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

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

Congenital Chagas Disease: Recommendations for Diagnosis, Treatment and Control of Newborns, Siblings and Pregnant Women

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

An unusual hantavirus outbreak in southern Argentina: person-to-person transmission? Hantavirus Pulmonary Syndrome Study Group for Patagonia.

Hantavirus pulmonary syndrome is a rodent-borne zoonosis first recognized in the United States in 1993. Person-to-person transmission has not been reported; however, in the outbreak of 20 cases reported here, epidemiologic evidence strongly suggests this route of transmission

Lineamientos básicos del tratamiento etiológico de enfermedad de Chagas

La enfermedad de Chagas, endémica en 21 países de las Américas, afecta a entre 6 y 8 millones de personas en la Región1. Menos del 1% de esos pacientes son diagnosticados y tratados adecuadamente. Para superar las barreras de accesibilidad al diagnóstico y tratamiento, se propuso trabajar en la difusión de conceptos que el personal de salud debe conocer y mejorar.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 ; ArgentinaFil: Altcheh, Jaime Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; ArgentinaFil: Riarte, Adelina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología ; ArgentinaFil: Freilij, Hector León. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez". Servicio de Parasitología y Chagas; ArgentinaFil: Fernández, Marisa Mariel. 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 ; ArgentinaFil: Lloveras, Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Pereiro, Ana. Fundación Mundo Sano; ArgentinaFil: Castellano, Luis Gerardo. Organización Panamericana de la Salud; Estados UnidosFil: Salvatella, Roberto. Organización Panamericana de la Salud; UruguayFil: Nicholls, Rubén S.. Organización Panamericana de la Salud; BrasilFil: Grupo de trabajo. No especifica

Efficacy and safety assessment of different dosage of benznidazol for the treatment of Chagas disease in chronic phase in adults (MULTIBENZ study): Study protocol for a multicenter randomized Phase II non-inferiority clinical trial

Background: Chagas disease (CD) continues to be a neglected infectious disease with one of the largest burdens globally. Despite the modest cure rates in adult chronic patients and its safety profile, benznidazole (BNZ) is still the drug of choice. Its current recommended dose is based on nonrandomized studies, and efficacy and safety of the optimal dose of BNZ have been scarcely analyzed in clinical trials.Methods/design: MULTIBENZ is a phase II, randomized, noninferiority, double-blind, multicenter international clinical trial. A total of 240 patients with Trypanosoma CD in the chronic phase will be recruited in four different countries (Argentina, Brazil, Colombia, and Spain). Patients will be randomized to receive BNZ 150 mg/day for 60 days, 400 mg/day for 15 days, or 300 mg/day for 60 days (comparator arm). The primary outcome is the efficacy of three different BNZ therapeutic schemes in terms of dose and duration. Efficacy will be assessed according to the proportion of patients with sustained parasitic load suppression in peripheral blood measured by polymerase chain reaction. The secondary outcomes are related to pharmacokinetics and drug tolerability. The follow-up will be 12 months from randomization to end of study participation. Recruitment was started in April 2018.Conclusion: This is a clinical trial conducted for the assessment of different dose schemes of BNZ compared with the standard treatment regimen for the treatment of CD in the chronic phase. MULTIBENZ may help to clarify which is the most adequate BNZ regimen in terms of efficacy and safety, predicated on sustained parasitic load suppression in peripheral blood.Fil: Molina Morant, D.. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; EspañaFil: Fernández, M. L.. 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: Bosch Nicolau, P.. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; EspañaFil: Sulleiro, E.. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; EspañaFil: Bangher, M.. Instituto de Cardiologia de Corrientes Juana Francisca Cabral.; ArgentinaFil: Salvador, F.. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; EspañaFil: Sanchez Montalva, A.. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; EspañaFil: Ribeiro, A.L.P.. Universidade Federal de Minas Gerais; BrasilFil: De Paula, A.M.B.. Universidad Federal de Montes Claros; BrasilFil: Eloi, S.. Universidade Federal de Minas Gerais; BrasilFil: Oliveira Correa, Ronaldo. Fundación Oswaldo Cruz; BrasilFil: Villar, J. C.. Instituto de Cardiología; ColombiaFil: 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; ArgentinaFil: Molina, I.. Universidad Autónoma de Barcelona. Hospital Vall D' Hebron; Españ