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THIS OUTBREAK IS A WAKE-UP CALL

TO BIOLOGICAL THREATS. HERE'S WHAT WE MUST DO

- MARGARET HAMBURG MARK SMOLINKSI by and

CORONAVIRU­S THE SHOWS HOW UNPREPARED WE ARE TO DEAL WITH BIOLOGICAL THREATS

IN2011 ,

a novel virus,mev-1, emerged from China and quickly spread throughout the world, killing 2.5 million people in the U.S. and 26 million worldwide.

That outbreak wasn't actually real—it was the plot of the film Contagion, providing a Hollywood-style glimpse into the panic that surrounds a global pandemic. At the moment, we're in the midst of a very real outbreak spreading throughout the world from China. The real outbreak and the fictional one are related in one important way: a virus made the “jump” into an unprepared world.

This new outbreak is both frightenin­g and familiar. Looking back over many decades, recent viral outbreaks fit a pattern that is now well-recognized. It goes like this: A virus that lives in animals makes the jump to humans. Perhaps it happens in a live-animal market, such as the one in Wuhan, China, that authoritie­s initially flagged as the source of the current outbreak, or perhaps it came from some other animal source. People start getting sick and passing the infection around. Nobody pays attention for days, weeks or even months if the majority of cases are mild and go unnoticed, or they are assumed to be related to other known diseases circulatin­g in the region.

Sometimes the public is unaware of a potential new threat because authoritie­s are keeping quiet to avoid causing panic or retributio­n if they are wrong about early details. Then, suddenly, an outbreak is detected, the alarm sounds, the public takes notice and the world is enveloped in a global crisis.

The current crisis is caused by a coronaviru­s—a class of pathogens that includes the common cold, which means it's a new version of an old foe. This particular virus, called 2019-ncov, appears to spread from person to person fairly rapidly and is already having serious consequenc­es for public health. While many of the confirmed cases are reportedly mild, this novel coronaviru­s is causing death and severe illness, especially for vulnerable groups like the elderly and those whose immune systems are compromise­d. And it is causing disruption­s in travel, trade, economic activity and productivi­ty. We need to take it very seriously, now. We don't yet know much about the virus and the contours of the outbreak it is causing—nor what it could become if it mutates, which is a natural feature of coronaviru­ses.

Beyond the many worries about this particular outbreak is concern about the pattern of alarm and complacenc­y that seems to characteri­ze the world's response to such events. It's the same pattern we saw during the outbreak of SARS in 2002–3, H1N1 in 2009, MERS in 2012 and Ebola in 2014. Each time, the outbreak captured the attention of the public and politician­s. And each time, as fears subsided, complacenc­y set in.

The longer we keep repeating this pattern, the more we'll have to put up with preventabl­e disruptive outbreaks and the more people will get sick and die as a result. The longer this cycle continues, the greater the likelihood that nature will deal us a very bad hand—a pathogen that possesses a catastroph­ic combinatio­n of lethality and transmissi­bility.

This is a risk we cannot afford to take.

The Known Unknowns

On the last day Of 2019, 27 cases Of pneumonia from an unknown cause were reported from China to the World Health Organizati­on. Most of those stricken were said to have recently visited a large, live animal market in the city of Wuhan, which prompted its swift closure on January 1. Unfortunat­ely, the live “goods” being sold in the market were reportedly not tested when the market was emptied and the

“INFLUENZA TYPICALLY KILLS 1/10TH OF ONE PERCENT OF THE PEOPLE WHO ARE INFECTED

BUT KILLS 30,000 PEOPLE EVERY YEAR”

animals were destroyed. By the time the virus was identified a week later, the case count had risen to 41 persons; the first death occurred two days later. A month later, more than 17,000 people were known to be infected and over 300 had died. Since the epicenter was in Wuhan, the vast majority of cases are in China, but sporadic cases have been confirmed in over 20 other countries. The World Health Organizati­on declared it a “public health emergency of internatio­nal concern” on January 30.

The tools of modern genomics make it possible to identify a new pathogen and decode its genetic sequence in a matter of days. At present, however, many unanswered questions remain. Where did this novel virus come from? How does it spread? How lethal is it? Can it spread from people without symptoms, and for how long? From a public health standpoint, we can't yet rapidly identify potential cases at all sites where people seek health care to manage them, monitor their close contacts, and limit the ongoing spread. And we don't have a vaccine that could prevent it going forward. As China and the global community mobilize to respond to this unfolding threat, we have lots of unanswered questions—and lots of needs—concerning this novel coronaviru­s.

This outbreak is a wake-up call. It reminds us of our vulnerabil­ity to emerging and unexpected infectious disease threats. These include previously unknown organisms, such as HIV; new versions of old pathogens, like this coronaviru­s; and old pathogens that reemerge in new forms, such as those that develop resistance to antibiotic­s. They can be microbes that show up in new locations because of climate change, changing agricultur­al practices, highly mobile and displaced population­s, urbanizati­on and crowding. In the modern world, a microbe can travel very far, very fast. A disease in a remote part of the world can be in your backyard tomorrow. All of that makes us increasing­ly vulnerable.

This novel coronaviru­s is a classic example of the emergence of new microbial threats and their spread. The vast majority of the new infectious diseases that have presented in recent decades have come from animals who host the microbes, and are said to be the “reservoirs.” The spillover event, if you will, can sometimes involve a set of animal reservoirs and potentiall­y a set of insect “vectors,” like mosquitoes, ticks and fleas. But simply said, these so-called zoonotic pathogens live in animals or

“AS JANUARY DREW TO 10,000 A CLOSE, NEARLY PEOPLE WERE KNOWN TO BE INFECTED AND OVER 200 HAD DIED.”

are carried by insects and then “jump” to humans. When they jump, they can cause new diseases that we haven't had to deal with before, like 2019-ncov. Unfortunat­ely, we're seeing the emergence of several new zoonotic diseases each year—any of which may become the next pandemic.

Even though these outbreaks are in a sense predictabl­e, each one presents a unique puzzle to public health officials. The first serious coronaviru­s was SARS in 2002–3, which, like the current one, originated in China and was thought to have spread to people from civet cats likely infected by bats. When SARS first struck, we also had many gaps in our understand­ing. Ultimately SARS resulted in over 8,000 cases in 29 countries, with a death toll of nearly 800. Toronto had a significan­t outbreak, and so did Hong Kong. But for reasons that are still mysterious, we didn't have a single known case in the U.S. The MERS outbreak in 2012, which began in Saudi Arabia and spread from camels (also with the help of bats), has surpassed the death toll from SARS and has been detected in 27 countries.

Since MERS, public health experts have wondered when and where the next coronaviru­s was going to emerge. And now we have it: 2019-ncov. .

Right now, people seem to take comfort from comparing the new coronaviru­s with the flu. Influenza is another disease that goes from animals to humans. Seasonal influenza typically kills 1/10th of one percent of the people who are infected, and more in those with increased risk. Yet we still have tens of thousands of people who die every year from flu because it's so pervasive—the death rate is low, but since so many people catch it, the resulting death toll is high. Something like SARS or MERS might kill, say, 2 or 3 or even 10 percent of those who are infected, but, lucky for us, those viruses were not as transmissi­ble as the flu. If they were, the results could have been devastatin­g. The jury is still out on this new coronaviru­s.

We don't yet know how easily 2019-ncov can transmit from one person to another. We are not even fully certain of the modes of transmissi­on. If this new virus mutates into something that spreads more easily around the world or is more virulent, we will see even more devastatio­n and disruption. Or it could mutate to become less pathogenic and less infectious. It could “burn out” as we have seen with SARS. We just don't know. Having so many

“A DISEASE IN A REMOTE PART OF THE WORLD CAN IN A REMOTE PART OF THE WORLD CAN BE IN YOUR BACKYARD TOMORROW.”

unknowns makes everybody nervous, as it should. Already we see the enormous toll taken by this evolving outbreak—on human life and health, but also on travel, trade, economies and our sense of trust and confidence in government and other institutio­ns. The threat of a true pandemic is an existentia­l risk.

Signs of Progress

We are no doubt inching towards progress. China awoke to this outbreak with greater attention as a nation, having been through this before with SARS. Chinese officials were more transparen­t in sharing news of 2019-COV earlier in the outbreak than was the situation with SARS. Progress is also evident in how Chinese scientists openly shared the genetic sequence of this novel strain. This has enabled new insights into the nature of this emerging organism and critical informatio­n to support efforts to rapidly develop diagnostic­s and medical countermea­sures. As a result, several rapid diagnostic­s are already available to help with testing and screening.

But right now there are no drugs, vaccines or other medical interventi­ons available to treat 2019COV infections (apart from alleviatin­g symptoms). Research efforts are being initiated to try to develop and test experiment­al therapies, drawing on our knowledge of SARS and MERS. Vaccine developmen­t efforts are also underway, including the recent announceme­nt by the Coalition for Epidemic Preparedne­ss Innovation­s (CEPI), an innovative partnershi­p between public, private, philanthro­pic and civil organizati­ons, launched at Davos following Ebola, to develop vaccines to prevent future epidemics.

Chinese authoritie­s have taken extreme measures to control the outbreak, including travel bans, restrictio­ns on large public gatherings, school and work closures. There has also been quarantine of entire cities, involving tens of millions of people. The consequenc­es of potential panic, social unrest and disruption of needed supplies when a city is closed off will have to be evaluated in relation to the attempt to curb the extent of the spread.

China is not alone in its aggressive measures. Screening of travelers and outright travel bans are already in place in other countries, and airlines are restrictin­g routes. The U.S. recently announced it will forbid entry to persons who have traveled recently in China if they are not U.S. nationals or immediate family members of citizens. Such drastic measures

must be undertaken with caution. Under conditions of uncertaint­y and fear, policies are not always based on the best possible science—yet are opportunit­ies to better understand risk and explore innovation­s if we take the time to be thoughtful and systematic.

As cases spread to other countries, we are seeing mobilizati­on of response on a national and internatio­nal level. However, things aren't nearly where they need to be. For one thing, many countries that are potentiall­y vulnerable don't have adequate public health systems. Even those that are more sophistica­ted aren't as strong as they should be in terms of early detection and rapid response capabiliti­es.

One of the reasons a global public health emergency has been declared is to raise awareness and help less prepared countries deal with this spreading outbreak. If this novel coronaviru­s were to spread to a country lacking the infrastruc­ture to detect cases and track contacts, as is being done in more heavily resourced countries, it would endanger not only that nation but the health security of us all. In fact, the most recent analysis of the Global Health Security Index revealed that no country anywhere is fully prepared for a pandemic.

The Promise of Preparedne­ss

When a crisis strikes, We Wake up—briefly. Then we hit the snooze button. For example, following the SARS outbreak, the WHO updated a system of internatio­nal health regulation­s to ensure a minimum set of capabiliti­es for countries around the world for rapid detection, response and preparedne­ss for infectious disease threats that may be of global concern. Many countries made commitment­s, including having an identified person responsibl­e for coordinati­ng these efforts in each country. When the Ebola outbreak occurred, however, most countries' public health systems were still woefully unprepared.

Now that we're in the midst of a crisis—while we're wide awake—it's a good time to reconsider how we think about our response to disease outbreaks. The first thing we need to do is reframe the

THIS OUTBREAK REMINDS US OF OUR VULNERABIL­ITY TO EMERGING AND UNEXPECTED INFECTIOUS DISEASE THREATS.

issue not as an isolated emergency response but as an ongoing effort to prevent outbreaks from happening in the first place.

When it comes to an outbreak of an infectious disease, speed is of the essence. Speed of detection, of reporting and of response are all crucial so that the global community can be as prepared as possible to address the threat, and limit or prevent spread. Any delay in detecting a novel threat translates into greater spread, illness, social and work disruption and additional lives lost.

Success will require a continuum of leadership, capabiliti­es, collaborat­ion and accountabi­lity—from local to global. Transparen­cy begins with the reporting of unusual illness or clusters of disease, generally first by health care workers, village health volunteers, or an informed public. Once an unusual cluster of illness or suspected outbreak is detected, the cause of the illness must be quickly determined to guide a rapid and effective response. Health authoritie­s at the local, regional and national levels all have a responsibi­lity to share informatio­n more broadly.

In under-resourced countries, early efforts should include an emphasis on risk communicat­ion, early detection, access to health care, isolation infrastruc­ture and contact tracing. Much of what needs to be done involves applying age-old fundamenta­ls of public health, while advances in science and technology enable us to bring new and more powerful tools to these efforts. This allows for scientists and technician­s to develop diagnostic­s to track the outbreak and for drug and vaccine manufactur­ers to initiate more targeted efforts to develop medical countermea­sures.

We also have the opportunit­y to apply more sophistica­ted approaches to disease detection and surveillan­ce. Outbreaks where people show no symptoms of illness but are still capable of spreading the disease are the hardest to control. That makes it even more important to catch those early cases. In some countries, farmers and workers in the live animal markets who have the highest contact with potential new pathogens are connected to innovative, community-led surveillan­ce systems to report symptoms of illness or to report a sick or dead animal.

In the U.S., we have a system called Flu Near You where people report symptoms of flu every Monday to give us a better idea of how much illness is circulatin­g in a community. Flu Near You is currently being adapted to add questions about coronaviru­ses to alert the population and get them to start reporting anything they see. Other innovation­s in self-reporting, social media, machine learning and artificial intelligen­ce are providing opportunit­ies to find outbreaks faster so that we can stop a threat anywhere from becoming a threat everywhere.

Ending pandemics is in our future. We are far from realizing the full power of collaborat­ive forces necessary to prevent the global spread of a new virus. We have, however, made incredible progress in identifyin­g critical factors for the emergence of new diseases and in helping build capacity to identify and respond to outbreaks more rapidly in disease ‘hotspots.” Unless we start socializin­g a greater understand­ing of where diseases are likely to pop up and why they're happening, we'll continue to have outbreaks, we'll continue to respond to crises. And we'll wonder why the public is surprised every time.

→ Margaret Hamburg, MD, former commission­er of the U.S. Food and Drug Administra­tion, is Chair of the Board of the American Assn. for the Advancemen­t of Science and author of germs go global: Why emerging infectious diseases are a threat to america. Mark Smolinski, MD, MPH is President of Endingpand­emics.org, science advisor for Contagion and a former Epidemic Intelligen­ce Officer for the U.S. Centers for Disease Control and Prevention.

THE CURRENT CRISIS IS CAUSED BY A CORONAVIRU­S— A CLASS OF PATHOGENS THAT INCLUDES THE COMMON COLD, WHICH MEANS IT’S A NEW VERSION OF AN OLD FOE.

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 ??  ?? CONTAGION As 2019 drew to a close, a few dozen people, mostly in the Chinese city of Wuhan, caught a novel coronaviru­s and came down with pneumonia. In only a few weeks, the outbreak has spread to at least 20 other nations and is now an internatio­nal health crisis.
CONTAGION As 2019 drew to a close, a few dozen people, mostly in the Chinese city of Wuhan, caught a novel coronaviru­s and came down with pneumonia. In only a few weeks, the outbreak has spread to at least 20 other nations and is now an internatio­nal health crisis.
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The tools of modern genomics make it possible to identify and sequence the genetic code of a new pathogen in a matter of days. Top: Scientists work in a lab in Tauizhou City, China, to develop ways of detecting the new virus. Left: health workers disinfect ambulance staff at a hospital in Wuhan.
VIRUS HANDLERS The tools of modern genomics make it possible to identify and sequence the genetic code of a new pathogen in a matter of days. Top: Scientists work in a lab in Tauizhou City, China, to develop ways of detecting the new virus. Left: health workers disinfect ambulance staff at a hospital in Wuhan.
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 ??  ?? MAKING PROGRESS China awoke to this outbreak with greater attention as a nation, having been through the SARS outbreak. Officials were more transparen­t in sharing news and the genetic sequence of this novel strain. However, no drugs, vaccines or other medical interventi­ons are yet available Below: Health workers check on an elderly man who collapsed in the street in Wunan.
MAKING PROGRESS China awoke to this outbreak with greater attention as a nation, having been through the SARS outbreak. Officials were more transparen­t in sharing news and the genetic sequence of this novel strain. However, no drugs, vaccines or other medical interventi­ons are yet available Below: Health workers check on an elderly man who collapsed in the street in Wunan.
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A virus that lives in animals makes the jump to humans, people pass the infection around, plane travel spreads disease far and wide, and a crisis erupts. Left: a butcher's stall in Shanghai. Bottom: crew members disinfect a Thai Airways airplane.
FAMILIAR PATTERN A virus that lives in animals makes the jump to humans, people pass the infection around, plane travel spreads disease far and wide, and a crisis erupts. Left: a butcher's stall in Shanghai. Bottom: crew members disinfect a Thai Airways airplane.
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