A whole blood test of interferon-gamma (INF-γ) release assay (IGRA), a cytokine elaborated by lymphocytes in response to tuberculosis antigens, is the recommended diagnostic test for persons older than 5 years of age in the United States. It has similar sensitivity as the TST but improved specificity because it is unaffected by prior bacille Calmette-Guérin vaccination.
The ultimate diagnostic confirmation relies on culture of the organism, a process that usually is more successful with tissue, such as pleura or pericardial membrane from biopsy, rather than pleural or pericardial fluid. Sputum is an excellent source for diagnosis in adults but is difficult to obtain in young children. Induced sputum or gastric fluid obtained via an indwelling nasogastric tube with samples taken before or immediately on waking contains swallowed sputum and provides appropriate samples in young children. Large volumes of fluid (CSF, pericardial fluid) yield a higher rate of recovery of organisms,
Induration ≥5 mm Children in close contact with persons with known or suspected contagious tuberculosis disease
Children suspected to have tuberculosis disease Findings on chest radiograph consistent with active or previously active tuberculosis Clinical evidence of tuberculosis disease†
Children receiving immunosuppressive therapy‡ or with immunosuppressive conditions, including HIV infection
Children <4 years of age Children with other medical conditions, including Hodgkin disease, lymphoma, diabetes mellitus, chronic renal failure, and malnutrition
Children with increased exposure to tuberculosis disease Children born, or whose parents were born, in high-prevalence regions of the world Children frequently exposed to adults who are HIV-infected, homeless, users of illicit drugs, residents of nursing homes, incarcerated or institutionalized, or migrant farm workers Children who travel to high-prevalence regions of the world
Induration ≥15 mm Children ≥4 years of age without any risk factors *These criteria apply regardless of previous bacille Calmette-Guérin immunization. Erythema at tuberculin skin test site does not indicate a positive test result. Tuberculin reactions should be read at 48 to 72 hours after placement.
†Evidence by physical examination or laboratory assessment that would include tuberculosis in the working differential diagnosis (e.g., meningitis).
‡Including immunosuppressive doses of corticosteroids.
but slow growth of the mycobacteria makes culture less helpful in very ill children. When the organism is grown, drug susceptibilities should be determined because of the increasing incidence of resistant organisms.
Antigen detection and DNA probes have expedited diagnosis, especially with CNS disease.
Because many cases of pulmonary tuberculosis in children are clinically relatively silent, radiography is a cornerstone for the diagnosis of disease. All lobar segments of the lung are at equal risk of being the focus of the initial infection. In 25% of cases, two or more lobes of the lungs are involved, although disease usually occurs at one site only. Spread of infection to regional lymph nodes occurs early.
The hallmark of childhood pulmonary tuberculosis is the relatively large size and importance of the hilar lymphadenitis compared with the less significant size of the initial parenchymal focus, together historically referred to as the Ghon complex (with or without calcification of the lymph nodes). Hilar lymphadenopathy is inevitably present with childhood tuberculosis. Partial bronchial obstruction caused by external compression from the enlarging nodes can cause air trapping, hyperinflation, and lobar emphysema. Occasionally children have a picture of lobar pneumonia without impressive hilar lymphadenopathy. If the infection is progressively destructive, liquefaction of the lung parenchyma leads to formation of a thin-walled primary tuberculous cavity. Adolescents with pulmonary tuberculosis may develop segmental lesions with hilar lymphadenopathy or the apical infiltrates, with or without cavitation, that are typical of adult reactivation tuberculosis.