Transcript Neonatal Infections

Neonatal Infections
Catherine M. Bendel, M.D.
Associate Professor of Pediatrics
Director, Neonatal-Perinatal Medicine Fellowship Program
Questions?
• Why are infants,
especially premies,
more susceptible to
infections?
• What are the clinical
manifestations of
neonatal infections?
• Bacterial?
• HSV?
• How to prevent
infections?
• Antibiotics indications,
contraindications,
cautions, resistance,
etc.
• How to interpret labs?
• Any precautions with
lines?
Objectives
• To briefly review neonatal immunology and why
neonates are so susceptible to infections
• To review the epidemiology, clinical presentation,
diagnosis and treatment of the most common
bacterial and HSV neonatal infections.
• To review modes of infection prevention.
• To differentiate between preterm and term infants
in all these areas
“Prematurity is an infectious disease.”
- James Todd, M.D.
Why are infants,
especially premies,
more susceptible to
infections?
Neonatal Immune System
• All neonates relatively immunocompromised
• Immature and Ineffective:
– Antibodies
– Complement
– Neutrophils
– Skin / mucosal barriers
Antibody
Antibodies
Infectious agent
Immunity
Figure 1.1 Antibodies (anti- foreign bodies) are produced by host while cells on contact with the invading micro-organism
which is acting as an antigen (e.g. generates antibodies). The individual may then be immune to further attacks.
(Modified From: Roitt, I: Essential Immunology, 4th edition, Blackwell Scientific Publications, 1980)
Antibodies
Infectious agent
x
x
Immunity
No contact with infectious agents = no antibody production
Maternal Transfer of Antibodies
• Antibody transfer
increases with GA
• Most during 3rd
trimester
• No guarantee
maternal antibodies
present to the
infecting organism
Remington and Klein, Sixth Edition, 2006
Complement
Neutrophils
Neonatal Neutrophils
• Immature
–
–
–
–
 Chemotaxis
 Deformability
 Phagocytosis
 Storage pool
• Adults 14-fold >
circulating pool
• Neonates only 2-fold
Manroe et al, J Pediatr, 1979
“Normal” VLBW neonates
Mouzinho et al, Pediatr 94:76, 1994
“Normal” VLBW neonates
Mouzinho et al, Pediatr 94:76, 1994
Neonatal Barriers to Infection
Neonatal Anatomic Barriers
• Immature skin and mucosal surfaces
– layers
– junctions between cells
– secretory IgA
• Umbilical cord
• Breaches - catheters, tape
Invasive Fungal Dermatitis in a
VLBW infant
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
JL Rowen, Sem Perinatal 27:406-413, 2003
QuickTime™ and a
TIFF (Uncompressed) decompressor
are needed to see this picture.
Epidemiology
Neonatal Sepsis: Incidence
• 2/1000 live births with culture proven sepsis
– Bacterial / Viral / Fungal
– 80% infants develop bacterial sepsis
– 20% infants perinatally acquired viral infections
– ~ 25% of infected infants have meningitis
• Higher rate with preterm birth
– 26/1000 preterm infants with BW < 1000g
– 8-9/1000 preterm infants with BW 1000-2000g
Remington and Klein, Sixth Edition, 2006
Neonatal Bacterial Sepsis:
Disease Patterns
• Early Onset Neonatal
Sepsis (EONS)
– Fulminant, multisystem illness
– < 5 days old
– Obstetrical
complications
– Prematurity
– Perinatal acquisition
– High mortality, 5-50%
• Late Onset Neonatal
Sepsis (LONS)
– Sepsis or meningitis
– 5 days to 3 months old
– Perinatal or postnatal
acquisition
– Lower mortality, 2-6%
Neonatal Infections
Sepsis
Meningitis
Pneumonia
Otitis Media
Diarrheal Disease
UTI
Osteomyelitis
Suppurative Arthritis
Conjunctivitis
Orbital Cellulitis
Cellulitis - - Omphalitis
Bacterial / Viral / Fungal
Etiologic Agents of Neonatal Sepsis
Frequency(%)
 Group B Streptococci
 Escherichia coli
Streptococcus viridans
Staphylococcus aureus
Enterococcus spp
Coagulase-negative staphylococci
Klebsiella pneumoniae
Pseudomonas spp
Serratia marcescans
Others
*Schuchat et al, Pediatrics 105: 21-26, 2000
40
17
7
6
6
5
4
3
2
10
Etiologic Agents of Neonatal Meningitis
Gram Positive Bacteria;
Frequency (%)
 Group B Streptococci
Listeria monocytogenes
Miscellaneous gram-positives
53
7
6
Gram Negative Bacteria:
 Escherichia coli
Klebsiella species
Haemophilus influenzae
Miscellaneous gram-negatives
19
8
1
8
Anaerobes
Feigen & Cherry, Fifth Edition, 2004
3
Incidence of Neonatal
Group B Streptoccal Sepsis
• 5-35% Pregnant women colonized
• 1/100-200 colonized women will have an
infant with early onset disease
• 1-7/1000
live births in 1993
• 0.44/1000 live births in 1999
Remington and Klein, Sixth Edition, 2006
Cases per 1000 live births
Rate of Early- and Late-onset GBS Disease
in the 1990s, U.S.
2.5
Group B Strep
1st ACOG & AAP
Association
statements
formed
CDC draft
2
guidelines published
Consensus
guidelines
1.5
1
0.5
0
1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000
Year
Early-onset
Schrag, New Engl J Med 2000 342: 15-20
Late-onset
Cases per 1000 live births
Rate of Early-Onset Disease by Race
1993-1998
2.5
Black
2
1.5
White
1
0.5
0
1993
Healthy People 2010
1994
Schrag, New Engl J Med 2000 342: 15-20
1995
1996
1997
1998
Current Estimates of Annual GBS
Early-Onset Disease in the U.S.
(2001 provisional, from ABCs/EIP Network)
~4,400 cases prevented per year
1720 cases still occurring annually
70 - 90 deaths
Remains leading infectious cause of neonatal
morbidity and mortality
What do we know about trends in
“other pathogens”?
• Most studies: stable rates of ‘other’ sepsis
• Concerns for increased rates of E. coli, all gram negatives,
or amp-R infections
• Population-based (multicenter) studies find stable rates of
total non-GBS and E. coli
• One multicenter study of very LBW infants found a
decrease in GBS by 4.2 /1,000, but an increase in E coli
rates of 3.6/1,000 (Stoll et al, NEJM, 2002, 347:240-7)
• % of E. coli sepsis w/ amp resistance may be increasing
• Increases restricted to low birth weight or preterm
deliveries
Ampicillin Susceptibility of E. coli from EarlyOnset Sepsis Cases, Full-Term Infants, ABCs,
Selected Counties CA and GA, 1998-2000
Number of Cases
Sensitive
Resistant
9
8
7
6
5
4
3
2
1
0
1998
N=22, p=0.52, linear trend
Hyde et al, Pediatrics 2002;110(4):690-5.
1999
Year
2000
Ampicillin Susceptibility of E. coli from EarlyOnset Sepsis Cases Preterm Infants, ABCs,
Selected Counties CA and GA, 1998-2000
Sensitive
Resistant
Number of Cases
20
15
10
5
0
1998
N=37, p=0.02, linear trend
Hyde et al, Pediatrics 2002;110(4):690-5.
1999
Year
2000
Susceptibility of GBS:
ABC/EIP Isolates, 1995-2000
•
1280 isolates from MN, GA, NY, OR (1173
invasive, 107 colonizing):
–
All susceptible to penicillin, ampicillin,
cefotaxime and vancomycin
–
19% erythromycin resistance
–
11% clindamycin resistance
Risk Factors for Early Onset
Neonatal Sepsis
• Primary (significant)
 Prematurity or low birth weight
– Preterm labor
– Premature or prolonged rupture of membranes
 Maternal fever / chorioamnionitis
– Fetal hypoxia
– Traumatic delivery
• Secondary
– Male
– Lower socioeconomic status
– African-American race
Remington and Klein, Sixth Edition, 2006
Factors associated with early-onset
GBS disease: multivariable analysis
Characteristic
Adjusted RR (95% CI)
GBS screening
0.46 (0.36-0.60)
Prolonged ROM (> 18 h)
1.41 (0.97-2.06)
Pre-term delivery
1.50 (1.07-2.10)
Black race
1.87 (1.45-2.43)
Maternal age <20 y
2.22 (1.59-3.11)
Previous GBS infant
5.54 (1.71-17.94)
Intrapartum fever
5.36 (3.60-7.99)
Schrag et al, NEJM 2002, 347:233-9
Early Onset Neonatal Sepsis:
Risk Factors - Maternal Fever
• Maternal fever is a significant risk factor for
EONS and may add in the identification of
infected but initially asymptomatic infant.
• 5.36 = adjusted RR
• 25% of asymptomatic infants, with culture
positive sepsis, had maternal fever as the ONLY
criteria for evaluation.
Chen et al, J of Perinatal, 2002, 22:653-657
Early Onset Neonatal Sepsis:
Presentation and Diagnosis
Early Onset Neonatal Sepsis:
Signs/Symptoms
?
Early Onset Neonatal Sepsis:
Signs/Symptoms
Strongly suggestive
hypoglycemia / hyperglycemia
hypotension
metabolic acidosis
apnea
shock
DIC
hepatosplenomegaly
bulging fontanelle
seizures
petechiae
hematochezia
respiratory distress
Early Onset Neonatal Sepsis:
Signs/Symptoms
Nonspecific
lethargy, irritability
temperature instability -- hypothermia or fever
poor feeding
cyanosis
tachycardia
abdominal distention
jaundice
tachypnea
Early Onset Neonatal Sepsis:
Signs/Symptoms - Fever
•
The infant with sepsis may have an elevated,
depressed or normal temperature.
•
Fever is seen in up to 50% of infected infants.
•
Fever is more common in term infants, while
hypothermia is more common in preterm infants
•
A single elevated temperature reading or fever as an
isolated finding is infrequently associated with sepsis.
•
Persistent fever for greater than 1 hour is more
frequently associated with infection.
•
Fever occurs more frequently with LONS or with viral,
rather than bacterial, sepsis.
Klein, Sem in Perinat, 5:3-8
Early Onset Neonatal Sepsis:
Laboratory Evaluation
•  Cultures 
• Chest Radiograph
• Complete Blood Cell Count
• Glucose
• Bilirubin
• Liver Function Tests
• Coagulation studies
• C-reactive Protein (CRP)
Early Onset Neonatal Sepsis:
Cultures -- Who and Which?
• Blood culture -- indicated in ALL infants with
suspected sepsis. Repeat cultures indicated if
initial culture positive.
• Urine culture -- low yield in EONS
– + in 1.6% EONS compared to 7.47% LONS
Klein, Sem in Perinat, 5:3-8
Early Onset Neonatal Sepsis:
Cultures -- Who and Which?
• CSF culture -- should always be considered
Meningitis frequently accompanies sepsis
- 50-85% meningitis cases have + blood culture
- Yield reportedly low if respiratory distress is the only
major sign of infection
- Specific signs & symptoms occur in less than 50% of
infants with meningitis
- Using “selective criteria” for obtaining CSF may result in
missed or delayed diagnosis in up to 37% of infants with
meningitis
Wiswell et al, Pediatrics, 1995
Laboratory Diagnosis of
Neonatal Meningitis
CSF
--
> 32 WBC/mm3
> 60% PMN
glucose < 50% - 75% of serum
protein > 150 mg/dl
organisms on gram stain
Early Onset Neonatal Sepsis:
Complete Blood Cell Counts
• Is the CBC helpful as an indicator of early
onset neonatal sepsis?
– Thrombocytopenia frequently
associated with sepsis
– WBC may be high, low or “normal” -timing of the sample important
– Persistent low WBC more predictive of
sepsis than elevated WBC (ANC < 1200)
– I:T quotient unreliable
Early Onset Neonatal Sepsis:
Complete Blood Cell Counts
Early Onset Neonatal Sepsis:
Complete Blood Cell Counts
• Single or serial neutrophil values
DO NOT assist in the diagnosis of
EONS or determining the duration of
therapy
• 99% of asymptomatic, culturenegative neonates > 35 weeks GA had
1 or more “abnormal” WBC values
Early Onset Neonatal Sepsis:
C-Reactive Protein
Early Onset Neonatal Sepsis:
C-Reactive Protein
• Measure of inflammation -- NOT specific for infection
• Elevated CRP, > 10 mg/L (>1 mg/dl), highly associated with
sepsis --- but NOT diagnostic
• Limited by lack of “normal” reference values for <24 hours old
or preterm infants
• Trend with multiple samplings correlates with infection as
takes time to rise -- two samples ~24 hours apart useful
• Potentially useful when maternal antibiotics given pretreatment interferes with cultures
Early Onset Neonatal Sepsis:
Empiric Treatment
Initial:
Ampicillin and Gentamicin IV
(Cefotaxime discouraged)
Duration:
“Rule out sepsis”
Pneumonia
Sepsis
Meningitis
48 - 72 hours
5 - 7 days
7 - 10 days
14 - 21 days
Primarily determined by etiologic organism cultured
Secondarily determined by clinical course/response
?CRP-guided determination of duration?
Remington and Klein, Sixth Edition, 2006
Early Onset Neonatal Sepsis:
Supportive Therapy
•
•
•
•
•
•
Ventilation
BP support - fluids, Dopamine/Dobutamine/HCTZ
TPN
FFP - clotting factors, C3, antibodies
G-CSF - stimulate WBC production/release
Steroids not indicated as anti-inflammatory
Remington and Klein, Sixth Edition, 2006
Treatment of GBS Infections
Initial
- Ampicillin and Gentamycin IV
(Gent synergy for first 3 days)
- May switch to Penicillin G IV
(with confirmation of diagnosis/sensitivities)
Duration (from first negative culture)
Uncomplicated sepsis
10 - 14 days
Meningitis
14 days minimum
Treatment of E. Coli Infections
Ampicillin and an Aminoglycoside IV
With confirmation of diagnosis /sensitivities:
- drop Amp
- substitute a third generation cephalosporin
Duration (from first negative culture)
Uncomplicated sepsis
10 -14 days
Meningitis
21 days minimum
Treatment of Listeria
Monocytogenes Infections
Ampicillin and an Aminoglycoside IV
Duration (from first negative culture)
Uncomplicated sepsis
10 -14 days
Meningitis
14 days minimum
Early Onset Neonatal Sepsis:
C-Reactive Protein
Pediatrics, 1997, 99:216-221
Early Onset Neonatal Sepsis:
C-reactive Protein
• CRP levels <10mg/L, determined >24 hours after beginning
therapy correctly identified 99% of infants not needing
further therapy.
• May be useful in determining end-point for “rule-out
sepsis” evaluations, especially with maternal antibiotic
treatment.
• CRP-guided determination of length of therapy, shortened
the treatment course for most infected infants without
increasing the rate of relapse.
• Limitations: no studies evaluating meningitis or infections
other than bacterial sepsis.
Early Onset Neonatal Sepsis:
Treatment & CRP
• “Exposure to antibiotics during labor did not
change the clinical spectrum of disease or onset
of clinical signs of infection within 24 hours of
birth for term infants with EOGBS infection.”
• Normal CRP values at 24 hours of age supported
these observations.
Pediatrics, 2000, 106:244-250
Prognosis
Neonatal Sepsis
Mortality 20 - 30% overall - highest in premature infants
Morbidity ?? 25% ??
Neonatal Bacterial Meningitis
Mortality 15 - 30% - - 5% if infant survives the first 24 hr
Morbidity up to 50%
30 - 35% mild to moderate neurologic sequelae
5 - 10% severe neurologic impairment
Early Onset Neonatal Sepsis:
Prognosis - Prematurity
Organism
Mortality for
BW <1500g
Mortality for
BW 1500-2500g
Mortality for
BW >2500g
Group B
Streptococci
73%
20%
10%
Escherichia coli
73%
42%
13%
Staphylococcus
aureus
44%
15%
5%
Other
67%
33%
13%
Total
67%
28%
10%
Remington and Klein, Sixth Edition, 2006
Early Onset Neonatal Sepsis:
Summary
• GBS is still the predominant organism isolated in EONS
• Our efforts at IAP have reduced, but not eliminated,
early onset GBS sepsis
• Obstetrical risk factors, including premature/near-term
delivery and maternal intrapartum fever, help to identify
the infants at highest risk for EONS
• Ancillary laboratory evaluations, including the CRP
value, may assist in determination of the most
appropriate length of therapy
Late Onset Neonatal Sepsis
Late Onset Neonatal Sepsis
• Perinatal acquisition with later onset
–
–
–
–
Term or preterm
Bacterial: GBS, Chlamydia
Viral: HSV, CMV, HepB, HIV
Fungal: Candida
• Nosocomial acquisition
– Health care associated infections
– Preterm or sick term infant
Late Onset GBS
• Transmission - Perinatally or postnatally -- intrapartum prophylaxis
or neonatal treatment of early onset disease does not decrease risk of late
onset disease
• Symptoms -
7days - 3 months. Typically 3-4 weeks old.
Occult bacteremia or meningitis most common. However, focal infections
(pneumonia, UTI, cellulitis, osteomylelitis, septic arthritis) may occur.
• Diagnosis - Culture of blood, sputum, urine, abscess or other body
fluid.
• Treatment - Penicillin, as with early onset disease.
Herpes Simplex Virus (HSV)
• Incidence
•
•
•
•
•
•
1/3000-20,000 live births
1/200 pregnant women
> 75% asymptomatic
Enveloped DS-DNA
75% HSV II
HSVI
• Transmission
• 5-8% transplacental (congenital)
• 85-90% perinatally
• Primary infection (risk 30-50%)
• Secondary infection (risk <5%)
• Impossible to distinguish 1o vs 2o
• 5-10% postnatally
• Parent, caregiver
• Usually non-genital - hand, mouth
• Nosocomial spread from other infants
via hands of health care professionals
HSV Specific Symptoms
1. Disseminated Disease
•
•
•
•
•
Multi-organ involvement
Sepsis syndrome, DIC
Liver, CNS, lung predominance
Severe liver & CNS dysfunction common
Wide temp variations characteristic
2. Localized Central Nervous System Disease
•
Seizures common
3. Disease localized to the skin, eye and mouth
•
•
•
•
Vesicles, cloudy cornea.conjunctivitis, ulcers
Onset 1-4 weeks of age
Clinical overlap exists
Skin lesions absent or appear late with
disseminated/CNS disease
HSV Diagnosis
• High index of suspicion
– History ±
– Age (1-4 weeks)
– Sepsis Syndrome unresponsive to antibiotic therapy
• PE - classic vesicular lesions
• Culture - readily grows within 1-3 days
– Mouth, nasopharynx, conjunctivae rectum -- swabs >48 hours of age
– Skin vesicles, urine, stool, blood and CSF
 PCR - diagnostic method of choice - best on CSF, other fluids possible
•
•
•
CSF pleocytosis (especially monos) and elevated protein
Coagulopathy/DIC, thrombocytopenia, severe liver dysfunction
EEG
HSV Therapy - Prognosis
• Acyclovir IV
– 21 days for disseminated or CNS
– 14 days for skin, eye and mouth
• Mimimal toxicity - primarily liver - large volume IV
• Decreases mortality with disseminated disease from
~75% to 25-40%
• Decreases morbidity from 90% to 65%
• Improvements in both mortality and morbidity
dependent upon early initiation of Acyclovir
Neonatal Herpes: Number of Patients and Outcome by
Body Site Involved in Infants with a Pre-Mortem
Diagnosis and Not Treated with Antivirals*
Type of Infection
Patients (%)
Death (%)
Outcome in Infant (%) Normal‡(%)
Sequelae†
Disseminated
without CNS involvement
with CNS involvement
38 (16)
78 (33)
87
71
3
15
10
14
Localized
CNS
skin
eye
mouth
61 (26)
39 (17)
13 (5)
4 (2)
37
10
0
0
51
26
31
0
12
64
69
100
2 (1)
0
0
100
235 (100)
49
25
26
Asymptomatic
TOTAL
* Modified from Nahmias et al.
265
† Primary severe neurologic sequelae.
‡ No apparent sequelae from available follow-up information.
Feigen & Cherry, Fifth Edition, 2004
Neonatal Nosocomial Infections
Risk Factors for Neonatal
Nosocomial Sepsis
•
•
•
•
•
•
•
Prematurity
ELBW > VLBW
Increased LOS
Abdominal surgery / NEC
Hyperalimentaion / Intralipids
Neutropenia, Thrombocytopenia
Catheters
– UAC, UVC, ETT, Foley, CT, Peritoneal drains, etc
Umbilical Arterial and
Venous Catheters
• Life-saving tools on the NICU
• Necessary evil
• Increased of infections
– Minimally at 7 days
– Significantly at 10-14 days or when clot present
• UVC > UAC
– Stasis, hyperal/IL, thrombin formation
Umbilical Arterial and
Venous Catheters
• Require strict protocols regarding use and
care to reduce infection rates
• Remove:
– when no longer needed
– when evidence of infection or clot formation
• Replace when required >14 days
– PICC / broviac / percutaneous a-line
Neonatal Infections
Sepsis
Meningitis
Pneumonia
Otitis Media
Diarrheal Disease
 UTI 
Osteomyelitis
Suppurative Arthritis
Conjunctivitis
Orbital Cellulitis
Cellulitis - - Omphalitis
Bacterial / Viral / Fungal
Multi-organ involvement common
Neonatal Nosocomial Infections: Microbiology
• Skin flora
 Coagulase negative Staphylococcus
 Candida spp
• Methicillin-resistant Staphylococcus aureus
– Source: infant, care-givers, parents
• Gram-negative bacteria
 Enterococcus spp, Enterobacter spp, E. coli
• Pseudomonas spp, Klebsiella spp, Seratia spp
– Source:
• Infant GI tract
• Person-to-person transmission from Nursery personnel
• Nursery environmental sites: sinks, multiple use
solutions, countertops, respiratory therapy equipment…
Late Onset Neonatal Sepsis:
Empiric Treatment
Initial:
Vancomycin and Aminoglycoside IV
(Cefotaxime discouraged)
Duration (from first negative culture):
“Rule out sepsis”
Pneumonia
Sepsis
Meningitis
48 - 72 hours
5 - 7 days
10 -14 days
14 - 21 days
Primarily determined by etiologic organism cultured
Secondarily determined by clinical course/response
?CRP-guided determination of duration?
Remington and Klein, Sixth Edition, 2006
Concerns for Antibioticresistant organisms
• Vancomycin- resistant
enterococcus (VRE)
– Theoretic risk on
NICU
–  risk with multiple
course of vanco
– Strict contact
isolation
• Methicillin-resistant
Staphylococcus
aureus (MRSA)
– Real risk on NICU
– Community /
maternal acquired
– Vanco use required
– Strict contact
isolation
Treatment of Coagulase Negative
Staphylococcal Infections
Vancomycin IV
(± Rifampin if difficult to clear)
Duration (from first negative culture)
Uncomplicated sepsis
10 -14 days
Meningitis
14 - 21 days
Removal of indwelling intravascular catheters
Treatment of Gram-Negative Infections
Aminoglycoside IV + “something” (based on sensitivities)
Duration (from first negative culture)
Uncomplicated sepsis
10 -14 days
Meningitis
14 - 21 days
Removal of indwelling intravascular catheters
Prognosis
Dependent upon organism and early initiation of
appropriate therapy
LOS increased in all cases
Morbidity also variable dependent upon organ
involvement - worse with meningitis
Thanks for all your excellent care
on the NICU!
Indications for GBS
Intrapartum Prophylaxis
AAP Redbook, 2006 Report of the Committee on Infectious Diseases
Empiric management of the
infant after maternal IAP
AAP Redbook, 2006 Report of the Committee on Infectious Diseases
Common Manifestations of
Viral Infections in the Newborn Infant
Specific Features (acute)
Hyper- or hypothermia
General: irritability, lethargy, jitters, poor feeding, vomiting
CNS: seizures, hyper- or hypotonia, full fontanelle,
meningitis, encephalitis
Skin: icterus, petechiae, purpura, vesicle, maculopapular
rash
Eye: conjunctivitis, keratitis
Heart: myocarditis, hypotension
Abdomen: hepatosplenomegaly, hepatitis
Lung: pneumonitis, respiratory distress, cyanosis
Feigen & Cherry, Fifth Edition, 2004
Early Onset Neonatal Sepsis:
Enteroviral infections
• Diagnosis:
– Culture of stool, rectum pharynx best
– Culture of urine, blood and CSF may be
positive
– Culture of mother may be diagnostic
– PCR more rapid, but less specific
• Therapy: supportive only
Time/Mode of Acquisition of Viral Agent
Time
Mode
Implications
CMV
Rubella
Herpes II
EBV
Echo
Coxsackie
HTLV-III
Influenza
Hepatitis B
Varicella
Adeno
Rotavirus
RSV
Parainfluenza type 3
Rhinovirus
Prenatal
Transplacental
Perinatal
Birth Canal or Ascending
Mother
Maternal
colonized
viremia,
in vagina
amnioitis
or GI tract
+ symptoms
+ symptoms
+
+
+
+ (rare)
+
+
+
+
+
+
-
+
+
+
+
+
-
Postnatal
Contact
Nosocomial
or horizontal
transmission
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+