Operational Handbooks

4.3.5.5. Repeat testing with molecular WHO-recommended rapid diagnostic tests

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.

4.3.5.4. Antigen detection in a lateral flow format (biomarker-based detection)

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.

4.3.5.3. Molecular WHO-recommended rapid diagnostic tests for TB

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).

4.3.5.2. WHO-recommended rapid diagnostic tests

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).

4.3.5.1. Sample types

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.

4.3.3. Clinical examination

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):

4.3.2. History of TB contact

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).

4.3.1. Typical symptoms of pulmonary TB

In most cases, children with TB disease develop chronic unremitting symptoms that persist for more than 2 weeks without sustained improvement or resolution following treatment for alternative diagnoses (e.g. antibiotics for pneumonia, antimalarials for fever, nutritional rehabilitation for failure to thrive or malnutrition). The most common clinical presentation of PTB in children is persistent cough and poor weight gain.