Operational Handbooks

Testing for M. tuberculosis infection using TST or IGRA is useful to support a diagnosis of TB in children with suggestive clinical features who are sputum smear-negative or who cannot produce sputum. A positive test for TB infection indicates prior or current infection with M. tuberculosis and can be particularly useful in the absence of known TB exposure (no positive contact history), as it confirms the child has been infected at some point in time (6, 15).

TST is considered positive (indicating infection with M. tuberculosis) if:

In children with signs and symptoms of PTB in settings with a pre-test probability of 5% or higher (prevalence of confirmed TB of 5% or above in this specific population), repeat testing with Xpert MTB/RIF or Ultra may be considered after an initial negative Xpert MTB/RIF or Ultra test if the clinician has a high index of suspicion that the child has TB, using any of the recommended specimen types.

The urine lateral flow lipoarabinomannan (LF-LAM) assay is an immunocapture assay based on the detection of the mycobacterial lipoarabinomannan antigen in urine. For specific populations, LF-LAM may be used together with other approved TB diagnostics tests and affords a distinct advantage as a point-of-care test. Although the assay lacks sensitivity, it can be used as a fast bedside rule-in test for people living with HIV, especially in urgent cases where a rapid TB diagnosis is critical for the person’s survival.

The Xpert MTB/RIF assay is a cartridge-based automated test that uses real-time polymerase chain reaction (PCR) on the GeneXpert® platform to identify M. tuberculosis complex and mutations associated with rifampicin resistance directly from sputum specimens in less than 2 hours (76).

The Xpert MTB/RIF Ultra assay uses the same GeneXpert platform and a new enhanced cartridge developed to improve the sensitivity and reliability of detection of M. tuberculosis complex and rifampicin resistance (76).

Depending on the availability, resources and capacity, appropriate specimens from suspected sites of involvement should be collected for rapid testing using mWRDs or culture, and histopathological examination should be done for children with EPTB whenever possible. WHO recommends that NTPs replace microscopy as the initial diagnostic test for TB with mWRDs, which can be used on various respiratory and non-respiratory specimens (Table 4.4) (76).

WHO-recommended clinical samples for the diagnosis of PTB in children and adolescents using Xpert MTB/RIF or Ultra include sputum (expectorated or induced), gastric or nasopharyngeal aspirates, and stool. Other mWRDs using respiratory samples have only been validated on sputum samples. Each of these specimen types has distinct advantages and disadvantages (Table 4.1). Annex 3 summarizes the types of respiratory and non-respiratory specimens.

Despite challenges with bacteriological confirmation of paucibacillary TB in young children, every effort should be made to establish bacteriological confirmation. In adolescents, who usually have adult-type disease, bacteriological confirmation is common.

Bacteriological confirmation is even more important for children and adolescents who:

TB may present in atypical ways, such as acute severe pneumonia (more common in children aged under 2 years and children living with HIV) or fixed airway wheezing (more common in young children aged under 5 years) (72).

Signs of severe pneumonia include:

Although there are no findings on clinical examination that can confirm TB, some clinical signs are highly suggestive. In addition, a variety of nonspecific signs should raise clinical suspicion and prompt an evaluation for TB disease. The following clinical features can alert care providers that the child may have TB (6, 72):

The index patient is the initially identified person of any age with new or recurrent TB in a specific household or other comparable setting to which others may have been exposed. An index case is the person on whom a contact investigation is centred but is not necessarily the source case (28).