Chagas disease: criteria of cure and prognosis.

Therapeutic protocols for treating the acute andrecent-chronic phases of Chagas disease wereunanimously agreed upon by participants of theSymposium on the Specific Treatment of ChagasDisease n 1985. However, long-term clinical trialsamong patients treated (cured and uncured) for theindeterminate-chronic and initial-cardiac diseaseforms were recommended to better evaluate thecurative action of drugs and to study the clinicalevolution of the disease. Clinical trials among thesegroups of patients were published because studiesreported low efficacy of benznidazole in chronicdisease (Ferreira 1970, Cancado 1980) while theevaluation of cure was defined as negative parasi-tologic and serologic test results (Cancado &Brener 1979). A decade later, specialists met inBrasilia under the auspices of the Chagas DiseaseControl Program of FNS/MS. Those present wereconcerned about doctors abandoning the specificmedication as well as the scarcity of studies on theimpact of treatment in the evolution of the diseaseamong untreated and treated patients. Therefore,the 1985 recommendations were reaffirmed.Today, the proposal of this International Sym-posium of Chagas Disease to discuss the evolu-tion of knowledge regarding chronic-phase treat-ment is as timely and relevant as ever.Regarding the role of the parasite in maintain-ing the inflammatory process in the chronic phase,recent studies by Kalil et al. (1993) and Higushi(1995) confirm the historic studies of Chagas andTorres and the results of experimental research bySegura et al. (1994) and Andrade et al. (1991). Thelatter has brought new hope to clinicians becausethey reported the interruption of the progressionof lesions in treated mice, and verified the effectof benznidazole in the regression of myocardialinflammatory lesions and in skeletal muscle ofchronically infected animals that presented para-sitologic cure even though serologic tests werepositive.Even though studies of Macedo and Silveira(1987) and Manzullo et al. (1982) reported no ob-served differences in the clinical evolution oftreated patients who had the indeterminate form ofchronic disease, in the 1990s, some investigationshave reported the lack of reliable parameters to de-termine treatment efficacy in the chronic form,which could be responsible for low levels of cureand calls into question the real benefit of treatment.Viotti et al. (1994) followed for an average of eightyears, 131 chronic chagasic patients treated withbenznidazole and 70 untreated subjects with anaverage age of less than 50 years. They reportedthat the treated subjects, independent of negativeserologic or parasitologic results, presented feweralterations in electrocardiograms (4.2%) comparedto the untreated patients (30%), and a lower inci-dence of changes in the clinical stage (2.1% vs17%). In Brazil, Fragata Filho et al. (1995) con-ducted a retrospective study that found that among61% of subjects with negative xenodiagnosis, only7% of treated patients (both cured and uncured)experienced worsened clinical states opposed to14.3% of the placebo group, after seven years offollow-up. In 1997, Coura et al. (1997). Treated26 chronic chagasic patients who had at least twopositive results out of three xenodiagnosis tests andverified that after one year, only 1.8% continuedto have positive xenodiagnosis even though sero-logic tests remained positive.In 1984, Krettli et al. observed that treatedchronic patients had persistently positive serologictests for long periods of time although lytic anti-bodies, which recognize epitopes on the surfaceof living trypomastigotes disappeared early, indi-cating the absence of active infection. Earlier stud-ies reported the possibility that immune memory(Cerisola et al. 1972) was responsible for persis-tently positive serologic tests while parasitemia wasnegative. Viotti (1994) reported that besides theimmune memory, pauciparasitemia, low sensitiv-