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Bacillus Calmette Guerin
Introduction
Bacillus Calmette-Guérin (BCG) is the live attenuated vaccine form of Mycobacterium bovis used to prevent tuberculosis and other mycobacterial infections. The vaccine was developed by Calmette and Guérin and was first administered to human beings in 1921. BCG is the only vaccine against tuberculosis. It is the most widely administered vaccine and usually a part of the routine newborn immunization schedule. BCG vaccine also offers protection against non-tuberculous mycobacterial infections like leprosy and Buruli ulcer. It is also used in the treatment of superficial carcinoma of the bladder.
BCG vaccine is a fairly safe vaccine and it is not associated with severe complications. Prior to the mycobacterial infection, vaccine-induced or acquired naturally can protect against subsequent infection due to mycobacteria including tuberculosis.[1] Prior infection with nontuberculous mycobacteria and Mycobacterium tuberculosis can confer natural protection against tuberculosis infection.[2][3] Protection against tuberculosis infection is usually due to the immune response to mycobacterial antigens. Prior contained latent infection with Mycobacterium tuberculosis can provide up to 80 percent protection against disease with subsequent exposure.[4] In patients with previous active disease, there is an increased risk of recurrence of active tuberculosis due to distinct strains in both HIV-uninfected and HIV-infected patients.[5][6][7][8][9][10] Bacille Calmette-Guérin (BCG) has been associated with a reduction in childhood mortality which is not attributable to tuberculosis. Reduction in childhood mortality may be due to epigenetic reprogramming of the nucleotide-binding oligomerization domain (NOD2) receptor.[11][12][13][14]
BCG vaccine can be given either intracutaneously or intradermally. Research is currently being conducted on respiratory administration since natural infection, and sensitization to Mycobacterium tuberculosis in humans tend to occur in the respiratory system.[15][16]
Indications
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Indications
Groups to consider for BCG vaccination include
Children: Newborns and infants have the greatest benefit from BCG vaccination
- Infants and children ≤five years with a high risk of exposure to active pulmonary TB.
- Healthy neonates [17]
- School-age children (aged 7 to 14) not previously vaccinated.[18]
Developed Countries: Consider BCG vaccination in infants and children ≤5 years in the following conditions [19][20]
- Prolonged exposure to a patient with untreated, inadequately treated, or isoniazid and rifampin-resistant M. tuberculosis if separation from such exposure is not possible.
Exposure to MDR-TB
- Consider vaccination in travelers, health care workers, and individuals in the community with exposure to multidrug-resistant (MDR-) tuberculosis.
- Administer to unvaccinated, tuberculin-negative individuals.
Health Care Workers
Routine vaccination of health care workers is not recommended in the United States since infection with tuberculosis is low. BCG vaccine also interferes with the result of a tuberculin skin test that is used to detect Mycobacterium tuberculosis infection. In health care workers, the efficacy of BCG vaccination is not definite.[21] Strict adherence to tuberculosis infection control practices should be emphasized in areas with a high incidence of disease transmission.
- Consider BCG vaccination in healthcare workers in regions with high TB transmission
- Consider vaccination in health care workers from low-risk countries taking care of patients or refugees in TB-endemic countries
BCG immunization guidelines depend on the prevalence of tuberculosis infection.[22][23] Childhood BCG immunization should be routine in countries with a high prevalence of tuberculosis. In countries with low to intermediate rates of TB (<5/100,000 smear-positive cases per year), BCG immunization should be administered to children at particular risk of TB exposure [23] ( ie children exposed to multidrug-resistant disease).
BCG vaccination policy is determined by the regional prevalence of tuberculosis infection. Routine neonatal vaccination is recommended by the WHO in countries with moderate to severe prevalence of tuberculosis. Close contacts of patients with TB infection and healthcare workers exposed to patients' multidrug-resistant tuberculosis infections with negative tuberculin tests should receive BCG vaccination. Routine BCG vaccination is not recommended in countries with a low prevalence of tuberculosis. Routine BCG vaccination has never been recommended in the United States given the low prevalence of tuberculosis infection. Routine BCG vaccination of children at age 13 and all neonates in high-risk groups was implemented between 1953 and 2005 in the United Kingdom. Routine vaccination was later discontinued in 2005 due to a decreased incidence of tuberculosis infection.
Treatment of Bladder Cancer
A single dose of M. bovis bacillus Calmette-Guérin immunotherapy has a great therapeutic benefit in the treatment of non-invasive forms of bladder cancer. It is administered intravesically and proven benefits include the delay and prevent the progression of the malignancy.[24][25][26]
Contraindications
Immunocompromised patients
BCG is a live vaccine and should not be given to:
- Immunocompromised persons with congenital immunodeficiency, HIV infection, malignancy, or those taking immunosuppressive drugs such as tumor necrosis factor-alpha blockers and corticosteroids
-
Adults with HIV infection living in areas of low TB prevalence
Complications
- Injection site reaction is the most common complication. Injection site reaction includes granulomatous lesions, lymphadenopathy of regional lymph nodes, and nodules or ulcers at the vaccination site with or without draining sinus tracts or fistulae. Mycobacterium bovis is positive when wound culture is obtained.
- One of the adverse effects of BCG is suppurative lymphadenitis, children with primary immunodeficiencies have been shown to have a higher risk of widespread suppurative lymphadenitis and should be avoided.[27][28] Other complications include:
- Osteitis
- Osteomyelitis
- Disseminated infection may occur in the setting of immunosuppression including HIV infection.
Clinical Significance
BCG vaccination after infancy has a substantial effect on tuberculin skin test (TST) reactivity. BCG trial in the United States showed that individuals who received BCG after infancy had tuberculin skin test reactions ≥10 mm up to 55 years post-immunization.[29]
Prior BCG vaccination should not affect the interpretation of TST results in individuals vaccinated at birth more than ten years earlier given that most individuals who receive the BCG vaccine come from areas where there is a high incidence of TB. Interferon-gamma release assays (IGRAs) should be used to interpret positive TSTs in persons with a history of BCG immunization since this test is not affected by BCG administration. In individuals exposed to serial tuberculin testing, previous BCG vaccination may be increased, leading to a positive skin test in an individual with a prior negative skin test. Greater than 50 percent of patients that received intravesical BCG for bladder cancer have been reported to result in conversion to a positive tuberculin skin test. This exposure to intravesical BCG should not result in a positive IGRA result.[30][31]
The rationale for the development of a booster vaccine is due to decreasing immunity about 15-20 years after the initial immunization at infancy [32]. However, studies done in Brazil and Malawi have shown that a booster dose of the BCG vaccine is not very effective against TB disease [33][34][35]. BCG vaccine may offer protection against infections due to nontuberculous mycobacteria.[36]
Studies have shown that the BCG vaccine decreases the risk of disease due to Mycobacterium leprae by 50 to 80 percent and this effect is increased with booster doses of BCG.[34][37] Prior studies had shown that the vaccine is also 50 percent effective in preventing Buruli ulcer disease due to M. ulcerans, but a more recent retrospective study failed to show evidence that BCG protected against Buruli ulcer disease.[38]
BCG vaccination also protects against childhood lymphadenitis due to M. avium complex [39] has been an increase in childhood adenitis due to non-tuberculous mycobacteria since the cessation of childhood BCG immunization.[40][41]
Tuberculin skin test (TST) reaction of 3 to 19 mm in size is expected in most individuals that received BCG immunization two to three months after vaccination. In a study of 5952 individuals who had BCG vaccination and subsequently underwent tuberculin skin testing 10 to 25 years later, only 8 percent had positive skin test results.[31]
Enhancing Healthcare Team Outcomes
BCG vaccination policy is determined by the regional prevalence of tuberculosis infection. Routine neonatal vaccination is recommended by the WHO in countries with moderate to the severe incidence of tuberculosis. Conversion of tuberculin skin test should not be used to determine the efficacy of the BCG vaccine among recipients.[34][35][42]
Routine BCG vaccination is not generally recommended in the United States due to a low incidence of tuberculosis infection and also due to interference of immunization with the PPD test. BCG vaccination is not recommended for health care workers in low-risk areas. Vaccination is also contraindicated in immunosuppressed patients.
BCG vaccination may be considered in situations where a high percentage of patients are infected with TB strains that are resistant to isoniazid and rifampin.[42] Vaccination can also be found in cases where the implementation of general infection precautions has failed and when transmission of multi-drug resistant strain of Mycobacterium tuberculosis is likely.[42] Nurses practitioners, physician assistants, and physicians that administer BCG should work together in an interprofessional team to assure the safe and effective administration, follow-up, and education of the patient. [Level 5]
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