Duration of BCG protection against tuberculosis and change in effectiveness with time since vaccination in Norway: a retrospective population-based cohort study

Nguipdop-Djomo, Patrick; Heldal, Einar; Rodrigues, Laura C.; Abubakar, Ibrahim; Mangtani, Punam

doi:10.1016/s1473-3099(15)00400-4

Cited by 156 publications

(111 citation statements)

References 21 publications

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“…The study findings are consistent with recent findings from Norway 41 and Brazil, 25 and provide additional evidence to that from the seminal MRC trial, 7 in which protection of 63% was seen 10-15 years after vaccination, with wide CIs (95% CI 17% to 84%), with no evidence of protection 15-20 years after vaccination (VE 9%, 95% CI negative to 71%).…”

Section: Observational Studies Of Bacillus Calmette-guérin Vaccine Efsupporting

confidence: 90%

“…The findings are consistent with the limited data emerging from other trials and observational studies, 23 as well as from a more recent Norwegian historical cohort study of the duration of protection of the BCG vaccine. 41 BCG vaccination at school age may thus have helped in the control of TB, including reducing the potential for developing multidrug-resistant disease, as those vaccinated at about 13 years of age have moved into adulthood. …”

Section: Resultsmentioning

confidence: 99%

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Observational study to estimate the changes in the effectiveness of bacillus Calmette–Guérin (BCG) vaccination with time since vaccination for preventing tuberculosis in the UK

Mangtani

Nguipdop-Djomo

Keogh

et al. 2017

Health Technol Assess

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Background Until recently, evidence that protection from the bacillus Calmette–Guérin (BCG) vaccination lasted beyond 10 years was limited. In the past few years, studies in Brazil and the USA (in Native Americans) have suggested that protection from BCG vaccination against tuberculosis (TB) in childhood can last for several decades. The UK’s universal school-age BCG vaccination programme was stopped in 2005 and the programme of selective vaccination of high-risk (usually ethnic minority) infants was enhanced. Objectives To assess the duration of protection of infant and school-age BCG vaccination against TB in the UK. Methods Two case–control studies of the duration of protection of BCG vaccination were conducted, the first on minority ethnic groups who were eligible for infant BCG vaccination 0–19 years earlier and the second on white subjects eligible for school-age BCG vaccination 10–29 years earlier. TB cases were selected from notifications to the UK national Enhanced Tuberculosis Surveillance system from 2003 to 2012. Population-based control subjects, frequency matched for age, were recruited. BCG vaccination status was established from BCG records, scar reading and BCG history. Information on potential confounders was collected using computer-assisted interviews. Vaccine effectiveness was estimated as a function of time since vaccination, using a case–cohort analysis based on Cox regression. Results In the infant BCG study, vaccination status was determined using vaccination records as recall was poor and concordance between records and scar reading was limited. A protective effect was seen up to 10 years following infant vaccination [< 5 years since vaccination: vaccine effectiveness (VE) 66%, 95% confidence interval (CI) 17% to 86%; 5–10 years since vaccination: VE 75%, 95% CI 43% to 89%], but there was weak evidence of an effect 10–15 years after vaccination (VE 36%, 95% CI negative to 77%; p = 0.396). The analyses of the protective effect of infant BCG vaccination were adjusted for confounders, including birth cohort and ethnicity. For school-aged BCG vaccination, VE was 51% (95% CI 21% to 69%) 10–15 years after vaccination and 57% (95% CI 33% to 72%) 15–20 years after vaccination, beyond which time protection appeared to wane. Ascertainment of vaccination status was based on self-reported history and scar reading. Limitations The difficulty in examining vaccination sites in older women in the high-risk minority ethnic study population and the sparsity of vaccine record data in the later time periods precluded robust assessment of protection from infant BCG vaccination > 10 years after vaccination. Conclusions Infant BCG vaccination in a population at high risk for TB was shown to provide protection for at least 10 years, whereas in the white population school-age vaccination was shown to provide protection for at least 20 years. This evidence may inform TB vaccination programmes (e.g. the timing of administration of improved TB vaccines, if they become available) and cost-effectiveness studies. Methods to deal with missing record data in the infant study could be explored, including the use of scar reading. Funding The National Institute for Health Research Health Technology Assessment programme. During the conduct of the study, Jonathan Sterne, Ibrahim Abubakar and Laura C Rodrigues received other funding from NIHR; Ibrahim Abubakar and Laura C Rodrigues have also received funding from the Medical Research Council. Punam Mangtani received funding from the Biotechnology and Biological Sciences Research Council.

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Section: Observational Studies Of Bacillus Calmette-guérin Vaccine Efsupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

Observational study to estimate the changes in the effectiveness of bacillus Calmette–Guérin (BCG) vaccination with time since vaccination for preventing tuberculosis in the UK

Mangtani

Nguipdop-Djomo

Keogh

et al. 2017

Health Technol Assess

Self Cite

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“…The only licensed vaccine, Bacille Calmette-Guérin (BCG), provides very limited protection against adult TB that leads to transmission (2), and therefore new strategies to control the disease are needed. Immunological responses considered critical for long-term mycobacterial control have focused on conventional T cell responses directed at peptide antigens presented by major histocompatibility complex (MHC) I and II, ultimately leading to secretion of anti-microbial cytokines, including TNF-α and IFN-γ (3,4).…”

Section: Introductionmentioning

confidence: 99%

CD1b-restricted GEM T cell responses are modulated byMycobacterium tuberculosismycolic acid meromycolate chains

Chancellor

Tocheva

Cave-Ayland

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Tuberculosis, caused by Mycobacterium tuberculosis, remains a major human pandemic. Germline-encoded mycolyl lipid-reactive (GEM) T cells are donor-unrestricted and recognize CD1b-presented mycobacterial mycolates. However, the molecular requirements governing mycolate antigenicity for the GEM T cell receptor (TCR) remain poorly understood. Here, we demonstrate CD1b expression in tuberculosis granulomas and reveal a central role for meromycolate chains in influencing GEM-TCR activity. Meromycolate fine structure influences T cell responses in TB-exposed individuals, and meromycolate alterations modulate functional responses by GEM-TCRs. Computational simulations suggest that meromycolate chain dynamics regulate mycolate head group movement, thereby modulating GEM-TCR activity. Our findings have significant implications for the design of future vaccines that target GEM T cells. Mycobaterium tuberculosis | GEM T cells | CD1b | Mycolate lipids |

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“…The protective effect of BCG decreases with age of immunization and distance from the equator, likely because exposure to environmental mycobacteria or M. tuberculosis increases as age and proximity to the equator increase. In populations where BCG is protective the effect can last for up to 20 years or even longer [14]. Therefore, if we are to replace BCG with an alternative live attenuated vaccine we must ensure that the protective efficacy of the replacement vaccine is at least the same (noninferior) as that of BCG.…”

Section: Biomarkers For Bcg Replacement Vaccinesmentioning

confidence: 99%

Human Biomarkers: Can they help us to Develop a new Tuberculosis Vaccine?

Fletcher

Dockrell

2016

Future Microbiol.

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The most effective intervention for the control of infectious disease is vaccination. The BCG vaccine, the only licensed vaccine for the prevention of tuberculosis (TB) disease, is only partially effective and a new vaccine is urgently needed. Biomarkers can aid the development of new TB vaccines through discovery of immune mechanisms, early assessment of vaccine immunogenicity or vaccine take and identification of those at greatest risk of disease progression for recruitment into smaller, targeted efficacy trials. The ultimate goal, however, remains a biomarker of TB vaccine efficacy that can be used as a surrogate for a TB disease end point and there remains an urgent need for further research in this area.

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Duration of BCG protection against tuberculosis and change in effectiveness with time since vaccination in Norway: a retrospective population-based cohort study

Abstract: Norwegian Institute of Public Health and London School of Hygiene & Tropical Medicine.

Cited by 156 publications

References 21 publications

Observational study to estimate the changes in the effectiveness of bacillus Calmette–Guérin (BCG) vaccination with time since vaccination for preventing tuberculosis in the UK

Observational study to estimate the changes in the effectiveness of bacillus Calmette–Guérin (BCG) vaccination with time since vaccination for preventing tuberculosis in the UK

CD1b-restricted GEM T cell responses are modulated byMycobacterium tuberculosismycolic acid meromycolate chains

Human Biomarkers: Can they help us to Develop a new Tuberculosis Vaccine?

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