Syphilis, Toxoplasmosis and CMV

Question 1

Definition of syphilis

Answer 1

A bacterial sexually transmitted infection caused by the spirochete Treponema pallidum, which results in substantial morbidity and mortality.

Question 2

How is the incidence of syphilis changing in the UK

Answer 2

The number of cases is on the rise in the UK, in part due to increased levels of immigration from countries where infection is prevalent.

Question 3

What is the prognosis of syphilis in pregnancy

Answer 3

• Mother-to-child transmission may occur if the expectant mother has syphilis and is usually devastating to the foetus if left untreated in pregnancy
• There is a foetal loss rate of 50%. Additionally, infection carries a risk of miscarriage, preterm birth, still birth and congenital syphilis.
• Around 2/3 of babies with congenital syphilis will be asymptomatic at birth but most will develop symptoms by 5 weeks of age

Question 4

Characteristics of neonatal syphilis

Answer 4

• Neonatal disease may manifest as rhinitis, a diffuse maculopapular, desquamative rash with extensive sloughing of the epithelium, particularly on the palms and soles
• Also presents with splenomegaly, anaemia, thrombocytopenia and jaundice
• 50% of infants will die in the neonatal period
• If left untreated, leads to physical and neurological impairment in the future

Question 5

What is the clinical course of syphilis

Answer 5

Characterised by STAGES:
* Primary and secondary where the person is symptomatic and highly infectious
* Latent (early/late)- asymptomatic
* Tertiary, where syphilis reactivates and serious complications are common

Question 6

Presentation of primary syphilis

Answer 6

Presents with a painless genital chancre
* < 2cm ulcer at the site of inoculation- classically solitary, painless, indurated, non-exudative (appears around 3 weeks after inoculation)

Question 7

Presentation of secondary syphilis

Answer 7

A manifestation of bacterial dissemination and classically presents with a diffuse, symmetric, copper maculopapular rash which is possibly pruritic (occurs 6 weeks to 6 months after infection)
* Commonly appears on the palms or soles. Mucus lesions, patchy alopecia, fever, headaches and generalised painless adenopathy may occur

Question 8

Presentation of tertiary syphilis

Answer 8

Without treatment, 14-40% of people with syphilis progress to tertiary disease- irreversible damage to any organ (primarily neurological, cardiovascular)

Question 9

When should syphilis be screened for in pregnancy, how is this done. What other investigations should be conducted for syphilis

Answer 9

At the booking visit
* Screening involves enzyme immunoassay- detects antibodies to Treponema pallidum
* Will be positive for antibodies against treponemal infections including non-syphilis treponemal infection and in those with a *previous *syphilis infection
* If positive repeat and perform TPPA

Genital ulcers can be swabbed and sent for microscopic identification of syphilis bacteria
Blood cultures
Confirmatory test= Treponema Pallidum particle agglutination (TPPA) or haemagglutination

Question 10

Diagnosis of congenital syphilis

Answer 10

• Ultrasound markers
• Non-immune hydrops fetalis
• FGR
• Lesions of the head and of the GI tract

Question 11

Management of syphilis in pregnancy

Answer 11

• Refer to the GUM clinic for appropriate contact tracing and determination of the stage of infection and complications
• Treatment for early disease (primary, secondary and early latent syphilis)= Benzylpenicillin G 2.4 million units once daily IM for 10 days
• In the case of penicillin allergy oral erythromycin or IM ceftriaxone can be used with caution (does not cross the placental barrier completely so foetus is left untreated)
• Treatment for late stage syphilis)= Benzylpenicillin G 2.4 million units IM once weekly for three consecutive weeks
• Parenteral penicillin has a 98% success rate at preventing congenital syphilis

Question 12

What is a Jarish-Herxheimer reaction

Answer 12

• Due to release of proinflammatory cytokines in response to dying organisms
• Presents with worsening of symptoms and fever for 12-24 hours after starting tx
• May be associated with uterine contractions and foetal distress
• So, women may be admitted at the time of treatment for monitoring

Question 13

Definition of toxoplasmosis

Answer 13

A disease caused by infection with the intracellular protozoan parasite Toxoplasma gondii, found in cat litter, soil and raw or undercooked meat. One third of the world’s population is infected with the parasite although it often remains unrecognised as patients do not exhibit symptoms.

Question 14

What is the incidence of toxoplasmosis in the Uk

Answer 14

Approximately 2 per 1000 pregnancies

Question 15

When is toxoplasmosis dangerous in pregnancy

Answer 15

• Placental infection is only a significant risk if the mother acquires the infection during or immediately before pregnancy (up to 3 months before conception)

Question 16

How long after inoculation does parasitaemia occur

Answer 16

Within 3 weeks (spread via blood and lymphatic system)

Question 17

What is the risk of congenital toxoplasmosis in first, second and third trimesters

Answer 17

o First trimester ~10 %
o Second trimester ~25%
o Third trimester >85%

Question 18

When is infection with toxoplasmosis most likely to cause congenital sequalae

Answer 18

Infection is more likely to cause congenital sequalae and complication in early pregnancy (85%) than late pregnancy (10%).

(more likley to cause congenital disease in late pregnancy)

Question 19

Presentation of toxoplasmosis in pregnancy

Answer 19

• Immunocompetent people are generally asymptomatic, or may exhibit non specific flu-like symptoms including fever, headache, muscle pain and lymphadenopathy.

Question 20

Manifestations and complications of toxoplasmosis in the neonate

Answer 20

Manifestations of toxoplasmosis in the neonate:
* Hydrocephalus, microcephaly, intracranial calcifications, retinochoroiditis, strabismus, blindness, epilepsy, psychomotor and mental retardation, petechiae due to thrombocytopenia, immunocompromised (most infants are asymptoatic at birth and develop symptoms later on)
* Significant risk of miscarriage and stillbirth
* Long term foetal effects include visual impairment due to persistence of a toxoplasmosis cyst that subsequently ruptures

Question 21

Evidence of toxoplasmosis spread to newborns through breastfeeding or human-human contact

Answer 21

None

Question 22

Investigations for toxoplasmosis in pregnancy

Answer 22

• Challenge is to distinguish between acute primary infection and past chronic infection

Serology (difficult to distinguish):
* IgM and IgG antibodies both rise within 1 to 2 weeks of acute infection but can persist for years (IgM) or throughout life (IgG)
* Absence of IgG or IgM antibodies indicates no previous infection (identifies women at risk during pregnancy)
* Four-fold increase in IgG antibody titre indicates a recent infection
* IgG antibody avidity testing can help confirm acute infection: Avidity of Ig binding to T.gonadii. Avidity shifts from low to a high index around 5 months after infection (low avidity index- suggests infection within past 5 months)
* Sabin-Fieldman dye test

Other:
* USS: may see hydrocephalus, microcephaly, intracranial calcification, ventricular dilation, ascites, IUGR
* Parasitic culture and molecular studies of amniotic fluid- PCR of amniotic fluid is highly accurate for identification of T.gonadii. Amniocentesis should only be offered if maternal primary infection is confirmed
* Screening is not routinely offered as it is rare for babies to be affected- women are advised to avoid eating raw meat, handling cats and cat litter and to wear gloves when gardening

Question 23

Management of Toxoplasmosis PCR +ve in mother, -ve in baby

Answer 23

Spiramycin (3-week course, 2-3g/day)
* Prevents vertical, transplacental infection. Spiramycin is a macrolide which cannot cross the placenta but remains concentrated in it
* Can be given before 20 weeks gestation and continued throughout pregnancy if no evidence of transmission to foetus

Question 24

Management of toxoplasmosis PCR +ve mother, +ve baby

Answer 24

Pyrimethamine + Sulfadiazine
* Need to discuss the options including TOP, or continuation of pregnancy with more aggressive antibiotic treatment
* Treat baby for up to 1 year after delivery (if no TOP)
* Clinical and ophthalmological examinations should be performed regularly for several years to screen for any sequalae
* Adjunct: Prednisolone

Question 25

Definition of CMV

Answer 25

A member of the human herpesvirus family and the most common viral cause of congenital infection

Question 26

Incidence of CMV in pregnancy

Answer 26

Arises in 0.2-2.2% of all live births

Question 27

Prognosis of CMV in pregnancy

Answer 27

• Responsible for significant morbidity, especially in infants who are symptomatic in the neonatal period- leading cause of sensorineural hearing loss (SNHL) and neurological disability
• 10-15% of neonates with congenital CMV will be symptomatic at birth (similar percentage will develop problem in later childhood)

Question 28

Classification of CMV infection

Answer 28

• May be a primary infection or secondary (reactivation or by infection of a different strain.)
• Transmission is more likely following maternal primary infection
• Infants born to mothers with primary infection have a risk of congenital infection of 30–40%, and 13% of these will be symptomatic at birth

Question 29

How is CMV trasmitted, what is its incubation period

Answer 29

• Transmission occurs via saliva, respiratory secretions, urine
• Incubation period= 4-8 weeks however the virus persists lifelong

Question 30

When is the risk of congenital infection and severe infection highest in pregnancy

Answer 30

• Risk of congenital infection rises from 30% in the first trimester, to 47% in the third trimester
• Risk of severe infection is higher in early pregnancy (similar to toxoplasmosis)

Question 31

Presentation of CMV

Answer 31

• The majority of women who acquire primary infection will remain asymptomatic
• A minority will experience symptoms similar to infectious mononucleosis including: Fever, malaise, myalgia, cervical lymphadenopathy and less commonly hepatitis or pneumonia

Question 32

Clinical features of neonatal CMV infection

Answer 32

• Jaundice, petechial rash, hepatosplenomegaly, microcephaly, SGA
• May also develop learning disability and seizures
• 87% will be asymptomatic or have subclinical manifestations of the disease (6-23% of these asymptomatic neonates will later develop some degree of hearing loss)

Question 33

Investigations for CMV in pregnancy

Answer 33

• Routine prenatal screening is not recommended outside research

Serology is offered to women who have developed flu-like symptoms or symptoms of glandular fever (with negative results for EBV) or hepatitis (with negative results for hepatitis A,B and C) or with suspicious ultrasound:
* IgM may persist for many months after the primary CMV infection.
* IgM may be detected during a secondary infection.
* There may be cross-reactivity with IgM due to another viral infection, e.g. Epstein–Barr virus.
* IgM may be detected as a result of nonspecific polyclonal stimulation of the immune system
* IgG avidity testing will better define the timing of the infection: A high avididty index (greater than 60% is suggestive of past infection more than 3 months prior)

Detailed ultrasound testing: features suggestive of CMV include ventriculomegaly, microcephaly, calcifications, intracranial haemorrhage, periventricular cysts, SGA, pericardial effusion, ascites, fetal hydrops

Question 34

When can CMV infection be diagnosed

Answer 34

The diagnosis of primary CMV infection in pregnancy can be made by one of the following findings:
* The appearance of CMV-specific IgG in a woman who was previously seronegative.
* The detection of CMV IgM antibody with low IgG avidity

Question 35

How is foetal infection with CMV diagnosed

Answer 35

• The mainstay of diagnosis of foetal infection is by identification of viral genome in the amniotic fluid:
• Amniocentesis and amniotic fluid PCR. This test should only be performed after 20 weeks gestation when foetal urination is well established (relies on foetal excretion of the virus in urine)
• In infected fetuses, cerebral MRI is indicated at 28–32 weeks of gestation (and sometimes repeated 3–4 weeks later)
• Congenital CMV should be confirmed at birth (e.g. urine or oral swab for CMV PCR within 3 weeks of birth)

Question 36

Management of CMV in pregnancy

Answer 36

• There is no licenced vaccine for CMV
• An alternative strategy to reduce the risk of infection is behavioural modification: Simple hygiene-based measures including handwashing after contact with urine or saliva, and avoiding sharing utensils, drinks or food with young children.
• Educational interventions
• Refer to a foetal medicine specialist for regular foetal surveillance including foetal USS every 2-4 weeks from diagnosis and foetal MRI at 28-32 weeks gestation
• If there is evidence of foetal infection on USS discuss the options:
  o Continuation of pregnancy with expectant management
  o TOP
• In neonates with symptomatic CMV infection, postnatal valgancicloir/ganciclovir treatment should be considered and commenced within 4 weeks of life. Treatment can reduce or prevent progression of SNLH
• Infant will require audiology and ophthalmology follow up