Adenovirus Infections

KEY FEATURES

• At least 88 serotypes across seven species (classified A–G), which produce a variety of clinical syndromes

• Usually self-limited or clinically inapparent except in immunocompromised persons, including

  • People living with HIV infection

  • People with COPD

  • Patients who have undergone solid organ and hematopoietic stem cell transplantation or cardiac surgery

  • People who have received cancer chemotherapy

CLINICAL FINDINGS

• Incubation period: 4–9 days

• Viral or bacterial coinfections occur in 15–20% of cases

• Clinical syndromes often overlap

  • Common cold

  • Nonstreptococcal exudative pharyngitis

  • Lower respiratory tract infections

  • Acute respiratory disease and atypical pneumonia

  • Pharyngoconjunctival fever

  • Epidemic keratoconjunctivitis

  • Acute hemorrhagic cystitis

  • Sexually transmitted genitourinary ulcers and urethritis

  • Acute gastroenteritis, mesenteric adenitis, acute appendicitis, rhabdomyolysis, and intussusception

  • Rarely associated with encephalitis, meningitis, cerebellitis, acute respiratory distress syndrome, acute flaccid myelitis, and pericarditis

• Risk factors associated with severity of infection

  • Youth

  • Chronic underlying infections

  • Recent transplantation

  • Serotypes 5 or 21

• Hepatitis (C5 adenovirus), pneumonia, and hemorrhagic cystitis (species B, types 11 and 34) tend to develop in infected liver, lung, or kidney transplant recipients, respectively

• Disease states that may develop in patients receiving hematopoietic stem cell transplant include

  • Hepatitis

  • Pneumonia

  • Diarrhea

  • Hemorrhagic cystitis

  • Tubulointerstitial nephritis

  • Colitis

  • Encephalitis

DIAGNOSIS

• Viral culture is considered the standard

  • Antigen detection assays (eg, direct fluorescence assay, enzyme immunoassay) are rapid and show sensitivity of 40–60% compared with viral culture

  • Samples with negative rapid assays require polymerase chain reaction (PCR) assays or viral cultures for diagnosis

• Quantitative real-time rapid-cycle PCR useful in distinguishing disease from colonization, especially in patients who have received hematopoietic stem cell transplants

• Multiplex nucleic acid amplification assays can test for multiple respiratory viruses simultaneously with increased sensitivity

• Appears as a multifocal consolidation or ground-glass opacity without airway inflammatory findings on chest CT imaging

TREATMENT

• Treatment is symptomatic

• Ribavirin or cidofovir

  • Used in immunocompromised patients with occasional success

  • Cidofovir is attendant with significant renal toxicity

• Brincidofovir

  • Lipid-conjugated prodrug of cidofovir

  • Has better oral bioavailability, is better tolerated, and achieves higher intracellular concentrations of active drug than cidofovir

  • Only available through compassionate use policies

• Intravenous immunoglobulin (IVIG) is used in immunocompromised persons, but data are still limited

• Topical steroids or tacrolimus may be used to treat adenoviral keratoconjunctivitis

• The commercially available synthetic corticosteroid mifepristone shows some in vitro activity against adenoviruses

• Epidemic adenoviral conjunctivitis is often difficult to control and requires

  • Meticulous attention to hand hygiene

  • Use of disposable gloves

  • Sterilization of equipment (isopropyl alcohol is insufficient, recommendations of manufacturers are preferred)

  • Cohorting of cases

  • Furloughing of employees

  • A combination of povidone-iodine 1.0% eyedrops and dexamethasone 0.1% eyedrops four times a day can reduce symptoms and expedite recovery

• Vaccines are not available for general use