Chapter | 30 | Jon S Friedland
Tuberculosis and other mycobacterial infections
Tuberculosis is the clinically most important of the mycobacterial
infections and is the subject of the first section of this chapter; the sec-
ond section covers other mycobacterial infections except for leprosy,
which is dealt with in Chapter 103. Details of antimycobacterial drugs
are to be found in Chapter 143. Tuberculosis and HIV co-infection is
also covered separately in Chapter 93. The clinical microbiology of
mycobacterial infections is discussed in Chapter 174.
Tuberculosis
Tuberculosis, a disease identified in skeletons over 6000 years old,
remains the most prevalent infectious disease in the world. This chap-
ter focuses on current understanding of pathophysiology, epidemiol-
ogy and clinical aspects of tuberculosis.
EPIDEMIOLOGY
Worldwide incidence and prevalence
Mycobacterium tuberculosis is estimated to infect 1.6 billion people
worldwide or approximately one-third of the world’s population.1
Usually infection is contained by the immune system so that about
14.4 million people have clinical disease at any one time. The World
Health Organization (WHO) reported that there were approximately
9.2 million new cases and 1.7 million deaths from tuberculosis in
2006 (http://www.who.int/tb/publications/global_report/2008/en/
index.html). Recent data on tuberculosis notification rates are shown
in Figure 30.1. However, notification data may be incomplete with
underreporting of cases. Confounding factors in global collection of
incidence and prevalence data include effects of treatment, difficul-
ties in identifying extrapulmonary disease and those associated with
tuberculin testing.
Over 96% of tuberculosis-related deaths occur in the poorer nations
of the world and the disease has huge social and economic costs. In
wealthier nations, rates of tuberculosis have been falling over the last
50 years in part due to social improvements, development of effec-
tive treatments, active case finding and use of the bacille Calmette–
Guérin (BCG) vaccine. Recently, this trend has been halted in some
countries due to increased incidence of tuberculosis in high-risk pop-
ulation groups including poorer communities, migrants and patients
with HIV infection. Levels of disease in homeless populations, intra-
venous drug users and prisoners in developed countries may also be
high.2 The worldwide prevalence of diabetes mellitus is increasing and
increases the risk of tuberculosis.3
The impact of HIV
The WHO estimate that there were 709 000 new cases of tuberculosis
associated with HIV in 2006. HIV-seropositive patients are more
susceptible to infection by M. tuberculosis. Reactivation of tubercu-
losis occurs at least 10 times more frequently than in age-matched
controls. The majority of people co-infected with tuberculosis and
HIV live in sub-Saharan Africa (over 85%), the Indian subcontinent
and South East Asia (Fig. 30.2). Patients tend to be sicker and in
greater need of hospitalization. The relationship between HIV and
tuberculosis is such that tuberculosis patients should be offered HIV
screening. Diagnosis of dual infection may be difficult since HIV pre-
disposes to atypical, nodal and extrapulmonary disease. The subject
of HIV–tuberculosis co-infection is explored in depth in Chapter 93
and is not considered further here.
Spread of infection
Spread of infection is dependent on inhalation of aerosols from indi-
viduals with pulmonary infection. Proximity to and duration of asso-
ciation with an index case are critical factors. Up to 25% of household
contacts of an index case may acquire infection although the extent
to which individual genetic predisposition or immunologic impair-
ment contributes to this is uncertain. Although contributory, the exact
role of factors such as vitamin D deficiency and iron overload in the
spread of tuberculosis is unknown. Spread of infection is separate to
development of disease which occurs in less than 10% of infected per-
sons and is significantly affected by impaired cell-mediated immunity.
Congenital transmission of tuberculosis is not a significant factor in
the natural spread of disease.
Transmission in closed institutions
Overcrowding contributes to the spread of tuberculosis amongst the
poor. Close proximity to infected individuals is a significant issue in
any closed institution and for health-care workers. Many countries have
specific guidelines for tuberculosis control in institutions. In prisons,
the situation is complicated by the fact that inmates have an increased
incidence of HIV, are frequently moved to other prisons or back into
the community with little warning and may be poorly managed in
terms of health services. Since release of prisoners is often into poor
circumstances and crowded hostels, the consequence of undetected
or  inadequately treated tuberculosis may be rapid spread of disease.
Mass incarceration can lead to an increase in cases of tuberculosis and
a rise in drug-resistant disease.4 An effective public health program with
an active community care component can overcome such problems.
Genetic techniques using restriction fragment length polymorphism
(RFLP) analysis (often of the insertion sequence IS6110) to provide
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