Microbiology Antenatal Screening - UCD National Virus Reference

NPW Microbiology
Antenatal Presentation
The Royal College of
Pathologists
• The Royal College which deals with:
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Clinical Chemistry
Microbiology
Histopathology
Haematology
Immunology
NPW Microbiology
Antenatal Presentation
The patient’s antenatal visit
The patient
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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?
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Hepatitis B
Hepatitis C
HIV
Syphilis
All of these
What infections could she have
acquired as a result of her lifestyle?
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Hepatitis B
Hepatitis C
HIV
Syphilis
All of these - CORRECT
Microbiology Tests Performed on blood
taken at the first antenatal visit
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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
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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?
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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?
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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?
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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?
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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 nonspecific 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
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%
• 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
Asian
Total
Number
of
Babies
51
European
ETHNIC
ORIGIN
Babies
HBsAg
POSITIVE
MOTHERS
HBeAg
POSITIVE
4 (8%)
8%
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
y
e
4
Location
Controls
HongKong
29/47 (62%)
Vaccine
Vaccine+HBIG
alone
15/63(24%) 9/64(14%)
7
China
21/26 (81%)
3/27 (11%)
0/27 (0%)
1
UK
15/21 (71%)
8/32 (25%)
1/8 (13%)
2
India
10/15 (67%)
1/7 (14%)
1/7 (14%)
2
Thailand
11/13 (85%)
2/18 (11%)
0/27 (0%)
5
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’
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Vaccine delivery failures –
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patients move away
compliance
failure of healthcare systems
true vaccine failures – variant viruses
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“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?
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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