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

Impact of COVID-19 Disruptions on Global BCG Coverage and Paediatric TB Mortality: A Modelling Study

The impact of COVID-19 disruptions on global Bacillus Calmette-Guérin (BCG) coverage and paediatric tuberculosis (TB) mortality is still unknown. To fill this evidence-gap and guide mitigation measures, we estimated the impact of COVID-19 disruptions on global BCG coverage and paediatric TB mortality. First, we used data from multiple sources to estimate COVID-19-disrupted BCG vaccination coverage. Second, using a static mathematical model, we estimated the number of additional paediatric TB deaths in the first 15 years of life due to delayed/missed vaccinations in 14 scenarios—varying in duration of disruption, and magnitude and timing of catch-up. We estimated a 25% reduction in global BCG coverage within the disruption period. The best-case scenario (3-month disruption, 100% catch-up within 3 months) resulted in an additional 886 (0.5%) paediatric TB deaths, and the worst-case scenario (6-month disruption with no catch-up) resulted in an additional 33,074 (17%) deaths. The magnitude of catch-up was found to be the most influential variable in minimising excess paediatric TB mortality. Our results show that ensuring catch-up vaccination of missed children is a critical priority, and delivery of BCG alongside other routine vaccines may be a feasible way to achieve catch-up. Urgent action is required to support countries with recovering vaccination coverages to minimise paediatric deaths.

MSF Paediatric Days: a step forward in operationalising ‘Humanitarian Paediatrics’

Around the world, one in four children live in a country affected by conflict, political insecurity and disaster. Healthcare in humanitarian and fragile settings is challenging and complex to provide, particularly for children. Furthermore, there is a distinct lack of medical literature from humanitarian settings to guide best practice in such specific and resource-limited contexts. In light of these challenges, Médecins Sans Frontières (MSF), an international medical humanitarian organisation, created the MSF Paediatric Days with the aim of uniting field staff, policymakers and academia to exchange ideas, align efforts, inspire and share frontline research and experiences to advance humanitarian paediatric and neonatal care. This 2-day event takes place regularly since 2016. The fourth edition of the MSF Paediatric Days in April 2021 covered five main topics: essential newborn care, community-based models of care, paediatric tuberculosis, antimicrobial resistance in neonatal and paediatric care and the collateral damage of COVID-19 on child health. In addition, eight virtual stands from internal MSF initiatives and external MSF collaborating partners were available, and 49 poster communications and five inspiring short talks referred to as ‘PAEDTalks’ were presented. In conclusion, the MSF Paediatric Days serves as a unique forum to advance knowledge on humanitarian paediatrics and creates opportunities for individual and collective learning, as well as networking spaces for interaction and exchange of ideas.

Current Prevalence and Treatment Outcome of Paediatric Tuberculosis in a South Indian District - A 2 Year Retrospective Observational Study

BACKGROUND Knowledge about the diagnosis and the treatment outcome of paediatric tuberculosis is very much essential for functioning of tuberculosis (TB) control programs in most countries like India. The current study was done to determine the prevalence of paediatric tuberculosis, different modalities used for diagnosis, drug resistance pattern, HIV-TB co-infection rate and treatment outcome. METHODS A 2-year retrospective study was done among all registered paediatric tuberculosis cases aged 18 years and below, who were diagnosed during the period January 2018 to December 2019. Data was extracted from the files and was analysed. RESULTS The prevalence of paediatric tuberculosis was found to be 0.51 per 1000 population. The proportion of paediatric tuberculosis among total TB cases was 5.9 %. Among 14,596 total TB cases registered at District Tuberculosis Centre (DTC) Anantapuramu, 867 (5.9 %) were paediatric TB cases, with a mean age of 12.5 ± 5.6 years. 62 % of the cases were above 12 years of age. Males (47.4 %) and females (52.6 %) were almost equally distributed (P > 0.05). 343 (39.6 %) cases were microbiologically confirmed TB and 524 (60.4 %) cases were clinically diagnosed TB. Drug resistance was found in 47 (13.7 %) of the 343 microbiologically confirmed TB cases. Of the total 867 paediatric TB cases studied, pulmonary type (56 %) was predominant than extra pulmonary type (44 %) (P < 0.05). Human immunodeficiency virus (HIV) co infection was found in 24 (2.8 %) cases. 423 cases (65.5 %) successfully completed the treatment and 173 cases (26.8 %) were cured adding to a favourable outcome of 92.3 %. 3 (0.5 %) cases had treatment failure, 35 (5.4 %) were defaulters and 12 (1.8 %) cases died during the treatment, adding to a poor outcome of about 7.7 %. CONCLUSIONS Majority of the paediatric tuberculosis cases were diagnosed clinically rather than microbiological confirmation. Efforts should be made to further improve the availability and sensitivity of diagnostic methods of paediatric TB. KEYWORDS Paediatric Tuberculosis, Drug Resistant TB, HIV TB Co Infection