Cytomegalovirus infection

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Cytomegalovirus infection

• Presented by Dr.D. Al-Masri.
• Moderated byDr.Y.Abu-Osbaa.

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Introduction

• It is the most common congenital infection in
  USA.
• It is a leading cause of hearing loss,mental
  retardation, and cerebral palsy.
• It is an opportunistic pathogen in
  Immunocompromised.

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Introduction

• It is a double stranded DNA virus.
• It is the largest member of herpesviridae
  family..
• Exit the cells by pinocytosis.
• Restriction endonuclease.

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Epidemiology

• The prevalence of CMV infection and the age at
  first infection vary according to living
  conditions,child rearing practices, and sexual
  behavior.
• Virus is present in saliva,tears,semen,urine,cervi
  cal secretions, and blood for months to years
  after initial infection as well as the milk of
  seropositive mothers.

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Epidemiology

• It has a worldwide distribution.
• Prevalence
• Health care providers are not at increased risk
  of infection from patients.

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Epidemiology

• It is transmitted via direct contact with body
  fluids, intimate contact, care of young children,
  blood transfusion, and organ transplant.
• Congenital CMV infection occurs in approximately
  0.5 to 1.5 of births. It is well known that CMV
  can be transmitted to the fetus even when
  maternal infection occurred long before
  conception.

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Epidemiology

• It occurs in immune mothers due to reactivation
  of latent virus during pregnancy ,chronic
  infection, or reinfection with a new strain.
• When primary infection occurs during pregnancy
  the risk of transmission to the fetus is 35. It
  occurs either by sexual contacts or contact with
  young children regardless of the gestational age.
• Intrapartum transmission or transmission by human
  milk occur more commonly than congenital
  infection.
• Infants who acquire the virus shed it in saliva
  and urine for years.

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Pathogenesis

• CMV is large complex virus that has 20 times the
  genetic material of HIV with DNA sequences
  encoding more than 100 proteins.
• The infection occurs due to impairment of T-cell
  immunity.
• Cytomegalic cells pathognomonic.

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Pathogenesis

• Important features in pathogenesis
• Ability of the virus to destroy host cells.
• Ability to infect wide range of cells and tissues
  .
• Ability to to evade and interfere with host
  defense mechanisms.
• Ability to persist indefinitely in the host.

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Pathogenesis

• Impaired organ function results from combination
  of lytic infection of cells and vascular
  compromise .
• Dissemination is due to infection of WBC and
  vascular endothelial cells.
• A small proportion of circulating monocytes in
  seropositive persons harbor latent CMV.

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Pathogenesis

• The ability of the virus to maintain active
  infection is due to
• Inhibition of host cytotoxic T-lymphocyte
  responses by interference with processing and
  presentation of viral antigens by MHC class I
  molecules.
• Interference with helper T-cell responses by
  degradation of MHC class II molecules.
• Inhibition of killing by natural killer cell.
• Interference with apoptosis and
  complement-mediated lysis or sequestration of
  chemokines.

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Clinical manifestations

• Mostly asymptomatic.
• CMV accounts for 50 of cases of
  heterophile-negative mononucleosis.
• Differ from EBV?
• Fever and malaise often persist for more than 2
  weeks.
• The expected outcome is complete recovery.
• Rare complications peripheral neuropathy,
  hemolytic anemia, thrombocytopenia, pneumonia,
  retinitis, gastrointestinal ulceration and
  encephalitis.

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Congenital CMV infection

• More than 90 of children have no clinical
  evidence of disease as newborns.
• Lab abnormalities reflect involvement of
  hepatobiliary , hematopoeitic and CNS.
• Newborns with symptomatic infection have wide
  range of severity.
• Mortality is 10-15
• Among symptomatic survivors, neonatal clinical
  abnormalities can be expected to resolve within
  weeks except for those involving CNS and hearing.

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Outcome

• Mental retardation.
• Hearing loss 7-15 in initially asymptomatic
  newborn
• Cerebral palsy.
• Retinal damage.

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Congenital CMV infection

• Factors associated with increased risk of CNS
  sequel
• Primary maternal infection during pregnancy.
• Abnormal neurologic examination findings.
• Microcephaly.
• Brain C.T.scan abnormalities.
• Increased CSF protein.
• Chorioretinitis.

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Perinatal/Neonatal CMV infection

• It is not associated with newborn illness or CNS
  sequel, except perhaps in very preterm newborns
  who have very low levels of passively acquired
  antibody at the time of infection and they may be
  left with residual neurologic sequelae
  psychomotor retardation.
• It is not associated with increase hearing loss,
  chorioretinitis or microcephaly.
• Transfusion acquired CMV to newborns whose
  mothers are seronegative can cause a picture
  similar to congenital infection and presents with
  jaundice, hepatosplenomegaly, abnormal liver
  function, thrombocytopenia, hearing loss and
  pulmonary problems.

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Differential diagnosis in the newborn

• TORCHS.
• Acute viral ,bacterial or systemic fungal
  infections.
• In born errors of metabolism can cause neonatal
  hepatitis,thrombocytopenia , hepatosplenomegaly ,
  encephalopathy and anemia.

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CMV in Immunocompromised children

• The majority are due to reactivation of the host
  CMV and these often are clinically silent.
• When primary infection occurs by blood products
  and transplanted organ, it is usually associated
  with disease.
• The clinical manifestation correlates with the
  degree of immunologic impairment.
• Primary CMV infection in transplant patients
  frequently is heralded by fever and leucopoenia,
  rash, arthralgia and elevated serum alanine
  aminotransferase levels.

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CMV in Immunocompromised children

• Complications in transplant patients
• Impaired function of the transplanted organ.
• Pneumonitis, G.I. Ulceration, hepatitis.
• Opportunistic fungal infection.

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CMV in Immunocompromised children

• Complications in AIDS patients
• Retinitis.
• Esophagitis , Colitis , Hepatitis.
• Encephalitis,peripheral neuropathy.
• Pneumonitis.
• Treatment is palliative requiring therapy with
  Ganciclovir, Foscarnet or Cidofovir followed by
  maintenance therapy with one of these drugs which
  is continued indefinitely or until the patient
  immune function improves and stabilizes.

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Laboratory diagnosis

• Congenital CMV infection is diagnosed by
• Detection of virus in the urine or saliva of a
  newborn
• PCR.
• CMV IgM transient.
• Detection of CMV within the first 3 weeks of life
  is considered proof of congenital CMV but after
  this period it is not certain if it is due to
  prenatal or perinatal infection.
• Viremia demonstrated by buffy coat or DNA
  indicates active infection.

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Laboratory diagnosis

• Diagnosis of CMV infections in immunocompromised
  patients is much more difficult.
• Serology is of limited value.
• CMV IgG is a good marker for past infection and
  identifies the problematic positive
  donor/negative recipient situation that carries a
  high risk for primary infection and CMV disease
  in the immediate post transplant period.

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Laboratory diagnosis

• Detection of CMV in blood is a much better
  predictor of disease among immunocompromised
  patients than is shedding of virus.
• Quantitative tests has good correlation with the
  clinical picture either by detection of WBC
  positive for CMV antigens by immunofluorescence
  or quantitative PCR.

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Laboratory diagnosis

• Congenital infection
• Virus isolation.
• IgG
• IgM

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Management

• Antiviral treatment has reduced the burden of
  CMV disease substantially in immunocompromised
  patients.
• Ganciclovir, Foscarnet, and Cidofovir.
• No antiviral agent is approved for treatment of
  congenital CMV infection but.
• Side effects include neutropenia ,
  thrombocytopenia , liver dysfunction
  ,reproductive toxicity and carcinogenicity.

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Management

• The approach to antiviral treatment in
  immunocompromised patients can vary with
• The clinical settings.
• The type of CMV infection.
• Clinical manifestations of CMV disease.
• Laboratory evidence of CMV infection.
• Degree of immunosuppression.

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Anticipatory management
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Prevention

• All preschool-age children should be considered
  potential sources of infection.
• Avoid contact with body fluids from young
  children and careful hand washing
• Educating women before getting pregnant.
• Vaccination.
• Limit transfusion-acquired CMV infection.
• Prophylactic antiviral treatment and passive
  immunization to prevent CMV disease after
  transplantation.

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Thank you