B-Cell Responses in Chronic Chagas Disease: Waning of Trypanosoma cruzi-Specific Antibody-Secreting Cells Following Successful Etiological Treatment.

BACKGROUND: A drawback in the treatment of chronic Chagas disease (American trypanosomiasis) is the long time required to achieve complete loss of serological reactivity, the standard for determining treatment efficacy. METHODS: Antibody-secreting cells and memory B cells specific for Trypanosoma cruzi and their degree of differentiation were evaluated in adult and pediatric study participants with chronic Chagas disease before and after etiological treatment. RESULTS: T. cruzi-specific antibody-secreting cells disappeared from the circulation in benznidazole or nifurtimox-treated participants with declining parasite-specific antibody levels after treatment, whereas B cells in most participants with unaltered antibody levels were low before treatment and did not change after treatment. The timing of the decay in parasite-specific antibody-secreting B cells was similar to that in parasite-specific antibodies, as measured by a Luminex-based assay, but preceded the decay in antibody levels detected by conventional serology. The phenotype of total B cells returned to a noninfection profile after successful treatment. CONCLUSIONS: T. cruzi-specific antibodies in the circulation of chronically T. cruzi-infected study participants likely derive from both antigen-driven plasmablasts, which disappear after successful treatment, and long-lived plasma cells, which persist and account for the low frequency and long course to complete seronegative conversion in successfully treated participants.

Sequential combined treatment with allopurinol and benznidazole in the chronic phase of Trypanosoma cruzi infection: a pilot study.

OBJECTIVES: Even though the use of combined drugs has been proved to be effective in other chronic infections, assessment of combined treatment of antiparasitic drugs in human Chagas' disease has not been performed. Herein, a pilot study was conducted to evaluate the tolerance and side effects of a sequential combined treatment of two antiparasitic drugs, allopurinol and benznidazole, in the chronic phase of Trypanosoma cruzi infection. PATIENTS AND METHODS: Changes in total and T. cruzi-specific T and B cells were monitored during a median follow-up of 36 months. Allopurinol was administered for 3 months (600 mg/day) followed by 30 days of benznidazole (5 mg/kg/day) in 11 T. cruzi-infected subjects. RESULTS: The combined sequential treatment of allopurinol and benznidazole was well tolerated. The levels of T. cruzi-specific antibodies significantly decreased after sequential combined treatment, as determined by conventional serology and by a multiplex assay using recombinant proteins. The frequency of T. cruzi-specific interferon-γ-producing T cells significantly increased after allopurinol treatment and decreased to background levels following benznidazole administration in a substantial proportion of subjects evaluated. The levels of total naive (CD45RA + CCR7 + CD62L+) CD4 + and CD8 + T cells were restored after allopurinol administration and maintained after completion of the combined drug protocol, along with a decrease in T cell activation in total peripheral CD4 + and CD8 + T cells. CONCLUSIONS: This pilot study shows that the combination of allopurinol and benznidazole induces significant modifications in T and B cell responses indicative of a reduction in parasite burden, and sustains the feasibility of administration of two antiparasitic drugs in the chronic phase of Chagas' disease.