Changes in Trypanosoma cruzi-specific immune responses after treatment: surrogate markers of treatment efficacy

TY - JOUR

T1 - Changes in Trypanosoma cruzi-specific immune responses after treatment

T2 - surrogate markers of treatment efficacy

AU - Laucella, Susana A

AU - Mazliah, Damián Pérez

AU - Bertocchi, Graciela

AU - Alvarez, María G

AU - Cooley, Gretchen

AU - Viotti, Rodolfo

AU - Albareda, María C

AU - Lococo, Bruno

AU - Postan, Miriam

AU - Armenti, Alejandro

AU - Tarleton, Rick L

PY - 2009/12/1

Y1 - 2009/12/1

N2 - BACKGROUND: As many as 20 million people are living with Trypanosoma cruzi infection in Latin American, yet few receive any treatment. The major limitation in developing and evaluating potential new drugs for their efficacy is the lack of reliable tests to assess parasite burden and elimination.METHODS: Adults volunteers with chronic T. cruzi infection were evaluated clinically and stratified according to the Kuschnir classification. Individuals with group 0 and group 1 clinical status were treated with benznidazole (5 mg/kg per day for 30 days). The changes in T. cruzi-specific T cell and antibody responses, as well as in clinical status, were measured periodically over the 3-5-year follow-up period and were compared with pretreatment conditions and with values in an untreated control group.RESULTS: The frequency of peripheral interferon (IFN)-gamma-producing T cells specific for T. cruzi declined as early as 12 months after benznidazole treatment and subsequently became undetectable in a substantial proportion of treated subjects. In addition, decreases in antibody responses to a pool of recombinant T. cruzi proteins also decreased in many of these same subjects. The shift to negative IFN-gamma T cell responses was highly associated with an early increase in IFN-gamma-producing T cells with phenotypic features of effector/effector memory cells in a subset of subjects. Benznidazole treatment also resulted in an increase in naive and early differentiated memory-like CD8(+) T cells in a majority of subjects.CONCLUSIONS: Benznidazole treatment during chronic Chagas disease has a substantial impact on parasite-specific immune response that is likely indicative of treatment efficacy and cure.

AB - BACKGROUND: As many as 20 million people are living with Trypanosoma cruzi infection in Latin American, yet few receive any treatment. The major limitation in developing and evaluating potential new drugs for their efficacy is the lack of reliable tests to assess parasite burden and elimination.METHODS: Adults volunteers with chronic T. cruzi infection were evaluated clinically and stratified according to the Kuschnir classification. Individuals with group 0 and group 1 clinical status were treated with benznidazole (5 mg/kg per day for 30 days). The changes in T. cruzi-specific T cell and antibody responses, as well as in clinical status, were measured periodically over the 3-5-year follow-up period and were compared with pretreatment conditions and with values in an untreated control group.RESULTS: The frequency of peripheral interferon (IFN)-gamma-producing T cells specific for T. cruzi declined as early as 12 months after benznidazole treatment and subsequently became undetectable in a substantial proportion of treated subjects. In addition, decreases in antibody responses to a pool of recombinant T. cruzi proteins also decreased in many of these same subjects. The shift to negative IFN-gamma T cell responses was highly associated with an early increase in IFN-gamma-producing T cells with phenotypic features of effector/effector memory cells in a subset of subjects. Benznidazole treatment also resulted in an increase in naive and early differentiated memory-like CD8(+) T cells in a majority of subjects.CONCLUSIONS: Benznidazole treatment during chronic Chagas disease has a substantial impact on parasite-specific immune response that is likely indicative of treatment efficacy and cure.

KW - Adult

KW - CD8-Positive T-Lymphocytes/immunology

KW - Chagas Disease/drug therapy

KW - Flow Cytometry

KW - Humans

KW - Interferon-gamma/metabolism

KW - Interleukin-2/metabolism

KW - Middle Aged

KW - Nitroimidazoles/therapeutic use

KW - T-Lymphocytes/immunology

KW - Treatment Outcome

KW - Trypanocidal Agents/therapeutic use

KW - Trypanosoma cruzi/immunology

KW - Young Adult

U2 - 10.1086/648072

DO - 10.1086/648072

M3 - Article

C2 - 19877967

SN - 1058-4838

VL - 49

SP - 1675

EP - 1684

JO - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

IS - 11

ER -