Elsevier

The Lancet

Volume 362, Issue 9387, 13 September 2003, Pages 887-899
The Lancet

Seminar
Tuberculosis

https://doi.org/10.1016/S0140-6736(03)14333-4Get rights and content

Summary

Among communicable diseases, tuberculosis is the second leading cause of death worldwide, killing nearly 2 million people each year. Most cases are in less-developed countries; over the past decade, tuberculosis incidence has increased in Africa, mainly as a result of the burden of HIV infection, and in the former Soviet Union, owing to socioeconomic change and decline of the health-care system. Definitive diagnosis of tuberculosis remains based on culture for Mycobacterium tuberculosis, but rapid diagnosis of infectious tuberculosis by simple sputum smear for acid-fast bacilli remains an important tool, and more rapid molecular techniques hold promise. Treatment with several drugs for 6 months or more can cure more than 95% of patients; direct observation of treatment, a component of the recommended five-element DOTS strategy, is judged to be the standard of care by most authorities, but currently only a third of cases worldwide are treated under this approach. Systematic monitoring of case detection and treatment outcomes is essential to effective service delivery. The proportion of patients diagnosed and treated effectively has increased greatly over the past decade but is still far short of global targets. Efforts to develop more effective tuberculosis vaccines are under way, but even if one is identified, more effective treatment systems are likely to be required for decades. Other modes of tuberculosis control, such as treatment of latent infection, have a potentially important role in some contexts. Until tuberculosis is controlled worldwide, it will continue to be a major killer in less-developed countries and a constant threat in most of the more-developed countries.

Section snippets

Epidemiology

Tuberculosis is the world's second commonest cause of death from infectious disease, after HIV/AIDS. There were an estimated 8–9 million new cases of tuberculosis in 2000, fewer than half of which were reported; 3–4 million cases were sputum-smear positive, the most infectious form of the disease.2 Most cases (5–6 million) are in people aged 15–49 years. Sub-Saharan Africa has the highest incidence rate (290 per 100 000 population), but the most populous countries of Asia have the largest

Pathophysiology

Tuberculosis is spread by airborne droplet nuclei, which are particles of 1–5 μm in diameter that contain Mycobacterium tuberculosis. Because of their small size, the particles can remain airborne for minutes to hours after expectoration by people with pulmonary or laryngeal tuberculosis during coughing, sneezing, singing, or talking.7, 8, 9 The infectious droplet nuclei are inhaled and lodge in the alveoli in the distal airways. M tuberculosis is then taken up by alveolar macrophages,

Genetic predisposition

Several studies have suggested that some patients have a genetic predisposition to tuberculosis. This idea has arisen from studies among monozygotic and dizygotic twins28 and in an assessment of tuberculosis risk according to ancestral history.29 Population-based studies have found an association between tuberculosis and some HLA alleles, as well as polymorphisms in the genes for natural resistance-associated macrophage protein (NRAMP1), the vitamin D receptor, and interleukin 1.30, 31, 32, 33,

Clinical manifestations

The most common clinical manifestation of tuberculosis is pulmonary disease. Extrapulmonary tuberculosis accounts for about 20% of disease in HIV-seronegative people but is more common in HIV-seropositive individuals.38 Among people not infected with HIV, extrapulmonary disease, particularly lymphatic tuberculosis, is particularly common in women and young children.39, 40

Pleural tuberculosis occurs as a result of either primary progressive M tuberculosis infection or reactivation of latent

Active disease

Criteria for the diagnosis of active tuberculosis vary according to the setting. Patients with persistent cough (eg, lasting longer than 2 weeks) should be assessed for tuberculosis.45, 46 Other common symptoms include fever, night sweats, weight loss, shortness of breath, haemoptysis, and chest pain.47 Among children, important diagnostic clues are a history of previous exposure to an individual with tuberculosis or evidence of tuberculosis infection (eg, a positive tuberculin skin test). To

Treatment

The goals of treatment are to ensure cure without relapse, to prevent death, to stop transmission, and to prevent the emergence of drug resistance. M tuberculosis can remain dormant for long periods. The number of tubercle bacilli varies widely with the type of lesion, and the larger the bacterial population, the higher the probability that naturally resistant mutants are present even before treatment is started.78 Long-term treatment with a combination of drugs is required.79 Treatment of

Control

To control tuberculosis, WHO and IUATLD recommend the DOTS strategy,145 which has five elements: political commitment, diagnosis primarily by sputum-smear microscopy among patients attending health facilities, short-course treatment with effective case management (ie, direct observation), regular drug supply, and systematic monitoring to assess outcomes of every patient started on treatment. Standard short-course regimens can cure more than 95% of cases of new, drug-susceptible tuberculosis.

BCG vaccination

Randomised and case-control trials have shown consistently high protective efficacy (mostly above 70%) of BCG against serious forms of disease in children (meningitis and miliary tuberculosis), but variable efficacy against pulmonary tuberculosis in adults.155 Thus, in high-prevalence areas, vaccination is recommended for children at birth or at first contact with health services, except for children with symptomatic HIV infection.156 Even with high coverage, BCG has not had any substantial

Conclusion

The current state of tuberculosis diagnosis, treatment, and control reveals striking contrasts. On the one hand, new diagnostic methods have been developed, and widespread application of control strategies has increased the number of patients effectively diagnosed and treated annually from 696 000 in 1995 to 2·4 million in 2001 (all forms of tuberculosis treated under DOTS), with more than 10 million patients treated in the past 10 years. Effective tuberculosis control is both inexpensive and

Search strategy and selection criteria

We searched PubMed/MEDLINE for articles with tuberculosis as major topic, and epidemiology, pathophysiology, diagnosis, treatment, or control as secondary topics. The Cochrane database was searched for reviews of tuberculosis. We also examined the websites and publications of the WHO, International Union Against Tuberculosis and Lung Disease, British Thoracic Society, American Thoracic Society, and US Centers for Disease Control and Prevention, as well as major current tuberculosis textbooks.

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