Adenovirus Infections

Basics

Description

  • Acute, typically self-limited, febrile illnesses characterized by inflammation of mucous membranes including the conjunctivae, respiratory, and GI tracts
  • Adenovirus infections occur in epidemic and endemic situations.
    • Common types:
      • Acute febrile respiratory illness—affects primarily children
      • Acute respiratory disease—affects adults
      • Viral pneumonia—affects children and adults
      • Acute pharyngoconjunctival fever—affects children, particularly after summer swimming
      • Acute follicular conjunctivitis—affects all ages
      • Epidemic keratoconjunctivitis—affects adults
      • Intestinal infections leading to enteritis, mesenteric adenitis, and intussusception
    • Conjunctivitis
  • System(s) affected: cardiovascular; GI; hematologic/lymphatic/immunologic; musculoskeletal; nervous; pulmonary; renal/urologic; ophthalmologic

Geriatric Considerations
Complications more likely in elderly populations

Pediatric Considerations
Viral pneumonia in infants and neonates (may be fatal)

Epidemiology

  • Predominant age: <10 years but epidemics in all ages
  • Predominant sex: male = female
  • Occurs worldwide and throughout the year but more frequently in warmer months

Incidence
  • Common infection: 2–5% of all upper respiratory infections (URIs) and >10% of URIs in children
  • Most individuals show evidence of prior adenovirus infection by age 10 years.
  • Many adenovirus infections are subclinical or asymptomatic.
  • 15–70% of conjunctivitis worldwide

Etiology and Pathophysiology

  • DNA virus 60 to 90 nm in size, 6 species (A through F) with >50 known serotypes
  • Adenovirus can remain dormant in lymphoreticular tissue (adenoids and tonsils) after exposure, and viral shedding may persist for months (1).
  • Transmission
    • Aerosol droplets, fomites, fecal–oral
    • Virus survives on skin and environmental surfaces.
    • Incubation period is 5 to 9 days (2).
  • Most common known pathogens:
    • Types 1 to 5, 7, 14, and 21 cause upper respiratory illness and pneumonia.
    • Types 3, 7, and 21 cause pharyngoconjunctival fever.
    • Types 31, 40, and 41 cause gastroenteritis.
    • Types 8, 19, 37, 53, and 54 cause epidemic keratoconjunctivitis.
    • Types 5, 7, 14, and 21 cause more severe illness.

Risk Factors

  • Large number of people gathered in a confined area (e.g., military recruits, college students, daycare centers, summer camps, community swimming pools)
  • Immunocompromised are at risk for severe disease.

General Prevention

  • Live, enteric-coated oral type 4 and type 7 adenovirus vaccine available for military recruits (or other personnel at high risk ages 17 to 50 years); reduces incidence of acute respiratory disease (3)
  • Frequent hand washing
  • Decontamination of environmental surfaces using chlorine, bleach, formaldehyde, or heat
  • Universal precautions, particularly when examining patients with epidemic keratoconjunctivitis; droplet precautions if suspected respiratory infection
  • Health care providers with suspected bilateral adenoviral conjunctivitis should avoid direct patient contact for 2 weeks after onset of symptoms in the second eye.

Commonly Associated Conditions

  • Otitis media
  • Conjunctivitis
  • Bronchiolitis
  • Viral enteritis
  • Less frequent syndromes (seen primarily in immunocompromised individuals): meningoencephalitis, hepatitis, myocarditis, pancreatitis, genital infections, intussusception and mesenteric adenitis hemorrhagic cystitis, and interstitial nephritis

Diagnosis

History

Depends on type (see “Differential Diagnosis”); common symptoms with most respiratory forms

  • Headache, malaise
  • Sore throat
  • Cough, coryza
  • Fever (moderate to high)
  • Vomiting, diarrhea, abdominal pain
  • Ear pain
  • Urinary symptoms/hematuria
  • Eye redness and pain
  • Irritative voiding symptoms (bladder involvement)

Physical Exam

  • Fever
  • Tonsillar erythema/exudate
  • Cervical lymphadenopathy
  • Otitis media
  • Conjunctivitis

Differential Diagnosis

  • Characteristics of adenovirus infections:
    • Acute respiratory illness
      • Mostly in children
      • Incubation period: 2 to 5 days
      • Malaise, fever, chills, headache, pharyngitis, hoarseness, dry cough
      • Fever lasting 2 to 4 days
      • Illness subsiding in 10 to 14 days
      • DDx: rhinovirus, influenza, parainfluenza, RSV
    • Viral pneumonia
      • Sudden onset of high fever, rapid infection of upper and lower respiratory tracts, skin rash, diarrhea
      • Occurs mostly in children from newborn to 3 years
      • DDx: bacterial pneumonia, RSV, influenza, parainfluenza
    • Acute pharyngoconjunctival fever
      • Spiking fever, headache, pharyngitis, conjunctivitis (typically unilateral), rhinitis, cervical adenitis
      • Subsides in 1 week
      • DDx: bacterial conjunctivitis, enterovirus, herpes simplex virus (HSV)
    • Epidemic keratoconjunctivitis
      • Unilateral onset of ocular redness and edema, periorbital edema, periorbital swelling, foreign body sensation
      • Lasts 3 to 4 weeks
      • DDx: bacterial conjunctivitis, enterovirus, HSV
    • Viral enteritis
      • Nausea/vomiting, diarrhea, abdominal pain
      • DDx: bacterial enteritis, bowel obstruction

Diagnostic Tests & Interpretation

Initial Tests (lab, imaging)
  • Confirmation necessary only in severe cases and epidemics
  • Viral cultures from respiratory, ocular, or fecal sources
  • Pharyngeal isolate suggests recent infection.
  • Adenovirus-specific ELISA; rapid but less sensitive than culture (4)[A]
  • Adenovirus DNA via polymerase chain reaction (PCR)
  • Rapid pathogen screening (Adeno Detector) is available for detecting adenoviral conjunctivitis (sensitivity, 89%; specificity, 94%); results in 10 minutes (5)[B]
  • Antigen detection in stool for enteric serotypes
  • Serologies (complement fixation): A 4-fold rise in serum antibody titer suggests recent adenoviral infection.
  • Radiographs: bronchopneumonia in severe respiratory infections

Diagnostic Procedures/Other
Biopsy (lung or other) may be needed in severe or unusual cases; usually only in immunocompromised patients

Test Interpretation
  • Varies with each virus
  • Severe pneumonia may show intranuclear inclusions.
  • Bronchiolitis obliterans may occur.

Treatment

General Measures

  • Treatment is supportive and symptomatic.
  • Infections are usually benign and short in duration.

Medication

First Line
  • Acetaminophen 10 to 15 mg/kg PO for analgesia (Avoid aspirin.)
  • Antivirals and immunotherapy for immunocompromised individuals and patients with severe disease:
    • No controlled trials showing benefit of any antiviral agents against human adenovirus infection; however, cidofovir (1 mg/kg every other day) is most commonly used.
    • For adenoviral conjunctivitis, topical ganciclovir 0.15% ophthalmic gel has been suggested for “off-label” use.

Complementary and Alternative Medicine

Echinacea has not been shown to be better than placebo for treatment of viral URIs.

Inpatient Considerations

  • Admission criteria/initial stabilization: ill infants or immunocompromised patients with severe illness
  • Hospitalized patients with adenoviral infections should be placed on contact precautions with droplet precautions added for those with respiratory illness.

Ongoing Care

Follow-up Recommendations

Rest during febrile phases

Patient Monitoring
For severe infantile pneumonia and conjunctivitis, daily physical exam until well

Diet

No special diet

Patient Education

  • Avoid aspirin in children.
  • Give instructions for saline nasal spray, cough preparations, frequent hand washing, and surface cleaning.

Prognosis

  • Self-limited, usually without sequelae
  • Severe illness and death in neonates and in immunocompromised hosts can occur; severe pneumonia in children <2 years can have a mortality rate as high as 16%.

Complications

Few, if any, recognizable long-term problems

Additional Reading

See Also

Conjunctivitis, Acute ; Intussusception ; Pneumonia, Viral

Codes

ICD-10

  • A08.2 Adenoviral enteritis
  • B30.1 Conjunctivitis due to adenovirus
  • B30.2 Viral pharyngoconjunctivitis
  • B34.0 Adenovirus infection, unspecified
  • J12.0 Adenoviral pneumonia

ICD-9

  • 008.62 Enteritis due to adenovirus
  • 077.2 Pharyngoconjunctival fever
  • 077.3 Other adenoviral conjunctivitis
  • 079.0 Adenovirus infection in conditions classified elsewhere and of unspecified site
  • 480.0 Pneumonia due to adenovirus

SNOMED

  • 186679007 Conjunctivitis due to adenovirus
  • 236063005 adenoviral gastroenteritis (disorder)
  • 25225006 Disease due to Adenovirus
  • 3163006 Acute adenoviral follicular conjunctivitis
  • 41207000 Adenoviral pneumonia (disorder)
  • 70385007 Adenoviral pharyngoconjunctivitis
  • 70880006 Adenoviral enteritis

Clinical Pearls

  • Adenovirus can mimic streptococcus pharyngitis with tonsillar exudates and cervical adenitis.
  • Adenovirus is the most common cause of strep-negative tonsillitis in young children.
  • Confirm diagnosis only in severe cases and epidemics.
  • Average incubation time is 5 to 6 days.
  • Adenovirus conjunctivitis is highly contagious; hand washing and universal precautions help prevent spread.

Authors


Crystal Nwagwu, MD
Fozia Akhtar Ali, MD

Bibliography

  1. Wy Ip W, Qasim W. Management of adenovirus in children after allogeneic hematopoietic stem cell transplantation. Adv Hematol. 2013;2013:176418.  [PMID:24288536]
  2. Lessler J, Reich NG, Brookmeyer R, et al. Incubation periods of acute respiratory viral infections: a systematic review. Lancet Infect Dis. 2009;9(5):291–300.  [PMID:19393959]
  3. Lyons A, Longfield J, Kuschner R, et al. A double-blind, placebo-controlled study of the safety and immunogenicity of live, oral type 4 and type 7 adenovirus vaccines in adults. Vaccine. 2008;26(23):2890–2898.  [PMID:18448211]
  4. Goto E. Meta-analysis of evaluating diagnostic accuracy of adenoclone (ELISA) for adenoviral infection among Japanese people. Rinsho Byori. 2010;58(2):148–155.  [PMID:16094232]
  5. Kaufman HE. Adenovirus advances: new diagnostic and therapeutic options. Curr Opin Ophthalmol. 2011;22(4):290–293. [PMID:21537185]


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