In the early summer of 1993, an enigmatic, catastrophic illness emerged in the southwestern United States. Previously healthy individuals suddenly developed symptoms of headache, fever, myalgia, and cough. This flu-like illness progressed to acute pulmonary insufficiency indistinguishable from adult respiratory distress syndrome. Within days of onset, death by respiratory failure occurred in at least two thirds of patients meeting the case definition. Such an unusual clinical scenario prompted a systematic quest to establish a pathogen responsible for this new and deadly illness.
After eliminating the possibilities of plague and environmental toxins as causative agents, investigators evaluated a wide array of antibody titers on sera from patients fitting case criteria. They discovered rising titers of antibodies to hantavirus in paired sera of several patients. Furthermore, immunohistochemical staining revealed hantavirus antigen in the autopsy specimens of some cases. Thus, laboratory evidence implicated a hantavirus as the culprit of the illness in the Southwest, yet the clinical profile was incongruent with other known illnesses induced by this pathogen. Whereas outbreaks of hantavirus infection with high mortality normally are marked by extensive hemorrhagic and renal complications, none of the present cases in the Southwest exhibited such pathology. Moreover, hantavirus infection, although endemic to many regions throughout the world, never had surfaced previously in the United States as the cause of acute illness.