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Knowledge of the prevalence of latent Mycobacterium tuberculosis infection is crucial for effective tuberculosis control, but tuberculin skin test surveys have major limitations, including poor specificity because of the broad antigenic cross-reactivity of tuberculin. The M. tuberculosis RD1 genomic segment encodes proteins, such as early secretory antigenic target (ESAT)-6, that are absent from M. bovis bacille Calmette-Guérin (BCG) and most environmental mycobacteria. We recently identified circulating ESAT-6-specific T cells as an accurate marker of M. tuberculosis infection. Here, interferon-gamma-secreting T cells specific for peptides derived from ESAT-6 and a second RD1 gene product, CFP10, were enumerated in 100 prospectively recruited healthy adults in Bombay (Mumbai), India. Eighty percent responded to >/=1 antigen, and many donors had high frequencies of T cells that were specific for certain immunodominant peptides. In contrast, of 40 mostly BCG-vaccinated, United Kingdom-resident healthy adults, none responded to either antigen. This study suggests an 80% prevalence of latent M. tuberculosis infection in urban India.

No data are available on the prevalence of sleep-disordered breathing (SDB) and obstructive sleep apnea-hypopnea syndrome (OSAHS) in Indians. We conducted a two-phase cross-sectional prevalence study for the same in healthy urban Indian males (35-65 years) coming to our hospital in Bombay for a routine health check. We also investigated its risk factors and evaluated the significance of the most commonly asked questions that best correlated with the presence of OSAHS. In the first phase, 658 subjects (94%) returned completed questionnaires regarding their sleep habits and associated medical conditions. In the second phase, 250 of these underwent an overnight home sleep study. The estimated prevalence of SDB (apnea-hypopnea index of 5 or more) was 19.5%, and that of OSAHS (SDB with daytime hypersomnolence) was 7.5%. Multiple stepwise logistic regression determined body mass index, neck girth, and history of diabetes mellitus as the principal covariates of SDB. The presence of snoring, nocturnal choking, unrefreshing sleep, recurrent awakening from sleep, daytime hypersomnolence, and daytime fatigue was each statistically significant for identifying patients with OSAHS. The higher prevalence of OSAHS in urban Indian men is striking and may have major public health implications in a developing country.

Extensively drug-resistant tuberculosis is a burgeoning global health crisis mainly affecting economically active young adults, and has high mortality irrespective of HIV status. In some countries such as South Africa, drug-resistant tuberculosis represents less than 3% of all cases but consumes more than a third of the total national budget for tuberculosis, which is unsustainable and threatens to destabilise national tuberculosis programmes. However, concern about drug-resistant tuberculosis has been eclipsed by that of totally and extremely drug-resistant tuberculosis—ie, resistance to all or nearly all conventional first-line and second-line antituberculosis drugs. In this Review, we discuss the epidemiology, pathogenesis, diagnosis, management, implications for health-care workers, and ethical and medicolegal aspects of extensively drug-resistant tuberculosis and other resistant strains. Finally, we discuss the emerging problem of functionally untreatable tuberculosis, and the issues and challenges that it poses to public health and clinical practice. The emergence and growth of highly resistant strains of tuberculosis make the development of new drugs and rapid diagnostics for tuberculosis—and increased funding to strengthen global control efforts, research, and advocacy—even more pressing.

Progressive fibrotic interstitial lung diseases (ILDs) are characterised by major reductions in quality of life and survival and have similarities to certain malignancies. However, palliative care expertise is conspicuously inaccessible to many patients with ILD. Unmet patient and caregiver needs include effective pharmacological and psychosocial interventions to improve quality of life throughout the disease course, sensitive advanced care planning, and timely patient-centred end-of-life care. The incorrect perception that palliative care is synonymous with end-of-life care, with no role earlier in the course of ILD, has created a culture of neglect. Interventions that aim to improve life expectancy are often prioritised without rigorous assessment of the individual's health and psychosocial needs, thereby inadvertently reducing quality of life. As in malignant disorders, radical interventions to slow disease progression and palliative measures to improve quality of life should both be prioritised. Efficient patient-centred models of palliative care must be validated, taking into account religious and cultural differences, as well as variability of resources. Effective implementation of palliative care for ILD will require multidisciplinary participation from clinicians, specialist nurses, psychologists, social workers, and, in some countries, non-governmental faith and community-based organisations with access to palliative care expertise.

Large studies on bedaquiline used to treat multidrug-resistant (MDR-) and extensively drug-resistant tuberculosis (XDR-TB) are lacking. This study aimed to evaluate the safety and effectiveness of bedaquiline-containing regimens in a large, retrospective, observational study conducted in 25 centres and 15 countries in five continents.428 culture-confirmed MDR-TB cases were analysed (61.5% male; 22.1% HIV-positive, 45.6% XDR-TB). MDR-TB cases were admitted to hospital for a median (interquartile range (IQR)) 179 (92-280) days and exposed to bedaquiline for 168 (86-180) days. Treatment regimens included, among others, linezolid, moxifloxacin, clofazimine and carbapenems (82.0%, 58.4%, 52.6% and 15.3% of cases, respectively).Sputum smear and culture conversion rates in MDR-TB cases were 63.6% and 30.1%, respectively at 30 days, 81.1% and 56.7%, respectively at 60 days; 85.5% and 80.5%, respectively at 90 days and 88.7% and 91.2%, respectively at the end of treatment. The median (IQR) time to smear and culture conversion was 34 (30-60) days and 60 (33-90) days. Out of 247 culture-confirmed MDR-TB cases completing treatment, 71.3% achieved success (62.4% cured; 8.9% completed treatment), 13.4% died, 7.3% defaulted and 7.7% failed. Bedaquiline was interrupted due to adverse events in 5.8% of cases. A single case died, having electrocardiographic abnormalities that were probably non-bedaquiline related.Bedaquiline-containing regimens achieved high conversion and success rates under different nonexperimental conditions.

SettingMumbai, India. A study conducted in Mumbai two decades ago revealed the extent of inappropriate tuberculosis (TB) management practices of private practitioners. Over the years, India's national TB programme has made significant progress in TB control. Efforts to engage private practitioners have also been made with several successful documented public-private mix initiatives in place.ObjectiveTo study prescribing practices of private practitioners in the treatment of tuberculosis, two decades after a similar study conducted in the same geographical area revealed dismal results.MethodsSurvey questionnaire administered to practicing general practitioners attending a continuing medical education programme.ResultsThe participating practitioners had never been approached or oriented by the local TB programme. Only 6 of the 106 respondents wrote a prescription with a correct drug regimen. 106 doctors prescribed 63 different drug regimens. There was tendency to over treat with more drugs for longer durations. Only 3 of the 106 respondents could write an appropriate prescription for treatment of multidrug-resistant TB.ConclusionsWith a vast majority of private practitioners unable to provide a correct prescription for treating TB and not approached by the national TB programme, little seems to have changed over the years. Strategies to control TB through public sector health services will have little impact if inappropriate management of TB patients in private clinics continues unabated. Large scale implementation of public-private mix approaches should be a top priority for the programme. Ignoring the private sector could worsen the epidemic of multidrug-resistant and extensively drug-resistant forms of TB.

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