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Zoonotic Threats: As Unpredictable as They Are Dangerous

MAR 29, 2018 | JARED KALTWASSER
In epidemiology, some things are highly predictable. For instance, it’s a sure bet that whenever the next outbreak of some strange-sounding disease occurs, the media will start calling, the public will start worrying, and the government will rush in with promises of new research funding. (See H1N1; West Nile; Ebola; Zika.) The boom-and-bust pattern of public attention repeats itself over and over again.

What is less predictable is which particular disease will spark the next global health crisis. Public health experts believe the biggest threats are diseases transmitted from animals to humans. According to the US Centers for Disease Control and Prevention (CDC), more than 6 in 10 known infectious diseases are believed to be zoonotic, and three-quarters of new or emerging infectious diseases in humans are zoonotic. Yet, the goal of predicting precisely which zoonotic diseases will become epidemic remains elusive.

Part of the reason it’s hard to predict which viruses will become dangers to humans is because a virus tends to optimize itself for its current host, said Richard J. Webby, PhD, director of the World Health Organization Collaborating Center for Studies on the Ecology of Influenza in Animals and Birds, and a faculty member at St. Jude Children’s Research Hospital.

“A virus’s main purpose in life is to grow in that host,” Dr. Webby told Contagion®. “...[Avian flu] is going to optimize itself to grow in chickens. It’s becoming clearer that that optimization for growth in chickens doesn’t increase risk in humans.”

Thus, while it’s important to monitor avian flu, a given strain of bird flu most likely won’t become a threat to humans. Unless it does.

Dr. Webby said transmission of a virus to another animal, such as a pig, could cause the virus to change and perhaps become more dangerous.

Juergen A. Richt, DVM, PhD, a professor in the Department of Veterinary Medicine at Kansas State University, said the worst-case scenario would be if a flu virus evolved to become airborne.

“If we have a deadly flu which is aerosolized and easily transmitted among people that will be a big problem because it takes 6 to 9 months before we have a vaccine,” he said.

That hasn’t happened yet, but Dr. Richt said the danger of zoonotic disease has increased in the past 2 to 3 decades as a number of zoonotic viruses have matured to a dangerous point. Why now? Dr. Richt cited a long list of human impacts on the environment, such as deforestation, the domestication of animals that used to be wild, and agricultural practices like feeding rendered beef products to natural herbivores like cows.

Casey Barton Behravesh, MS, DVM, DrPH, DACVPM, director of the CDC’s One Health Office in the National Center for Emerging and Zoonotic Infectious Diseases, agrees.

“Many factors have changed interactions between people, animals, and our environment in recent years,” she said. “Human populations are growing and expanding into new areas; the earth has experienced changes in climate and land use, and international trade and travel have increased. These changes have led to the emergence and reemergence of many diseases. In today’s connected world, a disease threat anywhere can mean a threat everywhere.”

Among the top concerns of public health officials are the H7N9 avian flu in China, the H5N1 bird flu strain in Egypt, and hemorrhagic fevers like Ebola and Marburg.

The vast array of potential threats, and the exceedingly rare odds that any particular virus becomes a pandemic, make the task of epidemiological surveillance particularly difficult.

Patrick Ayscue, DVM, director of epidemiology at the risk analytics firm Metabiota, said most outbreaks aren’t candidates for a pandemic.

“On any given day there’s a lot of outbreaks or epidemics going on in the world, and a lot of it looks like the Salmonella in the potato salad,” Dr. Ayscue said.

An outbreak rises to the level of concern when it has a particularly high mortality rate, spreads quickly, or has the potential for major economic disruption due to lost productivity or high-cost treatment.

Metabiota, among others, is trying to develop better ways to pick out which diseases are most likely to become epidemic or pandemic. That foresight could allow public health agencies to prepare vaccines or treatments, or simply to line up adequate resources to deal with patients. Such advanced notice could literally save hundreds of thousands, or even millions, or lives.

One of the key ways researchers are trying to switch from “reactive” to “proactive” is by using the power of Big Data.

Nita Madhav, MSPH, head of data science at Metabiota, said tracking and predicting the spread of zoonotic viruses is difficult.

“There are a lot of considerations that we have to take when we’re building these types of models,” Ms. Madhav said.

Depending on where the outbreak takes place, there might be a considerable amount of quality data, or there might be very little. In fact, the relative availability of data in and of itself can be an important factor for modeling, since countries without robust surveillance systems might also be less well-equipped to handle an outbreak. And 1 of the key factors that can cause a small outbreak to grow is a poor or slow response in the outbreak’s country of origin.

“We always have to be very aware of the situation on the ground and we do keep track of this through our monitoring,” she said. “I think it’s very important to keep in mind that as the outbreak is unfolding the response really does matter.”

Ms. Madhav said Metabiota is partnering with the African Union’s Africa Risk Capacity (ARC) agency to leverage predictive modeling in support of ARC’s insurance pool, which aims to provide rapid funding to member countries in cases of disease outbreaks.

Domestically, Dr. Barton Behravesh said the CDC is currently researching how viruses, bacteria, parasites, and fungi spread between animals and humans, how human behavior affects the risk of animal-to-human transmission, and how quickly these diseases spread.

She said they are also building public health capacity.

One way governments can prepare for epidemics is by developing vaccines. However, it’s tough to know which vaccines to prioritize, given that vaccine development is expensive, both in terms of time and money. Dr. Webby added that it’s hard to make a solid vaccine development cost-benefit case to the pharmaceutical industry.

“I guess from their perspective it’s a little hard to justify putting too many resources into developing a product that you may never use,” he said.

On the other hand, the National Institutes of Health and agencies like the World Health Organization have put considerable resources into such research. In some cases, according to Metabiota’s Dr. Ayscue, it’s possible to do initial research now that will have the effect of drastically shortening vaccine development times once an epidemic arises.

The Global Virome Project, for instance, a $1.2 billion effort to detect and characterize the world’s unknown viral threats. That project is an international collaboration and is expected to unfold over the next decade.

Dr. Richt, whose background is in veterinary medicine, said part of being proactive and not reactive should also be funding more research to contain diseases prior to human transmission.
“Here’s my concern;” he said. “If 1 dollar is spent for research for veterinary medicine and the stuff we do, $20 are spent in medical schools for the same thing.”

Personally, Dr. Richt said he’s been fortunate to have received considerable funding, but he said he is the exception. “Most researchers who work in the veterinary environment do not have good funding,” he said.

He hopes that algorithms will someday be able to pinpoint pandemics before they happen, but in the meantime, funding more veterinary research could help control diseases before they spread to humans. He noted that thus far, predictive models have failed to predict things like the H1N1 outbreak of the West African Ebola epidemic.

Ultimately, even as the science advances, Dr. Richt said he’s keenly aware that in the world of animal-to-human transmission, a single unpredictable event could have catastrophic implications. That fundamental tension in epidemiology—between the controllable and the uncontrollable—isn’t going away.

“These things will always happen,” he said. “This is normal. We have to live with that.”
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