How a virus spreads/SF Chronicle

August 14, 2013/San Francisco Chronicle

On June 24, 2012, a 60-year-old Saudi man died from severe pneumonia complicated by renal failure. He had arrived at a hospital in Jiddah 11 days earlier, and some of his symptoms were similar to those in severe cases of influenza or SARS, but this wasn’t either of those diseases.

This was something new.

Last September, an Egyptian virologist announced what it was: The illness was caused by a new virus in a family called coronaviruses, which includes the virus responsible for severe acute respiratory syndrome, or SARS. Several months later, epidemiologists named the new illness MERS, for Middle Eastern respiratory syndrome.

MERS, like its relative SARS, probably originated in animals.

Those revelations only bred more questions. First, where did this new virus come from, and how? Tracking a disease’s jump from animals to humans often means untangling a very complicated scientific mystery – a mystery that, in the interest of public health, must be solved quickly.

“The race is on,” said Dr. Peter Daszak, a disease ecologist and the president of EcoHealth Alliance, a scientific group working with scientists at Columbia University and the Saudi Ministry of Health in the hunt for the origins of MERS. “It’s a race against evolution.”

Diseases that can transmit from animals to humans, known as zoonoses, account for about 75 percent of emerging diseases. It’s a group of diseases that includes influenza, rabies and HIV. Bubonic plague is a zoonosis that killed a third of the human population in the 14th century.

Avian influenzas

In more recent years, epidemiologists have had their eye on avian influenzas – viruses that mostly infect birds, including a strain that spread through China this year – as sources of the next human pandemic. The SARS virus, meanwhile, caused global alarm in 2003 when it spread quickly from Hong Kong to almost every other continent.

Uncovering the roots of a virus is a “race,” as Daszak put it, because viruses are constantly evolving. The next iteration of a virus might very well pass more easily from beast to man, or spread more quickly among people once it does.

The MERS virus is now known to have infected at least 94 people, killing 46. In the past 50 years, known cases of spillover, as disease ecologists call the transfer of disease from animal to human, have increased dramatically.

“There are two major factors in a spillover,” said Dr. David Relman, a professor of immunology and microbiology at Stanford. “One has to do with the actual virus, and one has to do with the ecosystem and humans in general.”

Viruses, like all species, are first and foremost concerned with survival. A virus can reproduce only inside other living organisms. Often a virus will inhabit one particular species of animal – what scientists call a natural reservoir for the virus – with little or no consequence to the host.

More opportunities

On occasion, though, viruses find opportunity in a new species. Some viruses, such as rabies, can transmit between species easily. Others must first mutate in order to make the jump. Many scientists believe opportunities for animal disease to infect humans have only increased as the human population grows and expands its reach further into the domain of nature.

“This is something that’s going to continue to happen,” said Dr. Lee Riley, a UC Berkeley epidemiologist. “I think we’re going to see more coronaviruses continue to emerge because of what we’re doing to the environment. It’s our punishment.”

There is much that science has yet to uncover about why these spillovers occur. Yet pinpointing when and where a spillover happens, along with the virus’ reservoir speciesis just as crucial to learning more about these transactions and controlling disease.

“That’s how you stop a virus from spreading to pandemic levels,” Daszak said.

The Ebola virus, for example, emerged in the 1970s in Central Africa, but its reservoir species has yet to be firmly identified. Consequently, predicting when and where another outbreak might occur is next to impossible.

Clues in the genome

Scientists hope to do better with the new virus that causes MERS, a respiratory illness that so far has moved slowly among people. After researchers isolated and sequenced the genome of the MERS virus, the hunt for its origins began almost immediately.

Sequencing the genome told scientists quite a bit. It was a virus whose genome consisted of RNA rather than DNA, meaning it is among a class of viruses that are highly adaptable and mutate easily. The virus’ closest known relative was a coronavirus found in bats, giving scientists a clue where to begin their hunt for its reservoir.

Last October, scientists from Columbia, the Saudi government and the EcoHealth Alliance descended on rural areas of Saudi Arabia to look for bat specimens and observe the various ways bats might have interacted with people. They collected hundreds of bat specimens as well as specimens of cats, sheep, camels, goats and other species that might have acted as intermediaries between the reservoir and humans.

They also observed that bats were indeed in close contact with people – roosting in both abandoned and inhabited buildings, for example, or feeding on fruit in areas near people. It’s possible people could contract the virus through contact with bat excrement, said Dr. Jon Epstein, a veterinarian and epidemiologist at EcoHealth Alliance who was on the trip.

The team returned in April to collect more specimens and will probably return again. So far, Daszak said, more than 350 specimens have been tested, and none has been positive for MERS.

A study from a different research group last week found dromedary camels from Oman and the Canary Islands tested positive for antibodies to the virus, establishing the animals as a potential link between the virus in bats and humans.

When SARS emerged in China in 2003, scientists initially thought civets, catlike mammals common in Asia, were responsible for the outbreak, after animals from a market in Shenzen tested positive for the virus. Eventually, though, scientists traced the virus to Chinese horseshoe bats. Bats, curiously, are frequently the natural hosts for viruses. A study released in January found they may also be the reservoir for Ebola.

The discovery of SARS demonstrated the first known cases of a coronavirus causing serious illness in humans. Previously, they were known as causing little more than the common cold.

Shared characteristics

A recent study published in the Lancet Infectious Diseases found that SARS and MERS share many characteristics, though MERS patients are more likely to die of their illness and to have pre-existing health conditions.

Last month, the World Health Organization’s emergency MERS committee announced that the virus is not a global health emergency. The virus has reached beyond the Middle East to Italy, France and the United Kingdom, but it appears to spread slowly among people.

Still, local hospitals are on alert. At Stanford Hospital, anyone who comes in with respiratory issues and has either been in the Middle East or had contact with someone who’s been there will be treated with extreme caution and placed in “airborne isolation” in a negative airflow room.

Spreading slowly

The slow spread of MERS means the virus probably has not adapted to move easily between humans – to spread, that is, through coughs and sneezes. The virus, though, could always change. The number of mild cases that may have gone undiagnosed also remains a mystery.

Sasha Madison, manager of the Infection Prevention and Control Department at Stanford Hospital, said the volume of similar diseases in the past decade has made preparations for MERS seem routine.

“First it was SARS, then avian influenza,” she said. “Most institutions have become very comfortable dealing with emerging pathogens.”

Dr. Charles Chiu, an infectious-disease specialist at UCSF, said future research should focus on investigating diseases that occur in animals before they hop to humans, in order to better predict those that might eventually emerge.

“Coronaviruses have actually been known for more than 30 years now. They’re just variants that have originated in animal reservoirs,” said Chiu, who is working on getting a MERS sample sent to his laboratory for study. “In hindsight, it’s not unexpected that SARS would come from animals.”

It’s likely that we will see more viruses emerge from animal populations in the future, Chiu said. He has been investigating whether adenoviruses, which are DNA-based, might also move easily from animal to human. In a new study, published July 24 in the journal Plos One, Chiu found that an adenovirus identified in 2009 spreads among different primate species, amplifying concerns that similar types of viruses could spread to humans.

“I really believe we’ve only touched the tip of the iceberg,” he said. “Right now, we’re only looking at a subset of the viruses known to cause disease. We need to figure out what the rest of the iceberg is.”

In the meantime, the mystery of the latest disease spillover persists.

Researchers have “some clues,” Epstein said, but nothing firm enough to say where or how the spillover occurred with MERS. It could take testing hundreds more specimens before there are definitive answers.

“It really becomes a numbers game,” he said.

[Image: CDC]