ed an acute infection with a new species of hantavirus. This report describes the first 17 patients with this illness, which was characterized by rapidly progressive respiratory and hemodynamic deterioration due to a strain of hantavirus previously unrecognized in North America.
The hantavirus genus belongs to the Bunyaviridae family and includes the causative agents of a group of febrile nephropathies known collectively as hemorrhagic fever with renal syndrome, which occurs throughout Europe and Asia.2 The hallmarks of hemorrhagic fever with renal syndrome are hematologic abnormalities, prominent (often severe) renal involvement, and increased vascular permeability.3 Hantaan virus is the prototype hantavirus; isolated in 1977, it occurs predominantly in the Russian Far East, China, and Korea.4 Severe disease associated with the Hantaan virus is characterized by five phases: febrile, hypotensive, oliguric, diuretic, and convalescent. However, 30 to 40 percent of patients have minimal illness, and in only 20 to 30 percent is the illness moderate or severe.5–7 Respiratory symptoms are generally not pronounced, and pulmonary involvement has not been a prominent feature of the known hantaviral syndromes.8 Several species of rodents in the United States have been shown to be infected with hantaviruses. Although seroprevalence studies have detected antibodies to hantaviruses in a small percentage of people in the United States, there were no reports of acute illness resulting from hantavirus infection acquired in North America before the outbreak of cases described in this report.9,10
The case definition of acute, unexplained respiratory distress syndrome consisted of either of the following findings in any patient presenting after January 1, 1993: unexplained adult respiratory distress syndrome or radiographic evidence of acute, bilateral, interstitial pulmonary infiltrates with hypoxemia (arterial oxygen saturation, less than 90 percent while the patient is breathing room air), or autopsy findings of unexplained, noncardiogenic pulmonary edema. Physicians in New Mexico, Arizona, Colorado, and Utah were requested to report cases meeting this definition to their state health departments.
Serum samples were tested for antibodies against a panel of heterologous hantaviral antigens, and tissue samples were tested for evidence of hantavirus infection by means of the polymerase chain reaction in frozen lung-tissue specimens or immunohistochemical staining of formalin-fixed specimens11 (and Centers for Disease Control and Prevention [CDC]: unpublished data). A case of unexplained respiratory distress syndrome was considered to be confirmed as hantavirus infection if the results of antibody, polymerase-chain-reaction, or immunohistochemical testing were positive. Thirty-one patients meeting the case definition were identified by surveillance in the four-state area. As of July 11, 1993, 17 of the 31 had confirmed hantavirus infection; medical records were available for 16 of these patients. One additional patient, whose illness began before the surveillance period (November 1992), was identified and is included in the analysis.
Autopsy examinations were performed in 9 of 13 deceased patients (69 percent) at the New Mexico Office of the Medical Investigator. Autopsies were performed in 12 patients elsewhere, and the histopathological findings reviewed at the CDC. Medical records were abstracted by a single reviewer using a standardized data-collection form. Interviews with physicians were conducted to supplement the medical history in the case of two patients whose medical records were incomplete.
Data were stored and analyzed with the use of Epi-Info, version 5.01 (CDC and World Health Organization, Atlanta). A multiple logistic regression with a stepwise procedure was performed with SAS software (SAS Institute, Cary, N.C.).
During the study period, acute hantavirus infection was confirmed in 18 patients, 14 of whom died (78 percent). The median age was 31.0 years (mean, 32.2; range, 13 to 64); 11 of the patients (61 percent) were women. Thirteen patients (72 percent) were Native American, four (22 percent) were white, and one (6 percent) was Hispanic. Twelve patients (67 percent) resided in New Mexico, five (28 percent) in Arizona, and one (6 percent) in Colorado. In 12 patients (67 percent), the onset of illness occurred between May 1, 1993, and June 30, 1993. The medical records of 17 of the 18 patients were available for review.
A 19-year-old man living in rural New Mexico presented to an emergency department with a one-day history of fever, myalgia, chills, headache, and malaise; he did not have dyspnea or cough. The patient had been in excellent health and was a marathon runner; his fiancée, with whom he had lived, had died two days earlier of a rapidly progressive respiratory illness. His temperature was 39.4°C, his heart rate was 118 beats per minute, his blood pressure was 127/84 mm Hg, and his respiratory rate was 24 breaths per minute. The physical examination was normal.
The white-cell count was 7100 per cubic millimeter, with 66 percent segmented neutrophils and 10 percent band forms; the hematocrit was 49.6 percent, and the platelet count was 195,000 per cubic millimeter. The serum creatinine level was 1.1 mg per deciliter (100 µmol per liter), the blood urea nitrogen level was 9 mg per deciliter (3.2 mmol per liter), the serum albumin level was 4.8 mg per deciliter, and the serum lactate dehydrogenase level was 195 IU per liter (normal range, 100 to 190). Urinalysis revealed no protein or blood. Oxygen saturation, determined by pulse oximetry, was 91 percent while the patient was breathing room air, and the chest radiograph was normal. The patient was treated with erythromycin, amantadine, and acetaminophen and then discharged.
Two days later, the patient presented at a clinic with persistent symptoms plus vomiting and diarrhea. His temperature was 36°C, his heart rate was 80 beats per minute, his blood pressure was 90/70 mm Hg, and his respiratory rate was 22 breaths per minute. The physical examination was normal, with clear lung fields on auscultation; the patient was discharged with no change in the diagnosis or therapy. A cough that produced copious yellow sputum, sometimes blood-tinged, and progressive shortness of breath subsequently developed. The day after discharge, the patient had acute respiratory failure and cardiopulmonary arrest and could not be resuscitated. The