Table 3

 Summary of recent diagnostic advances, their potential application and perceived problems and/or benefits

Diagnostic approachApplicationProblems/BenefitsValidation
LAM, lipoarabinomannan; LTBI, latent tuberculosis infection; TST, tuberculin skin test.
Symptom-based
    Symptom-based screeningScreening child contacts of adult tuberculosis casesSimple, limited resources requiredNot well validated
Should improve access to preventive chemotherapy for asymptomatic high-risk contacts The use of well-defined symptoms and clinical follow-up provides reasonable diagnostic accuracy
    Refined symptom-based diagnosisDiagnosis of probable active tuberculosisSimple, limited resources requiredAdditional validation required
Should improve access to chemotherapy in resource-limited settings
Poor performance in HIV-infected children
Immune-based
    Antibody-based assaysDiagnosis of probable active tuberculosisSimple, point of care testingAdditional validation required
Variable accuracy and difficulty in distinguishing LTBI from active tuberculosis
    Antigen-based assays
        LAM detection assayDiagnosis of probable active tuberculosisSimple, point of care testingNot well validated
Limited clinical data on accuracy
        MPB64 skin patch testDiagnosis of probable active tuberculosisSimple and easy to useNot well validated
Limited clinical data on accuracy, but initial data suggests it distinguishes LTBI from active tuberculosis
    T cell assaysDiagnosis of LTBI; potentially a “rule-out” test for active diseaseLimited data in childrenNot well validated in children
Inability to differentiate LTBI from active tuberculosis
Large blood volumes required
Very expensive
Particular relevance in high-risk children, where LTBI treatment is warranted
Pathogen-based
    Colorimetric culture systems (eg, TK-Medium)Bacteriological confirmation of active tuberculosisSimple and feasible, limited resources requiredNot well validated in children
Potential for contamination in field conditions
    Phage-based tests (eg, FASTPlaque-tuberculosis)Diagnosis of active tuberculosis, and detection of rifampin resistanceRequires laboratory infrastructureNot well validated in children
Performs relatively poorly when used on clinical specimens
    Microscopic observation drug susceptibility assayDiagnosis of active tuberculosis, and detection of drug resistanceSimple and feasible, limited resources requiredNot well validated in children
    Electronic-nose technologyDiagnosis of active tuberculosisStill in developmentNever tested in children
    PCR-based testsDiagnosis of probable active tuberculosis, and detection of rifampin resistanceRarely available in endemic areasExtensively evaluated, but evidence not in favour of widespread use
Sensitivity tends to be poor in paucibacillary tuberculosis
Specificity a concern in endemic areas, where LTBI is common
Requires adequate quality control systems