Congenital and Perinatal Viral Infections Flashcards
Definitions: Intrauterine, Perinatal, Neonatal and Congenital
Intrauterine = in utero (before birth) Perinatal = birth-1 wk Neonatal = birth up to 4 wks
Congenital = in utero +/- perinatal (before birth to 1 wk old)
3 Key factors affecting severity of infection and clinical management
Primary vs Secondary infection/ reactivation
Timing during gestation
Overall risk - abortion
Common intrauterine infections (6)
Rubella, CMV, VZV, Parvovirus B19, Toxoplasma, Zika virus
Rubella infection - gestation and effect, symptoms of congenital rubella syndrome, postnatal infection symptoms
Congenital Infection:
- First 12 wks ==> Congenital Rubella Syndrome (90%)
- 13-16 wks ==> Deafness (20%)
- > 16 wks ==> Minimal effects, deafness and retinopathy possible
Congenital Rubella Syndrome:
- permanent defects in ear (MC, deafness), eye (e.g. CATARACTS, glaucoma), CNS (mental retardation), CVS (e.g. PDA, VSD), endocrine (e.g. DM, thyroid)
- transient effects e.g. low birth wt, low Plt, bone lesions, hepatosplenomegaly, meningoencephalitis (rare)
Postnatal Infection:
- transmitted by aerosol
- incubation: 2-3 wks
- rash: face –> trunk –> limbs
- fever, malaise, lymphadenopathy (post-auricular), low platelet
- arthritis of SMALL JOINTS (female)
- 25% asymptomatic
Rubella diagnosis: clinical vs laboratory, main method and interpretations, other available methods, screening
Clinical Dx inaccurate (fever, rash and LN can be caused by many viruses)
SEROLOGY
- Acute infection: IgM increase or 4-fold increase in antibody titre in convalescent sample
- IgG within 2 weeks of exposure = immunity
Virus isolation (urine/resp sample) -- takes a long time PCR (urine, NPA, amniotic fluid)
ALL ANTENATAL women screened for Rubella IgG regardless of vaccination history or previous Ab results
– if not present, usually recommend vaccine after delivery
Rubella epidemiology: seropositivity in HK, vaccine programs, notifiable disease?
Worldwide
Spring and early summer
Notifiable disease!!
90% child-bearing age in HK are IgG +ve
Selective immunisation in females since 1978
Combined immunisation of MMR since 1990 (1st dose at 1 yrs old, 2nd at 18 mths)
Cytomegalovirus: recall mechanism of infection, epidemiology
Member of Herpesviridae family
- common primary infection in childhood, usually asymptomatic (may have IM occasionally i.e. fever, rash, LNs)
- -> persistency (frequent shedding in urine and saliva) and latency (haematoprogenitor cells)
- -> secondary infection i.e. reactivation in immunocompromised leading to pneumonitis, hepatitis, retinitis
Seroprevalence in HK 90% in 1990s but decreasing trend due to better hygiene and lower transmission risks
(UK and US 60%)
CMV infection during pregnancy: primary vs secondary, risk of foetal infection, gestation period, outcomes, abortion?
Primary infection
- Mother: asymptomatic
- Foetus: 40% infected, damage can results from ALL STAGES OF GESTATION
Of these:
5-10% Cytomegalic inclusion body disease (“congenital cytomegalic disease”)
- growth retardation, hepatosplenomegaly, petechial haemorrhage, encephalitis (rare), blindness, chorioretinitis
10% Deafness and psychomotor retardation
Overall chance of stillbirth is low –> ABORTION NOT ENCOURAGED
Secondary Infection
- Reactivation is common during pregnancy
- Mother: Asymptomatic
- Foetus: very low risk (<1%) - maternal IgG clears virus quickly
Most cases in HK are secondary infections however more cases of primary infection recently due to less seropositivity in those of child-bearing age (less childhood infections)
CMV diagnosis: maternal infection, congenital infection in foetus specimen and method, congenital infection in newborn specimen and method (why not serology?)
Maternal infection:
- active search/screening ineffective because most adults are IgG+ve
Congenital infection in foetus:
- AMNIOTIC FLUID
- PCR or Virus isolation
- usually at 16-18 wks – but may be false negative if foetal renal system not fully developed yet (another sample at 21 wks; not popular choice since invasive)
Congenital infection in newborn:
- URINE or SALIVA
- PCR or Virus isolation
- WITHIN 3 WEEKS of birth (possible perinatal infection after 3 weeks)
- not IgM due to false +ve/-ve
- not Ab titres due to passive IgG from mother
Varicella Zoster Virus recap: primary infection symptoms in childhood and adults, latency, reactivation symptoms (4)
Primary infection: chickenpox
- common childhood infection
- vesicular rash, pustular, crusting
- more complications in adults (pneumonitis, encephalitis)
- life-threatening in neonates and immunodeficiency
Latency in DRG
Reactivation: shingles (zoster)
- pain and numbness before rash
- vesicular lesions in dermatome
- complications e.g. ophthalmic zoster, Ramsay-hunt
- post-herpetic neuralgia
- dissemination in immunodeficiency
> 90% HK adults are IgG+ve
VZV infection in pregnancy: effects on mother, risks, effects on foetus at each stage, outcomes of disease
Primary infection
- Mother: similar features as non-pregnant adults e.g. encephalitis, hepatitis, secondary bacterial infection, haemorrhage; also GBS and Reye’s syndrome
- – pneumonitis risk higher in 3rd trimester and in smokers (alters immunity, increase O2 demand, 10-20% incidence, day 2-5 onset, 40% mortality)
- Foetus: affected at ALL STAGES
- if severe maternal infection –> abortion
- 1st 20 wks ==> congenital varicella syndrome (1-2%)
- 2nd half ==> zoster in infancy
- perinatal ==> severe neonatal varicella
Congenital Varicella Syndrome:
- 2% – not a reason for abortion
- Zoster embryopathy: low birth weight, cutaneous scarring, limb hypoplasia, microcephaly, mental retardation, cortical atrophy
Zoster in infancy
- no embryopathy
- reactivation in infancy
Perinatal Varicella:
- maternal chickenpox 5 days before – 2 days after delivery
- inadequate time for mother produce Ab and pass to foetus in utero
- highest risk, potentially fatal
Secondary infection
- no harm to foetus
VZV diagnosis: clinical vs lab, specimens of choice and methods (2)
Characteristic clinical presentations
Lab Dx seldom necessary
- SKIN SCRAPING –> IMMUNOFLUORESCENCE for direct Ag detection (sensitive, rapid and specific)
- VESICULAR FLUID –> virus isolation or PCR
VZV treatment, prevention (3)
Antiviral: ORAL ACYCLOVIR indicated for all pregnant women with uncomplicated varciella (safe for breastfeeding; beware of overdose and maintain adequate hydration)
Expensive and limited supply
Post-exposure prophylaxis in high risk groups (VZIG)
- perinatal infection
- susceptible pregnant women (IgG-ve and exposed to infectious person i.e. 2 days before rash to rash crusting)
Chickenpox vaccine (part of MMRV)
- live attenuated (contraindicated in 1st trimester of pregnancy)
- 2 doses for adults, safe, 100% efficacy
- recommended for children at 1 yr old (CIP), all healthcare workers and adults
Zoster vaccine
- prevention of reactivation in >60
- has much higher conc of virus than MMRV – don’t give as primary prevention!
Parvovirus B19 transmission, presentation (4), effect on foetus (4)
Transmission by aerosol route
30% IgG +ve in HK
Presentation in Immunocompetent host:
- 50% asymptomatic
- non-specific flu like illness
- rash (fifth disease, erythema infectiosum)
- arthritis (LARGE JOINTS - c.f. postnatal rubella infection) - 80% females
- haemolytic anaemia, aplastic anaemia, encephalitis
Foetus:
- 1st 20 wks – transmission 25-33%
- -> anaemia, hydrops foetalis, foetal loss (9%)
- If they survive: most are healthy and given transfusion for foetal anaemia
Serology: IgM
Zika virus: transmission, common source, presentation in adults, presentation in foetus, lab diagnosis of infection and foetal infection
Flaviviridae family
- vector-borne disease (Aedes species of mosquito)
Infection mostly among return travellers from endemic areas
Transmission: mosquito bite, sexual, intrauterine
Presentation:
- 80% asymptomatic
- Dengue-like disease: fever, rash, myalgia, joint pain, conjuncitivitis
- Brazil 2015 outbreak –> GBS, microcephaly
- eye/ neural tube defects/ CNS dysfunction –> higher risk if infection during 1st trimester
Lab diagnosis:
- URINE and BLOOD for RT-PCR if within 14 days of symptoms or exposure
- IgM if onset >14 days or exposure 2-12 weeks prior
- – 2nd sample 2 weeks after 1st sample for rising Ab titre
- neurological symptoms: CSF for PCR (<7 days) or serology (>7 days); blood/urine from baby
Fetal infection dx:
- amniotic fluid for RT-PCR
- collect cord blood for RT-PCR or IgM testing
