Cytomegalovirus Infection
Cytomegalovirus Infection: Excerpt from The 5-Minute Pediatric Consult
Sujit S. Iyer, MDRakesh D. Mistry, MD
Cytomegalovirus Infection - BASICS
Cytomegalovirus Infection - description
Cytomegalovirus (CMV) is a ubiquitous double-stranded DNA virus that is a member of the herpesvirus family. Establishes latency in peripheral mononuclear cells
Cytomegalovirus Infection - general prevention
- Drainage and secretion, and pregnant women precautions, should be instituted for hospitalized patients known to be shedding CMV.
- Seriously ill neonates should receive blood products from cytomegalovirus-negative donors.
- CMV-seronegative solid-organ or bone marrow transplantation recipients should receive organs (and all blood products) from CMV-negative donors whenever possible.
- Controversy exists over the role of hyperimmune globulin to prevent disseminated CMV disease in CMV-negative recipients of CMV-positive transplantation.
Cytomegalovirus Infection - epidemiology
- Increased rates of primary infection are seen in early childhood, adolescence, and childbearing years.
- Transmission may occur by contact with infected respiratory secretions, urine, or breast milk, sexual contact, solid-organ transplantation, or transfusion of infective blood products.
Cytomegalovirus Infection - prevalence
Seroprevalence varies with socioeconomic status; 50% of middle- and 80% of lower-socioeconomic-status adults are seropositive.
Cytomegalovirus Infection - pathophysiology
Infection leads to intranuclear inclusions with massive enlargement of cells. Almost any organ may become infected with CMV in severe disseminated infection.
Cytomegalovirus Infection - associated conditions
- Congenital infection:
- Occurs in 1% of newborns
- Intrauterine transmission more common in mothers wth primary infection during pregnancy (40–50%) compared to recurrent infection (<1%)
- 10% of infected infants are symptomatic at birth, with severe disease characterized by growth retardation, hepatosplenomegaly, thrombocytopenia, and CNS involvement.
- 10–20% of infants who are asymptomatically infected at birth will develop long-term sequelae.
- Of symptomatically infected infants, 90% will have neurological sequelae. Degree of impairments may be predicted by CT findings and FOC at birth.
- Mononucleosis syndrome:
- CMV can cause a mononucleosis-like syndrome similar to that caused by Epstein-Barr virus (EBV) infection.
- The most common symptoms are malaise (67%) and fever (50%). ~70% of patients have abnormal liver enzymes.
- Pharyngitis and splenomegaly less common and severe than observed with EBV-induced mononucleosis.
- Interstitial pneumonitis:
- Seen primarily in immunosuppressed children and adults
- Begins with fever and nonproductive cough, but may progress to dyspnea and severe hypoxia over 1–2 weeks
- Mild, self-limited pneumonitis may occur in immunocompetent patients.
- Retinitis:
- Seen in ~30% of infants with symptomatic congenital infection
- Immunosuppressed children should have regular eye exams.
- Hepatitis:
- Occurs in healthy individuals with primary infections and in immunosuppressed patients with either primary or reactivated disease
- Fever, mild elevation of liver enzymes and hepatomegaly, are typical. Jaundice and severe hepatitis are uncommon.
- GI disease:
- Severely immunosuppressed patients may experience esophagitis, gastritis, colitis, or pancreatitis.
- Diagnosis requires endoscopy with biopsy.
- CNS disease:
- Commonly seen in infants with symptomatic congenital infection
- Characterized by microcephaly, periventricular calcifications, seizures, developmental delay, and sensorineural hearing loss
- Encephalitis or meningoencephalitis may occur postnatally in either healthy or immunocompromised patients.
- Deafness:
- CMV is the most common cause of congenital deafness.
- Onset of deafness often seen after 1st month of life and is progressive. May be missed by newborn hearing screen (if only done in 1st 2 weeks of life)
Cytomegalovirus Infection - DIAGNOSIS
Cytomegalovirus Infection - signs & symptoms
Cytomegalovirus Infection - history
- Day care attendance:
- Increased risk of infection
- Recent blood transfusion:
- Transfusion-associated CMV
- Use of immunosuppressive medications:
- Increased use of serious infection
- Prolonged fever:
- Mononucleosislike syndrome
- Blurred vision:
- Cough, dyspnea, wheezing:
- Vomiting, abdominal pain, diarrhea (watery or bloody):
Cytomegalovirus Infection - physical exam
- Microcephaly:
- White, perivascular retinal infiltrates and hemorrhage:
- Deafness (may require audiogram, brainstem evoked auditory responses):
- Photophobia, headache, nuchal rigidity:
- Tachypnea, rales:
- Hepatomegaly and/or splenomegaly:
- Mononucleosislike syndrome
- Rash:
- Petechiae, purpura, “blueberry muffin” lesions, rubelliform rash
- Adenopathy:
- Mononucleosislike syndrome
Cytomegalovirus Infection - tests
Cytomegalovirus Infection - lab
- Viral culture: Virus may be isolated from nasopharyngeal/oropharyngeal secretions, urine, stool, WBC. Isolation may take up to 4 weeks. Urine or saliva samples are most common way to diagnose congenital disease.
- Shell-vial assay system (staining for early antigen production) allows detection of virus 24–72 hours after inoculation
- Quantitative antigenemia assay: Detection of circulating CMV-infected mononuclear cells by indirect immunofluorescence. In an immunocompromised patient, may monitor response to therapy or identify viral reactivation
- Serology: Enzyme-linked immunosorbent assay or indirect fluorescent antibody assay to detect the presence of CMV IgM or IgG. CMV IgM usually persists for 6 weeks following primary infection, although it may persist up to 6 months.
- Due to frequency of asymptomatic shedding, mere isolation of virus does not necessarily establish an etiologic association.
- Severely immunocompromised patients who are actively infected with CMV may be seronegative.
- 4-fold rise in CMV IgG is not diagnostic of primary infection. Increased antibody titers may occur with reactivation.
Cytomegalovirus Infection - imaging
Noncontrast head CT:
- Periventricular calcifications, cystic abnormalities, ventriculomegaly, periventricular leukomalacia
Cytomegalovirus Infection - differencial diagnosis
- Congenital infection:
- Congenital rubella syndrome
- Toxoplasmosis
- Syphilis
- Neonatal herpes simplex virus
- Human immunodeficiency virus
- Enteroviral infection
- Mononucleosis syndrome:
- EBV infection
- Toxoplasmosis
- Hepatitis A or B infection
- Interstitial pneumonitis:
- Respiratory syncytial virus
- Adenovirus
- Measles
- Varicella
- Pneumocystis carinii
- Chlamydia
- Mycoplasma
- Fungal
- Drug/toxin-induced pneumonitis
- Retinitis:
- Ocular toxoplasmosis
- Candidal retinitis
- Syphilis
- Herpes simplex virus
- Hepatitis:
- EBV infection
- Hepatitis A, B, or C infection
- Enterovirus
- Adenovirus
- Herpes simplex virus
- Drug/toxin-induced
- GI disease:
- Herpes simplex virus
- Adenovirus
- Salmonella
- Shigella
- Campylobacter
- Yersinia
- Clostridium difficile
- Giardia
- Cryptosporidium
- CNS disease:
- Congenital disease (see “Congenital Infection,” above)
- Meningoencephalitis in immunocompetent host: Herpes simplex virus, EBV, varicella-Zoster virus, enterovirus, arbovirus
- Meningoencephalitis in immunocompromised host: In addition to organisms listed previously, should include HIV encephalitis, fungal meningitis, toxoplasmosis
Cytomegalovirus Infection - TREATMENT
Cytomegalovirus Infection - medication
- Ganciclovir will suppress viral replication but not eradicate virus (virostatic agent).
- Indications: CMV chorioretinitis in immunocompromised patients; tissue diagnosis (hepatitis, enteritis, pneumonitis) of CMV infection or isolation of CMV from buffy coat of immunocompromised patient; consider for neonate with documented CNS disease to prevent progressive postnatal hearing loss
- Side effects: Neutropenia (50%), thrombocytopenia (∼5%)
- Foscarnet—virostatic agent
- Indications: CMV chorioretinitis, pneumonitis, hepatitis, enteritis (biopsy proven) in immunocompromised patient who has failed to improve on ganciclovir therapy or who has experienced significant bone marrow toxicity related to ganciclovir use
- Side effects: Renal impairment (25%), headache (25%), seizures (10%)
Cytomegalovirus Infection - FOLLOW UP
Cytomegalovirus Infection - prognosis
Varies with nature of infection (see “Associated Conditions”)
Cytomegalovirus Infection - complications
Varies with nature of infection (see “Associated Conditions”)
Cytomegalovirus Infection - bibliography
- Boppana, et al. Neuroradiographic findings in the newborn period and long term outcome in children with symptomatic congenital cytomegalovirus infection. Pediatrics. 1997;99:409–414.
- Boppana SR, Pass RF, Britt WJ, et al. Symptomatic congenital cytomegalovirus infection. Pediatr Infect Dis J. 1992;11:939–999.
Demmler GJ. Acquired cytomegalovirus infections. In: Feigin RD, Cherry JD, eds. Textbook of Pediatric Infectious Diseases. 5th ed. Philadelphia: WB Saunders; 2004:1532–1547.- Fowler K, et al. Newborn hearing screening: Will children with hearing loss caused by congenital cytomegalovirus infection be missed? J Pediatr. 1999;135:60–64.
- Fowler KB, Stagno S, Pass RF, et al. The outcome of congenital cytomegalovirus infection in relation to maternal antibody status. N Engl J Med. 1992;326(10):663–667.
- Kimberlin DW, Lin CY, Sanchez PJ, et al. Effect of ganciclovir therapy on hearing in symptomatic congenital cytomegalovirus diseases involving the central nervous system: A randomized controlled trial. J Pediatr. 2003;143:16–25.
- Noyola D, et al. Early predictors of neurodevelopmental outcome in symptomatic congenital cytomegalovirus infection. J Pediatr. 2001;138:325–331.
- Stagno S, et al. Congenital cytomegalovirus infection: The relative importance of primary and recurrent maternal infection. N Engl J Med. 1982;306:945–949.
Cytomegalovirus Infection - CODES
Cytomegalovirus Infection - icd9
078.5 Cytomegaloviral disease
Cytomegalovirus Infection - FAQ
- Q: Should children with congenital cytomegalovirus infection be excluded from day care settings?
- A: No. Due to the high frequency of shedding of cytomegalovirus in the urine and saliva of asymptomatic children, especially those under 2 years of age, exclusion from out-of-home care is not justified for any child known to be infected with cytomegalovirus. Careful attention to hygienic practices, especially hand washing, is important.
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Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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