BCG Vaccination

The live attenuated strain of Mycobacterium bovis known as Bacillus Calmette-Guérin (BCG) uses shared antigens to stimulate the development of cross-immunity to M. tuberculosis and M. leprae,¹ see related Tuberculosis article.
It is also used as an intravesicular immunomodulator in the management of bladder carcinoma (see below).²

Worldwide efficacy rates of BCG vaccination have varied from 0-80% in studies of different patient populations.³ Evidence of reproducible efficacy has been limited but recent meta-analyses have shown that the BCG vaccination:

• Reduces the risk of TB in all forms by 50%.⁴
• Reduces severe, non-pulmonary forms such as childhood tuberculous meningitis by at least 70%.⁵

This protective effect lasts for 10 years but there is little evidence to support more prolonged benefit.⁶ There is also limited evidence of the efficacy of BCG when administered to adults. Older people with the highest risk of mortality and the main source of transmission are therefore likely to remain unprotected.⁷

The UK BCG immunisation programme

The BCG vaccination was introduced in 1953. The incidence of TB was already declining due to improved public health and social measures and so the impact of immunisation has been difficult to assess. Over the last 50 years, epidemiological changes have also occurred necessitating various alterations to the immunisation policy (see Tuberculosis).³

In 2005 the schools' BCG immunisation programme was stopped following continued decline in TB rates in the indigenous UK population.

The new immunisation schedule is based on risk assessment and involves targeted immunisation of neonates and others at high risk.
BCG immunisation is now recommended for:

• Infants (0 to 12 months of age) living in areas of the UK where the annual incidence of TB is significant (greater than 40/100 000).
• Infants (0 to 12 months of age) with a parent or grandparent who was born in a country with a significant annual incidence of TB (greater than 40/100 000) plus previously unvaccinated children aged up to 5 years with the same background.
• Previously unvaccinated, tuberculin-negative immigrants under the age of 16 years from countries with a significant incidence of TB (greater than 40/100 000).
• Previously unvaccinated, tuberculin-negative contacts of respiratory TB cases or individuals with high risk of occupational or travel exposure, as per British Thoracic Society (BTS) guidelines and patient information.⁸

It is important to note that:

• The majority of vaccinations should be given to neonates whilst still in hospital.
• However other individuals will also meet the criteria for immunisation and as the schools' programme has now ceased, local policy will be needed to identify these outliers.
• Individuals without risk factors for TB, who request vaccination should not be offered the BCG.

• The single dose of BCG vaccine is administered intradermally, into the lateral aspect of the abducted left upper arm.³ A small bleb is raised and a successful vaccination leads to the development of a small local swelling within 2 weeks. The lesion progresses to a papule or shallow ulcer of approximately 10mm diameter and heals within 12 weeks to form a small, flat scar.
• Patients should be advised not to cover the site with tight clothing or sealed dressings.
• The BCG can be given simultaneously with other live vaccines but if not given at the same time, further immunisations should be delayed for at least 4 weeks. No other immunisations should be given in the same arm for 3 months because of the risk of lymphadenitis.³
• All staff should be formally trained in tuberculin skin testing and vaccine administration.³

The BCG vaccine should not be given to patients with:

• Patients with a past history of TB.
• Patients with a positive pre-immunisation tuberculin test.
• Patients with previous anaphylactic reaction to vaccine component.
• Patients with compromised immunity due to treatment or disease.
• Patients with generalised septic skin conditions.
• Patients with acute illnesses with fever or systemic upset.
• HIV-positive individuals - The BCG is absolutely contraindicated in symptomatic HIV-positive patients.
  In the UK it is also recommended that the BCG is withheld from those known or suspected to be HIV-positive regardless of clinical condition. However infants born to HIV-positive mothers must be tested promptly and if persistently negative they should be given the BCG vaccination, as per BTS guidelines.
• Pregnancy - live vaccinations should not generally be administered during pregnancy although no adverse effects have been associated with the BCG. It is recommended that immunisation in the first trimester is avoided and should be delayed until after delivery if possible.
• Previous BCG vaccination - The BCG should not be given to previously vaccinated individuals. Those with an uncertain history should be tuberculin tested prior to BCG administration.

Severe injection site reactions, discharging ulcers, abscesses and keloid scars are generally caused by:

• Poor vaccination technique
• Excessive dose
• Immunisation of tuberculin-positive patients

Local reactions should be encouraged to dry out and spontaneous resolution will usually occur. Severe reactions such as deep ulceration, abscesses, caseous lesions or suppurative lymphadenitis should be referred to secondary care for investigation and further management.
Other reactions include headache, fever, enlargement of regional lymph nodes and occasionally osteomyelitis.
All adverse effects must be reported to the CSM using the yellow card system.

A tuberculin skin test is not required prior to BCG vaccination for children under 6 years of age providing there is no history of:

• Residence in a high-risk area
• Contact with a tuberculosis patient.

For all other patients a tuberculin test is necessary before BCG vaccination. The standard UK screening tool is now the Mantoux test. See Tuberculosis article (section on screening).

Many new vaccines are in development and entering into clinical trials. The new candidates include live attenuated M. tuberculosis, recombinant BCG, DNA vaccines and fusion proteins with novel adjuvants and all aim to provide a stronger and longer lasting immune response in heterogeneous populations.⁹

• Leon Calmette (1863-1933), medical officer in the French Navy, and director of the Pasteur Institute in Lille for 25 years, was the first person to develop an anti-venom serum, revolutionising the treatment of snakebite in both humans and domestic animals. Working with Camille Guerin, over a period of 13 years, from 1908 to 1921, they produced an attenuated strain suitable for vaccination.
• The idea for attenuating tubercle bacilli may have come from the Norwegian physician Kristian Andvord (1855-1934), and it was the Norwegians, Olaf Scheel, and his deputy Johannes Heimbeck, who changed the understanding of the pathogenesis of TB, using mandatory tuberculin testing in 1924, showed that half of student nurse entrants to the Ullevaal Hospital School of Nursing in Oslo, were not infected at entry, but almost all became so in their 3 years of training (this conflicted with the prevailing view that nearly all TB infection occurred in childhood). In a study of BCG vaccination from 1927-1936 in nursing students, and 1927-1939 in medical students, they showed an 80% protective effect in those accepting vaccination, and is regarded as a classic, despite not being a randomised control trial.