Mini-Symposium: TuberculosisAdvances in the diagnosis of pulmonary tuberculosis in children
Section snippets
Educational aims
The reader will be able:
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To highlight limitations in current diagnostic approaches for TB in children.
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To review the role of nucleic acid amplification assays in the diagnosis of TB in children.
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To identify specimen types most suitable for microbiological testing for TB in children.
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To identify promising new tests in development or under evaluation.
Limitations of current diagnostic approaches
The substantial gap between tuberculosis (TB) notifications in children and the estimated true burden of illness [1] may, in part, be due to lack of awareness and screening, but likely also reflects the difficulty in establishing a confirmed diagnosis of pulmonary (PTB) in children. Most PTB diagnoses in children globally are made on clinical and radiological evidence, and microbiological confirmation remains unusual [1].
The reasons for the difficulty in confirming a diagnosis of PTB in
Diagnostic approaches differ by setting
Diagnostic algorithms and approaches vary substantially depending on the level of care, resource availability and prevalence of TB. For example, in a well-resourced, low-prevalence setting, children presenting with respiratory symptoms compatible with TB may be given an initial course of antibiotics; lack of response might indicate chest radiography and blood testing for inflammatory markers such as C-reactive protein or complete blood count. A history of recent travel to an endemic area or
Advances in the clinical diagnosis of TB in children
Clinical symptoms in children are non-specific, and clinical scoring systems perform with wide variability [15]. Symptom scores encompass clinical features, chest radiology and tuberculin skin testing. Clinical diagnosis may be especially challenging in HIV-infected, malnourished or young children. While TB was previously regarded as a chronic disease in children with the key clinical features being chronic cough or loss of weight in the preceding 2 to 3 months, it is increasingly recognised
Microscopy and culture for the diagnosis of TB in children
Smear microscopy is an insensitive test for TB in children. A recent meta-analysis of 15 paediatric studies which compared standard microbiological testing to nucleic acid amplification testing with Xpert MTB/RIF, found the pooled sensitivity of smear microscopy to be 22% (gastric aspirate) or 29% (induced/expectorated sputum) compared with mycobacterial culture [6]. Mycobacterial culture remains the most sensitive method for microbiological confirmation of TB in children, but since many
Nucleic acid amplification tests for the diagnosis of TB in children
The development and implementation of automated nucleic acid amplification tests (NAATs) for TB has been a significant advance [13]. Xpert MTB/RIF has led the field [19], however the BD MAX MDR-TB assay [20] from Becton Dickinson, has recently demonstrated similar accuracy to Xpert MTB/RIF in clinical testing. There are several important advantages to these tests: both are simultaneously able to detect the presence of M. tuberculosis DNA and identify resistance to rifampicin (the BD MAX assay
Alternative specimen types for microbiological testing for TB in children
Several studies have compared the microbiological yield (culture or Xpert MTB/RIF) from induced sputum samples with that from gastric aspirate or lavage. Results are conflicting, with some studies showing improved yield from induced sputum [8], [26], others from gastric aspirate/lavage [27], [28] and others no difference [29]. It is possible that this variation may reflect familiarity and expertise with collection of particular specimen types. More recently, nasopharyngeal sampling (aspirate or
Host biomarkers for the diagnosis of TB in children
Whilst microbiological diagnosis aims to detect the causative pathogen, diagnostic approaches using host biomarkers aim to identify a characteristic immune or inflammatory response to M. tuberculosis. Biomarkers may be measured from blood samples tested directly ex vivo, or from samples which are first stimulated with mycobacterial antigens, to elicit M. tuberculosis-specific responses. Commercially-available interferon-gamma release assays are based on the latter principle, and, while specific
Directions for future research
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The assessment of diagnostic algorithms utilising clinical indicators and different diagnostic testing procedures.
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Investigation of the best readily gathered samples [Saliva, sputum, blood, stool, urine] matched to available technology at point of care for diagnostic testing.
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An evaluation of accurate, reliable and inexpensive testing kits for preferred diagnostic parameters at point of care sites.
Declarations of interest
The authors have received grant funding for paediatric TB diagnostic evaluation (Xpert MTB/RIF, Xpert MTB/RIF Ultra, AlereLAM, FujiLAM) from Regional Prospective Observational Research in Tuberculosis (RePORT TB) Consortium which is co-funded by the Medical Research Council of South Africa and the US Office of AIDS Research of the National Institutes of Health of the USA (DAA2-16-62066-1), the Medical Research Council of South Africa for the Tuberculosis Collaborating Centre for Child Health
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