We also acknowledge that further quantification of degree of exposure to tuberculosis cases, including proximity to the index case and the number of cases in close contact, was not possible in our study because the primary studies were not designed to compare exposure in children who were and were not immunised with BCG.

Reactivation of the bacille Calmette-Guérin scar following immune reconstitution during treatment of infant acute lymphoblastic leukemia. BCG scar reactivation has been associated with Kawasaki disease 30. - Trial registration PROSPERO registration No CRD42011001698 (www.crd.york.ac.uk/prospero/). Where assessed, the main differences in the subgroup analyses were for rating on the Newcastle-Ottawa scale, the P value for which was similar under the permutation test recommended by Higgins and Thompson.17 Similarly, the small number of studies limited the power to explore whether the variation in protection by BCG against tuberculosis is mostly through variation in protection against infection. We compared studies with a quality rating of 3-4 with those with a rating of ≥5 (fig C, appendix 1). Good news in the fight against typhoid: new vaccine study shows promising results, Winners at the Thames Valley Health Research Awards, OSPREA and OVG's recruitment success for study of maternal vaccines against RSV, New technology could allow multiple vaccines to be delivered in single jab, Typhoid vaccine set to have 'huge impact'. Cochrane handbook for systematic reviews of interventions. We assessed potential factors behind the heterogeneity with random effects meta-regression.18 The protective effect of BCG was described with risk ratios and 95% confidence intervals. The observed protection against M tuberculosis infection was independent of the assay method used for measurement.

To assess potential publication bias we used funnel plots and the Harbord test.19, Our literature search found 601 articles; based on a review of titles, we selected 546 abstracts for further assessment leading to the identification of 133 articles for full text review (fig 1).⇓ After we reviewed the full text, 112 articles did not meet the inclusion criteria. Restriction of the analysis to the six studies (n=1745) with information on progression to active tuberculosis at the time of screening showed protection against infection of 27% (risk ratio 0.73, 0.61 to 0.87) compared with 71% (0.29, 0.15 to 0.58) against active tuberculosis. Discrepancy in quality assessment was discussed and resolved by the two reviewers. Reduced infection rates in children immunised with BCG could also be caused by the fact that parents who are generally more aware of infection control measures are from higher educated families with lower exposure to M tuberculosis infection and have their children more comprehensively immunised, which includes BCG immunisation. One test was used per paper and in cases where both ELISpot and QuantiFERON data were available data from QuantiFERON testing were used, Fig 3 Protection against Mycobacterium tuberculosis infection (TB) as determined by interferon γ release assay (ELISpot v QuantiFERON) in children vaccinated with BCG. Given the incomplete control of tuberculosis, especially in high burden countries, optimisation of use of BCG is sensible. BCG vaccination can cause a false positive Mantoux test, although a very high-grade reading is usually due to active disease.. Investigation of the effect of age at vaccination at an individual level and of time from vaccination to exposure to an infectious case would be of particular interest. The purpose of this study was to evaluate the frequency of reactivation of the BCG in Mexican children diagnosed with KD. To determine the sensitivity of the bacillus Calmette-Guérin (BCG) scar as an indicator of previous vaccination and to ascertain the tuberculin skin test (TST) response in infancy after vaccination in a community from an area hyperendemic for tuberculosis (TB). In each arm children's BCG vaccination status was assessed by BCG scar reading and baseline information was collected. Analysis was performed with the DerSimonian and Laird random effects model, which incorporates variation between studies in the weighting. All authors contributed to planning, interpretation and writing of the manuscript and critically revised the manuscript for intellectual content. Interferon γ release assay status was not considered (whether performed or not) when we calculated the number of those who developed active tuberculosis within the population. In eight studies, the cut off for positive assay result was 0.35 IU/mL or they reported using the manufacturer’s; one used a cut off of 10 IU/mL29 and one provided no information—omission of this study does not alter the conclusion. Information extracted onto pretested data forms included study details (authors, year, geographical area, study design, sample size), the population (mean age, sex, and setting), exposure (method of assessment and timing), and two outcomes measures: interferon γ release assays (as a proxy for tuberculosis infection) and active tuberculosis (when reported). This, taken in combination with our symmetrical funnel plot, suggests that our findings are unlikely to be caused by publication or reporting bias. For these studies, we contacted the authors to obtain the raw data. This was achieved by examining, in this subset, the number of children with active disease (regardless of assay status) in those who received BCG versus those who did not. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Here we report on an extended follow up of the BCG-REVAC trial, a cluster randomised trial conducted in the Brazilian cities Salvador and Manaus including over 200,000 children aged 7–14 years aimed to evaluate the efficacy of BCG revaccination in children who had received neonatal BCG vaccination. The risk of BCG dissemination in immunocompromised infants is discussed and the use of antimycobacterial prophylaxis in … Swinson S., Hall G., Pollard AJ.

The limited number of studies reviewed from locations closer to the equator, however, means that firm conclusions must wait until new studies find similar results.

Infection was defined as any positive results of interferon γ release assays in contacts irrespective of whether they had evidence of active tuberculosis or not. © The effect of BCG vaccination, and its policy implications, would be different for countries with high versus low incidence of tuberculosis especially in terms of the cost effectiveness of policies. Setting Community congregate … Where results of both assays were available from a study we chose the QuantiFERON result as this was most used among the selected studies. Hot Topics In Infection And Immunity In Children 2016, Hot Topics In Infection And Immunity In Children 2017, Oxford Vaccine Group Immunisation Seminar, Hot Topics In Infection And Immunity In Children 2018 - The ESPID-Oxford Course, Thames Valley & Wessex Paediatric Infectious Diseases Course, Virtual Influenza Vaccination Update Training - 3 August 2020, Virtual Influenza Vaccination Update Training - 4 August 2020, Online Introduction to Immunisation Training - 7 October 2020, Online Introduction to Immunisation Training - 3 November 2020, Development and evaluation of vaccines against group B meningococcal disease (MenB), Nepal Pneumococcal Impact Assessment Project, Invasive non-typhoidal Salmonella disease. 24 A genetic factor could play a role since C-allele of ITPKC SNP have been associated with K D susceptibility and BCG scar reactivation in Taiwan. See: http://creativecommons.org/licenses/by-nc/3.0/. BCG revaccination is still used in some tuberculosis endemic countries. Two reviewers (AR and ME) assessed aspects of the quality of each selected study using a modified version of the Newcastle-Ottawa scale for assessment of observational cohort studies.15 This scale awards a maximum of nine points to each study: four points for the adequate selection of participants, two points for comparability of the studies based on the design and analysis, and three points for the adequate ascertainment of outcome. If this finding is confirmed, then the effect of latitude would be consistent with the variation in protection by BCG against pulmonary disease.8 In this case, the mechanism here could be the same: that the higher prevalence of non-tuberculous mycobacterial infection close to the equator decreases the measured protection with BCG. Declaration of transparency: IA affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. We found evidence of progression to active tuberculosis as identified at point of screening of index cases.

The most controversial aspect of BCG is the variable efficacy found in different clinical trials, which appears to depend on geography.

Exposure can differ because of variable duration of infectiousness of the index patient and the amount of effective contact. In addition, transparent reporting from outbreak and contact studies of individual ages and time of vaccination and exposure to tuberculosis of participants should allow future meta-analysis to investigate protection against infection. Design Systematic review and meta-analysis. Two reviewers (AR and ME) independently screened the titles and abstracts (when available) from the search results and identified studies for assessment of full text. Results The primary analysis included 14 studies and 3855 participants.

We tried to minimise bias from differences in exposure in the two groups by limiting the review to studies among contacts—that is, to outbreaks among contacts of infectious cases or known household exposure where exposure is likely to be similar in vaccinated and unvaccinated children. Instead, the BCG vaccine is a liquid placed directly onto the skin of your upper arm. Children were screened for infection with M tuberculosis with interferon γ release assays.