International Journal of Tuberculosis and Lung Disease 

About: International Journal of Tuberculosis and Lung Disease is an academic journal published by International Union Against Tuberculosis and Lung Disease. The journal publishes majorly in the area(s): Tuberculosis & Population. It has an ISSN identifier of 1027-3719. Over the lifetime, 6289 publications have been published receiving 167581 citations.

The natural history of childhood intra-thoracic tuberculosis: a critical review of literature from the pre-chemotherapy era.

Abstract: The pre-chemotherapy literature documented the natural history of tuberculosis in childhood. These disease descriptions remain invaluable for guiding public health policy and research, as the introduction of effective chemotherapy radically changed the history of disease. Specific high-risk groups were identified. Primary infection before 2 years of age frequently progressed to serious disease within the first 12 months without significant prior symptoms. Primary infection between 2 and 10 years of age rarely progressed to serious disease, and such progression was associated with significant clinical symptoms. In children aged >3 years the presence of symptoms represented a window of opportunity in which to establish a clinical diagnosis before serious disease progression. Primary infection after 10 years of age frequently progressed to adult-type disease. Early effective intervention in this group will reduce the burden of cavitating disease and associated disease transmission in the community. Although the pre-chemotherapy literature excluded the influence of human immune deficiency virus (HIV) infection, recent disease descriptions in HIV-infected children indicate that immune-compromised children behave in a similar fashion to immune immature children (less than 2 years of age). An important concept deduced from the natural history of tuberculosis in childhood is that of relevant disease. Deciding which children to treat may be extremely difficult in high-prevalence, low-resource settings. The concept of relevant disease provides guidance for more effective public health intervention.

False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria?

Abstract: SUMMARY of Epidemiology & Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada BACKGROUND: Despite certain drawbacks, the tuberculin skin test (TST) remains in widespread use. Important advantages of the TST are its low cost, simplicity and interpretation based on extensive published literature. However, TST specificity is reduced by bacille Calmette-Guerin (BCG) vaccination and exposure to non-tuberculous mycobacteria (NTM). METHODS: To estimate TST specificity, we reviewed the published literature since 1966 regarding the effect of BCG vaccination and NTM infection on TST. Studies selected included healthy subjects with documented BCG vaccination status, including age at vaccination. Studies of NTM effect had used standardised NTM antigens in healthy subjects. RESULTS: In 24 studies involving 240 203 subjects BCGvaccinated as infants, 20 406 (8.5%) had a TST of 10� mm attributable to BCG, but only 56/5639 (1%) were TST-positive if tested � 10 years after BCG. In 12 studies of 12 728 subjects vaccinated after their first birthday, 5314 (41.8%) had a false-positive TST of 10� mm, and 191/898 (21.2%) after 10 years. Type of tuberculin test did not modify these results. In 18 studies involving 1 169 105 subjects, the absolute prevalence of false-positive TST from NTM cross-reactivity ranged from 0.1% to 2.3% in different regions. CONCLUSIONS: The effect on TST of BCG received in infancy is minimal, especially � 10 years after vaccination. BCG received after infancy produces more frequent, more persistent and larger TST reactions. NTM is not a clinically important cause of false-positive TST, except in populations with a high prevalence of NTM sensitisation and a very low prevalence of TB infection.

The curious characteristics of pyrazinamide: a review.

Abstract: Pyrazinamide (PZA) is an important sterilising tuberculosis drug that helps to shorten the duration of current chemotherapy regimens for tuberculosis. When first discovered, it had activity in murine tuberculosis but no apparent in vitro activity, and its subsequent use in treatment depended largely on classic experiments at Cornell University, which showed its requirement for an acid pH for activity and its sterilising activity in the mouse. Recent studies have shown that PZA enters Mycobacterium tuberculosis by passive diffusion, is converted to pyrazinoic acid (POA) by nicotinamidase/pyrazinamidase (PZase) and is then excreted by a weak efflux pump. Protonated POA (HPOA) is reabsorbed into the bacilli under acid conditions and accumulates because the efflux pump is inefficient, causing cellular damage. Unlike other antibacterials, PZA has no defined target of action. PZA is more active against old than against actively growing cultures, probably because the energy production and efflux pump would be slowed down by low bacterial metabolism. This review deals with the activity of PZA in vitro, in macrophages and in animal models. It describes the evidence from clinical trials that it is an effective sterilising drug that acts synergistically with rifampicin. The highly diverse mutations in the PZase gene (pncA) that lead to loss of PZase activity cause PZA resistance. Methods for susceptibility determination either as tests against PZA or nicotinamide in liquid and solid media, as tests for PZase activity or for mutations in pncA, are reviewed.

The relationship between malnutrition and tuberculosis: evidence from studies in humans and experimental animals

Abstract: The oral traditions of medicine and public health have it that malnutrition is an important risk factor for the development of tuberculosis (TB). Malnutrition profoundly affects cell-mediated immunity (CMI), and CMI is the principle host defense against TB. It makes biological sense. Although most health professionals readily accept this principle, much of this belief is based on uncontrolled observations such as disaster situations or on backwards logic from the cachexia common among TB patients. In fact, the evidence in humans is surprisingly thin from the perspective of scientific rigor. And few data, if any, quantify the extent of the relative or attributable risk of TB due to malnutrition. Moreover, until recently, data from experimental animals were based on animal models that were largely not relevant to human TB infection and disease. This article reviews the scientific data supporting the contention that malnutrition is an important risk factor for TB concentrating on observations in humans and on experimental animal studies based on a highly relevant animal model. If it is true, malnutrition may account for a greater population attributable risk of TB than HIV infection, and certainly a much more correctable one.

Studies on the treatment of tuberculosis undertaken by the British Medical Research Council tuberculosis units, 1946-1986, with relevant subsequent publications.

Abstract: This review describes the studies on the treatment of tuberculosis carried out by the British Medical Research Council's tuberculosis units and their many collaborators throughout the world during the period from their formation in 1946 to their closure in 1986. References to all publications on studies during the period are listed. The review also includes selected publications by members of their staff who have continued the studies since closure of the units. The review is under four main headings: 1) controlled trials of chemotherapy, 2) bacteriological studies, 3) pharmacological studies, and 4) studies of surveillance and policies relevant to the control of tuberculosis.Major events in the development of modern chemotherapy and the control of tuberculosis are as follows:1 1946: The initial trial assessing the value of the addition of streptomycin to bed rest.2 1948: The demonstration that the emergence of bacterial resistance to either streptomycin or p-aminosalicylic acid (PAS) alone was greatly decreased when combined treatment was given with both drugs.3 1952-1955: Exploration of treatment with isoniazid alone and in combination with PAS or streptomycin.4 1958-1967: The search for affordable regimens for developing countries that led to the substitution of thiacetazone for PAS.5 1959: The demonstration that chemotherapy given at home was as effective as when given in a sanatorium and did not lead to any increase in the rate of infection in family contacts.6 1958 onwards: Initiation of the policy of full supervision of chemotherapy (directly observed treatment-DOT) and its later implementation in Hong Kong and Madras.7 1961 onwards: Exploration of intermittent regimens of chemotherapy to assist implementation of full supervision.8 1970: The first demonstration that inclusion of rifampicin or pyrazinamide in a regimen of streptomycin and isoniazid substantially reduced the subsequent relapse rate.9 1972-1974: Demonstration that the period of treatment could be shortened to 6 months by the inclusion of rifampicin and pyrazinamide in the regimen.10 1976: Delineation of modern short-course chemotherapy regimens by showing that the sterilising activity of pyrazinamide was confined to the first 2 months of treatment during the intensive phase, whereas the sterilising activity of rifampicin persisted throughout the continuation phase.11 1977 onwards: Demonstration of the value of intermittency in short-course regimens, particularly that three times weekly treatment throughout was as effective as, and less toxic and expensive than daily regimens.When the units were closed in 1986, all of the measures necessary for successful programmes for the control of tuberculosis had been delineated, particularly the regimens of treatment to be used, the need for full supervision of drug-taking (DOT) and the use of surveys to measure the extent to which national programmes were finding and treating infectious disease. These tools were then available to national organisations and to international organisations such as the World Health Organisation (WHO) and the International Union Against Tuberculosis and Lung Disease (IUATLD), to implement in control programmes.