Abstract

Approximately 100 million newborn children receive Bacille Calmette–Guérin (BCG) annually, because vaccination is consistently protective against childhood tuberculous meningitis and miliary TB. By contrast, BCG efficacy against pulmonary TB in children and adults is highly variable, ranging from 0% to 80%, though it tends to be higher in individuals who have no detectable prior exposure to mycobacterial infections, as judged by the absence of delayed-type hypersensitivity response (a negative tuberculin skin test, TST). The duration of protection against pulmonary TB is also variable, but lasts about 10 years on average. These observations raise the possibility that BCG revaccination, following primary vaccination in infancy, could be efficacious among TST-negative adolescents as they move into adulthood, the period of highest risk for pulmonary disease. To inform continuing debate about revaccination, this paper assesses the effectiveness and cost-effectiveness of revaccinating adolescents in a setting with intense transmission—Cape Town, South Africa. For a cost of revaccination in the range US$1–10 per person, and vaccine efficacy between 10% and 80% with protection for 10 years, the incremental cost per year of healthy life recovered (disability-adjusted life years, DALY) in the vaccinated population lies between US$116 and US$9237. The intervention is about twice as cost-effective when allowing for the extra benefits of preventing transmission, with costs per DALY recovered in the range US$52–$4540. At 80% efficacy, revaccination averted 17% of cases. Under the scenarios investigated, BCG revaccination is cost-effective against international benchmarks, though not highly effective. Cost-effectiveness ratios would be more favourable if we also allow for TB cases averted by preventing transmission to HIV-positive people, for the protection of HIV-negative people who later acquire HIV infection, for the possible non-specific benefits of BCG, for the fact that some adolescents would receive BCG for the first time, and for cost sharing when BCG is integrated into an adolescent immunization programme. These findings suggest, subject to further evaluation, that BCG revaccination could be cost-effective in some settings.

Highlights

  • In the aftermath of disappointing results from a phase IIb trial of candidate TB vaccine MVA85A [1], and while awaiting the results of further TB vaccine trials, this paper considers whether the vaccine we already have, Bacille Calmette–Guerin (BCG), is being used to its full effectiveness

  • BCG revaccination has not been recommended for children, adolescents and adults because it appears to confer limited protection against pulmonary TB, and only in some settings [2]

  • The analysis in this paper suggests that BCG revaccination deserves further investigation, at least in locations where there is little exposure to non-tuberculous mycobacteria, and where adolescent children are at a high risk of TB as they move into adulthood

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Summary

Introduction

In the aftermath of disappointing results from a phase IIb trial of candidate TB vaccine MVA85A [1], and while awaiting the results of further TB vaccine trials, this paper considers whether the vaccine we already have, Bacille Calmette–Guerin (BCG), is being used to its full effectiveness. If BCG revaccination is, cost-effective, it might be provided as one element of an immunization. Programme to protect adolescents against a variety of common, vaccine-preventable infectious diseases, and as a platform for the introduction of future TB vaccines. This analysis does not, on its own, suggest any changes to BCG revaccination policy, and is not a policy statement of the World Health Organization. Rather, it suggests that the costs and effectiveness of BCG revaccination are worth further consideration in some settings, preferably backed by further evidence from clinical trials

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