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 1930s 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 and Wales 1913 - 2000# Chemotherapy BCG vaccination Notifications 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, 8th July, 2005 WHC 2005 (077): Guidance on changes to the BCG vaccination programme, 6th 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 surface-exposed antigens Enhanced potency BCG, using antigen 85B (recombinant vaccine) Subunit vaccines New strategy could involve using a priming recombinant vaccine, and boosting the immune response