Clinical and pharmacological profile of benznidazole for treatment of Chagas disease

Abstract

Chagas disease (CD) is one of the most neglected public health problems in the Americas, where <1% of the estimated 6 million people with the infection have been diagnosed and treated. The goal of treatment is to eliminate the parasite, decrease the probability of cardiomyopathy and other complications during the chronic stage of infection, and interrupt the cycle of disease transmission by preventing congenital infection. Currently, only benznidazole (BZN) and nifurtimox are recognized by the World Health Organization as effective drugs for treatment of CD. In this paper, we provide an overview of the clinical pharmacology of BZN. Areas covered: This review covers the historical background, chemistry, mechanism of action, pharmacokinetics, preclinical research, resistance, clinical research, toxicology, adverse effects, and current regulatory status of BZN. Expert commentary: Ongoing investigations aim to optimize BZN therapy by adjusting the current standard regimen or by combining BZN with new chemical entities. These studies are assessing alternatives that improve safety while maintaining or increasing the efficacy of BZN. Timely diagnosis and antitrypanosomal treatment are critical components of programs to eliminate CD as a public health problem, and can dramatically reduce the heavy burden of morbidity and mortality caused by the disease.

Chagas Disease in the United States: a Public Health Approach

“…IgM TESA-blot showed sensitivity of 58% compared to a consensus definition of infection, and 80% compared to PCR in congenitally infected infants in Bolivia; in these two analyses, the specificity was 98% and 94% respectively (194,236) (1,250). Benznidazole is a prodrug, which requires metabolism by parasite enzymes to become active; metabolites appear to act through multiple mechanisms to interrupt T. cruzi glutathione and trypanothione pathways (250). Dermatologic side effects are frequent, and consist of rashes and photosensitization (251,252).…”

“…PCR has recently been IgM-based assays have been evaluated for the diagnosis of acute T. cruzi infection, with a special focus on use for congenitally infected infants in settings where molecular assays are not available (233). IgM TESA-blot showed sensitivity of 58% compared to a consensus definition of infection, and 80% compared to PCR in congenitally infected infants in Bolivia; in these two analyses, the specificity was 98% and 94% respectively (194,236) (1,250). Benznidazole is a prodrug, which requires metabolism by parasite enzymes to become active; metabolites appear to act through multiple mechanisms to interrupt T. cruzi glutathione and trypanothione pathways (250).…”

WHF IASC Roadmap on Chagas Disease

“…While positive PCR during the first 24 months after treatment is indicative of therapeutic failure, sensitivity is variable [97,98]. Post-treatment sero-negativization can take several years, depending on: (i) the age of the individual at time of treatment; (ii) the time elapsed between treatment and follow-up, and (iii) the region where the individual was infected [98,99,100]. Although complete sero-negativization can be obtained within five years in more than 70% of children treated, this rate only reaches about 30% in adult patients after roughly 20 years of follow-up ( Figure 10) [48,101,102,103,104].…”

MicroRNAs: Biological Regulators in Pathogen–Host Interactions

“…Benznidazole and nifurtimox, the treatments that are currently available, began to be used over 40 years ago. Moreover, both drugs have several limitations, such as long treatment times and being primarily effective for acute forms of disease [111]. Thus, new effective therapies and prognosis markers are required.…”