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 all of these? YES 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 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 West Midlands 8.1% Yorks and Humber 7.6% 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

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 Perinatal transmission associated with HBeAg positive mothers

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