1. Dr Gaurav Gupta
MAAP, MIAP
Author of „Clippings‟ in Indian Pediatrics since 2002
www.charakclinics.com
SAVE – Goa, 20th April, 2013

2. Conflict of Interest
 Received grants from various vaccine
manufacturers including
 - Sanofi Pasteur
 - GSK
 - MSD
 - Pfizer etc.

3. Scope
 Why do we need vaccination for Hep B?
 What is an ideal vaccination schedule?
 Quiz !

5. Dr. Gaurav Gupta, Charak Care Clinics, Mohali

6. Leading Causes of Infectious Disease
Deaths Worldwide
Disease
Lower respiratory tract infections
Diarrheal diseases
HIV/AIDS
Tuberculosis
Hepatitis viruses
Hepatitis B virus
Hepatitis C virus
Malaria
Pertussis
Neonatal tetanus
Measles
Est. Deaths per Year
~4.2 million
~2.2 million
~2.0 million
~1.5 million
~1 million
~620,000
~366,000*
~900,000
~295,000
~213,000
~197,000
Source: WHO, UNICEF, Perz et al, J Hepatology, 2006

7. Geographic distribution of chronic hepatitis B
virus (HBV) infection — worldwide, 2006*

8.  High (>8%): 45% of global population
 lifetime risk of infection >60%
 early childhood infections common
 Intermediate (2%-7%): 43% of global population
 lifetime risk of infection 20%-60%
 infections occur in all age groups
 Low (<2%): 12% of global population
 lifetime risk of infection <20%
 most infections occur in adult risk groups
Global Pattern of Chronic
HBV Infection

9. Problem statement
INDIA:
 Falls in intermediate endemicity group
 HBsAg prevalence between 2% to 7%.
 Estimated 43-45 million cases per year.
 40 million carriers.
 100,000 death annually by disease related to
HBV infection.
 Of 25 million newborn annually, 1 million
runs lifetime risk of HBV infection

10. HBsAg
HBcAg
HBeAg
Hepatitis B Virus

11. Acute hepatitis B infection
Asymptomatic
Or
Subclinical
infection
Clinical infection
-jaundice
-flu like symptom
Fulminant
hepatitis
Death
Chronic
Carrier
Recovery
Or
Immunity
Minimal
liver
Disease
Chronic
Hepatitis
Primary
hepatocellular
carcinoma
cirrhosis
DEATH

12. Chronic Hepatitis B Virus Infection
 Chronic viremia
 Responsible for most mortality
 Overall risk 10%
 25 % of chronic HBV patients will die
due to liver disease
 Higher risk with early infection

13. 0
10
20
30
40
50
60
70
80
90
100
Birth 1-6 mo 7-12 mo 1-4 yrs 5+ yrs
Age of infection
Carrierrisk(%) Risk of Chronic HBV Carriage by
Age of Infection

14. Global HBV-Related Deaths By Age at
Acquisition of Infection
Perinatal Period (21%)
Early Childhood Period (48%)
• children <5
Late Period (31%)
• children >5
• adolescents
• adults

16. THE BEST PREVENTIVE METHOD IS
VACCINATION
Hepatitis B

17. Success of Hepatitis B vaccine

18. Mechanism of Long-Term Protection
with Hepatitis B Vaccine
18
Primary vaccination series
Immune memory
Anamnestic antibody response
Rapid rise in anti-HBs
Protection from infection
Exposure
to HBV

19. 19
Serologic Response to Booster Dose of
Hepatitis B Vaccine
1
10
100
1000
10000
0 6 12 18 24 30 36 42 48 54 60 66 72 78 84
Age (months)
GMTAnti-HBs(mIU/ml)
Primary
series
Booster dose (simulating
natural infection)
Source: Williams and Goldstein, CDC
2 weeks post-booster
4 weeks post-booster
1 year
post-booster

20. 20
Long-Term Protection with
Hepatitis B Vaccine
Vaccine provides long-term protection
Immunity persists despite loss of anti-HBs
documented protection up to 15 years
 lifelong protection likely
continued follow-up needed to determine duration
of protection
Booster doses of hepatitis B vaccine NOT
currently recommended

21. Questions needed to be asked regarding Ideal
Schedule for Hep B vaccine?
1. Has it been used for extensive period of time?
2. Does it protect the highest “at risk” population?
3. Are there enough evidence regarding its
effectiveness?
4. Are other countries using the same in their National
Schedules?
5. Can it be piggy-backed on our National Schedule?

22. Golden Principles to Follow while choosing the
Schedule for Hep B Immunization
1st Dose – At birth - Prevents vertical transmission
2nd Dose – 4 wk later – Limited seroconversion after 1st
dose, hence closely spaced second dose – prevents
immediate horizontal transmission
3rd Dose -- Min 8 weeks after 2nd Dose,
-- Min 16 weeks after 1st Dose,
-- After 24 weeks age,
(ACIP/ AAP recommendations)
Increased gap between 2nd & 3rd dose increases Ab titres

23. Possible schedules for Hep B
vaccination
Hep B vaccine may be given in any of the following schedules:
(i) Birth, 1 and 6 months
(ii) Birth, 6 and 14 weeks
(iii) 6, 10 and 14 weeks
(iv) Birth, 6 weeks, 6 months
(v) Birth, 6 weeks,10 weeks, 14 weeks
The IDEAL schedule is 0 1 6 months.

24. Importance of vaccination schedule at 0-1-6 mo/o vs 2-4-6 mo/o.
Group 1
Hep.B at 0-1-6
Group 2
Hep.B at 2-4-6
Anti-HBs 10
mIU/mL
47% 9%
Greenberg D et al.- Ped. Inf. Dis. Journal. 21(8):769-776, August 2002
Results: Anti-HBs Post-dose 2

25. Importance of vaccination schedule at 0-1-6 mo/o vs 2-4-6 mo/o.
Group 1
Hep.B at 0-1-6
Group 2
Hep.B at 2-4-6
Anti-HBs 10 mIU/mL
100%
[97.2 ; 100]
99.0%
[94.3 ; 99.4]
GMTs
3 643 mIU/mL
[502;709]
1 052 mIU/mL
[163;253]
Greenberg D et al.- Ped. Inf. Dis. Journal. 21(8):769-776, August 2002
Results: Anti-HBs Post-dose 3

26. 749.12
23.44 79.70
6375.86
84.3941.7
0
1000
2000
3000
4000
5000
6000
7000
After 1st dose After 2nd dose After 3rd dose
GMT (mIU/ml)
GMT(mIU/ml)
GMT (mIU/ml) 0,1,2 schedule
GMT (mIU/ml) 0,1,6 schedule
Ab titres (ShanvacB) with 0-1-2 & 0-1-6
schedules

27. GMT in infant vaccinated against Hepatitis B by
different vaccination schedules

28. Comparison of vaccination schedule in
different countries throughout world
Country Schedule
USA Birth, 1-2, 6-18 m
Canada Birth, 1, 6m
England Birth, 1, 2, 6
Germany 2,4, 11-14 m
South Africa 6,10,14 weeks
Australia 0, 2, 4, 6m
China Birth, 1, 6m
India Birth, 6,10,14 weeks

29. International Schedules
Majority of schedules begin at birth
Most end at 6 months age or more
Gap of at least 8 weeks between 2nd and 3rd doses
If the gap is less, then a 4th dose given
Majority have monovalent Hep B vaccine

30. AAP recommendations
• Administer Monovalent HepB to all newborns before hospital discharge
• The second dose should be administered at age of 1 to 2 months
• The final dose should be administered no earlier than age 24 weeks

31. IAP Recommendations – Consensus
Statement 2012
 IAP now recommends 0 – 6 week – 6 month
schedule for routine Hepatitis-B vaccination in
office practice for children:
 the first dose at birth
 second dose at 6 weeks
 and third dose at 6 months
 Administering Birth dose to all infants before
hospital discharge critical
 Final dose not to be administered before 6m of
age

32. Rationale
 Closer to immunologically ideal and most widely
used 0-1-6 months schedule
 Confirms to latest ACIP recommendations wherein
the final dose of Hep B vaccine is administered no
earlier than age 24 weeks and at least 16 weeks
after the first dose.
 0-1-6 is the schedule widely followed across the
world and for which there is abundant evidence of
effectiveness (Taiwan, Thailand and USA)
 The classic 0, 1, and 6 months schedule yields a
high seroconversion rates and higher titers of anti-
HBs that will persist for an extended period of
time.

33. Quiz – All the best !
Anoushka, a 32 year mother has been
tested to be HbsAg +ve during delivery.
Till what (maximum) time after birth
would you recommend HBIG
administration?
a) Within 12 hours only
b) Within 24 hours
c) Within 48 hours
d) Within 7 days

34. Quiz – All the best !
Anoushka, a 32 year mother has been
tested to be HbsAg +ve during delivery.
Till what (maximum) time after birth
would you recommend HBIG
administration?
a) Within 12 hours only
b) Within 24 hours
c) Within 48 hours
d) Within 7 days

35. Anoushka also wants to know if she can
Breastfeed the baby?
a) No, top feed only
b) BF after completing 3 doses of vaccine
c) BF from birth
d) BF only if received HBIG

36. Anoushka also wants to know if she can
Breastfeed the baby?
a) No, top feed only
b) BF after completing 3 doses of vaccine
c) BF from birth
d) BF only if received HBIG

37. When should this baby (of Anoushka) be
tested for Hep B disease?
a) At birth
b) At 3 months
c) At 6 months
d) At 9 months

38. When should this baby (of Anoushka) be
tested for Hep B disease?
a) At birth
b) At 3 months
c) At 6 months
d) At 9 months

39. How soon after taking Hep B vaccine can
someone donate blood?
a) Immediately, there is no C/I
b) 1 month
c) 3 months
d) 6 months

40. How soon after taking Hep B vaccine can
someone donate blood?
a) Immediately, there is no C/I
b) 1 month
c) 3 months
d) 6 months
(Similarly draw blood for testing before
vaccination with Hep B vaccine)

41. After seeing this excellent presentation you
want to know if you are really protected
against Hep B. What should you do?
a) You have taken 3 doses, you are
obviously protected
b) Do an anti-HBs immediately.
c) Do an HBsAg immediately
d) You need to take 1 dose & then test for
anti-HBs
e) You need to take all 3 doses again & then
test for anti-HBs

42. After seeing this excellent presentation you
want to know if you are really protected
against Hep B. What should you do?
a) You have taken 3 doses, you are
obviously protected
b) Do an anti-HBs immediately.
c) Do an HBsAg immediately
d) You need to take 1 dose & then test for
anti-HBs
e) You need to take all 3 doses again & then
test for anti-HBs

43. Who all should be tested for antibodies
after Hep B vaccination?
a) Everyone
b) Immunodeficient & Hemodialysis cases
c) Health care workers dealing with blood
& blood products
d) Infants of HBsAg +ve mother
e) Family members of HBsAg +ve person

44. Who all should be tested for antibodies
after Hep B vaccination?
a) Everyone
b) Immunodeficient & Hemodialysis cases
c) Health care workers dealing with blood
& blood products
d) Infants of HBsAg +ve mother
e) Family members of HBsAg +ve person

45. What is the protective levels of anti-HBs
for preventing Hep B disease?
a) 0.1 mIU/ml
b) 1 mIU/ml
c) 10 mIU/ml
d) 100 mIU/ml

46. What is the protective levels of anti-HBs
for preventing Hep B disease?
a) 0.1 mIU/ml
b) 1 mIU/ml
c) 10 mIU/ml
d) 100 mIU/ml

47. You have been tested 2 months after completing
a course of Hep B vaccination, and your titres
are below 10, what should be done?
a) Nothing can be done, you will remain
susceptible
b) Do an HBsAg t/r/o HBV infection
c) Repeat another course, and if your titres
remain low, then you will be susceptible
d) If the second course fails, try ID Hep B
Vaccine
e) If the second course fails, try a course of
double dose Twinrix

48. You have been tested 2 months after completing
a course of Hep B vaccination, and your titres
are below 10, what should be done?
a) Nothing can be done, you will remain
susceptible
b) Do an HBsAg t/r/o HBV infection
c) Repeat another course, and if your titres
remain low, then you will be susceptible
d) If the second course fails, try ID Hep B
Vaccine
e) If the second course fails, try a course of
double dose Twinrix

49. You (the doctor) have been tested after 2
months and your titres are above 10, when
should you be tested again? Do you need
a booster as a HCW?
a) No need for tests & no booster – you are
protected for life
b) Tested every year, booster if level below
10
c) Tested every 5 years, booster as above
d) Tested every 10 years, booster as above

50. You (the doctor) have been tested after 2
months and your titres are above 10, when
should you be tested again? Do you need
a booster as a HCW?
a) No need for tests & no booster – you are
protected for life
b) Tested every year, booster if level below
10
c) Tested every 5 years, booster as above
d) Tested every 10 years, booster as above

51. In which patients would you consider
repeated testing of anti-HBs Ab?
a) In doctors
b) In patients with chronic liver disease
c) In patients of CRF
d) In HIV +ve & immunocompromised
children

52. In which patients would you consider
repeated testing of anti-HBs Ab?
a) In doctors
b) In patients with chronic liver disease
c) In patients of CRF
d) In HIV +ve & immunocompromised
children

53. Your staff has accidentally put the Hep B
vaccine in the freezer compartment & it
is now frozen. What should you do?
a) It has to be discarded
b) Thaw it gently and reuse once it is
completely liquid again
c) Use it as a combination vaccine with
DPT + Hib

54. Your staff has accidentally put the Hep B
vaccine in the freezer compartment & it
is now frozen. What should you do?
a) It has to be discarded
b) Thaw it gently and reuse once it is
completely liquid again
c) Use it as a combination vaccine with
DPT + Hib

55. B/o Arti has received the first dose of Hep B
vaccine with a different doctor. You do not
stock the same brand of Hep B vaccine.
What should you do?
a) Ask her to go back to the same doctor
b) Buy the same brand and give to the child
by calling it again after a few days
c) Use whatever brand is available with you

56. B/o Arti has received the first dose of Hep B
vaccine with a different doctor. You do not
stock the same brand of Hep B vaccine.
What should you do?
a) Ask her to go back to the same doctor
b) Buy the same brand and give to the child
by calling it again after a few days
c) Use whatever brand is available with you

57. While doing a procedure on a patient of unknown
HBsAg status, your resident Dr Nitin gets a
needlestick injury. What should be done?
a) If he is documented fully immunized – nothing
b) Documented fully immunized – 1 dose of Hep
B vaccine
c) Unvaccinated / partially vaccinated –Hep B
vaccine as per schedule immediately
d) Unvaccinated/ partially vaccinated – Hep B
vaccine + HBIG immediately

58. While doing a procedure on a patient of unknown
HBsAg status, your resident Dr Nitin gets a
needlestick injury. What should be done?
a) If he is documented fully immunized – nothing
b) Documented fully immunized – 1 dose of Hep
B vaccine
c) Unvaccinated / partially vaccinated –Hep B
vaccine as per schedule immediately
d) Unvaccinated/ partially vaccinated – Hep B
vaccine + HBIG immediately

59. While doing a procedure on an HBsAg +ve
patient, your resident Dr Nitin gets a
needlestick injury. What should be done?
a) If he is documented fully immunized with
post vaccination testing – nothing
b) If he is documented fully immunized but
without post vaccination testing – Single
dose of vaccine
c) Unvaccinated / partially vaccinated –
HBIG & Hep B vaccine

60. While doing a procedure on an HBsAg +ve
patient, your resident Dr Nitin gets a
needlestick injury. What should be done?
a) If he is documented fully immunized with
post vaccination testing – nothing
b) If he is documented fully immunized but
without post vaccination testing – Single
dose of vaccine
c) Unvaccinated / partially vaccinated –
HBIG & Hep B vaccine

61. Above what age would you use Hep B /
Twinrix Adult dose
a) 11 years
b) 13 years
c) 16 years
d) 18 years

62. Above what age would you use Hep B /
Twinrix Adult dose
a) 11 years
b) 13 years
c) 16 years
d) 18 years

63. Bhuvan is going abroad for higher studies in
1 month. He wants the Hep B vaccine.
What schedule can we follow?
a) There is only 1 recommended schedule
for adults 0,1 & 6 months
b) Accelerated schedule 0, 7, 21 days and
then booster after 1 year
c) Accelerated Schedule 0, 1, 2 month and
booster after 1 year

64. Bhuvan is going abroad for higher studies in
1 month. He wants the Hep B vaccine.
What schedule can we follow?
a) There is only 1 recommended schedule
for adults 0,1 & 6 months
b) Accelerated schedule 0, 7, 21 days and
then booster after 1 year
c) Accelerated Schedule 0, 1, 2 month and
booster after 1 year

65. When would NOT vaccinate a person with
Hep B vaccine?
a) HIV +ve
b) Pregnancy
c) Lactation
d) None of the above

66. When would NOT vaccinate a person with
Hep B vaccine?
a) HIV +ve
b) Pregnancy
c) Lactation
d) None of the above

67. The ideal Hep B vaccination schedule is
….

68. The ideal Hep B vaccination schedule is
….
0 – 1 – 6 months !