Fernando Augusto Fiuza de Melo

III Diretrizes para Tuberculose da Sociedade Brasileira de Pneumologia e Tisiologia

New scientific articles about tuberculosis (TB) are published daily worldwide. However, it is difficult for health care workers, overloaded with work, to stay abreast of the latest research findings and to discern which information can and should be used in their daily practice on assisting TB patients. The purpose of the III Brazilian Thoracic Association (BTA) Guidelines on TB is to critically review the most recent national and international scientific information on TB, presenting an updated text with the most current and useful tools against TB to health care workers in our country. The III BTA Guidelines on TB have been developed by the BTA Committee on TB and the TB Work Group, based on the text of the II BTA Guidelines on TB (2004). We reviewed the following databases: LILACS (SciELO) and PubMed (Medline). The level of evidence of the cited articles was determined, and 24 recommendations on TB have been evaluated, discussed by all of the members of the BTA Committee on TB and of the TB Work Group, and highlighted. The first version of the present Guidelines was posted on the BTA website and was available for public consultation for three weeks. Comments and critiques were evaluated. The level of scientific evidence of each reference was evaluated before its acceptance for use in the final text.

[Epidemiological features of multidrug-resistant tuberculosis in a reference service in São Paulo city].

In order to study certain epidemiological features of multidrug-resistant tuberculosis (MDR-TB) carriers and their influence on the control and treatment, a group of patients was evaluated over a four-year period, selected by: Mycobacterium tuberculosis isolation from sputum; resistance to Rifampin, Isoniazid and one more drug, or, failure of reserve regimen, all cases were from a tuberculosis reference unit in the City of S o Paulo. A total of 182 patients were reviewed, with a mean age of 35.7 +/- 6.8 years and 112 (61.5%) were male. These patients was classified according to therapeutic history, as: primary MDR-TB (with initial sensitivity test) 11 (6%); post primary MDR-TB (after irregular use previous treatment) 134 (74%), and indeterminate MDR-TB (failure after regular use of initial and reserve regimens) 37 (20%). Contagion was identified in 41/170 patients, acquired through domiciliary rather than institutional transmission. There were four familial outbreaks and none were institutional. The most frequent condition associated with these cases was abandonment of therapy (45%) followed by alcoholism (27%), sequential failure in the treatment regimens (23%), MDR contagion (15%), drug reaction (6%), HIV positive (4%) and diabetes (3%). There was resistance to Rifampin+Isoniazid in 100%, Streptomycin in 83% and Ethambutol in 47%. Conventional X-ray revealed cavities in all, though only 35 (19%) were unilateral. These cases are discussed and some suggestions presented.

Estudo de efetividade de esquemas alternativos para o tratamento da tuberculose multirresistente no Brasil

Purpose: To determine the effectiveness of alternative regimens for treating confirmed MDR TB cases in outpatient units: Methods: MDR TB cases were defined as culture isolation of M. tuberculosis resistant in vitro to at least rifampin/isoniazide and a third drug of standard regimens in Brazil, according to both the conventional method and the BACTEC system. Design: Multicentric non-randomized controlled clinical trial. From April 95 to December 97 187 patients were enrolled. As of April 98, there were 36 patients under treatment. The authors analyzed 149 patients that had an average 14 months of treatment duration. The regimens used were chosen according to sensitivity tests: 1) streptomycin (S)/ofloxacin (OFX)/terizidon (TZ)/ethambutol (E)/clofazimine (CZ) or capreomycin (CM)/OFX/TZ/CZ/E or amicacyn/OFX/TZ/E/CZ. Demography: Male, 68.4%; female, 31.5%; mean age-36.9 years; HIV prevalence 1.9%; primary resistance rate - 8%. Outcomes: cured-treated for 12 months with six months after two consecutive negative culture; abandoned-discontinued treatment and consultations; died _ deaths due to TB after two months of treatment; failed - remained positive in culture throughout the 12 months. Results: 120 (79.5%) patients converted to negative culture within 3 months. Cured: 53%, failed 31%, died 6%, abandoned 10%. Conclusions: The major predictor to MDR TB in Brazil is previous irregular and/or incomplete treatment. Sputum conversion rate was high and favorable overall response was 53%. Clinical implications: Because TB is endemic in Brazil and the number of MDR cases due to acquired resistance is increasing, greater efforts are needed to implement supervised treatment in tuberculosis particularly for non compliant patients.

Relationship of NAT2, CYP2E1 and GSTM1/GSTT1 polymorphisms with mild elevation of liver enzymes in Brazilian individuals under anti-tuberculosis drug therapy

The relationship of NAT2, CYP2E1 and GSTM1/GSTT1 polymorphisms with mild elevation of liver biomarkers was investigated in individuals under anti-tuberculosis drug therapy. Tuberculosis outpatients (18-70 y) with (n=59) and without (n=40) mild increase of liver enzymes (MILE) at two-month treatment were selected. Blood samples were obtained for DNA extraction and evaluation of serum markers of liver function. NAT2, CYP2E1 and GSTM1/GSTT1 polymorphisms were detected by DNA sequencing, PCR-RFLP, and PCR multiplex. Frequency of NAT2*5/*5 genotype was higher in MILE than in non-MILE group (p=0.04). Patients carrying NAT2*5/*5 genotype had increased susceptibility to MILE (OR: 9.00, 95CI: 1.46-55.48, p=0.018). CYP2E1*5B allele (*1A/*5B plus *5B/*5B genotypes) carriers had a trend for reduced risk for MILE (OR: 0.34, 95CI: 0.11-1.03, p=0.056) that was confirmed by lower levels of liver markers than CYP2E1*1A/*1A carriers after treatment (p<0.05). Moreover, increased post-treatment ALT, AST and total bilirubin were associated with GSTM1*1/GSTT1*1 genotypes (p<0.05). Patients taking CYP2E1 inhibitors had increased susceptibility to MILE (OR: 7.39, 95CI: 1.93-28.29, p=0.003), which was independent of the studied polymorphisms. These results are suggestive that NAT2, CYP2E1 and GSTM1/GSTT1 polymorphisms and concomitant use of CYP2E1 inhibitors contribute to the susceptibility to mild alterations in liver enzymes in patients under anti-tuberculosis drug therapy.

Cost Effectiveness of Antituberculosis Interventions

The treatment of tuberculosis (TB) is ranked as the most cost effective of all therapeutic programmes in terms of cost per year of life saved. Nevertheless, TB kills or debilitates more adults aged between 15 and 59 years than any other disease in the world; furthermore, about 2 to 4% of the burden of disease, 7% of all deaths and 26% of all preventable deaths are directly attributable to TB.About one-third of the world’s population is infected with the TB bacillus. In the developing world, more women of childbearing age die from TB than from causes directly associated with pregnancy and childbirth. The death of adults in their prime, who are parents, community leaders and producers in most societies, causes a particularly onerous burden besides being a serious public health problem. In the poorest countries, where the magnitude of the TB problem is greatest, those TB control strategies that are economically feasible tend to be less effective. Therefore, in low and middle income countries, cost-effectiveness considerations aimed at prioritising resource allocation in the health sector in general, and in TB control programmes in particular, are of paramount importance.Operationally, the main components of a TB control programme are: (i) detection and treatment of TB; and (ii) prevention of TB through BCG vaccination and chemoprophylaxis. Priority should be given to ensuring that TB patients complete their prescribed course of chemotherapy. Adequate treatment is the most effective way of preventing the spread of TB and the emergence of drug resistance. This article reviews evidence of the effectiveness and cost effectiveness of different approaches to TB care, particularly those that are applicable to low income countries, in both HIV-infected and noninfected patients. Financial implications and ways to implement directly observed therapy for TB in large urban areas are discussed, and the need to address some relevant operational issues is highlighted. The current role of chemoprophylaxis and BCG vaccination is also reviewed.

Efetividade do esquema 3(3SZEEt/9EEt) * no retratamento da tuberculose na rotina das unidades de saúde

atuação (gerência, laboratório, assistência ambulatorial e hospitalar), debateram e apresentaram as propostas em plenária. Os participantes no nível de gerência, sugeriram a formação de um grupo de estudos de nível central integrado por representantes do nível federal (CRPHF/ FUNASA e FIOCRUZ), Gerencias do PCT Estadual e Municipal e Universidades, para a homogeneização do conhecimento de biossegurança em tuberculose. Propuseram também, a criação de uma comissão de biossegurança, constituída por técnicos de nível central (Federal/Estadual/Municipal) que tenham conhecimento em biossegurança, para assessorar no processo inicial de implantação das medidas de âmbito intrainstitucional (hospitalar, unidades básicas e laboratório). Esta equipe seria então responsável pela supervisão, monitoração, avaliação das ações implantadas/implementadas, e contaria também com a colaboração de profissionais de Universidades, da FUNASA/MS, FIOCRUZ, Gerências do PCT que dariam apoio sistemático às Unidades de Saúde. As sugestões dos demais grupos apontavam para a formação de uma comissão de biossegurança institucional, que nos hospitais começariam pela Comissão de Controle de Infecção Hospitalar (CCIH), e nas Unidades básicas, pelo Programa de Controle da Tuberculose e/ou o núcleo de epidemiologia. Ressaltouse também a importância da participação de técnicos com conhecimento de arquitetura hospitalar, bem como em biossegurança, nas comissões de nível central e institucional, fundamental para orientação da adequação da área física. Complementando a proposta foi sugerida a participação da gerência médica e administrativa nas discussões sobre as medidas de biossegurança. As outras propostas referiam-se ao treinamento continuado em biossegurança, a disponibilização e atualização das informações para todos os profissionais; a integração inter e intrainstitucional das diversas categorias de profissionais de saúde incluindo médicos, enfermeiros, arquitetos, engenheiros, farmacêuticos, técnicos de laboratórios, entre outros; a retroalimentação das informações tanto no nível central para nível local e vice-versa; a sensibilização para o uso obrigatório de Equipamento de Proteção Individual (máscaras especiais, luvas, protetores oculares e facial, uniformes especiais); a adoção de medidas específicas de laboratório, no que se refere a utilização de cabinas de segurança biológica para todos os procedimentos laboratoriais, além da inclusão do tema biossegurança na grade curricular dos cursos de graduação da área de saúde, entre outras. Concluindo, a elaboração de estratégias de grande impacto voltadas para biossegurança são necessárias para sensibilizar os profissionais de saúde que atuam principalmente nas emergências/pronto atendimento, para que passem a pensar em tuberculose, tendo em vista a demanda expressiva de sintomáticos respiratórios à estes serviços. O estabelecimento e a garantia de um fluxo de referência e contra-referência entre hospitais de emergência e as unidades de saúde possibilitará uma melhoria na qualidade e humanização da assistência.

Anomalias das artérias coronárias

Coronary artery anomalies (CAAs) are a rare entity but their true incidence in the general population has yet to be determined. Most CAAs are asymptomatic, but they are nevertheless the second leading cause of sudden death in apparently healthy young athletes. The new imaging methods available to cardiologists, including CT angiography and MRI, now enable noninvasive diagnosis and characterization of these anomalies. The authors review the literature and present a retrospective study of 360 consecutive patients who underwent cardiac CT angiography. Demographic, clinical and angiographic characteristics were studied. The incidence of CAAs in this population was 2.69%. In order to better characterize this disorder, including diagnostic strategy, screening, treatment and prognosis, the authors suggest the establishment of a national registry of cardiac CT angiography. Such a registry would fill the existing gap in information on exams performed in the country, enriching current knowledge about this disease and noninvasive cardiac imaging in Portugal.

Resistência pós-primária do Mycobacterium tuberculosis às drogas antituberculosas segundo os antecedentes terapêuticos em uma unidade de referência na cidade de São Paulo

Foi revisto o perfil da resistencia pos-primaria (RPP) do Mycobacterium tuberculosis isolado do escarro de 349 pacientes portadores de tuberculose pulmonar, matriculados para retratamento em uma Unidade de Referencia na Cidade de Sao Paulo, em 1995, 1996 e 1997. Os pacientes foram classificados, de acordo com a historia de tratamento anterior constante nos prontuarios, como RA (retorno apos abandono), RC (recidiva apos a cura), F1 (falencia ao esquema inicial ou ao retratamento, reforcado ou nao com droga adicional) e MR (falencia ao esquema de segunda linha). A sensibilidade aos antimicrobianos foi obtida pelo metodos das proporcoes, por repique, apos primo cultivo em meio de Loweinstein Jensen. O perfil da RPP mostrou a taxa total de 69%, 38% para os RA, 41% para os RC, 79% para os F1 e 100% para os MR. A RPP para um antimicrobiano foi de 15% e a dois ou mais foi de 54%. Considerando somente os RA e os RC, a RPP foi de 39% para o total, 29% para um farmaco, 10% para dois ou mais e 6% para a dupla rifampicina e isoniazida. A resistencia do etambutol foi de 2% para os RA e RC, 9% para os F1 e 47% para os MR.

Rendimento da cultura de escarro na comparação de um sistema de diagnóstico automatizado com o meio de Lowenstein-Jensen para o diagnóstico da tuberculose pulmonar

BACKGROUND: Tuberculosis continues to be a global health problem. OBJECTIVE: To evaluate an automated system designed to diagnose tuberculosis, comparing it to sputum microscopy and culture in Lowenstein-Jensen medium. METHOD: A comparative study using 844 sputum samples, collected between September and December of 1999 at a reference center for tuberculosis in Sao Paulo, Brazil, to draw distinctions between the results obtained through the use of the automated system and those obtained through sputum microscopy and culture in Lowenstein-Jensen medium. RESULTS: Of the 844 samples evaluated, 27.1% tested positive for acid-fast bacilli, and 72.9% tested negative. In Lowenstein-Jensen culture, 34.7% were positive and 63% were negative, compared with 37.1% positivity and 56.9% negativity using the automated system. Sensitivity was 98.1% for the automated system and 91.9% for Lowenstein-Jensen culture. Specificity and positive predictive value were 100% for both methods. Negative predictive value was 98.9% for the automated system and 95.5% for Lowenstein-Jensen culture. The degree of accuracy was 99.3% for the automated system and 97% for Lowenstein-Jensen culture, and the Kappa was 0.99 for the automated system and 0.94 for Lowenstein-Jensen culture. The difference between the mean time to detection of mycobacteria using the automated system (10.5 days) and that found using Lowenstein-Jensen culture (34.7 days) was statistically significant. CONCLUSION: The difference between the culture yield obtained using the automated system and that achieved with Lowenstein-Jensen culture was statistically significant. Mean time to detection of mycobacteria was significantly shorter with the automated system. The higher yield provided by this new system justifies its use in a reference center for tuberculosis in Sao Paulo

Avaliação de uma sonda genética (Sistema Accuprobe, Gen Probe®) para identificação de organismos do complexo Mycobacterium tuberculosis, em comparação com métodos tradicionais de caracterização

BACKGROUND: The appearance of tuberculosis/human immunodeficiency virus co-infection and the growing number of diseases caused by nontuberculous mycobacteria, as well as the confusion that these can cause in relation to emerging multidrug-resistant strains, require more accurate and rapid laboratory results, not only in the isolation of strains but also in their identification. OBJECTIVE: A comparative study evaluating a new tool of molecular identification, which uses a genetic probe based on the 16S rDNA sequence of the Mycobacterium tuberculosis gene (Gen-Probe Accuprobe® Gen Probe, Inc.), and the classic methodology. METHOD: Fifty-five Mycobacterium strains, isolated from the sputum of patients treated at a tuberculosis reference clinic, were selected for study. Subcultures were performed in three tubes: one submitted to genetic identification, one analyzed through classical tests (production and accumulation of niacin; growth in the Lowenstein-Jensen medium with the inhibitor agents p-nitrobenzoic acid and thiophene-2-carboxylic acid hydrazide added), and one held in reserve. RESULTS: The probe identified 51 cases as belonging to the M. tuberculosis complex (one associated with M. kansasii) and the other 4 as nontuberculous mycobacteria, later identified as M. kansasii (3) and M. avium (1). Using traditional methods, 47 samples were identified as belonging to the M. tuberculosis complex, 4 were classified as fitting the profile of nontuberculous mycobacteria (in agreement with the genetic probe results), and 4 were unidentified, 1 of which presented the exact characteristics that 2 mycobacterium species have in common. CONCLUSION: The benefits of the molecular biology technique justify its implementation and routine use, in combination with classical methods, in a high-traffic clinic where complex cases of tuberculosis are treated.