Case-control study of vitamin D status and adult multidrug-resistant pulmonary TB.

BACKGROUND: India has the highest prevalence of multidrug-resistant TB (MDR-TB) globally. Vitamin D deficiency is potentially an important risk factor for MDR-TB.METHODS: We conducted a case-control study of 90 newly diagnosed adult MDR-TB cases, 180 household controls and 82 non-household controls in Mumbai, India. Serum 25-hydroxyvitamin D (25(OH)D), anthropometry, clinical status and history, dietary data and sociodemographic data were collected from each participant. Interferon-gamma release assay (IGRA) was also performed in controls to assess latent TB. Multivariable regression was performed to estimate associations between 25(OH)D vs. case status and IGRA positivity.RESULTS: Mean participant age was 33.8 ± 12.0 years; 72.8% had 25(OH)D <20 ng/ml. Mean 25(OH)D was significantly (P < 0.05) lower in cases (12.5 ± 7.9) than both household (17.5 ± 11.2) and non-household controls (16.4 ± 9.1). In multivariable models, 25(OH)D concentration was inversely associated with MDR-TB case status among cases and household controls (OR 0.95 per 1 ng/ml, 95% CI 0.92-0.99; P = 0.015), and among cases and non-household controls (OR 0.94 per 1 ng/ml, 95% CI 0.89-1.00; P = 0.033); 53.6% of controls were IGRA-positive. 25(OH)D status was not associated with IGRA positivity.CONCLUSION: Vitamin D status was independently associated with MDR-TB case status. Research should evaluate the effectiveness of vitamin D supplementation in prevention and adjunctive treatment of MDR-TB.

Pulmonary Non-tuberculous Mycobacterial Infections in Category II Failures from National Tuberculosis Programme.

Pulmonary infections due to non-tuberculous mycobacteria (NTM) are increasingly being reported. These can mimic drug-resitant tubercuolosis. A diagnosis of NTM infections needs a high degree of clinical suspicion and repeated isolation of the organism on culture. NTM infections occur commonly in immunocompromised individuals and in people with lung abnormalities. Currently there are no guidelines on drug combinations and the duration of treatment is not adequately defined. Two cases of pulmonary infection with NTM in immune-competent individuals are described in the present report. Although the bacteriological, radiological and clinical response to treatment was good; early discontinuation of treatment resulted in recurrence and change in drug susceptibility pattern, suggesting the need for prolonged treatment for achieving cure.

Observations on categorisation of new TB cases: implications for controlling drug resistance.

In the context of rising rates of drug-resistant tuberculosis (TB) in India, this communication presents some field observations during screening of new cases registered with the Revised National Tuberculosis Control Programme (RNTCP) in urban and rural areas of Maharashtra, India. It appears that erroneous categorisation and treatment that contributes to multiple drug resistance results from a lack of patient screening for previous treatment, ambiguity in categorisation and reluctance to disclose a history of anti-tuberculosis treatment. Suggested measures include detailed screening of new cases, computerisation of patient records and an empathetic dialogue between patient and health care provider.

Rhodococcus and Mycobacterium Tuberculosis: masquerade or mixed infection.

Rhodocci have a morphology similar to that of Mycobacterium tuberculosis (TB), and are indistinguishable from normal diphtheroid flora. Symptoms include fever, productive/non-productive cough and pleuritic chest pain. Rhodococcal infections, being resistant to routine anti-tuberculosis medications, may be misdiagnosed as drug-resistant TB, thus prompting treatment for TB with rifampicin-containing regimens that promote the emergence of resistance. We present here a sputum smear AFB-positive case who, although clinically cured, remains unresolved despite a series of technological investigations as to the cause of infection being purely rhodococci or mixed infection with M. tuberculosis.

Every provider counts: effect of a comprehensive public-private mix approach for TB control in a large metropolitan area in India.

SETTING: Mumbai, India. OBJECTIVES: To assess impact on case notification and treatment outcome of a public-private mix approach for tuberculosis (TB) control involving private providers, non-governmental organisations (NGOs), and public providers not previously involved in the Revised National TB Control Programme (RNTCP). METHODS: Under the stewardship of the RNTCP, providers were allocated different roles in referral, diagnosis, treatment initiation, directly observed treatment (DOT) provision, training and supervision. Referral forms were introduced and RNTCP registers were adapted to enable monitoring of case notification by different providers and cohort analysis disaggregated by provider type. RESULTS: A fraction of all non-RNTCP providers had become actively involved by the end of 2003. These providers contributed 2145 new smear-positive cases in 2003, an increment of 40% above the 5397 cases detected in RNTCP facilities. The treatment success rate for new smear-positive cohorts for 2002 was 85% in RNTCP facilities, 81% in private clinics, 88% in medical colleges, 91% in NGOs and 73% in the TB hospital (where the death rate was 16%). CONCLUSION: Active involvement of some key public and private providers can increase case notification substantially while maintaining acceptable treatment outcomes. The impact can be expected to be even larger when all health providers have been involved.

Longitudinal trends in serum levels of mycobacterial secretory (30 kD) and cytoplasmic (65 kD) antigens during chemotherapy of pulmonary tuberculosis patients.

Antigen 85 (mol. wt 30,000) (30 kD), secreted by actively growing mycobacteria under axenic conditions, and mol. wt 65,000 (65 kD), a cytoplasmic antigen released during mycobacterial lysis, were used to monitor the efficacy of chemotherapy in previously untreated pulmonary tuberculosis (UPTB) patients using enzyme-linked immunosorbent assay. Sera from 125 UPTB patients were examined for each of the 2 antigens individually and for the ratio of secretory (30 kD) to cytoplasmic (65 kD) antigen (SCR), before commencement of treatment, after intensive phase (IP), completion of optimum period of treatment (COPT) and 6 months post-COPT. 116 controls (normals and contacts) were also checked for these antigens. The detection of 30 kD and 65 kD antigens in UPTB patients had a sensitivity ranging from 50-57% (mean 30 kD value: 0.64 +/- 1.24 ngs/ml) to 20-22% (mean 65 kD value: 0.51 +/- 1.87 ngs/ml), respectively, whereas in controls it ranged from 2-8% (0.05 +/- 0.28 ngs/ml) to 14-47% (0.09 +/- 0.22 ngs/ml), respectively. Although the decline in 30 kD positivity was more evident at COPT, computation of the SCR denoted efficacy of chemotherapy more readily at IP. Similarly, SCR resolved the ambiguity between individual antigen levels and the clinical status of a patient. Since significant numbers of patients demonstrated 30 kD at IP it may be computed that the lifespan of circulating 30 kD in serum could be at least 2 months after the start of treatment, declining gradually thereafter. Although seromonitoring for secretory antigen generally reflects the efficacy of chemotherapy, the interpretation of findings clearly requires further elucidation.

Severe weight loss: the predominant clinical presentation of tuberculosis in patients with HIV infection in India.

BACKGROUND: Tuberculosis is endemic in India and its prevalence is reported to be increasing in patients with human immuno-deficiency virus (HIV) infection. Several factors, including the level of immune deficiency, influence the clinical presentation of HIV-associated tuberculosis. METHODS: Between April 1994 and April 1996, 1820 patients with confirmed HIV infection were studied for their clinical, radiological and laboratory parameters. Severe weight loss was observed as a frequent presenting complaint. Hence, a case-control analysis was performed using severe weight loss as the presenting criterion among HIV-seropositive patients. RESULTS: Of the 1820 patients with HIV infection, 410 (23%) presented with severe weight loss of > 10% of body weight within the preceding month. Of these 410 patients, 176 (43%) had tuberculosis, 94 (23%) had chronic diarrhoea, and 89 (22%) had recurrent fever. Among 176 patients with tuberculosis, the following types of HIV-associated tuberculosis were seen: 115/176 (66%) had pulmonary, 49/176 (28%) had extrapulmonary tuberculosis; of these 49 cases with extrapulmonary tuberculosis 33 (18%) had disseminated tuberculosis, and 12/176 (7%) had both pulmonary and extrapulmonary involvement. In the group as a whole, 45/176 (25%) cases had disseminated tuberculosis. Clinical features of HIV-associated tuberculosis in decreasing order of frequency were chronic fever, chronic cough, lymphadenopathy and hepatosplenomegaly. The Mantoux skin test was significantly anergic among patients with extrapulmonary and disseminated tuberculosis (p = 0.001). CONCLUSIONS: There was a significant correlation between severe weight loss and tuberculosis (RR 17.5), chronic diarrhoea (RR 12.8) and recurrent fever (RR 4.5). The diagnostic value of the Mantoux skin test among HIV-associated tuberculosis is reduced, more so among those with extrapulmonary and disseminated forms.