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

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Abstract

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.

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Pathogenesis of chronic Chagas heart disease.

José Marin-Neto, Edecio Cunha-Neto, Benedito Maciel … (2007)

Chagas disease remains a significant public health issue and a major cause of morbidity and mortality in Latin America. Despite nearly 1 century of research, the pathogenesis of chronic Chagas cardiomyopathy is incompletely understood, the most intriguing challenge of which is the complex host-parasite interaction. A systematic review of the literature found in MEDLINE, EMBASE, BIREME, LILACS, and SCIELO was performed to search for relevant references on pathogenesis and pathophysiology of Chagas disease. Evidence from studies in animal models and in anima nobile points to 4 main pathogenetic mechanisms to explain the development of chronic Chagas heart disease: autonomic nervous system derangements, microvascular disturbances, parasite-dependent myocardial aggression, and immune-mediated myocardial injury. Despite its prominent peculiarities, the role of autonomic derangements and microcirculatory disturbances is probably ancillary among causes of chronic myocardial damage. The pathogenesis of chronic Chagas heart disease is dependent on a low-grade but incessant systemic infection with documented immune-adverse reaction. Parasite persistence and immunological mechanisms are inextricably related in the myocardial aggression in the chronic phase of Chagas heart disease. Most clinical studies have been performed in very small number of patients. Future research should explore the clinical potential implications and therapeutic opportunities of these 2 fundamental underlying pathogenetic mechanisms.

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Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial.

Marcos Petti, Rodolfo Viotti, Alejandro Armenti … (2006)

Benznidazole is effective for treating acute-stage Chagas disease, but its effectiveness for treating indeterminate and chronic stages remains uncertain. To compare long-term outcomes of patients with nonacute Chagas disease treated with benznidazole versus outcomes of those who did not receive treatment. Clinical trial with unblinded, nonrandom assignment of patients to intervention or control groups. Chagas disease center in Buenos Aires, Argentina. 566 patients 30 to 50 years of age with 3 positive results on serologic tests and without heart failure. The primary outcome was disease progression, defined as a change to a more advanced Kuschnir group or death. Secondary outcomes included new abnormalities on electrocardiography and serologic reactivity. Oral benznidazole, 5 mg/kg of body weight per day for 30 days (283 patients), or no treatment (283 patients). Fewer treated patients had progression of disease (12 of 283 [4%] vs. 40 of 283 [14%]; adjusted hazard ratio, 0.24 [95% CI, 0.10 to 0.59]; P = 0.002) or developed abnormalities on electrocardiography (15 of 283 [5%] vs. 45 of 283 [16%]; adjusted hazard ratio, 0.27 [CI, 0.13 to 0.57]; P = 0.001) compared with untreated patients. Left ventricular ejection fraction (hazard ratio, 0.97 [CI, 0.94 to 0.99]; P < 0.002) and left ventricular diastolic diameter (hazard ratio, 2.45 [CI, 1.53 to 3.95]; P < 0.001) were also associated with disease progression. Conversion to negative results on serologic testing was more frequent in treated patients than in untreated patients (32 of 218 [15%] vs. 12 of 212 [6%]; adjusted hazard ratio, 2.1 [CI, 1.06 to 4.06]; P = 0.034). Nonrandom, unblinded treatment assignment was used, and follow-up data were missing for 20% of patients. Loss to follow-up was more common among patients who were less sick. Two uncontrolled interim analyses were conducted. Compared with no treatment, benznidazole treatment was associated with reduced progression of Chagas disease and increased negative seroconversion for patients presenting with nonacute disease and no heart failure. These observations indicate that a randomized, controlled trial should now be conducted.

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Side effects of benznidazole as treatment in chronic Chagas disease: fears and realities.

Rodolfo Viotti, Carlos Vigliano, Bruno Lococo … (2009)

Chagas disease is caused by a parasite, Trypanosoma cruzi, transmitted primarily by a triatomine insect and affects approximately 8 million people in Latin American countries. The principal aim of the management of the disease is to avoid the development of cardiomyopathy and transmission by blood transfusion, congenital and organ transplants. Currently, benznidazole is the only etiological treatment commercially available for the disease until new and better drugs can be developed and tested. Benznidazole has been used even though it does not have all the conditions of an ideal drug. The efficacy and tolerance of benznidazole is inversely related to the age of the patient, while its side effects are more frequent in elderly patients. The side effects are systematically evaluated only in controlled studies designed for that purpose. However, the true clinical impact of the side effects could be different, considering that the treatment is for a short duration (between 30 and 60 days) and only carried out once. In this article, we discuss the benefits and risks of the treatment with benznidazole from a clinical point of view to be considered for the management of the treatment of chronic adult Chagas disease patients in the current medical practice.

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Author and article information

Journal

Journal ID (publisher-id): mioc

Title: Memórias do Instituto Oswaldo Cruz

Abbreviated Title: Mem. Inst. Oswaldo Cruz

Publisher: Instituto Oswaldo Cruz, Ministério da Saúde (Rio de Janeiro, RJ, Brazil )

ISSN (Print): 0074-0276

ISSN (Electronic): 1678-8060

Publication date (Print and electronic): July 2009

Volume: 104

Issue: suppl 1

Pages: 167-180

Affiliations

[01] orgnameCentro Nacional de Diagnóstico e Investigación de Endemo-epidemias

[02] Buenos Aires orgnameConsejo Nacional de Investigaciones Científicas y Técnicas Argentina

[03] Buenos Aires orgnameInstituto de Efectividad Clínica y Sanitaria Argentina

[05] Buenos Aires orgnameMinisterio de Salud orgdiv1ANLIS Dr. Carlos G. Malbrán orgdiv2Instituto Nacional de Parasitología Dr. Mario Fatala Chaben Argentina

[04] Buenos Aires orgnameHospital Eva Perón de San Martín Argentina