Bacillus-Calmette-Guerin vaccine - Tuberculosis

What is BCG?

Bacillus-Calmette-Guerin vaccine.

What is the history behind the name?

Two French scientists, Calmette, a physician, and Guérin, a veterinarian, selected

a M. bovis strain isolated from a cow with tuberculous mastitis in 1908.

The vaccine was first used in 1921 in Paris, when it was given orally to infants.

Dr Albert Calmette

What are the different strains of BCG available worldwide?

Danish 1331 and Pasteur are 2 common strains that we are aware of but there are other strains as well named after the country or lab they are kept

Glaxo strain 1077

Tokyo strain

Russian strain BCG-I

Moreau

Montreal strain (Canada) and

the Tice strain (United States). The Tice strain is the only approved strain in USA.

What type of vaccine is BCG?

It is a live attenuated vaccine.

How is it packaged and stored?

It is supplied in a freeze - dried form(lyophilized) multi-dose, amber colored ampoules or 2 ml vial with normal saline as diluent.

Can BCG protect against covid-19? click here

What is lyophilization?

The process of isolating a solid substance from solution by freezing the solution and evaporating the ice under vacuum.

In lyophilized form BCG vaccine can be stored at 2-80⁰C for 12 months

Why are amber colored ampoules used for storing?

Since BCG is a photosensitive as well as heat sensitive vaccine to prevent it from losing its potency it is stored in colored/darkened ampoules.

What is used for dilution of vaccine?

Sterile normal saline.

How long can we use a reconstituted vaccine?

BCG vaccine has no preservative hence it cannot be used for more than 4-6 hours at 2-8⁰C after reconstitution.

If used high risk of bacterial infection and toxic shock syndrome.

Can BCG be used as a post exposure prophylaxis?

No

What is the route of administration?

Intradermal route with correct administration verified by a wheal of 5mm.

Are there any other routes?

As ID route is difficult route the only alternate route used currently is percutaneous administration with a multipuncture device.

A Phase IV trial conducted in South Africa compared multipuncture (percutaneous) and intradermal administration of the Japanese BCG strain and demonstrated equivalence between the two routes, in terms of both efficacy to prevent pulmonary TB and adverse events.

What is the recommended dose?

The recommended dose of BCG vaccine differs by vaccine strain and age of the recipient.

Similarly, the number of colony-forming units per dose varies by vaccine strain.

The standard dose of reconstituted vaccine is 0.05 mL for infants aged <1 year and 0.1 mL for infants aged >1 year and 0.1 mL for infants aged >1 year.

What is the site of administration?

Although many body sites can be used for vaccination, the most common site is the deltoid region of the arm, usually on the right. (left in India)

There are no details regarding efficacy and safety for other anatomic sites.

What are the changes visible at the site of vaccine administration?

After 2-3 weeks a papule is formed that increases to 4-8 mm after 5-6 weeks

Papule heals with ulcer after 6-12 weeks

Final scar is formed at the site of ulcer after few weeks

This is normal and no treatment is required.

Approx. 10% do not develop the vaccine scar and this doesn’t mean that protection isn’t achieved.

What is the ideal age of BCG immunization?

WHO recommends to give a single dose to newborns.

Some countries continue to give the first dose of BCG in infancy followed by one or multiple vaccinations throughout childhood.

Which type of immunity is induced by BCG vaccine?

Cell-mediated immunity.

CD4-T cell response should be induced by BCG vaccine to be effective.

 Can we determine the BCG induced immunity required for protection against?

As of now no determinants are available.

Can TST be used as a reliable indicator of previous BCG vaccination?

Often, we have been using TST assess whether a person has responded to BCG vaccination and

even revaccination was advised in cases of negative TST.

However, lately trials from Medical Research Council of Great Britain and South India have shown that no such correlation exists between TST positivity and vaccine immunogenicity.

Does the time of vaccine administration have any impact on vaccine efficacy?

There have been various studies assessing different vaccine schedules.

Some had tried delaying vaccination to 6 weeks of life instead of immediate newborn period with idea that the infant’s immune system will be more mature.

However, all such assessments have conflicting results.

Are there any benefits of vaccinating during infancy than during childhood or older age?

Various studies have shown that vaccinating children and adults already exposed to mycobacterium from environment may result in lower host response.

The preexisting mycobacterial infection may result in masking or blocking of host responses to BCG.

If so, can we vaccinate older children or adults in case they have missed during infancy or if they aren’t sure about the vaccination?

WHO recommends vaccination of children and adults in the following situations.

Unvaccinated TST negative or interferon-gamma release assay (IGRA) negative older children, adolescents and adults from settings of High TB and/or leprosy burden.

Unvaccinated TST negative or interferon-gamma release assay (IGRA) negative older children, adolescents and adults moving from low to high TB or leprosy burden settings

Unvaccinated TST negative or interferon-gamma release assay (IGRA) negative older children, adolescents and adults who are at risk of exposure. (health workers, lab workers, prisoners etc.)

What is the efficacy of BCG?

BCG appears most protective against disseminated forms of childhood TB, such as miliary TB and TB meningitis, with an overall efficacy of approximately 80%.

The efficacy against pulmonary infection is variable ranging from 0 to 80%

What are the factors that determine vaccine efficacy?

Effectiveness of vaccine strain which depends on the storage of vaccine, administration of vaccine

TST negative prior to vaccination increases efficacy.

No mycobacterium exposure before vaccination increases vaccine efficacy.

Can BCG provide protection against leprosy?

The vaccine is highly effective at preventing leprosy

What is the duration of protection once vaccinated?

A systemic review has concluded that after a primary vaccination during infancy the protection can last up to 15 years in some population.

However, it depends upon

Genetics of individual

Vaccine strain used.

Absence of mycobacterial exposure and TST negativity prolongs the duration of protection.

What are the Adverse Events Following Immunization seen in BCG?

Local skin reactions

Abscess formation if given SC instead of ID.

Disseminated BCG disease in cases of primary immunodeficiency

IRIS -immune reconstitution inflammatory syndrome in HIV patients

 BCG lymphadenitis.

Can we vaccinate the preterm infants with BCG?

BCG vaccination at birth to healthy preterm infants born at 32-36 weeks has been found to be safe and effective.

Can we administer BCG at the same time with other vaccines?

YES.

BCG vaccination is contraindicated for individuals known to be allergic to any component of the vaccine.

Can we vaccinate a pregnant and lactating mother with BCG?

Contraindicated in pregnancy but can be administered during lactation.

Can we vaccinate an infant born to HIV infected mother?

BCG vaccine in HIV infected infants can cause disseminated BCG infection.

If both mother and child are on ART, they can get vaccinated.

If maternal HIV is unknown and child is fine administer BCG.

Neonates with unknown HIV status born to mother with HIV not on ART should be vaccinated if there is no clinical evidence of infection in the neonate.

If a neonate is born to mother with pulmonary TB, we should first find out whether the infant TB or not. If no TB is detected, start the neonate on preventive therapy of isoniazid. At the end of preventive therapy if the child has no TB and is HIV negative vaccinate him/her.

What are other beneficial effects of BCG?

Studies have found that BCG can enhance the antibody response of other vaccines like Hep B, TT, pneumococcal.

It has been shown to prevent respiratory infections from bacteria and viruses as well.

 Around 16 new TB vaccines are under trial as of now.

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High yield points on BCG.