PATRICK DUFF, M.D. UNIVERSITY OF FLORIDA PREVENTION OF

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CONGENITAL INFECTIONS

• PATRICK DUFF, M.D.
• UNIVERSITY OF FLORIDA

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CONGENITAL INFECTIONSOVERVIEW

• Rubella
• CMV
• Parvovirus
• Toxoplasmosis

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CONGENITAL INFECTIONSOVERVIEW

• Epidemiology and pathophysiology
• Manifestations of congenital infection
• Diagnosis of congenital infection
• Prevention and treatment

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CONGENITAL INFECTIONSKEY QUESTIONS

• Manifestations of congenital infection
• Most valuable diagnostic tests
• Prevention and treatment

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CONGENITAL INFECTIONSBIG PICTURE

• Maternal infection in the first half of
  pregnancy, particularly the first trimester,
  poses the greatest risk to the fetus
• Organisms reach fetus by hematogenous
  dissemination across the placenta

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RUBELLAEPIDEMIOLOGY

• RNA virus
• Only a single serotype
• Occurs primarily in children and adolescents
• Most highly teratogenic of essentially all
  organisms

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RUBELLAEPIDEMIOLOGY

• With licensure of an effective vaccine in 1969,
  the frequency of infection has declined by 99
• Accordingly, congenital infection is extremely
  rare

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RUBELLAPATHOPHYSIOLOGY

• Transmission is by respiratory droplets
• Respiratory tract --gtcervical lymph
  nodes--gthematogenous dissemination
• Incubation period is 2 to 3 weeks

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RUBELLACLINICAL MANIFESTATIONS

• Malaise
• Headache
• Myalgias and arthralgias

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RUBELLACLINICAL MANIFESTATIONS

• Post-auricular adenopathy
• Conjunctivitis
• NON-PRURITIC, ERYTHEMATOUS, MACULOPAPULAR RASH

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RUBELLACLINICAL MANIFESTATIONS
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RUBELLACLINICAL MANIFESTATIONS
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RISK OF CONGENITAL RUBELLA

Time of Maternal Infection
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MANIFESTATIONS OF CONGENITAL RUBELLA

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CONSEQUENCES OF CONGENITAL RUBELLA

• Only 25 attend mainstream schools
• Estimated lifetime cost of caring for an affected
  child - 300,000

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OBSTETRIC MANAGEMENT OF CONGENITAL RUBELLA

• Diagnosis is by ultrasound
• Management options
• Pregnancy termination
• Expectant management

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PREVENTION OF CONGENITAL RUBELLA

• Vaccination
• Avoidance of exposure if susceptible

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CMVEPIDEMIOLOGY

• DNA virus
• Humans are only host
• May remain latent in host cells

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CMVEPIDEMIOLOGY

• Horizontal transmission
• Vertical transmission
• In utero greatest danger
• During delivery minimal risk
• Breast feeding minimal risk

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CMVCLINICAL MANIFESTATIONS

• Malaise
• Fever
• Lymphadenopathy
• Hepatosplenomegaly
• More severe manifestations if patient is
  immunosuppressed

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CMV DIAGNOSIS

• Cytology
• Serology
• IgM and IgG
• IgG avidity
• Culture
• PCR
• Urine and blood

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CONGENITAL CMVDETERMINANTS OF FETAL RISK

• Primary vs recurrent maternal infection
• Trimester of exposure

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CONGENITAL CMV DETERMINANTS OF FETAL RISK

• THE GREATEST RISK IS ASSOCIATED WITH PRIMARY
  MATERNAL INFECTION IN THE FIRST HALF OF PREGNANCY

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CONGENITAL CMVDETERMINANTS OF FETAL RISK

• Recurrent maternal infection poses much less risk
  to fetus
• Infection acquired during delivery or via breast
  feeding poses negligible risk

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RISK OF CONGENITAL CMV WITH PRIMARY MATERNAL
INFECTION

• 1 to 4 of pregnant women seroconvert?
• 40 - 50 of fetuses are infected?
• 5 - 15 of these fetuses will be symptomatic at
  birth

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OUTCOME OF PRIMARY CMV INFECTION

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MANIFESTATIONS OF SEVERE CONGENITAL CMV INFECTION

• Hepatosplenomegaly
• Intracranial calcifications
• Jaundice
• Growth restriction
• Chorioretinitis
• Hearing loss

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SEVERE CONGENITAL CMV INFECTION
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SEVERE CONGENITAL CMV INFECTION
Blueberry Muffin Baby
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RISK OF CONGENITAL CMV WITH RECURRENT MATERNAL
INFECTION

• Only 5 - 10 of infants become infected
• None are symptomatic at birth
• Late sequelae include hearing and visual defects
  and developmental delays

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DIAGNOSIS OF CONGENITAL CMV INFECTION

• Amniocentesis
• Viral culture
• PCR
• Ultrasound

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ULTRASOUND DIAGNOSIS OF CMV INFECTION
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ULTRASOUND DIAGNOSIS OF CMV INFECTION
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PREVENTION OF CONGENITAL CMV INFECTION

• Vaccine is not commercially available
• Anti-viral drugs do not prevent fetal injury
• Anti-CMV antibody may be effective
• Key to prevention is universal precautions

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PARVOVIRUSEPIDEMIOLOGY

• DNA virus
• Only a single serotype exists
• Humans are only known host

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PARVOVIRUSEPIDEMIOLOGY

• Transmission is by respiratory droplets and by
  blood
• Incubation period is 4 to 20 days

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PARVOVIRUSCLINICAL MANIFESTATIONS

• Erythema infectiosum (fifth disease)
• Transient aplastic crisis

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PARVOVIRUSERYTHEMA INFECTIOSUM
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PARVOVIRUSERYTHEMA INFECTIOSUM
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CONGENITAL PARVOVIRUSPATHOPHYSIOLOGY

• Virus crosses the placenta and destroys red cell
  precursors
• Fetal anemia --gt high output congestive heart
  failure --gt hydrops fetalis
• Virus also directly injures myocardial cells

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RISK OF CONGENITAL PARVOVIRUS INFECTION

Time of Maternal Infection
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PARVOVIRUS INFECTIONDIAGNOSIS IN THE MOTHER
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DIAGNOSIS OF CONGENITAL PARVOVIRUS INFECTION

• Ultrasound
• Identification of hydrops
• MCA doppler velocimetry

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TREATMENT OF CONGENITAL PARVOVIRUS INFECTION

• Intrauterine transfusion ? fetal umbilical vein

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CONGENITAL PARVOVIRUSPROGNOSIS

• If infant survives the hydropic state, the
  long-term prognosis is usually favorable

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TOXOPLASMOSISEPIDEMIOLOGY

• Toxoplasma gondii is a protozoan
• Organism exists in three forms
• Trophozoite
• Cyst
• Oocyst

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TOXOPLASMOSISEPIDEMIOLOGY
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TOXOPLASMOSISCLINICAL MANIFESTATIONS

• Most infections are asymptomatic
• When symptoms are present, they mimic
  mononucleosis

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TOXOPLASMOSISCLINICAL MANIFESTATIONS

• Toxoplasmosis may cause devastating infection in
  patients who are immune deficient
• Chorioretinitis
• CNS infection ? brain abscess

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TOXOPLASMOSISDIAGNOSIS

• Histology
• PCR
• Serology
• IgM antibody
• IgG antibody

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CONGENITAL TOXOPLASMOSIS

• The key danger is primary toxoplasmosis infection
• Greatest risk to the fetus results from maternal
  infection in first half of pregnancy
• Approximately 40 of fetuses will be infected
  when primary maternal infection develops at lt 20
  weeks gestation

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MANIFESTATIONS OF CONGENITAL TOXOPLASMOSIS

• Hepatosplenomegaly
• Chorioretinitis
• CNS injury
• Seizures
• Mental retardation

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DIAGNOSIS OF CONGENITAL TOXOPLASMOSIS

• Amniocentesis - PCR
• Ultrasound

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TREATMENT OF CONGENITAL TOXOPLASMOSIS

• Treatment of mother while fetus is still in utero
• Early treatment of the infant

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PREVENTION OF CONGENITAL TOXOPLASMOSIS

• Use precautions when handling cat litter box
• Do not eat inadequately cooked meat

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CONGENITAL INFECTIONSCONCLUSIONS

• Congenital rubella key is prevention by
  universal vaccination
• Congenital CMV key is prevention of exposure in
  pregnancy and treatment with hyperimmune globulin
  if fetus is infected

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CONGENITAL INFECTIONSCONCLUSIONS

• Congenital parvovirus avoidance of exposure is
  difficult, but intrauterine transfusion is
  life-saving

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CONGENITAL INFECTIONSCONCLUSIONS

• Congenital toxoplasmosis
• Avoid exposure during pregnancy
• Treat infected mother during pregnancy
• Treat neonate after delivery