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.

Sensibilidad in vitro a benznidazol, nifurtimox y posaconazol de cepas de Trypanosoma cruzi de Paraguay / In vitro susceptibility to benznidazole, nifurtimox and posaconazole of Trypanosoma cruzi isolates from Paraguay

Resumen: Introducción. Trypanosoma cruzi, agente causal de la enfermedad de Chagas, exhibe una sustancial heterogeneidad fenotípica y genotípica que puede influir en las variaciones epidemiológicas y clínicas de la enfermedad, así como en la sensibilidad a los fármacos utilizados en el tratamiento. Objetivo. Evaluar la sensibilidad in vitro al benznidazol, el nifurtimox y el posaconazol de 40 cepas clonadas de T. cruzi de Paraguay, con distintos genotipos, huéspedes y localidades de origen. Materiales y métodos. En su estado epimastigote, los parásitos se incubaron en medio de cultivo LIT (Liver Infusion Tryptose) con diferentes concentraciones de cada fármaco en ensayos por triplicado. El grado de sensibilidad se estimó a partir de las concentraciones inhibitorias del 50 y el 90% (IC50 e IC90) y se obtuvieron los valores promedio y la desviación estándar de cada cepa y fármaco. La significación estadística entre grupos se determinó mediante análisis de varianzas con el test no paramétrico de Wilcoxon/Kruskal-Wallis y valores de p<0,05. Resultados. Se observó un amplio rango de respuesta a los fármacos. Se identificaron dos grupos de parásitos (A y B) con diferencias significativas en la sensibilidad al benznidazol (p<0,0001), y tres grupos (A, B, C) en cuanto a la sensibilidad al nifurtimox y el posaconazol (p<0,0001). Conclusiones. En general, las cepas fueron más sensibles al nifurtimox que al benznidazol y el posaconazol. Estas diferencias evidencian la heterogeneidad de las poblaciones de T. cruzi que circulan en Paraguay, lo que debe considerarse en el tratamiento y el seguimiento de las personas afectadas.

Abstract: Introduction: Trypanosoma cruzi, the causative agent of Chagas disease, shows substantial phenotypic and genotypic heterogeneity, which can influence the epidemiological and clinical variations of the disease and the sensitivity to the drugs used in the treatment. Objective: To assess the in vitro susceptibility to benznidazole, nifurtimox, and posaconazole of 40 cloned strains of T. cruzi isolated in Paraguay belonging to different genotypes, hosts, and localities. Materials and methods: We incubated the parasites in their epimastigote stage in LIT culture medium with different concentrations of each drug in triplicate assays. The degree of susceptibility was estimated by the inhibitory concentrations of 50 and 90% (IC50 and IC90) to obtain the average values and the standard deviation for each strain and drug. We determined the statistical significance between groups by analysis of variances with the Wilcoxon/Kruskal-Wallis non-parametric test and values of p<0.05. Results: A wide range of drug response was observed. Two groups of parasites (A and B) were identified as having significant differences in susceptibility to benznidazole (p<0.0001), and three groups (A, B, C) to nifurtimox and posaconazole (p<0.0001). Conclusions: Overall, the isolates were more susceptible to nifurtimox than benznidazole and posaconazole. Such differences highlight the heterogeneity of T. cruzi populations circulating in Paraguay, an aspect to consider in the treatment and follow up of patients.

Herramientas farmacométricas para antichagásicos, aplicadas a estudios fármaco y toxicocinéticos en contexto pediátrico / Pharmacometric tools for antihagasics, applied to drug and toxicokinetic studies in a pediatric context

La enfermedad de Chagas afecta aproximadamente a 10 millones de personas en Sudamérica y 1,5 millones en la Argentina. La transmisión congénita es la más importante en áreas urbanas. Existen dos drogas aprobadas para el tratamiento: nifurtimox (Laboratorios Bayer) y benznidazol (BNZ) (Laboratorios Roche, LAFEPE y Elea) que fueron desarrolladas hace más de 40 años y cuya farmacología y metabolismo en humanos han sido poco estudiados. La información disponible es virtualmente inexistente en niños y mujeres embarazadas. Se busca aportar estudios sistemáticos hacia una farmacoterapéutica racional en niños ya que empíricamente ha demostrado gran efectividad. Se desarrollaron métodos bioanalíticos aplicables a matrices biológicas como plasma, orina y leche materna para las drogas madres y la identificación de metabolitos en muestras de pacientes bajo terapéutica. La farmacocinética poblacional pediátrica descripta aquí para BNZ es concluyente respecto de sus diferencias con la farmacocinética en adultos. Se identificaron tres compuestos presentados como metabolitos del BNZ. La transferencia de dicho fármaco a la leche materna no supone riesgo para el lactante. Estos resultados brindan información para mejorar los protocolos de tratamiento existentes buscando una farmacoterapéutica adaptada a la edad y un uso más seguro de los fármacos en niños y eventualmente en adultos.

Chagas disease affects approximately 10 million people in South America and 1.5 million in Argentina. Congenital transmission is most important in urban areas. There are two drugs approved for treatment: nifurtimox (Bayer) and benznidazole (BNZ) (Roche, LAFEPE, Elea),developed more than 40 years ago. Their pharmacology and metabolism in humans have been seldom studied. The information available on children and pregnant women is virtually non-existent. The aim of this study is to provide systematic studies towards a rational pharmacotherapeutic sin children, which has been empirically proven to be highly effective. Bioanalytical methods were developed for plasma, urine and breast milk for parent drugs and for the identification of their metabolites in samples of patients under treatment. The pediatric population pharmacokinetics described here for BNZ is conclusive about their differences from adult pharmacokinetics. Three compounds presented as BNZ metabolites were identified. The transfer of this drug to the breast milk does not present a risk to the infant. These evidences offer information to improve the existing treatment protocols, seeking a pharmacotherapy adapted to the age and a safer use of the drugs in children and eventually in adults.

A doença de Chagas afeta aproximadamente 10 milhões de pessoas na América do Sul e 1,5 milhão na Argentina. A transmissão congênita é a mais importante em áreas urbanas. Existem dois medicamentos aprovados para o tratamento: nifurtimox (Laboratórios Bayer) e benznidazol (BNZ) (Laboratórios Roche, LAFEPE e Elea), desenvolvidas há mais de 40 anos, e sua farmacologia e seu metabolismo em humanos têm sido pouco estudados. A informação disponível é praticamente inexistente em crianças e mulheres grávidas. O objetivo é fornecer estudos sistemáticos para uma farmacoterapêutica racional em crianças visto que foram comprovadas empiricamente como sendo altamente eficazes. Métodos bioanalíticos aplicáveis a matrizes biológicas como plasma, urina e leite materno para fármacos-mãe e para a identificação de metabólitos em amostras de pacientes em tratamento terapêutico foram desenvolvidos. A farmacocinética da população pediátrica aqui descrita para BNZ é conclusiva em relação às suas diferenças com a farmacocinética de adultos. Três compostos apresentados como metabólitos do BNZ foram identificados. A transferência do referido medicamento para o leite materno não representa risco para o lactente. Essas evidências oferecem informações para melhorar os protocolos de tratamento existentes, buscando uma farmacoterapia adaptada à idade e um uso mais seguro dos medicamentos em crianças e eventualmente em adultos.

Doença de Chagas: do surgimento ao tratamento - revisão da literatura / Chagas Disease: from emergence to treatment - a literature review

Embora a doença de Chagas seja endêmica em certas regiões da América Latina, os fluxos migratórios recentes permitiram sua expansão para áreas onde antes era desconhecida. Mais de 8 milhões de pessoas estão infectadas pelo Trypanosoma cruzi, o que resulta em aproximadamente 10.000 mortes por ano. Esta revisão tem como objetivo fornecer uma compilação sobre os tópicos mais importantes da doença de Chagas em um único trabalho: a descoberta por Carlos Chagas (1909), sua ocorrência, epidemiologia, vetores, via de transmissão, patologia, sinais e sintomas, diagnóstico, e tratamentos, ainda limitado a duas drogas utilizadas há mais de 40 anos: nifurtimox e benzonidazol

Although Chagas disease is endemic in certain regions of Latin America, recent migratory flows have allowed it to expand into areas where it was previously unknown. More than 8 million people are infected with Trypanosoma cruzi, causing around 10,000 deaths a year. This review aims to provide a compilation on the most important topics about the Chagas disease in a single place: its discovery by Carlos Chagas (1909), its occurrence, epidemiology, vectors, transmission route, pathology, signs and symptoms, diagnosis, and current treatments, which is still limited to two drugs for more than 40 years: nifurtimox and benzonidazole

Quantification of Immunoglobulin G against Trypanosoma cruzi in Individuals with Chronic Chagas Disease Treated with Nifurtimox and Evaluated in Prolonged Follow-Up

In the indeterminate chronic period of Chagas disease (ChD) the treatment has not been conclusive, because the serological negativization requires many years. This study aims to evaluate the efficacy of nifurtimox (NF) in the treatment of chronic ChD in prolonged follow-up by serological techniques of indirect immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA) IgG comparing 2 groups of patients, treated and non treated. Mann-Whitney test was performed for ELISA and IFA, with significant difference between the groups (P < 0.05). IgG levels were lower in individuals treated compared with untreated patients, indicating chemotherapeutic efficacy in prolonged follow-up.

Dipyridamole potentiated the trypanocidal effect of nifurtimox and improved the cardiac function in NMRI mice with acute chagasic myocarditis

BACKGROUND As chronic Chagas disease does not have a definitive treatment, the development of alternative therapeutic protocols is a priority. Dipyridamole (DPY) is an alternative to counteract the pathophysiological phenomena involved in Chagas cardiomyopathy. OBJECTIVE To evaluate the therapeutic efficacy of DPY associated with nifurtimox (Nfx) in epimastigote axenic cultures and in mice with acute Chagas disease. METHODS NMRI adult male mice were divided into nine groups: three healthy and six Trypanosoma cruzi-infected groups. Mice received vehicle, Nfx or DPY, alone or combined. The doses assayed were Nfx 10 and 40 mg/kg and DPY 30 mg/kg. The treatment efficacy was evaluated by clinical, electrocardiographic, parasitological, biochemical and histopathological methods. FINDINGS In vitro, DPY and Nfx had a trypanocidal effect with IC50 values of 372 ± 52 and 21.53 ± 2.13 µM, respectively; DPY potentiated the Nfx effect. In vivo, Nfx (40 mg/kg) with or without DPY had a therapeutic effect, which was reflected in the 84-92% survival rate and elimination of parasitaemia and heart tissue amastigotes. Nfx (10 mg/kg) had a subtherapeutic effect with no survival and persistence of amastigotes, inflammation and fibrosis in heart tissue; adding DPY increased the survival rate to 85%, and all tested parameters were significantly improved. MAIN CONCLUSION DPY has a trypanocidal effect in vitro and enhances the Nfx therapeutic effect in an in vivo murine model.

Enfermedad de Chagas del sistema nervioso central en un paciente con SIDA demostrada por métodos cuantitativos moleculares / Chagas disease affecting the central nervous system in a patient with AIDS demonstrated by quantitative molecular methods

Although infrequent, Trypanosoma cruzi reactivation is possible among patients with HIV/AIDS infection that develop a tumor-like or granulomatous lesion in the CNS. We report the case of a 60 years old male patient with HIV/AIDS and low CD4 lymphocytes count with cerebellar symptoms and mild paresis, associated to supra and infratentorial hypodense lesions and positive serology tests both to T. gondii and Trypanosoma cruzi. Empirical therapy against toxoplasmosis was prescribed together with antiretroviral therapy but without a favorable response. Brain Chagas disease was confirmed by quantitative PCR in the CSF but he died despite nifurtimox treatment. Despite its rare occurrence, Chagas disease affecting the CNS is possible among patients with HIV/AIDS infection. Epidemiological exposure, a positive Chagas serological test and the image pattern of brain lesions support the suspicion. Diagnosis can be confirmed by molecular test in CSF samples, including new quantitative methods. Despite an adverse prognosis, specific therapy can be attempted besides antiretroviral treatment.

La reactivación de la infección por Trypanosoma cruzi es un diagnóstico infrecuente pero posible en pacientes con infección por VIH/SIDA y una lesión de tipo tumoral o granulomatosa en el sistema nervioso central. Presentamos el caso clínico de un paciente de 60 años con VIH/SIDA y recuentos bajos de linfocitos CD4, con síntomas cerebelosos y paresia leve, lesiones hipodensas supra e infratentoriales y serología positiva para Toxoplasma gondii y T. cruzi. Se trató empíricamente como una toxoplasmosis cerebral y con terapia antiretroviral, sin respuesta clínica. La enfermedad de Chagas cerebral se confirmó por RPC cuantitativa en el LCR. El paciente falleció a pesar de recibir terapia con nifurtimox. Apoyan la posibilidad de un Chagas cerebral en pacientes con VIH/SIDA, la exposición epidemiológica, la serología positiva y el patrón de distribución de las lesiones en las imágenes. El diagnóstico puede mejorarse con técnicas moleculares cuantitativas en LCR. A pesar de su mal pronóstico, se puede intentar una terapia específica junto al tratamiento antiretroviral.

Experiencia terapéutica en un centro para la enfermedad de Chagas / Therapeutic experience in a Chagas disease center

American Trypanosomiasis or Chagas Disease is a major public health problem, endemic in the American continent since prehistoric times. Its natural course is towardschronicity in the immunocompetent host, often leading to severe cardiopathy or bowelinvolvement. Pharmacologic therapy is restricted to two drugs and only one of themis currently available in Chile. Both have poor effectiveness in the chronic stages ofthe disease and cause frequent adverse reactions. Many physicians avoid their use,despite published evidences about the usefulness. We herein report the experienceof our Center in the treatment of Chronic Chagas Disease in adults using the drugnifurtimox, emphasizing its degree of acceptability and its secondary effects.

Avaliação da associação do quimioterápico benzonidazol a outros fármacos com ação anti-T. cruzi no tratamento da doença de Chagas experimental / Evaluation of the association of benznidazole to other chemotherapeutic drugs with action anti-T cruzi in the treatment of experimental Chagas disease

A doença de Chagas (DC) é causada pelo protozoário hemoflagelado Trypanosoma cruzi. Estima-se que ainda existam 10 milhões de pessoas infectadas na América Latina. Para a quimioterapia específica da DC o benzonidazol (BZ) é o medicamento de escolha. A eficácia terapêutica dos compostos atualmente em uso clínico tem sido questionada, tendo em conta os diferentes índices de cura já registrados na literatura. A associação do BZ, com medicamentos que apresentem um efeito anti-T. cruzi poderá potencializar a ação antiparasitária do mesmo e possivelmente permitirá o uso de doses menores e consequentemente diminuição dos efeitos tóxicos. O objetivo da presente investigação é avaliar o efeito do tratamento com o BZ associado aos medicamentos nifurtimox (NF) e cetoconazol (CETO)...

Chagas’disease (CD) is caused by the hemoflagelate protozoa Trypanosoma cruzi. It is estimated that 10 million infected people are still living in Latin America. For the specific chemotherapy of CD, the Benznidazole (BZ) is the drug of choice. However, the therapeutic efficacy of the compounds now in clinical use is not confirmed, taking into account that different cure rates have been registered. It is possible that the association of BZ with other drugs with an anti-T. cruzi action could improve its anti-parasitic effect, with the use of lower dose and consequent decrease of the toxic effects. The objective of the present investigation is to evaluate the effect of the treatment with BZ in association with the drugs Nifurtimox (NF) and Ketoconazole (CETO)...

Eficacia de nifurtimox para el tratamiento de pacientes con enfermedad de Chagas crónica / Efficacy of nifurtimox for the treatment of chronic Chagas disease

Background: Most Chagas patients belong to the chronic indeterminate stage, in which pharmacological treatment has an inconclusive outcome. Objective: To evaluate the efficacy of nifurtimox treatment in chronic asymptomatic Trypanosoma cruzi infection. Methods: We performed a systematic review and meta-analysis of electronically published literature, with no language, type of study, age or gender restrictions, until September 2010. Studies of chronic asymptomatic Chagas disease patients treated exclusively with nifurtimox were included in the analysis. Treatment efficacy was evaluated using parasitological or serological parameters. Results: Of 463 identified studies, 7 were finally selected: 6 observational studies and 1 randomized clinical trial; 4 of the studies were in adults, 3 in children < 14 years. In 6 studies, outcomes were defined by serological techniques. Summary estimate (log odds) was 0.37 (CI9 -1.32 - 2.07). Conclusions: The analyzed studies gave discordant results. Those might be explained by differences in the populations studied, follow-up periods, diagnostic techniques, and sample size. More studies are necessary to obtain conclusive results about treatment efficacy of nifurtimox in this clinical phase of T. cruzi infection.

Introducción: La mayoría de los pacientes con enfermedad de Chagas se encuentran en fase crónica indeterminada donde los resultados de tratamiento farmacológico no han sido concluyentes. Objetivo: Evaluar la evidencia que apoya la eicacia del tratamiento con nifurtimox en la infección crónica por Trypanosoma cruzi asintomática. Método: Revisión sistemática y meta-análisis de literatura publicada en forma electrónica, sin restricción de lenguaje, tipo de estudio, edad y género, hasta septiembre de 2010. Se incluyeron estudios de pacientes con enfermedad de Chagas crónica asintomáticos que recibieron tratamiento exclusivo con nifurtimox. La eicacia del tratamiento fue evaluada mediante métodos parasitológicos o serológicos. Resultados: Se identiicaron 463 estudios primarios seleccionando inalmente siete: seis observacionales y un ensayo clínico randomizado; cuatro en pacientes adultos y tres en niños bajo14 años de edad. En seis estudios los resultados se midieron mediantes técnicas serológicas. La medida resumen (log de la chance) fue de 0,37 (IC95% -1,32 -2,07). Conclusiones: Los resultados son discordantes. La incertidumbre se maniiesta por las diferencias en las poblaciones estudiadas, periodos de seguimiento, técnicas diagnósticas y tamaño de las muestras. Es necesario realizar nuevos estudios que consideren las fuentes de incertidumbre para obtener resultados concluyentes sobre la eicacia del nifurtimox en esta fase clínica de la infección por T. cruzi.

Metodología UV para la determinación de los antichagásicos Nifurtimox y Benznidazol en sangre / UV methodology for determination of antichagasic drugs Nifurtimox and Benznidazol in blood / Metodologia UV para a determinação dos antichagásicos Nifurtimox e Benznidazol em sangue

El Mal de Chagas es una enfermedad parasitaria endémica en América del Sur y Central. Existen dos fármacos disponibles para el tratamiento médico de la enfermedad, el Nifurtimox (Nfx) y el Benznidazol (Bz). No existen protocolos estandarizados, validados y accesibles en laboratorios regionales para determinar niveles de los antichagásicos en sangre. En este trabajo se presenta un método espectrofotométrico para la determinación de Nfx y Bz en sangre. Los metabolitos en sangre se extraen con columnas Extrelut®. Los extractos se evaporan, se redisuelven en mezclas de metanol/agua y se analizan espectrofotométricamente a 400 nm y a 320 nm para Nfx y Bz, respectivamente. Se cuantifica comparando con soluciones estándar de Nfx o Bz en el solvente. La metodología utilizada fue validada entre 0,5 y 50 ug/mL de sangre para Nfx y entre 0,5 y 100 ug/mL de sangre para Bz. La exactitud, precisión, linealidad y robustez del método fueron satisfactorias. Se aplicó el procedimiento determinando concentraciones sanguíneas post administración de ambos fármacos a ratas.

Chagas' Disease is an endemic parasitic disease in South and Central America. There are two drugs available for medical treatment of the disease, Nifurtimox (Nfx) and Benznidazol (Bz). There are no standardized or accessible protocols in regional laboratorios to determine the levels of antichagasic drugs in blood. A spectrophotometric method for Nfx and Bz determination in blood is presented in the present work. Blood metabolites are extracted through Extrelut® columns. Extracts are evaporated, redissolved in metanol/water mixanalysed by spectrophotometry at 400 nm and 320 nm for Nfx and Bz, respectively. They are quantified comparing with standard Nfx or Bz solutions in the solvent. The methodology used was validated between 0.5 and 50 jg/mL of blood for Nfx, and between 0.5 and 100 jg/mL of blood for Bz. The accuracy, precision, lineality and robustness of the method were satisfactory. The procedure was applied determining blood concentrations after administration of both drugs to rats.

O Mal de Chagas é uma doenga parasitaria endémica na América do Sul e Central. Existem dois fármacos disponíveis para o tratamento médico da doença, o Nifurtimox (Nfx) e o Benznidazol (Bz). Não existem protocolos padronizados, validados e acessíveis em laboratorios regionais para determinarem níveis dos antichagásicos em sangue. Neste trabalho se apresenta um método espectrofotométrico para a determinação de Nfx e Bz em sangue. Os metabólitos em sangue são extraídos com colunas Extrelut®. Os extratos se evaporam, são redissolvidos em misturas de metanol/água e se analisam espectrofotometricamente a 400 nm e a 320 nm para Nfx e Bz, respectivamente. São quantificados comparando com soluções padrão de Nfx ou Bz no solvente. A metodologia utilizada foi validada entre 0,5 e 50 μg/mL de sangue para Nfx e entre 0,5 e 100 μg/mL de sangue para Bz. A exatidão, precisao, linearidade e robustez do método foram satisfatórias. Aplicouse o procedimento determinando concentrações sanguíneas pós- administragao de ambos os fármacos em ratos.

Chagas disease: Present status of pathogenic mechanisms and chemotherapy

There are approximately 7.8 million people in Latin America, including Chile, who suffer from Chagas disease and another 28 million who are at risk of contracting it. Chagas is caused by the flagellate protozoan Trypanosoma cruzi. It is a chronic disease, where 20 percent-30 percent of infected individuals develop severe cardiopathy, with heart failure and potentially fatal arrhythmias. Currently, Chagas disease treatment is more effective in the acute phase, but does not always produce complete parasite eradication during indeterminate and chronic phases. At present, only nifurtimox or benznidazole have been proven to be superior to new drugs being tested. Therefore, it is necessary to find alternative approaches to treatment of chronic Chagas. The current treatment may be rendered more effective by increasing the activity of anti-Chagasic drugs or by modifying the host's immune response. We have previously shown that glutathione synthesis inhibition increases nifurtimox and benznidazole activity. In addition, there is increasing evidence that cyclooxygenase inhibitors present an important effect on T. cruzi infection. Therefore, we found that aspirin reduced the intracellular infection in RAW 264.7 cells and, decreased myocarditis extension and mortality rates in mice. However, the long-term benefit of prostaglandin inhibition for Chagasic patients is still unknown.

Benznidazole biotransformation in rat heart microsomal fraction without observable ultrastructural alterations: comparison to Nifurtimox-induced cardiac effects

Benznidazole (Bz) and Nifurtimox (Nfx) have been used to treat Chagas disease. As recent studies have de-monstrated cardiotoxic effects of Nfx, we attempted to determine whether Bz behaves similarly. Bz reached the heart tissue of male rats after intragastric administration. No cytosolic Bz nitroreductases were detected, although microsomal NADPH-dependent Bz nitroreductase activity was observed, and appeared to be mediated by P450 reductase. No ultrastructurally observable deleterious effects of Bz were detected, in contrast to the overt cardiac effects previously reported for Nfx. In conclusion, when these drugs are used in chagasic patients, Bz may pose a lesser risk to heart function than Nfx when any cardiopathy is present.

Efeito protetor do nifurtimox contra a reativação parasitária em pacientes cronicamente infectados pelo Trypanosoma cruzi e tratados com corticoide em virtude de afecçoes associadas / Nifurtimox as a prophylactic drug to prevent reactivation in chronic chagasic patients treated with corticoid for associated diseases

Pacientes na fase crônica da doença de Chagas foram tratados com corticóide em virtude de afecções associadas e, a fim de tentar coibir reativação da infecção pelo Trypanosoma cruzi, houve uso concomitante do nifurtimox. Levando em conta o verificado em pesquisa anterior, quando corticóide de fato promoveu aumento da parasitemia detectada pelo xenodiagnóstico, pôde ser notado que o nifurtimox mostrou-se apto a evitar a citada acentuação parasitária, podendo tal constatação ser útil em procedimentos assistenciais, quando circunstancialmente estiverem presentes doença de Chagas e imunodepressão.

Patients in the chronic phase of Chagas' disease and receiving corticoid because of concommitant diseases were treated with nifurtimox. We proved in another paper that in the chronic phase of Chagas' disease corticoid use is associated with increased parasitemia, as evaluated by xenodiagnosis. In this study nifurtimox use prevented this increase, and we suggest that in immunocompromised patients with chronic Chagas' disease the use of this drug could be useful.