Long term follow up of HIV-infected patients with tuberculosis treated with 6-month intermittent short course chemotherapy.

BACKGROUND: Tuberculosis occurs in 60%-70% of HIV-positive persons in India. The outcome of HIV-positive patients treated with 6-month intermittent short course antituberculosis regimens in India is not well described. METHODS: This was a prospective observational feasibility study of 71 patients with HIV and tuberculosis who were treated with category I regimen of the Revised National Tuberculosis Control Programme (ethambutol, isoniazid, rifampicin and pyrazinamide thrice weekly for the initial 2 months followed by rifampicin and isoniazid thrice weekly for the next 4 months). Sputum was examined by smear and culture for Mycobacterium tuberculosis every month up to 24 months. Chest X-ray, CD4 cell count and viral load were done prior to and at the end of treatment. None of the patients received antiretroviral therapy. RESULTS: We present here the treatment response of patients with sputum culture-positive pulmonary tuberculosis to category I regimen. By efficacy analysis, among 43 patients treated with category I regimen, sputum smear conversion was observed in 79% and culture conversion in 82% at the second month. A favourable response was seen in 72% of patients. The mean (SD) CD4% fell from 12.6 (5.9) to 8.9 (4.9) (p < 0.001) with no significant change in mean (SD) CD4 cell count (169 [126] to 174 [158]; ns) at the end of treatment. Viral load change from 1.8 x 10(5) at baseline to 1.3 x 10(5) at the end of treatment was not statistically significant. Thirty-one patients, who completed the full course of treatment, were declared cured and were followed up for 24 months. Twelve had recurrent tuberculosis (39%); 16 of 43 (37%) patients had died by the end of 24 months, two-thirds due to causes other than tuberculosis. CONCLUSION: Though the early bacteriological response to intermittent short course antituberculosis regimen was satisfactory, the overall outcome was adversely affected by the high mortality (during and after completion of treatment) and recurrence rate among HIV-infected patients with tuberculosis. Immune status deteriorated in spite of antituberculosis treatment, highlighting the need for antiretroviral treatment in addition to antituberculosis treatment to improve the long term outcome. The results of this pilot study need to be confirmed by larger studies.

Miliary tuberculosis in human immunodeficiency virus infected patients not on antiretroviral therapy: clinical profile and response to shortcourse chemotherapy.

BACKGROUND: An increase in tuberculosis (TB) incidence has been associated with human immunodeficiency virus (HIV). AIMS: To describe the clinical characteristics and treatment outcome of patients with HIV and miliary TB treated with short-course intermittent chemotherapy in the absence of access to highly active antiretroviral therapy (HAART). SETTINGS AND DESIGN: Prospective study of HIV infected adults referred to a TB clinic between July 1999 and July 2004. MATERIALS AND METHODS: On diagnosis of miliary TB, patients were treated with a standard regimen of two months of isoniazid, rifampicin, ethambutol and pyrazinamide followed by four months of isoniazid and rifampicin (2EHRZ 3 /4RH 3 ) thrice weekly and followed up for 24 months. Patients were reviewed clinically every month and two sputa were collected. Chest radiographs and blood investigations were done at two months, end of treatment and every six months thereafter. RESULTS: Of 498 patients with HIV and tuberculosis, 31 (6%) were diagnosed as miliary tuberculosis. At diagnosis, sputum smear was positive for acid-fast bacilli (AFB) in 14 patients (45%) and Mycobacterium tuberculosis was isolated in 21 (68%). The mean CD4 cell count was 129 +/- 125 cells/mm3 . Twenty-five patients were declared cured at the end of treatment (81%) while one (3%) died and five (16%) failed. The recurrence rate was 19.4/100 person-years and the median survival was 17 months (95% CI 14 to 20). None of the patients received antiretroviral therapy. CONCLUSIONS: Miliary TB tends to occur among HIV infected patients with severe immunosuppression. Though the initial response to short-course chemotherapy was encouraging, a high recurrence rate and mortality was observed indicating poor prognosis in HIV.

Plant-based formulation in the management of chronic obstructive pulmonary disease: a randomized double-blind study.

BACKGROUND: A randomized double-blind placebo controlled clinical study was undertaken to investigate the safety and efficacy of a plant-based formulation (DCBT1234-Lung KR), which earlier through 2 trials was found to improve FEV1 and the quality of life of COPD patients. OBJECTIVE: The efficacy of DCBT1234-Lung KR was assessed using pulmonary function tests, arterial blood gas (ABG) analyses and the clinical symptoms of COPD in a 6-month study period against a matching placebo and a biomedical drug combination (salbutamol+theophylline+bromhexine). METHODS: One hundred and five subjects aged between 35 and 85 years with a smoking history of more than 20 pack years, showing little or no improvement in FEV1 upon a bronchial challenge of 200 microg of inhaled salbutamol and exhibiting ABG percentage of less than 85% of oxygen saturation were taken up for the study. The study had 3 arms viz., the plant-based formulation (DCBT1234-Lung KR), placebo and salbutamol (12 mg/day) plus theophylline (300 mg/day) plus bromhexine (24 mg/day). The end point of the study was determined as an improvement of FEV1 by 200 mL and/or increased ABG values (>90% PaO2) and clinical symptoms like dyspnoea, wheezing, cough, expectoration, disability, and sleep disturbances. RESULTS: DCBT1234-Lung KR patients showed statistically significant (95% level) improvement in FEV1 and PaO2 in comparison with salbutamol+theophylline+bromhexine and placebo patients. Twenty-three per cent of DCBT1234-Lung KR patients, 19% of salbutamol+theophylline+bromhexine group and 12% of placebo group patients showed the desired 200 mL improvement in FEV1 values in comparison with the other 2 arms. Improved PaO2 was observed in 15.4% of the DCBT1234-Lung KR patients while no improvement was seen with patients in any other arms. Symptoms like dyspnoea, wheezing, cough, expectoration, disability and sleep disturbances also significantly reduced in DCBT1234-Lung KR and the biomedical group patients, but not in the placebo arm. CONCLUSIONS: DCBT1234-Lung KR was equivalent, if not better than the present day treatment with salbutamol, theophylline and bromhexine combination in COPD patients and this was ascertained using FEV1 and ABG values.

Plant-based formulation for bronchial asthma: a controlled clinical trial to compare its efficacy with oral salbutamol and theophylline.

BACKGROUND: Plant-based medicine is the 3rd most popular choice of both adults (11%) and children (6%) suffering from Asthma. While several plant-based formulations have been reported for the treatment of asthma in the past, many authors have published their reservations on clinical trials carried out using complementary and alternative medicines. OBJECTIVES: The authors desired to eliminate the shortcomings of the earlier clinical trials carried out by many investigators in a structured study. Therefore, a 12-week randomized double-blind placebo-controlled clinical study was conducted to investigate the efficacy of a plant-based formulation (DCBT4567-Astha-15) in comparison with oral salbutamol, salbutamol + theophylline and a matching placebo in patients with reversible asthma. METHODS: Ninety-four patients between 15 and 50 years of age, showing 15% improvement in forced expiratory volume in 1 s (FEV(1)) 15 min after a bronchial challenge of inhaled salbutamol (200 microg) were recruited, and the end point of the study was determined as a 15% improvement in FEV(1) and clinical symptoms like dyspnoea, wheezing, cough, expectoration, disability, sleep disturbances and respiration rate. RESULTS: DCBT4567-Astha-15, salbutamol and salbutamol + theophylline patients showed statistically significant improvement in FEV(1), while placebo patients did not show any improvement. Fifty percent of DCBT4567-Astha-15, 48% of salbutamol, 58% of salbutamol + theophylline and 26% of placebo patients showed the desired 15% improvement in FEV(1). Improved mean FEV(1) values at the end of the trial indicated that the salbutamol - theophylline combination was superior followed by salbutamol and DCBT4567-Astha-15. Clinical symptoms like dyspnoea, wheezing, cough, expectoration, disability, and sleep disturbances were significantly reduced in DCBT4567-Astha-15 patients compared to patients of the other three arms. CONCLUSIONS: DCBT4567-Astha-15 was as efficacious as salbutamol (12 mg/day) or salbutamol (12 mg/day) in combination with theophylline (200 mg/day) in the treatment of reversible asthmatics. Quality of life of patients also improved with DCBT4567-Astha-15 drug treatment.

Prevalence of acquired MDR-TB and HIV co-infection.

BACKGROUND: Mounting prevalence of primary and acquired multidrug-resistant tuberculosis in India is a sorry reminder of all round failure in our fight against tuberculosis and also of the necessity for new effective strategies. OBJECTIVES: (1) To assess the prevalence and pattern of drug resistant pulmonary tuberculosis among treated patients or on those on treatment without adequate response and (2) to evaluate HIV seropositivity among MDR-TB patients. METHODS: Pulmonary TB patients, who had at least six months of unsuccessful anti-tuberculous treatment were selected for the study. Their sputum specimens were examined for M. tuberculosis culture and drug sensitivity pattern and serological examinations for HIV infection were carried out. RESULTS: Sputum specimens of 618 patients' (61.8%) of a total of 1000 examined had shown culturable M. tuberculosis. Four hundred ninty-five patients (49.5%) were found to expectorate tubercle bacilli resistant to one or more anti TB drugs. MDR-TB was detected in 339 patients (33.9%). HIV seropositivity among MDR-TB was 4.42%. Significantly, 245 patients (24.5%) had tubercle bacilli resistant to one or more reserve drugs too (ethionamide, kanamycin and/or ofloxacin). CONCLUSIONS: Prevalence of MDR-TB was high in the study population. It is essentially an acquired condition. Its association with HIV disease was at present on the lower side, an observation contrary to published western literature. Higher rates of resistance for reserve drugs (ethionamide, kanamycin and/or ofloxacin) in patients who never had these drugs in their earlier treatment schedules suggest the possibility of emerging spontaneous drug resistant mutants.

Reduced NK activity in pulmonary tuberculosis patients with/without HIV infection: identifying the defective stage and studying the effect of interleukins on NK activity.

SETTING: A study was undertaken to understand the non-major histocompatibility restricted cytotoxicity in order to delineate the role of natural killer (NK) cells towards the development of host immunity to tuberculosis. OBJECTIVE: (a) Enumeration of NK cell numbers and activity in normal individuals (35), pulmonary tuberculosis patients (32), HIV-infected TB patients (20) and patient contacts (10), (b) effect of treatment on NK status, (c) enumeration of effector-target conjugates and (d) effect of in vitro cytokine stimulation on NK activity. DESIGN: NK cells were enumerated by flow cytometry. NK activity was assessed by chromium release assay before and after treatment for tuberculosis and after stimulation with IL-2/IL-12. Novel flow cytometric method was standardized to enumerate effector-target conjugates. RESULTS: No changes were seen between different groups as far as number of NK cells and relative proportions of different conjugate types were concerned, but there was a decrease in NK activity in TB patients which increased after treatment. Augmentation of NK activity was observed after cytokine stimulation. CONCLUSION: Lowered NK activity during tuberculosis infection is probably the 'effect' and not the 'cause' for the disease as demonstrated by the follow-up study. Similar number of conjugates in both groups indicates no defect in the recognition/binding step but probably at subsequent steps of the cytotoxic process. Augmentation of NK activity with cytokines implicates them as potential adjuncts to tuberculosis chemotherapy.

Isolation, PCR based identification, and sensitivity pattern of environmental mycobacteria from leprosy and tuberculosis patients.

We have isolated and identified the biotype of environmental mycobacteria from the expectorate of leprosy patients, their contacts, their drinking water supply and also from the sputa samples of tuberculosis patients. 78% of the isolates from lepromatous leprosy patients and their contacts wereMycobacterium fortuitum- chelonae complex (MFC), 9%Mycobacterium avium complex (MAC), 9%Mycobacterium scrofulaceum and 4% wereMycobacterium smegmatis. Among the isolates from tuberculosis patients 63% belonged toM. fortuitum- chelonae complex, 19% toM. avium complex, 12% toMycobacterium Kansasii and 6% toM. smegmatis. All the isolates were multi-drug resistant when tested for sensitivity total of 21 drugs. TheMycobacterium fortuitum-chelonae complex organisms from leprosy contacts were more sensitive to rifampicin than those isolated from lepromatous leprosy and tuberculosis patients. Among 23 isolates from leprosy patients one isolate was resistant to 20 drugs, one isolate to 17 drugs and another isolate was resistant to 13 drugs. Among the 18 isolates from drinking water supply six showed resistance to more than 12 drugs. Polymerase Chain Reaction (PCR) and subsequent hybridisation with specific probes confirmed all the isolated strains as nontuberculous mycobacteria (Using genus primers and probe sensitivity 100%) and none asM. tuberculosis, suggesting that PCR could be used to rapidly identify mycobacteria at the genus level and to rule out tuberculosis in leprosy patients at an early stage to decide on appropriate course of therapy.

Primary pulmonary lymphoma. Report of a case diagnosed by fine needle aspiration cytology.

A case of primary pulmonary lymphoma, small lymphocytic type, with plasmacytoid differentiation (lymphoplasmacytic lymphoma) and IgM gammopathy, was diagnosed by fine needle aspiration of the lung. It was further substantiated by pleural fluid cytology, biochemical and immunologic parameters, and the clinical picture. This case is documented for its rarity along with a review of literature on the diagnosis of low grade small lymphocytic lymphomas.