Trypanocide treatment among adults with chronic Chagas disease living in Santa Fe city (Argentina), over a mean follow-up of 21 years: parasitological, serological and clinical evolution

Abstract

The efficacy of treatment with nifurtimox and/or benznidazole among adults with chronic Chagas disease with no previous electrocardiographic disturbances was evaluated over a mean follow-up of 21 years, by means of conventional serology, xenodiagnosis, clinical examination, electrocardiograms and chest X-ray. One hundred and eleven patients, between 17 and 46 years old, were studied: 54 underwent treatment (nifurtimox 27, benznidazole 27) and 57 remained untreated (control group). Xenodiagnosis was performed on 65% of them: 36/38 of the treated and 9/34 of the untreated patients had previous positive xenodiagnosis. Post-treatment, 133 xenodiagnoses were performed on 41 patients, all resulting negative. In the control group, 29 xenodiagnoses were performed on 14 patients; 2 resulted positive. Sera stored during the follow-up were simultaneously analyzed through conventional serology tests (IHA; DA-2ME; IIF). The serological evolution in the treated group was: a) 37% underwent negative seroconversion (nifurtimox 11, benznidazole 9); b) 27.8% decreased titers (nifurtimox 9, benznidazole 6), 9 showed inconclusive final serology (nifurtimox 7, benznidazole 2); c) 35.2% remained positive with constant titers (nifurtimox 7; benznidazole 12). The control group conserved the initial antibody levels during the follow-up. In the clinical evolution, 2/54 (3.7%) of the treated and 9/57 (15.8%) of the untreated patients showed electrocardiographic disturbances attributable to Chagas myocardiopathy, with a statistically relevant difference (p<0.05). Treatment caused deparasitation in at least 37% of the chronically infected adults and a protective effect on their clinical evolution.

Humoral Immune Response against P2β from Trypanosoma cruzi in Persons with Chronic Chagas Disease: Its Relationship with Treatment Against Parasites and Myocardial Damage

“…Consistent with findings in other reports [23][24][25] and extending our earlier findings, 26 treatment for infection with T. cruzi decreased specific antibody production, and in some patients led to a persistent negative serologic results and reduced disease progression. In addition, results of xenodiagnosis also became negative in persons treated with NIF or BZL.…”

2 nd Brazilian Consensus on Chagas Disease, 2015

“…For individuals with Chagas disease aged 19-50 years with no recent documented infection, antiparasitic treatment should be considered on an individual basis, whether in ICF (120) (252) (Class IIa, level of evidence B) or in the determined chronic form, without advanced cardiopathy (42) (120) (252) (295) (296) (297) (298) (Class IIb, level of evidence C). Specifically, treatment of chronically infected women of childbearing age, when provided before pregnancy, can reduce congenital transmission (104) (109) .…”

Chagas heart disease: pathophysiologic mechanisms, prognostic factors and risk stratification

“…In contrast, whether one or more of the autoimmune events described in experimental models and human cases of Chagas disease can contribute to, or aggravate, this pathology, has been more controversial and difficult to validate (Tarleton 2003a, b). The evidence supporting this viewpoint can be summarised as follows: (i) in recent years, more powerful and sensitive methods of parasite detection, such as immunohistochemistry and polymerase chain reaction (PCR), have demonstrated a higher frequency of T. cruzi antigens and parasite DNA in chronic lesions; also, a significant correlation between parasite persistence and tissue inflammation has been clearly documented; therefore, the supposed absence of parasites at or near sites of disease (the mainstay of the autoimmune theory), probably reflects the use of insensitive histological techniques in past decades (Tarleton & Zhang 1999); (ii) interventions that lessen the parasite burden, such as aetiologic treatment with benznidazole or nifurtimox, reduce clinical disease in humans (Viotti et al 2006, Fabbro et al 2007) and experimental animals (Andrade et al 1991, Garcia et al 2005, in contrast to immunosuppressive treatments/situations that clearly increase T. cruzi parasitemia (Rassi et al 1997) and usually aggravate the inflammatory response (Sartori et al 2007); (iii) reinfection or continued exposure (due to continued residence in areas of active transmission) seems to increase the parasite load and disease severity in experimental models and in human cases (Bustamante et al 2002, Storino et al 2002; (iv) although anti-self responses are encountered in T. cruzi infection, the nature of anti-self antibodies in experimental and human chronic Chagas disease is heterophilic, with a poor correlation with the heart lesions (i.e., there is no direct and definitive evidence that the immune reactions against the mimicked auto-antigens are actually pathogenic) (Tarleton 2003a, b); and (v) data supporting the direct involvement of either molecular mimicry or polyclonal activation in the pathogenesis of myocardial lesions ascribed to T. cruzi infection are sparse and inconclusive.…”