H5N1

Honigsbaum: How do pandemics end? In different ways, but it’s never quick and never neat

In The Guardian, Mark Honigsbaum writes: How do pandemics end? In different ways, but it’s never quick and never neat. Excerpt:

On 7 September 1854, in the middle of a raging cholera epidemic, the physician John Snow approached the board of guardians of St James’s parish for permission to remove the handle from a public water pump in Broad Street in London’s Soho. Snow observed that 61 victims of the cholera had recently drawn water from the pump and reasoned that contaminated water was the source of the epidemic. His request was granted and, even though it would take a further 30 years for the germ theory of cholera to become accepted, his action ended the epidemic. 

As we adjust to another round of coronavirus restrictions, it would be nice to think that Boris Johnson and Matt Hancock have a similar endpoint in sight for Covid-19. Unfortunately, history suggests that epidemics rarely have such neat endings as the 1854 cholera epidemic. Quite the opposite: as the social historian of medicine Charles Rosenberg observed, most epidemics “drift towards closure”. It is 40 years since the identification of the first Aids cases, for instance, yet every year 1.7 million people are infected with HIV. Indeed, in the absence of a vaccine, the World Health Organization does not expect to call time on it before 2030.  

However, while HIV continues to pose a biological threat, it does not inspire anything like the same fears as it did in the early 1980s when the Thatcher government launched its “Don’t Die of Ignorance” campaign, replete with scary images of falling tombstones. Indeed, from a psychological standpoint, we can say that the Aids pandemic ended with the development of antiretroviral drugs and the discovery that patients infected with HIV could live with the virus well into old age.  

The Great Barrington declaration, advocating the controlled spread of coronavirus in younger age groups alongside the sheltering of the elderly, taps into a similar desire to banish the fear of Covid-19 and bring narrative closure to this pandemic. Implicit in the declaration signed by scientists at Harvard and other institutions is the idea that pandemics are as much social as biological phenomena and that if we were willing to accept higher levels of infection and death we would reach herd immunity quicker and return to normality sooner. 

But other scientists, writing in the Lancet, say the Great Barrington strategy rests on a “dangerous fallacy”. There is no evidence for lasting “herd immunity” to the coronavirus following natural infection. Rather than ending the pandemic, they argue, uncontrolled transmission in younger people could merely result in recurrent epidemics, as was the case with numerous infectious diseases before the advent of vaccines.

It is no coincidence they have called their rival petition “the John Snow memorandum”. Snow’s decisive action in Soho may have ended the 1854 epidemic, but cholera returned in 1866 and 1892. It was only in 1893, when the first mass cholera vaccine trials got under way in India, that it became possible to envisage the rational scientific control of cholera and other diseases. The high point of these efforts came in 1980 with the eradication of smallpox, the first and still the only disease to be eliminated from the planet. However, these efforts had begun 200 years earlier with Edward Jenner’s discovery in 1796 that he could induce immunity against smallpox with a vaccine made from the related cowpox virus.

With more than 170 vaccines for Covid-19 in development, it is to be hoped we won’t have to wait that long this time. However, Professor Andrew Pollard, the head of the Oxford University vaccine trial, warns that we should not expect a jab in the near future. At an online seminar last week, Pollard said the earliest he thought a vaccine would be available was summer 2021 and then only for frontline health workers. The bottom line is that “we may need masks until July”, he said.

The other way the pandemic could be brought to a close is with a truly world-beating test-and-trace system. Once we can suppress the reproductive rate to below 1 and be confident of keeping it there, the case for social distancing dissolves. Sure, some local measures might be necessary from time to time, but there would no longer be a need for blanket restrictions in order to prevent the NHS being overwhelmed. Essentially, Covid-19 would become an endemic infection, like flu or the common cold, and fade into the background. This is what appears to have happened after the 1918, 1957 and 1968 influenza pandemics. In each case, up to a third of the world’s population was infected, but although the death tolls were high (50 million in the 1918-19 pandemic, about 1 million each in the 1957 and 1968 ones), within two years they were over, either because herd immunity was reached or the viruses lost their virulence.

The nightmare scenario is that Sars-CoV-2 does not fade away but returns again and again. This was the case with the 14th-century Black Death, which caused repeated European epidemics between 1347 and 1353. Something similar happened in 1889-90 when the “Russian influenza” spread from central Asia to Europe and North America. Although an English government report gave 1892 as the official end date of the pandemic, in truth the Russian flu never went away. Instead, it was responsible for recurrent waves of illness throughout the closing years of Queen Victoria’s reign.

WHO commemorates the 40th anniversary of smallpox eradication

A news release: WHO commemorates the 40th anniversary of smallpox eradication.

The World Health Organization commemorated the 40th anniversary of smallpox eradication today, recognizing the historic moment on 9 December 1979 when smallpox was confirmed to have been eradicated. Five months later, in May 1980, the 33rd World Health Assembly issued its official declaration that ‘the world and all its peoples have won freedom from smallpox’.   

A bronze plaque marking the end of a scourge that had afflicted millions for thousands of years was unveiled at WHO headquarters in Geneva in the very same meeting room where, four decades earlier, the 19 members of the Global Commission for the Certification of Smallpox Eradication certified that smallpox had been eradicated from the world.  

Speaking at the event attended by country representatives, UN representatives and WHO staff who worked on smallpox, WHO Director-General Tedros Adhanom Ghebreyesus said, “Today, smallpox is the only human disease ever eradicated, a testimony to what we can achieve when all nations work together. 

“When it comes to epidemic disease, we have a shared responsibility and a shared destiny.  With this plaque, we commemorate the heroes around the world who came together to fight smallpox and worked to keep future generations safe."  

Until it was wiped out, smallpox had plagued humanity for at least 3000 years, killing 300 million people in the 20th century alone. The last known endemic case of smallpox was reported and the outbreak promptly contained in Somalia in 1977.  

The successful smallpox eradication programme yielded vital knowledge and tools for the field of disease surveillance, the benefits of ring vaccination and the importance of health promotion in fighting diseases such as poliomyelitis and the Ebola virus. It also laid the foundation for stronger national immunization programmes worldwide, underpinning the establishment of primary health care in many countries and creating momentum toward Universal Health Coverage.  

Today’s commemoration kicks off a year-long campaign in which WHO and partners will mark the eradication of smallpox and raise awareness about the need to continue the fight against polio and other diseases and accelerate investments in global health security. A smallpox eradication exhibition will be unveiled at the World Health Assembly in May 2020 and is expected to travel to other events, including the United Nations General Assembly in New York.

The endless hunt for the perfect flu vaccine

Via The Guardian, a long read: The endless hunt for the perfect flu vaccine. Excerpt:

Vaccines are one of the great success stories of modern medicine. Because of them we are no longer vulnerable to smallpox or polio or measles. The flu vaccine, however, is a different story. Its effectiveness varies from patient to patient, from population to population, and from year to year. It needs to be updated each season, and even in a good year is usually no more than 50% effective. We may rely on it to avoid catching the flu, but its story demonstrates how far we still are from a reliable vaccine. 

Vaccination, the process of infecting a healthy person with a microbe to prevent disease, dates back at least a thousand years. But the start of vaccination as we think of it today is generally credited to the work of Edward Jenner, a British physician born in 1749. 

Jenner was a keen observer with a deep interest in the natural world, and found time for both serious study and artistic play. He investigated everything from hydrogen balloons to the life cycle of the cuckoo, wrote poetry and played the violin, but smallpox – or rather, the eradication of it – is his legacy. Because of Jenner, this virus is not on our list of worries today.  

Smallpox was a vicious disease that killed more than 30% of those who contracted it. In the 1700s, there was one demographic, however, that seemed to be immune: milkmaids. It had been observed that in the course of their job milking cows, women came into contact with the milder bovine version of the smallpox virus, called cowpox.  

These women then became immune to the deadlier human smallpox virus. There was something in the cowpox that protected against smallpox, and in 1796 Edward Jenner famously took material from the fresh pustules on a milkmaid’s hand and inserted it under the skin of a young boy named James Phipps. After a brief and mild illness, Phipps recovered completely. Jenner then infected him with scrapings from a smallpox lesion, again and again, but the boy never got sick. 

Jenner named this process “vaccination” after variolae vaccinae, a Latin term for cowpox. His technique quickly spread through 19th-century England and beyond, saving countless people, inspiring modifications to the technique and changing the course of history.

Drug to treat smallpox approved by FDA, a move against bioterrorism

Via The New York Times: Drug to Treat Smallpox Approved by F.D.A., a Move Against Bioterrorism. Excerpt:

The Food and Drug Administration on Friday approved the first drug intended to treat smallpox — a move that could halt a lethal pandemic if the virus were to be released as a terrorist bioweapon or through a laboratory accident.  

The antiviral pill, tecovirimat, also known as Tpoxx, has never been tested in humans with smallpox because the disease was declared eradicated in 1980, three years after the last known case.  

But it was very effective at protecting animals deliberately infected with monkeypox and rabbitpox, two related diseases that can be lethal. It also caused no severe side effects when safety-tested in 359 healthy human volunteers, the F.D.A. said. 

“This new treatment affords us an additional option should smallpox ever be used as a bioweapon,” said Dr. Scott Gottlieb, the F.D.A.’s commissioner. 

Having a drug that usually cures smallpox is an important medical breakthrough, according to several medical experts not associated with the F.D.A. or the company making the drug. 

F.D.A. approval is “definitely a good thing,” said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. 

Research on tecovirimat — originally designated ST-246 — began at the institute after the 9/11 terrorist attack on the World Trade Center, Dr. Fauci said. The research accompanied efforts to stretch the national stockpile of smallpox vaccine by safely diluting it.  

“It all started back then, but developing a licensed product took until today,” he added.  

The F.D.A. approval of the drug went to Siga Technologies of Corvallis, Ore., a private company that developed the medicine under a federal biomedical defense contract. 

Although circulating smallpox has been eradicated, two known stores of the virus exist in laboratory freezers — one in Russia and one at the Centers for Disease Control and Prevention in Atlanta.

Bioterrorism experts fear that other stocks may exist; for example, in 2014 several forgotten vials containing smallpox were found at the National Institutes of Health. 

More worrisome, experts say, is the possibility that a terrorist lab or even a sophisticated amateur could use modern gene-editing techniques to rebuild the virus and then unleash it, deliberately or accidentally, on an unprepared world.

A paper showing how to make a smallpox cousin just got published. Critics wonder why.

Via Science, Kai Kupferschmidt writes: A paper showing how to make a smallpox cousin just got published. Critics wonder why. Excerpt:

Today, a highly controversial study in which researchers synthesized a smallpox relative from scratch is finally seeing the light of day. The paper, in PLOS ONE, spells out how virologist David Evans at the University of Alberta in Canada, and his research associate Ryan Noyce ordered bits of horsepox DNA from the internet, painstakingly assembled them, then showed that the resulting virus was able to infect cells and reproduce. 

The study stirred alarm when Science first reported it in July 2017 because it might give would-be terrorists a recipe to construct smallpox virus, a major human scourge vanquished in 1980. And now that it's out, many scientists say the paper doesn’t answer the most pressing question: Why did they do it? 

The team claims its work, funded by Tonix, a pharmaceutical company headquartered in New York City, could lead to a safer, more effective vaccine against smallpox. But safe smallpox vaccines already exist, and there appears to be no market for a horsepox-based replacement, says virologist Stephan Becker of the University of Marburg in Germany. 

“It simply does not add up,” Becker says. Given the apparent lack of benefits, publishing the paper was “a serious mistake,” says Thomas Inglesby, director of the Center for Health Security at the Johns Hopkins University Bloomberg School of Public Health in Baltimore, Maryland. “The world is now more vulnerable to smallpox.” 

A spokesperson for the journal’s publisher, PLOS, wrote in an email that a committee on “dual use research of concern” at the journal unanimously agreed that the benefits of publication, including “the potential improvements in vaccine development” outweighed the risks. 

But Inglesby says that given its implications, national and global health authorities should have approved the work; currently, there is no requirement for such a review. “This ought to be a wake-up call for science agencies and governments,” Inglesby says.  

Vaccination against smallpox ended worldwide in the 1980s, and most people have no immunity. Experts worry that the virus that causes it, variola, could be used in an act of bioterror or biological warfare. The last samples of variola are kept under tight security in Russia and the United States. But the paper could provide another route for terrorists or other bad actors.

How Canadian researchers built a poxvirus for $100,000 using mail-order DNA

Thanks to Helen Branswell for tweeting about this report. Via Science, Kai Kupferschmidt writes a fascinating and disquieting account: How Canadian researchers built a poxvirus for $100,000 using mail-order DNA. Excerpt:

Eradicating smallpox, one of the deadliest diseases in history, took humanity decades and cost billions of dollars. Bringing the scourge back would probably take a small scientific team with little specialized knowledge half a year and cost about $100,000. 

That’s one conclusion from an unusual and as-yet unpublished experiment performed last year by Canadian researchers. A group led by virologist David Evans of the University of Alberta in Edmonton, Canada, says it has synthesized the horsepox virus, a relative of smallpox, from genetic pieces ordered in the mail. 

Horsepox is not known to harm humans—and like smallpox, researchers believe it no longer exists in nature; nor is it seen as a major agricultural threat. But the technique Evans used could be used to recreate smallpox, a horrific disease that was declared eradicated in 1980. 

"No question. If it’s possible with horsepox, it’s possible with smallpox,” says virologist Gerd Sutter of Ludwig Maximilians University in Munich, Germany. 

Evans hopes the research—most of which was done by research associate Ryan Noyce—will help unravel the origins of a centuries-old smallpox vaccine and lead to new, better vaccines or even cancer therapeutics. Scientifically, the achievement isn't a big surprise. Researchers had assumed it would one day be possible to synthesize poxviruses since virologists assembled the much smaller poliovirus from scratch in 2002. 

But the new work—like the poliovirus reconstitutions before it—is raising troubling questions about how terrorists or rogue states could use modern biotechnology. Given that backdrop, the study marks "an important milestone, a proof of concept of what can be done with viral synthesis,“ says bioethicist Nicholas Evans—who's not related to David Evans—of the University of Massachusetts in Lowell. 

The study seems bound to reignite a long-running debate about how such science should be regulated, says Paul Keim, who has spent most of his career studying another potential bioweapon, anthrax, at Northern Arizona University in Flagstaff. 

"Bringing back an extinct virus that is related to smallpox, that's a pretty inflammatory situation,” Keim says. "There is always an experiment or event that triggers closer scrutiny, and this sounds like it should be one of those events where the authorities start thinking about what should be regulated.”

Virus found in child mummy suggests recent rise of deadly smallpox

Via Science: Virus found in child mummy suggests recent rise of deadly smallpox. Excerpt and then a comment:

Ancient rashes that scar the faces of Egyptian mummies have long been cited as evidence that smallpox ravaged the region more than 3000 years ago. But now, a study of viral DNA extracted from a 17th century child mummy—the oldest known sample of any virus—suggests that the deadliest form of smallpox emerged in humans much more recently, just in time to hitchhike with New World explorers and decimate populations around the world.  

If the team’s analysis is right, it would “challenge many of the current beliefs about one of the most notorious pathogens in human history,” says historian Kyle Harper of the University of Oklahoma in Norman, who was not involved with the work. 

The team behind the new study recovered the smallpox virus by accident. Researchers in Lithuania and Finland hoping to gather DNA from a more obscure virus collected tissue from the mummified remains of a young child found within the mid-17th century crypt of the Dominican Church of the Holy Spirit of Vilnius. 

The child had no visible pox marks, but when the researchers sent the sample to the ancient DNA lab of Hendrik Poinar at McMaster University in Hamilton, Canada, his postdoc Ana Duggan got a big surprise. The sample was rich with variola, the virus that causes smallpox, the team reports today in Current Biology. 

The large quantity of the virus allowed the researchers to construct a high-quality copy of its genome, the first from such an old virus. (The most ancient pathogens sequenced have been from bacterial DNA, including one that caused the plague 1600 years ago.)  

The team was also surprised to find that the child mummy’s ancient viral DNA shared many distinct features with modern strains of the variola virus, including several mutations, suggesting they were closely related. The researchers built a family tree of 49 modern strains and the child’s ancient one, and traced the evolution of all of them back to a common ancestor that arose between 1530 and 1654 C.E.

This date is remarkably recent—only a hundred years or so before the time of the child mummy, and long after the dynasties of Egyptian pharaohs. It’s also much later than other accounts of epidemics, such as pustulous rashes from fourth century China and the Antonine Plague in Rome in 165 C.E., which have been attributed to smallpox by historians. These people may have suffered from chickenpox or measles instead, says Poinar, or from a different type of less deadly pox, which has since gone extinct.  

But where did this new, deadly strain of variola come from in the 16th and 17th centuries? One possibility is that it could have lurked in an animal host and jumped to humans. Alternately, a mutation may have arisen in variola in humans that made it more deadly. If it did come from animals, it could still persist there, with the potential of reinfecting humans again, Poinar says.

The question that springs to mind is what disease the Spanish were carrying when they invaded Mexico in 1520, ten years before the earliest emergence of smallpox. The Conquest was vastly aided by European diseases like measles, and smallpox is generally assumed to have been the chief killer.

Branswell on D.A. Henderson

Via STAT, Helen Branswell writes a memorable obituary: D.A. Henderson, who helped eradicate smallpox, dies. Excerpt:

There are few people in the field of global public health so well-known that you merely need to utter two initials to evoke instant recognition.  

But to raise in conversation Dr. Donald Ainslee Henderson, the man who led the successful effort to eradicate smallpox, all anyone ever bothered to say was “D.A.”  

Henderson, a few weeks shy of his 88th birthday, died late Friday of complications that arose after he recently fractured a hip.

Towering in physical stature as well as in reputation, Henderson had a booming voice, which he used to great effect. He did not hesitate to express his views — even if they were not shared by others.  

“D.A. was a giant intellectually, he was a giant in his personality, and he didn’t shy away from controversy,” said his friend Michael Osterholm, director of the University of Minnesota’s Center for Infectious Diseases Research and Policy.  

Dr. Bill Foege, a friend and colleague for over 50 years, agreed. 

“He was a person of strong convictions,” said Foege, who served as director of the Centers for Disease Control and Prevention from 1977 to 1983 and who first met Henderson at the CDC in 1962.  

“I always think that was one of the attributes that provided for leadership because people don’t like to follow someone who’s uncertain about where they’re going. He brought a certain certainty to everything he did.”

 Before taking the lead in the smallpox eradication program, Henderson was the CDC’s director of disease surveillance. His mentor had been Alexander Langmuir, the epidemiologist who founded the CDC’s renowned program to train disease detectives. 

“I remember with Alex once talking about a subject and he presented his side and I said: ‘But it’s worth looking at the other side,’” Foege recalled. “And he slammed his fist down on his desk and said ‘There is no other side.’”

“D.A. got part of his training in this environment of absolute certainty.” 

Henderson also shared Langmuir’s core belief that good surveillance is crucial to disease control. 

“He always stressed the fact that without comprehensive disease surveillance, you just couldn’t run an effective public health program,” said Osterholm.  

Tapped to lead the smallpox eradication program in 1966, Henderson moved to the World Health Organization, working as chief medical officer for the program.  

In 1977 the world saw its last case of wild smallpox infection — a few cases infected through lab accidents happened later — and the disease was declared eradicated in 1980. To this day smallpox remains the only human disease ever eradicated.

D.A. Henderson, leader of campaign to eradicate smallpox, dead at 89

Via UPI.com: D.A. Henderson, leader of campaign to eradicate smallpox, dead at 89. Excerpt:

Donald Ainslie Henderson, a former dean of Johns Hopkins Bloomberg School of Public Health who led the campaign to eradicate small pox, died in Baltimore on Friday. 

Henderson, who was known as D.A., died following complications from a hip fracture at the age of 89 the UPMC Center for Health Security reported.  

 "D.A. Henderson truly changed the world for the better," Director of the UPMC Center for Health Security Tom Inglesby said. "He led the effort to rid the world of smallpox. He advised presidents. He was honored by countries around the planet. He changed the way schools of public health teach the next generation. With all of that, he still took the time to be a mentor to countless young people, and was a great friend. He is truly irreplaceable, and I will miss him." 

Henderson was born on Sept. 7, 1928 in Lakewood, Ohio to David Alexander Henderson, an engineer with Union Carbide, and Grace Eleanor Henderson, a nurse.  

He graduated from Oberlin College, from University of Rochester School of Medicine and Johns Hopkins School of Hygiene and Public Health in 1960 and served as a medical resident at the Mary Imogene Bassett Hospital in Cooperstown, New York.  

From 1966 to 1977 he served as Director of the World Health Organization's global smallpox eradication campaign where he and his team became the only group to ever successfully eradicate a human disease.

Experts warn of threat of born-again smallpox from old Siberian graveyards

Via The Siberian Times: Experts warn of threat of born-again smallpox from old Siberian graveyards. This sounds like a scare story, but if nothing else it shows what some Russian scientists are thinking. Excerpt:

Currently 24 people are in hospital in Salekhard, on the Arctic Circle, after contracting potentially lethal anthrax from unfrozen reindeer or human burial sites, but scientists say this is far from the only threat as climate change grips Siberia.  

Anthrax spores are already 'on the loose' on the Yamal peninsula, according to one scientist, and this should act as a warning of the real risk of a return of eradicated smallpox from melting permafrost which allows the erosion of river banks at sites where victims were buried, said another. 

'Back in the 1890s, there occurred a major epidemic of smallpox,' said Boris Kershengolts, deputy director for research at the Institute for Biological Problems of Cryolithozone, of the Siberian Branch of the Academy of Sciences.

'There was a town where up to 40% of the population died. Naturally, the bodies were buried under the upper layer of permafrost soil, on the bank of the Kolyma River. Now, a little more than 100 years later, Kolyma's floodwaters have started eroding the banks.' 

Experts from the Novosibirsk-based Virology and Biotechnology Centre had conducted research in the area, said Sergey Netesov, chief of the bionanotechnology, microbiology and virology laboratory at the natural sciences department of Novosibirsk State University. 

The corpses they studied bore sores that looked like those smallpox might cause, he told an intriguing and troubling TASS video conference involving multi-disciplinary experts on the implications of the outbreak of anthrax on the Yamal peninsula in northern Siberia.  

While the virus itself was not found, some fragments of its DNA were noted. 'This type of research should go on,' he urged. 'Examining deeper burials might help clear up the situation.'   

Yamal and the anthrax outbreak now underway - the first for 75 years - should act as a warning, he said, calling for a more serious attitude to preventive measures against dangerous infections. 

While the number of people hospitalised with anthrax has halved since Friday, two dozen people remain infected by the disease which also killed more than 2,300 reindeer.   

'The Yamal outbreak is a reason enough to finance research into the diagnostics and prevention of exceptionally dangerous infections,' he said. 

He explained there are there are thousands of such cattle graves across Russia and many of them are inside the Arctic Circle, which last month - July - experienced the warmest temperatures on record rising to 35C.