BCG Vaccination Dr Lika Nehaul CCDC NPHS TB

BCG Vaccination Dr Lika Nehaul CCDC / NPHS TB Programme Lead Wales Immunisation Conference 2008

Acknowledgements • Nature (Scientific) Publishing Group • Health Protection Agency • World Health Organisation

Aspects covered • A brief reminder of some basic facts about TB • The origins of the BCG vaccine • Efficacy of BCG, and its contribution to tuberculosis control • BCG policy and its implementation in Wales • TB vaccine developments

Tuberculosis caused by mycobacteria species • Mycobacterium tuberculosis causes vast majority of cases • Mycobacterium bovis causes <1% of confirmed infections in the UK • M. africanum a very rare cause • Some other mycobacterial species can cause pulmonary disease resembling TB, referred to as atypical mycobacterial infection

Natural history of tuberculosis • Only between 5 & 10% of people with primary infection develop clinically apparent disease • In some individuals the immune system appears to overcome infection • In others the bacteria are held in check (latent TB infection) and can then reactivate in later life causing post-primary pulmonary TB • Tubercle bacilli contracted by the inhalation of M. tuberculosis bacilli in droplet nuclei

Summary of tuberculosis epidemiology • About one-third of the world’s population thought to be infected with M. tuberculosis • Nearly 9 million new (incident) cases each year • 2 million deaths per annum • WHO declared TB a global emergency in 1993, but incident cases still increasing year on year

Efficacy of BCG – clinical trials • Formal clinical trials only started in the late 1930 s • Protective efficacy varies from world region to region – from 70 – 80% to none at all • Inadequate protection against infectious, post-primary, pulmonary TB in adults • Protection shown to last for 10 to 15 years (JAMA 2004 – some protection up to 60 years)

Reasons for observed variations in efficacy • Differences in potency of various strains of BCG • Genetic or age differences in different populations • Reduced virulence of some strains of M. tb • Prior exposure to non-tuberculosis mycobacteria • (? Methodological problems with some trials)

BCG vaccine is good at: • Protection of neonates and children against serious forms of primary disease such as meningeal and disseminated TB • Protecting against death

Tuberculosis ( all forms )- Notifications, annual totals England Wales 1913 - 2000# Chemotherapy Notifications BCG vaccination Year Port Health Authorities not included - 1913 -1938 classified as pulmonary TB Figures for 1982 onwards exclude notifications for chemoprophylaxis # Data for 2000 provisional Source: Statutory Notifications to the Communicable Disease Surveillance Centre

Notification rates of all forms of TB in males in 1953 and 1999 PHLS

TB in England, Wales & NI -2005

Controlling tuberculosis • Early diagnosis and prompt treatment especially of pulmonary disease • Use of observed / supervised treatment where necessary • BCG vaccine

BCG Policy in the UK • JCVI advises UK Health Departments on immunisation policy • Welsh Assembly Government agreed to changes to BCG Immunisation Programme recommended by JCVI in Summer 2005 • JCVI recommendations should be followed rather than NICE TB Guidelines for BCG • TB Chapter in Green Book updated on line in November 2007* *see home page: www. dh. gov. uk

Recommendations for BCG • Infants living in an area of the UK with an incidence of TB of 40 / 100, 000 or greater • All infants, children and young people aged up to under 16 years of age with a parent or grandparent born in a country where the annual incidence is 40 / 100, 000 or greater • Previously unvaccinated, tuberculin negative, contacts of cases of respiratory TB (follow NICE TB Guideline)

Recommendations for BCG (con) • Previously unvaccinated, tuberculin-negative new entrants under 16 years of age who have lived for a prolonged period (at least 3 months) in a country with a high TB incidence • Individuals at occupational risk (page 397, TB Chapter (Nov 2007), Green Book (note advice on HCWs) • Travellers and those going to work abroad: may be required for previously unvaccinated, tuberculin negative, individuals aged under 16 going to live or work with local people in a country with a high incidence of TB • Where vaccine requested: assess for specific risk factors for TB

Guidance on BCG Immunisation • WHC 2005 (062): Changes to BCG Immunisation Programme, 8 th July, 2005 • WHC 2005 (077): Guidance on changes to the BCG vaccination programme, 6 th September, 2005 • NPHS has prepared a ‘Framework Document for BCG Vaccination of infants and children up to under 16 years of age in Wales’

Guidance on BCG (con) • BCG Programme in the UK now risk-based the key part being a neonatal programme targeted at those children most at risk of exposure to TB • Schools programme ceased from September 2005, but LHBs, in liaison with RICs, required to make alternative arrangements to protect at-risk children who will no longer be covered by the schools programme

TB vaccine developments • Candidate antigens- secreted and surfaceexposed antigens • Enhanced potency BCG, using antigen 85 B (recombinant vaccine) • Subunit vaccines • New strategy could involve using a priming recombinant vaccine, and boosting the immune response