Tuberculosis

The

n e w e ng l a n d j o u r na l

of

m e dic i n e

review article
current concepts

Tuberculosis
Alimuddin Zumla, M.D., Ph.D., Mario Raviglione, M.D., Richard Hafner, M.D.,
and C. Fordham von Reyn, M.D.

D

espite the availability of a cheap and effective treatment, tuberculosis still accounts for millions of cases of active disease and deaths
worldwide. The diseasedisproportionately affects the poorest persons in
both high-income and developing countries.1 However, recent advances in diagnostics, drugs, and vaccines and enhanced implementation of existing interventions have
increased the prospects for improved clinical care and global tuberculosis control.

Epidemiol o gy
In 2011, there were 8.7 million new cases of active tuberculosis worldwide (13%
ofwhich involved coinfection with the human immunodeficiency virus [HIV]) and
1.4 million deaths, including 430,000 deaths among HIV-infected patients1 representing a slight decrease from peak numbers in the mid-2000s (Fig. 1). It has been
estimated that there were 310,000 incident cases of multidrug-resistant tuberculosis, caused by organisms resistant to at least isoniazid and rifampin, amongpatients
who were reported to have tuberculosis in 2011 (Fig. 2). More than 60% of these
patients were in China, India, the Russian Federation, Pakistan, and South Africa.1,2
A total of 84 countries have reported cases of extensively drug-resistant tuberculosis,
a subset of multidrug-resistant tuberculosis with added resistance to all fluoroquinolones plus any of the three injectableantituberculosis drugs, kanamycin, amikacin,
and capreomycin.1-3 Sub-Saharan Africa has the highest rates of active tuberculosis
per capita, driven primarily by the HIV epidemic.1 The absolute number of cases is
highest in Asia, with India and China having the greatest burden of disease globally.1 In the United States and most Western European countries, the majority of
cases occur in foreign-born residentsand recent immigrants from countries in
which tuberculosis is endemic.4-6

From the Department of Infection, Division of Infection and Immunity, University College London Medical School,
London (A.Z.); STOP TB Department,
World Health Organization, Geneva
(M.R.); the Tuberculosis Clinical Research Branch, Division of AIDS, National Institute of Allergy and Infectious Diseases, NationalInstitutes of Health,
Bethesda, MD (R.H.); and the Section of
Infectious Disease and International
Health, Geisel School of Medicine at
Dartmouth, Hanover, NH (C.F.R.). Address reprint requests to Dr. Zumla at the
Division of Infection and Immunity, Centre for Clinical Microbiology, 2nd Fl., UCL
Royal Free Campus, Rowland Hill St.,
London NW3 OPE, United Kingdom, or
at a.zumla@ucl.ac.uk.
NEngl J Med 2013;368:745-55.
DOI: 10.1056/NEJMra1200894
Copyright © 2013 Massachusetts Medical Society.

Patho gene sis
Patients with active pulmonary tuberculosis are the source of Mycobacterium tuberculosis. In more than 90% of persons infected with M. tuberculosis, the pathogen is
contained as asymptomatic latent infection. Recent studies raise the possibility that
some persons acquire andeliminate acute infection with M. tuberculosis.7 The risk of
active disease is estimated to be approximately 5% in the 18 months after initial infection and then approximately 5% for the remaining lifetime.8 An estimated 2 billion persons worldwide have latent infection and are at risk for reactivation.1 Contained latent infection reduces the risk of reinfection on repeated exposure,
whereasactive tuberculosis is associated with an increased risk of a second episode
of tuberculosis on reexposure (Fig. S1 in the Supplementary Appendix, available
with the full text of this article at NEJM.org).8-10

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