Trypanocidal drugs for chronic asymptomatic Trypanosoma cruzi infection.
BACKGROUND
Prior guidelines stated that trypanocidal therapy should not be used for treating chronic asymptomatic Trypanosoma cruzi infections. However, the recent availability of clinical trials reporting high rates of parasitologic cure in children with early chronic T. cruzi infection have produced changes of these recommendations in some countries. Because of the uncertainty regarding best treatment for this stage of T. cruzi infections, the literature was reviewed systematically for a synthesis of the available evidence.


OBJECTIVE
To assess the effects of trypanocidal therapy for chronic asymptomatic T. cruzi infection.


METHODS
We searched The Cochrane Controlled Trials Register (Issue 1, 2000), MEDLINE (start-Nov 1999), EMBASE (start - Feb 2000), LILACS (start - Feb 2000) and the Tropical Diseases Research Division of WHO database (Start - Feb 2000). Reference lists of articles were searched for relevant material.


METHODS
Published RCTs of trypanocidal therapy for people with chronic, asymptomatic T. cruzi infections


METHODS
Two reviewers independently screened papers for inclusion criteria, quality assessment and data extraction. Forms were used to collect data. Reviewers resolved differences by discussion then a third reviewer if necessary.


RESULTS
Of 43 papers assessed for inclusion, five RCTs (total population=756) met the inclusion criteria. The quality of the trials was rated as low (n=3) or intermediate (n=2). Two RCTs tested benznidazole in school children and three tested different agents in adults. The Odds Ratios and their 95%CI (Fixed models) were: Incidence of ECG abnormalities: 0.41 (0.09, 1.85); Negative seroconversion (AT ELISA): 10.91 (6.07, 19.58); Negative xenodiagnosis during the follow up: 5.37 (3.34, 8.64); Standardised mean reduction of antibody titres: 0.54 (0.31, 0.84). Nitroimidazolic derivatives substantially and significantly modified parasite-related outcomes compared to placebo. Other agents showed borderline or not significant effect.


CONCLUSIONS
Despite major public health importance, trypanocidal.therapy for chronic asymptomatic T. cruzi infection has been tested in few, small size RCTs which were designed to assess parasitic-related, but not clinical outcomes. Therefore, the potential of trypanocidal therapy to prevent Chagas' disease among asymptomatic, chronically infected subjects is promising, but remains to be evaluated. trypanocidal therapy, particularly nitroimidazolic derivatives given to children or adults with positive xenodiagnosis improve parasite-related outcomes. The large contrast between the burden of Chagas disease and the existing evidence on its prevention points the need to test these or newer agents in more and larger RCTs that include clinical endpoints.
Villar
J C
JC
Department of Medicine, Population Health Institute, McMaster University, 237 Barton St East, Hamilton, Ontario, Canada, L8L 2X2. juan@ccc.mcmaster.ca
Marin-Neto
J A
JA
Ebrahim
S
S
Yusuf
S
S
D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy*; D002908:Chronic Disease; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D014344:Trypanocidal Agents / Q000627:therapeutic use*; D014349:Trypanosoma cruzi
D014344:Trypanocidal Agents