hep b vaccine – best schedule & a quiz !

HEP B VACCINE – MOST EFFECTIVE SCHEDULE

(& A QUIZ!)Dr Gaurav Gupta

MAAP, MIAPAuthor of ‘Clippings’ in Indian Pediatrics since 2002

www.charakclinics.com

SAVE – Goa, 20th April, 2013

http://www.charakclinics.com/

Conflict of Interest

Received grants from various vaccine manufacturers including - Sanofi Pasteur- GSK- MSD- Pfizer etc.

Scope

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

Dr. Gaurav Gupta, Charak Care Clinics, Mohali

Leading Causes of Infectious DiseaseDeaths Worldwide

DiseaseLower respiratory tract infectionsDiarrheal diseasesHIV/AIDSTuberculosisHepatitis virusesHepatitis B virusHepatitis C virusMalaria PertussisNeonatal tetanusMeasles

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

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

High (>8%): 45% of global populationlifetime risk of infection >60%early childhood infections common

Intermediate (2%-7%): 43% of global populationlifetime risk of infection 20%-60%infections occur in all age groups

Low (<2%): 12% of global populationlifetime risk of infection <20%most infections occur in adult risk groups

Global Pattern of Chronic HBV Infection

Problem statementINDIA: 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

HBsAg

HBcAg

HBeAg

Hepatitis B Virus

EXPOSURE

Acute hepatitis B infection

AsymptomaticOr

Subclinical infection

Clinical infection-jaundice-flu like symptom

Fulminant hepatitis

Death

ChronicCarrier

RecoveryOr

Immunity

Minimal liver

Disease

Chronic Hepatitis

Primary hepatocellular

carcinomacirrhosis

DEATH

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

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

Ca

rrie

r ri

sk

(%

)Risk of Chronic HBV Carriage by

Age of Infection

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

THE BEST PREVENTIVE METHOD IS

VACCINATION

Hepatitis B

Success of Hepatitis B vaccine

18

Mechanism of Long-Term Protectionwith Hepatitis B Vaccine

Primary vaccination series

Immune memory

Anamnestic antibody response

Rapid rise in anti-HBs

Protection from infection

Exposure to HBV

19

Serologic Response to Booster Dose ofHepatitis B Vaccine

1

10

100

1000

10000

0 6 12 18 24 30 36 42 48 54 60 66 72 78 84

Age (months)

GM

T A

nti-

HB

s (m

IU/m

l)

Primaryseries

Booster dose (simulating natural infection)

Source: Williams and Goldstein, CDC

2 weeks post-booster 4 weeks post-booster

1 yearpost-booster

20

Long-Term Protection withHepatitis B Vaccine

· Vaccine provides long-term protection· Immunity persists despite loss of anti-HBs

- documented protection up to 15 years lifelong protection likelycontinued follow-up needed to determine duration

of protection

Booster doses of hepatitis B vaccine NOT currently recommended

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?

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

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.

Importance of vaccination schedule at 0-1-6 mo/o vs 2-4-6 mo/o.

Group 1Hep.B at 0-1-6


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

Importance of vaccination schedule at 0-1-6 mo/o vs 2-4-6 mo/o.



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

749.12

23.44 79.70

6375.86

84.3941.70

1000

2000

3000

4000

5000

6000

7000

After 1st dose After 2nd dose After 3rd dose

GMT (mIU/ml)

GM

T (

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

GMT in infant vaccinated against Hepatitis B by different vaccination schedules

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

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

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

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

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.

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

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

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

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

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)

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

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

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

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

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

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

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

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

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

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

Above what age would you use Hep B / Twinrix Adult dose

a) 11 years

b) 13 years

c) 16 years

d) 18 years

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

When would NOT vaccinate a person with Hep B vaccine?

a) HIV +ve

b) Pregnancy

c) Lactation

d) None of the above

The ideal Hep B vaccination schedule is ….

The ideal Hep B vaccination schedule is ….

0 – 1 – 6 months !

hep b vaccine – best schedule & a quiz !

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