3The Royal College of Pathologists The Royal College which deals with:Clinical ChemistryMicrobiologyHistopathologyHaematologyImmunology
4NPW Microbiology Antenatal Presentation The patient’s antenatal visit
5The patient Ms Ivy User 22 years old No previous pregnancies 16 weeks pregnantCurrent intravenous drug userMultiple sexual partnersUnprotected sexSays she is always tired but no other symptoms
6What infections could she have acquired as a result of her lifestyle? Hepatitis BHepatitis CHIVSyphilisAll of these
7What infections could she have acquired as a result of her lifestyle? Hepatitis BHepatitis CHIVSyphilisAll of these - CORRECT
8Microbiology Tests Performed on blood taken at the first antenatal visit Hepatitis B surface antigenHIV antibody and antigenTreponema pallidum (syphilis) antibodyRubella virus antibody
9Results of microbiology blood tests taken at the first antenatal visit Hepatitis B surface antigen POSITIVEHIV antibody/antigen POSITIVETreponema pallidum antibody POSITIVERubella IgG antibody POSITIVE
11What do these HBV results mean? Hepatitis B surface antigen POSITIVEThis is a screening result which needs to be confirmed by other tests before we know her true HBV statusShe could be currently infected with hepatitis B virusThis could transmit to her baby at birthNeed to test for other hepatitis B markers:Confirmation second hepatitis B surface antigen testHepatitis B e antigen and antibodyHepatitis B core IgM antibody
12What do these HBV confirmatory results mean? (Hepatitis B surface antigen POSITIVE)Confirmation second hepatitis B surface antigen test– strongly positive – She IS infected with HBVHepatitis B e antigen and antibodyHepatitis B e antigen positive – She is very infectiousHepatitis B core IgM antibodyNegative – she has not been infected in the last few months and so is likely to be a persistently infected carrier of HBV
13How 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?
14How is Hepatitis B spread? By having unprotected sex? YESBy kissing? NOBy using a public toilet? NOBy standing next to an infected person on a bus? NOBy sharing mobile phones? NO
16What do these HIV results mean? HIV antibody/antigen POSITIVEThis is a screening result which needs to be confirmed in at least two other sensitive HIV antibody/antigen tests
17What do these HIV results mean? (HIV antibody/antigen POSITIVE)Second sensitive HIV antibody/antigen test – POSITIVEThird sensitive HIV test – POSITIVEConclusion – she has confirmed HIV infection and her baby could acquire infectionNeed a repeat blood to confirm that these results do relate to this patient
18How 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?
19How 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
21What 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.
22What do these syphilis results mean? Treponema pallidum antibody POSITIVEConfirmation testsTPPA – Treponema pallidum Particle Agglutination testRPR – Rapid Plasma Reagin testSera that are EIA positive andAre positive with a second test (TPPA) - this indicates presence of treponemal antibodyAre 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.
23How 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?
24How does congenital syphilis occur? By vertical transmission from an infected mother at any stage of pregnancy? YESDirectly from the father, via semen? NODirect from a syphilitic ulcer on the mother? NOBy transfer of antibody from the mother? NOTrans-vaginally during delivery? NO
26What do these Rubella results mean? Rubella IgG antibody POSITIVEThis result means this lady has immunity to rubella virusIf 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 deliveredIf 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
27Management of Hepatitis B Infection in Pregnancy
28Management of Hepatitis B in Pregnancy Confirm Hepatitis B surface antigen (HBsAg) status of the motherConfirm Hepatitis B e statusShe is HBe Antigen positive – HIGHLY INFECTIOUSConfirm if this is an acute case of HBV in pregnancyShe is anti-HBc IgM negative so she has not acquired HBV infection in the last few months and during this pregnancy
29Management of Hepatitis B in Pregnancy Hepatitis B e statusHBe Antigen positive means the woman is highly infectious and has a high risk of transmitting HBV to the baby at birthHBe Antigen positive people also have a high risk of transmitting infection to others via unprotected sex or through blood contactAnti-HBe positivity status implies people are much less infectious
30Management of Hepatitis B in Pregnancy If a pregnant woman has confirmed HBV infection in pregnancy there is a risk of transmission to her babyIf she has anti HBe antibody, the baby is given HBV vaccine soon after birth and then at months 1,2 and 12If 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
31Scale of the problem England – about 600,000 pregnancies a year Region% of all HBV mothersEast Midlands2.4%East of England5.8%London55.0%North East1.3%North West8.8%South East8.6%South WestWest Midlands8.1%Yorks and Humber7.6%England – about 600,000 pregnancies a yearAbout 3,000 (0.5%) women infected with hepatitis3,000 babies – up to 600 – at the highest risk of persistent infection
32Management 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 treatmentMother 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 positiveMother negative for both HBeAg and Anti-HBeMother 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
33Effect of hepatitis B vaccination on perinatal transmission Without intervention 70% - 90% of the babies born to HBeAg mothers would become persistently infectedWith 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)
34Perinatal transmission of hepatitis B - Birmingham studies Perinatal transmission associated with HBeAg positive mothers
35Prevention 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
36Systematic review of HBV vaccination of neonates at high risk Vaccine reduced HBV infections in babiesAddition of HBIG improved outcome for babies of HBeAg+ mothers, but no evidence of improved outcome for babies of HBeAg - mothersNo evidence that HBIG timing within the first 48 hours is crucialVaccine alone almost as good as with HBIG
37Neonatal Hepatitis B vaccination – outcome – blood test at 12 months for evidence of infection Why is outcome important?Measure of success of programmeIdentification of infected babies to ensure referral to specialist servicesRecognition of reasons for ‘failures’
38Neonatal Hepatitis B vaccination Recognition of reasons for ‘failures’Vaccine delivery failures –patients move awaycompliancefailure of healthcare systemstrue vaccine failures – variant viruses“vaccine escape mutants”HBeAg negative variantsmothers with very high maternal viraemia
40Management of HIV in pregnancy This lady is confirmed HIV positiveAny 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 diseaseIn pregnancy, the primary concern is to prevent transmission to the baby in late pregnancy, at delivery and early in lifeIf untreated, the risk of transmission to the baby could be as high as 30%
41How to reduce the risk of HIV transmission from mother to baby The risk can be reduced by giving HIV antiviral treatment in late pregnancyIn 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
43How 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.
45How do you think the baby did? Infected with HBV?Infected with HIV?Infected with Syphilis?Infected with two of these three ?Not infected?
46The outcome for the baby The baby is now 18 months oldIt is good newsThe hepatitis B vaccine and immunoglobulin prevented HBV infection in the babyThe baby has not been infected with HIV but precautions need to be taken to prevent infection from the mother in the futureThe maternal treponemal antibody has disappeared and the baby does not have congenital syphilis.
47Microbiology Antenatal Screening The Pathologists’ Roles
48The Pathologists’ Roles VirologistPerform virology tests – HBV, HIV, RubellaInterpret the findings of those testsGive advice on treatment and managementMicrobiologistPerform microbiology tests - Syphilis