On May 14, 1993, the New Mexico Office of the Medical Investigator was notified of the unexplained deaths of a couple living in the same household in rural New Mexico: a 21-year-old woman and a 19-year-old man. Both died of acute respiratory failure — the man within five days of the woman. By May 17, Indian Health Service physicians had reported five deaths from adult respiratory distress syndrome among previously healthy adults. Surveillance was initiated for an influenza-like illness followed by the rapid onset of  unexplained respiratory failure.

Background

Hantavirus Pulmonary Syndrome (HPS) is a potentially deadly respiratory disease that initially presents with flu-like symptoms. The cause is the Sin Nombre virus (SNV), one of a number Hantaviruses. It was first recognized during the outbreak in the Four Corners Region in 1993. which caught the attention of health officials immediately because it was associated with a greater than 50 percent mortality . Hantaviruses are emerging pathogens that have gained increasing attention over the past decade. These viruses are members of the family Bunyaviridae and are grouped in a separate genus known as Hantavirus. Serotypes Hantaan (HTN), Seoul (SEO), Puumala (PUU), and Dobrava (DOB) virus cause hemorrhagic fever with renal syndrome (HFRS), a hemorrhagic infection characterized by renal failure and shock.  These Hantavirus species are not known to cause disease in North America.  The virus causing HPS was identified as a novel Hantavirus, genetically distinct from those previously identified. The virus was given several names including Little Water virus, Four Corners virus, and Muerto Canyon virus before Sin Nombre, Spanish for virus with no name, was selected.

Hantavirus is carried by rodents. In the United States the deer mouse (Peromyscus maniculatus) and the cotton rat (Sigmodon hispidus) are the most common carriers. The animals shed virus in their urine, feces, and saliva. Human infections result from inhaling aerosolized urine, saliva, or powdered feces that contain the virus. Recent investigations have found that many individuals who have become ill have had repeated exposures to rodents or rodent droppings prior to infection.  Less common modes of infection are hand-to-mouth or hand-to-nose contact after handling contaminated materials, or direct contact from a rodent bite.  The virus is not transmitted from person-to-person.

In the initial outbreak, seventeen people suffered severe respiratory illness in the Four Corners region of New Mexico, Arizona, Colorado and Utah. Since then clusters of infections have arisen in both western and eastern parts of the United States, as well as Canada.  Other Hantaviruses causing HPS, such as the Bayou virus and Black Creek Canal virus, have been isolated from individuals who had not traveled to the Four Corners area.  Geographic expansion of Hantavirus reservoirs has been occurring over the past decade, leading to increased morbidity and mortality from these viruses.

Recently Hantavirus infections have occurred among wilderness travelers who come into contact with rodent droppings. Although the illness continues to be relatively rare, and mostly occurs in rural areas of the western US, it continues to be associated with a high mortality rate. The Centers for Disease Control cautions that “if you camp or hike in an area inhabited by rodents, you have a small risk of being exposed to infected rodents and becoming infected with Hantavirus.”

Prevention

Individuals who have an interaction with rodents or rodent droppings often are not aware of it. An increased awareness of evidence of rodent activity can help prevent or reduce contact with potentially contaminated materials. Some “rules of the road” to minimize risk of exposure include:

• Before settling into a wilderness cabin or enclosed shelter, it should be opened, allowed to air, and inspected for rodents.

• If rodents appear to be nesting in a cabin or shelter, it should not be used.

• Individuals camping in outdoor shelters or campsites should examine the site for rodent droppings and burrows before making camp.

• Tents should not be pitched or sleeping bags placed in areas with evidence of rodent feces or burrows.

• Tents and sleeping bags should be kept well away from potential rodent shelters such as wood piles or garbage dumps.

• Tents should have floors or a tarp should be under sleeping bags to avoid sleeping on bare ground.

• Food should be stored in rodent-proof containers .

• Waste should be removed from the camping area and discarded or burned as appropriate.

• Water for drinking, cooking, cleaning dishes, and brushing teeth should be disinfected by boiling, or by filtration and halogenation.

• Water should be kept in rodent-proof containers.

Hantavirus is susceptible to chlorine bleach that can easily be included in the wilderness traveler’s packing list. A diluted chlorine bleach solution can be used to wipe down tables and counters before they are used for food preparation or dining.

Recognition

Initial symptoms of HPS can appear as early as three days and as late as six weeks after exposure. Most commonly symptoms begin within two weeks. Early presentation is a flu-like syndrome that includes fever, headache, nausea and vomiting, as well as joint and low back pain. During the 1993 outbreak the most common prodromal symptoms were

fever and myalgia (100 percent), cough or dyspnea (76 percent), gastrointestinal symptoms (76 percent), and headache (71 percent). This early phase progresses for approximately three to ten days.

As the inflammatory response progresses in the lungs, fluid begins to accumulate and causes noncardiogenic pulmonary edema. During this phase individuals develop dyspnea, hypoxemia, and tachycardia. Fulminant HPS is characterized by bilateral interstitial pulmonary infiltrates and respiratory compromise. Individuals in this stage usually require supplemental oxygen and clinically resemble persons with acute respiratory distress syndrome (ARDS).  Individuals with advanced HPS can deteriorate quickly and generally are hemodynamically unstable.

Early recognition of signs of illness and management of potential exposures should be emphasized. Since early symptoms are difficult to differentiate from other viral illnesses, clues such as exposure to rodents or rodent droppings, geographic location, or complaints of severe back and leg pain can help narrow the differential. When exposure is suspected prior to the development of symptoms, persons should inform their physician of the potential contact with contaminated materials.

Management/Treatment

Pre-hospital care of HPS consists of supportive measures including aggressive fluid resuscitation, supplemental oxygen if available, and rapid transfer to a tertiary care center with ICU facilities. In a wilderness situation evacuation plans must be based on the distance from definitive care. The earlier initial signs are recognized, the more time is available to transport the person to medical attention before he becomes unstable.

Once in a more stable setting, individuals with more advanced HPS require continued fluid resuscitation and admission to the ICU for close observation and intervention.  Individuals with prodromal symptoms should be assessed, and admitted for observation.  No definitive treatment beyond supportive care is currently available for this infection.  The antiviral agent ribavirin may be administered under a research protocol coordinated by CDC and the University of New Mexico Health Sciences Center. This medication has been shown to be beneficial for HFRS caused by other Hantaviruses, but its role in HPS is still under investigation.

Prognosis

With increased recognition of the disease and more aggressive interventions for hemodynamic instability, the mortality rate for HPS has decreased to approximately 38 percent. Persons surviving the fulminant phase of the disease generally do very well and often recover with little or no residual deficits. Several months of fatigue and decreased exercise tolerance seem to be the most common sequelae of HPS.