The Bacillus Calmette–Guérin (BCG) vaccine is a vaccine primarily used against tuberculosis (TB).[8] It is named after its inventors Albert Calmette and Camille Guérin.[9][10] In countries where tuberculosis or leprosy is common, one dose is recommended in healthy babies as soon after birth as possible.[8] In areas where tuberculosis is not common, only children at high risk are typically immunized, while suspected cases of tuberculosis are individually tested for and treated.[8] Adults who are frequently exposed to tuberculosis may also be immunized.[8] BCG has some effectiveness against Buruli ulcer infection and other nontuberculous mycobacterial infections.[8] It is also often used as part of the treatment of bladder cancer.[11][12]
Rates of protection against tuberculosis infection vary widely and protection lasts up to 20 years.[8] Among children, it prevents about 20% from getting infected and among those who do get infected, it protects half from developing disease. The vaccine is injected into the skin.[8] No evidence shows that additional doses are beneficial.[8]
Serious side effects are rare. Redness, swelling, and mild pain often occur at the injection site.[8] A small ulcer may also form with some scarring after healing.[8] Side effects are more common and potentially more severe in those with immunosuppression.[8] Although no harmful effects on the fetus have been observed, there is insufficient evidence about the safety of BCG vaccination during pregnancy. Therefore, the vaccine is not recommended for use during pregnancy.[8] The vaccine was originally developed from Mycobacterium bovis, which is commonly found in cattle.[8] Although it has been weakened, it is still live.[8]
The BCG vaccine was first used medically in 1921.[8] It is on the World Health Organization's List of Essential Medicines.[13] As of 2004, the vaccine is given to about 100 million children per year globally.[14] However, it is not commonly administered in the United States.[15]
Medical uses
Tuberculosis
The main use of BCG is for vaccination against tuberculosis. BCG vaccine can be administered after birth intradermally.[16] BCG vaccination can cause a false positive Mantoux test.[17]
The most controversial aspect of BCG is the variable efficacy found in different clinical trials, which appears to depend on geography. Trials in the UK consistently show a 60 to 80% protective effect. Still, those trials conducted elsewhere have shown no protective effect, and efficacy appears to fall the closer one gets to the equator.
A 1994 systematic review found that BCG reduces the risk of getting tuberculosis by about 50%.[18] Differences in effectiveness depend on region, due to factors such as genetic differences in the populations, changes in environment, exposure to other bacterial infections, and conditions in the laboratory where the vaccine is grown, including genetic differences between the strains being cultured and the choice of growth medium.
Method of administration
A pre-injection tuberculin skin test is usually carried out before administering the BCG vaccine. A reactive tuberculin skin test is a contraindication to BCG due to the risk of severe local inflammation and scarring; it does not indicate immunity. BCG is also contraindicated in certain people who have IL-12 receptor pathway defects.[37]
BCG is given as a single intradermal injection at the insertion of the deltoid. If BCG is accidentally given subcutaneously, then a local abscess may form (a "BCG-oma") that can sometimes ulcerate, and may require treatment with antibiotics immediately, otherwise without treatment it could spread the infection, causing severe damage to vital organs. An abscess is not always associated with incorrect administration, and it is one of the more common complications that can occur with the vaccination. Numerous medical studies on the treatment of these abscesses with antibiotics have been done with varying results, but the consensus is once pus is aspirated and analysed, provided no unusual bacilli are present, the abscess will generally heal on its own in a matter of weeks.[38]
The characteristic raised scar that BCG immunization leaves is often used as proof of prior immunization. This scar must be distinguished from that of smallpox vaccination, which it may resemble.[37]
Adverse effects
BCG immunization generally causes some pain and scarring at the site of injection during infancy. The mechanism of this side effect is not fully understood, however it can be mitigated by performing the vaccination later in life. Usually wealthier regions have lower scar rate among the population, such as Western Europe, unlike its Eastern counterpart, where the BCG scar is considered widespread. The insertion to the deltoid muscle is typically used because the local complication rate is smallest for that site. In most countries it is the left shoulder, although some, like Brazil, administer the vaccination to the right. Nonetheless, the buttock is an alternative site of administration because it provides better cosmetic outcomes.[37]
BCG vaccine should be given intradermally. If given subcutaneously, it may induce local infection and spread to the regional lymph nodes, causing either suppurative (production of pus) or nonsuppurative lymphadenitis. Conservative management is usually adequate for nonsuppurative lymphadenitis. If suppuration occurs, it may need needle aspiration. For unresolved suppuration, surgical excision may be required. Evidence for the treatment of these complications is scarce.[40]
Usage
The person's age and the frequency with which BCG is given have always varied from country to country. The WHO recommends childhood BCG for all countries with a high incidence of tuberculosis and/or high leprosy burden.[8] This is a partial list of historic and active BCG practices around the globe. A complete atlas of past and present practice has been generated. As of 2022, 155 countries offer the BCG vaccine in their schedule.[49]
Manufacture
BCG is prepared from a strain of the attenuated (virulence-reduced) live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its ability to cause disease in humans. It is specially subcultured in a culture medium, usually Middlebrook 7H9.[98] Because the living bacilli evolve to make the best use of available nutrients, they become less well-adapted to human blood and can no longer induce disease when introduced into a human host. Still, they are similar enough to their wild ancestors to provide some immunity against human tuberculosis. The BCG vaccine can be anywhere from 0 to 80% effective in preventing tuberculosis for 15 years; however, its protective effect appears to vary according to geography and the lab in which the vaccine strain was grown.[99]
Several companies make BCG, sometimes using different genetic strains of the bacterium. This may result in different product characteristics. OncoTICE, used for bladder instillation for bladder cancer, was developed by Organon Laboratories (since acquired by Schering-Plough, and in turn acquired by Merck & Co.). A similar application is the product of Onko BCG[100]
History
The history of BCG is tied to that of smallpox. By 1865 Jean Antoine Villemin had demonstrated that rabbits could be infected with tuberculosis from humans;[111] by 1868 he had found that rabbits could be infected with tuberculosis from cows and that rabbits could be infected with tuberculosis from other rabbits.[112] Thus, he concluded that tuberculosis was transmitted via some unidentified microorganism (or "virus", as he called it).[113][114] In 1882 Robert Koch regarded human and bovine tuberculosis as identical.[115] But in 1895, Theobald Smith presented differences between human and bovine tuberculosis, which he reported to Koch.[116]
Research
Alternative routes of administration
In rhesus macaques, BCG shows "unprecedented" rates of TB protection when given intravenously.[125][126] Some risks must be evaluated before it can be translated to humans.[127]
The University of Oxford Jenner Institute is conducting a study comparing the efficacy of injected versus inhaled BCG vaccine in already-vaccinated adults.[128]
Non-TB conditions
Veterinary use
BCG is used in England by licensed individuals to vaccinate wild badgers by trapping and release. It reduces new bovine TB infection rates by up to 76% in vaccinated badgers. It also exhibits a herd immunity effect, where a badger social group with more than one-third vaccination coverage shows up to 79% lower new infection in cubs. There is no evidence that vaccinated badgers excrete live BCG into the environment. Vaccination initiatives have been lead both by the government's Animal and Plant Health Agency and by private individuals and groups such as farmers seeking to protect their livestock and landowners seeking to clear their land of TB.[145]
BCG vaccination in cattle has completed a phase II trial in the UK with satisfactory results. The phase III trial started in 2025.[146]
External links
References
- Summary for ARTG Entry:53569 BCG VACCINE Mycobacterium bovis (Mycobacterium bovis (Bacillus Calmette and Guerin (BCG) strain) (BCG) strain) 1.5mg powder for injection multidose vial with diluent vial Therapeutic Goods Administration (TGA), retrieved 31 July 2024^
- Regulatory Decision Summary - Verity-BCG Health Canada, 23 October 2014, retrieved 5 June 2022^
- Verity-BCG Product information