ABSTRACT
Background: In contrast to adults, Trypanosoma cruzi-infected children have more broadly functional Trypanosoma cruzi-specific T cells, and the total T-cell compartment exhibits fewer signs of immune exhaustion. However, not much is known about the link between immunocompetence and the treatment efficacy for human Chagas disease. Methods: Using cytokine enzyme-linked immunosorbent spot (ELISPOT) polychromatic flow cytometry, cytometric bead assay, multiplex serological assays and quantitative PCR, we evaluated T. cruzi-specific T-cell and antibody immune responses, T-cell phenotypes and parasitemia in children in the early chronic phase of Chagas disease undergoing anti-Trypanosoma cruzi treatment. Results: Treatment with benznidazole or nifurtimox induced a decline in T. cruzi-specific IFN-γ- and IL-2-producing cells and proinflammatory cytokines and chemokines. T-cell responses became detectable after therapy in children bearing T-cell responses under background levels prior to treatment. The total frequencies of effector, activated and antigen-experienced T cells also decreased following anti-T. cruzi therapy, along with an increase in T cells expressing the receptor of the homeostatic cytokine IL-7. Posttreatment changes in several of these markers distinguished children with a declining serologic response suggestive of successful treatment from those with sustained serological responses in a 5-year follow-up study. A multivariate analysis demonstrated that lower frequency of CD4+CD45RA-CCR7-CD62L- T cells prior to drug therapy was an independent indicator of successful treatment. Conclusions: These findings further validate the usefulness of alternative metrics to monitor treatment outcomes. Distinct qualitative and quantitative characteristics of T cells prior to drug therapy may be linked to treatment efficacy.
Subject(s)
Chagas Disease , Chemokines/immunology , Nitroimidazoles/administration & dosage , Parasitemia , T-Lymphocytes/immunology , Trypanosoma cruzi/immunology , Adolescent , Chagas Disease/drug therapy , Chagas Disease/immunology , Chagas Disease/pathology , Child , Child, Preschool , Female , Follow-Up Studies , Humans , Male , Parasitemia/drug therapy , Parasitemia/immunology , Parasitemia/pathology , T-Lymphocytes/pathologyABSTRACT
BACKGROUND: Adults with chronic Trypanosoma cruzi exhibit a poorly functional T cell compartment, characterized by monofunctional (IFN-γ-only secreting) parasite-specific T cells and increased levels of terminally differentiated T cells. It is possible that persistent infection and/or sustained exposure to parasites antigens may lead to a progressive loss of function of the immune T cells. METHODOLOGY/PRINCIPAL FINDINGS: To test this hypothesis, the quality and magnitude of T. cruzi-specific T cell responses were evaluated in T. cruzi-infected children and compared with long-term T. cruzi-infected adults with no evidence of heart failure. The phenotype of CD4(+) T cells was also assessed in T. cruzi-infected children and uninfected controls. Simultaneous secretion of IFN-γ and IL-2 measured by ELISPOT assays in response to T. cruzi antigens was prevalent among T. cruzi-infected children. Flow cytometric analysis of co-expression profiles of CD4(+) T cells with the ability to produce IFN-γ, TNF-α, or to express the co-stimulatory molecule CD154 in response to T. cruzi showed polyfunctional T cell responses in most T. cruzi-infected children. Monofunctional T cell responses and an absence of CD4(+)TNF-α(+)-secreting T cells were observed in T. cruzi-infected adults. A relatively high degree of activation and differentiation of CD4(+) T cells was evident in T. cruzi-infected children. CONCLUSIONS/SIGNIFICANCE: Our observations are compatible with our initial hypothesis that persistent T. cruzi infection promotes eventual exhaustion of immune system, which might contribute to disease progression in long-term infected subjects.
Subject(s)
Chagas Disease/immunology , T-Lymphocytes/immunology , Trypanosoma cruzi/immunology , Adolescent , Adult , CD40 Ligand/analysis , Child , Child, Preschool , Enzyme-Linked Immunospot Assay , Female , Flow Cytometry , Humans , Immunophenotyping , Interferon-gamma/metabolism , Interleukin-2/metabolism , Male , Middle Aged , T-Lymphocytes/chemistry , Tumor Necrosis Factor-alpha/metabolismABSTRACT
Objetivos: Comparar la morbilidad (policitemia, hipotermia, sepsis precoz, convulsiones, hipoglucemia, anemia) y mortalidad entre niños nacidos en su domicilio sin que esto hubiera sido planeado con la de los niños nacidos de parto natural en el Hospital Diego Paroissien. Material métodos: Se revisaron retrospectivamente las historias clínicas de 106 niños nacidos en su domicilio en forma no programada y recibidos vivos en el servicio de Neonatología del Hospital D. Paroissien dentro de las 24 hs posteriores al nacimiento durante el período comprendido entre el 1/1/88 hasta el 31/12/91 inclusive. Estas historias clínicas se compararon con las de un grupo formado por 106 bebes nacidos en el hospital apareados por peso y fecha de nacimiento. Resultados: Se observó mayor frecuencia de policitemia neonatal (22,64 por ciento) en los recién nacidos domiciliarios y de hipotermia al ingreso (28,3 por ciento) vs los niños nacidos en el hospital (p < 0,0001). La mortalidad no presentó diferencias estadísticamente significativas. Conclusiones: Los recién nacidos en domicilio constituyeron una población de alto riesgo (mayor incidencia de policitemia e hipotermia)
Subject(s)
Humans , Male , Female , Infant, Newborn , Home Childbirth/statistics & numerical data , Retrospective Studies , Home Childbirth/adverse effects , Hypothermia/complications , Polycythemia/complicationsABSTRACT
Objetivos: Comparar la morbilidad (policitemia, hipotermia, sepsis precoz, convulsiones, hipoglucemia, anemia) y mortalidad entre niños nacidos en su domicilio sin que esto hubiera sido planeado con la de los niños nacidos de parto natural en el Hospital Diego Paroissien. Material métodos: Se revisaron retrospectivamente las historias clínicas de 106 niños nacidos en su domicilio en forma no programada y recibidos vivos en el servicio de Neonatología del Hospital D. Paroissien dentro de las 24 hs posteriores al nacimiento durante el período comprendido entre el 1/1/88 hasta el 31/12/91 inclusive. Estas historias clínicas se compararon con las de un grupo formado por 106 bebes nacidos en el hospital apareados por peso y fecha de nacimiento. Resultados: Se observó mayor frecuencia de policitemia neonatal (22,64 por ciento) en los recién nacidos domiciliarios y de hipotermia al ingreso (28,3 por ciento) vs los niños nacidos en el hospital (p < 0,0001). La mortalidad no presentó diferencias estadísticamente significativas. Conclusiones: Los recién nacidos en domicilio constituyeron una población de alto riesgo (mayor incidencia de policitemia e hipotermia) (AU)