PREVENTION OF GROUP B STREPTOCOCCUS INFECTION IN THE NEONATE

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PREVENTION OF GROUP B STREPTOCOCCUS INFECTION IN
THE NEONATE

• Rene L. Santin M. D.
• Texas Tech University Health Sciences Center
• Pediatric Infectious Diseases Rotation

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EPIDEMIOLOGY

• KNOWN CAUSE OF BOVINE MASTITIS
• CONSIDERED AS SIGNIFICANT PATHOGEN SINCE 1970S
• INCIDENCE
• EARLY ONSET 1.1-3.7/1000 LIVE BIRTHS
• LATE ONSET 0.6-1.7/1000 LIVE BIRTHS
• CASE FATALITY RATIO 11-14

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IMPACT OF GBS INFECTION

• ESTIMATED 11,000 CASES/YEAR IN US
• 2500 INFANT DEATHS/YEAR
• 1350 CHILDREN WITH PERMANENT NEUROLOGIC SEQUELAE
• PERMANENT NEUROLOGIC SEQUELAE IN MENINGITIS
  SURVIVORS
• 25 - 50

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GROUP B STREPTOCOCCUS

• Streptococcus agalactiae
• GRAM DIPLOCOCCUS
• Beta-HEMOLYTIC, ENCAPSULATED
• 8 SEROTYPES
• Ia, Ib, Ic, II, III, IV, V, VI

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GBS COLONIZATION

• IN MOTHER
• LOWER GENITAL TRACT
• ANORECTUM
• URINARY TRACT
• IN NEONATES
• EXTERNAL EAR (IN FIRST 24 H )
• ANTERIOR NARES, THROAT
• ANORECTUM
• UMBILICUS

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TYPES OF GBS INFECTIONS

• EARLY ONSET
• LATE ONSET
• SYSTEMIC
• CNS
• BACTEREMIA W/O FOCUS
• SEPTIC ARTHRITIS, OSTEOMYELITIS
• CELLULITIS, ADENITIS
• OTHER SITES (UNUSUAL)

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EARLY ONSET GBS INFECTIONS

• ONSET lt 7 DAYS
• 60-80 PRESENT AT FIRST 24 H
• MEDIAN AGE AT ONSET
• TERM 8 HOURS
• PRETERM 6 HOURS

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RISK FACTORS FOR GBS INFECTION

• PREMATURE ONSET OF LABOR
• PROLONGED RUPTURE OF MEMBRANES gt 18 H BEFORE
  DELIVERY
• MATERNAL CHORIOAMNIONITIS
• EARLY POST PARTUM FEBRILE MORBIDITY
• MULTIPLE BIRTHS

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CLINICAL MANIFESTATIONS OF EARLY ONSET GBS
INFECTION
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GBS SEROTYPES IN EARLY ONSET INFECTION
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SIGNS AND SYMPTOMS OF EARLY GBS INFECTION

• APNEA
• GRUNTING
• TACHYPNEA
• CYANOSIS
• HYPOTENSION
• SHOCK
• COMA
• SEIZURES

• LETHARGY
• POOR FEEDING
• HYPOTHERMIA
• FEVER
• ABD. DISTENSION
• PALLOR
• TACHYCARDIA
• JAUNDICE

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CHEST X RAY IN EARLY GBS INFECTION

• CONSISTENT AND INDISTINGUISHABLE FROM
• HMD (60- 70 )
• CONGENITAL PNEUMONIA (30-35 )
• INCREASED VASCULAR MARKINGS
• SMALL PLEURAL EFFUSIONS
• NO FINDINGS

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MORTALITY IN EARLY GBS INFECTION

• Anthony and Okada, Ann Rev Med, 1977
• 55
• Weissman and Stoll, J Pediatr, 1992
• Yagupsky and Menegus, Pediatr Infect Dis J 1991
• 10-15

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BIRTH WEIGHT SPECIFIC MORTALITY RATES
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LATE ONSET GBS INFECTION

• 7 DAYS - 12 WEEKS AGE
• UNREMARKABLE EARLY NEONATAL HX
• LOWER MORTALITY RATE (2 - 6 )
• MENINGITIS IS COMMON
• 40 of cases
• serotype III

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GBS SEROTYPES IN LATE ONSET INFECTION
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CLINICAL MANIFESTATIONS OF LATE GBS INFECTION

• FEVER
• IRRITABILITY
• LETHARGY
• POOR FEEDING
• RESPIRATORY DISTRESS (20 - 30 )
• APNEA (10 - 15 )
• HYPOTENSION (10 - 15 )

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GBS SEPTIC ARTHRITIS AND OSTEOMYELITIS

• LATE ONSET DISEASE
• MEAN AGE AT DIAGNOSIS 20-30 d
• MOST COMMON SIGN OF INFECTION
• FAILURE TO MOVE THE EXTREMITY
• FEVER, WARMTH, ERYTHEMA 20
• MOST COMMON SITE
• SEPTIC ARTHRITS HIP
• OSTEOMYELITIS HUMERUS 55
• FEMUR
  10-15

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GBS MENINGITIS

• MORTALITY RATE 50 - 75
• 21 OF SURVIVORS HAVE MAJOR PERMANENT NEUROLOGIC
  SEQUELAE
• MENTAL RETARDATION (USUALLY PROFOUND)
• SPASTIC QUADRIPLEGIA
• CORTICAL BLINDNESS
• DEAFNESS
• UNCONTROLLED SEIZURES
• HYDROCEPHALUS
• HYPOTHALAMIC DYSFUNCTION

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GBS MENINGITIS

• 20 OF SURVIVORS HAVE MILD TO MODERATE
  NEUROLOGIC SEQUELAE
• BORDERLINE MENTAL RETARDATION
• LANGUAGE DELAY
• UNILATERAL HEARING LOSS

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GBS BACTEREMIA WITHOUT FOCUS

• LATE ONSET DISEASE
• UNCOMPLICATED PERINATAL COURSE
• NON-SPECIFIC SIGNS IN FIRST FEW WEEKS OF LIFE
• FEVER
• POOR FEEDING
• IRRITABILITY
• RINORRHEA
• R/O SEPSIS WORKUP

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TREATMENT OF PROVEN GBS INFECTIONS
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PREVENTION OF GBS INFECTION

• CHEMOPROPHYLAXIS
• IMMUNOPROPHYLAXIS

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CHEMOPROPHYLAXIS FOR GBS INFECTION

• FIRST SUGGESTED BY Franciosi et al,
• J. Pediatr, 1973
• EARLY STUDIES
• TREATMENT DURING 3RD TRIMESTER
• TREATMENT OF SEXUAL PARTNERS

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CHEMOPROPHYLAXIS FOR GBS INFECTION

• Boyer, Gottof et al, NEJM 1986
• Prospective, randomized, controlled trial
• GBS colonization detected at 26-26 wk gest.
• Women positive for GBS and those with ROM were
  randomized 79 non treated, 85 treated
• 2 g of ampicillin iv, then
• 1 g of ampicillin iv q 4 h until delivery

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CHEMOPROPHYLAXIS FOR GBS INFECTION

• RESULTS
• INCIDENCE OF GBS SEPSIS
• NON TREATED 5 CASES (1 DEATH)
• TREATED 0 CASES

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CHEMOPROPHYLAXIS FOR GBS INFECTION

• SELECTIVE
• PREMATURE LABOR
• PREMATURE RUPTURE OF MEMBRANES
• FEVER
• NON-SELECTIVE
• TREAT ALL GBS POSITIVE

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CHEMOPROPHYLAXIS FOR GBS INFECTION

• IDEALLY ADMINISTERED 4 H PTD
• HIGH DOSES OF ANTIBIOTICS
• Ampicillin 2 g IV
• Penicillin G 5,000,000 u IV
• NO EFFICACY IN PREVENTION OF LATE ONSET DISEASE

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MATERNAL RISK FACTORS

• PRETERM LABOR lt 37 WEEKS
• PRETERM PROM AT 37 WEEKS
• ROM AT ANY GESTATION AFTER 18 H
• FEVER DURING LABOR
• PREVIOUS DELIVERY OF SIBLING WITH INVASIVE GBS
  DISEASE
• MULTIPLE BIRTHS (AAP only)

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IMMUNOPROPHYLAXIS OF GBS DISEASE

• IVIG
• HYPERIMMUNE IVIG
• VACCINE
• HUMAN MONOCLONAL ANTIBODIES

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IVIG USE FOR GBS INFECTION

• FAILURE TO DEMONSTRATE EFFECT ON
• MORTALITY RATE
• EVOLUTION OF SEPSIS
• LENGTH OF HOSPITAL STAY
• NOT RECOMMENDED

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A polyclonal human IgG preparation hyperimmune
for type III GBS in vitro efficacy

• Givner LB, J Infect Dis, 1988
• IgG was isolated from serum of human volunteers
  after vaccination with III-PS
• RESULTS
• Increased opsonophagocytosis of GBS-III in
  neonatal sera in presence of PMNs

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IMMUNIZATION FOR GBS

• 80 - 90 OF CHILDBEARING WOMEN LACK PROTECTIVE
  LEVELS OF ANTIBODY
• PROTECTIVE LEVELS CAN LAST UP TO 5 - 7 YEARS
• POLYSACCHARIDE VACCINE 1986
• CONJUGATE VACCINE 1996

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IMMUNIZATION OF PREGNANT WOMEN WITH A
POLYSACCHARIDE VACCINE OF GBS

• Baker et al, NEJM, 1985
• 40 pregnant women at mean gest. 31 weeks
• Vaccination with 50 ug of type III capsular
  polysaccharide of GBS
• Cord blood was analyzed for IgG, IgM, IgA

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IMMUNIZATION OF PREGNANT WOMEN WITH A
POLYSACCHARIDE VACCINE OF GBS

• RESULTS
• ALL 40 INFANTS WERE HEALTHY AT BIRTH
• ANTIBODY WAS DETECTED IN MOTHERS AT
• 4 WEEKS AFTER VACCINE
• THE OVERALL VACCINE RESPONSE WAS 63
• LEVELS OF ANTIBODY REMAINED HIGH UP TO 3 MONTHS
  AFTER DELIVERY
• INFANT SERUM SAMPLES PROMOTED EFFICIENT
  BACTERIAL KILLING IN VITRO OF TYPE III GBS

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IMMUNE RESPONSE TO TYPE III GBS POLYSACCHARIDE
-TETANUS TOXOID CONJUGATE VACCINE

• Kasper et al. J Clin Invest 1996
• 100 women randomized
• GBS type III PS-TT conjugate (III-TT)
• Unconjugated type III PS
• Saline

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IMMUNE RESPONSE TO TYPE III GBS POLYSACCHARIDE
-TETANUS TOXOID CONJUGATE VACCINE

• RESULTS
• A gt or 4 fold rise in antibody concentration
• 90 in recipients of III-TT
• 50 in recipients of III-PS
• III-TT yielded enhanced immunogenicity compared
  to uncoupled III-PS

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SUMMARY

• GBS HAS SIGNIFICANT IMPACT ON MORBIDITY AND
  MORTALITY IN THE INFANT
• EARLY ONSET DISEASE lt 7 DAYS
• LATE ONSET DISEASE 7 d - 12 weeks
• TREATMENT OF CHOICE PENICILLIN

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SUMMARY (cont.)

• PREVENTION
• CHEMOPROPHYLAXIS
• AAP, ACOG, CDC GUIDELINES
• IMMUNOPROPHYLAXIS
• IVIG
• IMMUNIZATION

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• QUESTIONS ??