TABLE I. Reviews of the effect of aetiological treatment in patients with chronic Chagas disease.

	Number of patients	Stage of Chagas disease	Number and type of studies	Follow up	Outcomes
Villar et al. (2002)	756	Chronic phase (asymptomatic)	Five small randomised trials	1-4 years	None of the studies assessed clinically relevant hard outcomes, and two tested ineffective drugs (itraconazole and allopurinol) versus placebo, instead of benznidazole or nifurtimox. Overall, parasite-related outcomes were significantly (statistically) improved, including the seroconversion rate (OR 10.91, 95% CI 6.07-19.58), xenodiagnoses conversion rate (OR 5.37, 95% CI 3.34-8.64), and standardised mean reduction of antibody titres (OR 0.54, 95% CI 0.31-0.84).
Reyes and Vallejo (2005)	714a	Chronic phase (asymptomatic and symptomatic)	One small randomised trial, and six uncontrolled or non-randomised studies	1-23 yearsa	Overall results were insufficient to draw any conclusions.
Pérez-Molina et al. (2009)	1924	Chronic phase (asymptomatic and symptomatic)	Three randomised trials, and six observational studies	1-24 yearsa	Available information comparing benznidazole versus placebo or no treatment showed that children treated with benznidazole had a better tolerance and better parasite-related responses than adults did. More importantly, overall patients treated with benznidazole had a significantly lower risk of clinical events than those treated with placebo (OR 0.29, 95% CI 0.16-0.53).
Villar et al. (2014)	4229	Chronic phase (asymptomatic)	Six randomised trials, and seven observational studies	At least 4 years	Ten studies tested nifurtimox or benznidazole versus placebo and showed potentially important, but imprecise and inconsistent reductions in progression of chronic Chagas cardiomyopathy (four studies, 106 events, OR 0.74, 95% CI 0.32-1.73, I2 = 66%) and mortality (six studies, 99 events, OR 0.55, 95% CI 0.26-1.14, I2 = 48%).

a: calculated from the original studies included in the reviews; OR = odds ratio.