Hantavirus pulmonary syndrome: the Four Corners disease

To review the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of hantavirus infections, focusing on the recent outbreak of hantavirus pulmonary syndrome in the US.

A MEDLINE search (1966 to present) of English language literature pertaining to hantaviruses was performed. Additional literature was obtained from reference lists of pertinent articles identified through the search.

All articles were considered for possible inclusion in the review. Pertinent information, as judged by the authors, was selected for discussion.

Hemorrhagic fever with renal syndrome (HFRS) has long been recognized in Eurasia and is the predominant disease manifestation of hantavirus infection worldwide. Hantavirus pulmonary syndrome (HPS) recently has been described in the US and exhibits greater pulmonary involvement and mortality than HFRS. Historically, 4 hantavirus serotypes (Hantaan, Seoul, Puumala, Prospect Hill) are recognized; however, additional serotypes have been proposed as distinct serogroups, including the serotype responsible for HPS in the Four Corners area: the Four Corners virus (FCV). Phylogenetic analysis shows that FCV is most closely related to Prospect Hill virus, another hantavirus previously isolated in the US that has not yet been identified with human disease. Additional hantavirus serotypes isolated in the US may provide insight into the prevalence of hantavirus infection and disease in this country. Inhalation of aerosolized virus is the predominant mechanism of hantavirus infection. Diagnosis is based primarily on clinical findings and serologic evidence of hantavirus antibody or direct evidence in clinical tissue specimens. Limited clinical studies evaluating ribavirin as a therapeutic modality demonstrated that the agent improves clinical outcome in HFRS. However, the role of ribavirin in the treatment of HPS remains to be determined.

Hantavirus infections are becoming increasingly recognized as a cause of disease worldwide. Recognition of hantavirus disease in the US suggests enzoonosis of pathogenic hantaviruses. In the absence of a well-established cure, early diagnosis is imperative so that aggressive supportive care can be initiated.