Treatment Success in Trypanosoma cruzi Infection Is Predicted by Early Changes in Serially Monitored Parasite-Specific T and B Cell Responses

TY - JOUR

T1 - Treatment Success in Trypanosoma cruzi Infection Is Predicted by Early Changes in Serially Monitored Parasite-Specific T and B Cell Responses

AU - Alvarez, María G

AU - Bertocchi, Graciela L

AU - Cooley, Gretchen

AU - Albareda, María C

AU - Viotti, Rodolfo

AU - Perez-Mazliah, Damián E

AU - Lococo, Bruno

AU - Castro Eiro, Melisa

AU - Laucella, Susana A

AU - Tarleton, Rick L

PY - 2016/4/29

Y1 - 2016/4/29

N2 - BACKGROUND: Chagas disease is the highest impact parasitic disease in Latin America. We have proposed that changes in Trypanosoma cruzi-specific immune responses might serve as surrogate indicators of treatment success. Herein, we addressed in a long-term follow-up study whether cure achieved after treatment can be predicted by changes in non-conventional indexes of anti-parasite serological and T cell activities.METHODOLOGY/PRINCIPAL FINDINGS: T. cruzi-specific T cell responses, as measured by interferon-γ ELISPOT and T. cruzi-specific antibodies assessed by ELISA, hemagglutination and immunofluorescence tests as well as by a multiplex assay incorporating 14 recombinant T. cruzi proteins were measured in 33 patients at 48-150 months post-benznidazole treatment. Cure - as assessed by conventional serological tests - was associated with an early decline in T. cruzi-specific IFN-γ-producing T cells and in antibody titers measured by the multiplex serological assay. Changes in the functional status and potential of T. cruzi-specific T cells, indicative of reduced antigen stimulation, provided further evidence of parasitological cure following benznidazole treatment. Patients showing a significant reduction in T. cruzi-specific antibodies had higher pre-therapy levels of T. cruzi-specific IFN-γ- producing T cells compared to those with unaltered humoral responses post-treatment.CONCLUSIONS/SIGNIFICANCE: Monitoring of appropriate immunological responses can provide earlier and robust measures of treatment success in T. cruzi infection.

AB - BACKGROUND: Chagas disease is the highest impact parasitic disease in Latin America. We have proposed that changes in Trypanosoma cruzi-specific immune responses might serve as surrogate indicators of treatment success. Herein, we addressed in a long-term follow-up study whether cure achieved after treatment can be predicted by changes in non-conventional indexes of anti-parasite serological and T cell activities.METHODOLOGY/PRINCIPAL FINDINGS: T. cruzi-specific T cell responses, as measured by interferon-γ ELISPOT and T. cruzi-specific antibodies assessed by ELISA, hemagglutination and immunofluorescence tests as well as by a multiplex assay incorporating 14 recombinant T. cruzi proteins were measured in 33 patients at 48-150 months post-benznidazole treatment. Cure - as assessed by conventional serological tests - was associated with an early decline in T. cruzi-specific IFN-γ-producing T cells and in antibody titers measured by the multiplex serological assay. Changes in the functional status and potential of T. cruzi-specific T cells, indicative of reduced antigen stimulation, provided further evidence of parasitological cure following benznidazole treatment. Patients showing a significant reduction in T. cruzi-specific antibodies had higher pre-therapy levels of T. cruzi-specific IFN-γ- producing T cells compared to those with unaltered humoral responses post-treatment.CONCLUSIONS/SIGNIFICANCE: Monitoring of appropriate immunological responses can provide earlier and robust measures of treatment success in T. cruzi infection.

KW - Adult

KW - Antibodies, Protozoan/blood

KW - B-Lymphocytes/immunology

KW - Chagas Disease/drug therapy

KW - Drug Monitoring/methods

KW - Enzyme-Linked Immunospot Assay

KW - Follow-Up Studies

KW - Humans

KW - Interferon-gamma/metabolism

KW - Middle Aged

KW - Nitroimidazoles/therapeutic use

KW - Prognosis

KW - T-Lymphocytes/immunology

KW - Treatment Outcome

KW - Trypanosoma cruzi/immunology

KW - Young Adult

U2 - 10.1371/journal.pntd.0004657

DO - 10.1371/journal.pntd.0004657

M3 - Article

C2 - 27128444

SN - 1935-2727

VL - 10

JO - PLOS NEGLECTED TROPICAL DISEASES

JF - PLOS NEGLECTED TROPICAL DISEASES

IS - 4

M1 - e0004657

ER -