Short Report: Benznidazole Efficacy Among Trypanosoma Cruzi-Infected Adolescents After a Six-Year Follow-Up

Abstract

Abstract. Data from a six-year follow-up of Trypanosoma cruzi−infected adolescents enrolled in a randomized, double-blind, clinical trial of benznidazole showed successful chemotherapy in 64.7% (95% confidence interval [CI] ‫ס‬ 50.2−78.7) and 84.7% (95% CI ‫ס‬ 66.8−92.9), respectively, by intention-to treat and by per protocol analysis measured by seronegativity in a chemiluminescent enzyme-linked immunosorbent assay with a purified trypomastigote mucin antigen. No incident case of cardiomyopathy was detected by electrocardiogram assessment in this cohort of adolescents who had been infected in childhood. The persistent and consistently long-term negative serologic reactions suggest the absence of the parasite in the treated patients and reinforces the recommendation of early benznidazole chemotherapy for T. cruzi-infected infants as a public health policy in endemic areas.While the elimination of Chagas disease has been considered a reasonable public health goal, 1 controversies remain about the efficiency of trypanocidal chemotherapy, especially in chronic asymptomatic individuals. Currently, there is a need to find appropriate drugs or therapeutic regimens with existing drugs that can be used in Trypanosoma cruzi−infected individuals to prevent development of severe clinical forms of Chagas disease. In a previous randomized, double-blind, clinical trial carried out among infants in Brazil, we showed that a 60 day-course of benznidazole in patients with early chronic infections with T. cruzi was safe and effective in 55.8% of the children, as shown by seronegative conversion of specific antibodies after a 38-month follow-up, when compared with the placebo group.2 In addition, a short-term effect of benznidazole on the prevention of cardiac damage was also observed. A similar efficacy (62%) for benznidazole was also observed in a study conducted in Argentinean children.

Ergosterol biosynthesis and drug development for Chagas disease

“…However, their efficacies vary according to geographical area, most likely due to differences in drug susceptibility among different T. cruzi strains (Filardi & Brener 1987, Murta et al 1998, Kirchhoff 1999. Moreover, it has been reported in the last 15 years that BZN also exhibits significant curative activity in those with recent onset (up to a few years) of chronic disease; 60-70% of radical parasitological cures have been observed among children up to 14 years of age in Brazil and Argentina (de Andrade et al 1996, Andrade & Zicker 1997, Sosa Estani et al 1998, Sosa Estani & Segura 1999, Andrade et al 2004). On the other hand, other studies in patients of the same age range treated with either BZN or NFX contradict these conclusions (Silveira et al 2000, Solari et al 2001.…”

Usefulness of PCR-based assays to assess drug efficacy in Chagas disease chemotherapy: value and limitations

“…However, their efficacies vary according to the geographical area, probably due to differences in drug susceptibility among different T. cruzi strains, a fact correlated with the biological characteristics of the parasite (Andrade et al 1992, Cançado 1999. In the past decade, benznidazole has been reported to have significant curative activity in recent chronic disease (up to a few years post-infection), with up to 60% parasitological cure rates observed in infected children of Argentina and Brazil treated with this compound (Sosa-Estani & Segura 1999, Andrade et al 2004. Similar results were obtained in Chile with nifurtimox (Solari et al 2001).…”

Trypanosoma cruzi and Chagas' Disease in the United States

“…Several follow-up studies suggest that the earlier in life that children are treated, the higher the rate of reversion to negative serology (6,281). Together with growing clinical experience across Latin America, these studies revolutionized management of children with Chagas' disease, making early diagnosis and antitrypanosomal drug therapy the standard of care throughout the region (177,311).…”