONS: These results demonstrate the feasibility of implementing Chagas disease diagnosis and treatment programs in resource-limited settings, including remote rural areas, while addressing the limitations associated with drug-related adverse events. The variability in apparent treatment effectiveness may reflect differences in patient and parasite populations, and illustrates the limitations of current treatments and measures of efficacy. New treatments with improved safety profiles, pediatric formulations of existing and new drugs, and a faster, reliable test of cure are all urgently needed.

Tratamiento etiológico, efectos secundarios y seroconversión en pacientes con infección por el Trypanosoma cruzi. Experiencia de dos proyectos, en Honduras y Guatemala, América Central / No disponible

Entre 1999 y 2006, en Yoro, Honduras, y Olopa, Guatemala, Médicos sin Fronteras implementó dos proyectos en los que se evaluó la seguridad y eficacia del benznidazol en el tratamiento de niños menores de 15 años de edad con infección chagásica crónica reciente. En Honduras fueron tamizados 24.471 niños, de los cuales 232 fueron confirmados positivos (seroprevalencia del 0,93%). Se trataron con benznidazol 231 casos, con seguimiento semanal y evaluaciones serológicas postratamiento. El 88,2% presentaron seroconversión a los 18 meses y el 93,9% a los tres años. Se detectaron efectos adversos en un 50,2% de los pacientes tratados, siendo la gran mayoría leves, con necesidad de suspensión del tratamiento sólo en tres casos. Los más comunes fueron los gastrointestinales (53,4%), seguidos de los cutáneos (25,9%) y neurológicos (20,7%).En Guatemala fueron tamizados 8.927 niños, resultando positivos 124 (prevalencia 1,5%).Sus controles serológicos postratamiento aún están siendo procesados. Los efectos secundarios aparecieron en un 50,8% de los 124 pacientes, siendo más frecuentes los gastrointestinales (25,7%) y cutáneos (25,7%), seguidos de los neurológicos (22,8%). Los resultados de estas dos experiencias evidencian que en Centroamérica el diagnóstico y tratamiento de la infección chagásica crónica reciente son factibles, necesarios para la población infectada y éticamente incuestionables (AU)

Between 1999 and 2006 in Yoro, Honduras, and Olopa, Guatemala, Mèdecins Sans Frontières implemented two projects assessing the safety and efficacy of benznidazol for the treatment of children under fifteen of age with an early chronic phase of Trypanosomacruzi infection. In Honduras 24,471 children were screened, of which 232 were confirmed positive (seroprevalence of 0.93%). 231 patients were treated with weekly follow up and post-treatment serological follow-up. 88.2% of the patients seroconverted at 18 month sand 93.9% at 3 years after treatment. Side effects were present in 50.2% of the patients, but most of these were mild and only three patients had to stop their treatment. The most frequent were gastrointestinals (53.4%), followed by cutaneous (25.9%) and neurological(20.7%) manifestations. In Guatemala 8,927 children were screened, resulting in 124positive cases (prevalence 1.5%). Side effects were reported in 50.8% of the patients and the most common were gastrointestinal (25.7%) and cutaneous (25.7%), followed by neurological (22.8%) manifestations. In Guatemala the verification of the post-treatment seroconversion is currently ongoing. The results of these two treatment experiences show that in Central America both the diagnostic and treatment of T.cruzi infection are feasible, needed and ethically unquestionable (AU)