Published 13 November 2008, doi:10.1136/bmj.a2052
Cite this as: BMJ 2008;337:a2052

Research

Efficacy of percutaneous versus intradermal BCG in the prevention of tuberculosis in South African infants: randomised trial

Anthony Hawkridge, chief medical officer1, Mark Hatherill, senior clinical researcher1, Francesca Little, senior lecturer2, Margaret Ann Goetz, director of biostatistics and data management3, Lew Barker, senior medical adviser, regulatory affairs and quality assurance3, Hassan Mahomed, clinical director1, Jerald Sadoff, president and chief executive officer3, Willem Hanekom, associate professor and laboratory director1, Larry Geiter, senior director, epidemiology and field studies3, Greg Hussey, professor and director1, the South African BCG trial team

1 South African Tuberculosis Vaccine Initiative, University of Cape Town, South Africa, 2 Department of Statistical Science, University of Cape Town, 3 Aeras Global TB Vaccine Foundation, Rockville, MD, USA

Correspondence to: A Hawkridge, Aeras Global TB Vaccine Foundation, Africa Office, Belmont Square, Rondebosch, Cape Town 7700, South Africa thawkridge{at}aeras.org

Objective To compare the incidence of tuberculosis over two years in infants vaccinated at birth with intradermal BCG or with percutaneous BCG.

Design Randomised trial.

Setting South Africa.

Participants 11 680 newborn infants.

Interventions Infants were randomised by week of birth to receive Tokyo 172 BCG vaccine through the percutaneous route (n=5775) or intradermal route (n=5905) within 24 hours of birth and followed up for two years.

Main outcome measures The primary outcome measure was documented Mycobacterium tuberculosis infection or radiological and clinical evidence of tuberculosis disease. Secondary outcome measures were rates of adverse events, all cause and tuberculosis specific admissions to hospital, and mortality.

Results The difference in the cumulative incidence of definite, probable, and possible tuberculosis between the intradermal group and the percutaneous group, as defined using study definitions based on microbiological, radiological, and clinical findings was –0.36% (95.5% confidence interval –1.27% to 0.54%). No significant differences were found between the routes in the cumulative incidence of tuberculosis using a range of equivalence of "within 25%." Additionally, no significant differences were found between the routes in the cumulative incidence of adverse events (risk ratio 0.98, 95% confidence interval 0.91 to 1.06), including deaths (1.19, 0.89 to 1.58).

Conclusion Equivalence was found between intradermal BCG vaccine and percutaneous BCG in the incidence of tuberculosis in South African infants vaccinated at birth and followed up for two years. The World Health Organization should consider revising its policy of preferential intradermal vaccination to allow national immunisation programmes to choose percutaneous vaccination if that is more practical.

Trial registration ClinicalTrials.gov NCT00242047 [ClinicalTrials.gov] .


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