The international study of insulin and cancer.

www.thelancet.com Vol 376 September 4, 2010 769 in cured individuals, but it is also quite possible that drug-induced reduction (and not necessarily eradication) of the parasite load could be suffi cient to arrest the evolution of the disease and avert its irreversible long-term consequences. Moreover, even if one admits that the sero conversion rate after antitrypano somal treatment in the late chronic phase is quite low (let’s say 10%), for every 10 patients treated, one will be cured, and thousands of infected individuals could derive some clinical benefi t from a 60-day course of treatment. Of note, few therapeutic interventions in medicine have such a favourable number needed to treat. In the “small” trial mentioned by Victor Issa and Edimar Bocchi, 566 chronically infected adults were enrolled. After a median follow-up of 9·8 years, fewer treated patients had progression of disease (hazard ratio 0·24, 95% CI 0·10–0·59; p=0·002) or developed ECG abnormalities (0·27, 0·13–0·57; p=0·001). Other observational studies reported similar favourable results with benznidazole. Addition ally, a meta-analysis of studies on chronically infected patients of any age for whom treatment with benznidazole was compared with placebo or no treat ment showed a signifi cant reduction of clinical events with benznidazole (odds ratio 0·29, 95% CI 0·16–0·53; p<0·0001). Thus, we reaffi rm that anti trypanosomal treatment should always be off ered to all patients with acute or congenital Trypanosoma cruzi infection or reactivated infection, and to chronically infected children or adolescents (class I, level B). In adults aged 19–50 years without advanced heart disease, treatment should generally be off ered (class IIa, level B), and it is optional for those older than 50 years (class IIb, level C). These recom mendations are fully endorsed by a panel of Latin American experts, as well as by the US Centers for Disease Control and Prevention, and were recently included in the US guidelines for treatment of patients with Chagas disease. A multi centre randomised con trolled trial is underway to assess whether trypano cidal therapy reduces mortality and cardiovascular outcomes in 3000 patients (aged 18–75 years) with chronic Chagas heart disease. If the result is positive, the recom mend ations for trypanocidal therapy in this specifi c situation should move to class I (always indicated). If it is negative, to class III (not recommended).