para>Complications more likely in elderly populations á
Pediatric Considerations
Viral pneumonia in infants and neonates (may be fatal)
á
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.
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 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]
- 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 virus
- Severe 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.