BackgroundImmune responses to Mycobacterium tuberculosis antigens could serve as surrogate markers of treatment response.MethodsUsing the T-SPOT.TB assay and frozen peripheral blood mononuclear cells, we enumerated ESAT-6- and CFP-10-specific IFN-γ-producing T cells over time in pulmonary TB patients receiving directly observed treatment. T cell responses (measured as "spot forming cells" or "SFCs") were assessed prior to treatment and at 16 and 24 weeks of treatment.Results58 patients were evaluated, of whom 57 were HIV seronegative. Mean (SD) ESAT-6, CFP-10, and summed RD1 specific SFCs declined from 42.7 (72.7), 41.2 (66.4), and 83.8 (105.7) at baseline to 23.3 (39.4, p = 0.01), 23.2 (29.4, p = 0.18), and 46.5 (59.5, p = 0.02) at completion of 24 weeks of treatment, respectively. Only 10% of individuals with a baseline reactive test reverted to negative at treatment week 24. For the group that was culture positive at completion of 8 weeks of treatment compared to the culture negative group, the incidence rate ratio (IRR) of ESAT-6, CFP-10, and summed RD1 specific SFC counts were, respectively, 2.23 (p = 0.048), 1.51 (p = 0.20), and 1.83 (p = 0.047). Patients with cavitary disease had mean ESAT-6 specific SFC counts that were higher than those without cavitary disease (IRR 2.08, p = 0.034).ConclusionIFN-γ-producing RD1-specific T cells, as measured in the T-SPOT.TB assay, may be directly related to bacterial load in patients undergoing treatment for pulmonary TB. However, high inter-subject variability in quantitative results coupled with failure of reversion to negative of qualitative results in most subjects at treatment completion may limit the utility of this assay as a surrogate marker for treatment efficacy.

This is the first study to demonstrate that ectosomes that are shed from infected neutrophils influence mycobactericidal activity in macrophages in vitro, suggesting that these microvesicles have biological significance. Nevertheless, major gaps in our knowledge of microvesicle biology remain.

BACKGROUND We recently described the Mycobacterium tuberculosis RDRio genotype, a clonally derived sublineage within the Latin American–Mediterranean (LAM) family. Genetic diversity of M. tuberculosis likely affects the clinical aspects of tuberculosis (TB). Prospective studies that address this issue are scarce and remain controversial. OBJECTIVE To determine the association of differential clinical features of pulmonary TB with the RDRio M. tuberculosis etiology. METHODS Culture-proven pulmonary TB patients (n = 272) were clinically evaluated, including history, physical examination, chest X-ray and anti-human immunodeficiency virus serology. Isolates were classified as RDRio or non-RDRio M. tuberculosis by multiplex polymerase chain reaction and further spoligotyped. Clinical and M. tuberculosis genotype data were analyzed. RESULTS RDRio M. tuberculosis caused disease in 26.5% (72/270) of all TB cases. The LAM genotype, of which RDRio strains are members, was responsible for 46.0% of the TB cases. Demographic data, major signs and symptoms, radiographic presentation, microbiological features and clinical outcomes were not significantly different among patients with TB caused by RDRio and non-RDRio strains. CONCLUSIONS Disease caused by M. tuberculosis RDRio strains was not clinically distinctive or more severe than disease caused by non-RDRio strains in this series of TB patients. Larger prospective studies specifically designed to disclose differential clinical characteristics of TB caused by specific M. tuberculosis lineages are needed.

BackgroundThere are controversies regarding the accuracy of the tuberculin skin test (TST) and methods based on the production of interferon gamma by sensitized T cells for the diagnosis of latent tuberculosis infection (LTBI) in pediatrics and immunosuppressed patients. Our objectives are to study TST and ELISPOT/T. SPOT.TB in the diagnosis of LTBI in children and adolescents with JIA undergoing methotrexate, the correlation between both and the sensitivity and specificity of T. SPOT.TB.MethodsThis is an observational prospective longitudinal study in which children and adolescents with JIA undergoing methotrexate therapy were assessed for clinical and epidemiological data for LTBI, in addition to performing TST and T. SPOT.TB at baseline and after 3 and 12months.ResultsThere were 24 patients. The prevalence of LTBI at inclusion was 20.8%, the incidence after initiation of immunosuppressions 26.3% and the prevalence at the end of the study 41.6%. Epidemiological history positive for TB showed a relative risk of 2.0 for the development of LTBI. Only 2 patients had positive T. SPOT.TB but only in one it was useful for detecting early LTBI. T. SPOT.TB presented a sensitivity of 10%, specificity of 92.8%, and low correlation with TST. No patient developed TB disease at a mean follow-up of 47months.ConclusionsWe found a high prevalence of ILTB that doubled with immunosuppression and that epidemiological history was an important relative risk. T. SPOT.TB showed low sensitivity and high specificity, and no superiority over TST. There was low agreement and little influence of immunosuppression on the results of both tests.

In this study were analyzed 526 sera; the patients aged from two days to 65 years old presenting exanthema, which was the most frequent symptom observed, besides fever, adenomegaly, and arthralgia. These sera were negative by enzyme-linked immunosorbent assay (IgM-ELISA)

Objectives: To present an updated review concerning new assays for diagnosing tuberculosis based on in vitro interferon-gamma production by host T cells, and compare them with tuberculin skin test. Sources:A literature review was carried out based on Medline and LILACS databases (2000-2008) searching for the following keywords: tuberculosis, interferon-gamma, quantiFERON, ELISPOT and T-SPOT.TB. Summary of the findings:These new assays proved to have, in general, equal or superior sensitivity and specificity than the tuberculin skin test not only in adults but also in children and immunosuppressed patients for the diagnosis of both latent tuberculosis infection or active disease, with some advantages such as less cross-reactivity as a result of previous BCG vaccination, less influence of anergy and better accuracy in small children. In the United States, these assays have been used instead of the tuberculin skin test and, although still very expensive, the World Health Organization will be making its economic viability a priority. Conclusions:Always having in mind the importance of clinical and epidemiological histories, these new assays based on interferon-gamma release present promising results and should be considered in tuberculosis investigation procedures for all patients, however with a special concern in the risk groups (i.e., children and immunosuppressed patients).J Pediatr (Rio J). 2009;85(3):183-193: Tuberculosis, interferongamma, quantiFERON, ELISPOT, children, immunosuppression. ResumoObjetivo: Apresentar uma revisão atualizada sobre os novos métodos para o diagnóstico da tuberculose baseados na produção in vitro de interferon-gama (IFN-γ) por células T dos pacientes sob investigação, comparando-os com a tradicional prova tuberculínica. (2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008) utilizando as palavras-chave tuberculose, interferon-gama, quantiFERON, ELISPOT e T-SPOT.TB. Fontes dos dados: Revisão de literatura utilizando os bancos de dados MEDLINE e LILACS Síntese dos dados:Esses novos testes mostraram-se, de um modo geral, tão ou mais sensíveis e específicos que a prova tuberculínica, tanto em adultos como em crianças e imunossuprimidos, para o diagnóstico da infecção latente e da doença ativa, apresentando vantagens como a menor interferência da vacinação prévia pelo BCG, menor influência de estados anérgicos e melhor acurácia em crianças menores. Nos Estados Unidos, já estão sendo utilizados em substituição à prova tuberculínica, e apesar dos custos ainda elevados, a Organização Mundial de Saúde vai priorizar a sua viabilidade econômica. Conclusões:Sempre levando em conta a importância da história clínica e epidemiológica, os novos testes baseados na produção de IFN-γ apresentam resultados promissores e deverão ser considerados na investigação de tuberculose em qualquer paciente, mas especialmente nos grupos de risco, como as crianças e os imunossuprimidos.J Pediatr (Rio J). 2009;85(3):183-193

Objectives: To present an updated review concerning new assays for diagnosing tuberculosis based on in vitro interferon-gamma production by host T cells, and to compare them with tuberculin skin test.Sources: A literature review was carried out based on MEDLINE and LILACS databases (2000-2008) searching for the following keywords: tuberculosis, interferon-gamma, quantiFERON, ELISPOT and T-SPOT.TB. Summary of the findings:These new assays proved to have, in general, equal or superior sensitivity and specificity than the tuberculin skin test not only in adults but also in children and immunosuppressed patients for the diagnosis of both latent tuberculosis infection or active disease, with some advantages such as less cross-reactivity as a result of previous BCG vaccination, less influence of anergy and better accuracy in small children. In the United States, these assays have been used instead of the tuberculin skin test and, although still very expensive, the World Health Organization will be making its economic viability a priority. Conclusions:Always having in mind the importance of clinical and epidemiological histories, these new assays based on interferon-gamma release present promising results and should be considered in tuberculosis investigation procedures for all patients, however with a special concern in the risk groups (i.e., children and immunosuppressed patients).J Pediatr (Rio J). 2009;85(3):183-193: Tuberculosis, interferon-gamma, quantiFERON, ELISPOT, children, immunosuppression.

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