20 Tuberculosis

20.4 Vaccine

Note: Depending on world supply, BCG vaccine may not be available in New Zealand.

Bacillus Calmette-Guérin (BCG) vaccine types vary widely, with different strains. The incidence of side-effects with BCG vaccination differs between strains that are considered ‘strong’ (ie, those that elicit stronger immune responses in animal models) and strains that are considered ‘weak’.6 The strong strains have also been associated with a higher rate of lymphadenitis and osteitis, especially among neonates. Reducing the vaccination dosage for the strong strains also reduces the incidence of lymphadenitis.

20.4.1 Available vaccine

BCG vaccine (Seqirus (NZ) Ltd) is a live attenuated vaccine. The adult dose contains 2–8 x 105 colony-forming units (cfu) of the Danish 1331 strain of M. bovis, and the infant dose contains 1–4 x 105 cfu. Other components and residuals include sodium glutamate, magnesium sulphate heptahydrate, dipotassium phosphate, citric acid, L asparagine monohydrate, ferric ammonium citrate and glycerol.

20.4.2 Efficacy and effectivenessTop

The exact immune response elicited by BCG vaccination and the mechanism of action in the host are still not well understood. There is no reliable established laboratory correlate for immunity to M. tuberculosis.6 While it is unlikely that any single, simple measure of cellular immune function will be useful as a direct correlate of protection, new breakthroughs in technology that could improve the diagnostic tools available are on the horizon.

The principal role of BCG is to protect young children who are at greatest risk from severe disease, particularly miliary and meningeal disease.6 The vaccines provide protection against meningitis and disseminated TB in children, particularly in newborns and young infants. However, BCG vaccines do not prevent primary infection, are only partially effective against severe infection in children, are unreliable against adult pulmonary TB, and are not effective against reactivation of latent pulmonary infection. In persons infected with TB, subsequent vaccination with BCG does not augment the immune response.6

The efficacy of BCG vaccines ranges from 0 to 80 percent.6 There are significant differences in efficacy across populations and geographical areas. Maternal factors, genetic factors, nutritional factors and environmental factors all appear to influence efficacy. Efficacy and immunogenicity responses vary considerably across vaccine strains, but the data to date cannot differentiate which strains are overall more effective.7 In developing countries, a birth dose of BCG significantly reduces overall infant mortality.8 One possible aspect of this effect may be that BCG appears to enhance the production of vitamin D.9 HIV exposed uninfected infants show a blunting of the immune response to BCG given in early infancy.10

BCG has had little effect in reducing the population rate and transmission of TB,11 so there are no herd immunity effects. Duration of protection is unknown, possibly 10 to 15 years, but it may be much longer in some populations.6

There have been a number of different approaches to using BCG in the control of TB in developed countries.12 The US has not had a BCG programme, whereas New Zealand (see Appendix 1) and the UK had programmes until 1990 and 2005, respectively. The WHO recommends that countries with low rates of active TB, such as New Zealand, target BCG vaccination at children who are at significantly increased risk of TB exposure through household contact.13 New Zealand (see section 20.5) and the UK now only offer BCG vaccine to high-risk individuals. A study from the Netherlands suggests that around 9000 children from countries with rates greater than 50 per 100,000 population would have to be given BCG to prevent a severe case.14

The current recommendation to use neonatal BCG vaccination in populations with high rates of active TB is just part of a comprehensive control and treatment programme for TB in New Zealand, which includes active contact tracing and treatment of LTBI.

There are large international efforts working to enhance TB control by improving BCG vaccine and by developing new, more effective vaccines.15

20.4.3 Transport, storage and handlingTop

Transport according to the National Guidelines for Vaccine Storage and Distribution.16 Store in the dark at +2oC to +8oC. Do not freeze.

BCG vaccine is presented as freeze-dried material with a diluent in a separate ampoule. Reconstituted vaccine should be stored at 4oC and used within four hours.

20.4.4 Dosage and administrationTop

From 4 January 2017, only authorised vaccinators with BCG endorsement will be able to administer BCG vaccine (see Appendix 4).

After reconstitution, the dose for infants aged under 12 months is 0.05 mL, and the dose for adults and children aged over 12 months is 0.1 mL.

The vaccine is administered by intradermal injection over the point of insertion of the left deltoid muscle. This is not much higher than the mid-point of the upper arm. For full details about administration, refer to the Technical Guidelines for Tuberculin Testing and BCG Vaccination 199617 (or the current edition).

No follow-up tuberculin skin testing is required.

BCG immunisation given in other countries

Care must be taken when assessing for previous vaccination. BCG is one of the vaccines that are part of the WHO Expanded Programme on Immunization. It is given at birth in most low-income countries.

The following Pacific Island countries18 recommend BCG vaccination at birth: Cook Islands, Fiji, Kiribati, Nauru, Niue, Papua New Guinea, Samoa, Solomon Islands, Tonga, Tuvalu and Vanuatu.

Usually BCG vaccine is administered in the left deltoid area, but other sites of administration have also (although uncommonly) been used, such as the right deltoid. Revaccination with BCG is not recommended by the WHO.13

Co-administration with other vaccines

BCG can be given simultaneously with any other vaccine. However, it must be administered into a separate site in a separate syringe. Because of the risk of local lymphadenitis, no further vaccinations should be given into the arm used for BCG for at least three months. If not given concurrently, BCG should be given at least four weeks after MMR or varicella vaccines. Note that no time interval is required between administration of BCG and rotavirus vaccines.

Hepatitis B immunoglobulin (given at birth to babies of mothers with chronic hepatitis B infection) or normal immunoglobulin is thought not to reduce the effectiveness of BCG immunisation, which principally acts through cell-mediated immunity.