LIMITATIONS OF BCG :
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Waning of protective immunity with time. Published data suggests that duration of protection is not more than 10 years.
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Data from different studies indicates that BCG efficacy ranges from 0-80%.
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Effectiveness is reduced in disseminated tuberculous disease.
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Problem of a live vaccine in immunocompromised host.
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Not protective against reactivation of tuberculosis or HIV associated Koch’s.
There is therefore an urgent need for the development of more effective, better-standardized, affordable vaccine with durable activity and fewer side effects.
NEWER VACCINES BEING DEVELOED :
Many of these vaccines have been tested for immunogenicity and protective efficacy in experimental animals. In addition alternate routes of tuberculosis vaccine delivery (e.g. oral, respiratory, gene gun) and various combinations of priming or boosting an experimental vaccine with BCG have been examined in relevant animal models.
BCG in SPECIAL SITUATIONS
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BCG & LBW Infant : BCG vaccine and OPV administered in early neonatal life showed successful BCG reaction in 95.5% Infants.
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One recent study from India suggested that BCG vaccination has an immunomodulatory role in case of IDDM & NIDDM.
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BCG & Other Vaccines : Administration of BCG at the time of priming markedly increased the cellular & antibody responses to Hepatitis B & oral polio vaccine.
References :
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McMurray DN. Recent progress in the development and testing of vaccines against human tuberculosis. Int J Parasitol. 2003;33(5-6):547-54
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Britton WJ, Palendira U. Improving vaccines against tuberculosis. Immunol Cell Biol. 2003 ;81(1):34-45.
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von Reyn CF, Vuola JM. New vaccines for the prevention of tuberculosis. Clin Infect Dis. 2002;35(4):465-74.
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Dhar N, Rao V, Tyagi AK. Recombinant BCG approach for development of vaccines: cloning and expression of immunodominant antigens of M. tuberculosis. FEMS Microbiol Lett. 2000;90(2):309-16.
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Kaur S, Faridi MM, Agarwal KN. BCG vaccination reaction in low birth weight infants. Indian J Med Res 2002;116:64-9.
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Sanjeevi CB,Das AK, Shtauvere-Brameus A. BCG vaccination and GAD65 and IA-2 autoantibodies in autoimmune diabetes in southern India. Ann N Y Acad Sci 2002 Apr;958:293-6.
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Horwitz MA, Harth G. New vaccine against tuberculosis affords greater survival after challenge than the current vaccine in the guinea pig model of pulmonary tuberculosis. Infect Immun 2003;71(4):1672-9.
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Wang J, Zganiacz A, Xing Z. Enhanced immunogenicity of BCG vaccine by using a viral-based GM-CSF transgene adjuvant formulation. Vaccine 2002;20(23-24):2887-98.
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Ota MO, Vekemans J, Schlegel-Haueter SE et al. Influence of Mycobacterium bovis bacillus Calmette-Guerin on antibody and cytokine responses to human neonatal vaccination. J Immunol 2002;168(2):919-25.
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Hess J; Kaufmann SH.Development of live recombinant vaccine candidates against tuberculosis. Scand J Infect Dis 2001;33(10):723-4
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Core information for the development of Immunization Policy. WHO- Vaccines and Biologicals. 2002 Update
Last Updated on 05-11-2004 Courtesy Pediatric Oncall
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BCG VACCINE
Dr. Nitin Shah
Hon. Pediatrician- UHC, LTMG Hospital, Mumbai.
Treasurer, Indian Academy of Pediatrics, 1998-2001. |
1. What is a BCG vaccine?
1. BCG vaccine is a live bacterial vaccine given for protection against tuberculosis, mainly severe forms of childhood tuberculosis. It stands for Bacillus Calmette Gurrain, the strain of bovine tuberculosis used in the vaccine & attenuated by French scientists Calmette & Gurrain.
2. How is BCG vaccine available?
2. BCG vaccine is available as a lyophilized powder in an ampoule. Diluent used is buffered saline that is available separately. It is available in a multidose ampoule containing 20 doses.
3. How is BCG vaccine stored?
3. BCG vaccine stocks can be stored frozen in freezer compartment. Working stock can be stored in the chiller compartment. Even diluents should be stored in the refrigerator’s lower racks at 2-8oC.
4. How is BCG prepared?
4. BCG vaccine ampoules should be cut with a file very slowly & not snapped open because it has vacuum inside or else the glass will splinter and fly if cut very suddenly. It may be safer to hold the ampoule in a cloth to avoid injury should the glass splinter. Once prepared, BCG vaccine should be used within 2-3 hours & discarded thereafter.
5. When is BCG given?
5. BCG is given anytime from birth to 15 days of life along with the zero dose of oral polio vaccine. It is to be given to all children as part of EPI schedule as recommended by Govt. of India.
6. How is BCG vaccine given?
6. BCG vaccine is given intradermally i.e. in the layers of skin using 26 no. needle. It is given conventionally over left deltoid area (to differentiate it from small pox vaccine scar, which was conventionally given over right deltoid area). 0.1 ml of vaccine is given using BCG syringe which is a 1 ml. glass syringe with steel plunger to identify it so that it is not used for any other purpose. A wheal or swelling of 6 mm is raised above the surface. No spirit or antiseptic should be applied over the site before injection. Good bath with soap and water is enough to clean the local injection site. At the most one can use normal saline to clean the area.
7. When is a booster dose of BCG vaccine given?
7. Neither Govt. of India nor Indian Academy of Pediatrics recommends a booster dose of BCG in India. Some countries like in Gulf recommend one or more booster doses.
8. What is the efficacy of BCG vaccine?
8. In a country like ours where tuberculosis is endemic, children catch the germs early in life & develop primary complex. In children younger than 3-5 years of age, this can spread & lead to severe & serious forms of childhood tuberculosis like tuberculous meningitis, disseminated tuberculosis, miliary tuberculosis, tuberculosis of organs like bones, urinary tract etc. BCG being live vaccine itself induces a benign primary complex, which leads to some immunity. Such a child when comes in contact with a patient with tuberculosis can still catch the wild germ and develop primary complex, but the spread will be mostly prevented by previous BCG immunity. Hence such children will not develop serious forms of childhood tuberculosis. Such children when they grow as adults can catch tuberculosis again & develop adult form of tuberculosis which is a different type of tuberculosis altogether. This adult type of tuberculosis is not prevented by BCG. Hence BCG does not prevent primary complex but prevents spread of the primary complex & hence the severe forms of childhood tuberculosis. This explains the outcome of the famous Chingleput trial on BCG vaccine efficacy, which failed to show the protective efficacy of BCG against adult type of tuberculosis.
Incidentally BCG also cross protects against leprosy & the efficacy is 20%.
9. What is the normal reaction to BCG vaccine?
9. Immediately after the BCG vaccine there is a small swelling at the injection site which persists for 6-8 hours. After that the swelling disappears & the injection site looks normal. After 6-8 weeks a swelling reappears which looks like a mosquito bite. It grows in size & forms a nodule which breaks open & discharges some fluid & forms an ulcer. The ulcer heals by forming a scar. The whole process takes 2-5 weeks. Some times this process of ulceration & healing recurs 2-3 times. Ultimately the typical puckered scar is formed which remains for lifetime.
If ulceration occurs within 7 days of injection, one must report to the doctor, as it may be a sign of tuberculosis in the child.
10. What local care should we take at injection site?
10. Injection site should not be pressed or rubbed. It should not be fomented. Nothing needs to be applied locally. Infact, bath with soap and water should suffice even when it has ulcerated.
11. What if the child develops fever?
11. BCG does not lead to fever. Hence search for another cause & treat accordingly.
12. What are the complications of BCG?
12. In 1-2 % of vaccinees, local lymphadenitis can occur involving axillary lymph nodes or rarely supraclavicular gland, especially if injection is given very high over arm. In children with immune compromised state like AIDS, BCG can lead to progressive systemic disease.
13. Can BCG be given over thigh from beauty point of view so that scar is hidden?
13. As we saw before, 1-2% of children develop local BCG lymphadenitis. If that happens following injection over thigh, it will involve superficial & deep inguinal lymph nodes, which can prove dangerous. Also, by convention BCG scars are looked for over the left arm & hence it is easier to recognize for the doctor when parents do not remember whether BCG was given in the past or not. Hence BCG should only be given over left arm & nowhere else.
14. What should be done for BCG lymphadenitis?
14. Local lymphadenitis can occur due to superadded infection over BCG ulcer. One should try oral antibiotics & anti-inflammatory with good local hygiene (Soap & water). If the lymph node does not shrink or disappear, it is true BCG lymphdenitis. In these cases if the size of node is less than 10mm – 15mm, if it is firm, non-painful & not matted; no treatment is required & only observation is required. It will usually disappear on its own in the next few months time. If the glands are bigger than 15mm, soft, fluctuating with signs of inflammation or softening, painful and matted or if already an abscess has formed with or without discharge, treatment is definitely required. One can either remove the entire gland surgically or try a course of anti-tuberculous drugs in form of Isoniazid 5 mg/kg/day & Rifampicin 10mg/kg/day on empty stomach for a period of 3-6 months.
15. What if BCG is not given at birth?
15. BCG should be given as early as possible in life, before child comes in contact with tuberculosis. It can be given up to 5 years of age. If it is given beyond 6 months it is preferable to do a prior Mantoux test to see if the patient is already sensitized to tuberculosis. If patient is already sensitized as shown by positive MT, BCG is not necessary. If prior MT is not done, at least check for accelerated reaction to BCG in first week after vaccination which may suggest presence of tuberculosis in the child.
16. Why is BCG not recommended in USA?
16. In developed countries like USA, very few cases of tuberculosis occur. As BCG does not prevent primary complex or the adult type of tuberculosis no benefit will be derived by routine BCG vaccination in such countries. In fact BCG can interfere with interpretation of Mantoux test done subsequently. Hence BCG is not recommended in USA routinely. With the spread of HIV, incidence of tuberculosis is rising in USA. Under such circumstances they may have to reconsider about routine BCG vaccination.
17. What if scar is not seen after BCG vaccination?
17. Formation of scar is neither necessary nor is the only indication of success of BCG vaccine. However it is the only simple & convenient way of determining success of BCG vaccine. It may take 3-6 months for the scar to form. If no scar is visible at all after 6 months one needs to do Mantoux test. If negative, one should give repeat BCG
18. Can BCG be given with other vaccines?
18. BCG can be given with other vaccines. In fact, BCG is given along with zero dose of OPV & 1st Dose of Hepatitis B vaccine at birth. As measles can depress cell mediated immunity & as BCG induces cell mediated immunity BCG should not be given along with measles or MMR
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