ISSUES & ANSWERS

Hantavirus Pulmonary Syndrome:
A New Clinical Illness

Dr. Charles W. Berry - B.A. Hendrix College; M.S. Louisiana Tech University; Ph.D. Baylor University; Professor, Department of Microbiology, Baylor College of Dentistry; Member International Association for Dental Research, American Society for Microbiology. Pi Sigma Eta, Sima XI, Professor Microbiology at Dallas Institute of Funeral Service.

New clinical syndromes and infections associated with previously unknown pathogens often are recognized only after clinicians and public health officials become aware of clusters of cases. In May and June of 1993, the recognition and reporting of 24 cases of severe respiratory illness among the residents of the southwestern United States, led to an investigation by local and state health agencies which resulted in the identification of Hantavirus Pulmonary Syndrome (HPS). This new disease is associated with an organism named Hantavirus and occurs principally in otherwise healthy adults. Although HPS affects both male and female adults, other hantaviruses affect predominately males. Another hantavirus, the Muerto Canyon virus, has a substantially higher case-fatality rate for persons affected in contrast to persons infected with other hantaviruses. Interestingly, although most cases occurred west of the Mississippi River, the primary reservoir of the virus, the deer mouse, inhabits all areas of the United States except for the southeast and Atlantic seaboard. Regional variations in the occurrence of this disease and observed differences in the racial/ethnic and age distribution may reflect differences in either activities associated with exposure or transmission, differences in local detection of cases, or the prevalence of the virus in the rodent host. Specifically, persons involved in agricultural activities near habitats of infected rodents are at a likely higher risk for contracting the infection than those not frequenting rodent infested areas. Recognizing a more geographic widespread occurrence of HPS emphasizes the need for health-care providers to consider HPS in the differential diagnosis of adult respiratory syndrome.

Hantavirus - The agent which causes HPS (characterized by a febrile period, followed by the rapid onset of noncardiogenic pulmonary edema and hypotension and shock) is a newly named Hantavirus. To date, three new hantaviruses have been identified. Two were identified from the lung tissue from HPS patients and a third from the cotton rat. Most of the cases of HPS have been caused by a single virus isolated from the deer mouse (Peromyscus maniculatus). The hantaviruses are a group of organisms from the Family Bunyaviridae which are lipid-enveloped viruses composed of RNA nucleic acids. They are sensitive to a hydrogen ion concentration of 5 or less, and at neutral pH values, can persist for several hours at 37oC and for several days at a lower temperature. In dried environments, the virus can survive for up to 2 days. This virus may persist in blood, organs, saliva, feces or urine of the infected animals. In studies of the rodent vector, approximately one-third carried hantavirus antibodies. Viral RNA with hantavirus sequences was demonstrated by PT-PCR in the tissues of virtually all antibody-positive and some antibody-negative deer mice.

Human Infections - Aerosols from infective saliva or excreta of rodents have been clearly implicated in the transmission of hantaviruses to humans. Persons visiting animal holding areas in laboratories where infected rodents were housed have been infected after approximately five minutes of exposure. The relative importance of primary aerosols from freshly shed material compared to secondary aerosols from dried excreta in bedding or nests is comparable. Correspondingly, the possibilities of infection associated with ingestion of food contaminated with the virus, contact with mucous membranes, or contamination of breaks in the skin barrier have not been clearly evaluated. However, humans have become infected as a result of rodent bites. Most cases of human illness associated with hantavirus have resulted from exposure to naturally infected wild rodents. Arthropod vectors such as fleas, ticks, lice or mites are not known to transmit the hantavirus. Also, person-to-person transmission has not been reported with any of the hantaviruses primarily associated with HPS in the United States. It is interesting to note that although fleas and other ectoparasites do not transmit hantaviruses, rodent fleas do transmit the bubonic plague. Rodent-feeding deer ticks may also transmit the etiologic agent for Lyme disease. Thus, persons who handle field-trapped rodents, collect rodent sera, tissues or contact traps contaminated with rodent excreta also should be aware of the risk for exposure to materials contaminated with hantavirus and other disease agents.

Clinical Manifestations - The following discussion is of a typical case of HPS. The clinical manifestations of hantavirus-caused pulmonary syndrome include: fever, chills, headache, myalgia, nausea, vomiting and diarrhea. Patients may become hypotensive and increasingly short of breath. Laboratory findings include: Leukocytosis, hemoconcentration, thrombocytopenia and an elevation of SMAC values of blood urea nitrogen, creatine, asparatate aminotransferase, lactic dehydrogenase and lipase levels. Prothrombin and activated partial prothrombin times are also elevated. A chest x-ray indicates bilateral diffuse infiltrates and the patient may require respiratory and circulatory support.

Through July 24, 2000 a total of 260 cases of hantavirus pulmonary syndrome had been reported in the United States. The case count was started when the disease was first recognized in May 1993. 39% of all cases ever reported have resulted in death. A total of 180 cases have been reported since January 1, 1994, after the well-known 1993 outbreak had receded. When this group is considered alone, the proportion of deaths drops to 31%. Of persons ill with HPS, 60% have been male, 40% female. The age of confirmed case patients has ranged from 10 to 75 years, and the mean age is 37 years. Cases have been reported in 31 states, including most of the western half of the country and some eastern states as well. These findings suggest that contracting a hantavirus disease is possible in any of the contiguous states and emphasizes the continued importance of minimizing exposure to rodents and their excreta. Persons engaging in outdoor activities such as camping or hiking should take precautions to reduce exposure with rodents.

Treatment and Prevention - Although the overall incidence of HPS is unknown, this syndrome appears to be and must be assumed to be widespread. Recognition of HPS during its early stages may be difficult because of the nonspecificity of symptoms. Later in the syndrome, tachypnea, hemoconcentration, thrombocytopenia, leukocytosis with a high proportion of "bands" is suggestive of HPS. Prompt control of hypoxia, avoidance of excessive fluid administration and the early use of inotropic and pressor drugs appear to be important in treating HPS. In summary, prevention and treatment of HPS with antibiotics is not possible because of the lack of susceptibility of viruses to antibiotics in general, therefore antivirals such as intravenous ribavirin has had some degree of success as an anti-infective protocol.

Importance to Morticians - At this time it is unknown whether the blood of post-mortem samples are infectious. However, vital antigens have been detected in necropsy specimens by the RT-PCR technique which detects viral genetic materials. The National Communicable Disease Centers in Atlanta, Georgia make the following recommendations regarding the precautions to be followed when preventing hantavirus disease transmission for morticians or post-mortem examination personnel: CDC recommends that universal precautions be followed whenever human blood is contacted or handled. Additionally, mucous membrane protection is advised when the possibility of aerosol-generating procedures exist. Respiratory protection is necessary.