BCG vaccine
The Bacillus Calmette–Guérin 'vaccine' is a vaccine primarily used against tuberculosis. It is named after its inventors Albert Calmette and Camille Guérin. In countries where tuberculosis or leprosy is common, one dose is recommended in healthy babies as soon after birth as possible. 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. Adults who are frequently exposed to tuberculosis may also be immunized. BCG has some effectiveness against Buruli ulcer infection and other nontuberculous mycobacterial infections. It is also often used as part of the treatment of bladder cancer.
Rates of protection against tuberculosis infection vary widely and protection lasts up to 20 years. 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. No evidence shows that additional doses are beneficial.
Serious side effects are rare. Redness, swelling, and mild pain often occur at the injection site. A small ulcer may also form with some scarring after healing. Side effects are more common and potentially more severe in those with immunosuppression. 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. The vaccine was originally developed from Mycobacterium bovis, which is commonly found in cattle. Although it has been weakened, it is still live.
The BCG vaccine was first used medically in 1921. It is on the World Health Organization's List of Essential Medicines., the vaccine is given to about 100 million children per year globally. However, it is not commonly administered in the United States.
Medical uses
Tuberculosis
The main use of BCG is for vaccination against tuberculosis. BCG vaccine can be administered after birth intradermally. BCG vaccination can cause a false positive Mantoux test.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%. 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.
A systematic review and meta-analysis conducted in 2014 demonstrated that the BCG vaccine reduced infections by 19–27% and reduced progression to active tuberculosis by 71%. The studies included in this review were limited to those that used interferon gamma release assay.
The duration of protection of BCG is not clearly known. In those studies showing a protective effect, the data are inconsistent. The MRC study showed protection waned to 59% after 15 years and to zero after 20 years; however, a study looking at Native Americans immunized in the 1930s found evidence of protection even 60 years after immunization, with only slightly waning in efficacy.
BCG seems to have its greatest effect in preventing miliary tuberculosis or tuberculosis meningitis, so it is still extensively used even in countries where efficacy against pulmonary tuberculosis is negligible.
The 100th anniversary of the BCG vaccine was in 2021. It remains the only vaccine licensed against tuberculosis, which is an ongoing pandemic. Tuberculosis elimination is a goal of the World Health Organization. The development of new vaccines with greater efficacy against adult pulmonary tuberculosis may be needed to make substantial progress.
Efficacy
Several possible reasons for the variable efficacy of BCG in different countries have been proposed. None has been proven, some have been disproved, and none can explain the lack of efficacy in low tuberculosis-burden countries and high tuberculosis-burden countries. The reasons for variable efficacy have been discussed at length in a WHO document on BCG.; Genetic variation in BCG strains
; Genetic variation in populations
; Interference by nontuberculous mycobacteria
; Interference by concurrent parasitic infection
Mycobacteria
BCG has protective effects against some nontuberculosis mycobacteria.- Leprosy: BCG has a protective effect against leprosy in the range of 20–80%.
- Buruli ulcer: BCG may protect against or delay the onset of Buruli ulcer.
Cancer
- Several cancer vaccines use BCG as an additive to provide an initial stimulation of the person's immune system.
- BCG is used in the treatment of superficial forms of bladder cancer. Since the late 1970s, evidence has become available that the instillation of BCG into the bladder is an effective form of immunotherapy in this disease. While the mechanism is unclear, it appears a local immune reaction is mounted against the tumor. Immunotherapy with BCG prevents recurrence in up to 67% of cases of superficial bladder cancer.
- BCG has been evaluated in many studies as a therapy for colorectal cancer. The US biotech company Vaccinogen is evaluating BCG as an adjuvant to autologous tumour cells used as a cancer vaccine in stage II colon cancer.
Method of administration
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 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.
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.
When given for bladder cancer, the vaccine is not injected through the skin but is instilled into the bladder through the urethra using a soft catheter.
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.BCG vaccine should be given intradermally. If given subcutaneously, it may induce local infection and spread to the regional lymph nodes, causing either suppurative 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.
Uncommonly, breast and gluteal abscesses can occur due to haematogenous and lymphangiomatous spread. Regional bone infection and disseminated BCG infection are rare complications of BCG vaccination, but potentially life-threatening. Systemic antituberculous therapy may be helpful in severe complications.
When BCG is used for bladder cancer, around 2.9% of treated patients discontinue immunotherapy due to a genitourinary or systemic BCG-related infection, however while symptomatic bladder BCG infection is frequent, the involvement of other organs is very uncommon. When systemic involvement occurs, liver and lungs are the first organs to be affected.
If BCG is accidentally given to an immunocompromised patient, it can cause disseminated or life-threatening infection. The documented incidence of this happening is less than one per million immunizations given. In 2007, the WHO stopped recommending BCG for infants with HIV, even if the risk of exposure to tuberculosis is high, because of the risk of disseminated BCG infection.