Long-Term Study by Colorado State University Virologist Seeks Links Between Deer Mouse Population, Hantavirus Infections in Humans

A professor of microbiology at Colorado State University thinks there’s a connection between the number of deer mice in Colorado carrying Sin Nombre virus and the likelihood of humans catching the often-fatal disease it causes.

Since 1994 Charles Calisher, a virologist, has trapped deer mice and tested them to see if they carry antibodies to this hantavirus in an effort to establish why this virus fluctuates geographically and over time. Sin Nombre is one of many hantaviruses but is the principal cause of hantavirus pulmonary syndrome (HPS) in humans in the United States.

Hantaviruses do not appear to affect mice but do induce them to generate antibodies, an easy measure of the virus’ spread in the mouse population. The virus is passed to humans who inhale dust containing dried saliva, urine or excrement from infected deer mice.

In Colorado, HPS has been reported primarily in far southwestern Colorado, although a case has been reported recently near Loveland. After Sin Nombre virus was identified during the Four Corners outbreak in 1993, cases dropped for several years, only to start climbing again in 1996.

This year, Calisher is finding high numbers of antibody-carrying mice. Recently, examination of Western Slope mice showed that 40 percent were infected, while at Pinon Canon Maneuver Site in southeastern Colorado near Rocky Ford, where rates of infected mice usually hover near 1 percent, the 1999 level has been as high as 8 percent.

A retired 27-year veteran of the Centers for Disease Control, Calisher was brought to Colorado State by microbiologist Barry Beaty and shortly afterward began the hantavirus project. He is assisted by mammalogist Jeff Root and by visiting scholars and graduate students. Their work, supported by the Centers for Disease Control, is the first long-term study of hantaviruses and their rodent carriers in Colorado. Similar efforts are under way in New Mexico and Arizona.

Calisher spends about three days every six weeks at each site, passing on the Western Slope sites in winter. His sites consist of 12 lines of 12 traps each, the lines radiating from a center trap like wheel spokes. This arrangement helps track mouse movements. Calisher, Root and associates bait the traps and check them daily. Donning respirators, gloves and surgical gowns, the team examines all trapped animals before releasing them. When a rodent is caught, the researchers take a series of measurements and a blood sample and insert an ear tag. Only 10-20 percent are recaptured. Among the measurements noted (trap site, date, genus, species, gender, size and so on) are some arcane determinations of breeding readiness.

"We have data suggesting that sexual preparedness (readiness to mate) will be useful as an indicator of population increases," Calisher said. "It doesn’t seem to be temperature but the amount and timing of precipitation that affects population densities. Deer mice eat plant seeds, but unless rains come at certain times, certain plants may not produce seeds. There’s some evidence, however, that mice may require (chemicals found in) plants to ovulate."

For example, Calisher says, in a certain area, given a cold, wet winter and normal losses to predation and sickness, only 50 of 100 deer mice might survive until spring.

"On the other hand, given a warm, wet winter, 75 might survive and will breed earlier, say in February instead of March," he said. "With plenty of food, they would have a higher survival rate and those first litters could breed, so that 75 could turn into 250. If a second warm, wet winter occurs, 150 to 175 might survive, so that by fall you could be swimming in mice."

"You could not only have a lot of mice, but you could have a high proportion that are infected," Calisher said.

As for answers, Calisher’s database of deer mice, Sin Nombre antibodies and breeding readiness keeps growing. He doesn’t know when the effort may end.

"We’re going to just keep doing it as long as the funding holds out," he said. "The question is, can we find an indicator that will give us an early warning system for humans?"

The answer, he thinks, is "yes" and that the team has already found at least one indicator.

"Taking into consideration both the number of animals and the percent that are antibody-positive, we can construct an index. Sudden increases in this index over the past couple of years appear to correlate with the approximate onset dates of human infections.

"However, this doesn’t necessarily imply causality, so we have a lot more work to do."

Worldwide, each hantavirus strain is carried by a specific rodent species, which makes the two Western Slope sites easier places to work, since they harbor only Sin Nombre-carrying mice, some chipmunks and not much more in the way of rodents. The Pinon Canon Maneuver Site has 18 rodent species, including deer mice and pinon mice.

Calisher, a self-described "lab guy, used to working with viruses," checked reference books to identify the rodents he trapped in the early years but now has the assistance of Root, an expert on mammals. Calisher, who has trapped more than 2,000 deer mice during his study, expects that the results of all this work will be useful in preventing HPS, which kills nearly half its victims.