Hantavirus Pulmonary Syndrome (HPS, Orthohantavirus)

Figure 1: Picture of Sin Nombre hantavirus particles; SOURCE: CDC/D. Loren Ketai, MD

The term hantavirus represents several groups of RNA-containing viruses (that are members of the virus family of Bunyaviridae) that are carried by rodents and can cause severe respiratory infections termed hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS).

HPS is found mainly in the Americas (Canada, U.S., Argentina, Brazil, Chile, Panama, and others) while hemrrhatic fever with renal syndrome (HFRS) is found mainly in Russia, China, and Korea but may be found in Scandinavia and Western Europe and occasionally in other areas.

Like HPS, HFRS results from hantaviruses that are transmitted by:

• rodent urine,
• rodent droppings, or
• saliva (rodent bite), by direct contact with
• the animals
• by aerosolized dust contaminated with rodent urine or feces to human skin breaks or mucous membranes of the mouth, nose, or eyes.

The vast majority of HPS and HFRS infections do not transfer from person to person.

The goal of this article is to discuss HPS; however, much of what is presented about HPS applies to HFRS -- the main difference is that the predominant symptoms in the late stages of disease vary somewhat between the two diseases (lung fluid and shortness of breath in HPS and low blood pressure, fever, and kidney failure in HFRS).

HPS is a disease caused by hantavirus that results in human lungs filling with fluid (pulmonary edema) and causing death in about 38% of all infected patients.

HPS syndrome causes

The cause of HPS is an infection of the patient by hantavirus. Currently, about 14 subtypes of hantaviruses have been identified. Many subtypes have been named:

• Sin Nombre
• Black Creek hantavirus
• Seoul virus
• New York hantavirus

Some researchers and doctors simply them under the term "New World hantaviruses." The Sin Nombre subtype has caused the majority of current HPS diseases.

Hantavirus damages cells that compose blood vessel capillaries, causing them to leak fluids. This fluid leak, if it is profound in the lungs, causes life-threatening pulmonary syndrome.

Hantaviruses live their lifecycle in rodents but do no harm; the viruses multiply and shed in the rodent's urine, feces, and saliva. A recent study in California suggested about 15% of all deer mice examined tested positive for hantavirus. Although the deer mouse has been the source of most HPSinfections, many other rodents may carry a different hantavirus subtype virus (for example, the white-footed mouse, the cotton rat, and the rice rat).

HPS risk factors

The major risk factor for HPS is an association with:

• Rodent infestation.
• Rodent saliva.
• Rodent urine.
• Feces or with dust, dirt.
• Surfaces contaminated with such rodent excretions, either by direct contact or by aerosol.
• Barns, sheds, homes, or buildings easily entered by rodents (for example, deer mouse or Peromyscus maniculatus) are potential places for hantaviruses to come in contact with humans.
• Rural areas that have forests and fields that can support a large rodent population are areas that increase the risk of exposure to hantavirus.
• Camping and hiking in areas known to have a high rodent population and occupying areas where rodents may seek shelter increase one's risk.
• Working in areas that may be shelters for rodents (for example, crawl spaces, vacated buildings, and construction sites) may also have an increased risk of hantavirus syndrome.
• The risk is higher in people who work in areas known to have produced hantavirus pulmonary syndrome infections.

Figure 2: Chest X-ray of a patient with hantavirus pulmonary syndrome (HPS); SOURCE: CDC/Brian W.J. Mahy, Ph.D.; Luanne H. Elliott, MS

The symptoms and signs of HPS fall into early and late stages.

Early HPS signs and symptoms begin about one to five weeks after the person contacts hantavirus associated with rodent urine, feces, or saliva. The early symptoms are flu-like, last about four to 10 days, and include:

• fatigue,
• fever, and
• muscle aches, especially large muscles in the legs, back, and hips).

Almost every infected person develops these symptoms. Other symptoms of HPS that may occur in about half of infected patients include:

• abdominal pain (with nausea, vomiting, and diarrhea),
• headaches,
• chills, and
• dizziness.

Early symptoms can cause diagnostic confusion. In 2018, Kiley Lane, a 27-year-old mother who lived in New Mexico, was diagnosed as having the flu but her symptoms got worse. She was diagnosed with having hantavirus about a month after her flu diagnosis and died about one month later of the disease.

Late symptoms of HPS occur about four to 10 days after the early symptoms and include:

• coughing,
• chest pain, and
• shortness of breath that can become severe.

Some infected people may develop hemorrhagic fever and kidney failure that may require dialysis (HFRS or hemorrhagic fever with renal syndrome).

What is the incubation period for hantavirus?

• According to the CDC, in North America, the incubation period (time from initial exposure to the virus and development of the first symptoms) is between one to five weeks after initial exposure to infected rodent urine, droppings, or saliva.
• In South American outbreaks, researchers estimate that the incubation period varies from about 12-27 days.

Is hantavirus contagious?

There is no evidence that HPS is not contagious from person to person contact in the US. The virus spreads from rodents to humans. Although outbreaks seem like there is person-to-person transfer, outbreaks are usually noted among groups of people exposed to the same infected rodent population while those with hantavirus infections do not transfer them to other uninfected individuals.

How long is hantavirus contagious?

• As of January 2017 in the US, hantavirus has affected about 800 people.
• In South America, an estimated 16-35 days was the contagious period for a rare few patients who investigators considered to have exhibited person-to-person transfer with a type of hantavirus termed Andes virus.
• While this is the situation in North America, there are reports that in 1996, mild infections with hantaviruses were transmissible in an outbreak in Argentina. 
• Small outbreaks are reported each year; for example, Texas had its first person diagnosed with hantavirus in 2015.

A test considered to diagnose HPS is a positive serological test result, which is evidence of viral antigen in tissue by immunohistochemistry, or the presence of amplifiable viral RNA sequences in blood or tissue, with compatible history of HPS, which is considered diagnostic for HPS.

Consequently, most patients diagnosed with HPS are usually cared for in the intensive care unit by specialists trained in critical care, and consultation with an infectious-disease doctor. Because the lungs are the most compromised organ in these infections, a lung doctor (pulmonologist) also is usually consulted. Moreover, specialists from the CDC are often involved to help locate the outbreak source and to help healthcare personnel at the outbreak site prevent further infections.

• Unfortunately, hantavirus infections can lead to HPS. According to the CDC, hantavirus infections according have a mortality rate of about 38%.
• At this time, there is no definitive treatment for HPS other than early recognition of HPS and subsequent medical support (usually consisting of symptomatic medical treatment and respiratory support or mechanical ventilation).
• The CDC suggests that early treatment in an intensive care unit may allow the patient to survive severe HPS.
• Experimentally, doctors have administered the antiviral medication ribavirin (Rebetol, Copegus), but there are no clear data currently that establish that the drug is effective against HPS; however, its use against HFRS early in the disease suggests ribavirin can decrease illness and deaths.
• There is no vaccine available to protect against any hantaviruses to date.

The major complication of HPS is death from respiratory failure. Those who survive may take a few weeks to recover fully. Those patients who survive do not have chronic infections nor do they experience other chronic problems or complications.

The prognosis of HPS is fair to poor because currently, about 62% of patients recover, while about 38% will die. The prognosis may be better if the patient gets his/her diagnosis early and is given support in an intensive care unit in a hospital. However, the early diagnosis of HPS is difficult; some patients did not know they had been exposed to rodents that carried hantavirus.

There are no vaccines available to protect against any hantavirus types. The CDC recommends the elimination or reduction of contact with any rodents (for example, at home, worksites, campsites, barns, sheds) by reducing rodent access or rodent-proofing. Sealing up gaps and holes, placing traps, and keeping areas as clean and food free as possible will help. If a person must come in contact with rodents or areas where they live, precautions such as gloves and masks may reduce the chances for infection; disinfectant treatment of possible contaminated surfaces may also help prevent the disease.

Do not attempt to use a vacuum or use a broom to remove rodent urine or feces; this action may increase the risk of HPS by generating an aerosol. The risk of HPS can be reduced by inactivating hantaviruses in the environment by using a household detergent and 1½ cups of bleach per gallon of water to wipe or spray the potentially infected area and while minimizing contact by wearing gloves and a mask. Take similar precautions with rodents caught in traps.

• In 1993, health officials noted the first recognized outbreak of HPS in the "Four Corners" area of the U.S., where the states of Arizona, New Mexico, Colorado, and Utah meet. Two otherwise healthy young people, a Navajo Indian, and his fiancée, suddenly became short of breath and died. This unusual situation triggered a review of deaths in the four states that resulted in the identification of five other young people who recently died with similar breathing problems. During the next few weeks, health care providers treated additional people in the same geographic area with similar pulmonary syndromes.
• Tissues from affected patients were sent to the CDC, where researchers searched for causes and found a link among the patients: infection with a previously unknown type of hantavirus. Since other known hantaviruses (in Asia and Europe) were known to be transmitted to people by rodents, the researchers started trapping rodents from June to August 1993 to determine if the virus was associated with the animals.
• In November 1993, a rodent (a deer mouse) trapped by CDC researchers in a house where a person who developed pulmonary syndrome lived yielded the previously unknown virus. In addition, army researchers soon isolated the same virus from an infected patient who also had exposure to mice. This new hantavirus was first termed Muerto Canyon virus, then Sin Nombre virus (SNV), and eventually simply hantavirus.
• The disease caused by this virus was termed hantavirus pulmonary syndrome (HPS).
• Further investigations suggested that other people had died from this infection in the past, as autopsy tissue contained the virus.
• When health researchers studied Navajo Indian medical traditions, the Navajo medical culture recognized the disease and associated it with mice.
• The outbreak in 1993 probably occurred because environmental factors led to favorable survival and proliferation of mice. The mouse population was about tenfold greater in 1993 than in 1992 in the Four Corners area.
• A large, more recent outbreak of HPS occurred at Yosemite National Park, California, in 2012. The outbreak was linked to deer mouse dropping contamination in campsites (tent-cabins) used by tourists.
• This zoonotic (animal-to-person) transmission probably happened with a rodent infestation augmented by favorable nesting conditions like woodpiles in or near the campsites. At least three deaths occurred, and seven other infected people recovered.