Controle de crianças e adolescentes comunicantes de tuberculosos, Rio de Janeiro, RJ

OBJECTIVE: To detect tuberculosis (TB) disease or infection among contacts of pulmonary TB patients. METHODS: Cross-sectional study in a Primary Healthcare unit in Rio de Janeiro (Brazil) with 184 child and adolescent contacts of pulmonary TB patients between March 1995 and March 1997. Subjects underwent clinical evaluation, chest radiographs, and tuberculin skin tests (TST); sputum smears were performed whenever possible. TB cases found were submitted to treatment and infected patients to chemoprophylaxis. Tuberculin converters, who tested positive for TST eight weeks after an initial negative result, received chemoprophylaxis. RESULTS: The sample included 98 boys and 86 girls; age ranged from 0 to 15 years; 26.9% were malnourished according to the Gomez criteria. Concerning the source of infection, 170 cases (92.4%) had household contacts, of which 66.5% were the child's parents. BCG vaccination was verified in 98.4% of children, and 14.7% of children had been revaccinated. Strong TST reactions were observed in 110/181 children. Seventy-six children (41.3%) were considered as infected by M. tuberculosis and 25 cases (13.6%) of TB were detected, of which seven (28%) were asymptomatic. There was greater occurrence of disease when the contact lived with more than one source of infection (p=0,02). CONCLUSIONS: The detection of TB disease and infection was high in the studied population. Contact control must be emphasized, for it allows for the diagnosis of TB in children who are still asymptomatic, in addition to identifying infected subjects who may profit from chemoprophylaxis.OBJETIVO: Detectar doença ou infecção tuberculosa em comunicantes de pacientes com tuberculose pulmonar. MÉTODOS: Estudo descritivo, transversal, realizado em centro municipal de saúde da cidade do Rio de Janeiro, RJ, com 184 crianças e adolescentes, de 0 a 15 anos de idade, comunicantes de tuberculosos, no período de março de 1995 a março de 1997. Os comunicantes foram submetidos à avaliação clínico-radiológica, teste tuberculínico e baciloscopia de escarro, quando possível. Os doentes foram submetidos à quimioterapia anti-tuberculose e os infectados à quimioprofilaxia. Foi pesquisada a viragem tuberculínica nos comunicantes não reatores ao teste tuberculínico por meio de um segundo teste realizado após oito semanas e, quando presente, a quimioprofilaxia era instituída. RESULTADOS: A casuística foi composta por 98 meninos e 86 meninas, com idades variando entre 0 e 15 anos. Segundo o critério de Gomez, 26,9% das crianças eram desnutridas. Em relação à fonte de infecção, 170 (92,4%) foram intradomiciliares, das quais 66,5% eram os pais. A vacinação BCG foi constatada em 98,4% crianças e 14,7% haviam sido revacinadas. O teste tuberculínico foi reator forte em 110/181 crianças. Consideraram-se infectadas pelo M. tuberculosis 76 (41,3%) crianças e detectaram-se 25 (13,6%) casos de tuberculose pulmonar, dos quais sete (28%) estavam assintomáticos. Houve maior adoecimento quando o comunicante convivia com mais de uma fonte de infecção (p=0,02). CONCLUSÕES: A detecção de doença e de infecção tuberculosa foi elevada na população estudada. O controle de comunicantes deve ser enfatizado, pois permite o diagnóstico de tuberculose em crianças ainda assintomáticas e identifica infectados, os quais podem se beneficiar da quimioprofilaxia

Pediatric tuberculosis in the metropolitan area of Rio de Janeiro

Aim: To evaluate the clinical characteristics, diagnostic approach, and treatment outcomes of tuberculosis (TB) in children living in a high-burden metropolitan area. Methods: This was a retrospective study, based on a medical chart review, involving children under 15 years old treated for TB between 2007 and 2016, in four primary health units (PHU) and three reference centers (RC) in five cities of Rio de Janeiro metropolitan area. Factors associated with TB treatment setting, microbiological diagnosis, and treatment outcomes were evaluated. Results: A total of 544 children were enrolled; 71% were treated in PHU, 36% were under 5 years old, and 72% had pulmonary TB (PTB). The HIV prevalence was 10% (31/322). Fifty-three percent had at least one microbiological test for TB, 68% of them (196/287) had TB confirmed. Among 222 children with previous TB contact, information on LTBI was available for 78 (35%), and only 17% (13/78) were treated. Extrapulmonary TB (56% vs 32%), microbiologically confirmed TB (77% vs 60%), and HIV positivity (18.5% vs 4.0%) were significantly more frequent in RC. Treatment in RC (odds ratio (OR) 3.08, 95% confidence interval (CI) 1.74–5.44) and PTB (OR 2.47, 95% CI 1.34–4.56) were independently associated with a microbiological diagnosis of TB. The treatment success rate was 85%. In the logistic regression analysis, HIV-infected children had a 2.5-fold higher risk of an unfavorable outcome (OR 2.53, 95% CI 1.0–6.38; p = 0.05). Conclusions: Opportunities for TB prevention and early TB treatment are missed due to suboptimal close contact screening. Microbiological diagnosis of TB and drug susceptibility testing in children should be made available through more sensitive and accessible tests

Development of treatment-decision algorithms for children evaluated for pulmonary tuberculosis: an individual participant data meta-analysis.

Background: Many children with pulmonary tuberculosis remain undiagnosed and untreated with related high morbidity and mortality. Recent advances in childhood tuberculosis algorithm development have incorporated prediction modelling, but studies so far have been small and localised, with limited generalisability. We aimed to evaluate the performance of currently used diagnostic algorithms and to use prediction modelling to develop evidence-based algorithms to assist in tuberculosis treatment decision making for children presenting to primary health-care centres. Methods: For this meta-analysis, we identified individual participant data from a WHO public call for data on the management of tuberculosis in children and adolescents and referral from childhood tuberculosis experts. We included studies that prospectively recruited consecutive participants younger than 10 years attending health-care centres in countries with a high tuberculosis incidence for clinical evaluation of pulmonary tuberculosis. We collated individual participant data including clinical, bacteriological, and radiological information and a standardised reference classification of pulmonary tuberculosis. Using this dataset, we first retrospectively evaluated the performance of several existing treatment-decision algorithms. We then used the data to develop two multivariable prediction models that included features used in clinical evaluation of pulmonary tuberculosis-one with chest x-ray features and one without-and we investigated each model's generalisability using internal-external cross-validation. The parameter coefficient estimates of the two models were scaled into two scoring systems to classify tuberculosis with a prespecified sensitivity target. The two scoring systems were used to develop two pragmatic, treatment-decision algorithms for use in primary health-care settings. Findings: Of 4718 children from 13 studies from 12 countries, 1811 (38·4%) were classified as having pulmonary tuberculosis: 541 (29·9%) bacteriologically confirmed and 1270 (70·1%) unconfirmed. Existing treatment-decision algorithms had highly variable diagnostic performance. The scoring system derived from the prediction model that included clinical features and features from chest x-ray had a combined sensitivity of 0·86 [95% CI 0·68-0·94] and specificity of 0·37 [0·15-0·66] against a composite reference standard. The scoring system derived from the model that included only clinical features had a combined sensitivity of 0·84 [95% CI 0·66-0·93] and specificity of 0·30 [0·13-0·56] against a composite reference standard. The scoring system from each model was placed after triage steps, including assessment of illness acuity and risk of poor tuberculosis-related outcomes, to develop treatment-decision algorithms. Interpretation: We adopted an evidence-based approach to develop pragmatic algorithms to guide tuberculosis treatment decisions in children, irrespective of the resources locally available. This approach will empower health workers in primary health-care settings with high tuberculosis incidence and limited resources to initiate tuberculosis treatment in children to improve access to care and reduce tuberculosis-related mortality. These algorithms have been included in the operational handbook accompanying the latest WHO guidelines on the management of tuberculosis in children and adolescents. Future prospective evaluation of algorithms, including those developed in this work, is necessary to investigate clinical performance. Funding: WHO, US National Institutes of Health

Epidemiologia da tuberculose infantil na cidade do Rio de Janeiro, RJ

Data was drawn from a study on the epidemiological trends of tuberculosis among children of Rio de Janeiro county, Brazil. There was an increased incidence of tuberculosis among children and epidemiological health indicators were above the national average.De um estudo sobre tendência epidemiológica da tuberculose infantil no Município do Rio de Janeiro, RJ, foram extraídos dados importantes observados na população estudada. Os resultados mostraram aumento da incidência de tuberculose infantil no município, com indicadores epidemiológicos muito acima da média do País

Diagnosis of pulmonary tuberculosis by score system in children and adolescents: a trial in a reference center in Bahia, Brazil

Since 2002, the Brazilian Ministry of Health has recommended a score system for tuberculosis diagnosis of children and adolescents that does not need bacteriological positivity, because most cases in this age group have few bacteria. An observational, transversal study was carried out at the outpatient health care service of the reference medical service in Salvador, Bahia, including 164 patients with pulmonary tuberculosis, with ages ranging between 1 and 15 years of age, who were treated from 1990 to 2001. The gold standard used to establish the diagnosis was clinical, radiological, epidemiological and based on follow-up data. The score system for diagnosis purposes was tested retrospectively. The median age and the average age of the 164 patients were 6 and 6.62 years (SD ± 4.33), respectively. About 65% of the sample reported a history of close contact with a tuberculous adult. The BCG vaccine coverage was 70.7% (116/164). It was found that 26% (43/164) of the patients had severe malnutrition. Out of this group, 26/43 (60.47%) were < 5mm reactive to the tuberculin test. On the other hand, out of the 91 patients with tuberculin test < 5mm, 29% (26/ 91) had severe malnutrition. The use of the score gave the following distribution: a) TB very likely in 81.7% (134/164) of the patients; b) possible TB in 15.9% (26/164) and TB unlikely in 2.4% (4/164). Among patients who had been vaccinated more than 2 years before, there was a 9 times higher risk of finding a tuberculin test above 10 mm in individuals with probable TB in comparison with the patients with possible or unlikely TB

O desafio da tuberculose na faixa etária pediátrica frente a novas técnicas diagnósticas The challenge of pediatric tuberculosis in face of new diagnostic techniques

OBJETIVOS: Apresentar uma revisão atualizada sobre os novos métodos para o diagnóstico da tuberculose baseados na produção in vitro de interferon-gama (IFN-&#947;) por células T dos pacientes sob investigação, comparando-os com a tradicional prova tuberculínica. FONTES DOS DADOS: Revisão de literatura utilizando os bancos de dados MEDLINE e LILACS (2000-2008) utilizando as palavras-chave tuberculose, interferon-gama, quantiFERON, ELISPOT e T-SPOT.TB. 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-&#947; 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.<br>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)

Effectiveness and cost-effectiveness of first BCG vaccination against tuberculosis in school-age children without previous tuberculin test (BCG-REVAC trial): a cluster-randomised trial.

BACKGROUND: Neonatal BCG vaccination is part of routine vaccination schedules in many developing countries; vaccination at school age has not been assessed in trials in low-income and middle-income countries. Catch-up BCG vaccination of school-age children who missed neonatal BCG vaccination could be indicated if it confers protection and is cost-effective. We did a cluster-randomised trial (BCG REVAC) to estimate the effectiveness (efficacy given in routine settings) of school-age vaccination. METHODS: We assessed the effectiveness of BCG vaccination in school-age children (aged 7-14 years) with unknown tuberculin status who did not receive neonatal BCG vaccination (subpopulation of the BCG REVAC cluster-randomised trial), between July, 1997, and June, 2006, in Salvador, Brazil, and between January, 1999, and December, 2007, in Manaus, Brazil. 763 schools were randomly assigned into BCG vaccination group or a not-vaccinated control group. Neither allocation nor intervention was concealed. Incidence of tuberculosis was the primary outcome. Cases were identified via the Brazilian Tuberculosis Control Programme. Study staff were masked to vaccination status when identified cases were linked to the study population. We estimated cost-effectiveness in Salvador by comparison of the cost for vaccination to prevent one case of tuberculosis (censored at 9 years) with the average cost of treating one case of tuberculosis. Analysis of all included children was by intention to treat. For calculation of the incidence rate we used generalised estimating equations and correlated observations over time. FINDINGS: We randomly assigned 20,622 children from 385 schools to the BCG vaccination group and 18,507 children from 365 schools to the control group. The crude incidence of tuberculosis was 54·9 (95% CI 45·3-66·7) per 100,000 person-years in the BCG vaccination group and 72·7 (62·8-86·8) per 100,000 person-years in the control group. The overall vaccine effectiveness of a first BCG vaccination at school age was 25% (3-43%). In Salvador, where vaccine effectiveness was 34% (8-53%), vaccination of 381 children would prevent one case of tuberculosis and was cheaper than treatment. The frequency of adverse events was very low with only one axillary lymphadenitis and one ulcer greater than 1 cm in 11,980 BCG vaccinations. INTERPRETATION: Vaccination of school-age children without previous tuberculin testing can reduce the incidence of tuberculosis and could reduce the costs of tuberculosis control. Restriction of BCG vaccination to the first year of life is not in the best interests of the public nor of programmes for tuberculosis control. FUNDING: UK Department for International Development, National Health Foundation