BCG or Bacillus Calmette Guerin is a vaccine used for prevention of Tuberculosis(TB) in humans since 1921.Approximately 100 million children were administered (vaccinated) with BCG in almost 170 countries in the world.The BCG vaccine is prepared from a strain of attenuated,live tuberculosis bacilli—Mycobacterium Bovis. That has lost it’s virulence in humans by being specially cultered in an artificial medium for years.The bacilli have retained enough strong antigenecity to become an effective Vaccine for the prevention of tuberculosis in human beings.
BCG Vaccine is one of the most widely used vaccines in the world. Its efficacy against TB meningitis in the pediatric age-group is established; but its efficacy against pulmonary TB is appears to be variable. Many countries use BCG for prevention of TB. But a few countries like U.S, they do not use BCG for routine vaccination. This is probably because they believe in detecting the active disease by a reliable Mantoux test, instead of practicing the routine vaccination against a relatively rare condition i.e, the incidence of TB is very low.
History:-
Bovine TB was first recognized in 1854. Robert Koch first distinguished Mycobacterium Bovis from Mycobacterium tuberculosis.
Albert Calmette, a French Bacteriologist & his colleague Calmette Guerin a veterinarian were working at pasteur institute in Lille in 1908. They started sub-culturing the virulent strains of tubercle bacillus and noted that sub-culturing the strain in glycerin-bile-potato made it less virulent. Their hypothesis that repeated sub-culturing of a virulent strain of Myco bovis would result in an alternated strain & hence could be used as a vaccine against TB was proved right BCG vaccine was first used in humans 1921.
The bacilli have retained enough, strong antigericity to become a somewhat effective vaccine for prevention of TB in human beings.
Efficacy:-
The most controversial aspect of BCG is its variable efficacy when used in various clinical trials. This appears to depend on the geography. The efficacy of 14% to 84% upto 5 years after immunization. However a clinical trials conducted in South India showed no protective effect.
But BCG vaccine seems to be very effective in preventing miliary TB & TB meningitis. Hence it is still extensively used in countries where efficacy against pulmonacy TB is negligible.
The possible reasons for variable efficacy are many:
- Genetic variation of the population
- Genetic variation in BCG strains used
- Background exposure to the disease-TB.
- Non-specific immune responses against Mycobacteria by non-tuberculous mycobacteria
- Immune response with simultaneous infection with parasites, which may blunt the effect of BCG
Adverse effects:-
BCG is one of the widely used vaccines with on unparalleled safety record.
It is recommended that BCG vaccine be given by intra-dermal injection by staff skilled in the technique. BCG immunization causes pain & leaves a scar at the site of injection. The main adverse effects are keloids or large, ugly scars. The insection of deltoid is used for BCG vaccination, because of the least complication when that site is used.
Adverse events to BCG vaccine are mostly localized, and long term complication are rare. If the vaccine is given subcutaneously, it causes a local skin reaction, spreading to the regional lymph adenitis and may cause suppurative lymphadenitits.
95% of subjects vaccinated with BCG develop a local reaction like erythema, induration, muscle soreness, ulceration etc., which is followed by healing & scar formation within 3 months.
Other complication include osteitis (0.01 per million in Japan) & disseminated BCG diseases (0.19 to 1.56 cases per million.
The BCG vaccinated people may not give the potency ratios of the same order as that of naturally infected individuals because of the fact that BCG vaccination leads to a relatively low degree of sensitisation and it may be of a different specificity.
The basic standards of BCG Vaccine:-
- The level of alternation must be such that it avoids severe local lesions or generalized symptoms or progressive tuberculosis.
- The viability of the vaccine must remain high until it is used.
- The vaccine must have the ability to convert the tuberculin reaction within a reasonable time after vaccination.
- The vaccine must have sufficient immunizing potency.
- The cultural & morphologic appearance must be characteristic.
- The vaccine must be free from all other organisms.
BCG Policy:-
WHO Policy:- WHO recommends that BCG be given to all children born in countries highly endemic for Tuberculois because it offers protection against TB meningitis and miliary TB.
INDIA introduced BCG mass immunization in the year 1948, the first Non-European country to do so.
BCG ONCO BP FOR Immunotherapy
Description: BCG ONCO BP (Intravesical) is a live freeze-dried preparation made from Bacillus Calmette-Guerin strain, which is an attenuated strain of Mycobacterium bovis. The BCG is propagated as a live attenuated strain obtained as a primary seed (Strain – Danish 1331). Bacillus Calmette-Guerin (BCG) immunotherapy has been widely accepted as the optimal treatment for carcinoma in situ and high grade superficial transitional Urinary Bladder Carcinoma. It is not intended as an immunizing agent for the prevention of tuberculosis. BCG ONCO is not a vaccine for the prevention of cancer.
Composition: Each vial contains 40 mg of BCG, having 1 – 8 x 108 CFU. 5% Sodium glutamate is used as the stabilizer. Reconstitute each vial with 50 mL of Sodium Chloride (0.9% w/v) injection.
Indications: Carcinoma in situ of urinary bladder prophylaxis and treatment, BCG is used intravesically for prophylaxis and treatment of primary multifocal, high grade and relapsed superficial transitional bladder carcinoma. It is used to reduce the frequency of tumor recurrence after transurethral resection and to eliminate existing tumors, including Ta and T1 tumors and carcinoma in situ (CIS tumors) with or without associated papillary tumors. It is not indicated for the treatment of papillary tumors occurring alone or for prevention of papillary tumors after transurethral resection.
Dosage Form: Freeze-Dried Lyophilized preparation.
Dosage & Administration:Per instillation, the contents of 2 or 3 vials (80 mg-120 mg) are required. Reconstitute each vial with 50 mL sodium chloride injection for instillation into the urinary bladder. Intravesical treatment with BCG ONCO should begin between 7 to 14 days after biopsy or Trans Urethral Resection (TUR).
Draw 1 mL of sterile diluent (preservative free 0.9% w/v Sodium chloride injection) into a syringe and add to one vial of BCG ONCO to resuspend. Leave them in contact for about 1 min. Then mix the suspension by withdrawing it into the syringe and expelling it gently back into the vial 2 or 3 times. Dilute the reconstituted product in an additional 49 mL of diluent, bringing the total volume to 50 mL.
Precautions should be taken particulary in common preparation areas, to avoid cross contamination of parenteral products with BCG ONCO. BCG ONCO should not be handled by persons with an immunological deficiency. Exposure to artificial light should be kept to a minimum period of time. The resuspended BCG ONCO should be used immediately after preparation. Discard unused portion after two hours.
Contraindications: Active tuberculosis, Immunodeficiency/immunosuppressive therapy, trauma to the urinary bladder, a patient with fever needs careful evaluation before therapy is instituted, safety of this mode of therapy in pregnant women, nursing mothers and children has not be evaluated.
Storage: BCG ONCO should be stored in dark between 2 – 8 °C. Do not expose to light. Use immediately after reconstitution.
BCG ONCO has a shelf life of 24 months, provided it is stored in dark between 2 – 8 °C and protected from light.
WARNING: THIS PREPARATION SHOULD NOT BE USED AS A VACCINE AGAINST TUBERCULOSIS
