ADENOVIRUSES

WHAT ARE ADENOVIRUSES?

Adenoviruses are double-stranded, linear DNA viruses, nonenveloped (naked) and icosahedral. They are medium sized (90-100 nm) and at least 42 serotypes affect humans which belong to 1 of 6 subgroups which are responsible for 5-10% of upper respiratory infections in children and in adults also (gastrointestinal and urinary tracts)

Diagram 1 shows the transmission of the electron micrograph of 2 adenovirus particles. Diagram 2 shows the structure of the adenovirus. 1= penton capsomeres 2= hexon capsomeres 3= viral genome (linear dsDNA)

REPLICATION
Adenoviruses possess a linear ds (double stranded) DNA genome and are able to replicate in the nucleus of mammalian cells using the hosts replication machinery

Adenovirus infections most commonly cause illness of the respiratory system; however, depending on the infecting serotype, they may also cause various other illnesses such as gastroenteritis, conjunctivitis, cystitis and rash illness. Symptoms of respiratory illness range from the common cold to pneumonia, croup and bronchitis. Patients with compromised immune systems are especially susceptible to severe complications of adenovirus infection. Acute respiratory disease (ARD), first recognized in World War II, can be caused by adenovirus infections during stress and conditions of crowding.

CLINICAL FINDINGS
Acute respiratory disease pharyngitis, which may be exudative, is a finding. Conjunctivitis may occur in this setting Patients have pulmonary rhonchi and rales Pharngoconjunctival feverFever; coryza; pharngitis, which may be exudative; follicular, bulbar and plapebral conjunctivitis (typically mild granular appearance); and headache are reported Cervical lymphadenopathy is a finding. The hallmark is preauricular lymphadenopathy (ie, Parinuad syndrome), with small lymph nodes palpable just anterior to the rear.this finding is not common; however, its presence in the setting of a viral conjunctivitis is very suggestive of adenovirus infection

Epidemic keratoconjunctivitis Severe follicular keratoconjunctivitis is reported. Palpebral conjunctiva may be granular. Palpebral edema is a finding. Preauricular lymphadenopathy is not common but is a pathognomonic finding with adenovirus infection. Hemorrhagic conjunctivitis may develop Visual haziness or impairment resulting from keratitis develops and may persist for months to years.

Acute hemorrhagic cystitis/nephritis No significant features are described in the setting of hemorrhagic cystitis, other than evidence of blood in the urine. Nephritis is characterized by flank pain. Patients with hemorrhagic cystitis are afebrile. Nephritis is characterized by fever. Gastroenteritis: if severe, the patient has signs of dehydration. Adenoviral infections in immunocompromised hosts: features include dyspnea, dry cough, pulnonary rhonchi and rales, grossly bloody urine, and diarrhea.

LABORATORY DIAGNOSIS

Adenovirus is stable in routine viral transport medium, including specimens if nasopharyngeal, rectal, and corneal secretions; urine; and unfixed biopsy tissue. Detection is enhanced if specimens are taken early in the clinical course as promptly shipped cold or frozen to the laboratory. Many adenovirus serotypes can be isolated in cell culture lines commonly used in diagnostic virology laboratories; however, others fail to grow. Primary human embryonic kidney cells support growth of many fastidious adenovirus serotypes, but their additiona; cost may be prohibitive in some settings

Indirect immunofluorescence assays may be used for direct examination of tissue specimens (ELISA) Serology- the complement fixation (CF) test is an easily applied method for detecting infection by any member of the adenovirus group. A greater rise in CF antibody titer between acute phase and convalescent phase sera indicates current infections with an adenovirus.

The following laboratory studies are suggested in the given syndromes, both to diagnose adenoviral infections and to evaluate for other diagnoses in the differential of each syndrome. Acute respiratory disease

-nasopharyngeal swab for culture of respiratory viruses (eg, influenza virus, adenovirus) is suggested
-consider Monospot assay or respiratory syncytial virus culture for Epstein-Barr virus and respiratory syncytial virus -consider rapid group A Streptococcus throat swab and culture

Pharyngoconjuctival fever -the same considerations as those for Acute respiratory disease Epidemic keratoconjunctivitis: viral and bacterial swab cultures of conjunctival secretions and scrapings are suggested. Acute hemorrhagic cystitis or nephritis: urinalysis and cultures for bacterial and viral pathogens are suggested. Gastroenteritis: consider stool Wright stain, ova and parasites examination, culture for bacterial enteric pathogens, rotavirus assay, and clostridium difficile toxin assay.

EPIDEMIOLOGY AND IMMUNITY

Adenoviruses exist in all parts of the world and are spread often by the fecal-oral route but may also be transmitted by respiratory droplets In contrast to most respiratory agents, the adenoviruses induce effective and long lasting immunity against re-infection.

TREATMENT
Ribavirin and cidofovir therapy have been used with variable success in immunosuppressed hosts. Most infections are mild and require no therapy or only symtomatic treatment. Bcause there is no virus-specific therapy, serious adenovirus illness can be managed only by treating the symptoms and complications of the infection. Deaths are exceedingly rare but have been reported.

PREVENTION AND CONTROL

Effective isolation procedures, handwashing and sterilization of instruments can prevent nosocomial infection Adequate chlorination of swimming pools may prevent waterborne outbreaks.