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Scientists one step closer to understanding and possibly treating hantavirus infections

By Michael Howell

A group of scientists, including three from Rocky Mountain Laboratories in Hamilton –Doctors David Safronetz, Joseph Prescott and Heinz Feldman – have created an animal model that promises to unlock some of the secrets of how Hantavirus Pulmonary Syndrome (HPS), a disease spread by deer mice, actually works when it infects humans. Identifying early signals of the disease could help scientists develop effective therapeutics and vaccines against such Hantaviral diseases.

HPS is an acute respiratory disorder that was initially described in 1993 during an outbreak in the Four Corners region of the southwestern U.S. Since then more than 2,000 cases have been reported, 639 in the United States. Montana ranks sixth in the nation with 37 reported cases. Over one third (38%) of the people who get the disease die from it. The infecting culprit was identified quickly as a novel hantavirus and subsequently named “Sin Nombre virus” (SNV).

In North America the disease is exclusively found in deer mice. Mice carrying the virus do not get sick, but the virus is passed on in the urine, feces and saliva of the animal. Humans inhale the virus when they breathe in contaminated dust.

According to the Centers for Disease Control website, due to the small number and sporadic episodes of HPS cases, the “incubation time” is not positively known. However, on the basis of limited information, it appears that symptoms may develop between one and 5 weeks after exposure to fresh urine, droppings, or saliva of infected rodents. Early symptoms include fatigue, fever and muscle aches, especially in the large muscle groups – thighs, hips, back, and sometimes shoulders. These symptoms are universal.

There may also be headaches, dizziness, chills, and abdominal problems, such as nausea, vomiting, diarrhea, and abdominal pain. About half of all HPS patients experience these symptoms.

Four to 10 days after the initial phase of illness, the late symptoms of HPS appear. These include coughing and shortness of breath, with the sensation of, as one survivor put it, a “…tight band around my chest and a pillow over my face” as the lungs fill with fluid.

One thing holding back research on the disease and how it works in humans has been the lack of good surrogate disease models with which to perform pathogenetic studies. Currently the only model of lethal hantavirus disease was the Syrian hamster, which after infection with Andes (the most virulent south American species of hantavirus) develops severe disease that faithfully recapitulates the cardiopulmonary phase of HPS in humans. But nonhuman primates, like the rhesus macaques, are often viewed as the “gold standard model” for study of emerging viral pathogens, especially those that are immunopathogenic, because these animals are believed to manifest most accurately the underlying deleterious host immune responses associated with disease progression in humans.

“This model provided the first, to our knowledge, in-depth pathogenesis study in the nearest surrogate host and identified virus replication, systematic hematologic abnormalities, and lung specific proinflammatory responses as hallmarks of HPS pathogenesis,” states the report.

Dr. Dave Safronetz of Rocky Mountain Laboratories was an undergraduate student in Canada in the early 1990s when the Hantavirus was first described in the Four Corners area. Already interested in studying zoonotic and special pathogens, he focused on the newly discovered Hantavirus for his PhD work in Winnipeg before coming to Rocky Mountain Lab in 2008.

Safronetz said that the latest development of a hantavirus model in rhesus macaques was very exciting and hopes are up, he said, that the new model will lead to some effective treatment for the currently untreatable disease and perhaps even the development of a vaccine.

The big problem is that the disease is recognized far too late,” said Safronetz. “We usually don’t see the patient until the final respiratory phase.” At that point all that can be done is to try and make the patient as comfortable as possible as the disease takes its final toll. By successfully infecting rhesus macaques the scientists have been able to spot a few “early markers” of infection prior to the manifestation of obvious physical symptoms. They are also trying out some vaccines already approved for use to see if they might work on hantavirus as well.

Safronetz said that now is the time when people are most likely to be exposed to the virus when they go about cleaning out the barn or the old cabin in springtime. He said if you are doing that kind of cleanup work it’s best to open up the building as much as possible to air it out and to use a dust mask and gloves, not just a painter’s mask or ordinary dust mask, but a good tight fitting mask with a filter. It is also recommended to spray the area down with a 10% bleach solution before sweeping.

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