The Lancet Infectious Disease
Apr 2012  Volume 12  Number 4  p255 – 354
http://www.thelancet.com/journals/laninf/issue/current

Comment
New studies of BCG: implications for tuberculosis vaccines
C Fordham von Reyn

Preview
BCG has been given to over 3 billion people since the early part of the 20th century. Although the vaccine is effective, its use was implemented before clinical-trial design had reached its current sophistication, and before sensitive in-vitro techniques of assessing cellular immune responses were available. Recent studies and reinterpretation of previous trials have helped to clarify the true efficacy of BCG against both infection with and disease caused by Mycobacterium tuberculosis, while large cohort studies have provided an accurate side-effect profile in recipients with HIV infection.

Articles
Effectiveness and cost-effectiveness of first BCG vaccination against tuberculosis in school-age children without previous tuberculin test (BCG-REVAC trial): a cluster-randomised trial
Susan M Pereira, Mauricio L Barreto, Daniel Pilger, Alvaro A Cruz, Clemax Sant’Anna, Miguel A Hijjar, Maria Y Ichihara, Andreia C Santos, Bernd Genser, Laura C Rodrigues

Summary
Background
Neonatal BCG vaccination is part of routine vaccination schedules in many developing countries; vaccination at school age has not been assessed in trials in low-income and middle-income countries. Catch-up BCG vaccination of school-age children who missed neonatal BCG vaccination could be indicated if it confers protection and is cost-effective. We did a cluster-randomised trial (BCG REVAC) to estimate the effectiveness (efficacy given in routine settings) of school-age vaccination.

Methods
We assessed the effectiveness of BCG vaccination in school-age children (aged 7—14 years) with unknown tuberculin status who did not receive neonatal BCG vaccination (subpopulation of the BCG REVAC cluster-randomised trial), between July, 1997, and June, 2006, in Salvador, Brazil, and between January, 1999, and December, 2007, in Manaus, Brazil. 763 schools were randomly assigned into BCG vaccination group or a not-vaccinated control group. Neither allocation nor intervention was concealed. Incidence of tuberculosis was the primary outcome. Cases were identified via the Brazilian Tuberculosis Control Programme. Study staff were masked to vaccination status when identified cases were linked to the study population. We estimated cost-effectiveness in Salvador by comparison of the cost for vaccination to prevent one case of tuberculosis (censored at 9 years) with the average cost of treating one case of tuberculosis. Analysis of all included children was by intention to treat. For calculation of the incidence rate we used generalised estimating equations and correlated observations over time.

Findings
We randomly assigned 20 622 children from 385 schools to the BCG vaccination group and 18 507 children from 365 schools to the control group. The crude incidence of tuberculosis was 54·9 (95% CI 45·3—66·7) per 100 000 person-years in the BCG vaccination group and 72·7 (62·8—86·8) per 100 000 person-years in the control group. The overall vaccine effectiveness of a first BCG vaccination at school age was 25% (3—43%). In Salvador, where vaccine effectiveness was 34% (8—53%), vaccination of 381 children would prevent one case of tuberculosis and was cheaper than treatment. The frequency of adverse events was very low with only one axillary lymphadenitis and one ulcer greater than 1 cm in 11 980 BCG vaccinations.

Interpretation
Vaccination of school-age children without previous tuberculin testing can reduce the incidence of tuberculosis and could reduce the costs of tuberculosis control. Restriction of BCG vaccination to the first year of life is not in the best interests of the public nor of programmes for tuberculosis control.

Funding
UK Department for International Development, National Health Foundation.