Review Article

Classic and New Diagnostic Approaches to Childhood Tuberculosis

Table 2

Pros and cons of most common diagnostic tests for childhood TB.

MethodologyProsCons

SymptomsNo need for lab infrastructure, diagnostic value if appropriate risk stratification is appliedThis criterion has been approved only in conjunction with the TST and suggestive chest radiography

Traditional chest radiographThe basic equipment is very common in hospitals and some research centers.The images are not always clear and the lesions in children are often subjective

Thorax CT scanEnhanced visualization of small lesions not seen on chest radiograph. X-ray high-resolution computed tomography, it is the most sensitive tool currently available to detect hilar adenopathy and/or early cavitation can be used for follow-upCostly; requires scanner which is not readily available in many settings

AlgorithmsThey are very helpful and easy to use in countries with restricted technologyIs not commonly used due to lack of validation, it is based on responses of patients to which scores are given which are thought to be very subjective

M. tuberculosis cultureGold standard for definitive diagnosis of adult TBCulture usually takes weeks (or four days in accelerated culture), low sensitivity (˂50% in gastric aspirate/sputum)

Smear stain RapidVery low sensitivity (˂50% in gastric aspirate/sputum), difficulty in obtaining sputum samples, and poor performance of smear microscopy

Tuberculin skin test (TST)Very common and cheap reagent, easy to use and to interpret the resultsInespecific, only indicates infection with a mycobacteria or prior BCG vaccination

Polymerase Chain Reaction (PCR)This is a rapid, sensitive, specific and affordable methodThese tests are not performed correctly in all clinical laboratories. The cost involved, the need for thermocycler (or boiling pots at specific temperature), and scrupulous technique to avoid cross-contamination of specimens preclude the use of PCR techniques in many developing countries

In-house nucleic acid amplification assaysMean sensitivity of 60%, with a proper technique could be done efficientlyThese assays are dependent of operator’s skill

Adenosin deaminaseThis method does not require sputum, only blood. Very high sensitivity and specificityThe report presents unclear case definition, exclusion of nontuberculous patients, and a relatively small TB patient population (20 with active TB)

Serology and antigen detectionIn this method, the sample is blood which is easier to obtain than sputum (in PTB). It is very rapid and does not require specimen from the site of diseaseSensitivity and specificity depend on the antigen used

In vitro interferon-gamma (IFN-γ) released assays (IGRAs)These methods can replace TST for detection of latent TB infection. Rapid test versions are inexpensive, and dozens of commercial kits are on the market; high specificity (98–100%)The test may have impaired sensitivity for very young children, for whom it should not be used to exclude the presence of M. tuberculosis

GeneXpert MTB/RIF systemThis requires minimal manipulation of sample and operator training. It utilizes real-time PCR technology to both diagnose TB and detect rifampicin resistance. Results in ~105 min.Only one report in a children population from South Africa. There is a need to validate in other populations

Gas sensor array electronic nose (E-Nose)High specificityWithout data in children populations