The term tuberculosis describes a broad range of clinical illnesses caused by Mycobacterium tuberculosis. Although M. tuberculosis may affect any organ, pulmonary tuberculosis is the most common form, the most communicable, and the focus of the present review. Approximately 1.7 billion people, nearly one third of the worlds population, are thought to be infected with M. tuberculosis, with an estimated that two million deaths each year (Jasmer 2002).

Tuberculosis is transmitted through inhalation of droplet nuclei from infected people. The pathogenesis of tuberculosis involves three phases, transmission and acquisition of infection, latency, and progression of latent infection into active disease. In most instances, the infection is asymptomatic and the only evidence of infection is a positive skin hypersensitivity test, also known as a Mantoux or tuberculin test. Tuberculin testing is performed by injecting a standard dose of tuberculin into the skin of the forearm and measurement of the subsequent skin reaction (an induration or palpable raised hardened area). A person who has been exposed to the bacteria is expected to mount an immune response in the skin containing the bacterial proteins. The reaction is read by measuring the diameter of induration in millimetres. Calcific foci in the lung are seen only in a minority of cases, with viable bacilli in an even smaller minority. Approximately 3% to 4% of people with latent infection acquire active tuberculosis during the first year after tuberculin conversion (converting from a negative to positive skin reaction to a tuberculin test), and an additional 5% to 15% of people with latent infection develop active disease during their lifetime (Mandell 2000).

It should be noted that people who have been received a Bacille Calmette‐Guérin vaccine (BCG), a live‐attenuated mycobacterial strain derived from Mycobacterium bovis, may have a reaction to a tuberculin test. No reliable method has been developed to distinguish tuberculin reactions caused by vaccination with BCG from those caused by natural mycobacterial infections, although reactions of greater than 20 mm of induration are not likely caused by BCG. Therefore, a positive reaction to tuberculin in BCG‐vaccinated persons indicates infection with M. tuberculosis when the person tested is at increased risk for recent infection or has medical conditions that increase the risk for disease (ATS 2000). People with increased risk for developing active tuberculosis due exposure to M. tuberculosis include people with recent skin test conversion, children under the age of five, and people with particular clinical conditions such as immunosuppression (ATS 2000).

Symptoms of tuberculosis include cough (sometimes with haemoptysis or blood in the sputum), chest pain, breathlessness, night sweats, and signs of pneumonia. In advanced disease, there may be extreme weight loss. Approximately a quarter of sufferers from the disease die, most of them young adults (Dye 2002).

The emergence and spread of multiple‐drug‐resistant tuberculosis (MDR‐TB), caused by strains of M. tuberculosis resistant to at least isoniazid and rifampicin, is a threat to global tuberculosis control. Treatment of MDR‐TB is prolonged, expensive, more toxic than treatment of susceptible tuberculosis, and often unsuccessful (Pablos‐Mendez 2002).

MDR‐TB is essentially a man‐made disease. Exposure to a single drug, whether as a result of poor adherence to treatment, inappropriate prescribing (including inappropriate multiple‐drug therapy), irregular drug supply, or poor drug quality, suppresses the growth of bacilli susceptible to that drug but permits the multiplication of pre‐existing drug‐resistant mutants. The patient then develops acquired resistance. Subsequent transmission of such bacilli to other people may lead to disease that is drug resistant from the outset, an occurrence known as primary resistance (WHO/IUATLD 2004).

According to the World Health Organization (WHO), the prevalence of MDR‐TB between 1999 and 2002 among new cases ranged from 0% to 14.2% (1.1% median). Among previously treated cases, the prevalence ranged between 0% and 60% (7% median). When all cases were combined, the prevalence ranged between 0% and 26.8% (1.7% median); and rates of over 10% were documented in 11 countries (WHO/IUATLD 2004).

Treatment of latent tuberculosis infection has been a key component in tuberculosis control for several decades. The American Thoracic Society recommends using isoniazid, rifampicin, as chemoprohylactic agents for treating latent tuberculosis in groups at high risk for susceptible tuberculosis (ATS 2000). A Cochrane review demonstrated that treating HIV‐negative people at increased risk of developing active tuberculosis with isoniazid resulted in a reduced risk of developing active tuberculosis when compared with placebo (relative risk (RR) of 0.40, 95% confidence intervals (95%CI) 0.31 to 0.52) (Smieja 2004). According to another Cochrane review of HIV‐positive people, any treatment regimen of latent tuberculosis results in a reduced risk of active tuberculosis (RR 0.64, 95% CI 0.51 to 0.81) (Woldehanna 2004). Treatment of MDR‐TB contacts is complicated by resistance of the source isolates to recommended drugs and unproven cost‐effectiveness of alternative treatment.

While the level of evidence regarding the effectiveness of treatment of latent tuberculosis for people at risk of susceptible tuberculosis is high, experts are still undecided on the management of people exposed to MDR‐TB (Passannante 1994). According to a statement issued by the American Thoracic Society and adopted by the Centers for Disease Control and Prevention, immunocompetent people exposed to MDR‐TB should be followed up for six months, whether treated or not. In cases where they are treated, the American Thoracic Society recommends the following two drug regimens for six to 12 months if the organisms from the index case patient are known to be susceptible to these agents (ATS 2000): pyrazinamide and ethambutol; or pyrazinamide and a quinolone (levofloxacin or ofloxacin). However, frequent adverse have been documented in people prescribed treatment of latent tuberculosis using the above agents. These adverse effects include hepatitis, hyperuricemia, rash (pyrazinamide) and optic neuritis (ethambutol) (Yee 2003).

This review will appraise and summarize the evidence on the effectiveness of antituberculous drugs for preventing active tuberculosis in people exposed to MDR‐TB.