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NEONATAL SEPSIS AND NEONATAL SEPSIS AND CONGENITAL INFECTIONS CONGENITAL INFECTIONS Camille Sabella Sabella, MD , MD Camille August 28, 2012 August 28, 2012 Objectives Objectives Objectives At the end of the presentation, the

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1 NEONATAL SEPSIS AND CONGENITAL INFECTIONS NEONATAL SEPSIS AND CONGENITAL INFECTIONS

Camille Camille Sabella Sabella, MD , MD August 28, 2012 August 28, 2012

Objectives Objectives Objectives

  • At the end of the presentation, the

At the end of the presentation, the participant will be able to: participant will be able to:

  • List the pathogens that cause neonatal

List the pathogens that cause neonatal sepsis sepsis

  • Discuss the epidemiology of the

Discuss the epidemiology of the common pathogens of sepsis common pathogens of sepsis

  • Know the agents that are responsible

Know the agents that are responsible for congenital infections for congenital infections

  • Discuss the clinical features of the

Discuss the clinical features of the causes of congenital infections causes of congenital infections

NEONATAL INFECTIONS NEONATAL INFECTIONS

  • Bacterial neonatal sepsis

Bacterial neonatal sepsis

  • Viral infections mimicking bacterial

Viral infections mimicking bacterial sepsis sepsis

  • In

In-

  • utero

utero infections (congenital infections (congenital infections) infections)

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SLIDE 2

2

NEONATAL SEPSIS NEONATAL SEPSIS

  • Bacterial

Bacterial vs vs viral viral

  • Early

Early-

  • onset
  • nset vs

vs Late Late-

  • onset
  • nset
  • Perinatal

Perinatal vs vs Nosocomial Nosocomial vs vs Community Community acquisition acquisition

  • Clinical syndromes similar regardless of

Clinical syndromes similar regardless of etiology etiology

BACTERIAL NEONATAL SEPSIS BACTERIAL NEONATAL SEPSIS

  • Overall incidence 1

Overall incidence 1-

  • 5 per 1000 live births

5 per 1000 live births

  • Early

Early-

  • onset sepsis
  • nset sepsis
  • symptom onset within 6 days of life

symptom onset within 6 days of life

  • maternal complications common

maternal complications common

  • vertical transmission of organisms

vertical transmission of organisms colonizing genital tract colonizing genital tract

BACTERIAL NEONATAL SEPSIS BACTERIAL NEONATAL SEPSIS

  • Late

Late-

  • onset sepsis
  • nset sepsis
  • symptom onset after 6th day of life

symptom onset after 6th day of life

  • 2 distinct groups of neonates

2 distinct groups of neonates

  • healthy newborns who have been

healthy newborns who have been discharged to home discharged to home

  • high

high-

  • risk hospitalized neonates who

risk hospitalized neonates who develop hospital develop hospital-

  • associated

associated infection infection

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3

QUESTION #1 QUESTION #1

  • Of the following, the organism LEAST

Of the following, the organism LEAST likely to cause early likely to cause early-

  • onset neonatal
  • nset neonatal

sepsis is: sepsis is: A.

  • A. Listeria

Listeria monocytogenes monocytogenes B.

  • B. Group B Streptococci

Group B Streptococci C.

  • C. Streptococcus

Streptococcus pneumoniae pneumoniae D.

  • D. E. coli
  • E. coli

E.

  • E. viridans

viridans streptococci streptococci

ETIOLOGY OF EARLY ETIOLOGY OF EARLY-

  • ONSET

ONSET BACTERIAL SEPSIS BACTERIAL SEPSIS

  • Group B Streptococci

Group B Streptococci

  • dramatic decline since implementation of

dramatic decline since implementation of intrapartum intrapartum prophylaxis prophylaxis

  • Escherichia coli

Escherichia coli

  • probably most common now

probably most common now

  • Listeria

Listeria monocytogenes monocytogenes

  • Less Common

Less Common

  • viridans

viridans streptococci streptococci

  • non

non-

  • typeable

typeable Haemophilus Haemophilus influenzae influenzae

QUESTION #2 QUESTION #2

  • All of the following are important causes

All of the following are important causes

  • f late
  • f late-
  • onset neonatal sepsis, EXCEPT:
  • nset neonatal sepsis, EXCEPT:

A. A. Streptococcus Streptococcus pyogenes pyogenes B. B. Coagulase Coagulase-

  • negative

negative Staphylococci Staphylococci C. C. Staphylococcus Staphylococcus aureus aureus D. D. Gram Gram-

  • negative bacilli

negative bacilli E. E. Candida Candida albicans albicans

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4

ETIOLOGY OF LATE ETIOLOGY OF LATE-

  • ONSET

ONSET NEONATAL SEPSIS NEONATAL SEPSIS

  • Healthy newborns previously discharged from

Healthy newborns previously discharged from hospital hospital

  • Group B Streptococci

Group B Streptococci

  • L.
  • L. monocytogenes

monocytogenes

  • E. coli
  • E. coli
  • Salmonella

Salmonella species species

  • Less frequent causes:

Less frequent causes:

  • H.
  • H. influenzae

influenzae-

  • nontypeable

nontypeable

  • Neisseria

Neisseria meningitidis meningitidis

  • Streptococcus

Streptococcus pneumoniae pneumoniae

ETIOLOGY OF LATE ETIOLOGY OF LATE-

  • ONSET

ONSET SEPSIS* SEPSIS*

  • High risk newborns

High risk newborns (VLBW infants in NICU) (VLBW infants in NICU)

  • Coagulase

Coagulase-

  • negative Staphylococci

negative Staphylococci--

  • -48%

48%

  • Most common cause of late

Most common cause of late-

  • onset
  • nset

sepsis in hospitalized high sepsis in hospitalized high-

  • risk

risk neonates neonates

  • Gram

Gram-

  • negative bacilli (

negative bacilli (E. coli

  • E. coli,

, Klebsiella Klebsiella sp, sp, Enterobacter Enterobacter sp, sp, Pseudomonas Pseudomonas sp) sp)— —20% 20%

  • S.
  • S. aureus

aureus— —8% 8%

  • Candida

Candida albicans albicans— —12% 12%

  • Enterococci

Enterococci— —3% 3% N

*NICHD Neonatal Network, Pediatrics 2002;110:285

BACTERIAL NEONATAL SEPSIS: RISK BACTERIAL NEONATAL SEPSIS: RISK FACTORS FOR VLBW INFANTS FACTORS FOR VLBW INFANTS

  • Invasive procedures

Invasive procedures

  • Mechanical ventilation

Mechanical ventilation

  • Indwelling intravascular catheters

Indwelling intravascular catheters

  • Total

Total Parenteral Parenteral Nutrition Nutrition

  • Widespread use of broad

Widespread use of broad-

  • spectrum

spectrum antibiotics antibiotics

  • H

H2

2 blockers

blockers

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5

CLINICAL MANIFESTATIONS CLINICAL MANIFESTATIONS OF NEONATAL SEPSIS OF NEONATAL SEPSIS

  • Signs and symptoms often subtle and

Signs and symptoms often subtle and nonspecific nonspecific

  • Features of neonatal meningitis often

Features of neonatal meningitis often indistinguishable from sepsis indistinguishable from sepsis

  • Noninfectious illnesses have similar

Noninfectious illnesses have similar features features

  • RDS; Congenital heart disease;

RDS; Congenital heart disease; Metabolic disorders Metabolic disorders

  • Most neonatal pathogens produce similar

Most neonatal pathogens produce similar symptoms symptoms

GROUP B STREPTOCOCCI: GROUP B STREPTOCOCCI: MATERNAL COLONIZATION MATERNAL COLONIZATION

  • 15

15-

  • 40% of all pregnant women are colonized with

40% of all pregnant women are colonized with GBS GBS

  • Genital and GI tracts

Genital and GI tracts

  • Highest: African

Highest: African-

  • Americans, <20yo

Americans, <20yo

  • Lowest: Asian, Mexican

Lowest: Asian, Mexican-

  • Americans

Americans

  • Colonization

Colonization

  • Constant or intermittent

Constant or intermittent

  • Colonization during one pregnancy does

Colonization during one pregnancy does not predict colonization in subsequent not predict colonization in subsequent pregnancy pregnancy

Mother to Infant Transmission of GBS Mother to Infant Transmission of GBS Mother to Infant Transmission of GBS

GBS colonized mother Non-colonized newborn 50% Colonized newborn 50% Asymptomatic 98% Early-onset sepsis, pneumonia, meningitis 2%

CDC Prevention Guidelines, 2010

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6

Additional Risk Factors for Early-onset GBS Disease Additional Risk Factors for Early Additional Risk Factors for Early-

  • onset GBS
  • nset GBS

Disease Disease

  • Obstetric risk factors:

Obstetric risk factors:

  • Preterm delivery

Preterm delivery

  • Prolonged rupture of membranes

Prolonged rupture of membranes

  • Infection of the placental tissues or amniotic fluid /

Infection of the placental tissues or amniotic fluid / fever during labor fever during labor

  • GBS in the mother

GBS in the mother’ ’s urine during pregnancy (marker for heavy s urine during pregnancy (marker for heavy colonization) colonization)

  • Previous infant with GBS disease

Previous infant with GBS disease

  • Low maternal levels of anti

Low maternal levels of anti-

  • GBS antibodies

GBS antibodies

  • Demographic risk factors

Demographic risk factors

  • African American

African American

  • Young maternal age

Young maternal age

CDC Prevention Guidelines, 2010

Question #3: Which of the following is a TRUE statement concerning early-onset GBS neonatal sepsis? Question #3: Which of the following is a Question #3: Which of the following is a TRUE statement concerning early TRUE statement concerning early-

  • onset
  • nset

GBS neonatal sepsis? GBS neonatal sepsis?

  • A.
  • A. Pneumonia and apnea are the most

Pneumonia and apnea are the most common clinical features common clinical features

  • B.
  • B. Meningitis is present in 80% of cases

Meningitis is present in 80% of cases

  • C.
  • C. The case

The case-

  • fatality rate is lower than with

fatality rate is lower than with late late-

  • onset GBS infection
  • nset GBS infection
  • D.
  • D. Septic shock occurs in 75% of patients

Septic shock occurs in 75% of patients

  • E.

E. The mean age of onset is 72 hours of The mean age of onset is 72 hours of life life

GBS INFECTION:EARLY VS LATE GBS INFECTION:EARLY VS LATE ONSET ONSET

Early-onset Late-onset Incidence 0.3/1000 (1-4/1000 before IAP) 0.3/1000 Mean age at onset 8 hours 27 days Incidence of prematurity Increased Not increased Obstetric complications Common Unusual Manifestations Pneumonia(40%) Meningitis(5-10%) Septic Shock(25%) Bacteremia Meningitis Bone/joint/skin Mortality rate 10-15% 2-6%

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7

NEONATAL SEPSIS/MENINGITIS NEONATAL SEPSIS/MENINGITIS DUE TO DUE TO E. COLI

  • E. COLI INFECTION

INFECTION

  • Incidence approx 1 per 1000 live births

Incidence approx 1 per 1000 live births

  • Most cases early

Most cases early-

  • onset
  • nset
  • Ki

Ki capsular antigen present in 80% of capsular antigen present in 80% of cases of meningitis cases of meningitis

  • Vertical transmission major route of

Vertical transmission major route of transmission transmission

  • Infants with

Infants with Galactosemia Galactosemia particularly particularly susceptible to susceptible to E. coli

  • E. coli infection

infection

  • CFR high(20%) and

CFR high(20%) and sequelae sequelae in 30 in 30-

  • 50%

50%

NEONATAL LISTERIOSIS NEONATAL LISTERIOSIS

Early-onset Late-onset Age at onset At birth 1-8 weeks Birthweight Often LBW Usually term Obstetric complications Common (amnionitis, brown staining) Infrequent Source of isolate Blood(75%) CSF(90%) Fatality rate 25% 5%

NEONATAL LISTERIOSIS NEONATAL LISTERIOSIS

  • Maternal

Maternal prodromal prodromal illness common illness common-

  • 65%

65%

  • Elevated

Elevated monocyte monocyte count present in 50% count present in 50%

  • f
  • f bacteremic

bacteremic infants infants

  • Monocytes

Monocytes not typically found in CSF of not typically found in CSF of infants with meningitis infants with meningitis

  • Erythematous

Erythematous rash with 1 rash with 1-

  • 2mm pale

2mm pale nodules on skin and pharynx occasionally nodules on skin and pharynx occasionally seen ( seen (granulomas granulomas on path)

  • n path)
  • granulomatosis

granulomatosis infantisepticum infantisepticum

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SLIDE 8

8

NEONATAL BACTERIAL NEONATAL BACTERIAL SEPSIS:DIAGNOSIS SEPSIS:DIAGNOSIS

  • Isolation of organism from blood or CSF definitive

Isolation of organism from blood or CSF definitive

  • Latex Particle agglutination for GBS and

Latex Particle agglutination for GBS and E. coli

  • E. coli

limited by poor sensitivity and specificity limited by poor sensitivity and specificity

  • Hematologic abnormalities often accompanying

Hematologic abnormalities often accompanying sepsis sepsis

  • elevated ratio immature to total neutrophils

elevated ratio immature to total neutrophils (>0.2) (>0.2)

  • neutropenia

neutropenia

  • elevated

elevated neutrophil neutrophil count count

  • thrombocytopenia

thrombocytopenia

EMPIRIC THERAPY FOR EMPIRIC THERAPY FOR NEONATAL SEPSIS NEONATAL SEPSIS

  • Early

Early-

  • onset sepsis
  • nset sepsis
  • Ampicillin

Ampicillin + + Aminoglycoside Aminoglycoside

  • Cephalosporins

Cephalosporins should not be used should not be used empirically empirically

  • Late

Late-

  • onset sepsis
  • nset sepsis
  • VLBW infants in the NICU

VLBW infants in the NICU

  • Oxacillin

Oxacillin or

  • r Vancomycin

Vancomycin + + Aminoglycoside Aminoglycoside

  • r 3rd gen cephalosporin
  • r 3rd gen cephalosporin
  • “

“Community Community” ” acquired acquired

  • Ampicillin

Ampicillin + 3rd gen cephalosporin + 3rd gen cephalosporin

TREATMENT OF NEONATAL TREATMENT OF NEONATAL LISTERIOSIS LISTERIOSIS

  • Ampicillin

Ampicillin and and Gentamicin Gentamicin initially initially (bactericidal), then (bactericidal), then ampicillin ampicillin alone alone

  • Cephalosporins

Cephalosporins NOT active against NOT active against L. L. monocytogenes monocytogenes

  • 2

2-

  • 3 week duration

3 week duration

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9

TREATMENT OF GRAM TREATMENT OF GRAM-

  • NEGATIVE

NEGATIVE SEPSIS AND MENINGITIS SEPSIS AND MENINGITIS

  • Ampicillin

Ampicillin and and Gentamicin Gentamicin

  • initial empiric therapy

initial empiric therapy

  • Cefotaxime

Cefotaxime safe and effective alternative and safe and effective alternative and

  • ften used in combo with
  • ften used in combo with aminoglycoside

aminoglycoside for for meningitis meningitis

  • Even with appropriate therapy, CSF cultures

Even with appropriate therapy, CSF cultures remain positive for at least 2 remain positive for at least 2-

  • 3 days after initiation

3 days after initiation

  • f therapy
  • f therapy
  • Failure to sterilize CSF should prompt search for

Failure to sterilize CSF should prompt search for brain abscess or other complication brain abscess or other complication

  • 3

3-

  • week course recommended for meningitis

week course recommended for meningitis

BRAIN ABSCESS AND GRAM- NEGATIVE MENINGITIS BRAIN ABSCESS AND GRAM BRAIN ABSCESS AND GRAM-

  • NEGATIVE MENINGITIS

NEGATIVE MENINGITIS

  • Propensity to cause Brain Abscess

Propensity to cause Brain Abscess

  • Citrobacter

Citrobacter koseri koseri (formerly (formerly diversus diversus) )

  • Enterobacter

Enterobacter sakazakii sakazakii

  • Serratia

Serratia marcescens marcescens

PREVENTION OF EARLY-ONSET GBS SEPSIS PREVENTION OF EARLY PREVENTION OF EARLY-

  • ONSET

ONSET GBS SEPSIS GBS SEPSIS

  • 2002 and 2010 CDC guidelines

2002 and 2010 CDC guidelines

  • Based on data showing

Based on data showing that the screening method that the screening method was >50% more effective was >50% more effective than the risk than the risk-

  • factor

factor strategy strategy

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SLIDE 10

10

Rate of Early- and Late-Onset GBS, 1990-2008 Rate of Early Rate of Early-

  • and Late

and Late-

  • Onset GBS,

Onset GBS, 1990 1990-

  • 2008

2008

Early-onset GBS Late-onset GBS

Before national prevention policy Transition Universal screening Source: Active Bacterial Core surveillance / Emerging Infections Program

Key Prevention Strategies Remain Unchanged in 2010 Key Prevention Strategies Remain Unchanged Key Prevention Strategies Remain Unchanged in 2010 in 2010

  • Universal screening of pregnant women for GBS at 35

Universal screening of pregnant women for GBS at 35-

  • 37

37 weeks gestational age weeks gestational age

  • Intrapartum

Intrapartum antibiotic prophylaxis for: antibiotic prophylaxis for:

  • GBS positive screening test

GBS positive screening test

  • GBS colonization status unknown with

GBS colonization status unknown with

  • Delivery <37 weeks

Delivery <37 weeks

  • Temperature during labor

Temperature during labor > >100.4 100.4˚ ˚ F ( F (> >38.0 38.0˚ ˚ C) C)

  • Rupture of membranes

Rupture of membranes > >18 hours 18 hours

  • Previous infant with GBS disease

Previous infant with GBS disease

  • GBS in the mother

GBS in the mother’ ’s urine during current s urine during current pregnancy pregnancy

CDC Prevention Guidelines, 2010

Key Prevention Strategies Remain Unchanged in 2010 Key Prevention Strategies Remain Unchanged Key Prevention Strategies Remain Unchanged in 2010 in 2010

  • Penicillin preferred drug for IAP

Penicillin preferred drug for IAP

  • Ampicillin

Ampicillin acceptable alternative acceptable alternative

  • Cefazolin

Cefazolin preferred for penicillin preferred for penicillin-

  • allergic

allergic at low risk of anaphylaxis at low risk of anaphylaxis

CDC Prevention Guidelines, 2010

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SLIDE 11

11

Intrapartum GBS Prophylaxis Not Indicated Intrapartum Intrapartum GBS Prophylaxis Not GBS Prophylaxis Not Indicated Indicated

  • Colonization with GBS during a previous pregnancy

Colonization with GBS during a previous pregnancy

  • Unless another indication during the current pregnancy

Unless another indication during the current pregnancy

  • GBS

GBS bacteriuria bacteriuria during a previous pregnancy during a previous pregnancy

  • Unless another indication during the current pregnancy

Unless another indication during the current pregnancy

  • Negative vaginal and rectal GBS screening test during the curren

Negative vaginal and rectal GBS screening test during the current t pregnancy pregnancy

  • Regardless of

Regardless of intrapartum intrapartum risk factors risk factors

  • Cesarean delivery performed before labor onset on a woman with

Cesarean delivery performed before labor onset on a woman with intact amniotic membranes intact amniotic membranes

  • Regardless of maternal GBS test status

Regardless of maternal GBS test status

  • Regardless of gestational age

Regardless of gestational age

CDC Prevention Guidelines, 2010

QUESTION #4 QUESTION #4

Of the following, the virus Of the following, the virus least least likely to likely to cause symptoms at birth that mimic cause symptoms at birth that mimic bacterial neonatal sepsis is: bacterial neonatal sepsis is:

  • A.
  • A. Herpes simplex virus

Herpes simplex virus

  • B.
  • B. Human immunodeficiency virus (HIV)

Human immunodeficiency virus (HIV)

  • C.
  • C. Cytomegalovirus

Cytomegalovirus

  • D.
  • D. Enterovirus

Enterovirus

  • E.
  • E. Adenovirus

Adenovirus

ETIOLOGY OF NEONATAL VIRAL ETIOLOGY OF NEONATAL VIRAL SEPSIS SEPSIS

  • Herpes simplex virus types I and II

Herpes simplex virus types I and II

  • Enteroviruses

Enteroviruses

  • Echoviruses

Echoviruses

  • Coxsackie

Coxsackie

  • Cytomegalovirus

Cytomegalovirus

  • Respiratory viruses

Respiratory viruses

  • RSV

RSV

  • Influenza

Influenza

  • Adenovirus

Adenovirus

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SLIDE 12

12

Neonatal HSV Infections Neonatal HSV Infections Neonatal HSV Infections

  • Most occur from infected maternal

Most occur from infected maternal genital tract at delivery genital tract at delivery

  • Signs of infection by 4

Signs of infection by 4-

  • 5 weeks of age

5 weeks of age

  • Risk largely influenced by maternal

Risk largely influenced by maternal antibody status antibody status

  • 50% transmission with primary

50% transmission with primary infection infection

  • 5% transmission with recurrent

5% transmission with recurrent infection infection

Neonatal HSV Infections Neonatal HSV Infections Neonatal HSV Infections

  • High prevalence of asymptomatic maternal

High prevalence of asymptomatic maternal infection infection

  • Thus, most infants (>75%) with neonatal

Thus, most infants (>75%) with neonatal HSV are born to HSV are born to asymptomatic asymptomatic mothers who mothers who have have no past history no past history of genital HSV infection

  • f genital HSV infection
  • r clinical findings during pregnancy
  • r clinical findings during pregnancy

Neonatal HSV Infections Neonatal HSV Infections Neonatal HSV Infections

25% 25% Disseminated Infection Disseminated Infection 30% 30% CNS Infection CNS Infection 45% 45% Skin, Eyes, Mucus Membranes Skin, Eyes, Mucus Membranes (SEM) (SEM) % % Type of Infection Type of Infection

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SLIDE 13

13

NEONATAL HSV INFECTION NEONATAL HSV INFECTION NEONATAL HSV INFECTION

  • Skin, eyes and/or mouth (SEM)

Skin, eyes and/or mouth (SEM)

  • 7

7-

  • 14 days of life

14 days of life

  • Vesicles

Vesicles-

  • often at sites of trauma
  • ften at sites of trauma

(scalp electrode site) (scalp electrode site)

  • Conjunctivitis

Conjunctivitis

  • No mortality with treatment

No mortality with treatment

  • 5% morbidity with treatment

5% morbidity with treatment

  • 75% progress without treatment

75% progress without treatment

Neonatal Disseminated HSV Infection Neonatal Disseminated HSV Neonatal Disseminated HSV Infection Infection

  • Disseminated disease

Disseminated disease

  • 5

5-

  • 12 days of life

12 days of life

  • 58% have skin lesions

58% have skin lesions

  • Lesions often absent at presentation

Lesions often absent at presentation

  • Mimics bacterial sepsis

Mimics bacterial sepsis

  • DIC

DIC

  • Pneumonia

Pneumonia

  • Hepatitis

Hepatitis

  • CNS involvement (60

CNS involvement (60-

  • 70%)

70%)

  • Seizures in 22%

Seizures in 22%

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SLIDE 14

14

Neonatal Disseminated HSV Infection Neonatal Disseminated HSV Infection Neonatal Disseminated HSV Infection

  • Disseminated disease

Disseminated disease

  • Rapid deterioration

Rapid deterioration

  • Unremitting shock

Unremitting shock

  • Progressive liver failure

Progressive liver failure

  • Bleeding

Bleeding

  • Respiratory failure

Respiratory failure

  • 30% mortality with treatment

30% mortality with treatment

Neonatal HSV Encephalitis Neonatal HSV Encephalitis Neonatal HSV Encephalitis

  • Encephalitis (CNS)

Encephalitis (CNS)

  • 16

16-

  • 19 of life

19 of life

  • 45

45-

  • 63% have skin lesions

63% have skin lesions

  • Seizures (generalized or focal)

Seizures (generalized or focal)

  • Lethargy

Lethargy

  • Irritability

Irritability

  • Poor feeding

Poor feeding

  • Temp instability

Temp instability NEONATAL HERPES SIMPLEX NEONATAL HERPES SIMPLEX INFECTIONS:DIAGNOSIS INFECTIONS:DIAGNOSIS

  • Diagnosis difficult in absence of vesicular

Diagnosis difficult in absence of vesicular lesions lesions-

  • need high clinical suspicion

need high clinical suspicion

  • Viral Culture

Viral Culture

  • cutaneous

cutaneous lesion lesion

  • nasopharynx

nasopharynx

  • CSF

CSF

  • conjunctiva

conjunctiva

  • urine

urine

  • Direct Fluorescent Antibody

Direct Fluorescent Antibody

  • rapid diagnosis

rapid diagnosis

  • requires vesicular lesions

requires vesicular lesions

  • Polymerase Chain Reaction

Polymerase Chain Reaction-

  • CSF

CSF

slide-15
SLIDE 15

15

Treatment of Neonatal HSV Treatment of Neonatal HSV Infections Infections

  • Intravenous acyclovir treatment of choice

Intravenous acyclovir treatment of choice

  • 20mg/kg/dose q8h IV standard dose

20mg/kg/dose q8h IV standard dose

  • Monitor for

Monitor for neutropenia neutropenia (20%) and (20%) and nephrotoxicity nephrotoxicity (renal tubular (renal tubular crystalization crystalization with dehydration) with dehydration)

  • 21

21-

  • day course for disseminated or CNS

day course for disseminated or CNS infections infections

  • 14

14-

  • day course for SEM disease

day course for SEM disease

Corey L, Wald A. NEJM 2009;361:1376

Outcome of Neonatal HSV Infections

NEONATAL ENTEROVIRAL NEONATAL ENTEROVIRAL INFECTIONS INFECTIONS

  • Echoviruses 9,11,30 and Coxsackie B

Echoviruses 9,11,30 and Coxsackie B viruses most common today viruses most common today

  • Most neonatal infections mild and non

Most neonatal infections mild and non-

  • specific, but 20% severe and life

specific, but 20% severe and life-

  • threatening

threatening

  • Diagnosis very difficult to distinguish

Diagnosis very difficult to distinguish from bacterial or HSV infection from bacterial or HSV infection

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SLIDE 16

16

NEONATAL ENTEROVIRAL NEONATAL ENTEROVIRAL INFECTIONS: CLINICAL FEATURES INFECTIONS: CLINICAL FEATURES

  • Macular or

Macular or maculopapular maculopapular rash rash--

  • - 40%

40%

  • Hepatitis/Hepatic necrosis

Hepatitis/Hepatic necrosis

  • Myocarditis

Myocarditis

  • Meningoencephalitis

Meningoencephalitis

  • Maternal history of viral illness

Maternal history of viral illness

  • Lack of obstetrical complications

Lack of obstetrical complications

  • Summer and fall

Summer and fall

  • Isolation of virus from NP, throat, stool, CSF

Isolation of virus from NP, throat, stool, CSF confirms confirms Dx Dx

IN UTERO CONGENITAL IN UTERO CONGENITAL INFECTIONS INFECTIONS

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SLIDE 17

17

COMMON MANIFESTATIONS OF COMMON MANIFESTATIONS OF IN UTERO INFECTIONS IN UTERO INFECTIONS

  • General Characteristics

General Characteristics

  • Manifestations present at birth or

Manifestations present at birth or shortly thereafter shortly thereafter

  • Presence of congenital defects

Presence of congenital defects (CHD, ocular abnormalities, (CHD, ocular abnormalities, calcifications, etc) calcifications, etc)

COMMON MANIFESTATIONS OF COMMON MANIFESTATIONS OF IN UTERO INFECTIONS IN UTERO INFECTIONS

  • Specific Features

Specific Features

  • Small for Gestational age

Small for Gestational age

  • CNS:

CNS: microcephaly microcephaly, seizures, cerebral , seizures, cerebral calcification calcification

  • Skin:

Skin: icterus icterus, , petechiae petechiae, , purpura purpura, vesicles , vesicles

  • Eye:

Eye: chorioretinitis chorioretinitis, cataracts, , cataracts, microphthalmia microphthalmia

  • Heart: PDA, PS

Heart: PDA, PS

  • Abdomen: HSM, hepatitis

Abdomen: HSM, hepatitis

  • Lung:

Lung: pneumonitis pneumonitis

  • Musculoskeletel

Musculoskeletel: bone lesions, limb : bone lesions, limb hypoplasia hypoplasia

QUESTION #5 QUESTION #5

Of the following, the most common agent Of the following, the most common agent causing congenital infection is: causing congenital infection is:

  • A.

A. Toxoplasma Toxoplasma gondii gondii

  • B.

B. Cytomegalovirus Cytomegalovirus

  • C.

C. Rubella Rubella

  • D.

D. Parvovirus B 19 Parvovirus B 19

  • E.

E. Varicella Varicella-

  • zoster virus

zoster virus

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SLIDE 18

18

Question #6: Which is a true statement concerning congenital cytomegalovirus infection? Question #6: Which is a true statement Question #6: Which is a true statement concerning congenital cytomegalovirus concerning congenital cytomegalovirus infection? infection?

  • A.

A. Chorioretinitis Chorioretinitis is the most common is the most common clinical manifestation clinical manifestation

  • B.

B. 1% of all infants born have CMV 1% of all infants born have CMV infection infection

  • C.

C. Fetal infection occurs only after Fetal infection occurs only after primary maternal infection primary maternal infection

  • D.

D. Infants with asymptomatic infection Infants with asymptomatic infection have have no risk of long no risk of long-

  • term

term sequelae sequelae

  • E.

E. Serology represents the most reliable Serology represents the most reliable diagnostic test diagnostic test

CMV:EPIDEMIOLOGY CMV:EPIDEMIOLOGY

  • Most common congenital infection

Most common congenital infection

  • 1% of all newborn infants have congenital

1% of all newborn infants have congenital CMV infection CMV infection

  • Virus transmitted from both immune

Virus transmitted from both immune mothers as well as non mothers as well as non-

  • immune mothers

immune mothers

  • Severe fetal damage occurs almost

Severe fetal damage occurs almost exclusively w/1 exclusively w/1º º infection infection

  • Infection can occur prenatally,

Infection can occur prenatally, natally natally, or , or postnatally postnatally

SIGNS OF PRENATAL CMV SIGNS OF PRENATAL CMV INFECTION IN THE NEWBORN INFECTION IN THE NEWBORN

Finding Frequency Asymptomatic 90% Symptomatic 10% Petechiae Thrombocytopenia 76% 77% Jaundice 67% HSM 60% SGA CT Calcifications 50% 50% Microcephaly 53% Retinitis 10% Seizures 7%

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SLIDE 19

19

FEATURES OF CONGENITAL CMV IN SYMPTOMATIC INFANTS FEATURES OF CONGENITAL CMV FEATURES OF CONGENITAL CMV IN SYMPTOMATIC INFANTS IN SYMPTOMATIC INFANTS

  • Elevated transaminases

Elevated transaminases-

  • 83%

83%

  • Thrombocytopenia (<100K)

Thrombocytopenia (<100K)-

  • 77%

77%

  • Conjugated hyperbilirubinemia

Conjugated hyperbilirubinemia-

  • 81%

81%

  • Hemolysis

Hemolysis-

  • 51%

51%

  • Increased CSF protein (>120mg/dL)

Increased CSF protein (>120mg/dL)-

  • 46%

46%

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SLIDE 20

20

LONG LONG-

  • TERM OUTCOME OF

TERM OUTCOME OF CONGENITAL CMV INFECTION CONGENITAL CMV INFECTION

  • Symptomatic infants

Symptomatic infants

  • Death (30%)

Death (30%)

  • Sensorineural

Sensorineural hearing loss(58%) hearing loss(58%)

  • IQ<70 (55%)

IQ<70 (55%)

  • Microcephaly

Microcephaly, seizures, paresis (52%) , seizures, paresis (52%)

  • Chorioretinitis

Chorioretinitis (20%) (20%)

  • Asymptomatic infants

Asymptomatic infants

  • Sensorineural

Sensorineural hearing loss (7%) hearing loss (7%)

  • IQ < 70 (4%)

IQ < 70 (4%)

  • Microcephaly

Microcephaly (3%) (3%)

  • Chorioretinitis

Chorioretinitis (2.5%) (2.5%)

LABORATORY DIAGNOSIS OF LABORATORY DIAGNOSIS OF CONGENITAL CMV INFECTION CONGENITAL CMV INFECTION

  • Definitive

Definitive

  • Isolation of virus from urine or saliva

Isolation of virus from urine or saliva by three weeks of age by three weeks of age

  • Not Useful

Not Useful

  • CMV

CMV IgG IgG and and IgM IgM antibody antibody

  • False positives and negatives

False positives and negatives common common

QUESTION #7 QUESTION #7

A newborn infant has A newborn infant has microcephaly microcephaly, is , is SGA, has a SGA, has a “ “blueberry muffin blueberry muffin” ” rash, rash, and bilateral cataracts. The most likely and bilateral cataracts. The most likely congenital heart lesion associated with congenital heart lesion associated with this infection is: this infection is:

  • A.

A. PDA PDA

  • B.

B. ASD ASD

  • C.

C. TGA TGA

  • D.

D. Tricuspid Tricuspid atresia atresia

  • E.

E. Coarctation Coarctation of the aorta

  • f the aorta
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SLIDE 21

21

CONGENITAL RUBELLA CONGENITAL RUBELLA INFECTION INFECTION

  • Almost all cases due to maternal

Almost all cases due to maternal primary primary infection infection

  • Overall risk to fetus 20% (70% in first

Overall risk to fetus 20% (70% in first trimester) trimester)

  • Imported cases from Asia and Europe

Imported cases from Asia and Europe

  • No congenital infection seen with

No congenital infection seen with inadvertent maternal vaccination during inadvertent maternal vaccination during pregnancy pregnancy

  • Diagnosis

Diagnosis

  • Viral culture from NP, urine, cataract

Viral culture from NP, urine, cataract

CONGENITAL RUBELLA:CLINICAL MANIFESTATIONS CONGENITAL RUBELLA:CLINICAL CONGENITAL RUBELLA:CLINICAL MANIFESTATIONS MANIFESTATIONS

  • Most infants asymptomatic at birth

Most infants asymptomatic at birth

  • Cataracts

Cataracts

  • Blueberry muffin spots (dermal

Blueberry muffin spots (dermal erythropoesis erythropoesis) )

  • CHD (PDA, PS)

CHD (PDA, PS)

  • “

“Salt and pepper Salt and pepper” ” retinopathy retinopathy

  • IUGR and postnatal growth restriction

IUGR and postnatal growth restriction

  • Reticuloendothelial

Reticuloendothelial (HSM, jaundice) (HSM, jaundice)

CDC Public Health Image Library

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SLIDE 22

22

CDC Public Health Image Library

QUESTION #8 QUESTION #8

Which of the following is True regarding Which of the following is True regarding congenital congenital Toxoplasma Toxoplasma infection? infection?

  • A.

A. The incidence is constant despite The incidence is constant despite geographic location geographic location

  • B.

B. Prenatal diagnosis is not possible Prenatal diagnosis is not possible

  • C.

C. Treatment of infected pregnant women Treatment of infected pregnant women is not is not recommended recommended

  • D.

D. Neurological and visual problems Neurological and visual problems become apparent in the majority of become apparent in the majority of infected asymptomatic infants infected asymptomatic infants

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SLIDE 23

23

CONGENITAL TOXOPLASMOSIS CONGENITAL TOXOPLASMOSIS

  • Exposure to

Exposure to oocytes

  • ocytes: cat feces and

: cat feces and ingestion of raw beef major sources ingestion of raw beef major sources

  • Fetal infection occurs only with maternal

Fetal infection occurs only with maternal primary primary infection infection

  • Incidence 1/1000

Incidence 1/1000-

  • 10000 live births

10000 live births

CONGENITAL TOXOPLASMOSIS: FETAL INFECTION RATES CONGENITAL TOXOPLASMOSIS: CONGENITAL TOXOPLASMOSIS: FETAL INFECTION RATES FETAL INFECTION RATES

7% 7% 35% 35% Stillborn/ Stillborn/perinatal perinatal death death 8% 8% 41% 41% Severe Severe 10% 10% 18% 18% 6% 6% Mild Mild 90% 90% 67% 67% 18% 18% Subclinical disease Subclinical disease 60% 60% 30% 30% 15% 15% Overall rate of infection Overall rate of infection 3rd 3rd 2 2nd

nd

1 1st

st

Trimester Trimester

CONGENITAL TOXOPLASMOSIS: CLINICAL FEATURES CONGENITAL TOXOPLASMOSIS: CONGENITAL TOXOPLASMOSIS: CLINICAL FEATURES CLINICAL FEATURES

  • Majority of infected neonates are asymptomatic

Majority of infected neonates are asymptomatic

  • 80% Develop eye/

80% Develop eye/neuro neuro disease by adulthood disease by adulthood

  • Classic Triad

Classic Triad

  • Chorioretinitis

Chorioretinitis-

  • 86%

86%

  • Hydrocephalus

Hydrocephalus-

  • 20%

20%

  • Cerebral Calcifications

Cerebral Calcifications-

  • 37%

37%

  • Cerebral Calcifications

Cerebral Calcifications

  • Distributed throughout the brain

Distributed throughout the brain-

  • unlike CMV

unlike CMV

  • Chorioretinitis

Chorioretinitis

  • Focal necrotizing retinitis

Focal necrotizing retinitis

  • Can be recurrent and progressive

Can be recurrent and progressive

  • May develop later in life without any other features of

May develop later in life without any other features of congenital infection congenital infection

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SLIDE 24

24

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SLIDE 25

25

CONGENITAL TOXOPLASMOSIS:DIAGNOSIS CONGENITAL CONGENITAL TOXOPLASMOSIS:DIAGNOSIS TOXOPLASMOSIS:DIAGNOSIS

  • Prenatal

Prenatal

  • Toxo

Toxo DNA in amniotic fluid or fetal blood DNA in amniotic fluid or fetal blood

  • Isolating parasite by mouse inoculation or

Isolating parasite by mouse inoculation or tissue culture tissue culture

  • Serial fetal US

Serial fetal US— —look for increased size of lateral look for increased size of lateral ventricles ventricles

  • Postnatal

Postnatal

  • T

T gondii gondii DNA by PCR amniotic fluid, fetal blood, DNA by PCR amniotic fluid, fetal blood, blood, CSF blood, CSF

  • Histopathology placenta, infected organ/tissue

Histopathology placenta, infected organ/tissue

  • Mouse inoculation assays of infant

Mouse inoculation assays of infant’ ’s blood, s blood, placenta, umbilical cord placenta, umbilical cord

  • Serology

Serology-

  • IgG

IgG, M, A, E on Mom and infant , M, A, E on Mom and infant

CONGENITAL TOXOPLASMOSIS:TREATMENT CONGENITAL CONGENITAL TOXOPLASMOSIS:TREATMENT TOXOPLASMOSIS:TREATMENT

  • Mother

Mother

  • Spiramycin

Spiramycin to decrease transmission to decrease transmission

  • Pyramethamine

Pyramethamine and sulfadiazine if fetal and sulfadiazine if fetal infection confirmed after 17 weeks infection confirmed after 17 weeks gestation gestation

  • Infant

Infant

  • Decreases severity of disease and

Decreases severity of disease and frequency of frequency of sequelae sequelae

  • Pyrimethamine

Pyrimethamine and sulfadiazine and sulfadiazine

  • Therapy continued for 1 year

Therapy continued for 1 year

QUESTION #9 QUESTION #9

A 1 A 1-

  • week old infant develops a copious bloody nasal

week old infant develops a copious bloody nasal discharge, lymphadenopathy, discharge, lymphadenopathy, hepatomegaly hepatomegaly and and hemolytic anemia. Which of the following is the hemolytic anemia. Which of the following is the most likely additional feature in this infant? most likely additional feature in this infant?

  • A.

A. hydrocephalus hydrocephalus

  • B.

B. periostitis periostitis

  • C.

C. limb limb hypoplasia hypoplasia

  • D.

D. seizures seizures

  • E.

E. hydrops hydrops

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SLIDE 26

26

CONGENITAL SYPHILIS CONGENITAL SYPHILIS

  • 30

30-

  • 40% of infected fetuses are stillborn

40% of infected fetuses are stillborn

  • Of infected neonates who are live

Of infected neonates who are live-

  • born,

born, 70% are asymptomatic at birth and are 70% are asymptomatic at birth and are identified by prenatal maternal identified by prenatal maternal screening screening

  • Because fetus acquires infection via

Because fetus acquires infection via hematogenous hematogenous route, widespread route, widespread involvement (rather than primary stage) involvement (rather than primary stage) is usual is usual

UNIQUE FEATURES OF UNIQUE FEATURES OF CONGENITAL SYPHILIS CONGENITAL SYPHILIS

  • Generalized lymphadenopathy more common

Generalized lymphadenopathy more common than other congenital infections than other congenital infections

  • Coombs

Coombs-

  • negative hemolytic anemia

negative hemolytic anemia

  • Snuffles (rhinitis)

Snuffles (rhinitis)-

  • in 25% of infants

in 25% of infants

  • Exanthem

Exanthem

  • maculopapular

maculopapular rash with scaling and rash with scaling and desquamation most common desquamation most common

  • vesicobullous

vesicobullous lesions ( lesions (pemphigus pemphigus syphiliticus syphiliticus) )

UNIQUE FEATURES OF UNIQUE FEATURES OF CONGENITAL SYPHILIS CONGENITAL SYPHILIS

  • Bony lesions

Bony lesions-

  • may be most frequently

may be most frequently encountered manifestation encountered manifestation

  • osteochondritis
  • steochondritis
  • osteomyelitis
  • steomyelitis
  • periostitis

periostitis

  • CNS manifestations

CNS manifestations

  • pleocytosis

pleocytosis; high protein, ; high protein, reaginic reaginic antibody antibody

  • Chorioretinitis

Chorioretinitis

  • “

“salt & pepper salt & pepper” ”-

  • like Rubella

like Rubella

slide-27
SLIDE 27

27

INDICATIONS FOR EVALUATION INDICATIONS FOR EVALUATION OF CONGENITAL SYPHILIS OF CONGENITAL SYPHILIS

  • Mother with positive non

Mother with positive non-

  • treponemal tests

treponemal tests confirmed by a positive confirmed by a positive treponemal treponemal test and: test and:

  • Untreated or inadequately treated syphilis

Untreated or inadequately treated syphilis

  • Treatment in pregnancy with non

Treatment in pregnancy with non-

  • penicillin

penicillin regimen regimen

  • Lack of expected decrease in non

Lack of expected decrease in non-

  • treponemal antibody titer after treatment

treponemal antibody titer after treatment

  • Treatment < 1 month before delivery

Treatment < 1 month before delivery

  • Treatment not documented

Treatment not documented

  • Insufficient follow

Insufficient follow-

  • up to assess response

up to assess response

slide-28
SLIDE 28

28

Evaluation for Congenital Syphilis Evaluation for Congenital Syphilis Evaluation for Congenital Syphilis

  • PE

PE

  • Quatitative

Quatitative nontreponemal nontreponemal (RPR) and (RPR) and treponemal treponemal (FTA (FTA-

  • ABS) test on infant

ABS) test on infant’ ’s s serum serum

  • Antitreponemal

Antitreponemal IgM IgM if available if available

  • CSF for VDRL, cell count, protein

CSF for VDRL, cell count, protein

  • Long

Long-

  • bone radiographs

bone radiographs

  • CBC, platelets

CBC, platelets

  • Chest radiography,

Chest radiography, LFT LFT’ ’s s

  • as clinically indicated

as clinically indicated

Congenital Syphilis: Who needs Treatment? Congenital Syphilis: Who needs Congenital Syphilis: Who needs Treatment? Treatment?

  • Infants with proven or probable disease

Infants with proven or probable disease

  • Infants who warrant evaluation in which

Infants who warrant evaluation in which infection cannot be ruled out infection cannot be ruled out

  • Infants whose follow

Infants whose follow-

  • up cannot be assured

up cannot be assured

  • Infants whose infected mothers can

Infants whose infected mothers can’ ’t be t be treated, treated inadequately, or treated treated, treated inadequately, or treated within 1 month of delivery within 1 month of delivery

  • Infants of mothers not having 4

Infants of mothers not having 4-

  • fold

fold decrease in titer decrease in titer

Treatment for Congenital Syphilis Treatment for Congenital Syphilis Treatment for Congenital Syphilis

  • Aqueous Penicillin G for 10

Aqueous Penicillin G for 10-

  • 14 days preferred

14 days preferred therapy for proven or presumed infection therapy for proven or presumed infection

  • Procaine penicillin (IM) may also be used

Procaine penicillin (IM) may also be used

  • CSF concentrations may not be adequate

CSF concentrations may not be adequate

  • Single dose

Single dose benzathine benzathine Penicillin Penicillin

  • recommended by some experts for:

recommended by some experts for:

  • asymptomatic infants with normal

asymptomatic infants with normal evaluation and whose follow evaluation and whose follow-

  • up can

up can be assured, but whose mothers have be assured, but whose mothers have not been treated adequately or do not been treated adequately or do not have 4 not have 4-

  • fold decrease in titer

fold decrease in titer

slide-29
SLIDE 29

29 Question #10 Question #10 Question #10

Of the following, the congenital infection Of the following, the congenital infection most associated with most associated with hydrops hydrops fetalis fetalis is: is:

  • A.
  • A. Varicella

Varicella-

  • zoster virus

zoster virus

  • B.
  • B. HIV

HIV

  • C.
  • C. Human herpes virus 6 (HHV

Human herpes virus 6 (HHV-

  • 6)

6)

  • D.
  • D. Parvovirus B19

Parvovirus B19

  • E.
  • E. Borrelia

Borrelia burgdorferi burgdorferi

EPIDEMIOLOGY OF PARVOVIRUS B19 INFECTIONS EPIDEMIOLOGY OF PARVOVIRUS EPIDEMIOLOGY OF PARVOVIRUS B19 INFECTIONS B19 INFECTIONS

  • About 50% of women are

About 50% of women are seropositive seropositive for the virus prior to pregnancy for the virus prior to pregnancy

  • Likelihood of infection after a close

Likelihood of infection after a close exposure estimated to be 30 exposure estimated to be 30-

  • 50%

50%

  • Estimates of fetal loss following

Estimates of fetal loss following infection during pregnancy range from infection during pregnancy range from 2 2-

  • 6%

6%

  • Thus, overall risk of fetal loss due to

Thus, overall risk of fetal loss due to this virus is 1 this virus is 1-

  • 2%

2%

slide-30
SLIDE 30

30

CONGENITAL PARVOVIRUS B19 CONGENITAL PARVOVIRUS B19 INFECTION INFECTION

  • Consequences of maternal parvovirus infections

Consequences of maternal parvovirus infections

  • Asymptomatic newborn

Asymptomatic newborn

  • IUGR

IUGR

  • Hydrops

Hydrops fetalis fetalis

  • severe anemia

severe anemia

  • high output cardiac failure

high output cardiac failure

  • extramedullary

extramedullary hematopoiesis hematopoiesis

  • Stillbirth

Stillbirth

  • Isolated pleural or pericardial effusions

Isolated pleural or pericardial effusions

Answers to Questions Answers to Questions Answers to Questions

  • 1.

1. C C

  • 2.

2. A A

  • 3.

3. A A

  • 4.

4. B B

  • 5.

5. B B

  • 6.

6. B B

  • 7.

7. A A

  • 8.

8. D D

  • 9.

9. B B

  • 10.
  • 10. D

D