rita espinoza, mph emerging and acute infectious disease branch may 11, 2010 screening of pregnant...

Rita Espinoza, MPHEmerging and Acute Infectious Disease Branch

May 11, 2010

Screening of Pregnant Women for Hepatitis B and Overview of Hepatitis B

Virus Serological Markers

Objectives

• Review screening requirements for pregnant women in Texas

• Review serological markers for hepatitis B virus infections

Outline

• Historical perspective/rationale

• Screening requirements in Texas

• Serologic markers– Importance of serologic markers– Review serologic markers

• Acute infection• Chronic infection

• Case Studies

Background Information

• 1991 hepatitis B screening of pregnant women recommended by ACOG, AAP, ACIP

• Risk of perinatal transmission– HBsAg and HBeAg + at delivery - 70-90%– HBsAg + only 5-20%

• 90% of infants infected perinatally will become chronic carriers of hepatitis B

• 25% of those infected will die of HBV-related disease

Strategies to Reduce HBV Disease

• Continue and enhance vaccination efforts– School and childcare requirements– HCW– Adults (20-44 years)– Birth dose

• Surveillance• Early detection • Education • Perinatal hepatitis B prevention program

Texas Rules

• Health & Safety Code, Chapter 81, Section §81.090

• Texas Administrative Code, Title 25, Part 1, Chapter 97– Subchapter A, Rule §97.1 – §97.6– Subchapter F, Rule §97.135

Screening Requirements in Texas – Health and Safety Code, Chapter 81,

Section §81.090

Sec. 81.090. DIAGNOSTIC TESTING DURING PREGNANCYAND AFTER BIRTH. (a) A physician or other person permitted by law to attend a

pregnant woman during gestation or at delivery of an infant shall:(1) take or cause to be taken a sample of the woman's blood or other appropriate specimen at the first examination and visit;(2) submit the sample to an appropriately certified laboratory for diagnostic testing approved by the United States Food and Drug Administration for:

(A) syphilis;(B) HIV infection; and(C) hepatitis B infection; and

(3) retain a report of each case for nine months and deliver the report to any successor in the case.


Section §81.090, (cont’d)

(a-1) A physician or other person permitted by law to attend a pregnant woman during gestation or at delivery of an infant shall:(1) take or cause to be taken a sample of the woman's blood or other appropriate specimen at an examination in the third trimester of the pregnancy;(2) submit the sample to an appropriately certified laboratory for a diagnostic test approved by the United States Food and Drug Administration for HIV infection; and(3) retain a report of each case for nine months and deliver the report to any successor in the case.

(b) A successor is presumed to have complied with this section if the successor in good faith obtains a record that indicates compliance with Subsections (a) and (a-1), if applicable.


Section §81.090, (cont’d)

(c) A physician or other person in attendance at a delivery shall:(1) take or cause to be taken a sample of blood or other appropriate specimen from the mother on admission for delivery; and(2) submit the sample to an appropriately certified laboratory for diagnostic testing approved by the United States Food and Drug Administration for:

(A) syphilis; and(B) hepatitis B infection.

Summary of Requirement

• Women should be tested– during pregnancy

And – At delivery

• Women should be educated on– Transmission– Prevention– Treatment

Serological Markers

Possible Outcomes of Hepatitis B Infection

Clinical Manifestations of HBV Infection

• S/SX not unique to HBV infection• Only 50% of adult infections are

symptomatic • Need diagnostic tests to distinguish• Incubation period - 45 to 180 days (average = 60-90 days)• Communicability – 1 to 2 months before

and after onset of symptoms; chronic carrier

Hepatitis B Lab MarkersMarker Abbreviation Use

Hepatitis B surface antigen HBsAg Detection of acutely or chronically infected persons; antigen used in hepatitis B vaccine

M class immunoglobulin antibody to hepatitis B core antigen

IgM Anti-HBc

Anti-HBc, IgM

HBcAb, IgM

Identification of acute or recent HBV infections (including those in HBsAg-negative persons during the “window” phase of infection)

Antibody to hepatitis B core antigen

Anti-HBc

HBcAb

Identification of persons with acute, resolved, or chronic HBV infection

(not present after vaccination)

Antibody to Hepatitis B surface antibody

Anti-HBs

HBsAb

Identification of persons who have resolved infection with HBV; determination of immunity after immunization

Hepatitis B e antigen HBeAg Identification of infected persons at increased risk for transmitting HBV

Antibody to Hepatitis B e antigen

Anti-HBe

HBeAb

Identification of infected person with lower risk for transmitting HBV

Typical Serological Markers for Acute Hepatitis B Infection

HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100

Acute Hepatitis B Virus Infection with RecoveryAcute Hepatitis B Virus Infection with RecoveryTypical Serologic CourseTypical Serologic Course

Weeks after ExposureWeeks after Exposure

TiterTiter

HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100



TiterTiter

HBV DNA

HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100



TiterTiter

HBV DNA

HBeAg

HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100



TiterTiter

HBeAg anti-HBe

HBV DNA

HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100



TiterTiter

HBeAg anti-HBe

Symptoms

HBV DNA

IgM anti-HBcIgM anti-HBc

HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100



TiterTiter

HBeAg anti-HBe

Symptoms

HBV DNA


HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100



TiterTiter

HBeAg anti-HBe

Symptoms

Total anti-HBcTotal anti-HBc

HBV DNA


HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100



TiterTiter

HBeAg anti-HBe

Symptoms

anti-HBsanti-HBs


HBV DNA


HBsAgHBsAg

0 4 8 12 16 20 24 28 32 36 52 100



TiterTiter

HBeAg anti-HBe

Symptoms

anti-HBsanti-HBs


HBV DNA

Window Period

Typical Serological Markers for Chronic Hepatitis B Infection

Chronic Hepatitis B Virus Infection Typical Serologic CourseTypical Serologic Course

0 1 2 3 4 5 6 7 8 9 10

Tite

r

Years After Exposure

HBsAg

0 1 2 3 4 5 6 7 8 9 10

Tite

r


HBsAg

Total anti-HBc


0 1 2 3 4 5 6 7 8 9 10

Tite

r


HBsAg

Total anti-HBc

HBV DNA


0 1 2 3 4 5 6 7 8 9 10

Tite

r


HBsAg

Total anti-HBc

HBV DNA

IgM, anti-HBc


0 1 2 3 4 5 6 7 8 9 10

Tite

r


HBsAg

Total anti-HBc

HBV DNA

HBeAg


0 1 2 3 4 5 6 7 8 9 10

Tite

r


HBsAg

Total anti-HBc

HBV DNA

HBeAg Anti-HBe


Progression to Chronic Hepatitis B Virus InfectionProgression to Chronic Hepatitis B Virus InfectionTypical Serologic CourseTypical Serologic Course


TiterTiter

IgM anti-HBc

Total anti-HBc

HBsAg

Acute(6 months)

HBeAg

Chronic(Years)

anti-HBe

0 4 8 12 16 20 24 28 32 36 52 Years

Acute vs. Chronic HBV Infection

Acute• HBsAg+ < 6 mos.• IgM anti-HBc +

positive• Infection will

resolve and person will have lifelong immunity

• HBsAb+ and HBcAb+

Chronic• HBsAg + for at least 6

months • Also known as a

“carrier”• Infection does not

resolve and the person remains infectious

• HBsAb- and HBcAB+

Hepatitis B, acute Surveillance Case Definition

• Confirmed:– Positive anti-HBc, IgM with or without

symptoms or – Meets clinical case definition and is

HBsAg-positive and anti-HAV IgM negative, if done

Hepatitis B, perinatal Surveillance Case Definition

• Confirmed:– HBsAg-positive– < 24 months of age– Born to an HBsAg-positive woman

Hepatitis B, chronicSurveillance Case Definition

• Confirmed: case that is laboratory-confirmed (2 positives 6 months apart or HBsAg+, anti-HBc+, and IgM-)

• Probable: case with a single HBsAg or HBeAg or HBV DNA positive lab when no IgM anti-HBc results are available

CASE STUDIES

Case Study A

Patient History:

John went to his doctor with jaundice, fatigue and abdominal pain. After reviewing John’s liver panel, the doctor diagnosed him with acute hepatitis B infection.

Question 1

What might his hepatitis B panel look like?

Answer

Marker Result

HBsAg Positive

HBeAg Positive

anti-HBc Positive

IgM anti-HBc Positive

anti-HBeAg Negative

anti-HBs Negative

Case Study B

Sara visits his doctor and has a hepatitis panel done. Her results are as follows:

HBsAg Positive

anti-HBc Positive

IgM anti-HBc Negative

anti-HBs 6mIU/mL

Question 1

How would you interpret Sara’s results?

Answer

• Chronic hepatitis B infection

Question 2

What significance is the anti-HBs?

Answer

• No biological significance

Case Study C

Jada went to her doctor for a routine physical. A hepatitis panel was done and her results were as follows:

HBsAg Negative

anti-HBs Positive

anti-HBc Negative

Question 1

• How would you interpret her results?

Answer

• She received the hepatitis B vaccine and is protected (immune)

Case Study D

Jeff went in for a routine annual physical. His doctor decided to run a hepatitis panel. His results are as follows:

HBsAg Positive

anti-HBs Negative

anti-HBc Positive

anti-HBc, IgM Positive

HBeAg Positive

Question 1

• How would you interpret his results?

Answer

• He has acute hepatitis B infection.

Case Study E

Stacy is pregnant. Her prenatal HBsAg test was negative. Upon admission for delivery, the HBsAg screen was repeated. The results came back positive.

Scenario 1:

Stacy insisted that there was no way

she could have contracted hepatitis B.

she had not engaged in any high-risk

activities. The doctor decided to

repeat the test.

Question 1

• What tests should be ordered?

Answer

• HBsAg

• anti-HBc

• anti-HBc, IgM

• anti-HBs

Her results were as follows:

HBsAg Negative

anti-HBs Negative

anti-HBc Negative

anti-HBc, IgM Negative

How would you interpret?

Answer

• False positive

Scenario 2: Stacy’s baby received the HBIG andhepatitis B vaccine at birth. The family isenrolled in the local perinatal hepatitis Bprevention program. Three months post-partum, Stacy’s physician decides to re-test her. Her results are as follows:

HBsAg Negativeanti-HBc Positiveanti-HBs Positive

Question 2

• What do the results indicate?

Answer

• Resolved Infection

Test Results Interpretation

HBsAg

anti-HBc

anti-HBs

Negative

Negative

Negative

Susceptible

(Never infected or vaccinated)

HBsAg

anti-HBc

anti-HBs

Negative

Negative

Positive

Immune

(Due to vaccine)

HBsAg

anti-HBc

anti-HBs

Negative

Positive

Positive

Immune

(Resolved Infection)

HBsAg

anti-HBc

IgM anti-HBc

anti-HBs

Positive

Positive

Positive

Negative

Acutely Infected

HBsAg

anti-HBc

anti-HBs

IgM anti-HBc

Positive

Positive

Negative

Negative

Chronically Infected

HBsAg

anti-HBc

anti-HBs

Negative

Positive

Negative

Four Possible Interpretations

Interpretation of Serological Tests

Four Possible Interpretations

• May be recovering from acute HBV infection

• May be distantly immune and test not sensitive enough to detect very low level of anti-HBs in serum

• May be susceptible with a false positive anti-HBc

• May be undetectable level of HBsAg present in the serum and the person is actually a carrier

Summary

• Pregnant women should be screened during pregnancy and at delivery– Eliminate perinatal transmission– Documentation necessary

• Determination of hepatitis status is complicated

Resources

• American Academy of PediatricsRed Book – American Academy of Pediatrics (www.aap.org)

• DSHShttp://www.dshs.state.tx.us/idcu/disease/hepatitis/hepatitis_b/perinatal/Statistics/

• CDC – Pink Book http://www.cdc.gov/vaccines/pubs/pinkbook/default.htm

– On-line CE Training From CDC on Serological Markershttp://www.cdc.gov/hepatitis/Resources/Professionals/Training/SerologyStart.htm

– Online resources

http://www.cdc.gov/hepatitis/HBV/index.htm• Immunization Action Coalition

http://www.immunize.org/hepatitis-b/

rita espinoza, mph emerging and acute infectious disease branch may 11, 2010 screening of pregnant...

Documents

b hepatitis b infection

c hepatitis b infection

hepatitis b vaccine

hepatitis b virus infections

syphilis b hiv infection

transmitting hbv slide

chronic hbv infection

hbv related disease