NPW Microbiology Antenatal Presentation

The Royal College of Pathologists

• The Royal College which deals with:– Clinical Chemistry– Microbiology– Histopathology– Haematology– Immunology

NPW Microbiology Antenatal Presentation

The patient’s antenatal visit

The patient

• Ms Ivy User• 22 years old• No previous pregnancies• 16 weeks pregnant• Current intravenous drug user• Multiple sexual partners• Unprotected sex• Says she is always tired but no other

symptoms

What infections could she have acquired as a result of her lifestyle?

• Hepatitis B

• Hepatitis C

• HIV

• Syphilis

• All of these

What infections could she have acquired as a result of her lifestyle?

• Hepatitis B

• Hepatitis C

• HIV

• Syphilis

• All of these - CORRECT

Microbiology Tests Performed on blood taken at the first antenatal visit

• Hepatitis B surface antigen

• HIV antibody and antigen

• Treponema pallidum (syphilis) antibody

• Rubella virus antibody

Results of microbiology blood tests taken at the first antenatal visit

• Hepatitis B surface antigen POSITIVE• HIV antibody/antigen POSITIVE• Treponema pallidum antibody POSITIVE• Rubella IgG antibody POSITIVE

Hepatitis B

What do these HBV results mean?

• Hepatitis B surface antigen POSITIVE• This is a screening result which needs to be

confirmed by other tests before we know her true HBV status

• She could be currently infected with hepatitis B virus

• This could transmit to her baby at birth• Need to test for other hepatitis B markers:

• Confirmation second hepatitis B surface antigen test

• Hepatitis B e antigen and antibody• Hepatitis B core IgM antibody

What do these HBV confirmatory results mean?

• (Hepatitis B surface antigen POSITIVE)

• Confirmation second hepatitis B surface antigen test – strongly positive – She IS infected with HBV

• Hepatitis B e antigen and antibody– Hepatitis B e antigen positive – She is very

infectious• Hepatitis B core IgM antibody

– Negative – she has not been infected in the last few months and so is likely to be a persistently infected carrier of HBV

How is Hepatitis B spread?

• By having unprotected sex?

• By kissing?

• By using a public toilet?

• By standing next to an infected person on a bus?

• By sharing mobile phones?

How is Hepatitis B spread?

• By having unprotected sex? YES• By kissing? NO

• By using a public toilet? NO

• By standing next to an infected person on a bus? NO

• By sharing mobile phones? NO

HIV

What do these HIV results mean?

• HIV antibody/antigen POSITIVE• This is a screening result which needs to be

confirmed in at least two other sensitive HIV antibody/antigen tests

What do these HIV results mean?

• (HIV antibody/antigen POSITIVE)

• Second sensitive HIV antibody/antigen test – POSITIVE

• Third sensitive HIV test – POSITIVE• Conclusion – she has confirmed HIV infection

and her baby could acquire infection• Need a repeat blood to confirm that these

results do relate to this patient

How can you catch HIV?

• By sharing towels with blood on them?

• By having unprotected sex?

• By sharing intravenous drug needles?

• By breastfeeding?

• By all of these?

How can you catch HIV?

• By sharing towels with blood on them?

• By having unprotected sex?

• By sharing intravenous drug needles?

• By breastfeeding?

• By all of these? YES

Syphilis

What do these syphilis results mean?

• (Treponema pallidum antibody POSITIVE)

• A screening test using an enzyme immunoassay (EIA) is used to indicate the possibility of treponemal infection.

• The EIA is highly sensitivity and can give non-specific reactions in pregnant women.

• The EIA positive result requires confirmation before we know whether she has syphilis currently or has had syphilis in the past.

• If infection is current or inadequately treated in the past this can be transmitted to the baby with serious outcomes.

What do these syphilis results mean?

• Treponema pallidum antibody POSITIVE

• Confirmation tests– TPPA – Treponema pallidum Particle Agglutination

test– RPR – Rapid Plasma Reagin test

• Sera that are EIA positive and– Are positive with a second test (TPPA) - this

indicates presence of treponemal antibody– Are reactive in the RPR test – this can indicate

current infection (above a titre of =>32)– Are negative with TPPA and RPR indicates a non-

specific reaction – No evidence of syphilis infection.

How does congenital syphilis occur?

• By vertical transmission from an infected mother at any stage of pregnancy?

• Directly from the father, via semen? • Direct from a syphilitic ulcer on the mother? • By transfer of antibody from the mother?

• Trans-vaginally during delivery?

How does congenital syphilis occur?

• By vertical transmission from an infected mother at any stage of pregnancy? YES

• Directly from the father, via semen? NO• Direct from a syphilitic ulcer on the mother?

NO• By transfer of antibody from the mother? NO• Trans-vaginally during delivery? NO

Rubella

What do these Rubella results mean?

• Rubella IgG antibody POSITIVE

• This result means this lady has immunity to rubella virus

• If she had been negative, any rubella-like illness would have been carefully investigated and she would have been recommended to have rubella vaccine after she delivered

• If a pregnant woman has rubella infection in the first 16 weeks of pregnancy, the baby could be born with brain, ear, heart and eye damage and could even die

Management of Hepatitis B Infection in Pregnancy

Management of Hepatitis B in Pregnancy

• Confirm Hepatitis B surface antigen (HBsAg) status of the mother

• Confirm Hepatitis B e status• She is HBe Antigen positive – HIGHLY

INFECTIOUS

• Confirm if this is an acute case of HBV in pregnancy

• She is anti-HBc IgM negative so she has not acquired HBV infection in the last few months and during this pregnancy

Management of Hepatitis B in Pregnancy

• Hepatitis B e status• HBe Antigen positive means the woman

is highly infectious and has a high risk of transmitting HBV to the baby at birth

• HBe Antigen positive people also have a high risk of transmitting infection to others via unprotected sex or through blood contact

• Anti-HBe positivity status implies people are much less infectious

Management of Hepatitis B in Pregnancy

• If a pregnant woman has confirmed HBV infection in pregnancy there is a risk of transmission to her baby

• If she has anti HBe antibody, the baby is given HBV vaccine soon after birth and then at months 1,2 and 12

• If she has no anti-HBe antibody or the mother acquired HBV infection during pregnancy, the baby should receive HBV vaccine as above PLUS hepatitis B immunoglobulin as soon after birth as possible

Scale of the problem

• England – about 600,000 pregnancies a year

• About 3,000 (0.5%) women infected with hepatitis

• 3,000 babies – up to 600 – at the highest risk of persistent infection

Region % of all HBV mothers

East Midlands

2.4%

East of England

5.8%

London 55.0%

North East 1.3%

North West 8.8%

South East 8.6%

South West 2.4%

West Midlands

8.1%

Yorks and Humber

7.6%

Management of Hepatitis B in Pregnancy

• Mother to be referred to a ‘liver doctor’ or infectious disease physician for clinical review – she may benefit from antiviral treatment

• Mother to be informed that baby will need immunisation at birth and at 1, 2 and 12 months old – the addition of hepatitis B immune globulin (ready made antibody) might also be required at birth based on the following criteria: Mother HBeAg positive Mother negative for both HBeAg and Anti-HBe Mother positive for anti-HBc IgM (indicating an acute

infection in pregnancy) Mother had high level of virus DNA (>1,000,000IU/ml)

• Baby will need a blood test at 12months to ensure that he/she has not become infected

Effect of hepatitis B vaccination on perinatal transmission

• Without intervention 70% - 90% of the babies born to HBeAg mothers would become persistently infected

• With vaccination started just after birth 30% may become infected (70% are protected)

• With vaccination after birth with immune globulin less than 10% become infected (over 90% protection)

Perinatal transmission of hepatitis B - Birmingham studies

ETHNIC ORIGIN

Total Number

of Babies

Babies HBsAg

POSITIVE

MOTHERS HBeAg

POSITIVE

Asian 51 4 (8%) 8%

European 39 0 0%

Black 13 4 (30%) 33%

Oriental 15 10 (66%) 75%

Others 5 0 0

TOTAL 123 18 (15%) 15%

Perinatal transmission associated with HBeAg positive mothers

Prevention of perinatal transmission of hepatitis B by immunization - Studies - % infected children

Study date

Location Controls Vaccine alone

Vaccine+HBIG

1984 HongKong

29/47 (62%) 15/63(24%) 9/64(14%)

1987 China

21/26 (81%) 3/27 (11%) 0/27 (0%)

1991 UK

15/21 (71%) 8/32 (25%) 1/8 (13%)

1992 India

10/15 (67%) 1/7 (14%) 1/7 (14%)

1992 Thailand

11/13 (85%) 2/18 (11%) 0/27 (0%)

1995 China

19/29 (66%) 2/27 (7%) 1/16 (6%)

Vaccine alone - works well - some improvement if HBIG added actual %Improvement varies from 0% to 12%: average 7.5% in this comparison

Systematic review of HBV vaccination of neonates at high risk

• Vaccine reduced HBV infections in babies• Addition of HBIG improved outcome for

babies of HBeAg+ mothers, but no evidence of improved outcome for babies of HBeAg - mothers

• No evidence that HBIG timing within the first 48 hours is crucial

• Vaccine alone almost as good as with HBIG

Neonatal Hepatitis B vaccination – outcome – blood test at 12 months

for evidence of infection

Why is outcome important?• Measure of success of programme • Identification of infected babies to

ensure referral to specialist services• Recognition of reasons for ‘failures’

Neonatal Hepatitis B vaccination

Recognition of reasons for ‘failures’• Vaccine delivery failures –

• patients move away• compliance• failure of healthcare systems

• true vaccine failures – variant viruses• “vaccine escape mutants”• HBeAg negative variants• mothers with very high maternal viraemia

HIV Management

Management of HIV in pregnancy

• This lady is confirmed HIV positive• Any person who is HIV positive benefits from

early diagnosis so that anti- HIV treatment can be given as soon as possible to slow down the advance of the disease

• In pregnancy, the primary concern is to prevent transmission to the baby in late pregnancy, at delivery and early in life

• If untreated, the risk of transmission to the baby could be as high as 30%

How to reduce the risk of HIV transmission from mother to baby

• The risk can be reduced by giving HIV antiviral treatment in late pregnancy

• In rich countries combination HIV treatment has reduced the risk of infecting the baby to 1-2%

• In poor countries even giving one dose of anti-HIV drug at delivery and to the newborn baby can reduce the risk

Syphilis Management

How to reduce the risk of syphilis infection in the baby

• All pregnant women should be screened for treponemal antibody.

• Any women with confirmed positive tests for treponemal antibody should be urgently referred to a GUM clinician for specialist care.

• Women with infectious syphilis should be treated with benzathine penicillin or procaine penicillin.

• Retreatment of previous cases where treatment history is unknown should be considered.

• Management of the mother should be in close liaison with obstetric, midwifery, GUM and paediatric departments.

The Outcome in the Baby

How do you think the baby did?

• Infected with HBV?• Infected with HIV?• Infected with Syphilis?• Infected with two of these three ?• Not infected?

The outcome for the baby

• The baby is now 18 months old• It is good news• The hepatitis B vaccine and immunoglobulin

prevented HBV infection in the baby• The baby has not been infected with HIV but

precautions need to be taken to prevent infection from the mother in the future

• The maternal treponemal antibody has disappeared and the baby does not have congenital syphilis.

Microbiology Antenatal Screening

The Pathologists’ Roles

The Pathologists’ Roles

• Virologist• Perform virology tests – HBV, HIV, Rubella• Interpret the findings of those tests• Give advice on treatment and management

• Microbiologist • Perform microbiology tests - Syphilis• Interpret the findings of those tests• Give advice on treatment and management