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.
SeminarTuberculosis
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
References (166)
- et al.
HIV-1/AIDS and the control of other infectious diseases in Africa
Lancet
(2002) - et al.
Tumor necrosis factor-alpha is required in the protective immune response against Mycobacterium tuberculosis in mice
Immunity
(1995) - et al.
Immune responses in tuberculosis
Curr Opin Immunol
(2000) - et al.
Influence of vitamin D deficiency and vitamin D receptor polymorphisms on tuberculosis among Gujarati Asians in west London: a case-control study
Lancet
(2000) - et al.
A double-blind, placebo-controlled study of vitamin A and zinc supplementation in persons with tuberculosis in Indonesia: effects on clinical response and nutritional status
Am J Clin Nutr
(2002) - et al.
Linkage of tuberculosis to chromosome 2q35 loci, including NRAMP1, in a large aboriginal Canadian family
Am J Hum Genet
(2000) - et al.
Transmission of Mycobacterium tuberculosis from patients smear-negative for acid-fast bacilli
Lancet
(1999) - et al.
Comparison of T-cell-based assay with tuberculin skin test for diagnosis of Mycobacterium tuberculosis infection in a school tuberculosis outbreak
Lancet
(2003) - et al.
Randomized controlled trial of directly observed treatment (DOT) for patients with pulmonary tuberculosis in Thailand
Trans R Soc Trop Med Hyg
(1999) Directly observed treatment for tuberculosis
Lancet
(1999)
Frequency and type of reactions to antituberculosis drugs: observations in routine treatment
Tuberc Lung Dis
A clinician's guide to tuberculosis
The growing burden of tuberculosis: global trends and interactions with the HIV epidemic
Arch Intern Med
Global tuberculosis control: surveillance, planning, financing, WHO Report 2003 (WHO/CDS/TB/2003.316)
The resurgence of tuberculosis in Russia
Philos Trans R Soc Lond Biol Sci
Anti-tuberculosis drug resistance in the world. Report no 2. Prevalence and trends (WHO/CDS/TB/2000.278)
On air-borne infection: study II, droplets and droplet nuclei
Am J Hygiene
Droplet expulsion from the respiratory tract
Am Rev Respir Dis
Aerial dissemination of pulmonary tuberculosis: a two-year study of contagion in a tuberculosis ward
Am J Hygiene
The prognosis of a positive tuberculin reaction in childhood and adolescence
Am J Epidemiol
Recent studies in the epidemiology of tuberculosis, based on the risk of being infected with tubercle bacilli
Adv Tuberc Res
The host immune response to tuberculosis
Am J Respir Crit Care Med
Clinical correlates of interferon-gamma production in patients with tuberculosis
Clin Infect Dis
Review: The immune response in human tuberculosis: implications for tuberculosis control
J Infect Dis
Mycobacterium tuberculosis inhibits IFN-gamma transcriptional responses without inhibiting activation of STAT1
J Immunol
An essential role for interferon-gamma in resistance to Mycobacterium tuberculosis infection
J Exp Med
Structural deficiencies in granuloma formation in TNF gene targeted mice underlie the heightened susceptibility to aerosol Mycobacterium tuberculosis infection, which is not compensated for by lymphotoxin
J Immunol
Targeted tuberculin testing and treatment of latent tuberculosis infection
Am J Respir Crit Care Med
Depressed T-cell interferon-gamma responses in pulmonary tuberculosis: analysis of underlying mechanisms and modulation with therapy
J Infect Dis
HIV-seronegative adults with extrapulmonary tuberculosis have abnormal innate immune responses
Clin Infect Dis
Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent
N Engl J Med
Partial interferon-gamma receptor 1 deficiency in a child with tuberculoid bacillus Calmette-Guerin infection and a sibling with clinical tuberculosis
J Clin Invest
Interleukin-12 receptor beta1 deficiency in a patient with abdominal tuberculosis
J Infect Dis
Tuberculosis in twins: a re-analysis of the Prophit survey
Am Rev Respir Dis
Genetics and resistance to tuberculosis
Ann Intern Med
Human leukocyte antigen (HLA)-linked control of susceptibility to pulmonary tuberculosis and association with HLA-DR types
J Infect Dis
Association of an HLA-DQ allele with clinical tuberculosis
JAMA
Variations in the NRAMP1 gene and susceptibility to tuberculosis in West Africans
N Engl J Med
Tuberculosis and chronic hepatitis B virus infection in Africans and variation in the vitamin D receptor gene
J Infect Dis
Influence of polymorphism in the genes for the interleukin (IL)-1 receptor antagonist and IL-1beta on tuberculosis
J Exp Med
Interleukin-10, polymorphism in SLC11A1 (formerly NRAMP1), and susceptibility to tuberculosis
J Infect Dis
Ethnic-specific genetic associations with pulmonary tuberculosis
J Infect Dis
Tuberculosis in patients infected with human immunodeficiency virus: perspective on the past decade
Clin Infect Dis
Extrapulmonary tuberculosis in the United States
Am Rev Respir Dis
Epidemiologic basis of tuberculosis control
Primary serofibrinous pleural effusion in military personnel
Am Rev Tuberc
Tuberculous meningitis
J Neurol Neurosurg Psychiatry
Tuberculous meningitis in patients infected with the human immunodeficiency virus
N Engl J Med
Tuberculosis of the genitourinary tract
Treatment of tuberculosis: guidelines for national programmes
Cited by (864)
Drug combinations for inhalation: Current products and future development addressing disease control and patient compliance
2023, International Journal of PharmaceuticsA rare case of cervical tuberculous lymphadenitis followed by impaired consciousness
2022, Journal of Oral and Maxillofacial Surgery, Medicine, and PathologyThe cleavage kinetics of hydrazide derivatives of isoniazid by HPLC-UV/DAD and its impact on activity against Mycobacterium tuberculosis
2022, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life SciencesEfficacy and safety of combined isoniazid-rifampicin-pyrazinamide-levofloxacin dry powder inhaler in treatment of pulmonary tuberculosis: A randomized controlled trial
2021, Pulmonary Pharmacology and TherapeuticsThe Added Value of Bronchoalveolar Lavage for Pulmonary Tuberculosis Diagnosis in High-Risk Hospitalized Patients with Negative Sputum Samples
2024, Advances in Respiratory Medicine