The live attenuated strain of Mycobacterium bovis known as bacillus Calmette-Guérin (BCG) uses shared antigens to stimulate the development of cross-immunity to Mycobacterium tuberculosis and Mycobacterium leprae.
It is also used as an intravesicular immunomodulator in the management of bladder carcinoma (see below).
Prevention of tuberculosis
Worldwide efficacy rates of BCG vaccination have varied from 0-80% in studies of different patient populations. Evidence of reproducible efficacy has been limited but recent meta-analyses have shown that the BCG vaccination:
- Reduces the risk of tuberculosis (TB) in all forms by around 50%.
- Reduces severe, non-pulmonary forms, such as childhood tuberculous meningitis, by at least 70%.
This protective effect lasts for 10 years but there is limited evidence to support more prolonged benefit. There is also limited evidence of the efficacy of BCG vaccination when administered to adults. Older people with the highest risk of mortality and the main source of transmission are therefore likely to remain unprotected.
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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 separate article Tuberculosis).
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), or neonates born into a family where there has been a family member with TB in the past 5 years..
- Infants (0 to 12 months of age, and children who have not previously been immunised) with a parent or grandparent who was born in a country with a significant annual incidence of TB (greater than 40/100,000).
- Previously unvaccinated children aged 1 to 5 years with the same background (that is, with a parent or grandparent who was born in a country with a significant annual incidence of TB greater than 40/100,000) and this can be done without tuberculin testing.
- Children aged 6 to 16 years who are previously unvaccinated and tuberculin-negative with a parent or grandparent who was born in a country with a significant annual incidence of TB (greater than 40/100,000) after opportunistic identification and, in this case, negative tuberculin testing.
- 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.
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 vaccine.
Occupational risk factors
The Green Book recommends vaccination of unvaccinated, tuberculin-negative individuals under the age of 35 in the following occupations:
- Healthcare workers who will have contact with patients or clinical materials.
- Laboratory staff who will have contact with patients, clinical materials or derived isolates
- Veterinary staff and staff such as abattoir workers who handle animal species known to be susceptible to TB, eg simians.
- Prison staff working directly with prisoners.
- Staff of care homes for the elderly.
- Staff of hostels for homeless people and facilities accommodating refugees and asylum seekers.
Efficacy of vaccination over the age of 35 is unknown but it may be offered where the risk of TB is considered particularly high.
- The single dose of BCG vaccine is administered intradermally, into the lateral aspect of the abducted left upper arm. 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 10 mm 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.
- All staff should be formally trained in tuberculin skin testing and vaccine administration.
The BCG vaccine should not be given to patients with:
- A past history of TB.
- A positive pre-immunisation tuberculin test.
- A previous anaphylactic reaction to vaccine component.
- Compromised immunity due to treatment or disease.
- Generalised septic skin conditions.
- Acute illnesses with fever or systemic upset.
- HIV-positive individuals - the BCG vaccine is absolutely contra-indicated in symptomatic HIV-positive patients.
In the UK it is also recommended that the BCG vaccine be 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 British Thoracic Society guidelines.
- Pregnancy - live vaccinations should not generally be administered during pregnancy, although no adverse effects have been associated with the BCG vaccination. It is recommended that immunisation in the first trimester be avoided and should be delayed until after delivery if possible.
- Previous BCG vaccination - the BCG vaccine should not be given to individuals previously vaccinated. Those with an uncertain history should be tuberculin tested prior to BCG vaccine administration.
Adverse drug reactions
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 Committee on Safety of Medicines (CSM), using the Yellow Card Scheme.
Tuberculin tests prior to BCG vaccination
A tuberculin skin test is not required prior to BCG vaccination for children under 6 years of age, provided 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 section under Prevention and Screening heading in the separate Tuberculosis article.
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.
Treatment of bladder cancerThe BCG vaccine is used as an intravesicular chemotherapeutic agent in the management of superficial bladder carcinoma:
- In the initial treatment of high-risk cancers.
- To delay or prevent recurrence after transurethral resection.
The use of BCG vaccine as bladder irrigation is contra-indicated in the presence of:
- Impaired immune response, such as HIV infection.
- Active tuberculosis - so patients must be tuberculin screened prior to treatment.
- Frank haematuria or urinary tract infection.
- Pregnancy or breast-feeding.
- Pyrexia of unknown origin.
- 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 antivenom serum, revolutionising the treatment of snakebite in both humans and domestic animals. Working with Camille Guérin, 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. This 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 from 1927-1939 in medical students, they showed an 80% protective effect in those accepting vaccination, and it is regarded as a classic, despite not being a randomised control trial.
Further reading & references
- Improving outcomes in urological cancers, NICE Cancer Service Guidance (2002)
- Immunisation against infectious disease - the Green Book; Dept of Health (latest edition)
- Colditz GA, Brewer TF, Berkey CS, et al; Efficacy of BCG vaccine in the prevention of tuberculosis. Meta-analysis of the published literature. JAMA. 1994 Mar 2;271(9):698-702.
- Aronson NE, Santosham M, Comstock GW, et al; Long-term efficacy of BCG vaccine in American Indians and Alaska Natives: A JAMA. 2004 May 5;291(17):2086-91.
- Rodrigues LC, Diwan VK, Wheeler JG; Protective effect of BCG against tuberculous meningitis and miliary tuberculosis: a meta-analysis. Int J Epidemiol. 1993 Dec;22(6):1154-8.
- Sterne JA, Rodrigues LC, Guedes IN; Does the efficacy of BCG decline with time since vaccination? Int J Tuberc Lung Dis. 1998 Mar;2(3):200-7.
- Chan ED, Iseman MD; Current medical treatment for tuberculosis. BMJ. 2002 Nov 30;325(7375):1282-6.
- Tuberculosis, NICE Clinical Guideline (March 2011)
- Stedwell RE, Allen KM, Binder LS; Hypokalemic paralyses: a review of the etiologies, pathophysiology, presentation, and therapy. Am J Emerg Med. 1992 Mar;10(2):143-8.
- Mitropoulos DN; Novel insights into the mechanism of action of intravesical immunomodulators. In Vivo. 2005 May-Jun;19(3):611-21.
- Intravesical microwave hyperthermia with intravesical chemotherapy for superficial bladder cancer, NICE Interventional Procedure Guideline (October 2007)
|Original Author: Dr Richard Draper||Current Version: Dr Huw Thomas|
|Last Checked: 22/06/2011||Document ID: 480 Version: 6||© EMIS|
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