Basics
Description
Adenoviruses are ubiquitous, nonenveloped, double-stranded DNA viruses capable of causing respiratory tract disease and gastroenteritis.
Epidemiology
- Primary infection usually occurs early in life (by age 5 years) and is, most often, characterized by upper respiratory symptoms.
- Military trainees are especially susceptible to infection, probably due to crowded living conditions.
- Respiratory and enteric infections may occur at any time of year. In temperate climates, peaks tend to occur in winter months.
- Cause approximately 5% of all pediatric respiratory tract infections and 5-10% of pneumonias
- Transmission of respiratory disease occurs via infected droplets.
- Transmission of enteric adenoviruses is via the fecal-oral route.
- Transmission can less commonly occur via contact with infected conjunctiva.
- Outbreaks of pharyngoconjunctival fever have been associated with inadequately chlorinated swimming pools and shared towels.
- One of the most common causes of viral myocarditis in children and adults
Incidence
Peaks in the first 2 years of life
Risk Factors
Exposure to adenovirus
General Prevention
Precautions for hospitalized patientsView LargePrecautions for hospitalized patientsSymptomsType of precautionsRespiratory diseaseContact and dropletGastrointestinalContactConjunctivitisContact
A live oral vaccine for prevention of acute respiratory tract disease is used in military personnel.
Pathophysiology
Adenoviruses may cause a lytic infection or a chronic/latent infection. In addition, they are capable of inducing oncogenic transformation of cells, although the clinical significance of this observation remains unclear.
Etiology
There are at least 57 identified human serotypes classified into 7 species (species A to G).
Commonly Associated Conditions
- Respiratory infections
- Upper respiratory tract infections: otitis media, common cold, pharyngitis
- Lower respiratory tract infection: pneumonia, pertussis-like syndrome, croup, necrotizing bronchitis, bronchiolitis (serotypes 3, 7, and 21 predominant in pneumonia epidemics)
- Pharyngoconjunctival fever
- Low-grade fever associated with conjunctivitis, pharyngitis, rhinitis, and cervical adenitis
- 15% of patients may have meningismus.
- Increased incidence in summer months
- Common source outbreaks most often associated with type 3
- Epidemic keratoconjunctivitis
- Bilateral conjunctivitis with preauricular adenopathy
- May persist for up to 4 weeks
- Corneal opacities may persist for several months.
- Associated with types 8, 19, and 37
- Myocarditis preceding viral illness
- Present with cardiovascular collapse, congestive heart failure, respiratory distress, or ventricular tachycardia
- Prognosis is poor.
- High mortality; a large number require transplant, and a portion develop dilated cardiomyopathy.
- Hemorrhagic cystitis may cause microscopic or gross hematuria.
- If present, gross hematuria persists on average for 3 days.
- Often associated with dysuria and urinary frequency
- More common in males than females
- Associated with types 11 and 21
- Can occur in both immunocompetent and immunocompromised hosts
- Infantile diarrhea
- Watery diarrhea associated with fever
- Symptoms may persist for 1-2 weeks
- Associated with types 40, 41, and less often 31
- CNS infection epidemics (associated with outbreaks of respiratory disease) and sporadic cases of encephalitis and meningitis have been observed; often associated with pneumonia
- Immunocompromised hosts
- Can cause disseminated disease including pneumonia, hepatitis, and gastroenteritis
- Frequently observed in transplanted patients; up to 40% of pediatric human stem cell transplant recipients and in 5-10% of solid organ transplant recipients
- Fatality rates much higher, up to 30-75% in hematopoietic stem cell transplant patients
- Miscellaneous: associated with intussusception (isolated in up to 40% of cases) and fatal congenital infection
Diagnosis
History
- Fever
- Rhinitis
- Upper respiratory infection (URI)
- Laryngitis, sore throat
- Nonproductive or croupy cough
- Headache, myalgias
- Hematuria (gross or microscopic), dysuria, urinary frequency
- Watery diarrhea
- Conjunctivitis, rhinitis, exudative pharyngitis, and meningismus
- Typical findings of adenovirus
Physical Exam
- Pulmonary tachypnea, wheezing, rales
- Tachycardia, tachypnea, gallop rhythm, hepatomegaly
- Abdominal tenderness, distention
Diagnostic Tests & Interpretation
Lab
- CBC
- Leukocytosis or leukopenia, often with left shift in the differential counts
- Erythrocyte sedimentation rate (ESR)
- Viral isolation
- From nasopharyngeal secretions, urine, conjunctivae, or stool
- Viral identification
- Observe viral antigen in infected cells by immunofluorescence, amplify genome by polymerase chain reaction.
- Stool antigen enzyme immunoassay (EIA) test
- Highest yield from nasopharyngeal swab or stool
- Adenovirus polymerase chain reaction (PCR) may be helpful in narrowing differential diagnosis, especially regarding the immunocompromised host, and can be used for prognostic purposes.
- ECG
- Low-voltage QRS
- Low-amplitude or inverted T waves
- Small or absent Q wave in V5 and V6
Imaging
- Echocardiogram for suspected myocarditis
- Chest x-ray
- Bilateral patchy interstitial infiltrates (lower lobes) or enlarged heart
- Cardiomegaly
Differential Diagnosis
- Respiratory infection
- Influenza
- Parainfluenza
- Human metapneumovirus
- Pertussis
- Mycoplasma pneumonia
- Bacterial pneumonia
- Bocavirus
- Pharyngoconjunctival fever
- Group A Streptococcus
- Epstein-Barr virus
- Parainfluenza
- Enterovirus
- Measles
- Kawasaki disease
- Epidemic keratoconjunctivitis
- Herpes simplex
- Chlamydia
- Enterovirus
- Myocarditis
- Enteroviruses
- Herpes simplex
- Epstein-Barr virus
- Influenza
- Bacterial myocarditis
- Hemorrhagic cystitis
- Glomerulonephritis
- Vasculitis
- Renal tuberculosis
- Infantile diarrhea
- Rotavirus
- Calicivirus (including norovirus)
- Astrovirus
- Salmonella
- Shigella
- Campylobacter
- CNS infection
- Enterovirus
- Herpes simplex virus
- Mycoplasma
- Bacterial meningitis
Treatment
General Measures
- Supportive care
- Monitor for secondary bacterial infections.
- Avoid steroid-containing ophthalmic ointments.
Medication
First Line
- Cidofovir
- Has been shown to have benefit in immunocompromised patients with disseminated disease, specifically in hematopoietic stem cell transplant (HSCT) patients, where a reduction in adenovirus-related mortality compared with historical controls has been reported
- However, a risk of developing a dose-limiting nephrotoxicity exists and optimal dosing is not known.
- Reducing immunosuppression in transplanted patients should be considered for those with adenovirus disease.
- Infusion of AdV-specific cytotoxic T cells or intravenous immunoglobulin (IVIG) may have some benefit in immunocompromised patients, particularly HSCT patients.
Ongoing Care
Prognosis
Most syndromes are self-limited in the immunocompetent host.
Complications
- Bronchiolitis obliterans (rare)
- Corneal opacities with visual disturbance (usually resolves spontaneously)
- Congestive heart failure
- Dilated cardiomyopathy
Additional Reading
- Bowles NE, Ni J, Kearney KL, et al. Detection of viruses in myocardial tissues by polymerase chain reaction: evidence of adenovirus as a common cause of myocarditis in children and adults. J Amer Coll Cardiol. 2003;42(3):466-472. [View Abstract]
- Hammond S, Chenever E, Durbin JE. Respiratory virus infection in infants and children. Pediatr Dev Pathol. 2007;10(3):172-180. [View Abstract]
- Leruez-Ville M, Midard V, Lacaille F, et al. Real-time blood plasma polymerase chain reaction for management of disseminated adenovirus infection. Clin Infect Dis. 2004;38(1):45-52. [View Abstract]
- Lindemans CA, Leen AM, Boelens JJ. How I treat adenovirus in hematopoietic stem cell transplant recipients. Blood. 2010;116(25):5476-5485.
- Tebruegge M, Curtis N. Adenovirus: an overview for pediatric infectious diseases specialists. Pediatr Infect Dis J. 2012;31(6):626-627. [View Abstract]
Codes
ICD09
- 79 Adenovirus infection in conditions classified elsewhere and of unspecified site
- 8.62 Enteritis due to adenovirus
- 478.9 Other and unspecified diseases of upper respiratory tract
ICD10
- B34.0 Adenovirus infection, unspecified
- A08.2 Adenoviral enteritis
- B97.0 Adenovirus as the cause of diseases classified elsewhere
- J39.8 Other specified diseases of upper respiratory tract
SNOMED
- 25225006 Disease due to Adenovirus
- 70880006 Adenoviral enteritis
- 61958003 Adenoviral respiratory disease
FAQ
- Q: Is there anything one can do to prevent these infections?
- A: Washing hands and avoiding contact with ill persons will help slow the spread of these infections.