The tuberculosis taboo.

The treatment of latent tuberculous infection (TBI) is a productive and meaningful approach to tuberculosis (TB) control, and an important component of the World Health Organization's (WHO's) new End TB Strategy, especially in high-risk contacts. Unfortunately, although recognized and recommended by the WHO, it continues to be underutilized, and has even been ignored for decades in some high-risk groups, as though it were a taboo. Historical approaches to treating TBI in contacts of drug-susceptible and drug-resistant TB are presented and discussed as compelling experiences. In the United States, the Centers for Disease Control and Prevention have recently shown that a directly observed or even self-administered 12-month regimen to treat TBI with once-weekly isoniazid (INH) and rifapentine is as effective as 9 months of daily INH. Treating TBI in drug-susceptible cases and their contacts should not still be considered taboo-such a short, effective regimen is more akin to the Holy Grail. While not yet confirmed in a clinical trial, treating contacts of drug-resistant TB with the same drugs that are effective in the source case would be expected intuitively and practically to prevent TB in contacts and should be introduced now instead of waiting until clinical trials are completed.

Western Pacific Regional Green Light Committee: progress and way forward.

The Western Pacific Regional Green Light Committee (rGLC WPR) was established in 2011 to promote the rational scale-up of programmatic management of drug-resistant tuberculosis (PMDT). We reflect on its achievements, consider the challenges faced, and explore its potential future role. Achievements include the supervision and support of national PMDT action plans, increased local ownership, contextualized guidance, and a strong focus on regional capacity building, as well as a greater awareness of regional challenges. Future rGLC activities should include (1) advocacy for high-level political commitment; (2) monitoring, evaluation, and supervision; (3) technical support and contextualized guidance; and (4) training, capacity building, and operational research. Regional activities require close collaboration with both national and global efforts, and should be an important component of the new Global Drug-resistant TB Initiative.

TIMEBOMB revisited 10 years later: can we sustain progress or are we losing the war?

TIMEBOMB: The Global Epidemic of Multidrug-Resistant Tuberculosis was published in September 2001 to call attention to a deteriorating global tuberculosis (TB) situation. Although its impact was blunted by the events of 11 September, it is sobering to compare its description of TB problems at that time with the state of global TB control at present. TB--and the even worse resistant forms of the disease, multi-, extensively and even totally drug-resistant TB, a problem completely of our own making-is out of control due to neglect and inattention. Urgent attention is required to begin to rectify the situation.

Ethical issues in tuberculosis diagnosis and treatment.

Drug-resistant tuberculosis (TB) has highlighted the need for discussion of ethical questions about TB diagnosis and treatment. Drug resistance is a human-made phenomenon. It is caused by lack of patient adherence in drug taking and/or physician failure in prescription making. The global burden of TB is also partly explained by the lack of industry motivation to develop new TB drugs and diagnostics. This article explores the primary ethical issues associated with TB diagnosis and treatment: the human rights requirements regarding universal access to care and universal standards of care, treatment exclusion and cessation, privacy and stigmatisation in the context of directly observed therapy, and diagnostic challenges posed by limited laboratory capacity. Inter alia, it argues that: 1) the ethical imperative to improve individual patient care is partly based on the need to prevent the spread of infection and the exacerbation of the problem of drug resistance; 2) human rights and the imperative to protect the greater good of public health may call for increased regulation of the private sector; and 3) industry should be given further incentives to develop new tools for TB control.

Smoking and tuberculosis: the epidemiological association and immunopathogenesis.

There is increasing evidence of a link between tuberculosis and smoking. This paper reviews the epidemiological evidence from the UK, China, India and the USA, summarizing some of the main papers which indicate an association. Where an association has been found there seems to be an increase in tuberculosis case rates of between two- and four-fold for those smoking in excess of 20 cigarettes a day, but it may be difficult to control for other factors, particularly alcohol consumption. The final part of the paper reviews possible mechanisms. A likely possibility is that nicotine turns off the production of TNF-alpha by the macrophages in the lungs, rendering the patient more susceptible to the development of progressive disease from latent Mycobacterium tuberculosis infection.

Permanent declines in pulmonary function following pneumonia in human immunodeficiency virus-infected persons. The Pulmonary Complications of HIV Infection Study Group.

Human immunodeficiency virus (HIV)-associated respiratory infections, most notably Pneumocystis carinii pneumonia (PCP), but also bacterial pneumonia (BP), result in reductions in lung function that have been studied mainly during the course of acute infection. Whether HIV-associated pneumonias also cause permanent changes in pulmonary function is unknown. In this study we investigated the long-term effects of PCP and BP on pulmonary function in a cohort of HIV-infected persons. One thousand, one hundred forty-nine HIV-infected persons were followed in a prospective, observational cohort study at six centers in the United States. Study participants had pulmonary function testing performed at regular preset intervals. PCP and BP diagnoses were verified with defined criteria. Longitudinal multivariate analysis was used to model pulmonary function in terms of demographic data and occurrence of PCP or BP. We found that PCP or BP was associated with permanent decreases in FEV(1), FVC, FEV(1)/FVC, and the diffusing capacity of carbon monoxide. Neither infection resulted in statistically significant changes in TLC. We conclude that PCP and BP result in expiratory airflow reductions that persist after the acute infection resolves. The clinical implications of these changes are unknown, but they may contribute to prolonged respiratory complaints in HIV-infected patients who have had pneumonia.

Impact of bacterial pneumonia and Pneumocystis carinii pneumonia on human immunodeficiency virus disease progression. Pulmonary Complications of HIV Study Group.

The course of pneumonia caused by pyogenic bacteria and Pneumocystis carinii was examined in a multicity cohort study of HIV infection. The median duration of survival among 150 individuals following initial bacterial pneumonia was 24 months, compared with 37 months among 299 human immunodeficiency virus (HIV)-infected control subjects matched by study site and CD4 lymphocyte count (P<.001). For 152 subjects with P. carinii pneumonia, median survival was 23 months, compared with 30 months for 280 matched control subjects (P = .002). Median durations of survival associated with the two types of pneumonia differed by only 47 days, despite a higher median CD4 lymphocyte count associated with bacterial pneumonia. These results suggest that both P. carinii pneumonia and bacterial pneumonia are associated with a significantly worse subsequent HIV disease course. The similarity of prognosis after one episode of bacterial pneumonia vs. an AIDS-defining opportunistic infection and the proportion of cases occurring in association with a CD4 lymphocyte count of >200 suggest that measures to prevent bacterial pneumonia should be emphasized.

Risk factors and outcomes associated with identification of Aspergillus in respiratory specimens from persons with HIV disease. Pulmonary Complications of HIV Infection Study Group.

STUDY OBJECTIVES: To examine the significance of previously suggested risk factors and assess outcomes associated with Aspergillus identification in respiratory specimens from HIV-seropositive individuals. DESIGN: This was a nested case-control study. Patients who had Aspergillus species identified in respiratory specimens were matched at the time of study entry 1:2 with control subjects according to study center, age, gender, race, HIV transmission category, and CD4 count. SETTING: The multicenter Pulmonary Complications of HIV Infection Study. PARTICIPANTS: HIV-seropositive study participants. MEASUREMENTS AND RESULTS: Between November 1988 and March 1994, Aspergillus species were detected in respiratory specimens from 19 (1.6%) participants. The rate of Aspergillus identification among participants with CD4 counts <200 cells per cubic millimeter during years 2 through 5 after study entry ranged from 1.2 to 1.9%. Neutropenia, a CD4 count <30 cells per cubic millimeter, corticosteroid use, and Pneumocystis carinii infection were associated with subsequent identification of Aspergillus in respiratory specimens. Cigarette and marijuana use, previously suggested risk factors, were not associated with Aspergillus respiratory infection. A substantially greater proportion of patients with Aspergillus compared with control subjects died during the study (90% vs 21%). Excluding four cases first diagnosed at autopsy, 67% died within 60 days after Aspergillus was detected. CONCLUSIONS: Although Aspergillus is infrequently isolated from HIV-infected persons, the associated high mortality would support serious consideration of its clinical significance in those with advanced disease and risk factors.