Severe community-acquired adenovirus pneumonia treated with oral ribavirin: a case report

Adenoviruses are double-stranded DNA viruses belonging to the family Adenoviridae. They cause infections involving the upper and lower respiratory tract, gastrointestinal tract, and conjunctiva [1]. More than 80% of adenovirus infections occur in children under 4 years old because of a lack of humoral immunity [1]. Although adenovirus infections are generally self-limiting, severe and disseminated infections can occur in patients with impaired immunity including organ transplantation recipients, those with human immunodeficiency virus, and those with congenital immunodeficiency. Outbreaks of adenovirus pneumonia in immunocompetent patients have occasionally been reported among military recruits and adults in long-term care facilities or hospital wards, which included some fatal cases [2–4]. However, community-acquired adenovirus pneumonia in immunocompetent adults has rarely been described. Herein, we report a case of severe adenovirus pneumonia occurring in a previously healthy man which was successfully treated with oral ribavirin.

Adenovirus causes 1–7% of adult respiratory tract infections and present as non-specific febrile illness which subsides spontaneously within several days [1]. Adenovirus pneumonia occasionally occurs in immunocompromised hosts and is characterized by rapid clinical deterioration compared to other viral pneumonias with a reported fatality rate of 50%. Community-acquired adenovirus pneumonia in immunocompetent hosts is very rare.

A recent review of 21 cases of community-acquired adenovirus pneumonia revealed that patients frequently have respiratory compromise with hypoxemia at the time of presentation, while the classical features of adenoviral infection such as pharyngitis, conjunctivitis, rash, or diarrhea, are usually absent [5]. Most patients deteriorate rapidly after admission and require intubation and mechanical ventilation. Laboratory findings are typical of viral infections; a normal white blood cell count, relative lymphopenia, thrombocytopenia and elevated transaminase are frequently observed [5]. Although widespread bilateral interstitial shadowing was the most common radiologic finding, lobar consolidation was observed in about one quarter of the cases [5].

Traditionally, adenovirus infections are diagnosed using viral cultures and virus-specific immunofluorescent stains, which are time-consuming and costly. The recently-adopted multiplex real-time RT-PCR assay is beneficial for its rapid and highly sensitive detection of different respiratory pathogens simultaneously. In this case, initially atypical presentation and rapidly progressing clinical manifestations led us to suspect atypical pneumonia including viral pneumonia and we performed the assay, which allowed for very early detection of the pathogen and initiation of antiviral therapy, which was critical for the favorable clinical outcome.

The optimal treatment for severe adenovirus infections has not been established. A recent study reported that cidofovir, a nucleotide analogue, showed possible effect in some immunocompetent patients [6]. However, it is expensive and is not easily accessible in our country, and severe side effects including renal and hematologic toxicity should be considered. Ribavirin, a nucleoside analogue, is less toxic and has long been used for the treatment of hepatitis C. Although it has shown efficacy in treating severe adenovirus infections in infants, children, and immunocompromised adults, only high dose intravenous ribavirin was used in those cases [1, 4, 7, 8]. Despite of thorough review of literatures, the clinical efficacy of oral ribavirin for the community-acquired adenovirus pneumonia has not been reported. Although two case series reported that ribavirin was used in some immunocompetent patients for severe community-acquired adenovirus pneumonia, the treatment outcome according to the use of ribavirin and the administration route of ribavirin are not described in either of those studies [9, 10]. Our case clearly describes the successful use of oral ribavirin in the treatment of community-acquired adenovirus pneumonia in a previously healthy patient. Although more studies are required to determine its efficacy, oral ribavirin could be considered as a therapeutic option especially in the cases where cidofovir or intravenous ribavirin is not readily available.

In conclusion, community-acquired adenovirus pneumonia is a rare but rapidly deteriorating condition. Clinical suspicion and early detection using multiplex real-time RT-PCR is critical for the diagnosis and rapid initiation of treatment. Our case suggests that oral ribavirin could be a therapeutic option for adenovirus pneumonia at least in immunocompetent patients, and facilitates future randomized trial to prove its efficacy in those population.