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Adenovirus Infections

- 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).

- 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

para>Complications more likely in elderly populations á

Pediatric Considerations

Viral pneumonia in infants and neonates (may be fatal)

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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).
  • TransmissionAerosol droplets, fomites, fecal-oralVirus 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.

DIAGNOSIS

HISTORY

Depends on type (see "Differential Diagnosis"Ł). Common symptoms with most respiratory forms (4,5) á

  • 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

  • The following are the primary characteristics of the major adenovirus infections:Acute respiratory illnessMostly in childrenIncubation period: 2 to 5 daysMalaise, fever, chills, headache, pharyngitis, hoarseness, dry coughFever lasting 2 to 4 daysIllness subsiding in 10 to 14 daysDDx: rhinovirus, influenza, parainfluenza, RSVViral pneumoniaSudden onset of high fever, rapid infection of upper and lower respiratory tracts, skin rash, diarrheaOccurs mostly in children aged a few days up to 3 yearsDDx: bacterial pneumonia, RSV, influenza, parainfluenzaAcute pharyngoconjunctival feverSpiking fever, headache, pharyngitis, conjunctivitis (typically unilateral), rhinitis, cervical adenitisSubsides in 1 weekDDx: bacterial conjunctivitis, enterovirus, herpes simplex virus (HSV)Epidemic keratoconjunctivitisUsually unilateral onset of ocular redness and edema, periorbital edema, periorbital swelling, foreign body sensationLasts 3 to 4 weeksDDx: bacterial conjunctivitis, enterovirus, HSVViral enteritisNausea/vomiting, diarrhea, abdominal painDDx: 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 sourcesPharyngeal 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]
  • 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 á

Test Interpretation

  • Varies with each virusSevere pneumonia may show extensive intranuclear inclusions.
  • Bronchiolitis obliterans may occur.

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"Ł use.

COMPLEMENTARY & ALTERNATIVE MEDICINE

Echinacea has not been shown to be better than placebo for treatment of viral URIs (8)[B]. á

INPATIENT CONSIDERATIONS

Admission Criteria/Initial Stabilization

Severely ill infants or immunocompromised patients with severe illness á

Nursing

Hospitalized patients with adenoviral infections should be placed on contact precautions with droplet precautions added for those with respiratory illness. á

ONGOING CARE

FOLLOW-UP RECOMMENDATIONS

Rest during febrile phases á

Patient Monitoring

For severe infantile pneumonia and conjunctivitis, daily physical exam until well. á

DIET

No special diet á

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 á

REFERENCES

11 Wy Ip áW, Qasim áW. Management of adenovirus in children after allogeneic hematopoietic stem cell transplantation. Adv Hematol. 2013;2013:176418.22 Lessler áJ, Reich áNG, Brookmeyer áR, et al. Incubation periods of acute respiratory viral infections: a systematic review. Lancet Infect Dis. 2009;9(5):291-300.33 Lyons áA, Longfield áJ, Kuschner áR, 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):2890-2898.44 Dominguez áO, Rojo áP, de Las Heras áS, et al. Clinical presentation and characteristics of pharyngeal adenovirus infections. Pediatr Infect Dis J. 2005;24(8):733-734.55 Centers for Disease Control and Prevention. Adenovirus symptoms. http://www.cdc.gov/adenovirus/about/symptoms.html.66 Goto áE. Meta-analysis of evaluating diagnostic accuracy of adenoclone (ELISA) for adenoviral infection among Japanese people. Rinsho Byori. 2010;58(2):148-155.77 Kaufman áHE. Adenovirus advances: new diagnostic and therapeutic options. Curr Opin Ophthalmol. 2011;22(4):290-293.88 Barrett áBP, Brown áRL, Locken áK, 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 áC, Valappil áM, Waugh áS, et al. Severe adenovirus infection: an under-recognized disease with limited treatment options. JICS. 2012;13(4), October.
  • Majeed áA, Naeem áZ, Khan áDA, 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 áAM. Epidemic keratoconjunctivitis: a review of current concepts in management. J Optom. 2013;6(2):69-74.

SEE ALSO

Conjunctivitis, Acute; Intussusception; Pneumonia, Viral á

CODES

ICD10

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

ICD9

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

SNOMED

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

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.