For the past 20 years, Amy Kuenzi has spent three days of every month traveling to a ranch near Gregson, Montana, and setting out traps that contain peanut butter and oats. Her quarry is deer mice. She takes blood samples, looks for scars and fleas, and attaches ear tags.
"Mice are fairly trap happy and easy to catch," she said. "But it can be kind of a miserable job in the winter."
Kuenzi's goal is to better understand how a type of hantavirus called Sin Nombre spreads through these mouse populations.
Kuenzi, a professor of biology at Montana Technological University, and her colleague Angie Luis, a professor of biology at the University of Montana, are among a growing number of researchers working to predict where viruses may be likely to spill over from animals to humans. Sixty percent of human diseases, including the Sin Nombre hantavirus, originate in animals, and two-thirds of those originate in wildlife.
By understanding hantavirus and the complex ecology that governs it, Kuenzi and Luis also hope to create a model system to better understand the ecology of many other viruses, including coronaviruses.
The researchers have built six large enclosures at the Bandy Ranch, a University of Montana research facility. There, they can study how deer mice behave when they're the sole occupants and then introduce the mice's main rodent competitors, voles, to see how mouse populations, mouse behavior, and disease prevalence change.
"We're asking how competitors affect the transmission of disease," Luis said of the research, recently funded with a $2.5 million National Science Foundation grant. "We are trying to understand that as we stress animals, as we add or remove competitors, how does that change the transmission?"
The role of biodiversity in zoonotic diseases is complex and can have both positive and negative effects. For example, competition from other rodents can lower deer mice numbers and reduce how often the mice interact, limiting infections. At the same time, the presence of more competitors can stress deer mice, and stress in animals has been shown to lower their immunity and greatly increase their viral load.
Climate change is also a factor. Warmer temperatures and fluctuations in rain and snow are changing habitats, which can affect infection rates. The first recognized outbreak of hantavirus in humans, in 1993, is thought to have been driven by a wet winter that provided more food for mice.
The Montana study area has only two main rodents, making it a simple system for carrying out research. Kuenzi and Luis are also gathering data in the Southwest, where Sin Nombre is far more prevalent — and complicated. "At one site in Arizona, we caught 29 species of rodent-sized small mammals," Kuenzi said. The larger number of species appears to decrease the prevalence of the disease, Luis said.
Sin Nombre, Spanish for "without a name," is one of several types of hantavirus. It is transmitted through the inhalation of airborne particles from mouse droppings. The disease is rare in humans but can be deadly. In 1993, the first known outbreak was on the Navajo Nation in the Southwest. It killed 13 people, half of those it infected.
The disease is most prevalent in rural areas, where mice and other rodents are common, and public health officials urge people to take special care when cleaning homes or buildings that have been closed for the winter or when working in areas like crawl spaces or vacant buildings where rodents may be present.
In 2012, Sin Nombre in tent cabins in Yosemite National Park killed three people. In 2004, the deputy superintendent of Glacier National Park died from the disease. From Sin Nombre's discovery in 1993 through 2019, fewer than 900 infections were reported in the U.S.
The hope for the research in Montana is that it will lead to recommendations on how to manage land in ways that don't increase the prevalence of the disease.
This is just one thread in the tapestry of disease ecology. The long list of factors that increase the possibility that pathogens will spill over from animals to humans is getting a lot of attention from researchers around the world in response to the pandemic caused by SARS-CoV-2. Viral outbreaks are a product of the ways that humans are altering the natural world, though researchers are seeking to determine precisely how.
In the big picture, research from the past 20 years shows that keeping nature intact will help minimize the risk of another pandemic. "Evidence is mounting that biodiversity dilutes out disease," Luis said. "As we lose biodiversity, we see greater disease prevalence."
When animals can move to find food when they need to and avoid humans and domestic animals, "we are not going to see spillover events," said Raina Plowright, a professor at Montana State University, who studies the disease ecology of bats.
Activities that bring people into contact with wildlife — such as farming, logging, and building homes in wild areas, all of which change the ecosystem — may amplify the risk of spillover.
It could, for example, drive the competitors of deer mice out completely. "Deer mice like disturbance," Luis said. As land is developed, species that compete with deer mice may scatter, and without competitors, deer mice increase in number. With more mice come more encounters between them and the spread of Sin Nombre.
Early studies of biodiversity and disease took place in upstate New York, where the fragmentation of forest habitat by development had led to the loss of foxes, owls, hawks, and other predators. Those changes drove a five-fold surge in the number of white-footed mice, which are potent reservoirs for the bacteria that cause Lyme disease.
But the idea that biodiversity has protective effects is more complicated than first thought. "There are lots of exceptions to this idea that biodiversity dilutes out disease," Luis said. "You can get both positive and negative effects of biodiversity at the same time. There is an overall dilution effect because competitors lower the density of deer mice," she said, but there might be amplification from stress caused by competitors.
Kevin Lafferty is an ecologist with the U.S. Geological Survey's Western Ecological Research Center in Santa Barbara, California, and studies the ecology of parasites. Focusing on the ecology of mice and hantavirus makes sense, he said: "If wild rodents … are going to become more abundant because we disturb the environment, then those particular diseases might be the kind of things we should worry about."
However, the broad notion of protecting biodiversity to prevent disease is "wishful thinking," he said. "That's a vague and ineffective way to solve human health problems," Lafferty said. Instead, he added, researchers should focus on how the viruses' hosts respond to the environment.
Luis agreed that more work needs to be done on a complicated topic. "Outbreaks that are moving from animals to humans have only become more common over the last 30 to 40 years," Luis said. "This is not the last pandemic. We need to understand how what we are doing leads to these outbreaks."