TREATMENT WITH BENZNIDAZOL OF Trypanosoma cruzi INFECTED PATIENTS UNDERGOING THE INDETERMINATE PHASE (IP): EFFECTIVENESS AND TOLERANCE

SOSA-ESTANI S, SEGURA EL

Cartagena, Colombia

Congreso; XVth International Congress for Tropical Medicine and Malaria; 2000

Soc Int Med Trop

In the Americas, there are approximately 16 million patients undergoing the indeterminate (IP) and chronic (CP) phases of Chagas´ disease. There is still the need to count with a safe and effective therapy against the infection by Trypanosoma cruzi. Nifurtimox (1972) and Benznidazol (1974) have been accepted by almost all the Latin American Ministries of Health as the specific chemotherapy against T. cruzi. The goals of specific treatment against T. cruzi infection are to eliminate the parasite from the infected people, to diminish the probability of developing illness (Chagas’ Disease), and to hinder the chain of T. cruzi transmission (Sosa Estani 1993). Nifurtimox and Benznidazol began to be assessed for the acute phase, and later for the IP of the disease. At the end of the 1960s several authors have suggested the convenience of administering the treatment with Nifurtimox in the IP and CP (Cerisola 1969, Boca Tourres 1969, Cançado et al. 1969, Cichero et al. 1969). Twenty years of silence passed, because of the recommendation by several authors (Brener 1972, Cançado, 1972), about the useless of these drugs to treat patients in IP. Coinciding with the beginning of the control of T. cruzi transmission in the Southern Cone of America, we and other authors, worked in Argentina and other regions of Brazil, and have demonstrated through clinical trials, the effect of the specific treatment in the IP and CP. The trials’ results have shown a decrease of serological titers when using total antigens (Viotti 1994, de Andrade 1996, Sosa Estani 1998, 1999); negative serological results, around 65%, using recombinant antigen (Sosa Estani 1998) or a purified mucin-like glycoconjugate from cell-cultured trypomastigotes like antigen (de Andrade 1996, Almeida 1999); negative xenodiagnosis (Sosa Estani 1998, 1999); and a significant decrease of the plasmatic concentration of p-Selectin (Adhesion Molecule) (Laucella 1999). Clinical observations have shown a better cardiac evolution among those patients undergoing IP or CP that received the treatment, than the control patients (Viotti 1994, de Andrade 1996). These results permitted to the Public Health Authorities to introduce changes in the guidelines of the specific treatment of T. cruzi infection, after the meeting of Southern American specialists (Argentina: Sosa Estani & Segura 1999, Brazil: Diaz Gontijo & Costa Rocha, 1998) and in a recent PAHO meeting at Rio de Janeiro (PAHO/WHO 1999). We have observed the effectiveness in a double blind clinical trial performed between 1991-1995 (Sosa Estani 1998) where patients received benznidazol 6 mg/kg/day by 60 days or placebo. In 1998 we evaluated the clinical and serological evolution of 3 groups of patients (Sosa Estani 1999): Benznidazol treated children in 1991 (BTCh=34); placebo treated children in 1991 without benznidazol treatment until 1998, due to non attendance to the convocation for the treatment (PTCh=20); and Benznidazol treated children in 1997 (Placebo 1991) (BTCh97=13). The seroconvertion to non-reactive among BTCh treated increased from 11.4% at 48 months of follow-up to 24.2% at 84 months of follow-up, using total antigen. The frequency of children with at least 2 or 3 non reactive tests was greater among BTCh (51.5%) than BTCh97 (15.4%) and PTCh (5.5%) (p<0.01 DF 2). The frequency of children with non reactive serological result using EIA F29 (DO<0.180) was 69.7% for BTCh 69.7% (23/33), versus 33.3% (11/33) for BTCh97 and PTCh (p<0.005). The xenodiagnosis performed after the follow-up at 84 months was positive in 50.0% (10/20), 7.6% (1/13) and 3.0% (1/33) of PTCh, BTCh97 and BTCh (p<0.001, 2 DF), respectively. During the treatment, patients always were under direct medical supervision. The tolerance during the treatment was good and the patients did not show any serious side effects. In our experience the side effects observed, included dermal or gastrointestinal manifestations, and less frequently we observed peripheral neurotoxicy. Laboratory tests showed normal bilirrubin values, while rarely elevation of transaminases was observed without toxic hepatitis. We have observed leucopenia once among 600 patients treated. Side effects are more frequently observed in adolescents and adults than in children and babies. In all cases, side effects disappear when the dose is diminished or the treatment is suspended. Seven years later the patients did not show any pathologic sign and symptom for the cardiovascular, digestive, neurological and locomotive system associated to the specific treatment in the clinical examination. The effect of the specific treatment in the IP or CP of Chagas´ disease, is a dynamic phenomenon in, which should be consider i. the age of the patient at the moment he/she received the treatment, ii. The time lapsed between treatment and follow-up, iii. The diagnostic tools used (ex. serological studies using total antigens or another) because at the same time negative values are 23% for total AG and 60% for recombinant AG, and iv. the region where the patients were infected. The search for better drugs than the ones available at this time to find a solution for the 16 million infected people is a challenge for the researchers of America. Meanwhile, Benznidazol and Nifurtimox continue to be the best-studied alternative.