International study suggests benefits of TB vaccine have been underestimated

The BCG vaccine used to prevent tuberculosis has a bigger role in protecting children than previously thought, according to a new study.

The BCG vaccine used to prevent tuberculosis (TB) has a bigger role in protecting children than previously thought, according to an international study led by investigators at Imperial College London and published in the American Journal of Respiratory and Critical Care Medicine. BCG was understood to prevent severe illness from tuberculosis, but not to prevent infection with TB bacteria. Now data collected from five countries in Europe suggest that the vaccine is also effective at preventing infection.

The BCG vaccine is made from a weakened form of bacteria closely related to human TB. The vaccine is 70-80 per cent effective against the most severe forms of TB, such as TB meningitis in children. In the UK, it is not given as part of the routine childhood vaccination schedule unless a baby is thought to have an increased risk of coming into contact with TB.

TB is the second biggest killer, after HIV/AIDS, out of all infectious diseases worldwide. It is caused by bacteria called Mycobacterium tuberculosis that infect the lungs, but people can be infected for years without showing any symptoms. This latent infection can be treated using a long course of antibiotics, but the most widely-used diagnostic test, the tuberculin skin test, can give false positive results in people who have had a BCG vaccine. This makes it difficult to establish whether BCG protects against infection using this test.

In the last decade, a new blood test called the interferon gamma release assay (IGRA) has been introduced, enabling latent TB infection to be diagnosed more accurately.

The new study, by a network of paediatricians from Europe called ptbnet, analysed skin test and blood test results from 1,128 children in Greece, Spain, Italy, Bulgaria and the UK to establish whether BCG prevents TB infection. The researchers also looked to address questions about the reliability of these tests and how they should be used in children.

The results show that children who had the BCG vaccine were over 50 per cent less likely to show evidence of infection with the blood test, suggesting that BCG doesn’t just prevent severe disease but also protects against TB infection.

Although there has been a concern that the blood test does not perform as well in children compared to adults, the test produced indeterminate results in less than 4 per cent of children in the study. A relatively high proportion of children had negative skin test results, but positive IGRA results. UK guidelines recommend that individuals are only given the IGRA test if they have a positive skin test, but the results from this study suggest that this policy may underestimate latent TB, and both tests should be used together in children.

The senior author of the study, Professor Beate Kampmann from the Department of Medicine at Imperial College London, said: “We set up a paediatric tuberculosis network in Europe in 2009 which has enabled us to compile a much bigger dataset than we’ve had before. This has given us the opportunity to answer important questions about childhood TB such as how the blood test performs in children and what role the BCG vaccine plays in preventing infection.”

The first author, Dr Robin Basu Roy, said: “We found that BCG does prevent TB infection, which has been underappreciated until now. This is a very significant result and it suggests that TB infection rates should be closely monitored in countries that have discontinued BCG vaccination campaigns. It also helps us to evaluate new vaccines in the pipeline – we should expect them to show at least the same benefits against infection and better protection against disease.”

Funding from the Wellcome Trust, Medical Research Council, and National Institute for Health Research contributed to this study.

Reference

R Basu Roy et al. ‘Identifying predictors of interferon-gamma release assay results in pediatric latent tuberculosis: a protective role of BCG?’ American Journal of Respiratory and Critical Care Medicine, 15 August 2012 vol. 186 no. 4 378-384