Discussion
The adenoviruses are a family of a globally distributed, perennial, DNA viruses that commonly cause a self-limiting febrile illnesses in children. It is the most common cause of viral conjunctivitis in children older than 6 years.3 Fatal infections can occur in immunocompromised hosts with a low cell mediated immunity, and are rarely seen in healthy individuals.4 Over sixty human adenovirus serotypes, further classified into seven species (A-G) based on biologic properties, have been described. Species B serotypes 3 and 7 are the most common. Species B, C with serotypes 5, 7, 14, and 21 are primarily responsible for a severe infection.5Infections are prevalent in daycare centers and crowded settings. The mode of transmission is via aerosol, fecal-oral route, or contaminated fomites. Long periods of survival on inanimate surfaces and resistance to lipid disinfectants due to its non-enveloped structure contribute to a faster and wider spread. Most individuals have a serologic evidence of prior infection during the first decade of their life.6
The age and immunocompetency of the host dictate the range of clinical manifestations in the patient. While respiratory tract infections like pharyngitis, coryza, and pneumonia are common, gastrointestinal, ophthalmologic, and genitourinary involvement can also be seen. Adenovirus can cause severe hemorrhagic conjunctivitis which can mimic bacterial cellulitis leading to an unnecessary antimicrobial treatment such as seen with our patient.7 The illness usually lasts five days to two weeks with further lengthening in the case of a bacterial super-infection. The classic presentation is that of a pharyngo-conjunctival fever with follicular conjunctivitis, febrile pharyngitis, cervical adenitis, and associated systemic manifestation, leading to a clinically indistinguishable picture from the group A streptococcal infection.8 A whitish membrane seen on the palpebral conjunctiva (pseudomembrane), along with eyelid edema is a common physical examination sign seen in such patients.7 Ophthalmologic involvement in the form of epidemic keratoconjunctivitis, caused by species D serotypes 8, 19, and 37, is a serious infection characterized by blurry vision, bilateral conjunctivitis, preauricular adenopathy, and painful corneal opacities.8 The adenoviral disease spectrum may include an exanthem, hemorrhagic cystitis (species B serotypes 11 and 21), otitis media, pertussis-like syndrome, bronchiolitis, myocarditis, viral myositis, acute respiratory distress syndrome, meningoencephalitis, hepatitis, tubulointerstitial nephritis, urethritis, neutropenia, and disseminated intravascular coagulation.9 Immunocompromised hosts, such as patients with hematopoietic stem cell or solid organ transplant, may have a higher risk of disseminated infection causing pneumonia, hepatitis, colitis, nephritis, and encephalitis.4
Adenoviral antigen or polymerase chain reaction assays can be used to detect the virus from an eye swab sample.4 Serum DNA testing via microbial cell-free DNA test offers rapid identification of virus, especially when the viral versus bacterial diagnosis is in doubt, thus avoiding cumbersome viral culture which is not high yielding.10,11 Next generation sequencing creates full sequences from the free or fragmented DNA present in the plasma, and compares it with stored DNA sequences in the database to find an exact match. Such technique can scan for the presence of DNA of multiple organisms, including bacterial, fungal, parasitic, and viral in one serum sample.12 Shorter turnaround time when compared to traditional culture provides an additional benefit. Currently, the sensitivity in detecting viral infections of distant organs via next generation sequencing is still unclear. Sensitivity is better for disseminated infections, where micro-organism is expected to cross plasma. Early and accurate identification of viral etiology helps to de-escalate antibiotics sooner thus reducing the adverse effects. It also allows initiation of topical steroids, which otherwise would be contraindicated in a typical bacterial infection, leading to faster recovery. While supportive therapy and steroids are mainstay in treatment, the re-introduction of adenovirus vaccination in military recruits showed significant reduction in the incidence of adenovirus related febrile respiratory illness.9,13