Hantavirus Pulmonary Syndrome

Etiology

Hantaviruses are a genus in the family Bunyaviridae, which are lipid-enveloped viruses with a negative-sense RNA genome composed of three unique segments. Several pathogenic viruses that have been recognized within the genus include Hantaan virus, which causes the most severe form of hemorrhagic fever with renal syndrome (HFRS) seen primarily in mainland Asia (see Chapter 297 ); Dobrava virus, which causes the most severe form of HFRS seen primarily in the Balkans; Puumala virus, which causes a milder form of HFRS with a high proportion of subclinical infections and is prevalent in northern Europe; and Seoul virus, which results in moderate HFRS and is transmitted predominantly in Asia by urban rats or worldwide by laboratory rats. Prospect Hill virus, a hantavirus that is widely disseminated in meadow voles in the United States, is not known to cause human disease. There are an increasing number of case reports of European hantaviruses causing HPS.

HPS is associated with sin nombre virus, isolated from deer mice, Peromyscus maniculatus, in New Mexico. Multiple HPS-like agents in the American hemisphere isolated to date belong to a single genetic group of hantaviruses and are associated with rodents of the family Muridae, subfamily Sigmodontinae. These rodent species are restricted to the Americas, suggesting that HPS may be a Western hemisphere disease.

Epidemiology

Persons acquiring HPS generally have a history of recent outdoor exposure or live in an area with large populations of deer mice. Clusters of cases have occurred among individuals who have cleaned houses that were rodent infested. P. maniculatus is one of the most common North American mammals and, where found, is frequently the dominant member of the rodent community. About half of the average of 30+ cases seen annually occurs between the months of May and July. Patients are almost exclusively 12-70 yr of age; 60% of patients are 20-39 yr of age. Rare cases are reported in children younger than 12 yr of age. Two thirds of patients are male, probably reflecting their greater outdoor activities. It is not known whether almost complete absence of disease in young children is a reflection of innate resistance or simply lack of exposure. Evidence of human-to-human transmission has been reported in Argentine outbreaks.

Hantaviruses do not cause apparent illness in their reservoir hosts, which remain asymptomatically infected for life. Infected rodents shed virus in saliva, urine, and feces for many weeks, but the duration of shedding and the period of maximum infectivity are unknown. The presence of infectious virus in saliva, the sensitivity of these animals to parenteral inoculation with hantaviruses, and field observations of infected rodents indicate that biting is important for rodent-to-rodent transmission. Aerosols from infective saliva or excreta of rodents are implicated in the transmission of hantaviruses to humans. Persons visiting animal care areas housing infected rodents have been infected after exposure for as little as 5 min. It is possible that hantaviruses are spread through contaminated food and breaks in skin or mucous membranes; transmission to humans has occurred by rodent bites. Person-to-person transmission is distinctly uncommon but has been documented in Argentina.

Pathogenesis

HPS is characterized by sudden and catastrophic pulmonary edema, resulting in anoxia and acute heart failure. The virus is detected in pulmonary capillaries, suggesting that pulmonary edema is the consequence of a T-cell attack on virus-infected capillaries. The disease severity is predicted by the level of acute-phase viremia titer. A useful hamster model of HPS is available.