Changes in the immune response after treatment with benznidazole versus no treatment in patients with chronic indeterminate Chagas disease.
Symptomatic chronic Chagas disease affects up to 40% of patients infected with Trypanosoma cruzi. The lack of reliable early markers of cure after therapy hinders disease management and clinical trials with new drugs. We performed a study with 18 months of follow-up to compare changes in immune parameters and T. cruzi-specific immune responses as surrogate markers of response to therapy between patients treated with benznidazole and untreated patients. This was a pilot, open-label, randomised clinical trial of treatment with benznidazole versus no treatment in patients with indeterminate chronic T. cruzi infection. In both groups we investigated changes in T-cell activation, T-cell subpopulations, regulatory T-cell counts, IL6, and sCD14 levels, and T. cruzi-specific immune responses (Th1, Th2, and Th17 responses). Fourteen patients were included in the study (seven in each group). Median age was 35 years (P25-7531-43), 57% were female, and 93% were Bolivian. Benznidazole was administered at 5mg/kg/day for 60days. Three patients discontinued benznidazole owing to adverse reactions and were not evaluated. At the end of the follow-up period, treated patients showed significantly less immune activation and lower regulatory T-cell counts, with an increased Th17 and Th1 response. This randomised pilot clinical trial administering benznidazole to patients with indeterminate chronic Chagas disease brings about changes in the adaptive immunity, leading to a general decrease in inflammatory status. This apparently beneficial response could act as the basis for monitoring new antiparasitic drugs.
Laboratory of Immunovirology, Infectious Diseases Department, University Hospital Ramón y Cajal, Institute Ramón y Cajal for Health Research (IRYCIS), Madrid, Spain. Electronic address: alejandro.vallejo@salud.madrid.org.
Alejandro
A
Vallejo
Tropical Medicine CSUR, Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Institute Ramón y Cajal for Health Research (IRYCIS), Madrid, Spain.
Begoña
B
Monge-Maillo
Laboratory of Cellular Virology. Infectious Diseases Department, University Hospital Ramón y Cajal, Institute Ramón y Cajal for Health Research (IRYCIS), Madrid, Spain.
Carolina
C
Gutiérrez
Tropical Medicine CSUR, Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Institute Ramón y Cajal for Health Research (IRYCIS), Madrid, Spain.
Francesca F
FF
Norman
Tropical Medicine CSUR, Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Institute Ramón y Cajal for Health Research (IRYCIS), Madrid, Spain.
Rogelio
R
López-Vélez
Tropical Medicine CSUR, Infectious Diseases Department, Hospital Universitario Ramón y Cajal, Institute Ramón y Cajal for Health Research (IRYCIS), Madrid, Spain. Electronic address: jperezm@salud.madrid.org.
José A
JA
Pérez-Molina
D000328:Adult; D000368:Aged; D015415:Biomarkers; D014355:Chagas Disease / Q000188:drug therapy* / Q000276:immunology; D002908:Chronic Disease; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009593:Nitroimidazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D014344:Trypanocidal Agents / Q000627:therapeutic use*; D014349:Trypanosoma cruzi / Q000276:immunology*
D015415:Biomarkers; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; C009999:benzonidazole
Chagas disease; Clinical studies; Drug studies; Emerging diseases; Immunology; Infectious diseases; Parasitology; Tropical medicine