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Published: October 2012

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Hantaviruses are a group of viruses that may be carried by some rodents. The rodents shed the virus in their urine, droppings, and saliva. The virus is mainly transmitted to people when they breathe in air contaminated with the virus and can cause hantavirus pulmonary syndrome, a serious condition with a mortality rate of approximately 40%. While there is no specific treatment, cure, or vaccine available, early diagnosis is key to quickly provide effective supportive care.

Presenter: Matthew Binnicker, PhD

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Thanks for the introduction, and thanks to all the viewers who have joined me for this video Hot Topic.  In this presentation, we’ll review the key clinical and diagnostic information related to hantavirus, which is an important emerging infection in North America.  As many of you are probably aware, hantavirus has been prominent in the news during the summer of 2012, due to an outbreak of cases associated with travelers to Yosemite National Park.  Because of the increased awareness to hantavirus infection, it’s important to understand how the disease is transmitted, what the clinical signs and symptoms are, and how the illness is diagnosed. 

Before we get started, I should mention that I have no financial or corporate conflicts of interest that need to be disclosed.

So let’s get started.  In this presentation, we’ll first review the basics of hantavirus infection, including the causative agent, how the disease is transmitted, and the clinical manifestations associated with the illness.  We’ll then discuss the laboratory methods used in the diagnosis of hantavirus, and finally, review how individuals can prevent being infected.

Hantavirus is an RNA virus and a member of the Bunyaviridae family.  This family of viruses are vector-borne, meaning that they are transmitted to humans by either arthropods, such as mosquitos or ticks, or by rodent hosts.  The name “hantavirus” is derived from the Hantan River is South Korea where the initial member of the Hantaan virus group was isolated in the 1970s.  Interestingly, the first outbreak of hantavirus in the United States was identified in 1993 in the Four Corners region of the southwest United States, which is the region where Colorado, New Mexico, Arizona and Utah share borders.  During this initial outbreak, the causative agent of the infection was unclear, so the virus was called “Sin Nombre virus”, which translates to “Nameless virus.” 

Although we’ve now characterized the cause of hantavirus infection, the name “Sin Nombre virus” has been retained to describe the strain of virus that is responsible for the majority of cases in the United States.  As I mentioned earlier, Bunyaviruses are vector-borne, and it is now known that the host of the Sin Nombre virus is the deer mouse, or Peromyscus maniculatus, which is most prevalent in the central and western regions of the United States. 

There are several other types of hantavirus in the United States, including the New York hantavirus, which is most common in the Northeast portion of the country and is harbored within the white-footed mouse population.  The other type is the Black Creek hantavirus, which causes outbreaks of disease in the southeast United States and is carried by the cotton rat.

So how is Hantavirus transmitted to humans?  These viruses are shed in the urine, droppings, or saliva of the rodent host.  People can acquire hantavirus through several different routes.  The primary route is through inhalation of air containing the virus.  A second mechanism is when an individual comes in contact with a surface contaminated with hantavirus, and then transmits the virus from their hands or a fomite to their nose or mouth.  Third, hantavirus can be acquired by eating food contaminated with urine, droppings, or saliva of an infected rodent.  And finally, the infection can be acquired through the bite of an infected rodent, although this mode of transmission is believed to be extremely rare. 

It’s very important to emphasize that the types of hantavirus that are prevalent in the United States can NOT be spread from one person to another.

There are certain activities that place an individual at higher risk for acquiring hantavirus infection.  As we’ve discussed, these activities involve contact with rodent droppings, urine, saliva, or nesting materials.  Patients that have hantavirus often report cleaning previously unused buildings, such as cabins, sheds, barns, basements, or storage facilities where rodents are more prevalent.  In addition, individuals employed in construction, utility, or pest control are often more likely to come in contact with rodent material.  Finally, campers and hikers may be at increased risk for hantavirus infection.

Following exposure to hantavirus, the incubation period is typically 2 to 4 weeks until the onset of symptoms.  There are 2 main categories of hantavirus disease.

The first is hemorrhagic fever with renal syndrome (HFRS), which is not a common form of the disease in the United States.  HFRS is categorized by early onset of fever, chills, nausea, headache and generalized malaise.  As the disease progresses, patients often suffer from hypotension, or low blood pressure.  In the later stages, patients may experience renal failure, which can be accompanied by proteinuria and increased urination. 

The second category of disease is hantavirus pulmonary syndrome, or HPS, which is the most prominent form of the disease in the Americas.  Patients with HPS may experience a nonspecific, flu-like illness during the early stage of disease, with fever, fatigue, muscle aches, nausea and vomiting.  Four to 10 days later, patients may then develop coughing, shortness of breath, and respiratory distress.  HPS is a very serious illness, and carries an approximate 40% mortality rate.

The diagnosis of hantavirus pulmonary syndrome may be made on clinical grounds, if patients meet the clinical case definition that has been established by the Centers for Disease Control.  A case of HPS is defined by a febrile illness with bilateral diffuse interstitial edema that develops in a previously healthy individual within 72 hours of hospitalization.  Patients with HPS may also be defined by an unexplained respiratory illness resulting in death, with an autopsy demonstrating noncardiogenic pulmonary edema without an identifiable cause.

Due to the nonspecific clinical presentation of hantavirus disease, laboratory testing is often needed to support or confirm the diagnosis.  In regards to laboratory testing, serology is the most common method that is used.  A diagnosis of acute exposure to hantavirus is supported by the detection of anti-hantavirus IgM antibodies, and/or the conversion of IgG antibodies from negative in an acute serum sample to positive in a convalescent phase serum sample. 

Polymerase chain reaction, or PCR, is another laboratory method that can be used to diagnose hantavirus, but this method is mainly limited to state health laboratories or the CDC. Antemortem, PCR can be performed on lung biopsy tissue, bone marrow aspirate, or blood samples.  If specimens are collected during postmortem autopsy, PCR testing is commonly performed on tissue collected from the spleen, lung, kidney, liver, or lymph nodes. 

A third laboratory method that can be used in the diagnosis of hantavirus is immunohistochemistry, in which specific, tagged antibodies are used to identify hantavirus within fixed tissue samples.  As with PCR, immunohistochemistry is not a common laboratory approach, and this method is typically performed postmortem at state health labs or the CDC.

Unfortunately, there is no specific treatment or vaccine available for hantavirus infection.  Because of this, early recognition is key, and it is important for health care providers to obtain a detailed history and determine if patients have had rodent exposure or have been involved in high-risk activities.  Patients with hantavirus pulmonary syndrome require intense supportive care, often including intubation and oxygen therapy due to severe respiratory distress.  Due to the lack of specific therapy and the severe nature of hantavirus infection, it is important to highlight that prevention is the best medicine.  This involves avoiding contact with rodents and taking precautions when cleaning areas that are potentially contaminated with rodents or their nesting materials.

In conclusion, hantavirus is transmitted by contact with contaminated rodent droppings, urine, or saliva.  Hantavirus pulmonary syndrome, or HPS, is the most common form of disease in the United States and is a serious medical condition with a mortality rate of approximately 40%.  There is no specific therapy available for HPS, so patients rely on early diagnosis and intensive supportive care.  The diagnosis is typically made on clinical grounds with the use of serology, but laboratory methods such as PCR and immunohistochemistry are also available at state health laboratories or the CDC.

If you have further questions regarding hantavirus, I’d recommend you visit the CDC website listed on this slide, which has additional information on this important, emerging infection.   Thanks again for joining me today.

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