A member of the Bunyaviridae family, the genus Hantavirus (first isolated in 1977) is responsible for HPS. The Sin Nombre virus is the hantavirus primarily responsible for HPS. However, closely related strains (Bayou and Black Creek Canal viruses), found in the southeastern United States, produce a variant characterized by a greater degree of renal failure. The New York virus is the cause of cases in New York and Rhode Island.

Disease transmission is associated with exposure to aerosols (such as dust) contaminated by urine or feces from infected rodents, the primary reservoir for this virus. Data suggest that the deer mouse is the main source, but pinon mice, brush mice, and western chipmunks in close proximity to humans in rural areas are also sources. Hantavirus infections have been documented in people whose activities are associated with rodent contact, such as farming, hiking or camping in rodent-infested areas, and occupying rodent-infested dwellings.

Infected rodents manifest no apparent illness but shed the virus in feces, urine, and saliva. Human infection may occur from inhalation, ingestion (of contaminated food or water, for example), contact with rodent excrement, or rodent bites. Transmission from person to person or by mosquitoes, fleas, or other arthropods hasn’t been reported.

The basic lesion of HPS infections is a generalized increase in capillary permeability resulting from endothelial damage. This stems from the immunologic response to viral antigens that penetrate the endothelium. This increased capillary permeability gives rise to widespread edema. The particular organs affected depend on the specific species of hantavirus; patients with HPS have edema concentrated in the pleura and lungs.

The endothelial cells appear swollen. An interstitial pneumonitis occurs, made up of edema fluid,
mononuclear cells, and lymphocytes with polymorphonuclear leukocytes. Hyaline membranes appear, and as the disease progresses, the alveolar septa become increasingly fibrotic. The spleen also shows infiltration of immunocompetent cells. Severe cases present with noncardiogenic pulmonary edema accompanied by pulmonary capillary leak syndrome (the heart isn’t directly affected). This pulmonary capillary leak syndrome is the primary defect responsible for both cardiopulmonary and renal dysfunction. Hypoxia also contributes to the state of shock.

Noncardiogenic pulmonary edema distinguishes the syndrome. Other signs and symptoms include:

• myalgia

• fever

• headache

• nausea

• vomiting

• cough

• respiratory distress that typically follows the onset of a cough

• a course typified by fever, hypoxia and, in some patients, serious hypotension

• rising respiratory rate (28 breaths/minute or more)

• increased heart rate (120 beats/minute or more).

• Respiratory failure

• Death

Despite ongoing efforts to identify clinical and laboratory features that distinguish HPS from other infections with similar features, diagnosis currently is based on clinical suspicion along with a process of elimination developed by the Centers for Disease Control and Prevention and the Council of State and Territorial Epidemiologists. Serologic testing for hantavirus can also be performed. (See Screening for hantavirus pulmonary syndrome, page 84.)

Laboratory tests usually reveal an elevated white blood cell count with a predominance of neutrophils, myeloid precursors, and atypical lymphocytes; an elevated hematocrit; a decreased platelet count; an elevated partial thromboplastin time; and a normal fibrinogen level. Usually, laboratory findings demonstrate only minimal abnormalities in renal function, with serum creatinine levels no higher than 2.5 mg/dl. Chest X-rays eventually show bilateral diffuse infiltrates in almost all patients (findings consistent with acute respiratory distress syndrome).