Perinatal infections CMV HSV Syphillis Rubella Toxoplasmosis Flashcards
What public health intervention should be taken to combat congenital CMV infection? Justify your answer.
- All women should receive advice on CMV during routine antenatal care
- Avoid kissing small children on the mouth
- Wash hands regularly, and especially after wiping the nose, mouth or toileting young children
- Wash surfaces with antibacterial after contact with urine/saliva of small children
- Do not share food or drink utensils
- Don’t put dummies into the mouth
- There is no evidence for routine serological screening during scheduled antenatal care
Justification
- Children under 3 years old are particularly likely to excrete virus, and at a higher titre than adults
- This risk is increased if they go to day care
- They excrete virus in urine and saliva
- Both primary and secondary infections (reinfection), or reactivation, can result in transmission to the fetus and potentially cause congenital CMV
- Though transmission to the fetus is less in secondary infection or reactivation as compared to primary infection (1-3% vs 30-40%), the rate of seropositivity (and hence latent phase of infection) in the the Australian population is 40-60%, and the largest burden of congenial CMV is attributed to secondary infection/reactivation
- Consequently any public health approach needs to target all women, regardless of their existing CMV serological status
Describe the transmission of CMV, and the risk for congenital CMV.
Primary CMV: 30-40%
Reactivation: 1-3% transmission risk
1st trimester infection: neurodisability risk higher
2nd/3rd: acute visceral disease more likely
- The mother often contracts CMV from other children (particularly under 3 years, or attending day care); it can be transmitted in their urine or saliva
- Adults transmit CMV from the cervix, semen and other bodily fluids
- It can be contracted from direct contact with infected fluid, or via fomites
- Transmission to the fetus is across the placenta, or can be during or after delivery
- The highest risk of transmission to the fetus is during primary infection in the first trimester, when the risk is 30-40%; roughly 1/3 will develop symptoms of congenital CMV (10% overall)
- The risk of transmission to the fetus in secondary infection or reactivation is 1-3%; however, once infected, the risk of morbidity and mortality is comparable to during primary infection
- 90% foetuses will have no signs/symptoms of congenital CMV at birth; however 10-15% of these may develop longer term sequelae in early childhood (SNHL, chorioretinitis most common)
A woman who is 24 weeks pregnant presents acutely with flu-like symptoms, a fever, and cervical lymphadenopathy. Describe your approach to screening and diagnosing possible congenital CMV in this case.
- History
- Examination
- Serological testing (CMV IgM, IgG …+/- IgG specific avidity)
- USS findings +/- MRI
- Amniocentesis and CMV nucleic acid PCR- 6-8 weeks after infection
Outline the interpretation of different CMV serological results
IgM -, IgG - = no previous CMV, still susceptible
IgM -, IgG + = Previous CMV infection, no current infection
IgM +, IgG - = false positive IgM, or possible early primary infection; repeat test in 2 weeks
IgM +, IgG +, low IgG avidity = Primary infection within last 3 months
IgM +, IgG +, intermediate IgG avidity = Possible primary infection within last 3 months - manage as acute primary infection
IgM +, IgG +, high IgG avidity = Infection > 3months, reinfection or reactivation
Retrospective assessment of booking bloods can also be helpful to determine a primary infection, by demonstrating seroconversion within the pregnancy
What investigations can be used to diagnosis congenital CMV?
Maternal Serology
USS +/- MRI of head
Amniocentesis
- Ideally after 21wks gestation and >8 weeks after acute infection for best sensitivity and specificity (high false negative <21 wks gestation)
CMV testing on saliva or urine within first 3 wks of birth
What is the management for babies affected by congenital CMV?
Antenatal:
- Refer to MFM specialist
- Serial US for growth monitoring
- MRI to assess for congenital abnormality, particularly intracranial and neurological defects
- If US and MRI are normal, there is a very good prognosis
After birth:
- Newborn hearing assessment
- Ophthalmology and head USS +/- MRI after birth
- Referral to paediatric with specialist interest in congenital CMV
- 3-6 monthly review for first 2 years of life, including hearing and neurodevelopment assessment
- Treatment dependent on level and site of organ involvement
- IV ganciclovir for 6 weeks or oral valganciclovir for up to 6 months has demonstrated some benefits in improving hearing and neurological outcomes at 6 and 12 months
- Breast feeding should be encouraged, there is no evidence that transmission after birth has any significant sequelae
What are the findings and sequelae associated with congenital CMV infection?
- SGA
- polyhydramnios or oligohydramnios
- microcephaly
- Intracerebral calcification
- ascites/hydrops
- chorioretinitis
- hepatosplenomegaly
- anaemia/thrombocytopenia
- still birth and neonatal death
Long term sequelae:
- sensorineural hearing loss (not always present at birth)
- cerebral palsy
- developmental delay
- visual impairment
- Poor school performance
What 3 infections can be transmitted in utero and cause congenital defects?
- CMV
- Rubella
- VZV (chicken pox)
What is the prevalence of CMV congenital infection?
- 2.2% pregnancies
- It is the commonest of congenital infections
What causes toxoplasmosis and how is it transmitted?
- Toxoplasmosis Gondii (a protozoan parasite)
- Common gut parasite in cats (can be in any animal); after ingesting infected food cats excrete oocysts in their faeces for several weeks - kittens tend to shed highest numbers due to primary infection
- Transmission to humans is food borne (contaminated, undercooked food or poor food hygiene during preparation); zoonoses via cat faeces; congenital vertical transmission
What is the presentation of toxoplasmosis in adults?
- In the adult most are asymptomatic; 10% get flu-like illness, fever, cervical lymphadenopathy, chorioretinitis
- After acute infection it remains in the body in an inactive state, which can be reactivated during times of immune suppression
- Severe presentations are common in the immune compromised and can be reactivated during immune suppression; pneumonitis, myocarditis and encephalitis
What are the sequelae of congenital toxoplasmosis?
- Can cause miscarriage, stillbirth and neonatal death
- Majority of babies born with toxoplasmosis are asymptomatic
- 10% of affected babies are born with chorioretinitis and blindness
- 20% have generalised disease: hepatosplenomegaly, anaemia, jaundice, neurological symptoms and seizures
In congenital toxoplasmosis, what are the risks to the fetus in each trimester?
If the mother is immune (20-35% reproductive population), the risks of transmission and significant sequelae are low.
First trimester
- Low risk MTFT (4-15%)
- High risk of morbidity/mortality
Second trimester
- Intermediate risk MTFT (25-40%)
- Intermediate risk of morbidity/mortality
Third trimester
- High risk MTFT (30-75%)
- Low risk of morbidity/mortality; majority born without symptoms
How is toxoplasmosis diagnosed in pregnancy?
- Maternal serology
- USS +/- MRI - poor sensitivity and specificity
- Amniocentesis and T.Gondii PCR (>4 weeks after acute infection)
Once confirmed, what are the management options for toxoplasmosis infection during pregnancy?
- Termination of pregnancy
- Pyrimethamine and sulfadiazine from 18 weeks gestation ( with folinic acid)
- Full examination after birth, with ophthalmology and hearing review, head USS +/-MRI, fetal serology IgA/IgM, T.Gondii PCR
- If any of the above are abnormal, the infant should be treated with 12 months of pyrimethamine and sulfadiazine with folinic acid; they will require ongoing monitoring of vision, hearing and neurodevelopment delay through early childhood
Which 3 congenital infections are most strongly associated with SGA?
CMV, rubella, syphilis
What are the sequelae of congenital syphilis?
Saddle nose, interstitial keratitis, Hutchinsons incisors, sensorineural deafness, CN palsies, learning difficulties, Cluttons joint (arthritis typically affecting the knees)
How does gestation affect the risk of birth defects with congenital rubella syndrome?
The greatest risk is within the first 16 weeks gestation. Between 16-20 wks low risk of deafness only. After 20 wks the risk of congenital abnormality is minimal.
Interpret this routine antenatal serology screen and discuss its implications and management?
- Rubella IgM positive, Rubella IgG negative
- This may be a non-specific IgM rise, or could be an acute infection
- Repeat serology in 1-2 weeks to check for IgG seroconversion
- If there is no evidence of seroconversion it is likely a false positive
- If seroconversion occurs maternal infection is confirmed and the mother requires counselling based on the pregnancy gestation
How is congenital rubella investigated and diagnosed?
- History of rash-like illness or contact with suspected/confirmed rubella case
- USS findings: SGA, cardiac defects (VSD, pulmonary stenosis), echogenic bowel, eye defects
What management can be offered for congenital rubella syndrome?
- Maternal infection in first trimester should be offered termination due to high risk congenital defects (85%)
- Maternal infection in the second trimester - offer fetal testing (CVS or amniocentesis for rubella PCR, culture and fetal IgM). This should occur >6wks after maternal infection and after 20wk gestation to avoid false negatives
- Maternal infection in the third trimester is very rarely associated with congenital defects so no treatment is required
- Affected pregnancies should have neonatal screening - checking for signs of congenital rubella, cardiac/opthalmology/hearing screening, serology, urine and throat swabs for rubella PCR +/- culture
How is syphilis diagnosed?
- Syphilis serology
(EIA or TPPA detects IgG and IgM, is specific for syphilis, but will remain positive once infected, even if fully treated; VDRL or RPR, non-specific, measured as a titre, positivity suggests ongoing infection requiring treatment) - Swab lesions for syphilis PCR or dark ground microscopy for treponemes
How is syphilis treated in each trimester of pregnancy?
- 1st & 2nd trimester 2.4MU benzathine benzylpenicillin IM (single dose)
- 3rd trimester 2.4MU benzathine benzylpenicillin IM (2 doses, 1 week apart)
- Tertiary syphilis requires 2.4MU benzathine benzylpenicillin IM (3 doses, 1 week apart)
- Serology should be repeated monthly till delivery, and 3, 6, 12 months from treatment)
What advice would you give a pregnant woman with recurrent genital herpes?
- Offer prophylactic acyclovir from 36 weeks
- Advise even with active lesions at the time of delivery the risk of transmission to the baby is low 1-3%
- If she has active lesions at the time of delivery, she would have the option of caesarean delivery, though routinely vaginal birth is considered safe
- If has PROM augment with syntocin
- Invasive procedures (FSE/FBS) do not need to be avoided if indicated
How would you manage a woman with the first episode of genital herpes in her current pregnancy?
- Manage acute episode with 5 day course acyclovir / valaciclovir
- Do type specific serology to check if acute infection
- Prophylactic acyclovir from 36 weeks
- If active lesions within 6 weeks of delivery offer an elective caesarean
- If active lesions at time of delivery requires caesarean
- If vaginal birth desired, give will require acyclovir in labour
- Inform neonatologist, the baby may require treatment with acyclovir after delivery
A pregnant woman presents with an ulcer in pregnancy, you suspect HSV. What investigations do you do?
- decide if first or recurrent presentation.
- If first presentation then need to do viral PCR to determine correct diagnosis and if HSV 1 or 2.
- Test blood serology to confirm first presentation (IgG result negative but positive swab).
- Counsel re risk
- Prophylactic aciclovir (400mg TDS) from 36/40 (and treat lesion)
- CS if primary lesion >34/40
Risks of transmission of HSV:
Active recurrent infection at time of delivery, HSV 1
• 15%
Risks of transmission of HSV:
Recurrent HSV2
<0.01% HSV2
Overall quote is 1-3% risk if combining HSV 1 and 2 risk
Risks of transmission of HSV:
Active primary infection at time of delivery
25-50%
• Indications for CS for HSV:
primary lesion in third trimester or seen at time of delivery.
If active lesion but recurrence- discussion with woman necessary based on risks.
• Avoid FSE/instrumental/FBS
Management of baby if HSV suspected at time of delivery
o Asymptomatic and low risk (ie recurrent infection or seroconversion 6/52 before delivery)- observe and monitor for signs of infection
o Asymptomatic and high risk OR symptomatic- viral screen (LP, swabs, serology etc) and start acyclovir treatment
Risks of transmission of HSV:
Primary infection in pregnancy but seroconversion well before delivery (ie before 36/40)
Same risk as recurrent HSV
Neonatal signs/symptoms of HSV infection
Vesicular skin lesions or atypical pustular or bullous lesions, especially on presenting part (note: may be absent) • Seizures • Unexplained sepsis with -ve blood cultures not responding to antibiotics • Low platelets • Elevated LFTs • DIC (disseminated intravascular coagulation) • Respiratory distress (after day 1 of life) • Corneal ulcer/keratitis
What causes syphillis?
Bacteria- Treponema Pallidum
What are the stages of syphillis? And risk of transmission to fetus?
Primary: Chancre. High risk
Secondary: Systemic illness including but not limited to fever, rash, hepatitis, lymphadenopathy, meningoencephalitis. Medium risk
LatentL Asymptomatic: <2 years-early; >2 years-late, Low risk
Tertiary: Cardiovascular, Neurological, Gummatous lesions. Risk: negligible.
Treatment of syphillis according to stage:
Early syphilis (primary, secondary or early latent syphilis) treatment: – Benzathine penicillin 1.8g (= 2.4 million units) IM, as a single dose OR – Procaine penicillin 1.5g IM, daily for 10 days
Late syphilis (>2 years or unknown duration) treatment:
– Benzathine penicillin 1.8g (= 2.4 million units) IM, once weekly for 3 weeks OR
– Procaine penicillin 1.5g IM, daily for 15 days
Syphillis: Investigations of the neonate
- Infant serology
- Neonatal examination: rash, mucosal lesions, hepatomegaly, nasal discharge, bony tenderness,
eye lesions - Placental histopathology +/- PCR
Syphilis: Next steps if initial investigations of the neonate are negative?
Repeat again at 3 and 6 months
If remain negative then can be confident that no infection
Syphillis: General management of neonate if suspicion of congenital syphillis?
IV ben pen for 10/7
Then:
Follow up serology 1, 2, 4, 6, 12
months of age or until non reactive
on 2 occasions. If neurosyphilis
repeat CSF examination at 6 months
Syphillis- alternatives to Ben Pen and their challenges?
Erythromycin- but doesn’t cross placenta
Ceftriaxone
Risks of syphillis
Stillbirth Early fetal death LBW Prematurity Congenital infection
What do RPR tests show?
Non-treponemal test
Detect anti lipid IgM or IgG antibodies
Present in other diseases so not specific for syphilis and can give false positive results
Downside of non-treponemal tests?
- Not specific so can produce false positives
- May be negative for up to four weeks after the
lesion of primary syphilis first appears and can be
negative in late latent syphilis;
-In primary and secondary syphilis, these tests may be false negative due to a prozone reaction
Therefore may require repeat testing at 2 and 4 weeks
If still negative after 3/12 then syphillis not present
What can non-treponemal tests be used for in addition to diagnosis?
Quantitative tests give a titre that can be used to calculate a response to treatment
What is the use of treponemal tests?
Specific to syphilis but don’t differentiate venereal from endemic syphillis
Typically used as a confirmatory test once a non-treponemal test is positive
May stay positive for a lifetime
Example: TPPA
