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Adenovirus Infection, Pediatric

Basics

Description

- 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

- 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

- 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

- Epidemic keratoconjunctivitis - Herpes simplex - Chlamydia - Enterovirus

- Hemorrhagic cystitis - Glomerulonephritis - Vasculitis - Renal tuberculosis

- 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.

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 infectionsUpper respiratory tract infections: otitis media, common cold, pharyngitisLower respiratory tract infection: pneumonia, pertussis-like syndrome, croup, necrotizing bronchitis, bronchiolitis (serotypes 3, 7, and 21 predominant in pneumonia epidemics)
  • Pharyngoconjunctival feverLow-grade fever associated with conjunctivitis, pharyngitis, rhinitis, and cervical adenitis15% of patients may have meningismus.Increased incidence in summer monthsCommon source outbreaks most often associated with type 3
  • Epidemic keratoconjunctivitisBilateral conjunctivitis with preauricular adenopathyMay persist for up to 4 weeksCorneal opacities may persist for several months.Associated with types 8, 19, and 37
  • Myocarditis preceding viral illnessPresent with cardiovascular collapse, congestive heart failure, respiratory distress, or ventricular tachycardiaPrognosis 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 frequencyMore common in males than femalesAssociated with types 11 and 21Can occur in both immunocompetent and immunocompromised hosts
  • Infantile diarrheaWatery diarrhea associated with feverSymptoms may persist for 1-2 weeksAssociated 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 hostsCan cause disseminated disease including pneumonia, hepatitis, and gastroenteritisFrequently observed in transplanted patients; up to 40% of pediatric human stem cell transplant recipients and in 5-10% of solid organ transplant recipientsFatality 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
  • RhinitisUpper 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 meningismusTypical findings of adenovirus

Physical Exam

  • Pulmonary tachypnea, wheezing, rales
  • Tachycardia, tachypnea, gallop rhythm, hepatomegaly
  • Abdominal tenderness, distention

Diagnostic Tests & Interpretation

Lab

  • CBCLeukocytosis or leukopenia, often with left shift in the differential counts
  • Erythrocyte sedimentation rate (ESR)
  • Viral isolationFrom nasopharyngeal secretions, urine, conjunctivae, or stool
  • Viral identificationObserve viral antigen in infected cells by immunofluorescence, amplify genome by polymerase chain reaction.Stool antigen enzyme immunoassay (EIA) testHighest yield from nasopharyngeal swab or stoolAdenovirus polymerase chain reaction (PCR) may be helpful in narrowing differential diagnosis, especially regarding the immunocompromised host, and can be used for prognostic purposes.
  • ECGLow-voltage QRSLow-amplitude or inverted T wavesSmall or absent Q wave in V5 and V6

Imaging

  • Echocardiogram for suspected myocarditis
  • Chest x-rayBilateral patchy interstitial infiltrates (lower lobes) or enlarged heartCardiomegaly

Differential Diagnosis

  • Respiratory infectionInfluenzaParainfluenzaHuman metapneumovirusPertussisMycoplasma pneumoniaBacterial pneumoniaBocavirus
  • Pharyngoconjunctival feverGroup A StreptococcusEpstein-Barr virusParainfluenzaEnterovirusMeaslesKawasaki disease
  • Epidemic keratoconjunctivitisHerpes simplexChlamydiaEnterovirus
  • MyocarditisEnterovirusesHerpes simplexEpstein-Barr virusInfluenzaBacterial myocarditis
  • Hemorrhagic cystitisGlomerulonephritisVasculitisRenal tuberculosis
  • Infantile diarrheaRotavirusCalicivirus (including norovirus)AstrovirusSalmonellaShigellaCampylobacter
  • CNS infectionEnterovirusHerpes simplex virusMycoplasmaBacterial meningitis

Treatment

General Measures

  • Supportive care
  • Monitor for secondary bacterial infections.
  • Avoid steroid-containing ophthalmic ointments.

Medication

First Line

  • CidofovirHas 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 reportedHowever, 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.