untitled2. 3C Protease Inhibitors • Block protein synthesis • Phase I trials
3. Capsid-binding compounds • Prevent viral attachment & uncoating • Pleconaril (Picovir®)
Pleconaril in neonatal enteroviral sepsis
• Phase III open-label compassionate use trial • 14 subjects with proven EV infection • 12 treated with full 7 day course • 10 survived
Cytomegalovirus
Cytomegalovirus
Epidemiology
• Breastmilk • Cervical secretions • Transplacental • Transplant tissue
• 10% shedding virus at any one time
• 90% of immunosuppressed patients
Seroepidemiology 2
• Increased rate during childhood, adolescence and child-bearing years
• Developed countries: 1 year 14% 2 years 26% 10 years 33% Adults 40 - 60%
Seroepidemiology 3
• Developing countries:
Routes of Infection
• Later - toddlers in day-care etc.
• Adults - sexual / non-sexual close contact
Congenital CMV
– 1o infection (3-6/1000 pregnancies) – 10% symptomatic – Mortality 10-30% – Long-term sequelae
Rash
Hepatosplenomegaly
infection
• Reactivation:
Neonatal disease
• Asymptomatic (90%):
Serology
1. Was the maternal illness at 6/40 gestation a primary
CMV infection ?
• CMV culture unhelpful
2. Risks to the fetus
• Fetal infection risk: 20-50%
• 90% chance of being normal at birth with 10-15% chance of later problems
• 10% chance of symptomatic congenital CMV at birth with high risk (>90%) of long term problems
3. How can we confirm fetal infection ?
3. Confirming fetal infection
• Amniotic fluid - culture + PCR sensitivity dependent on timing >95% after 20/40 80% before 20/40
• Fetal (cord) blood: IgM sensitivity 70-80%, specificity 97% CMV culture sensitivity 10% non-specific - anaemia, platelets, LFT
• Serial ultrasound
4. If the fetus is infected, what action should be taken ?
4. Action if fetus infected
• 10-20% of infected fetuses have symptomatic CMV at birth
• Counselling for termination ??
• Serial ultrasounds - NAD
• 39/40, spontaneous NVD • Female, 3760g, Apgar 61, 95
• Active and generally well • Bilateral ‘clicky hips’ • Urine CMV culture 1/52 - no growth
5. If the baby is normal at birth, what action should be
taken ?
5. Action if baby normal at birth
• Serial audiometry - deafness 5-15% (3% bilateral) delayed up to 5 years
• Serial visual assessment - chorioretinitis / optic atrophy (2%)
• Psychomotor assessment - microcephaly, dev. delay, behavioural
• Pneumonitis 1 - 4 months, rare
6. If the baby is symptomatic at birth, what action should
be taken?
• Confirm diagnosis with CMV culture in first 2 weeks
• Cranial ultrasound + other imaging • Multidisciplinary approach to management
- developmental paediatrician - early intervention program - physiotherapy, speech & O.T. - audiometry, visual assessment
Ganciclovir Treatment
neonates • 12mg/Kg/day for 6/52 • Reduced viraemia and shedding • Long-term follow-up required • Concerns about carcinogenicity and
reproductive toxicity
CMV Vaccine
• Experimental live attenuated vaccine • Reduces occurrence of severe illness in
immunosuppressed subjects by 80-100% • No effect on rate of infection • Degree of fetal protection unknown
• Future: DNA, subunit, vector vaccines
Rubella
Rubella • 1752 Described in Germany • 1881 Accepted as a distinct disease • 1938 Viral aetiology confirmed • 1941 Associated with congenital syndrome • 1962 Isolated in tissue culture • 1967 Commercial serological tests • 1969 First vaccines • 1971 Vaccination in Australia commenced
(boys vaccinated from 1989)
Rubella Virus
outbreak
• IP 14-21 days
Rubella – Clinical Presentation
– maculopapular; face → trunk → limbs
• Polyarthralgia / arthritis
• Risk of damage • <4/40 85% • 4-8/40 20% • 9-12/40 5% • >16/40 Rare
• Gestational age influences defects • >12/40 retinopathy and deafness only
Congenital Rubella Syndrome
• 1/3 live with parents
Congenital Rubella Syndrome
thrombocytopenia, radiolucent bone disease • Late endocrinopathies - IDDM (20%; 200x general
population); thyroid dysfunction (5%)
Investigation of illness/contact
• Serological confirmation • IgG seroconversion or rising titre • IgM – confirm with re-bleed or fractionation
• Fetal diagnostic testing • AF, cord blood, CVS • Fetal IgM • PCR
• Vaccine (live attenuated) • 95% immunogenic • 90% lifelong protection
• Seronegative women vaccinated postpartum • Avoid vaccination during pregnancy
• Immunoglobulin • Reduces clinical infection (87% to 18%) • May use as pre-exposure prophylaxis • May not influence foetal infection • Use if termination not possible
Rubella - Prevention
Herpes Simplex Virus
– 1o infection near delivery • SEM, encephalitis, disseminated
– Type-specific serology for clinically discordant couples
Case - Baby Nadia
• 38/40, uneventful pregnancy • NVD, Apgar 91 105, 3420g
• Day 4 • Reduced feeding with weak cry • Coughing and cyanosis with feeds • Febrile, 38.7oC
Investigations
• toxic granulation
→ Ampicillin + gentamicin
D ay
• no evidence of TOF • suggestive of malrotation
– Abdominal ultrasound • whirlpool sign
• Day 6-7 • + acyclovir • decreased urine output • generalised oedema
• Day 8 • oozing from venepuncture sites • worsening LFT’s and clotting
Results
Diagnosis ?
• Father: recurrent cold sores
Progress
• Day 9 • Rectal bleeding - 3 litres in 48 hours • Oliguric renal failure
• Scalp lesion • HSV IF positive (day 9) • HSV PCR positive (day 9) • HSV-1 isolated (day 11)
• Cerebrospinal fluid • HSV + EV PCR negative
Scalp lesion: immunofluorescence HSV-1
Further Progress
• Day 22 – ascites, unsettled – contrast study: no perforation – peritoneal drain: PMN +++, E. coli
→ vancomycin, gentamicin, metronidazole
Progress - Day 23
Laparotomy - Day 23
MWt Colon HSV-1 Water HSV-2
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