Tuberculin skin test and ELISPOT/T. SPOT.TB in children and adolescents with juvenile idiopathic arthritis.

BACKGROUND: There 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. METHODS: This 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. RESULTS: There 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. CONCLUSIONS: We 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.

The challenge of pediatric tuberculosis in face of new diagnostic techniques.

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. METHODS: 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. RESULTS: 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).

Discovery of a novel Mycobacterium tuberculosis lineage that is a major cause of tuberculosis in Rio de Janeiro, Brazil.

The current study evaluated Mycobacterium tuberculosis isolates from Rio de Janeiro, Brazil, for genomic deletions. One locus in our panel of PCR targets failed to amplify in approximately 30% of strains. A single novel long sequence polymorphism (>26.3 kb) was characterized and designated RD(Rio). Homologous recombination between two similar protein-coding genes is proposed as the mechanism for deleting or modifying 10 genes, including two potentially immunogenic PPE proteins. The flanking regions of the RD(Rio) locus were identical in all strains bearing the deletion. Genetic testing by principal genetic group, spoligotyping, variable-number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR), and IS6110-based restriction fragment length polymorphism analysis cumulatively support the idea that RD(Rio) strains are derived from a common ancestor belonging solely to the Latin American-Mediterranean spoligotype family. The RD(Rio) lineage is therefore the predominant clade causing tuberculosis (TB) in Rio de Janeiro and, as indicated by genotypic clustering in MIRU-VNTR analysis, the most significant source of recent transmission. Limited retrospective reviews of bacteriological and patient records showed a lack of association with multidrug resistance or specific risk factors for TB. However, trends in the data did suggest that RD(Rio) strains may cause a form of TB with a distinct clinical presentation. Overall, the high prevalence of this genotype may be related to enhanced virulence, transmissibility, and/or specific adaptation to a Euro-Latin American host population. The identification of RD(Rio) strains outside of Brazil points to the ongoing intercontinental dissemination of this important genotype. Further studies are needed to determine the differential strain-specific features, pathobiology, and worldwide prevalence of RD(Rio) M. tuberculosis.

Efeitos adversos hepáticos durante o tratamento para tuberculose em hospital geral referência para Aids, Rj, Brasil / Hepatic adverse efects anti-tuberculosis tratment in a geral hospital, Rio de Janeiro, Brasil

Introdução: a frequência de efeitos adversos hepáticos e os fatores associados com a sua ocorrência em um hospital universitário referência para Aids e tuberculose não é completamente conhecida. Métodos: foi realizado um estudo tipo caso-controle com o objetivo de medir prevalência de efeitos hepáticos adversos (EAH) em pacientes sob tratamento medicamentoso anti-tuberculose (TB) e de fatores associados à sua ocorrência. Resultados: foram analisados 588 prontuários médicos de pacientes que fizeram uso de esquema anti-TB com isoniazida, rifampicina e pirazinamida, acrescido ou não de etambutol, atendidos no período de Janeiro de 1994 a dezembro de 1995. EAH foi observado em 40 (6,8%) casos. Foram pareados 200 casos para o grupo controle. Na análise univariada dos grupos caso e controle não houve diferença estatisticamente significativa entre a ocorrência de EAH e os seguintes parâmetros: a idade, gênero esquema inicial de tratamento anti-TB, a história prévia de hepatopatia e/ou presença de alcoolismo. Entretanto, a ocorrência de EAH esteve significamente associada a hospitalização no momento do diagnóstico da TB, a presença de síndrome de imunodeficiência adquirida (SIDA/AIDS), a forma disseminada da TB, a apresentação radiográfica atípica da TB pulmonar, a sorologia positiva para hepatite a vírus B e/ou C, e a evolução clínica desfavorável ou tratamento. Na análise multivariada, somente a hospitalização e o diagnóstico de SIDA permaneceram associados significantemente a EAH. Conclusões: em um hospital Universitário, referência para AIDS e TB, a presença de Aids, de imagem radiológica de TB pulmonar atípica e a TB disseminada estão associados a uma maior taxa de EAH.

Introduction: the frequency of hepatic adverse effects and factors associated with its occurrence in an Universitary Hospital, reference for AIDS and tuberculosis (TB) is not completely known. Methods: a case-control study was conducted to assess the prevalence of hepatic adverse effects of patients using anti-TB treatment and the factors associated with its occurrence. Results: 588 medical charts of TB patients receiving anti-TB treatment with isoniazid, ripampin, pirazinamide, with or without ethambutol attendent betwee January, 1994 and December, 1995 were analyzed. HAE was observed in 40 (6.8%) patients. Two-hundred patients were included as control group. Using univariate analysis to evaluate case and control groups no statistically difference was found between HAE and the following variables: age, gender, anti-TB treatment, liver disease in the past and/or alcohol abuse. However, HAE was significantly associated with hospitalization at the time that TB diagnosis was made, immunosupression, disseminated TB, radiographic atypical presentation of pulmonary TB, seropositivy for B and C hepatitis and clinical unfavorable evolution. In multivariate analysis only hospitalization and Aids were associated to HAE. Conclusion: in a University Hospital, reference for TB and AIDS, the presence of Aids, radiographic atypical presentation of pulmonary TB and disseminated form of TB were associated with higher prevalence of HAE.