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Robert Koch (1843–1910) identified Mycobacterium tuberculosis as the cause of tuberculosis (TB) in 1882. It is now recognized that M. tuberculosis is an archetypical human pathogen and that its evolutionary origin is closely related to the controlled use of fire, which is unique to Homo sapiens and has created an environmental niche for mycobacteria to be transmitted via the respiratory route.1 This long period of coevolution explains why M. tuberculosis is so well adapted to its human host and why only a small minority of people infected with M. tuberculosis ever progress to active disease.

Despite its ancient origins, TB remains the number one infectious disease killer of humans. In 2015 it was responsible for an estimated 10.4 million incident cases (1 million in children) and 1.8 million deaths.2 It is rarely appreciated that TB is a major cause of mortality in children aged <5 years living in endemic areas.3 However, most TB deaths in young children are attributed to other common causes, such as pneumonia, malnutrition, or human immunodeficiency virus (HIV) infection.3,4 On a global scale, TB is sustained in conditions of poverty and social inequality, and in sub-Saharan Africa, in particular, it is fueled by HIV coinfection.5 Rising rates of drug-resistant TB is a particular concern,6,7 especially in settings where these strains are actively transmitted and also infecting young children.8,9

In endemic countries, TB control programs traditionally focused on the diagnosis and treatment of the most infectious cases (adults with sputum smear–positive TB) in an attempt to achieve epidemic control. As a result, childhood TB received little public health emphasis, since young children tend to have paucibacillary disease and are rarely infectious.4 In recent years there has been increased awareness that children in endemic areas carry a huge disease burden and experience considerable TB-related morbidity and mortality, which are preventable and treatable.10 Poor countries carry the bulk of the TB disease burden, as both exposure to M. tuberculosis and the vulnerability to progress to disease following infection are increased in these settings (Figure 39-1).

FIGURE 39-1.

The main variables that contribute to the prevalence of TB in adults and, by extrapolation, the burden of childhood TB. [Reprinted with permission of the International Union Against Tuberculosis and Lung Disease. Copyright © The Union. Marais BJ, Obihara CC, Warren RM, et al. The burden of childhood tuberculosis: a public health perspective. Int J Tuberc Lung Dis. 2005 Dec;9(12):1305-1313.]

The risk for developing active TB following infection is determined mainly by the age and immune status of the child.11 Very young (<2–3 years of age) immunity-immature children or those of any age with significant T-cell immunity compromise (Table 39-1) are at greatest risk. If children do progress ...

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