Pre and post exp prophylaxis

1. Prevention of Hepatitis B & C
Sqn Ldr Rajneesh Thakur

2. Problem Statement- India
• Overall rate of HBsAg positivity: 2-4.7%
• Pregnant women : 0.9-6.3%
• The common genotypes : A followed by D

3. Modes of transmission

4. High-Risk Populations
• Persons born in countries/regions with a high
(>8%) and intermediate (>2%) prevalence of
HBV infection.
• Household and sexual contacts of persons
with hepatitis B
• Persons who have used injection drugs
• Persons with multiple sexual contacts or a
history of sexually transmitted disease

5. High-Risk Populations
• Men who have sex with men
• Persons with persistent elevated alanine or
aspartate aminotransferase levels
• Persons with HCV or HIV infection
• Hemodialysis patients
• Pregnant women
• Persons who require immunosuppressive or
cytotoxic therapy

6. Risk of transmission (p/c exposure)
• The risk of developing clinical hepatitis :HBsAg
+ and HBeAg + : 22%–31%
• Developing serologic evidence of HBV
infection - 37%–62%.
• If with HBsAg + , HBeAg-: 1%–6%,
• Serologic evidence of HBV infection: 23%–37%
WHO 2015

7. • HBV has been demonstrated to survive in dried
blood at room temperature for at least 1 week.
• HBV infections with no history of
nonoccupational exposure or occupational
percutaneous injury might have resulted from
direct or indirect blood or body fluid exposures
that inoculated HBV into cutaneous scratches,
abrasions, burns, other lesions, or on mucosal
surfaces

8. • HCV is not transmitted efficiently through
occupational exposures to blood
• The average incidence of anti-HCV
seroconversion : 1.8% (range: 0%–7%)
• Transmission rarely occurs from mucous
membrane exposures to blood
• No transmission in HCP has been
documented from intact or nonintact skin
exposures to blood
MMWR 2013,62(RR10);1-19

9. • Average risk of HIV transmission after a
percutaneous exposure : 0.3% (95%
confidence interval [CI] = 0.2%–0.5%) and
• After a mucous membrane exposure,
approximately 0.09% (95% CI = 0.006%–0.5%)

10. Immunization
• Active immunization
• Passive immunization

11. HBIG
• Hyperimmune serum globulin with high anti HBs titre
• Standard dose 0.06 mL/kg
• Temporary protection : 3–6 months
• Deep IM deltoid or gluteal muscle
• Indications:
– for sexual contacts of persons with acute HBV infection
– babies born to mothers infected with hepatitis B
– victims of parenteral exposure (e.g. needle stick) to HBsAg
positive blood
– To prevent HBV reinfection in patients who undergo liver
transplantation for HBV related liver disease.

12. • Each plasma donation used for the HBIG is
tested by FDA licensed Nucleic Acid testing
(NAT) for HIV-1/2, HCV and HBV
• Plasma also tested by NAT for hepatitis A virus
(HAV) and parvovirus B19 (B19)
• IgG seperated by anion exchange
chromatography and purified by nanofilters
and Solvent and detergent method

13. Adverse events
• Rare.
• Local pain and tenderness at the injection site,
urticaria and angioedema might occur;
anaphylactic reactions, although rare,
• Persons with a history of anaphylactic reaction
to IG should not receive HBIG.

14. HBV Vaccine
• Two types- Plasma Derived & Recombinant
• Recombivax & Engerix-B (yeast derived)
• Combination Vaccine
– Hep A (Twinrix)
– Diptheria
– Hib

15. • HBV vaccine consists of the highly immunogenic surface antigen
(HepBsAg) protein.
• When administered, it interacts with antigen presenting cells
present in the blood (HepBsAg specific B cells) where it is lysed and
processed.
• This epitope coupled with an major histocompatibility complex
(MHC)-II molecule on the cell surface is then presented to TH-2
cells.
• The TH-2 cells, when activated, stimulate the differentiation of B-
cells to plasma cells.
• These cells then release hepatitis B surface antibodies (HepBsAb) in
large quantities as well as induce development of memory B and T
cells. These memory cells then play an important role in long-term
protection[15]

16. HBV Vaccine
• Efficacy (Anti HBs antibody titre > 10 mIU/mL)
– In adolescents and healthy adults aged <40 years,
– 30%–55% after the first vaccine dose,
– 75% after the second, and
– >90% after the third.
– Vaccine-induced immune memory has been
demonstrated to persist for at least 20 years**
• Post vaccination testing
– Routine post-vaccination testing for anti-HBs is not
recommended by WHO/CDC #
– High risk population only
– 1 to 2 mo after 3 doses
Sherlocks 12 Ed
# WHO 2015

17. HBV Vaccine
Sherlocks 12 Ed

18. Primary series
• Three different 3-dose schedules for
adolescents and adults
• These vaccines can be administered at
0, 1, and 6 months;
0, 1, and 4 months; and
0, 2, and 4 months.
CDC 2015

19. 2016 ACIP Adult Immunization Schedule- Medical/Occupational and Behavior-Based
Recommendations (USA)
Pregn
ancy
Immunoco
mpromisin
g
conditions
excluding
HIV
HIV &
CD4
Count
<200
cell/
µl
>200
cell/
µl
Men
having
sex
with
men
(MSM)
Heart
disease,
chronic
lung
diseases,
chronic
alcoholic
Aspleni
a
includi
ng
elective
Splenec
tomy
Chro
nic
liver
dise
ases
Diabete
Kidney
failure,
ESRD,
on
hemodi
lysis
Health
-Care
perso
nnel
Acknowledgment of a specific risk factor by those who seek protection is not needed.

20. Adverse events
• Pain at the injection site and mild to moderate
fever
• Vaccine Adverse Event Reporting System (VAERS)
of alopecia in children and adults after
administration of plasma-derived and
recombinant hepatitis B vaccine
• No association between hepatitis B vaccine and
the occurrence of serious adverse events,
including Guillain-Barré syndrome, transverse
myelitis, multiple sclerosis, optic neuritis, and
seizures (
CDC, unpublished data, 1991)

21. • a regimen combining HBIG and initiation of
the hepatitis B vaccine series at birth is 85%–
95% effective in preventing HBV infection
Regimens involving either multiple doses of
HBIG alone or the hepatitis B vaccine series
alone are 70%–75% effective in preventing
HBV infection (46 )

22. HBV Vaccine
Sherlocks 12 Ed

23. Non responders
• A nonresponder is defined as a person with anti-
HBs <10 mIU/mL after ≥6 doses of HepB vaccine.
• 10% of healthy adults do not mount an anti-HBs
response (≥10 mIU/mL) to the primary
immunization schedule
• Individuals who do not develop protective HBs
antibody levels 1–2 months after revaccination :
repeat vaccination (0, 1 and 2 months with a 6-
month booster) with double the standard dosage
of vaccine ( protective antibody levels in 44–80%
of individuals)
CDC 2011

24. INTRADERMAL ADMINISTRATION OF THE VACCINE
• Efficacy of high-dose intra-dermal hepatitis B
virus vaccine in previous vaccination non-
responders with chronic liver disease. Dhillon S, Moore
C, Li SD, Aziz A, Kakar A, Dosanjh A, Beesla A, Murphy L, Van Thiel DH Dig Dis Sci.
2012 Jan; 57(1):215-20
• Intradermal versus intramuscular hepatitis B
vaccination in hemodialysis patients: a
prospective open-label randomized controlled
trial in nonresponders to primary vaccination.Barraclough
KA, Wiggins KJ, Hawley CM, van Eps CL, Mudge DW, Johnson DW, Whitby M,
Carpenter S, Playford EG .Am J Kidney Dis. 2009 Jul; 54(1):95-103

25. IMPROVED IMMUNOGENICITY
• Adding pre-S1, pre-S2 particle or
nucleocapsids containing core antigen (HBcAg)
to the S-protein to enhance efficacy of the
vaccine.
• Clinical experience with a new recombinant hepatitis-B vaccine in previous non-
responders with chronic renal insufficiency.Haubitz M, Ehlerding G, Beigel A, Heuer
U, Hemmerling AE, Thoma HA. Clin Nephrol. 1996 Mar; 45(3):180-2.)

26. • Phase 3 clinical trials are underway for
HEPLISAV-B™, a toll like receptor (TLR) agent
in which HepBsAg is combined with
immunostimulatory TLR 9 agonist to enhance
response on a 2 dose regimen over 1 mo
compared to the current 6 mo 3 dose
regimen.
• Cooper C, Mackie D. Hepatitis B surface antigen-1018 ISS adjuvant-containing
vaccine: a review of HEPLISAV™ safety and efficacy. Expert Rev
Vaccines. 2011;10:417–427.

27. • A nasal based vaccine, Nasvac, combination of HBV surface
and core antigen has shown good efficacy in healthy as well
as chronic HepB carriers possibly by stimulating naive
human B cells
• In Phase 1 trials of NASVAC, a mixture of 50 mcg of HBsAg
and HBcAg were administered via nasal spray to healthy
adults (age 18-45) in five doses at 0, 7, 15, 30 and 60 d.
• Anti-HBc seroconversion in 100% of patients as early as day
30 with anti-HBs titers > 10 IU/L in 75% of the patients at
day 90 with no major side effects
• Phase I clinical trial in healthy adults of a nasal vaccine candidate containing
recombinant hepatitis B surface and core antigens. Int J Infect Dis. 2007 Sep;
11(5):394-401

28. • A once daily Oral preparation, V-5 Immunitor™, has
shown efficacy both in development of protective
antibody as well as normalization of liver function tests
in chronically infected individuals. When administered
to ten patients with chronic hepatitis B, it resulted in
normalization of liver enzymes in 100% of the patients
(112.4 to 44.4 U/L for aspartate aminotransferase and
118.8 to 46.1 U/L for alanine aminotransferase) while
half of the patients became HBsAg negative at the end
of one month Batdelger D, Dandii D, Jirathitikal V,
Bourinbaia AS. Open label trial of therapeutic hepatitis
B vaccine V-5 Immunitor (V5) delivered by oral
route. Lett Drug Des Discov. 2007;4:540–544.

29. Causes of non response
HLA DRB1*0301, HLA-B8, SC01, DR-3, HLAB44,
FC-31, DR-7

30. Postexposure Prophylaxis
• Average risk of transmission depends upon HBeAg status of
the patient
• Wash the skin/mucous membrane with soap & water
• No Squeezing
• Test the patient for HBsAg + status
• HBIG
• Vaccine
HBeAg +ve 22.0% - 30.0%
HBeAg -ve 1.0% - 6.0%
HCV 1.8%
HIV 0.03%

31. Postexposure Prophylaxis
• HBIG & Hep B vaccine ideally within 24 hrs;
70% to 90% effective
• HBIG not later than 14 days
• Vaccine- 0,1,6 months
• Antibody testing – 1 to 2 mnths after last dose
• Pregnancy- No contraindication
World Gastroenterology Organisation

32. Postexposure Prophylaxis
Vaccination and/or
antibody response status
of exposed person
HBsAg positive HBsAg negative Source unknown or not
available for testing
Unvaccinated/non-immune HBIG ×1; initiate HBV
vaccine series
Initiate HBV vaccine series Initiate HBV vaccine series
Previously
vaccinated,known
responder
No treatment No treatment No treatment
Previously
vaccinated,known non-
responder
HBIG ×1 and initiate
revaccination,
or HBIG ×2
No treatment No treatment unless
known high-risk source; if
high-risk source,then treat
as if source were HBsAg
positive
Previously
vaccinated,antibody
response unknown
Single vaccine booster dose No treatment No treatment unless
known high-risk source; if
high-risk source,then treat
as if source were HBsAg
positive
If still undergoing
vaccination
HBIG ×1; complete series Complete series Complete series
World Gastroenterology Organisation 2009

33. CDC 2013

34. Non occupational exposure
Source Unvaccinated Vaccinated
HbsAg +
Percutaneous /mucosal HBIG x 1 + Vaccine series Single booster
Sex /needle sharing HBIG x 1 + Vaccine series Single booster
Sexual assault HBIG x 1 + Vaccine series Single booster
Unknown Hbs Ag status
Percutaneous /mucosal Vaccine series No Rx
Sex /needle sharing Vaccine series No Rx
Sexual assault Vaccine series No Rx
December 8, 2006 / 55(RR16);30-31

35. Materno fetal transmission
HBIG- newborn infants whose mothers are HBsAg-positive, particularly if they
are also HBeAg-positive.
In HIV-infected pregnant and breastfeeding women (including pregnant
women in the first trimester of pregnancy and women of childbearing age), a
once-daily fixed-dose combination of tenofovir + lamivudine (or emtricitabine)
+ efavirenz is recommended as first-line ART. This recommendation applies
both to lifelong treatment and to ART initiated for PMTCT and then stopped.
(Strong recommendation, low to moderate quality of evidence)

36. Health care setting

37. Sexual transmission

38. Hepatitis C