Approximately 50 immunologically distinct types of adenoviruses have been recovered from humans, with type-specific variability in epidemiology, communicability, clinical manifestations, and severity (see Chapter 187, Adenoviruses). Some have estimated that adenoviruses are responsible for 2% to 24% of viral respiratory illnesses in children. They are the sole cause of epidemic pharyngoconjunctival fever and the usual cause of sporadic cases. Epidemic disease has been associated most often with adenovirus type 3, with adenovirus type 7 second in prevalence; one or more epidemics have been caused by adenovirus types 2, 4, 7a, 11, and 14. Sporadic pharyngoconjunctival fever has been associated with these and with types 1, 4, 5, 6, 8, 19, and 13/30 (an intermediate type).

Pharyngoconjunctival fever occurs in large community epidemics (usually associated with public swimming facilities), in local outbreaks (e.g., hospitals, clinics, child-care centers, schools, and camps), and sporadically. Infection can occur at any age. The circumstances of inoculation are most important. Close contact probably is necessary for person-to-person spread (by aerosolized droplets to the conjunctiva and upper respiratory tract) or self-inoculation (after hand contact with contaminated secretions from infected individuals and fomites). This last factor probably was the mode of transmission in an outbreak in a child-care center. Direct inoculation of eyes occurs from contaminated swimming pool water. The increase in frequency noted in outbreaks that occur in the summer and at camps probably reflects the risk of conjunctival inoculation in swimming pools. Inadequately chlorinated water was implicated in one epidemic of adenovirus disease. Direct inoculation of patients’ conjunctivae from improperly sterilized ophthalmologic tools or the contaminated hands of staff has been responsible for multiple outbreaks of keratoconjunctivitis caused by adenovirus. Hospital-associated outbreaks otherwise have occurred primarily in intensive-care settings, where injury of the conjunctivae, direct inoculation, or both may predispose to infection. Nosocomical neonatal infection can be fatal.

Usually, conjunctival infection is the result of direct inoculation. The same serotypes of adenovirus that cause the pharyngoconjunctival fever associated with swimming-pool outbreaks rarely cause sporadic cases of conjunctivitis. Volunteer studies have documented that pharyngoconjunctival fever occurs after conjunctival, but not after nasopharyngeal, inoculation.

The route of inoculation of adenoviruses causing pharyngoconjunctival fever determines the pathophysiologic sequence.
Biopsies of conjunctivae in infected volunteers reveal, predominantly, infiltration of lymphocytes in the submucosa. Biopsy material from tonsils and involved lymph nodes reveals hypertrophy and hyperplasia of the lymphoid tissue, with congestion and edema of connective tissue. Primary infection, regardless of the clinical syndrome, generally confers protection against clinical illness caused by that strain. Adenoviruses do not destroy the cells they infect in vivo. Virus can persist in the nuclei of cells and can replicate intermittently to detectable levels. Although adenoviruses are most communicable during the first few days of acute illness, shedding can persist for long periods, even months.

The incubation period of swimming pool-associated infections is 5 to 7 days. Although individuals infected with the same adenovirus type can have variable manifestations of primary infection, by definition, patients with pharyngoconjunctival fever exhibit pharyngitis (hoarseness, sore throat, cough, or local signs of pharyngeal inflammation) and conjunctivitis (eye pain, itching, excessive tearing, hyperemic conjunctivae, sticky discharge) in addition to fever. Fever onset is abrupt, and the temperature is greater than 39.2°C (102.6°F) in more than 50% of cases. Throat complaints range from mild irritation to severe pain and dysphagia. Usually, tonsils are enlarged, and approximately one-third of patients have follicular exudates. Conjunctival abnormalities are more severe than are symptomatic complaints. Symptoms frequently begin in one eye and then become bilateral. Itching, aching, and soreness are common; photophobia, exudate, and keratitis occur less frequently. Conjunctivae are erythematous and edematous. The palpebral conjunctiva appears granular, and 1- to 3-mm yellow-gray collections of lymphocytes on hyperemic epithelium sometimes are visible (so-called follicles). During epidemics or school or family outbreaks, not all infected individuals have the triad of signs and symptoms. Common additional symptoms and signs include nasal complaints related to adenoidal infection and hypertrophy (coryza, stuffiness, epistaxis), posterior nasal discharge causing cough, systemic complaints (headache, malaise, achiness, anorexia), tender anterior and posterior cervical lymph node enlargement, and flushed appearance of the face.