Infections in the Newborn and beyond

Tony RyanUniversity College Cork

Objectives1. 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

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

Congenital, Perinatal, and Neonatal Viral Infections

TORCHSIntrauterine Viral Infections

RubellaCytomegalovirus (CMV)Parvovirus B19Varicella-Zoster (VZV)EnterovirusesHIVHTLV-1Hepatitis CHepatitis BLassa FeverJapanese Encephalitis

Perinatal and Neonatal Infections

Human Herpes SimplexVZVEnterovirusesHIVHepatitis BHepatitis CHTLV-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 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.

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

Parvovirus B 191/400 pregnancies

15% risk of miscarriage3% 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 been successfully treated in utero by intrauterine transfusions

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

Rotunda Hospital (1995-2002)

65 HIV positive women

2 infected babies with HIV protocol

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

Herpetic Stomatitis

Herpes Simplex

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

Herpangina

Coxsakie virus

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

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.

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

Mumps

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

Blueberry muffin baby

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

Prevention of Infection• Reducing stress and overwork • Controlling antibiotic use• Encourage use of human milk• Microbiological surveillance

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

Any Questions?Any Questions?

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

Adenoviruses causeGastroenteritis

Croup

Lower respiratory tract infections

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

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

polyhydramnios

IUGR

non-immune hydrops

ascites

effusions

Microcephaly

dilated ventricles

calcification

pseudomeconium ileus

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

microcephaly

calcification

chorioretinitis

hearing loss

hepatosplenomegaly

jaundice

Petechiae

thrombocytopenia

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 upWho cares where they

come downThat’s not my departmentSays 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 1997Diptheria (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

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000

© S.T.A.B.L.E.®

2000© S.T.A.B.L.E.®

2000