Low expression of antigen-presenting and costimulatory molecules by lung cells from tuberculosis patients

Costimulatory and antigen-presenting molecules are essential to the initiation of T cell immunity to mycobacteria. The present study analyzed by immunocytochemistry, using monoclonal antibodies and alkaline phosphatase-anti-alkaline phosphatase method, the frequency of costimulatory (CD86, CD40, CD40L, CD28, and CD152) and antigen-presenting (MHC class II and CD1) molecules expression on human lung cells recovered by sputum induction from tuberculosis (TB) patients (N = 22) and non-TB controls (N = 17). TB cases showed a statistically significant lower percentage of HLA-DR+ cells than control subjects (21.9 ± 4.2 vs 50.0 ± 7.2 percent, P < 0.001), even though similar proportions of TB cases (18/22) and control subjects (16/17, P = 0.36) had HLA-DR-positive-stained cells. In addition, fewer TB cases (10/22) compared to control subjects (16/17) possessed CD86-expressing cells (P = 0.04; OR: 0.05; 95 percentCI = 0.00-0.51), and TB cases expressed a lower percentage of CD86+ cells (P = 0.04). Moreover, TB patients with clinically limited disease (£1 lobe) on chest X-ray exhibited a lower percentage of CD86-bearing cells compared to patients with more extensive lung disease (>1 lobe) (P = 0.02). The lower expression by lung cells from TB patients of HLA-DR and CD86, molecules involved in antigen presentation and activation of T cells, may minimize T cell recognition of Mycobacterium tuberculosis, fostering an immune dysfunctional state and active TB.

Mutations in the rpoB gene of rifampicin-resistant Mycobacterium tuberculosis strains isolated in Brazil and France

We evaluated the mutations in a 193bp of the rpoB gene by automated sequencing of rifampicin (RMP)-resistant and susceptible Mycobacterium tuberculosis strains isolated from Brazil (25 strains) and France (37 strains). In RMP-resistant strains, mutations were identified in 100 percent (16/16) from France and 89 percent (16/18) from Brazil. No mutation was detected in the 28 RMP-susceptible strains. Among RMP-resistant or RMP-susceptible strains deletion was observed. A double point mutation which had not been reported before was detected in one strain from France. Among French resistant strains mutations were found in codons 531 (31.2 percent), 526, 513 and 533 (18.7 percent each). In Brazilian strains the most common mutations were in codons 531 (72.2 percent), 526 (11.1 percent) and 513 (5.5 percent). The heterogeneity found in French strains may be related to the fact that most of those strains were from African or Asian patients

Drug Resistance Patterns among Hospitalized Tuberculous Patients in Rio de Janeiro, Brazil, 1993-1994

The purpose of this study was to analyze the prevalence and risk factors for drug resistance among hospitalized patients in two tertiary care centers, an acquired immunodeficiency syndrome (AIDS) reference center and a sanatorium, in Rio de Janeiro, Brazil. From 1993-1994, 389 patients were diagnosed as having tuberculosis (TB). Isolates from 265 patients were tested for in vitro susceptibility to rifampin and isoniazid. Resistance to one or more drugs was detected in 44 patients (16.6 percent) and was significantly more common among recurrent cases in both hospitals (p=0.03 in the AIDS center and p=0.001 in the sanatorium). Twenty seven patients (10.2 percent) had isolates resistant to both isoniazid and rifampin. Multi-drug resistance was associated with human immunodeficiency virus (HIV) infection among patients who had never been treated for TB. In conclusion, drug-resistant TB is high in hospitalized patients in Rio de Janeiro, especially among HIV infected patients. Therefore, measures to control TB and prevent nosocomial transmission need urgently to be set up in the Brazilian hospitals

Avaliaçäo de modificaçöes na rotina laboratorial do líquido pleural no rendimento diagnóstico de tuberculose pleural / Evaluation of laboratory routine of pleural fluid in diagnostic yield for pleural tuberculosis

Foi comparado o rendimento diagnóstico de tuberculose obtido em estudo propesctivo do líquido pleural de 80 pacientes e em análise retrospectiva de 105 prontuários médicos. Na série prospectiva foi introduzido o controle de qualidade, quando atençäo especial foi dada à colheita, transporte e processamento (precedido ou näo de descontaminaçäo) do líquido pleural. Na série retrospectiva utilizou-se a rotina do Serviço de Bacteriologia da Tuberculose, que consistia em descontaminaçäo de todos os materiais. Na abordagem prospectiva, 97 por cento dos pacientes tiveram seu diagnóstico confirmado. Este foi obtido histopatologicamente em 87 por cento e bacteriologicamente em 56 por cento dos casos. No estudo retrospectivo, a confirmaçäo diagnóstica ocorreu em 94 por cento dos casos. Na série prospectiva, a sensibilidade da cultura no líquido pleural näo precedida de descontaminaçäo (36 por cento) foi superior àquela observada no material submetido a descontaminaçäo (29 por cento) (p = 0,02). O rendimento da cultura do líquido pleural submetido a descontaminaçäo foi de 29 por cento e o oservado no exame bacteriológico do fragmento pleural, de 42 por cento (p < 0,02). Entretanto, na ausência de descontaminaçäo, o rendimento bacteriológico do líquido pleural (36 por cento) e o do fragmento pleural (42 por cento) foram semelhantes (p = 0,22). O controle de qualidade introduzido na série prospectiva aumentou o rendimento da cultura do líquido pleural de 26 por cento para 29 por cento.

Relationship mbetween immune response and clinical manifestations in patients with tuberculosis

Cutaneous reactivityy to purified protein derivative (PPD) and antibody levels were investigated in 122 adults and 28 children with tuberculosis. IgG anti-PPD levelks (measured by ELISA and reported as absorbance at 405 nm) were higher in adult patients with the disease for more than one year (0.533 ñ 0.391, N=38 vs 0.224 ñ 0.256, n+50 in patients with the disease for less than one year) as well as inn children with disseminated tuberculosis (0.138 ñ 0.137, N=11, vs 0.072 ñ 0.55, N=15 in children with localized disease). The cut-off values (mean + 2SD) for healthy children and adults were 0.09 and 0.22 absorbance at 405 nm. In both adult and pediatric patients, cutaneous reactivity to PPD was inversely correlated with antibody levels. The present data provide additional evidence for the existence of an unstable spectrum of immune response in tuberculosis patients in whom changes in clinical situation are dynamic