Paediatric tuberculosis diagnosis using Mycobacterium tuberculosis real-time polymerase chain reaction assay: a systematic review and meta-analysis.

BACKGROUND: Rapid and accurate diagnosis of paediatric tuberculosis (TB) is key to manage the disease and to control and prevent its transmission. Collection of quality sputum samples without invasion methods from paediatrics (age < 16 years) with presumptive pulmonary tuberculosis (PTB) remains a challenge. Thus, the aim of this meta-analysis was to assess the overall accuracy of a real-time polymerase chain reaction (RT-PCR)-based assay, for routine diagnosis of MTB in different samples from paediatrics with active pulmonary and extra-pulmonary tuberculosis using mycobacterial culture as the gold standard in clinical microbiology laboratories. METHODS: We conducted a systematic review and meta-analysis to examine the diagnostic test accuracy of RT-PCR based assay for the detection of MTB in paediatric clinical samples. A systematic literature search was performed for publications in any language. MEDLINE via PubMed, EMBASE, and Web of Science were among 9 bibliographic databases searched from August 2019 until November 2020. Bivariate random-effects model of meta-analysis were performed to generate pooled summary estimates (95% CIs) for overall accuracy of RT-PCR based assay compared to mycobacterial culture as the reference standard. RESULTS: Of the 1592 candidate studies, twenty-one eligible studies met our inclusion criteria. In total, the review and meta-analysis included 5536 (3209 PTB and 2327 EPTB). Summary estimates for pulmonary TB (11 studies) were as follows: sensitivity 56 (95% CI 51-62), specificity 97 (95% CI 96-98) and summary estimates for extra-pulmonary TB (10 studies) were as follows: sensitivity 87 (95% CI 82-91)) specificity 100 (95% CI 99-100). There was significant heterogeneity in sensitivity and specificity among the enrolled studies (p < 0.001). CONCLUSIONS: Our results suggested that the RT-PCR based assay could be a useful test for the diagnosis of paediatrics TB with high sensitivity and specificity in low-income/high-burden and upper medium income/low-burden settings. From the study, RT-PCR assay demonstrated a high degree of sensitivity for extra-pulmonary TB and good sensitivity for pulmonary TB which is an important factor in achieving effective global control and for patient management in terms of initiating early and appropriate anti-tubercular therapy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018104052.

Paediatric tuberculosis diagnosis using Mycobacterium tuberculosis real-time polymerase chain reaction assay: protocol for systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) diagnosis in children is a major challenge with up to 94% of children with TB treated empirically in TB high-burden countries. Paediatric tuberculosis (PTB) remains a major cause of morbidity and mortality globally, particularly in developing countries. Most deaths/morbidity from TB in paediatrics could be prevented with early diagnosis and appropriate treatment. The main objective of this systematic review is to examine the evidence whether real-time polymerase chain reaction assay could be the most accurate clinical laboratory diagnostic methodology for the Mycobacterium tuberculosis (MTB) detection in paediatrics. METHODS: We will search MEDLINE/PubMed, EMBASE, BIOSIS, LILACS, Cochrane Infectious Diseases Group Specialised Register (CIDG SR), Global Health, and CINAHL for published studies that recruited children less than 16 years of age being investigated for Mycobacterium tuberculosis (MTB) infection using real-time polymerase chain reaction assay accompanied by mycobacteriological culture investigation as the reference standard. There will be no restriction regarding the language, date of publication, and publication status. We will include randomised controlled trials and observational studies (cohort, cross-sectional) in the review. Selection of studies, data extraction and management, assessment of risk of bias, and quality of evidence will be performed by two independent reviewers (EB and BC). A third researcher will be consulted in case of discrepancies. Depending on the availability and quality of the data, a meta-analysis will be performed. Otherwise, findings will be qualitatively reported. DISCUSSION: To our knowledge, this is the first systematic review and meta-analysis assessing the detection of MTB from all clinical sample types using real-time polymerase chain reaction assay in paediatric population. This review will make available evidence on the accuracy, approach, and interpretation of results of this assay in the context of MTB diagnosis which will meet an urgent need, considering the challenges of MTB diagnosis in paediatrics. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42018104052.