Download Congenital Infections

Infections in the Newborn and
beyond
Tony Ryan
University College Cork
Objectives
1. The common means of transmission of
these infections.
2. The major manifestations of congenital
and perinatal infections.
3. Diagnose and prevent these infections.
Some pictures
• The infectious diseases Lucky Box
Infection in the Newborn
•
•
•
•
Overall < 1%
NICU 16%
VLBW (<2500 g) 30%
Mortality 30%
Perinatal acquired infections
• Transplacental
• Intrapartum (vertical)
• Postnatal (horizontal)
Colonization
•
•
•
•
Intrapartum (mothers flora)
Postnatal (ward environment)
CUMH 8500 deliveries
Group B Streptococcus
– 25% of mothers colonized
(2000)
– 50 % of babies colonized (1000)
– 1-3% of babies infected (10-30)
Preventing infection
• Handwashing
– before and after touching any
baby
– no watches, bracelets, nail varnish
– sleeves rolled up
– full scrub on arrival in NICU
– 10 second wash in between
– alcohol solutions
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2000
Congenital, Perinatal, and Neonatal
Viral Infections
TORCHS
Intrauterine Viral Infections
Rubella
Cytomegalovirus (CMV)
Parvovirus B19
Varicella-Zoster (VZV)
Enteroviruses
HIV
HTLV-1
Hepatitis C
Hepatitis B
Lassa Fever
Japanese Encephalitis
Perinatal and Neonatal
Infections
Human Herpes Simplex
VZV
Enteroviruses
HIV
Hepatitis B
Hepatitis C
HTLV-1
Clinical Features
• maculopapular rash
• lymphadenopathy
• fever
• arthropathy (up to 60% of cases)
Rubella
History
1881 Rubella accepted as a distinct disease
1941 Associated with congenital disease (Gregg)
1961 Rubella virus first isolated
1967 Serological tests available
1969 Rubella vaccines available
Risks of rubella infection during
pregnancy
Preconception
minimal risk
0-12 weeks
100% risk of fetus being congenitally infected
Spontaneous abortion occurs in 20% of cases.
13-16 weeks
deafness and retinopathy 15%
after 16 weeks
normal development, slight risk of deafness
and retinopathy
Outcome Congenital Rubella
• 1/3 rd will lead normal independent lives
• 1/3 rd will live with parents
• 1/3rd will be institutionalised
Prevention
Antenatal screening
•
Non-immune women vaccinated post partum
•
Effective live attenuated vaccine (95% efficacy)
•
Universal vaccination (MMR)
•
Selectively vaccination of schoolgirls
Congential CMV
• Herpes virus
– H simplex (i/ii), Varicella, EBV, HHV 6,7,8
• Large DNA virus
– inclusion bodies
• Characteristics
– latency
– reactivation
• Infection
– primary, recurrent, reactivation
Cytomegalovirus
• member of the herpesvirus
• primary infection usually asymptomatic. Virus
then becomes latent and is reactivated from
time to time.
• transmitted by infected saliva, breast milk,
sexually and through infected blood
• 60% of the population eventually become
infected. In some developing countries, the
figure is up to 95%.
Congenital Infection
• Isolation of CMV from the saliva or urine within 3
weeks of birth.
• Commonest congenital viral infection, affects 0.3 - 1% of
all live births.
• The second most common cause of mental disibility
after Down's syndrome
• Transmission to the fetus may occur following primary
or recurrent CMV infection. 40% chance of transmission
to the fetus following a primary infection.
Cytomegalic Inclusion Disease
• CNS abnormalities
– - microcephaly, mental retardation, spasticity, epilepsy,
– periventricular calcification.
• Eye - choroidoretinitis and optic atrophy
• Ear - sensorineural deafness
• Liver - hepatosplenomegaly and jaundice which is due to hepatitis.
• Lung - pneumonitis
• Heart - myocarditis
• Thrombocytopenic purpura, Haemolytic anaemia
• Late sequelae in individuals asymptomatic at birth
– hearing defects and reduced intelligence.
Diagnosis
• Isolation of CMV from the urine or saliva of the
neonate.
• Presence of CMV IgM from the blood of the
neonate.
• Detection of Cytomegalic Inclusion Bodies from
affected tissue (rarely used)
Management Of Congenital CMV
• Primary Infection - termination of pregnancy?
– 40% chance of the fetus being infected.
– 10% chance that congenitally infected baby will be
birth or develop sequelae later in life.
symptomatic at
– 4% chance (1 in 25) of giving birth to an infant with CMV problems.
• Recurrent Infection - termination not recommended as risk of
transmission to the fetus is much lower.
• Antenatal Screening – impractical.
• Vaccination - may become available in the near future.
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2000
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Parvovirus B 19
1/400 pregnancies
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15%
3%
risk of miscarriage
risk of hydrops
Parvovirus
• Causative
agent
of
Fifth
disease
(erythema
infectiosum), clinically difficult to distinguish from
rubella.
• Also
causes
aplastic crisis in individuals
with
haemolytic anaemias as erythrocyte progenitors are
targeted.
• Spread
by the respiratory route, 60-70% of the
population is eventually infected.
• 50% of women of childbearing age are susceptible to
infection.
Congenital Parvovirus Infection
• Known to cause fetal loss
– hydrops fetalis; severe anaemia, congestive heart failure, generalized
oedema and fetal death
• No evidence of teratogenecity.
• Risk of fetal death highest in second trimester (12%).
• Minimal risk to the fetus in first or third trimesters
• Maternal infection during pregnancy does not warrant termination
of pregnancy.
• Cases of diagnosed hydrops fetalis had
treated in utero by intrauterine transfusions
been
successfully
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2000
Rotunda Hospital (1995-2002)
65 HIV positive women
2 infected babies with HIV protocol
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Herpetic Stomatitis
Herpes Simplex
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Herpangina
Coxsakie virus
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Neonatal Varicella
• VZV can cross the placenta in the late stages of pregnancy
• Neonatal varicella may vary from a mild disease to a fatal
disseminated infection.
• If rash in mother occurs more than 1 week before delivery, then
sufficient immunity would have been transferred to the fetus.
• Zoster immunoglobulin should be given to susceptible pregnant
women who had contact with suspected cases of varicella.
• Zoster immunoglobulin should also be given to infants whose
mothers develop varicella during the last 7 days of pregnancy or the
first 14 days after delivery.
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Mumps
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Blueberry muffin baby
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Prevention of Infection
•
•
•
•
Reducing stress and overwork
Controlling antibiotic use
Encourage use of human milk
Microbiological surveillance
Any Questions?
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Adenoviruses cause
Gastroenteritis
Croup
Lower respiratory tract
infections
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Summary CMV
• 1% newborns infected (0.2% - 2.5%)
• 90% asymptomatic
• Higher infection rate with primary maternal
(50%) than after recurrent maternal (1%)
• Urine culture (gold standard)
• worse outcome with
– retinitis, microcephaly, neurological
findings
• Prevention is better than cure!
Features of the Host
• Portals of entry
– (skin, cord, cannulae)
• Host immunity
– (poor local inflammatory response)
• Antibiotic exposure
• (superinfection, yeasts)
• Prematurity
– (immune-deficient, sicker)
Congenital Viral Infections
An Overview
Congenital Rubella Syndrome
Classical triad consists of cataracts, heart defects, and sensorineural
deafness. Many other abnormalities had been described and these are
divided into transient, permanent and developmental.
Transient
low birth weight, hepatosplenomegaly, thrombocytopenic purpura
bone lesions, meningoencephalitis, hepatitis, haemolytic anemia
pneumonitis, lymphadenopathy
Permanent
Sensorineural deafness, Heart Defects (peripheral pulmonary stenosis,
pulmonary valvular stenosis, patent ductus arteriosus, ventricular
septal defect) Eye Defects (retinopathy, cataract, microopthalmia,
glaucoma, severe myopia) Other Defects (microcephaly, diabetes
mellitis, thyroid disorders, dermatoglyptic abnormalities
Developmental Sensorineural deafness, Mental retardation, Diabetes Mellitus,
thyroid disorder
Disease is spread by
• Faecal - oral route
– gastroenteritis
• Respiratory (coughing)
– colds, viruses
• Person to person
– Streptococcus, cold sores, scabies
• Contact with blood, urine, saliva
– CMV, hepatitis
Incidence of Cytomegalic Disease
U.S.A.
U.K.
No. of live births p.a.
3,000,000
700,000
Rate of congenital CMV
1%
0.3%
No. of infected infants
30,000
2100
Symptomatic at birth (5 - 10% )
1,500-3,000
105
Fatal disease (~ 20% )
300-600
22
No. with sequelae (90% of survivors)
1080-2160
83
Asymptomatic (90 - 95% )
27000
1995
No. with late sequelae
1350-4550
315
Characteristics of Rubella
• RNA enveloped virus, member of the togavirus
family
• Spread by respiratory droplets.
• In the prevaccination era, 80% of women were
already infected by childbearing age.
Infection increased by certain
features of microorganisms
• Pathogenicity
– GBS, CONS, E.Coli, etc.
• Dose
– heavy colonization increases infection
• Competition
– e.g. inhibition of yeasts by bacteria
Laboratory Diagnosis
Diagnosis of acute infection
• Rising titres of antibody (mainly IgG)
• Presence of rubella-specific IgM -
Typical Serological Events following
acute rubella infection
level
Neonatal Herpes Simplex (1)
• Incidence of neonatal HSV infection varies inexplicably from country
to country e.g. from 1 in 4000 live births in the U.S. to 1 in 10000
live births in the UK.
• The baby is usually infected perinatally during passage through the
birth canal.
• Premature rupturing of the membranes is a well recognized risk
factor.
• The risk of perinatal transmission is greatest when there is a florid
primary infection in the mother.
• There is an appreciably smaller risk from recurrent lesions in the
mother, probably because of the lower viral load and the presence of
specific antibody.
• The baby may also be infected from other sources such as oral
Neonatal Herpes Simplex (2)
• The spectrum of neonatal HSV infection varies from a mild disease
localized to the skin to a fatal disseminated infection.
• Infection is particularly dangerous in premature infants.
• Where dissemination occurs, the organs most commonly involved are
the liver, adrenals and the brain.
• Where the brain is involved, the prognosis is particularly severe. The
encephalitis is global and of such severity that the brain may be
liquefied.
• A large proportion of survivors of neonatal HSV infection have
residual disabilities.
• Acyclovir should be promptly given in all suspected cases of neonatal
HSV infection.
• The only means of prevention is to offer caesarean section to
mothers with florid genital HSV lesions.
Varicella-Zoster Virus
• 90% of pregnant women already immune, therefore primary infection
is rare during pregnancy
• Primary infection during pregnancy carries a greater risk of severe
disease, in particular pneumonia
First 20 weeks of Pregnancy
up to 3% chance of transmission to the fetus,
recognised congenital varicella syndrome;
• Scarring of skin
• Hypoplasia of limbs
• CNS and eye defects
• Death in infancy normal
Prevention of Infection
•
•
•
•
Reduce contact
Breast feeding
Early discharge home
Environment
– Unit design
– Equipment (own stethescope,
thermometer, humidification, ventilators)
• Controlling admissions (transitional
care)
Prevention of Infection
• Cleanliness of baby
• Cord care
– dry care vs alcohol swabs
• Other babies, staff, visitors
– RSV, varicella zoster
• Invasive procedures
– sterile technique
Cytomegalovirus CMV
Epidemiology of CMV
• Shed
– body secretions, urine
• Transfer
–
–
–
–
–
–
Intimate contact
transplacental
during birth
breast feeding
blood products
organ transplantation
CMV in the newborn
• 1% newborns infected (0.2% - 2.5%)
• Higher infection rate with primary
maternal (50%) than after recurrent
maternal (1%)
• 50% of babies fed CMV infected
breast milk get infection
CMV in Toddlers
•
•
•
•
Day care
Can shed for up to a year
Plastic toys
Hands of day care workers
CMV in Pregnancy
• 90% of women asymptomatic
• Primary infection 1 - 4% of
pregnancies
• Foetal transmission 25 - 75% (~ 40%)
• More neuro sequelae in infants of
primary infection
• Maternal antibody does not protect
against infection but may be
associated with less sequelae
Diagnosis in Pregnancy
•
•
•
•
Usually asymptomatic
Sometimes ‘flu-like illness (like EBV)
Conversion to IgG positive
Rising titres not helpful
CMV and foetus
• Transmission can occur in all trimesters
• Adverse neuro outcome more likely in 1st
trimester infection
Oligohydramnios
Microcephaly
polyhydramnios
dilated ventricles
IUGR
calcification
non-immune
hydrops
pseudomeconium
ileus
ascites
effusions
Diagnosis in foetus
• Remember most foetuses look normal
• Ultrasound findings
• CMV IgM (sensitivity = 75%)
– negative result does not exclude infection
• Amniocentesis/cordocentesis
– culture/PCR
– LFTs, thrombocytopenia, leucopenia
• Antenatal counseling difficult
CMV and newborn
• 90% newborn asymptomatic
• 10% have clinical signs
SGA
hepatosplenomegaly
microcephaly
jaundice
calcification
Petechiae
chorioretinitis
thrombocytopenia
hearing loss
meningitis
Lab diagnosis in newborn
• Urine culture (gold standard)
– positive in first 3 weeks suggests congenital
• CMV IgM (sensitivity = 75%)
– negative result does not exclude infection
• CMV PCR (urine)
• LFT’s, thrombocytopenia, anaemia,
leucopenia
Long term Follow-up essential
“When the rockets go up
Who cares where they come
down
That’s not my department
Says Werner von Braun”
CMV in older
children/adolescents
•
•
•
•
•
Intrafamilial
sexual contact
blood products
Day care workers
Socioeconomic
– developing countries (80% of 3 year olds;
100% of adults)
– UK/USA upper SE class 40-60%; lower
SE class 80%
Prevention of CMV
•
•
•
•
Vaccine
Focus on high-risk (childbearing)
Education
CMV negative blood
Follow up
•
•
•
•
Neuro-developmental
Opthalmology
Hearing (BAER)
Educational
– dyspraxia
– learning difficulties
Better outcome
• Reticulo-endothelial involvement
• When CNS not involved
Worse outcome
•Chorio-Retinitis
•Microcephaly
•Early neurological findings
‘Silent’ CMV outcome
• Hearing loss 15%
• mostly normal neurologically
Infectious diseases (U.S.)
pre vaccination and 1997
Diptheria (1921)
206,939
5
Measles
(1941)
894,134
135
Mumps
(1968)
152,209
135
Pertussis (1934)
265,269
5,519
Polio
(1952)
21,269
0
Rubella
(1968)
57,686
161
Tetanus
(1948)
1560
43
TB
(1948)
20,000
165
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© S.T.A.B.L.E.
2000
®
© S.T.A.B.L.E.
2000