HEPATITIS A VIRUS
RNA Picornavirus
Single serotype worldwide
Acute disease and asymptomatic infection
No chronic infection
Protective antibodies develop in response to infection - confers lifelong immunity

"HEPATITIS A - CLINICAL FEATURES"
HEPATITIS A - CLINICAL FEATURES

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GEOGRAPHIC DISTRIBUTION OF
HEPATITIS A VIRUS INFECTION

ACUTE HEPATITIS A CASE
DEFINITION FOR SURVEILLANCE
Clinical criteria

An acute illness with:
discrete onset of symptoms (e.g. fatigue, abdominal pain, loss of  appetite, intermittent nausea, vomiting), and
jaundice or elevated serum aminotransferase levels
Laboratory criteria
IgM antibody to hepatitis A virus (anti-HAV) positive
Case Classification
Confirmed. A case that meets the clinical case definition and is laboratory confirmed or a case that meets the clinical case definition and occurs in a person who has an epidemiologic link with a person who has laboratory-confirmed hepatitis A (i.e., household or sexual contact with an infected person during the 15-50 days before the onset of symptoms).

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"Close personal contact
(e.g..."
Close personal contact
(e.g., household contact, sex contact, child day-care centers)
Contaminated food, water
(e.g., infected food handlers)
Blood exposure (rare)
(e.g., injection drug use, rarely by transfusion)

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  PREVENTING HEPATITIS A
Hygiene  (e.g., hand washing)
Sanitation  (e.g., clean water sources)
Hepatitis A vaccine (pre-exposure)
Immune globulin (pre- and post-exposure)


    HEPATITIS A VACCINES



HEPATITIS A VACCINES

SAFETY OF HEPATITIS A VACCINE
Most common side effects
Soreness/tenderness at injection site - 50%
Headache - 15%
Malaise - 7%
No severe adverse reactions attributed to vaccine
Safety in pregnancy not determined – risk likely low
Contraindications - severe adverse reaction to previous dose or allergy to a vaccine component
No special precautions for
immunocompromised persons

DURATION OF PROTECTION AFTER
HEPATITIS A VACCINATION
Persistence of antibody
At least 5-8 years among adults and children
Efficacy
No cases in vaccinated children at 5-6 years of follow-up
Mathematical models of antibody decline suggest protective antibody levels persist for at least 20 years
Other mechanisms, such as cellular memory, may contribute

COMBINED HEPATITIS A 
HEPATITIS B VACCINE
Approved by the FDA in United States for persons >18 years old
Contains 720 EL.U. hepatitis A antigen and
20 μg. HBsAg
Vaccination schedule: 0,1,6 months
Immunogenicity similar to single-antigen vaccines given separately
Can be used in persons > 18 years old who need vaccination against both hepatitis A and B
Formulation for children available in many other countries

"Pre-exposure"
Pre-exposure
travelers to intermediate and high
HAV-endemic regions
Post-exposure (within 14 days)
Routine
household and other intimate contacts
Selected situations
institutions (e.g., day-care centers)
common source exposure (e.g.,
food prepared by infected food handler)

INCREMENTAL IMPLEMENTATION OF ROUTINE HEPATITIS A VACCINATION OF CHILDREN
1996 - Children living in communities with the highest rates
1999- Children living in states/communities with consistently elevated rates during “baseline period”
All children nationwide

Reported Hepatitis A Cases, By Year
  Northern Plains Indian Reservation
  South Dakota, 1968-2002

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ACIP RECOMMENDATIONS
PERSONS AT INCREASED
RISK OF INFECTION, 1996
Men who have sex with men
Illegal drug users
International travelers
Persons who have clotting factor disorders
Persons with chronic liver disease

STD Treatment Guidelines
MMWR May 10, 2002 51(RR06)

HEPATITIS A IN THE UNITED STATES -2002
National rate lowest yet recorded
Continued monitoring needed to determine if low rates sustained and due to vaccination
Evaluation of age-specific rates to assess impact of vaccination strategy
Rates increasing in some states
Occurring among adults in high risk groups (e.g. MSM, drug users)

HEPATITIS A VACCINATION
IN THE UNITED STATES
CHALLENGES FOR THE FUTURE
Continue implementation of the current recommendations for vaccination of children
Sustain vaccination in face of falling rates
Further reduce incidence
Vaccination of high-risk adults
Vaccination of children nationwide

Hepatitis B :
A Clinical Perspective

Hepatitis B Overview
Serious: Causes death from liver disease in up to 25% of those infected at birth.
Cancer related: Liver cancer especially prevalent in areas of world where hepatitis B
is common.
Disease of refugees: New arrival Southeast Asian refugees (1 out of 2 is immune, 1 out of 7 is a carrier, 1 out of 3 is susceptible).
Preventable: Safe, effective, and affordable vaccination is available.

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Hepatitis B Incidence
in U.S., 2001
Estimated incidence
 78,000 cases/year
Reported cases
Acute hepatitis B: 7,844

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Transmission of HBV (1)
Concentration of HBV in various body fluids
High: Blood, serum, wound exudates
Medium: saliva, semen, and vaginal secretions
Low/not detectable: urine, feces, sweat, tears, breastmilk
Perinatal – transplacental transmission, rare (2-5%)
Sexual transmission – unprotected sex

Transmission of HBV (2)
Percutaneous transmission – sharing of injection drug use equipment, needle stick injury,
ear-piercing, body piercing, tattooing, inadequate sterilization of medical equipment, scarification
Household and interhousehold transmission – less risk but significant - can occur in settings such as shared toothbrushes, razors, combs, washcloths

Transmission of HBV (3)
Passed from child to child by biting, shared objects, oozing cuts, impetigo, etc.
Virus can exist on environmental surfaces for up to one week and remain infectious.
Pre-chewing food for babies, or sharing food that has been chewed by someone else (chewing gum).

Transmission of HBV (4)
Institutionalized settings – risks of biting,
sexual abuse
More than 1/4 of acute cases have no readily identifiable risk factor
Not spread by sneezing or coughing, sharing eating utensils.

Risk Groups for HBV Infection (1)
Immigrants/refugees from areas of high HBV endemicity (Asia, Pacific Islands, Sub-Saharan Africa, Amazon Basin, E. Europe, Middle East)
Children born in U.S. to immigrants from areas of high HBV endemicity
Alaska Natives and Pacific Islanders
Household contacts and sex partners of people with chronic HBV infection

Risk Groups for HBV Infection (2)
People who have or who have had sexually transmitted diseases
Heterosexuals with >1 sex partner in 6 months
Men who have sex with men
Users of illicit injectable drugs
Health care workers in contact with blood

Risk Groups for HBV Infection (3)
Adopted children from mod/high-risk countries
Hemodialysis patients
Recipients of certain blood products
Clients/staff at institutions for the developmentally disabled
Inmates of long-term correctional facilities

Hepatitis B Nomenclature
and/or Lab Tests (1)
HBV: Hepatitis B virus.
HBsAg: Hepatitis B surface antigen. Marker of infectivity when found in serum.
anti-HBs: Antibody to HBsAg. Marker of immunity when found in serum.
HBcAg: Hepatitis B core antigen. No commercial test available for this.
anti-HBc: Antibody HBcAg. Marker of past or current infection.

Hepatitis B Nomenclature
and/or Lab Tests (2)
IgM anti-HBc: IgM is an antibody subclass of
anti-HBc. Indicates recent infection with HBV
(<4-6 mos.).
IgG anti-HBc: IgG is a subclass of anti-HBc. Indicates “older” infection with HBV.
HBeAg: Hepatitis B “e” antigen. Can only be present if HBsAg is positive. Marker of high degree of infectivity.
Anti-HBe: Antibody to “e” antigen. May be present in infected or immune person.

Hepatitis B Nomenclature
and/or Lab Tests (3)
HBIG: Hepatitis B immune globulin. Passively delivered antibody that provides “instant” protection against HBV.
HCC/PHC: Hepatocellular carcinoma, primary hepatocellular carcinoma.
HDV: Hepatitis D virus (the delta virus). Etiologic agent of delta hepatitis. Can cause infection only in the presence of HBV infection.

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Signs and Symptoms
Symptom
there may be none
loss of appetite, malaise, nausea, vomiting, abdominal pain, arthralgias, myalgias
Signs
there may be none
jaundice, fever, dark urine

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Natural History
Likelihood of becoming a carrier varies inversely with the age at which infection occurs.
Pool of carriers in U.S. is 1-1.25 million persons.
~5000 persons die/yr. from HBV-related cirrhosis.

Risk of Becoming
Chronically Infected with HBV
2% - 6% of older children and adults
20% - 50% of children <5 yrs
85% - 90% of infants infected at birth

Treatment for HBV
Three FDA-licensed treatment options available for adults in the United States
interferon alfa-2b (IntronA), recombinant administered subcutaneously qd or 3x/wk
also licensed for use in children
lamivudine (Epivir-HB) administered by mouth qd
adefovir dipivoxil (Hepsera) administered by mouth qd

Consult a liver specialist to assist
in determining whether your patient is
a treatment candidate.

Monitoring HBsAg+ Patients
Discuss monitoring with a liver specialist having much experience in managing viral liver diseases.
Annual physical exam.
Blood work every 6-12 mos.
Liver biopsy?
Liver ultrasound or CT scan every 6-12 mos.
"fetoprotein (AFP) every 6-12 mos.
Education of patient about disease.

Management of Family Members of HBsAg+ Patients
Test all family members with hepatitis B panel (HBsAg, antiHBc, antiHBs)
For those susceptible, vaccinate
For susceptible sex partner(s), test after 3 doses to be sure s/he converts to antiHBs+
Education of family members

This Khmer woman died
of hepatoma, four months after arriving in a refugee camp in Thailand.

Hepatocellular Carcinoma – HCC (1)
HBV leads to liver cancer
epidemiologic correlation in many populations
risk for HCC is 12-300 times greater in HBsAg+ persons
HBV DNA is incorporated into DNA of hepatoma cells
Incidence
peak incidence is in 40-60 yr olds
in Taiwan, #1 cause of death for men >40 yrs
0.25-1 million deaths/year in the world
over 1500 persons die/yr in the U.S. from HCC
HCC is 3-4x more common in HBsAg+ men than women

Hepatitis B Prevention (1)
Hepatitis B Immune Globulin (HBIG)
provides temporary passive protection
indicated in certain postexposure settings
Hepatitis B Vaccine
vaccinate all children 0-18 years of age
infant schedule: birth dose preferred (0, 1-2, 6), (0, 1-4, 6-18)
Schedule if using monovalent vaccine followed by
Comvax ®: (0, 2, 4, 12)
children/teens: (0, 1, 6), ( 0, 1-2, 4) (0, 1, 6-12) or (0, 12, 24) month schedule. There is also a two-dose schedule for 11-15 year olds using Recombivax HB ® only. This schedule is
0, 4-6 months.

Hepatitis B Prevention (2)
Hepatitis B Vaccine (continued)
Vaccinate all high-risk individuals
Adult schedule (0, 1-2, 6)
Testing can be done if concern that patient has been previously infected, but do not delay administering first dose of vaccine until a later visit; test, then give first dose.
Hepatitis B Prenatal Testing
Test EVERY pregnant woman during every pregnancy for HBsAg, even if she has been immunized against hepatitis B or is chronically infected.
Send a copy of the original lab report to the hospital.

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Prevention Schedule for Infants of HBsAg-POSITIVE Mothers
HBIG 0.5 ml IM within 12 hrs. of birth.
Dose #1 of Hep B vaccine in the opposite thigh within 12 hrs. of birth.
Dose #2 of Hep B vaccine at 1-2 mos.
Dose #3 of Hepatitis B vaccine at 6 mos.
Testing for antiHBs and HBsAg 9-15 mos.
If negative for both, repeat the series and test 1–2 months later!

Schedule for infants of mothers with UNKNOWN HBsAg status
Test mother for HBsAg in hospital ASAP.
If mother’s test is positive, give HBIG ASAP (within 7 days of birth).
Give dose #1 of Hep B vaccine within 12 hrs. of birth. DO NOT DELAY THIS DOSE waiting for the lab result.
Dose #2 of Hep B vaccine at 1-2 mos.
Dose #3, follow dosing schedule based on mother’s HBsAg status.

Schedule for infants with
HBsAg-NEGATIVE mothers
Dose #1 recommended to be given at birth.
Dose #2 can be given at 1-4 mos. of age
Dose #3 at 6-18 mos. of age
Final dose should NOT be given before
age 6 mos.
May also give monovalent hepatitis B #1 at birth followed by 3 does of Comvax ®
at 2, 4, and 12-15 mos., or 3 doses of Pediarix ®  at 2, 4, and 6 mos.

Dosing schedule for older children
and teens (NOT INFANTS)
Rule #1: There must be at least 4 wks. between dose #1 and dose #2.
Rule #2: There must be at least 8 wks. between dose #2 and dose #3.
Rule #3: There must be at least 4 mos. between dose #1 and dose #3.
Rule #4: No matter how delayed dose #2 or #3 is, do not start the series over again.
Suggested spacing options: 0, 1-2, 4-6 mos.;
0, 2, 12 mos.; 0, 12, 24 mos.

Dosing Schedule for Adults
0, 1, 6 month interval is standard for HCWs
Space dose #1 and #2 four wks. apart
Space dose #2 and #3 five mos. apart
Alternative schedules 0, 2, 4;  0, 1, 4
Never re-start the series if dosing was delayed. Continue from where you left off.
Use a 1” or 1.5” needle. If obese, use 2”.
Injection must be intramuscular in deltoid.

Recommended post-exposure prophylaxis
for exposure to HBV

Elimination of Hepatitis B Virus Transmission: United States
Objectives
Prevent chronic HBV Infection
Prevent chronic liver disease
Prevent primary hepatocellular carcinoma
Prevent acute symptomatic HBV infection

Elimination of Hepatitis B Virus Transmission: United States
Strategy
Prevent perinatal HBV transmission
Routine vaccination of all infants
Vaccination of children in high-risk groups
Vaccination of adolescents
all unvaccinated children at 11-12 years of age
“high-risk” adolescents at all ages
Vaccination of adults in high-risk groups

AAP, AAFP, and ACIP Recommend Hepatitis B “Catch-up”
Give hepatitis B vaccine to all children 0-18 y.o.
“Providers should make special efforts” to
catch-up children (of parents) from moderate/high risk endemic areas.

"Remember…"
Remember…
You should never start the
hepatitis B vaccine series over again,
no matter how long
each dose is delayed!

References
Deborah L. Wexler, MD
Executive Director
Immunization Action Coalition
www.immunize.org