Viewpoint - Is the universal BCG vaccination necessary?

Dr Simon Barry and Professor Peter Ormerod argue the case for and against BCG.

FOR: The cost of dealing with an outbreak is greater than the cost of a vaccine programme. By Dr Simon Barry.

A large meta-analysis concluded that the BCG is an effective vaccine, providing approximately 70 per cent protection against pulmonary TB, death from TB and tuberculous meningitis when given to newborns and infants.1 The range of protection, however, spans from almost zero to very high levels, with the greatest benefits being achieved in countries furthest from the equatorial belt.

Better protection associated with geographical location is thought to reflect the benefits of relative affluence and a lack of environmental mycobacteria associated with temporal latitudes when compared with those closer to the equator.

The vaccine is less effective when given to school-age children when compared with neonates,2 but even at school age it has been shown to give 70-80 per cent protection in the UK.3

The argument against universal BCG vaccination is one based on an assessment of health economic data. In 1953, the UK adopted a policy of universal vaccination of school children, as TB was found to be most prevalent in the 15-29 age group.

However, there has been a progressive decline in the proportion of TB in UK-born Caucasians of all ages, from 85 per cent in 1985 to <30 per cent in 2008.4 This has been due to a progressive rise in the number of cases in those from Africa and the Indian sub-continent, since overall the numbers of new infections per year has remained relatively stable at 7,000-8,400.

Declining rates
As a result of the declining TB rates in the majority Caucasian population, a targeted approach has been adopted, focusing on providing BCG vaccination to infants from defined high-risk groups. These include regions where the prevalence of TB is greater than 40/100,000 (such as London), or any infants that have parents or grandparents belonging to ethnic groups where the incidence is also higher than 40/100,000.

In addition, older immigrants from high-incidence environments should also be assessed for BCG.

It is clear in the current NICE guidelines on TB that England and Wales meet the international criteria for the cessation of universal BCG in a low prevalence country.

This document argues that the universal schools vaccination programme is not cost-effective with a calculated incremental cost-effectiveness ratio (cost per QALY gained) of between £696,100 and £767,800 for low-risk individuals.5

The argument about the cost-effectiveness of universal BCG vaccination is not new in this country.6

Dealing with an outbreak
While working in a low TB incidence area of the UK, I was involved in managing an outbreak involving school children travelling on a bus where the driver had smear positive TB. Despite a median exposure time of only 24 hours, 55 per cent were infected and only three out of the 33 children had been BCG vaccinated. Other studies have confirmed the high rates of infection in those not BCG vaccinated.7-9

One of these outbreaks was used explicitly to argue for a continuation of the schools vaccination programme, as most of those who had been infected had missed the school BCG vaccination for a variety of reasons.7

While at a macro-level, the prevalence of TB in a given population can be used to inform health procedures, including vaccination policies, at a micro-level populations have become increasingly fluid.

Immigrants from high TB prevalence areas in Eastern Europe, Asia and Africa seek opportunities for work and study in relatively resource-rich countries such as the UK.

Conclusion
TB remains a disease that is stigmatised and the public has yet to modify its view.

With an increasingly non-TB-immune population, TB outbreaks can be expected to increase in number. It may be economically difficult to justify, but the cost of dealing with an outbreak is greater than simply the cost of administering drugs to those who become infected.

  • Dr Barry is consultant chest physician at Llandough Hospital, Penarth, Vale of Glamorgan
  • Declaration of interest: none

AGAINST: The current vaccination policy is rational and evidence based. By Professor Peter Ormerod

To advocate a return to universal BCG vaccination in the UK shows a complete lack of understanding of the efficacy of BCG vaccination, its duration of protection, and the current epidemiology of TB, particularly in England and Wales.

When studied in the UK, BCG vaccination has shown a protective efficacy of between 52 and 64 per cent in neonates and infants by cohort or case-control study, 1,2 and up to 75 per cent if given at age 10-13,3 in the original MRC trial with up to 20 years of follow up.

The duration of such protection only lasts up to 15 years,3 and wanes after 10 years, but has been assumed to last for 15 years for the purposes of later economic appraisals (see below).

Repeat BCG vaccination has no additional benefit.4 Many countries used to give BCG at birth, and again at age 6 or 7 years, and withdrawal of those second, and even first BCG vaccinations, have not altered the pattern of childhood TB within these countries.

The number of TB cases affecting Caucasians in England and Wales has been falling for the past 50 years, from 38 per cent of all cases in 1998 to 21 per cent in 2007.5,6

Not only is there a fall in the proportion of Caucasian patients with TB, but the absolute numbers (2,292 versus 1,626) are also falling.

Within the Caucasian TB cases with a population rate of only 3/100,000/year, there is a very skewed distribution with the median age being over 55 years.

The rate of clinical TB in children and teenagers, who presumably would be targeted for universal BCG by its proponents, is extremely low at under 2/100,000/year,6 and has been consistently low since 1998.5

Over 72 per cent of all cases of TB in England and Wales are now in persons who are non-UK born.6 Proper assessment of new entrants from high-prevalence countries to detect and treat latent infection would be far more effective (and cost-effective) at reducing TB, both in those immigrants and the population in general.

The health economics of using unselective and selective BCG vaccination were appraised in detail in the 2006 NICE guidelines (CG33).7 This clearly showed that the universal 'Schools' programme was grossly uneconomic. The calculations in Table 17 (Chapter 11) of the guideline showed that:

  • If BCG has a protective efficacy for 10 years, the cost of gaining one QALY (incremental cost effectiveness ratio, ICER), with a 10-year risk of TB of 0.03 per cent, was £767,800.
  • If BCG has a protective efficacy for 15 years, the cost of gaining one QALY, with a 15-year risk of TB of 0.03 per cent, was £696,100.2

Since the annual risk of TB for those receiving unselected vaccination from above is 0.00002 per cent, the 10 and 15 years actual risks are 0.0002 per cent and 0.0003 per cent, respectively. These are 150 and 100 times lower than assessed.

The costs quoted above would, therefore, be at least 10 times higher than stated. The level used for cost-effectiveness under NICE analysis is approximately £30,000/QALY.

Unselective BCG vaccination as a 'safety net' system to plug gaps for those high-risk patients, who have missed selective BCG, is only cost-effective if nearly 15 per cent of the whole cohort are high-risk without prior BCG.7

The 'Schools' programme was widely recognised as uneconomic 20 years ago, and there was very serious consideration of cessation in 1990. The only factor that prevented this happening was the arrival of the HIV virus in the 1980s. Because the TB-HIV interaction could not be calculated, the BCG programme was not stopped. We now know, however, that there is relatively little TB-HIV interaction in the UK.

The final nail in the coffin of the proponents of universal BCG vaccination is that, if a new vaccine was developed with the protective efficacy of the current BCG, and with the cost/benefit characteristics shown above for universal vaccination, it would never be considered for use.

If that applies to a potential new vaccine, then it should certainly apply to an old one.

Until replacement or adjunctive vaccines for TB are available, which is at least 10-15 years away, the current vaccination policy is rational and evidence based. Vaccination policy should be determined by science not emotion, as the MMR debacle has shown.

  • Professor Ormerod is a consultant chest physician at Royal Blackburn Hospital and professor of medicine at Lancashire Postgraduate Medical School
  • Declaration of interest: Professor Ormerod was the clinical adviser to the NICE Guidelines 2006 and has been a member of the BCG Committee (now Respiratory Vaccines Panel) of the JCVI since 1987

References (For)
1. Colditz G A, Berkley C S, Mosteller F et al. The efficacy of bacillus Calmette-Guerin vaccination of newborns and infants in the prevention of tuberculosis: meta-analysis of the published literature. Pediatrics 1995; 96: 29-35.

2. Menzies D. What does tuberculin reactivity after Bacille Clamette-Guerin Vaccination tell us? Clin Inf Dis 2000; 31: S71-4.

3. Sutherland I, Springett V H. The effects of the scheme for BCG vaccination of schoolchildren in England and Wales and the consequences of discontinuing the scheme at various dates. J Epidemiol Community Health 1989; 43: 15-24.

4. Tuberculosis in the UK. Annual report on tuberculosis surveillance in the UK. London: Health Protection Agency Centre for Infections, 2008.

5. National Collaborating Centre for Chronic Conditions. Tuberculosis: clinical diagnosis and management of tuberculosis and measures for its prevention and control. London: Royal College of Physicians, 2006.

6. Research Committee of the British Thoracic Association. Report. Effectiveness of BCG vaccination in Great Britain in 1978. Br J Dis Chest 1980; 74: 215-27.

7. Hill J D, Stevenson D K. Tuberculosis in unvaccinated children, adolescents and young adults: a city epidemic. BMJ 1983; 286: 1,471-3.

8. Shannon A, Kelly P, Lucey M et al. Isoniazid resistant tuberculosis in a school outbreak: the protective effect of BCG. Eur Resp J 1991; 4: 778-82.

9. Soysal A, Millington K A, Bakir M et al. Effects of BCG vaccination on risk of Mycobacterium tuberculosis infection in children with household tuberculosis contacts: a prospective community-based study. Lancet 2005; 366: 1,443-51.

References (against)
1. Rodrigues L C, Gill O N, Smith P G. BCG vaccination in the first year of life protects children of Indian subcontinent ethnic origin against tuberculosis in England. J Epidemiol Community Health 1991; 45: 78-80.

2. Packe G E, Innes J A. Protective efficacy of BCG vaccination in infant Asians. A case controlled study. Arch Dis Child 1988; 63: 277-81.

3. Sutherland I, Springett V H. The effects of the scheme for BCG vaccination of school children in England and Wales and the consequences of discontinuing the scheme at various dates. J Epidemiol Community Health 1989; 43: 15-24.

4. Rodrigues L C, Pereira S M, Cunha S S et al. Effect of BCG revaccination on incidence of tuberculosis in school-aged children in Brazil: the BCG REVAC cluster randomised trial. Lancet 2005; 366: 1,290-5.

5. Rose A M C, Watson J M, Graham C et al. Tuberculosis at the end of the 20th Century in England and Wales: results of a national survey in 1998. Thorax 2001; 56: 173-9.

6. Tuberculosis in the UK. Annual report on tuberculosis surveillance in the UK. London: Health Protection Agency Centre for Infections 2008.

7. National Collaborating Centre for Chronic Conditions. Tuberculosis: clinical diagnosis and management of tuberculosis and measures for its prevention and control. London: Royal College of Physicians 2006.

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