Th2 immune response by the iron-regulated protein HupB of Mycobacterium tuberculosis.

BACKGROUND: HupB is an iron-regulated protein essential for the growth of Mycobacterium tuberculosis inside macrophages. To investigate if HupB induced a dominant Th2 type immune response, we studied the effect of rHupB on PBMCs from TB patients and by infecting mouse macrophages with wild type and hupB KO mutants. METHODS: PBMCs from pulmonary TB (n = 60), extra pulmonary TB (n = 23) and healthy controls (n = 30) were stimulated with purified HupB and the cytokines secreted were assayed. The sera were screened for anti-HupB antibodies by ELISA. Mouse macrophages cell line (RAW 264.7) was infected with wild type, hupB KO and hupB-complemented strains of M. tuberculosis grown in high and low iron medium and the expression of cytokines was assayed by qRT-PCR. RESULTS: Murine macrophages infected with the hupB KO strain produced low levels of the pro-inflammatory cytokines IFN-γ, TNF-α, IL-1, and IL-18 and high levels of IL-10. HupB induced IL-6 and IL-10 production in PBMCs of TB patients and down-regulated IFN-γ and TNF-α production. The influence of HupB was remarkable in the EPTB group. CONCLUSION: HupB shifted the immune response to the Th2 type. Low IFN-γ and elevated IL-10 in EPTB patients is noteworthy.

Study of treatment outcomes of multidrug-resistant tuberculosis under programmatic conditions and factors influencing the outcomes in Hyderabad District.

BACKGROUND: Treatment outcomes for Multidrug-Resistant Tuberculosis (MDR TB) is generally poor. The study aims to know about the treatment outcomes of MDR-TB under programmatic conditions in Hyderabad District and to analyze the factors influencing the treatment outcomes. METHODS: This is a retrospective study in which 377 patients of Hyderabad district, Telangana state who were diagnosed with MDR TB and registered at Drug Resistance TB Treatment site of Government General & Chest Hospital, Hyderabad from 4th quarter 2008 to 4th quarter 2013 were included in the study. Impact of Demographic factors (age, sex; Nutritional status (BMI); Co-morbid condition (Diabetes, HIV, Hypothyroidism); Programmatic factors (time delay in the initiation of treatment); Initial Resistance pattern on the outcomes were studied and analyzed. RESULTS: The treatment outcomes of Multidrug-Resistant Tuberculosis under Programmatic Conditions were: 57% cured, 21.8% died, 19.6% defaulted, 1.1% failed and 0.5% switched to XDR. Age, Sex, BMI had a statistically significant impact on treatment outcomes. Hypothyroidism and Delay in the initiation of treatment >1 a month had an impact on the outcomes though not statistically significant. NO impact on treatment outcomes was found when Rifampicin resistance & INH sensitive patients were compared with those resistant to both INH and Rifampicin. CONCLUSION: To reduce MDR-TB transmission in the community, improvement of treatment outcomes, via ensuring adherence, paying special attention to elderly patients is required. The Programmatic Management of Drug Resistance Tuberculosis (PMDT) should seriously think of providing Nutritional support to patients with low BMI to improve outcomes. In the programmatic conditions if we could address the problems like delay in initiation of treatment and proper management of comorbidities like HIV, Diabetes, Hypothyroidism would definitely improve the treatment outcomes.

Clinico-radiological profile and treatment outcome of pulmonary tuberculosis with and without type 2 diabetes mellitus.

BACKGROUND: The bidirectional association between tuberculosis (TB) and diabetes mellitus (DM) is currently one of the major concerns for clinicians, as DM affects the disease presentation and clinical outcome of TB and vice versa. The interest in diabetes mellitus and tuberculosis is mounting rapidly and it promises to be an exciting time for researchers involved in the study of dual diseases. METHODS: A prospective case control study was conducted over a period of one year, on patients diagnosed with pulmonary tuberculosis (PTB) with and without associated type 2 diabetes mellitus, who were admitted in a tertiary care hospital. Pulmonary TB patients with diabetes were labelled as the case group, and those without diabetes were labelled as the control group. A total number of 63 patients in the case group were compared with 63 patients in the control group. RESULTS: In the present study, clinical symptoms were similar in both the case and control groups, except for haemoptysis (27% vs. 12.7%) and weight loss (96.8% vs. 84.1%), which were significantly more predominant in the case group. There was a significant radiological involvement of the lower lung fields (46% vs. 17.5%) with cavitations (42.9% vs. 20.6%) in the case versus the control group. The sputum conversion at the end of the 2nd month was 92.1% in the control group and 55.6% in the case group (p = 0.001). In addition, cure rate in the control group was notably higher than in the case group (81% vs. 61.9%). The proportion of treatment failures were more among the case group (14.3%) as compared to the control group (1.6%). CONCLUSION: The present study concludes that, diabetes certainly affects the clinical, bacteriological and radiological presentation and treatment outcome of pulmonary tuberculosis.

Prevalence of multidrug resistance among retreatment pulmonary tuberculosis cases in a tertiary care hospital, Hyderabad, India.

BACKGROUND: India is one of the high tuberculosis (TB) burden countries in the world. India ranks second in harboring multi drug resistant (MDR)-TB cases. About 50,000 of MDR cases are recorded in retreatment pulmonary TB cases. This study was conducted in a tertiary care facility (Government General and Chest Hospital) in Hyderabad, India. OBJECTIVES: TOASSESS: Proportion of the TB patients having MDR-TB at the initiation of retreatment regimen; the prevalence of isoniazid (INH) resistance in this geographical area. MATERIALS AND METHODS: An analytical, observational, prospective cohort study of patients attending the out-patient department from December 2010 to March 2011. RESULTS: Sputum samples from 100 patients were subjected to acid fast bacilli (AFB) culture and drug sensitivity testing. Of these, 28 (28%) were MDR-TB, 42 (42%) were non-MDR-TB and 39% being INH resistance. CONCLUSIONS: In conclusion, one third of the retreatment pulmonary TB cases attending a tertiary care institute for TB will be MDR-TB at the initiation of treatment and there is a need to include ethambutol in the continuation phase of new TB case treatment in view of high INH resistance.

Are tuberculosis patients in a tertiary care hospital in Hyderabad, India being managed according to national guidelines?

SETTING: A tertiary health care facility (Government General and Chest hospital) in Hyderabad, India. OBJECTIVES: To assess a) the extent of compliance of specialists to standardized national (RNTCP) tuberculosis management guidelines and b) if patients on discharge from hospital were being appropriately linked up with peripheral health facilities for continuation of anti-Tuberculosis (TB) treatment. METHODS: A descriptive study using routine programme data and involving all TB patients admitted to inpatient care from 1(st) January to 30(th) June, 2010. RESULTS AND CONCLUSIONS: There were a total of 3120 patients admitted of whom, 1218 (39%) required anti-TB treatment. Of these 1104 (98%) were treated with one of the RNTCP recommended regimens, while 28 (2%) were treated with non-RNTCP regimens. The latter included individually tailored MDR-TB treatment regimens for 19 patients and adhoc regimens for nine patients. A total of 957 (86%) patients were eventually discharged from the hospital of whom 921 (96%) had a referral form filled for continuing treatment at a peripheral health facility. Formal feedback from peripheral health facilities on continuation of TB treatment was received for 682 (74%) patients. In a tertiary health facility with specialists the great majority of TB patients are managed in line with national guidelines. However a number of short-comings were revealed and measures to rectify these are discussed.

Emerging trends in the diagnosis of tuberculosis--RNTCP and beyond.

Though the Koch's bacillus was discovered 128 years ago, still there lies some dilemma in its diagnosis in certain clinical situations. Here in this article two basic approaches have been described for its diagnosis. One is the 'direct' approach in which detection of mycobacteria or its products is done, the other being 'indirect' approach, which includes measurements of humoral and cellular responses of the host against tuberculosis. 'Direct' methods include sputum smear microscopy, culture and molecular amplification methods. The 'indirect' methods include antibody detection, antigen defection, cellular immunity mediated tests and biochemical assays. All the methods have been narrated in a nutshell in this article.