BCG Vaccine
Introduction
The Bacillus Calmette-Guérin (BCG) vaccine is a live attenuated vaccine primarily used for protection against tuberculosis (TB). It is one of the most widely used vaccines globally, with over 100 million infants receiving it annually. The vaccine is named after its developers, Albert Calmette and Camille Guérin.
Key points:
- Developed in the early 20th century
- Contains live attenuated Mycobacterium bovis
- Primarily used for TB prevention, especially severe forms in children
- Also has non-specific immune-boosting effects
- Efficacy varies widely depending on geography and strain
History
The BCG vaccine has a rich history spanning over a century:
- 1908: Albert Calmette and Camille Guérin begin work on attenuating Mycobacterium bovis at the Pasteur Institute in Lille, France
- 1921: First human trial of BCG vaccine on an infant whose mother had died of TB
- 1924: BCG vaccine distribution begins in France
- 1948: UNICEF initiates a campaign to vaccinate children with BCG
- 1974: BCG becomes part of the WHO Expanded Programme on Immunization
The vaccine's development marked a significant milestone in the fight against tuberculosis, which was a major cause of mortality in the early 20th century.
Composition
The BCG vaccine is composed of live attenuated Mycobacterium bovis bacteria. Key aspects of its composition include:
- Strain: Multiple strains exist (e.g., Danish 1331, Tokyo 172, Russian BCG-I), each with slight genetic differences
- Attenuation: Achieved through serial passaging, resulting in loss of virulence genes
- Formulation: Typically lyophilized, requiring reconstitution before use
- Preservatives: Generally free of preservatives or adjuvants
- Stabilizers: May contain stabilizers like sodium glutamate
The specific composition can vary slightly between manufacturers and strains, but all contain live bacteria capable of inducing an immune response.
Mechanism of Action
The BCG vaccine works through complex immunological mechanisms:
- Innate Immunity:
- Stimulates pattern recognition receptors (PRRs) like Toll-like receptors
- Enhances natural killer (NK) cell activity
- Induces trained immunity in innate immune cells
- Adaptive Immunity:
- Triggers Th1-type CD4+ T cell responses
- Induces production of IFN-γ, TNF-α, and IL-2
- Generates memory T cells specific to mycobacterial antigens
- Cross-protection:
- Provides some protection against leprosy and Buruli ulcer
- May have non-specific beneficial effects on overall childhood mortality
The vaccine's ability to induce both innate and adaptive immune responses contributes to its protective effects against TB and potentially other diseases.
Indications
The primary indication for BCG vaccination is the prevention of tuberculosis, particularly severe forms in children. However, indications can vary by country and epidemiological context:
- Universal neonatal vaccination: In countries with high TB prevalence
- Selective vaccination: In low-prevalence countries, for high-risk groups such as:
- Healthcare workers
- Travelers to high-prevalence areas
- Close contacts of TB patients
- Other indications:
- Prevention of leprosy in endemic areas
- Immunotherapy for bladder cancer
The decision to vaccinate should be based on local TB epidemiology, healthcare resources, and individual risk factors.
Administration
Proper administration of the BCG vaccine is crucial for its efficacy:
- Route: Intradermal injection
- Site: Usually the left upper arm, over the deltoid muscle
- Dose: 0.05 ml for infants under 12 months, 0.1 ml for older children and adults
- Technique:
- Use a short (10 mm) 26-gauge needle
- Insert needle bevel-up at a 5-15 degree angle
- A correct injection produces a pale, flat-topped swelling (a "bleb")
- Post-administration:
- A small papule forms at the injection site within 2-3 weeks
- May progress to a small ulcer that heals over several weeks
- A small, flat scar usually remains
Proper training in intradermal injection technique is essential for healthcare providers administering the BCG vaccine.
Efficacy
The efficacy of the BCG vaccine varies widely, which has been a subject of extensive research:
- Overall efficacy: Ranges from 0% to 80% in different studies
- Protection against severe TB:
- Highly effective (up to 90%) in preventing miliary TB and TB meningitis in children
- Less effective in preventing pulmonary TB in adults
- Geographical variation:
- Generally more effective in northern latitudes
- Less effective near the equator
- Factors affecting efficacy:
- Genetic differences in populations
- Exposure to environmental mycobacteria
- Nutritional status
- BCG strain used
- Duration of protection: Generally wanes after 10-15 years
Despite variable efficacy, the BCG vaccine remains an important tool in TB prevention, especially for its ability to prevent severe forms of TB in children.
Side Effects
While generally considered safe, the BCG vaccine can cause various side effects:
- Local reactions:
- Erythema and induration at injection site (common)
- Small ulcer formation (expected)
- Keloid scar formation (rare)
- Localized lymphadenitis (uncommon)
- Systemic reactions:
- Fever (rare)
- Fatigue and malaise (uncommon)
- Severe adverse events (very rare):
- Disseminated BCG infection
- Osteitis/osteomyelitis
Severe adverse events are extremely rare in immunocompetent individuals, occurring in less than 1 per million vaccinations. However, they can be more common in immunocompromised patients, highlighting the importance of proper patient screening before vaccination.
Contraindications
BCG vaccination is contraindicated in certain populations due to increased risk of adverse events:
- Absolute contraindications:
- Known immunodeficiency disorders (e.g., SCID, HIV)
- Symptomatic HIV infection
- Pregnancy
- Generalized skin conditions
- Relative contraindications:
- Asymptomatic HIV infection (decision based on CD4 count and local guidelines)
- Infants born to HIV-positive mothers until HIV status is confirmed
- Severe malnutrition
- Ongoing immunosuppressive therapy
- Precautions:
- Delay vaccination in case of acute febrile illness
- Avoid vaccination if the individual has a positive tuberculin skin test
Careful assessment of an individual's health status and risk factors is crucial before administering the BCG vaccine.
Global Use
The use of BCG vaccine varies globally, reflecting differences in TB epidemiology and national health policies:
- High TB burden countries:
- Universal neonatal BCG vaccination is common
- Often part of national immunization programs
- Low TB incidence countries:
- Selective vaccination of high-risk groups
- Some countries (e.g., USA) do not routinely use BCG
- Global coverage:
- Estimated global coverage of 88% in 2019 (WHO data)
- One of the most widely used vaccines worldwide
- Policy changes:
- Some countries have discontinued universal BCG programs due to changing TB epidemiology
- Ongoing debates about the cost-effectiveness of universal vs. targeted vaccination
The global use of BCG vaccine continues to evolve as countries adapt their strategies to local TB epidemiology and emerging evidence.
Future Prospects
Research on BCG and TB vaccines continues, with several promising developments:
- New TB vaccines:
- Subunit vaccines (e.g., M72/AS01E)
- Viral vector vaccines (e.g., MVA85A)
- Whole-cell mycobacterial vaccines (e.g., VPM1002)
- BCG revaccination:
- Studies exploring the potential benefits of BCG revaccination in adolescents and adults
- Alternative routes of administration:
- Research on aerosol and oral BCG delivery
- Non-TB applications:
- Ongoing research into BCG's potential effects on other diseases (e.g., type 1 diabetes, multiple sclerosis)
- Investigation of BCG's role in trained immunity
While BCG remains an important tool in TB prevention, ongoing research aims to develop more effective vaccines and explore new applications for this century-old vaccine.
BCG Vaccine
- What does BCG stand for in the context of vaccines?
Bacille Calmette-Guérin - What disease does the BCG vaccine primarily protect against?
Tuberculosis (TB) - What type of vaccine is BCG?
Live attenuated vaccine - At what age is BCG vaccine typically administered in countries where it is part of the routine immunization schedule?
At birth or soon after birth - What is the recommended route of administration for the BCG vaccine?
Intradermal injection - In which part of the body is the BCG vaccine typically administered?
Upper arm (deltoid region) - What is the typical dose volume of BCG vaccine for infants?
0.05 mL - How many doses of BCG vaccine are typically recommended?
One dose in a lifetime - What is the efficacy of BCG vaccine in preventing pulmonary TB in adults?
Variable, ranging from 0% to 80% - Is BCG vaccine effective in preventing TB meningitis and miliary TB in children?
Yes, it is highly effective (up to 80% protection) - Can BCG vaccine be given to HIV-positive individuals?
Generally not recommended for HIV-positive individuals due to risk of disseminated BCG disease - What is the most common adverse reaction to BCG vaccination?
Local reaction at the injection site (small, red, tender lump) - How long does it typically take for the BCG injection site to heal?
2-3 months - What is BCG lymphadenitis?
Swelling of lymph nodes, usually in the axilla, as a complication of BCG vaccination - Can BCG vaccination cause a positive tuberculin skin test (TST)?
Yes, it can cause a false-positive TST result - Is BCG vaccination recommended in the United States for routine use?
No, it is not part of the routine immunization schedule in the US - What is the contraindication for BCG vaccination?
Known or suspected congenital immunodeficiency - Can pregnant women receive the BCG vaccine?
Generally not recommended, but can be given if benefits outweigh risks - What is the storage temperature requirement for BCG vaccine?
2°C to 8°C (35°F to 46°F) - How long is the reconstituted BCG vaccine stable for use?
Usually 4-6 hours after reconstitution - What is the role of BCG vaccine in bladder cancer treatment?
It can be used as an immunotherapy to treat early-stage bladder cancer - Can BCG vaccine protect against leprosy?
Yes, it provides some protection against leprosy - What is the "BCG scar"?
A small, raised scar that typically forms at the site of BCG injection - Is revaccination with BCG recommended?
Generally not recommended due to lack of evidence for additional protection - What is the WHO's current recommendation regarding BCG vaccination?
A single dose should be given to all infants living in countries with a high TB burden - Can BCG vaccine be given simultaneously with other vaccines?
Yes, it can be administered with other vaccines - What is the minimum age for BCG vaccination?
It can be given immediately after birth - Is there a shortage of BCG vaccine globally?
Yes, there have been global shortages due to manufacturing issues - What is the role of BCG vaccination in TB control programs?
It is used as a preventive measure, especially to protect children from severe forms of TB - Can BCG vaccination cause TB disease?
Very rarely, in severely immunocompromised individuals - What is the recommended needle size for BCG intradermal injection?
26 or 27 gauge, 10 mm long - How long does immunity from BCG vaccination last?
Uncertain, but protection appears to wane after 10-15 years - What is the "BCG wheal"?
A pale, raised area (like a mosquito bite) that appears immediately after correct intradermal injection - Can BCG vaccine be used as a post-exposure prophylaxis for TB?
No, it is not recommended for post-exposure prophylaxis
