Adenoviruses

Etiology

Adenoviruses are known as etiologic agents of the gastrointestinal tracts, eye, respiratory, kidney, and other organs (of significance in cases of immunosuppression). Group C adenoviruses are noted to be a critical infective agent of the lower respiratory tract.[3] However, most adenovirus infections are self-limiting, with significant morbidity and death occurring mainly in immunocompromised individuals. Cases are often observed in military recruits, those living close in proximity, and the pediatric population. It is usually transmitted via aerosolized droplets, but the oral-fecal route is also a common transmission mode. Adenovirus infections are common in daycare centers, closed or crowded places such as military barracks, public swimming pools, a household with young children, and medical facilities.[4]

Epidemiology

Adenovirus infection is most common in the early spring or winter but can also occur throughout the year with no distinct seasonality. Susceptibility in children is most often from 6 months to 2 years of age and can occur as well in 5 to 9-year-old children. Infection can also occur from exogenous sources (eg, linens, pillows, lockers, guns), reactivation of the previous virus, and exposure to infected persons by inhalation of aerosolized droplets, conjunctival inoculation, fecal-oral spread. Adenovirus infects military recruits in the United States and other countries as well. Types 3, 4, and 7 leads to pneumonia, acute respiratory diseases in these people. The incubation period lasts from 2 to 14 days.[5] Significantly, latent Adenovirus may exist in renal parenchyma in lymphoid tissue and other tissues for years; in immunocompromised patients, reactivation may occur. Asymptomatic Adenovirus may continue for weeks or months. Though Adenovirus is resistant to many disinfectants, 95% ethanol solution is an active disinfectant. Adenovirus is a widespread cause of upper respiratory tract infections and conjunctivitis. The genome of the Adenovirus within the capsid is highly associated with protein VII--a virus-encoded, histone-like protein. The core protein VII has been associated with the adenovirus genome during the acute phase of infection.[6]

Pathophysiology

Adenovirus is an icosahedral capsid double-stranded DNA virus 70 to 90 nm in size. The spot of entry usually dictates the place of infection; gastrointestinal tract infection results from fecal-oral transmission, whereas respiratory tract infection results from droplet inhalation. After exposure to adenovirus infection, different relations with the cells may occur, as discussed.[7] See Image. Adenovirus, Smudge Cells.

• Lytic infection occurs when an adenovirus enters human epithelial cells and lasts until the entire replication cycle, leading to cytokine production, cytolysis, and initiation of the host inflammatory response.
• The exact process of chronic or latent infection is unknown and often involves asymptomatic lymphoid tissue infection.
• The oncogenic transformation has been detected in rats, and the adenovirus gives rise to potent E1A proteins that exalt main rodent cells by changing cellular transcription, eventually causing malignant transformation and deregulation of apoptosis. After getting inside the nucleus, E1A triggers the expression of other viral genes essential for viral replication by interacting with other regulatory proteins necessary for gene transcription and cellular transcription factors.[8]

History and Physical

Most adenovirus infections are asymptomatic. Adenovirus symptoms include epidemic keratoconjunctivitis, acute hemorrhagic cystitis, and gastroenteritis. Depending on the organ system affected, one may observe fever, pharyngitis, cervical adenopathy, coryza, watery eyes, gross bloody urine, and dyspnea. On physical examination, cervical adenopathy, pharyngoconjunctivitis, and tonsillitis can be seen.

Evaluation

Adenovirus is diagnosed based on clinical presentation. Other lab work, such as viral culture, PCR, viral antigen assay, and serology, can also help.

Treatment / Management

In most cases, the treatment of adenovirus infection is supportive. Hydration, NSAIDs, and bed rest for a few days may be beneficial. Antiviral drugs rarely treat adenovirus infections in immunocompetent patients but may be used in immunosuppressed people. Unfortunately, many antivirals, including ganciclovir and vidarabine, also have potential adverse effects. Adenovirus can further be prevented by vaccination (oral, live, enteric-coated), particularly in military recruits between 17 and 50 years old.[9] Other measures, such as chlorination of swimming pool water, droplets, and contact precautions, are helpful.[10] Adenoviruses are outstanding antigens, and vaccination has been successful. Though viral vaccines have not typically been used for adenoviruses, they are noted to play a role in tumorigenesis in cell cultures and animals. Furthermore, adenovirus infections rarely cause serious complications. Nevertheless, vaccines can be produced by recombinant DNA technology. Purified fiber or hexon preparations encourage high levels of neutralizing antibodies, and vaccines created by these proteins have been tested efficaciously.

Differential Diagnosis

The differential diagnosis for adenoviruses include the following:

• Rhinoviruses
• Coronaviruses
• Influenza viruses
• Parainfluenza viruses
• Enteroviruses
• Human metapneumoviruses
• Respiratory syncytial virus

Prognosis

Adenovirus infection has an excellent prognosis except in immunocompromised hosts; mortality rates can be up to 70% in immunocompromised individuals.

Complications

• Bronchiolitis obliterans
• Disseminated adenovirus infection
• Bronchiectasis