In 1918 Flu Pandemic, Timing Was a Killer APRIL 30, 2014
American Red Cross workers collecting victims of the 1918 flu in St. Louis. A new study suggests why people in their late 20s were so vulnerable in that epidemic. Credit St. Louis Post-Dispatch
Sometimes a virus can cause more devastation than all the world’s armies. In 1918, at the end of World War I, influenza spread around the planet, reaching even Pacific islands and Arctic villages. The virus infected a third of all people on earth, and caused an estimated 50 million deaths — more than three times the number of people killed in World War I.
Since 1918, four new global flu pandemics have struck. None have come anywhere close to 1918’s toll, leaving scientists to puzzle about why 1918 was so deadly.
Adding to the mystery was that people in their late 20s were at greatest risk of dying in 1918. Typically, children and old people are more likely to die in flu outbreaks.
In a provocative new study published recently in The Proceedings of the National Academy of Sciences, a team of scientists argues that there wasn’t anything particularly sinister about the 1918 virus. The pandemic was the result of some disastrously bad luck.
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More Matter Columns The mysteries that surround the 1918 flu inspired a hunt for the virus itself. In the mid-1990s, scientists recovered its genes from tissue samples still preserved in hospitals.
After comparing the genes of the 1918 flu virus to those of other flu viruses, some scientists argued that the pandemic started when a flu virus in birds jumped into humans.
Discovering the 1918 virus also led to some new ideas about why it killed so many young adults. When scientists infected mice and monkeys with that virus, the animals developed a dangerously strong immune response. That led some scientists to suggest that the 1918 flu virus set off a lethal overreaction. If that were true, then the people who had the strongest immune system would be at the greatest risk.
But Michael Worobey, a biologist at the University of Arizona and an author of the new study, finds this explanation weak. “I just don’t buy it,” he said.
Teenagers and people in their early 20s also have strong immune systems. But they were at much less risk of dying in 1918 than people in their late 20s.
To get some new clues to the 1918 flu, Dr. Worobey recently launched an investigation with Guan-Zhu Han of the University of Arizona and Andrew Rambaut of the University of Edinburgh. The scientists conducted a detailed comparison of the 1918 virus to other flu viruses. Their evidence suggests that the 1918 virus did not, in fact, leap into humans right before the pandemic.
Instead, the virus became a human virus a decade earlier. This proto-1918 virus then inobtrusively circulated for years.
Influenza viruses sometimes produce hybrids. This occurs when two flu viruses infect the same cell. Their genes get mixed together as the cell makes new viruses.
The new study suggests that after a quiet decade, the proto-1918 virus mixed its genes with a bird flu virus. The result was the 1918 virus that caused the pandemic.
“That seems to tie a bunch of confusing observations together and makes sense of them,” said Dr. Worobey.
He argues that people under the age of 25 were protected from the new virus because they had already been exposed to its weaker version as their first experience with influenza.
When people have the flu, they make antibodies that can provide some protection to similar viruses years later. Some studies suggest that the first flu infection that children get has the biggest effect on their defenses later in life.
Children born after about 1900 would have been infected with that mild, proto-1918 virus. When the full-blown 1918 pandemic arrived, they had antibodies that protected them from a serious case of the stronger version of the virus.
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Older people were first exposed to influenza in the 19th century. To see how that first flu affected them, Dr. Worobey and his colleagues looked for clues to the nature of those earlier outbreaks.
The oldest people in 1918 would have been first infected with the flu in the early and mid-1800s. The research of Dr. Worobey and other researchers suggests that the flu viruses at that time were similar to the 1918 virus. In other words, old people in 1918 were protected from the new virus.
But in 1889, a new pandemic swept the planet. A few clues about its nature come from the antibodies that people made in response.
In the 1950s, scientists tested the antibodies of elderly people who had been alive during the 1889 pandemic, and found that their antibodies bound strongly to flu viruses that are only distantly related to the 1918 flu virus. That would suggest that people who were infected in the 1889 pandemic didn’t get the protection to the 1918 virus that older and younger people did.
In other words, the people in their late 20s were the victims of timing. When they grew up, they didn’t have strong defenses against the 1918 flu.
Other factors made the pandemic even worse for those young adults. Vulnerable soldiers were packed in battlefield trenches or aboard troop transport ships. The virus could spread easily from one host to another.
And in 1918, doctors could do little to treat the flu. They had no vaccines, no antiviral drugs and no antibiotics to stop the bacterial pneumonia that often came with bad cases of the flu.
Some flu experts hailed the new study by Dr. Worobey and his colleagues as a fascinating new way to think about the 1918 pandemic. But other scientists want more evidence.
“I’m not fully persuaded,” said Dr. David Morens, an expert on the 1918 flu at the National Institutes of Health. “It’s fine to speculate over a beer, but when we do that, we should be very cautious and realize that we’re only speculating and brainstorming.”
The only way to gain a better understanding of what happened in 1918, Dr. Morens said, would be to track down the genes of flu viruses from the 19th century, not just the antibodies. “We have to have the viruses,” said Dr. Morens.
If Dr. Worobey is right, the story of the 1918 pandemic should actually be a cause for guarded optimism. The 1918 flu was not especially dangerous, but simply took advantage of some historical flukes.
Today, we are better prepared to battle a pandemic. Flu vaccines can protect people who did not get the right antibodies when they were young, for example.
The flu still remains a serious public health risk, killing up to half a million people worldwide every year. But Dr. Worobey suspects the ghost of 1918 pandemic can be put to rest.
Larry Brilliant is humanity's best hope against the next pandemic...
30 APRIL 14
This article was taken from the May 2014 issue of Wired magazine. Be the first to read Wired's articles in print before they're posted online, and get your hands on loads of additional content by subscribing online.
On November 16, 2002, a 45-year-old man was admitted to hospital in Foshan City in Guangdong, China. His condition was consistent with pneumonia, a high fever, muscle aches, shortness of breath, coughing and respiratory difficulties.
Four other members of the patient's family soon fell ill with similar symptoms. Three weeks later, a 35-year-old man was brought from his home in nearby Heyuan to Guangzhou provincial hospital after becoming ill. He infected the doctor who had accompanied him in an ambulance, and then seven of the medical team treating him. Whatever his illness, it was highly infectious: antibiotics proved ineffective, meaning that clinical strategy -- which would later be replicated elsewhere -- amounted to keeping him alive in the hope that his immune systems would fight off the disease.
Clusters of such outbreaks occurred throughout Guangzhou over the following months and, although physicians were acutely aware of the danger that the new, highly communicable disease posed, they were baffled as to its cause. Later analysis revealed that it was a coronavirus -- the virus associated with the common cold. This information confused scientists: it's extremely rare for a coronavirus to kill human beings, yet around 15 per cent of those infected were dying.
According to David Quammen's book Spillover, over the next few weeks 28 cases were recognised in Zhongshan, 95km south of Guangzhou. Symptoms were similar to the earlier cases and included "severe and persistent coughing, coughing up bloody phlegm, and progressive destruction of the lungs, which tended to stiffen and fill with fluid, causing oxygen deprivation that, in some cases, led to organ failure and death."
Then the outbreak really took hold: two "super spreaders" distributed it beyond where it had been found up to that point. The first, Zhou Zuofeng, arrived at Guangzhou hospital with symptoms now familiar to the staff. He transmitted the disease to at least 30 healthcare workers before being transferred to a specialist hospital. On the way, he infected two doctors, two nurses and the ambulance driver. At the second hospital, 23 doctors and nurses, plus 18 other patients and their relatives and 19 members of Zhou's family, became ill, prompting staff at the hospital to name him the Poison King.
On February 21, 2003, Liu Jianlun, a nephrology professor and one of the doctors who had treated Zhou, travelled to Hong Kong to attend his nephew's wedding. While staying at the Hotel Metropole, in the heart of one of the city's busiest shopping districts, he began to feel ill. During his stay, Liu unwittingly infected a number of people who were staying in rooms on the same floor. One of them was a 78-year-old Canadian. On February 22, she boarded a flight for Toronto. Eleven days later, she died, but not before passing the condition on to her son. The virus then spread throughout the hospital where he was treated. Over the following weeks there were at least six transmission chains in Canada; 400 people became seriously ill, 25,000 were placed in quarantine and 44 died.
In late February the Centers for Disease Control -- the US organisation that monitors and responds to emerging health threats -- and the World Health Organisation (WHO) began to investigate. However, scientists were working in the dark; they knew only that the disease was highly contagious, that it made those who contracted it become severely ill and that dozens of people had died (later -- following an admission from the Chinese government -- it would emerge that the number of deaths was in the hundreds). There was no medication -- treatment was limited to administering steroids to reduce inflammation in the lungs.
On March 12, following the news that one of its top epidemiologists had died after contracting the disease in Hanoi, the WHO issued a global health alert for what it called Severe Acute Respiratory Syndrome (SARS). It was the first time the organisation had taken such a step. The microbe responsible for the disease still hadn't been identified, prompting an unparalleled coming together of global research facilities and laboratories to pool resources. A month later, a team at the Michael Smith Genome Sciences Centre in Vancouver, Canada, announced that it had decoded the virus's DNA. The good news was that the virus wasn't mutating -- its stability meant that it would be possible to develop a vaccine that could target the way in which its proteins latched on to human cells, although this would likely take years. Eventually, public health practices put in place across the world contained the virus.
Mark Smolinski, the epidemiologist behind the Flu Near You programmeJason Madara The 2003 SARS epidemic infected 8,096 people worldwide, killing 744 of them. These are not big numbers compared to other pandemics -- smallpox, black death and flu have killed hundreds of millions since they emerged millennia ago, and the swine flu outbreak of 2009 infected up to 89 million -- but it offered a rapidly globalising world an insight into how quickly an outbreak of a killer disease can cross continents. The so-called Spanish flu pandemic that followed the first world war killed between 50 million to 100 million people. If there were a proportional outbreak today -- when the global population is over seven billion -- there could be upwards of 300 million deaths. SARS, although infectious, wasn't as virulent as first feared, but its effects were amplified by the way carriers moved across the world: there is no evidence that the Canadian woman who brought the disease to Toronto met the Chinese "super spreader" in Hong Kong. It is likely the virus spread through the air in a lift or via a point of contact such as a door handle. Such unfortunate encounters are now part of the modern world.
Once, pathogens could spread only at the speed at which human beings could walk. Now they can move between any major city on Earth within 24 hours, meaning that early detection -- reading the very first signs of an outbreak of a virus such as flu, which has an incubation period of between one and four days -- could be the difference between a localised and treatable situation and a global pandemic. Much is made of the role of technology in the spread of disease; after all, without air travel SARS would have probably remained localised in Asia, instead of spreading rapidly across the globe. Equally, however, governmental communication and co-operation -- prompted by epidemiologists who make the significance of outbreaks clear through early detection -- can mean that disease is contained and controlled.
"If you catch a virus within one incubation period there will only be five cases -- and you can stop it," says the epidemiologist Larry Brilliant. "If you wait seven incubation periods it will be in the thousands. You go a couple more and it's in the billions." The 70-year-old knows something about the spread of disease, having led the WHO team in south Asia that eradicated smallpox. His mission now is to bring together government, the private sector and citizens to develop digital tools to detect outbreaks early. The four months it took for the global health community to mobilise following the outbreak of SARS could prove catastrophic should a more virulent disease emerge. Brilliant is clear about the stakes: "We're in a race against time."
One hazy Bangkok morning last November, Brilliant stands before a group of Thai health officials. He has slicked-back grey hair, a trimmed beard and, despite the warmth, he wears a black suit that causes him to perspire. He has wrapped an LED screen around his torso, which he has programmed with a Raspberry Pi. The red flashing lights make up letters that read: "DETECT DISEASES FASTER". Brilliant has a dry sense of humour and speaks calmly. He often places his hand on the person he is addressing and uses the phrase "but my question is…" to draw them in. He usually runs late, prompting his colleagues to inform him that meeting times are earlier than scheduled in order to guarantee his presence on time.
Brilliant is president of the Skoll Global Threats Fund (SGTF), an organisation funded by billionaire Jeff Skoll, the cofounder of eBay, that seeks to confront threats imperilling humanity. Brilliant and the pandemics team -- Mark Smolinski and Jennifer Olson ("I'm manager of pandemics, which is a really fun title," she says) -- arrived the night before from Cambodia. The Thai Ministry of Health, those working in public health, telcos, Google Thailand, data analysts, academics, social innovators and technologists are all present.
Epidemiologists often use the word "zoonotic" -- meaning diseases that can be communicated between humans and animals. This is because there is not one of them who doesn't think that the next global pandemic will originate from the blood of a wild animal. It might result from a pig that's been bitten by a bat in Thailand; it could be a monkey that's been killed and eaten in a Cameroonian rainforest. (The SARS outbreak was traced back to the civet, a cat-like wild animal eaten throughout southern China.) Deforestation and urbanisation are bringing humans into contact with species and viruses that have, until recently, been deep in natural ecosystems. This close contact gives formerly unknown pathogens the opportunity to move to a new species: human beings. "Those who think that the sharing of vital fluids in sexual relations is the most intimate way that you can exchange genetic material with another person are wrong," Brilliant says. "The most intimate encounter you can have with another creature is to eat it." Brilliant says that the number of wild animals eaten in Africa per year is close to a billion. "Every cell in every piece of bush meat you're eating may represent a novel encounter between a human and an animal that harbours a virus." According to Brilliant, over the past 30 years, three dozen previously unknown viruses have jumped species -- a phenomenon epidemiologists call "spillover".
The first quantitative analysis identifying risk factors for human disease emergence was conducted in 2001 by Louise Taylor, Sophia Latham and Mark Woolhouse at the Centre of Tropical Veterinary Medicine at the University of Edinburgh. "A comprehensive literature review identifies 1,415 species of infectious organisms known to be pathogenic to humans, including 217 viruses and prions, 538 bacteria and rickettsia, 307 fungi, 66 protozoa and 287 helminths. Out of these, 868 (61 per cent) are zoonotic," they wrote. But the part of the paper that is particularly alarming relates to so-called "emerging" pathogens -- infectious organisms that, over the past two decades, have either been detected in humans for the first time, are increasing in incidence or are occurring in regions they had not previously occurred. Seventy-five per cent were found to be zoonotic. "This is substantially more than expected if zoonotic and non-zoonotic species were equally likely to emerge," Taylor et al write.
MIT maps US airports most likely to spread a pandemic...
A team at MIT has published a paper revealing how its network theory computer model can predict which US airports will be the worst offenders when it comes to a pandemic's global spread.
The team's model differs from previous versions in that it focuses on the first ten days of an outbreak, rather than the hotspots that emerge once the disease has already spread significantly. By taking into account geographical locations, individuals' travel patterns, connectivity and airport waiting times, the team managed to generate a ranking system which sees New York's JFK airport taking the top spot, followed closely by Los Angeles' LAX and Honolulu airport -- traffic from the three are highlighted in blue, green and yellow respectively in the video embedded in this post.
By addressing the issue using a variety of factors and throwing out the random diffusion model that fails to take specific human travel patterns into account, the team has created a viable tool for predicting and preparing for the days following an outbreak. For instance, despite seeing only 30 percent of JFK's traffic, Honolulu is singled out as a significant contributor to a pandemic's spread because its position in the Pacific means it is connected to a wide spread of global hubs.
"The findings could form the basis for an initial evaluation of vaccine allocation strategies in the event of an outbreak, and could inform national security agencies of the most vulnerable pathways for biological attacks in a densely connected world," said Ruben Juanes, a professor of energy studies at MIT's Civil and Environmental Engineering department and author of the paper, published in the PLoS journal.
Juanes is a computational geoscientist and engineer by trade, whose background is in studying the flow of fluids through rocks and porous materials. In a collaboration with MIT's Marta González, who maps human mobility patterns using mobile phone data and social network studies, Juanes realised that the spread of a disease is not random, just as human travel patterns are replicable and not random (particularly when taking into account return flights). Therefore he and his team replaced traditional random diffusion models for a system similar to the advective flow of fluids uncovered in geoscience. "The advective transport process relies on distinctive properties of the substance that's moving, as opposed to diffusion, which assumes a random flow," explains one of the paper's author's, MIT research assistant Christos Nicolaides. "If you include diffusion only in the model, the biggest airport hubs in terms of traffic would be the most influential spreaders of disease. But that's not accurate."
Using data from the 40 largest airports in the US, the team applied a Monte Carlo simulation (an algorithm that uses repeated random sampling) to generate predictions for the movements of individual travellers. The breakdown saw airports like Anchorage in Alaska singled out as "powerful regional spreaders" and JFK and LAX as "global super spreaders" that tick all the necessary boxes for the perfect pandemic storm -- connectivity, traffic and geography.
"We are currently capable of modelling with some detail real disease outbreaks, but we are less effective when it comes to identifying new countermeasures to minimise the impact of an emerging disease," commented Yamir Moreno of the University of Zaragoza, who studies the pattern spreads of epidemics.
"The work done by the MIT team paves the way to find new containment strategies, as the newly developed measure of influential spreading allows for a better comprehension of the spatiotemporal patterns characterising the initial stages of a disease outbreak."
Researchers uncover clues to deadly 1918 flu pandemic Published April 29, 2014 FoxNews.com Medical mysteries
The deadly 1918 pandemic flu spread faster than any other illness in recorded history – and now researchers may understand why.
In a new study lead by the University of Arizona (UA), researchers sought to understand the 1918 virus itself, as well as ways improve vaccination strategies and avoid future pandemics, Medical News Today reported. The 1918 flu virus killed more than 50 million people— three times the number of people who died in World War I.
Typically, the human influenza A virus is most threatening to infants and the elderly, but the 1918 virus killed many young adults, puzzling scientists. To understand this, researchers developed a technique that analyzes the rate at which mutations build up in specific parts of DNA. This “molecular clock” allowed them to reconstruct the 1918 pandemic virus’s origins, as well as those of the classic swine flu and the postpandemic seasonal H1N1 flu virus that circulated between 1918 and 1957.
They found that the 1918 strain originated from a human H1 virus that had been circulating among humans since around 1900. This virus then picked up genetic material from a bird flu virus.
When the immune system is exposed to a virus, it reacts to the proteins on the surface of the virus and creates antibodies to prevent future infection from similar viruses. But when a new strain is genetically altered from previous strains to which the body has been exposed, the body’s protective antibodies are less effective, making infection more likely.
Researchers suggest that the young adults affected in 1918 may have had protection, due to childhood exposure, from a H3N8 virus circulating in the population. However, they were unprotected from the new pandemic strain, because their immune systems made antibodies for the original virus.
"We believe that the mismatch between antibodies trained to H3 virus protein and the H1 protein of the 1918 virus may have resulted in the heightened mortality in the age group that happened to be in their late 20s during the pandemic,” said study author Michael Worobey, a professor in UA College of Science's department of ecology and evolutionary biology.
Their findings, published in the Proceedings of the National Academy of Sciences, suggest deaths from seasonal and new flu strains could be dramatically reduced by implementing immunization strategies that mimic the protection that early childhood exposure provides.
American Red Cross workers collecting victims of the 1918 flu in St. Louis. A new study suggests why people in their late 20s were so vulnerable in that epidemic. Credit St. Louis Post-Dispatch Continue reading the main story
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Continue reading the main story Sometimes a virus can cause more devastation than all the world’s armies. In 1918, at the end of World War I, influenza spread around the planet, reaching even Pacific islands and Arctic villages. The virus infected a third of all people on earth, and caused an estimated 50 million deaths — more than three times the number of people killed in World War I.
Since 1918, four new global flu pandemics have struck. None have come anywhere close to 1918’s toll, leaving scientists to puzzle about why 1918 was so deadly.