1. Infections in the Newborn and beyond
Tony Ryan
University College Cork

2. Objectives The common means of transmission of these infections.
The major manifestations of congenital and perinatal infections.
Diagnose and prevent these infections.
Some pictures
The infectious diseases Lucky Box

3. Infection in the Newborn
Overall < 1%
NICU 16%
VLBW (<2500 g) 30%
Mortality 30%

4. Perinatal acquired infections
Transplacental
Intrapartum (vertical)
Postnatal (horizontal)

5. 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)

6. 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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8. 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

9. Clinical Features maculopapular rash lymphadenopathy fever
arthropathy (up to 60% of cases)

10. 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

11. 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

12. Outcome Congenital Rubella
1/3 rd will lead normal independent lives
1/3 rd will live with parents
1/3rd will be institutionalised

13. Prevention Antenatal screening Non-immune women vaccinated post partum
Effective live attenuated vaccine (95% efficacy)
Universal vaccination (MMR)
Selectively vaccination of schoolgirls

15. Congential CMV Herpes virus Large DNA virus Characteristics Infection
H simplex (i/ii), Varicella, EBV, HHV 6,7,8
Large DNA virus
inclusion bodies
Characteristics
latency
reactivation
Infection
primary, recurrent, reactivation

16. 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%.

17. Congenital Infection
Isolation of CMV from the saliva or urine within 3 weeks of birth.
Commonest congenital viral infection, affects % 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.

18. 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.

19. 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)

20. Management Of Congenital CMV
Primary Infection - termination of pregnancy?
40% chance of the fetus being infected.
10% chance that congenitally infected baby will be symptomatic at birth or develop sequelae later in life.
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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24. Parvovirus B 19 1/400 pregnancies 15% risk of miscarriage
3% risk of hydrops
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25. 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.

26. 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 been successfully treated in utero by intrauterine transfusions

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28. 2 infected babies with HIV protocol
Rotunda Hospital ( )
65 HIV positive women
2 infected babies with HIV protocol
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37. Herpetic Stomatitis
Herpes Simplex
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38. Herpangina
Coxsakie virus
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41. 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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43. Mumps
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44. Blueberry muffin baby
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46. Prevention of Infection
Reducing stress and overwork
Controlling antibiotic use
Encourage use of human milk
Microbiological surveillance

47. Any Questions?
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49. Adenoviruses cause Gastroenteritis Croup
Lower respiratory tract infections
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50. 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!

51. Features of the Host Portals of entry Host immunity
(skin, cord, cannulae)
Host immunity
(poor local inflammatory response)
Antibiotic exposure
(superinfection, yeasts)
Prematurity
(immune-deficient, sicker)

52. Congenital Viral Infections
An Overview

53. 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

54. Disease is spread by Faecal - oral route Respiratory (coughing)
gastroenteritis
Respiratory (coughing)
colds, viruses
Person to person
Streptococcus, cold sores, scabies
Contact with blood, urine, saliva
CMV, hepatitis

55. Incidence of Cytomegalic Disease

56. 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.

57. 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

58. Laboratory Diagnosis Diagnosis of acute infection
Rising titres of antibody (mainly IgG)
Presence of rubella-specific IgM -

59. Typical Serological Events following acute rubella infection
level

60. 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 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 lesions from the mother or a herpetic whitlow in a nurse.

61. 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.

62. 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

63. Prevention of Infection
Reduce contact
Breast feeding
Early discharge home
Environment
Unit design
Equipment (own stethescope, thermometer, humidification, ventilators)
Controlling admissions (transitional care)

64. Prevention of Infection
Cleanliness of baby
Cord care
dry care vs alcohol swabs
Other babies, staff, visitors
RSV, varicella zoster
Invasive procedures
sterile technique

65. Cytomegalovirus CMV

66. Epidemiology of CMV Shed Transfer body secretions, urine
Intimate contact
transplacental
during birth
breast feeding
blood products
organ transplantation

67. 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

68. CMV in Toddlers Day care Can shed for up to a year Plastic toys
Hands of day care workers

69. CMV in Pregnancy 90% of women asymptomatic
Primary infection 1 - 4% of pregnancies
Foetal transmission % (~ 40%)
More neuro sequelae in infants of primary infection
Maternal antibody does not protect against infection but may be associated with less sequelae

70. Diagnosis in Pregnancy
Usually asymptomatic
Sometimes ‘flu-like illness (like EBV)
Conversion to IgG positive
Rising titres not helpful

71. CMV and foetus Transmission can occur in all trimesters
Adverse neuro outcome more likely in 1st trimester infection
Oligohydramnios
polyhydramnios
IUGR
non-immune hydrops
ascites
effusions
Microcephaly
dilated ventricles
calcification
pseudomeconium ileus

72. 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

73. CMV and newborn 90% newborn asymptomatic 10% have clinical signs SGA
microcephaly
calcification
chorioretinitis
hearing loss
hepatosplenomegaly
jaundice
Petechiae
thrombocytopenia
meningitis

74. 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

75. 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”

76. 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%

77. Prevention of CMV Vaccine Focus on high-risk (childbearing) Education
CMV negative blood

78. Follow up Neuro-developmental Opthalmology Hearing (BAER) Educational
dyspraxia
learning difficulties

79. Better outcome Worse outcome Reticulo-endothelial involvement
When CNS not involved
Worse outcome
Chorio-Retinitis
Microcephaly
Early neurological findings

80. ‘Silent’ CMV outcome
Hearing loss 15%
mostly normal neurologically

81. Infectious diseases (U.S.) pre vaccination and 1997

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