Adenovirus

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Content

Indications for Testing

  • Severe pneumonia in
    • Immunocompromised patient
    • Military recruit
    • Young child

Laboratory Testing

  • CDC diagnosis recommendations for adenovirus
  • Immunocompetent patients
    • Most cases are diagnosed based on clinical presentation alone
    • Antigen/DNA testing
      • DFA – respiratory specimens or nasopharyngeal swabs
      • RT PCR (qualitative) – highly sensitive; nasopharyngeal swabs
        • Standard of care for diagnosing adenovirus in tissue specimen
      • EIA – most useful in fecal samples for types 40, 41in gastroenteric disease
    • Serologic testing relies on demonstration of antibodies to group-specific antigens
      • Typically used in epidemiological studies
      • Often requires acute and convalescent sera
  • Immunocompromised patients
    • PCR
      • Standard screening tool for immunocompromised patients suspected of have adeno infection
      • Peripheral blood viremia appears to be the only site indicative of disseminated infection
    • Viral culture
      • Gold standard
      • Use of blood samples – not recommended due to lack of sensitivity
      • Slow growth makes early diagnosis difficult
      • Not recommended for most patients

Histology

  • Immunohistochemistry – adenovirus stain

Differential Diagnosis

Adenoviruses usually cause mild, self-limiting respiratory illnesses, primarily in children. In immunocompromised patients, it may cause severe, fatal disease.

Epidemiology

  • Prevalence
    • Causes 5-7% of respiratory infections in children
    • Year-round infection
    • Rarely fatal, but 50% of infants and young children have prolonged, intermittent disease
  • Age – usually <10 years (primary infection)
  • Transmission
    • Respiratory droplet transfer (fecal-oral)
    • Neonatal transmission following vaginal delivery (rare)
    • Nosocomial transmission reported

Organism

  • Double-stranded DNA virus; belongs to Adenoviridae family
  • Classified into 7 species, A-G – 60 serotypes identified
    • Types 4 and 7 are common in military recruit outbreaks
    • Type 14 commonly associated with severe and sometimes fatal respiratory illnesses

Risk Factors

  • Military service (recruit)
  • Immunocompromised status
  • Malnutrition in children <2 years
  • Transplant patients
    • Highest risk in allogeneic hematopoietic transplants with T-cell depletion, ATG treatment, or in the presence of graft versus host (grades III, IV)
    • Autologous transplants – much lower risk

Clinical Presentation

  • Immunocompetent patients
    • Most infections are mild, self-limited respiratory illness
    • Bronchiolitis, pneumonia (types 3, 7, 21)
    • Acute diarrhea (types 40, 41)
    • Hemorrhagic cystitis (types 7, 11, 21, 34, 35)
    • Epidemic keratoconjunctivitis (types 8, 19, 37)
    • Fatal adenovirus infections can occur in infants and immunocompromised adults (type 14)
    • Complications – hepatitis, acute colitis, cystitis, meningitis, encephalitis
  • Immunocompromised patients
    • Post-transplantation – solid organ
      • Usually 2-3 months after transplant
      • First symptoms – fever, enteritis, elevated transaminases, and pancytopenia
      • More severe disease in pediatric population
      • Often first manifests in organ of transplantation
    • Post-transplantation – hematopoiectic stem cell (HSCT)
      • Ranges from mild gastroenteritis, respiratory disease to severe disease (multi-organ failure)
      • Disseminated disease is frequently fatal

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations.
Click on number for test-specific information in the ARUP Laboratory Test Directory

Respiratory Viruses DFA with Reflex to Viral Culture, Respiratory 0060281
Method: Direct Fluorescent Antibody Stain/Cell Culture

Respiratory Viruses Rapid Culture 2001504
Method: Cell Culture/Immunofluorescence

Limitations

Other viruses such as HSV, CMV, or human metapneumovirus not routinely detected in this culture

Limited sensitivity for adenovirus compared to conventional culture

Adenovirus, Quantitative PCR 2007192
Method: Quantitative Real-Time Polymerase Chain Reaction

Limitations

Lower false-negative rate compared to DFA

Adenovirus by Qualitative PCR 2007473
Method: Qualitative Real-Time Polymerase Chain Reaction

Limitations

Lower false-negative rate compared to DFA

Adenovirus 40-41 Antigens by EIA 0065066
Method: Qualitative Enzyme Immunoassay

Adenovirus by Immunohistochemistry 2003430
Method: Immunohistochemistry

Viral Culture, Non-Respiratory and Cytomegalovirus Rapid Culture 2006496
Method: Cell Culture/Immunofluorescence

Limitations

Slow growth; not ideal for acute identification

Additional Tests Available

Adenovirus Antibody, Serum 2013015
Method: Semi-Quantitative Complement Fixation

Comments

Not recommended for diagnosis of active adenovirus infection

Direct detection of virus is recommended (culture, DFA, PCR, or antigen detection as clinically indicated by suspected site of infection)

Respiratory Viruses DFA 0060289
Method: Direct Fluorescent Antibody Stain

Comments

Not a preferred stand-alone test

Low sensitivity compared to culture; culture or PCR backup recommended

Rotavirus and Adenovirus 40-41 Antigens 0065067
Method: Qualitative Enzyme Immunoassay

Comments

Confirm etiologic agent of gastroenteritis

Viral Culture, Respiratory and Cytomegalovirus Rapid Culture 2006497
Method: Cell Culture/Immunofluorescence

Comments

Viruses that can be isolated – adenovirus; CMV; enterovirus; HSV; influenza A and B; parainfluenza types 1,2, and 3; RSV; and VZV

Virus-specific tests are recommended

Molecular diagnostics are preferred for suspected invasive CMV

General References

Echavarría M. Adenoviruses in immunocompromised hosts. Clin Microbiol Rev. 2008; 21(4): 704-15. PubMed

Kehl S, Kumar S. Utilization of nucleic acid amplification assays for the detection of respiratory viruses. Clin Lab Med. 2009; 29(4): 661-71. PubMed

Lenaerts L, De Clercq E, Naesens L. Clinical features and treatment of adenovirus infections. Rev Med Virol. 2008; 18(6): 357-74. PubMed

Lion T. Adenovirus infections in immunocompetent and immunocompromised patients. Clin Microbiol Rev. 2014; 27(3): 441-62. PubMed

Lynch J, Fishbein M, Echavarría M. Adenovirus. Semin Respir Crit Care Med. 2011; 32(4): 494-511. PubMed

Sivan A, Lee T, Binn L, Gaydos J. Adenovirus-associated acute respiratory disease in healthy adolescents and adults: a literature review. Mil Med. 2007; 172(11): 1198-203. PubMed

Tebruegge M, Curtis N. Adenovirus: an overview for pediatric infectious diseases specialists. Pediatr Infect Dis J. 2012; 31(6): 626-7. PubMed

Medical Reviewers

Last Update: January 2016