Disease Vectors

Bat images courtesy of Raina Plowright

Bat, mouse studies may help predict outbreaks

UM graduate student Andreas Eleftheriou holds a mouse in a study area near Polson. (Angie Luis photo)By Deborah Richie

What do Ebola, SARS, Nipah and hantavirus have in common? All four viruses originated in wildlife and spread to people.

Across the world, scientists are scrambling to understand deadly new diseases. They study the viruses in a race against time in hopes of developing vaccines and preventing epidemics. However, the virus is only one half of the equation, says Angie Luis, UM assistant professor of population and disease ecology.

“I would argue that it’s important to understand what’s happening in the wildlife if we want to prevent these spillovers into humans,” Luis says.

Her research embraces the wide field of population, community and disease ecology to answer big questions. What leads to outbreaks? What are the environmental triggers? Can we predict when outbreaks will occur? How does transmission from animals to humans work?

Luis currently focuses on two wildlife disease hosts: mice and bats. She applies mathematical models fed with reams of data to come up with patterns that can lead to answers. Discuss the power of math applied to wildlife biology, and Luis reveals her passion right away.

“I find mathematical modeling really powerful,” says Luis, who joined UM’s College of Forestry and Conservation in 2014 after completing postdoctoral research at Princeton University in ecology and evolutionary biology. “We can predict things.”

Predicting Hantavirus Outbreaks

In 2015, Luis produced significant results that could mean fewer deaths from hantavirus, a disease transmitted from deer mice to people and one that’s relevant to Montanans. While cases are few, the mortality rate is one out of three.

“We can potentially predict the times of increased risk of hantavirus months in advance,” she says of her published research in the journal Ecology. Luis is the lead author with three co-authors of “Environmental fluctuations lead to predictability in Sin Nombre hantavirus outbreaks.”

The predictive ability resulted from analyzing 20 years of field data in the state gathered by her colleagues at Montana Tech in Butte.

“Their data show huge fluctuations in mouse populations and hantavirus prevalence within the mice,” she says.

Crowded mice Portends Hantavirus

When mice reach a density of at least 17 per hectare (2 1/2 acres) outbreaks result, but not right away. Luis explains that if mice reach very high densities of 70 per hectare, the transmission rates increase and an outbreak could occur about four months later. The lower the density of mice, the longer the time lag. A density of 35 mice per hectare would give 11 months’ warning before hantavirus becomes a real threat.

“The time lag gives us time to warn people to take precautions,” Luis says. The most common way to contract hantavirus is from contact with fresh droppings, and spraying them with a bleach solution kills the virus.
The challenge is to monitor mice population changes in differing habitats to predict outbreaks with accuracy, says Luis. For example, mice may skyrocket in numbers after plentiful rainfall leads to lush plant growth and seeds that mice eat. Yet not all parts of the state have similar conditions.

Heat-Stressed mice more Vulnerable

Angie Luis mouse photoThe Luis lab now is investigating hantavirus in mice related to climate change and competition with other species for food. When it’s hot outside, we might head indoors to stay cool. For mice, higher temperatures may add stress that depresses the immune system and invites replication of hantavirus, Luis suggests. In turn, higher doses of the virus in saliva could raise transmission rates when a mouse bites another mouse. As climate changes, food resources also change, affecting mice densities.

To study stress in mice, Luis is writing a grant to test whether stress hormone levels rise as competition grows. The research would entail setting up enclosures stocked with mice and then adding in competitors, like voles, to see how mice respond.

Meanwhile, Luis advises people not to stress out too much about hantavirus.

“You’re twice as likely to be struck by lightning as you are to contract hantavirus,” she says.

The epidemic potential of some other hosts Luis studies can be dramatic in comparison.

Why Bats Survive and Transmit Viruses

UM researcher Angie LuisBats can live with not one but sometimes multiple viruses, especially in tropical climates where the bat species diversity is high. Sometimes those viruses spill over to humans. Ebola likely originated from bats in Central Africa. SARS and Nipah virus are linked to bats in Southeast Asia.

Luis once again takes advantage of mathematical modeling to find telling patterns that offer clues to why bats are such effective conveyers of disease to people.

Her work does not diminish her appreciation for bats, which decorate her office as silhouettes.

“Bats are really important, and we need to conserve them,” she says of their role as pollinators and predators of insects like mosquitoes. “What we need to do is to stop contact with humans and not kill bats.”

Bats come into contact with people more often when they lose natural habitats, she explains. The Nipah virus, for example, is connected to cutting down native trees in Malaysia that sustained fruit bats. To survive, the bats roosted in domestic fruit trees. They ate fruit that then dropped to the ground and was in turn eaten by pigs foraging below. The first outbreak in 1999 showed the virus came from eating pigs. Out of 300 cases, 100 people died.

“Ecological factors are important, as are the number of species and the potential contacts of species with each other,” Luis says.

She points out that certain kinds of bats naturally will roost in colonies numbering in the millions, often with multiple bat species.

“It’s the perfect place for bats to interact, leading to high contact rates and transmissions across species,” she says.

Bats fly. They cover long distances and can spread the virus to different regions, and meanwhile most bats remain unaffected by the viruses they carry. (See sidebar). The exception is rabies, which does kill bats that contract it. The case of the white-nose syndrome that has killed millions of bats in the eastern U.S. is different, because the disease comes from a newly introduced fungus.

To find patterns, Luis is leading a research effort that entails sifting through 70 years of data on viruses identified in bats and rodents. So far, she’s documented that bats host more viruses per species than rodents do.
That seems strange at first glance, with 2,200 species of rodents compared to 1,100 species of bats. The two groups rank No. 1 and No. 2 in highest numbers of species among mammals.

In her newest article in Ecology Letters, Luis focuses on the ability of bats to transmit viruses from one species to another and how that common occurrence may help explain why bats serve as reservoirs for emerging viruses. She examined them in a community context, rather than as individual species, and compared them to rodents. The results suggest that viruses cross over more easily in bat species than in rodent species. Social bats and those that migrate share and spread more viruses.

Her colorful graphic displays a network of arcing lines depicting how social bat species and those that migrate share and spread more viruses. The converging lines pinpoint certain communities and individual species of both bats and rodents that may be the highest contenders for transmitting wildlife diseases, narrowing the field for future studies.

“Understanding the dynamics in wildlife is important to understand what leads to spillover into humans,” Luis stresses. “It’s urgent right now.”

The Feverish Flight of Bats

The only mammal that flies, a bat’s metabolism increases up to 15 times its resting rate, with body temperatures escalating to fever levels. Luis hypothesizes that this feverish flight may explain why a bat can host viruses that are not harmful to the bat, yet once transmitted to people can prove deadly.

Fever is one mechanism that helps our immune system fight infections, but it fails when encountering a disease like Ebola.

“Viruses in bats may have evolved to handle the ramped up immune response,” Luis explains. “In humans that would mean our immune system isn’t effective.”