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ZOONOTIC THREATS: AS UNPREDICTABLE AS THEY ARE DANGEROUS

March 29, 2018
Jared Kaltwasser






Public health officials cite zoonotic disease as the top pandemic threat, yet
the task of predicting or preparing for a pandemic remains difficult.



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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