A five year follow-up study of children treated for tuberculous meningitis with short course chemotherapy

A total of 215 patients with tuberculous meningitis were treated for a period of 9 months. Of these, 30 patients were excluded from analysis for various reasons. Of the remaining 185, 57 died during treatment leaving 128 patients (5 with severe sequelae, 43 with moderate, 18 with mild and 62 with complete recovery) for long term follow-up. The noteworthy features of the study are 100% coverage, low relapse rate and development of late sequelae in 10 patients during follow-up period

Acute respiratory infection in children

Only recently, it has been realised that Acute Respiratory infection (ARI) is a major cause of death in children. Out of nearly 15 million children under five, dying each year, four million die of ARI, and two thirds of these are infants, and more than 90% of all these deaths occur in developing countries1. In India2, 15-20% mortality in infants and children are due to ARI. During first five years of life, on an average, a child in urban area and in rural area may suffer from 5-8 episodes3 and 1-3 episodes4 of ARI per year respectively. The higher incidence of episodes in urban area may be due to over-crowding and urban air pollution

Rehabilitation for chronic obstructive pulmonary disease patients exercise training component

Even though Barach in 1964 advocated physical exercise for patients with chronic lung diseases (1), it was only in early 1970s that a liberal use of exercise training was included in pulmonary rehabilitation programmes (2). The relentless downhill course of chronic obstructive pulmonary disease (COPD) over many years and the concomitant worsening of dyspnoea limit the activity of patients, leading to a vicious cycle of increasing inactivity and dyspnoea. This in turn aggravates the debilitating effects of the disease. Exercise training has been advocated as an important component in pulmonary rehabilitation to improve well-being and to reduce subsequent hospital admissions in patients with chronic obstructive pulmonary disease

Primary tuberculosis of skin (Tuberculous chancre) in an infant of tuberculous mother - a case report

A case of proven primary skin tuberculosis in an infant born to a mother with sputum positive pulmonary tuberculosis is reported. Both were treated successfully with short-course chemotherapy

Persistng alveolitis in miliary tuberculosis despite treatment with short-course chemotherapy

Bronchoalveolar lavages in two patients with miliary tuberculosis have shown lymphocytic alveolitis. A 6-month regimen with an initial intensive 2- month phase resulted in remarkable clinical and radiographic improvement in both. However, bronchoalveolar lavage following treatment has shown that there was a persistence of lymphocytic alveolitis, though with reduced intensity. The significance of the persisting alveolitis, despite treatment, is not known at present. There is also a suggestion that compartment-alisation of lymphocytes may occur in miliary tuberculosis of the lung

715. Chandra G, et al. BamH1 polymorphism of Human Cytochrome P450 gene, CYP2D6, in quiescent and relpse patients of pulmonary tuberculosis

BamH l polymorphism of the human cytochrome P450 gene, CYP2D6, which encodes drug metabolizing enzyme, was studied to find out whether variant genotypes of this gene are associated with the susceptibility or resistance to bacteriological relapse of pulmonary tuberculosis after stopping treatment with short-course chemotherapy of 6-8 months duration. The study was carried out in control subjects (n=158), patients with pulmonary tuberculosis (n=154), patients with bacteriological relapse (n=50) and quiescent patients (n=50). No difference in the frequency of variant genotypes of BarnH l polymorphism of CYP2D6 gene was observed between pulmonary TB patients and control subjects. A trend towards an increased frequency of 22 genotype (homozygous for infrequent allele 2) was observed in bacteriological relapse patients than quiescent patients (odds ratio, OR: 2). Similar increase was observed in male relapse patients than male quiescent patients (OR: 2.2). The present study suggests that 22 genotype of BamH l polymorphism of CYP2D6 of human cytochrome P450 gene either alone or in combination with closely linked genes may be associated with bacteriological relapse especially in male patients of pulmonary tuberculosis

Short course chemotherapy study in tuberculous meningitis in children

A total of 215 patients with tuberculous meningitis were treated for nine months with one of the following two regimens: The first regimen consisted of 5 drugs namely Streptomycin, Isoniazid and Ethambutol given daily, supplemented with Rifampicin and Pyrazinamide thrice a week for the first two months, followed by Rifampicin and Isoniazid twice a week for the next seven months. Regimen II was similar to Regimen I excepting that Rifampicin and Pyrazinamide were given twice a week during the first two months of intensive phase, instead of thrice a week. As a general policy, steroids were administered to all the patients for a period of 6 to 8 weeks. On admission, 56% of the patients were aged less than 2 years and 75% less than five years. Forty-five patients (21%) were classified as stage I, 160 (74%) as stage II and only 10 (5%) as stage III. Cerebrospinal fluid culture was positive for tubercle bacilli either by smear, culture or both in 47%. Smear was negative and culture alone was positive in 74 patients and in 14 patients both smear and culture were positive. Of the 88 culture positive patients, in 7 (8%) the cultures were resistant to Streptomycin alone, in 12 (14%) to INH alone, in 11 (12%) to both Streptomycin and INH, while in 2 (2%) patients, they were resistant to all the three drugs. The response to therapy was similar in both the regimens. The mortality was very high, namely 31%, despite using intensive regimens. There was a strong association between the stage on admission and the mortality rate, the latter being highest in stages II and III. This emphasises the need for early diagnosis and treatment in tuberculous meningitis

HLA-DR2 subtypes & immune responses in pulmonary tuberculosis

Background & objectives: HLA-DR2 has been shown to be associated with the susceptibility to pulmonary tuberculosis and altered antibody and lymphocyte response in pulmonary tuberculosis. In the present study, the influence of DR2 subtypes on antibody titre and lymphocyte response ,to Mycobacterium tuberculosis culture filtrate antigens (10 μg/ml) was studied in 22 patients with active pulmonary TB (ATB), 50 inactive (cured) TB (ITB) patients and 36 healthy control subjects. Methods. HLA-DR2 gene was amplified by polymerase chain reaction (PCR) and dot-blotted. Genotyping of DRBl*1501, *1502, *1503, *1601 and *1602 was carried out using sequence specific oligonucleotide probes (SSOPs) and detected by chemiluminescence method. Antibody titre as well as lymphocyte response to M.tuberculosis antigens were measured by enzyme linked immunosorbent assay (ELISA) and lymphocyte transformation test (LTT) respectively. Results: The allele frequency of DRB1*15Ol was significantly increased in pulmonary tuberculosis patients as compared to controls (P<0.05). No marked difference in the antibody titre and lymphocyte response to M. tuberculosis antigens was observed between the DRBl *1501, *1502 and *1503 positive or negative controls, ATB and ITB patients. DRBl *1501 and *1502 positive as well as negative ATB patients showed a higher antibody titre as compared to controls and ITB patients. ITB patients with *1502 showed a higher lymphocyte response as compared to *1502 positive controls (P<0.001) and ATB patients (P<0.05). Similarly, an increased lymphocyte response was observed in *1501, and *I503 negative ITB patients compared to *1501 and *1503 negative controls and ATB patients. Interpretation & conclusion: The present study revealed that DRBl *1501 may be associated either alone or with other DR2 alleles, with the susceptibility to pulmonary tuberculosis. None of the DR2 alleles influenced the antibody and lymphocyte response to M tuberculosis culture filtrate antigens. This suggested that HLA-DR2 gene/gene products as a whole may influence the immune response in pulmonary tuberculosis

Influence of non-MHC genes on lymphocyte response to Mycobacterium tuberculosis antigens and tuberculin status in Pulmonary tuberculosis

Background & objectives : Major histocompatibility complex (MHC) genes are known to influence the immune functions. In the present study, the influence of non-MHC genes such as mannose binding protein (MBP), vitamin D receptor (VDR) and interleukin-1 receptor antagonist (IL-IRA) gene polymorphisms on lymphocyte response to Mycobacterium tuberculosis culture filtrate antigen (10 μg/ml) was studied in 44 patients with active pulmonary TB and the family contacts (35) and in 32 normal healthy subjects. The influence of these gene polymorphisms on tuberculin (1TU of PPD of M. tuberculosis) reactivity status in 146 pulmonary TB patients was also studied. Methods : The MBP and VDR genes were amplified using polymerase chain reaction (PCR) and genotyping was carried out using sequence specific oligonucleotide probes by dot blot and IL-1RA by agarose gel electrophoresis. Results : A significantly decreased lymphocyte response to M. tuberculosis antigen was seen in pulmonary TB patients positive for functional mutant homozygotes of MBP (00) compared to heterozygote carriers (AO; P<0.02) and wild homozygotes (AA; P<0.01). The variant mutant genotype (tt) of VDR gene was associated with an increased lymphocyte response in control subjects compared to active TB patients with tt genotype (P<0.05). Heterozygote carriers of MBP (AO) were associated with a significantly (P<0.001) decreased tuberculin reactivity compared to wild homozygotes (AA). The VDR genotype Tt (heterozygote carrier) was associated with an increased tuberculin reactivity in female TB patients as compared to male patients (P<0.001). Interpretation & conclusions : The present study suggested that MBP and VDR genes influence the cell mediated immune response in pulmonary TB patients. Non-MHC genes along with HLA-Class II genes/gene products may be playing an immunoregulatory role in the mechanism of susceptibility/resistance to tuberculosis

Vitamin D receptor and interleukin-1 receptor antagonist gene polymorphism in spinal tuberculosis

Our earlier studies revealed that both MHC (Major Histocomptibility Complex) and non-MHC genes are associated with the susceptibility to pulmonary tuberculosis (TB). To find out whether non-MHC genes such as vitamin D receptor (VDR) and interleukin-1 receptor antagonist (IL-1RA) genes are associated with the susceptibility to spinal TB (extrapulmonary form of TB), the present study was carried out in spinal TB patients (n=66) and spouses of TB patients (spinal-TB and pulmonary-TB) ( n = 80) (family contacts). A trend towards an increased per cent genotype frequency of IL-1RA genotype variant 22 (12.1%) was seen in spinal TB patients when compared to the controls (3.8%) (spouses of the patients) (P=0.057; odds ratio 3.5). No difference was observed in the frequency of VDR genotypes between the overall spinal TB patients and the family contacts. However, the VDR mutant genotype tt was seen at a higher frequency in female patients with TB spine (TBS) (12.8%) than female contacts (4.2%) ( P >0.05 not significant; odds ratio 3.5). Among the contacts, a significantly increased frequency of wild type genotype TT (wild homozygotes) was seen in female contacts (55.1%) than male contacts (16.1%) (P =0.0012). Similarly a significant decrease in tt genotype was seen in female contacts (4.1%) than male contacts (25.8%) (P=0.012). The present study suggests that IL-1RA genotype 22 may be associated with the susceptibility to spinal TB. Moreover, vitamin D receptor tt genotype may be associated with the susceptibility to spinal TB in female patients. The study reveals that multicandidate genes may be associated with the susceptibility to spinal TB