Tuberculosis in children

Abstract

Many clinicians regard tuberculosis as an adult pulmonary disease, but tuberculosis (TB) is a major cause of disease, both pulmonary and extrapulmonary, and death in young children from TB-endemic countries, especially in areas affected by poverty, social disruption, and human immunodeficiency virus (HIV) infection. This article reviews the disease burden and the natural history of disease in children with TB. It also provides guidance regarding the diagnosis, treatment, and prevention of TB in children.

Figure 1.

Schematic time line following primary pulmonary infection with M. tuberculosis. Data of time line of tuberculosis is adapted from Marais et al. (2005a), first described by Wallgren (1948). 0, Incubation; I, tuberculin skin test conversion; II, Ghon focus and/or disseminated (miliary) disease; III, lymph node disease (<5 yr of age)/pleural effusion (>5 yr of age); IV, adult-type disease (>10 yr of age).

Figure 2.

Factors that influence the dynamic balance between M. tuberculosis and host immunity in children. (Adapted from Marais et al. 2005a.)

Figure 3.

Uncomplicated Ghon focus—apex of the left lower lobe (Gie 2003; Marais et al. 2004b). Place where the “eagle has landed,” rarely seen because it is usually transient.

Figure 4.

Complicated Ghon focus (Gie 2003; Marais et al. 2004b). This image reflects poor disease containment at the point of entry; infants and severely immune-compromised individuals are particularly vulnerable.

Figure 5.

Intrathoracic lymph node disease (anteroposterior view) (Gie 2003; Marais et al. 2004b). Lymph nodes are part of the Ghon complex and the main site of disease; however, they are often difficult to visualize with certainty.

Figure 6.

Intrathoracic lymph node disease (lateral view) (Gie 2003; Marais et al. 2004b). It is essential to perform good quality AP and lateral views. One can see density behind and below the carina, which is not the area where normal physiological structures occur. Also, some fluid in the horizontal and transverse fissures indicates some inflammatory response (not indicative of TB). The dense circular ring around the hilum (so-called doughnut sign) is indicative of perihilar lymph node involvement.

Figure 7.

Airway obstruction with “check valve” effect (Gie et al. 2003; Marais et al. 2004b). The enlarged lymph nodes frequently cause airway complications, especially in young children with small and pliable airways. Hyperinflation (ball valve effect) of left lung. See remnant of Ghon focus and large left-sided perihilar nodes.

Figure 8.

Caseating (expansile) pneumonia (Gie 2003; Marais et al. 2004b). TB lymph nodes cause airway narrowing (almost pathognomonic), because, unlike other mass lesions, it traps and compresses the airway. Lymph nodes can also “rupture” (with sinus formation) into the airway (as occurs with scrofula), which may result in aspiration of caseous material and development of dense (expansile) caseating pneumonia. If this was any other organism, the child would have been in the intensive care unit. Always think of TB when there is this dichotomy between the radiological severity of disease and the clinical signs and symptoms (children often chronically ill, but rarely hyperacute—probably because of reduced V/Q [ventilation/perfusion ratio] mismatch).

Figure 9.

Pleural effusion (Gie 2003; Marais et al. 2004b). Uncommon in children of <6–8 yr. Usually a hypersensitivity response (may develop TB empyema) with typical presentation, well localized chest pain with intermittent fever, and the child otherwise remarkably well. Unilateral dullness on percussion. Fluid characteristically clear with yellow discoloration; TST (tuberculin skin text) very reactive >15–20 mm.

Figure 10.

Disseminated (miliary) disease (Gie 2003; Marais et al. 2004b). Usually in very young children (<2–3 yr of age) or severely immune-compromised within 6 mo after primary infection. Incidence proven to be reduced by BCG vaccination in HIV-uninfected/unexposed children (not in HIV-infected). Mtb spreads via the bloodstream; therefore, tubercles are not restricted to the lungs, but also affect other organs (e.g., liver, spleen) and is frequently associated with TB meningitis (consider lumbar puncture to exclude TBM—management the same).

Figure 11.

Adult-type disease (Gie 2003; Marais et al. 2004b). This type of disease manifestation is not seen in young children, emerges with the onset of puberty at ∼8–10 yr of age, and seems to be associated with an excessive and poorly regulated immune response (excessive hypersensitivity type response). Any child with cavitary disease is infectious (as infectious as an adult sputum smear-positive case) and should be regarded as a potential source case.

Figure 12.

Algorithm for diagnosis and classification of tuberculosis in children. HIV, human immunodeficiency virus; TST, tuberculin skin test; IGRA, interferon-γ release assay; Mtb—Mycobacterium tuberculosis. ^#None of the immune-based tests (TST/IGRA) can “rule out” TB disease with confidence and conversion may be delayed for 2–3 mo after documented exposure. Diagnostic labels: ¹No TB exposure or infection; ²TB exposure/infection with low risk of progression to disease; ³TB exposure/infection with high risk of progression to disease; ⁴unlikely TB disease; ⁵TB disease. (Data adapted from Perez-Velez and Marais 2012.)

Figure 13.

The main variables that contribute to the burden of childhood TB in a particular community. (Data adapted from Marais et al. 2005b.)