> Table of Contents > Adenovirus Infections
Adenovirus Infections
Crystal Amadi, MD
Fozia Akhtar Ali, MD
image BASICS
DESCRIPTION
  • Acute, typically self-limited, febrile illnesses characterized by inflammation of mucous membranes including the conjunctivae, and the respiratory and GI tracts.
  • Adenovirus infections occur in epidemic and endemic situations:
    • Common types are as follows:
      • 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-F) with over 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 can survive 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 adenoviral respiratory infection.
  • Health care providers with suspected bilateral adenoviral conjunctivitis should avoid direct patient contact for 2 weeks after onset of symptoms in 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.
image DIAGNOSIS
PHYSICAL EXAM
  • Fever
  • Tonsillar erythema/exudate
  • Cervical lymphadenopathy
  • Otitis media
  • Conjunctivitis
DIFFERENTIAL DIAGNOSIS
  • The following are the primary characteristics of the major 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 aged a few days up 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
      • Usually 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 (6)[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 (7)[B]
  • P.27

  • Antigen detection in stool for enteric serotypes
  • Serologies (complement fixation) with a fourfold rise in serum antibody titer, identify 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 extensive intranuclear inclusions.
  • Bronchiolitis obliterans may occur.
image TREATMENT
GENERAL MEASURES
  • Treatment is supportive and symptomatic.
  • Infections are usually benign and of short 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 are as follows:
    • 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 & ALTERNATIVE MEDICINE
Echinacea has not been shown to be better than placebo for treatment of viral URIs (8)[B].
INPATIENT CONSIDERATIONS
Admission Criteria/Initial Stabilization
Severely ill infants or immunocompromised patients with severe illness
Nursing
Hospitalized patients with adenoviral infections should be placed on contact precautions with droplet precautions added for those with respiratory illness.
image 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%.
REFERENCES
1. Wy Ip W, Qasim W. Management of adenovirus in children after allogeneic hematopoietic stem cell transplantation. Adv Hematol. 2013;2013:176418.
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.
3. Lyons A, Longfield J, Kuschner R, et al. A doubleblind, 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.
4. Dominguez O, Rojo P, de Las Heras S, et al. Clinical presentation and characteristics of pharyngeal adenovirus infections. Pediatr Infect Dis J. 2005;24(8):733-734.
5. Centers for Disease Control and Prevention. Adenovirus symptoms. http://www.cdc.gov/adenovirus/about/symptoms.html.
6. Goto E. Meta-analysis of evaluating diagnostic accuracy of adenoclone (ELISA) for adenoviral infection among Japanese people. Rinsho Byori. 2010;58(2):148-155.
7. Kaufman HE. Adenovirus advances: new diagnostic and therapeutic options. Curr Opin Ophthalmol. 2011;22(4):290-293.
8. Barrett BP, Brown RL, Locken K, et al. Treatment of the common cold with unrefined echinacea. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 2002;137(12):939-946.
Additional Reading
  • Houlihan C, Valappil M, Waugh S, et al. Severe adenovirus infection: an under-recognized disease with limited treatment options. JICS. 2012;13(4), October.
  • Majeed A, Naeem Z, Khan DA, et al. Epidemic adenoviral conjunctivitis report of an outbreak in a military garrison and recommendations for its management and prevention. J Pak Med Assoc. 2005;55(7):273-275.
  • Pihos AM. Epidemic keratoconjunctivitis: a review of current concepts in management. J Optom. 2013;6(2):69-74.
See Also
Conjunctivitis, Acute; Intussusception; Pneumonia, Viral
Codes
ICD10
  • B34.0 Adenovirus infection, unspecified
  • B30.1 Conjunctivitis due to adenovirus
  • J12.0 Adenoviral pneumonia
Clinical Pearls
  • Adenovirus can mimic streptococcus pharyngitis with tonsillar exudates and cervical adenitis.
  • Most common cause of strep-negative tonsillitis in young children
  • Diagnosis only needs to be confirmed in severe cases and epidemics.
  • Average incubation time is 5 to 6 days.
  • Adenovirus conjunctivitis is highly contagious, handwashing and universal precautions help prevent spread.