Lower Chagas Disease Mortality Seen With Benznidazole

By Will Boggs MD

November 03, 2018

NEW YORK (Reuters Health) - Benznidazole treatment is associated with lower mortality, reduced parasite counts and reduced markers of cardiomyopathy in patients with Chagas disease, according to results from the NIH SaMi-Trop study.

"Previous studies of specific treatment in early course of the disease have shown parasitological and morbidity benefits, without consistent results in mortality, and a large randomized trial in those with advanced cardiopathy has not shown clinical benefit at all," said Dr. Clareci Silva Cardoso from Federal University of Sao Joao del-Rei, in Divinopolis, Brazil.

"Our study fills a gap in the literature, showing benefit, even with reduction of mortality, related to the use of benznidazole in the early course of disease," she told Reuters Health by email.

Chagas disease, caused by the protozoan Trypanosoma cruzi, is a leading cause of cardiomyopathy and death in Latin America, where an estimated 5.7 million people are infected. The chronic phase of the disease can persist for decades without symptoms or can evolve into the cardiac or intestinal forms of the disease.

Benznidazole has proven antiparasitic efficacy, but its effectiveness during the chronic phase in preventing progression of disease and in reducing mortality remains unclear.

Dr. Cardoso and colleagues investigated whether previous treatment with benznidazole is associated with less advanced cardiac disease, lower prevalence of detectable parasitemia and lower mortality, compared with no treatment, in an observational study of 493 treated patients and 1,320 untreated controls with chronic Chagas disease.

Most patients in both groups had been diagnosed with Chagas disease for more than 10 years before being interviewed.

Overall mortality after two years of follow-up was 6.3%, and was significantly lower in the benznidazole-treated group (2.8%) than in the control group (7.6%), with 63% lower odds of death in the benznidazole group after adjustment for other factors.

The odds of having high age-adjusted NT-proBNP levels were 59% lower and the odds of major ECG abnormalities were 36% lower in the benznidazole group than in the untreated control group, the researchers report in PLoS Neglected Tropical Diseases, online November 1.

T. cruzi PCR was positive in blood samples from 16.6% of benznidazole-treated patients versus 36.4% of controls, a significant 65% reduction in odds after adjustment for other factors.

"Our study reinforces previous evidence that benznidazole should be used in Chagas disease patients without apparent cardiopathy that are younger than 50 years old," Dr. Cardoso said. "Disease management should be comprehensive, including specific antiparasitic treatment in the early course of the disease and treatment of cardiac and digestive complications."

"Chagas disease is mostly a neglected disease, affecting millions of persons around the world," she said. "Chagas disease patients are in general poor persons living in the endemic countries or in the developed world as immigrants. It is a preventable and treatable condition, and the international scientific and medical community could help in the task of discovering new drugs and providing medical treatment to those in need."

Dr. Jignesh Patel from Cedars-Sinai Heart Institute, in Beverly Hills, California, who recently reviewed the diagnosis and management of Chagas cardiomyopathy in the U.S., told Reuters Health by email, "This is an important disease that is increasingly impacting the USA due to migrant populations and even documented local transmission."

"As this is cross-sectional data with an unbalanced population (control patients had more cardiac risk factors including diabetes, hypertension, older, more diuretics, digoxin, and amiodarone), this data emphasizes the importance of (conducting) a prospective randomized controlled trial to assess true benefit, especially in light of the one negative study reported," he said.

"Surveillance, detection, and treatment of this population may have an important impact on long-term survival," said Dr. Patel, who was not involved in the study.

SOURCE: https://bit.ly/2yMRfBI

PLoS Negl Trop Dis 2018.