No abstract

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.