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Spanish Flu May Have Lingered Two Years Before 1918 Outbreak And Vaccine Could Have Treated It
The most severe pandemic in recent history, killing some 50 million people worldwide, the Spanish influenza, may have emerged up to two years earlier than previously believed. And, according to a new and influential study, its early manifestation was ignored at the time as a "minor infection."
It is believed that, if doctors had recognized that influenza was the cause of an illness which was killing soldiers in Etaples, France, and Aldershot, England, in 1916, scientists would then have had better grounds to embark on a two-year vaccination programme and some of the worst effects of the Spanish influenza could have been avoided. Such are the findings of a new paper, launched by Professor John S. Oxford, the UK's top expert on influenza, and Douglas Gill, a military historian.
Published in Human Vaccines & Immunotherapeutics, the study uses modern day scientific technology and delves through literature published in The Lancet from the time, to not only track the origins of the virus, but to seek how we can use this information to learn from the past to prevent the spread of an influenza pandemic.
In their quest, Oxford and Gill trace the origins of the Spanish influenza as it emerged in 1915 and 1916 in the Etaples Administrative District in northern France. At the time, up to 30,000 soldiers were admitted each year to British army hospitals in France and England, suffering from typical influenza symptoms. In early 1917, however, a medical group in Etaples treated hundreds of patients infected with what they described as an "unusually fatal disease" presenting "complex" respiratory symptoms.
In Aldershot, in the south of England, three senior physicians were also tackling a problem whose hallmarks looked very much the same. In both instances, the disease was characterized by a 'dusky' cyanosis, a rapid progression from quite minor symptoms to death -- with death in any case usually resulting from a superinfection involving staphylococcus, streptococcus, etc.
Both medical groups were encountering a case fatality in the order of 50%, and they were learning from colleagues in England and France (who were publishing in The Lancet in 1917) that the malady was occurring elsewhere.
It is this information which has helped Oxford and Gill to track what was then believed to be a minor respiratory infection as the very origins of the biggest killing pandemic of the 20th century.
"We have identified long-neglected outbreaks of infection: outbreaks which, judged as minor at the time, can now be seen as increasingly important, and a portent of the disaster to come," explains Professor Oxford, of Queen Mary University, London.
"The research undertaken in the production of the Etaples paper was particularly exhaustive in its scope and depth. Not only were the usual examinations undertaken, of tissue and sputum, but a postmortem examination was conducted of every single soldier dying of disease, throughout a period of seven weeks in early 1917."
The findings of the literature as to the origins of the Spanish influenza are further supported in modern papers analysed by Oxford and Gill, wherein scientific methods, namely phylogenetic (the study of evolutionary relationships among biological entities -- often species, individuals or genes) and molecular clock analysis, point to all eight genes of the H1N1 family of influenza A viruses as emerging in 1915-1916.
These modern studies have also shown that the 'emerging virus' began with aquatic geese, ducks, and swans as a reservoir. It is likely that this disease was then passed on to the soldiers through the faeces of migrating water birds.
So what happened between 1915-1916 and 1918-1919 to make this pre-pandemic virus to become pandemic?
Professor Oxford explains.
"In essence, the virus must have mutated. It lost a great deal of its virulence, but gained a marked ability to spread. Recent experiments with a pre-pandemic 'bird flu' called H5N1, deliberately mutated in the laboratory, have shown that as few as five mutations could have permitted this change to take place."
"We appreciate today that a unique characteristic of a pre-pandemic virus lies in its inability to spread from person to person," Professor Oxford added. "The teams at Etaples and Aldershot, although strong in clinical diagnosis, were misled by the lack of spread of this infection. Accordingly, they failed to pinpoint influenza as the underlying cause."
There was, however, a silver lining to a very dark cloud.
"Pathologists in the United States and in France strove to construct the first universal vaccines against influenza. Their efforts were not misdirected, because the ultimate cause of death in nearly all cases flowed from superinfections with respiratory bacteria."
Oxford and Gill conclude: "We remain impressed by the care and initiative shown by our predecessors 100 years ago. Their efforts did have an impact on the level of fatalities, but -- not unexpectedly -- had no effect upon spread: the result, of course, of everyone's misunderstanding of the nature of the pathogen involved.
"Once the virus is able to spread from human to human, disaster strikes. With a generation time of two to three days, from just three patients who were infected originally, a million infections can be caused in around 40 days. And this is probably exactly what happened in 1918-1919."
Today, the World Health Organisationis on full alert; and every nation in the world has been asked to plan for a pandemic of bird influenza A (H5N1) or (H7N9).
By understanding the origins of the Spanish influenza via analyzing modern day research and papers written in 1917, it is hoped this study could help us prevent a new influenza pandemic.
Professor Oxford thinks that existing vaccines have a role to play.
"Something similar to what happened at the beginning of the twentieth century could easily be repeated. As a precaution, governments everywhere are stockpiling vaccines against the pneumococcus that usually develops as a secondary infection after the flu, and which causes fatalities on a very large scale."
What Hispanic Publications Reveal About The 1917-18 Influenza Pandemic
The 1917-18 flu pandemic was one of the most deadly infections, killing approximately 50 million people at its peak. Despite its severity and impact, information surrounding the pandemic was limited because of the heavy censorship during World War I. However, Hispanic publications of the time allow us to have a better understanding of the impact of this disease.
Last year, partnering with the University of Houston's Recovering the US Hispanic Literary Heritage Program, I researched the impact the influenza pandemic had as reflected in publications of the time.
Most countries fighting in the war, including the United States, were concerned the pandemic decreased public morale toward the war effort and censored media outlets, documents and news articles regarding the subject.
However, as a neutral power throughout the war, Spain did not engage in wartime censorship and had widespread publications and reporting on the influenza pandemic. Yet, because Spain was the only country reporting on the illness, general opinion mistakenly held that nation responsible for the disease. Hence, the popularized term — the "Spanish flu."
Opinion
These censorship efforts had consequences, and today there is limited documentation of the illness, the spread, or precautions taken, severely limiting our knowledge of the flu pandemic.
Nonetheless, Hispanic publications in the United States were not restricted by the same levels of censorship because of the language barrier and continued to report on the pandemic and its spread to communities of color. The Recovery Program has collected, preserved and digitized over 1,400 historical periodicals to study them and better understand life in U.S. Hispanic communities, dating from 1808 to the 1980s.
"El Mañana" from McAllen, a Soanish publication from the influenza pandemic era, in 1917-18. Publications in Spanish reveal what was censored in the English speaking media at the time, says Carolina Lopez-Herrera.(HANDOUT) These periodicals include various published during the 1917-18 pandemic epidemic, such as San Antonio's La Prensa, Los Angeles' El Heraldo de México, Tucson's El Tucsonense, Laredo's Evolución, and McAllen's El Mañana, among others. As an intern for the University of Houston's Research for Aspiring Coogs in the Humanities Program, I was able to work with these archival newspapers.
The more I interacted with the documentation, the clearer it became that Hispanic communities throughout WWI were victims of discrimination as their ethnicity and language characterized them as carriers of the erroneously nicknamed "Spanish flu."
In particular, a column in El Mañana stuck out to me as a clear example of the daily mistreatment that Hispanic communities experienced. The author writes about how he was quietly sitting in a corner of a bar he visited regularly, smoking a cigar when he noticed a white man entering. After looking around the empty bar, the man approached the author. When the author raised his head, the stranger began yelling obscenities about how "his people" started the pandemic.
Throughout this altercation, the author reflected on his country of origin. He could not comprehend why he was the recipient of anger toward Spaniards when he was from a South American country. Additionally, the stranger was not the only one negatively impacted by this pandemic; he too had lost loved ones. It was unfair to be blamed for a tragedy that had also taken from him. In the end, angered by these frustrating thoughts, the man decided to leave as the man kept yelling.
This article illustrates the frustration, anger and exhaustion reflected in many of the articles that appear in Hispanic periodicals during this time. There was a sense of confusion and alienation felt by many Hispanic communities that were also severely impacted by the influenza. Moreover, it shows how unwanted Hispanics had become in places they had visited and enjoyed frequently. These discriminatory attitudes extended to every aspect of their lives, including the workplace. The author did not imagine that over a century later, members of the Asian community would suffer from the same prejudices during the COVID-19 pandemic.
What the article fails to articulate, however, is the feeling of hopelessness and dread about loved ones becoming ill and the frenzy of fear and panic that erupted within the community as the systems that were supposed to support them suppressed them. For example, other articles compared how inequitable care was when compared between Hispanics and their white counterparts. White Americans had medics on call and could receive prescriptions without issue, yet Hispanic Americans were either turned away by physicians or had to haggle for help. Furthermore, while white individuals often had the benefit of being able to quarantine, Hispanic populations could not always afford risking a loss of income, something that has replicated in the COVID-19 pandemic as well with essential workers, many of them Hispanics as well.
Other articles in the collection also highlight how hectic and harmful living situations could be throughout the influenza pandemic as Hispanic households often included multiple generations of a family, increasing chances of exposure. The core of these injustices was discrimination, which left Hispanic communities to fend for themselves rather than seek out resources from their local authorities.
The depth of insight into the daily struggles and societal attitudes uncovered within these newspapers will be available in the forthcoming 1917-1918 Influenza Epidemic Collection, part of the Recovering the US Hispanic Literary Heritage Digital Collections website.
The collection includes newspaper articles and advertisements from various Hispanic periodicals related to the 1917-18 health crisis alongside interventions, treatments and community reactions.
Despite being a century apart, the COVID-19 pandemic shares many parallels to the 1917 pandemic, including but not limited to mandatory quarantines, face coverings, public unrest, increase in prejudice to a certain ethnic group, government uncertainty, economic instability and lower-income communities being the most affected, demonstrating that we must continue investigating both pandemics to best prepare against future public health emergencies.
Carolina Lopez-Herrera is a master's degree student of public policy and applied economics at the University of Houston. She wrote this column for The Dallas Morning News.
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A Shot-in-the-dark Email Leads To A Century-old Family Treasure — And Hope Of Cracking A Deadly Flu's Secret
Late one night Michael Worobey began poking around on the internet, looking for descendants of a World War I British military doctor named William Rolland.
Rolland, a pathologist, had written a report in 1917, the year before the start of the Spanish flu. It described cases of British soldiers in France who had contracted an unusually fatal respiratory illness. Worobey, an evolutionary biology professor with a particular interest in the 1918 pandemic, wanted to know whether any of Rolland's samples might still be lying about a century later.
Within a few hours, he had found a possible contact and fired off an email. Across the Atlantic, 5,000 miles away, a retired family physician in England's picturesque Lake District received it. He replied immediately.
When Worobey read it, he was thunderstruck. "I almost fell out of my chair, for real," he recalled. "I actually did cry real tears."
The University of Arizona scientist had connected with a man named Jim Cox. And Cox just so happened to have in his possession a collection of human tissue slides that Rolland had handed down through the generations. Those slides, it turns out, could now help rewrite the history of the 1918 Spanish flu — altering our understanding of when it began and how it spread.
It makes for one heck of a story, one that could enter a new chapter next spring when Worobey and his team start trying to unlock the secrets contained within 10 rectangular glass time capsules.
Worobey has had the slides for several years now, but has waited to look for evidence of old viruses in them while he and his team honed the technique they plan to use. The goal is to sample a bit of tissue from each slide, while preserving them to return to the owners, for whom they represent part of a precious family heirloom.
"We've messed around with similar slides to try to even just figure out what's the best way of getting at the partial specimen without ruining the whole," Worobey explained. "I don't want to crack open the cover slip on any of these before I really know that I have the best possible method of doing the work."
"It's kind of one chance for a clean shot," he admitted.
There's no guarantee the specimens will contain any evidence that points to answers to Worobey's questions. "But at the same time," he said, "if these people were loaded with influenza virus, it's certainly possible that we'll get something."
Health workers prepare to retrieve victims of the 1918 influenza epidemic in St. Louis. Library of Congress via AP Lingering mysteries The Spanish flu pandemic, which swept the globe in a series of waves from 1918 to 1920, is the deadliest infectious disease outbreak in known history. An estimated 50 million people worldwide died from the infection. Puzzlingly, many of the dead were in their late 20s, in the prime of life.
The pandemic occurred before the age of molecular virology. Back then it wasn't even known what caused influenza; influenza viruses were first detected in 1930. In the decades that followed, though, it was recognized that the pandemic was caused by an influenza A virus of the H1N1 subtype. In the late 1990s, U.S. Army scientists found and deciphered the virus's genetic code.
Still, questions remain about when and where the virus started circulating in people.
A prevailing theory, outlined in historian John Barry's 2004 best-seller "The Great Influenza," is that the virus emerged in Haskell County, Kan., in January 1918, after having jumped into humans from another host.
It circulated through that spring without causing unusually severe illness. By the following autumn, however, an influenza outbreak with a high attack rate and an off-the-charts lethality swamped hospitals and overwhelmed the capacity of undertakers to bury the dead across the United States and elsewhere.
But other theories exist.
"There are published claims for Kansas, for England, for France, and for China. And I don't believe any of them are definitive. And we'll never really know," said Niall Ferguson, an Australian historian who has also studied the origins of the 1918 flu.
Another lingering mystery relates to the fact that the outbreak was unusually deadly among young adults. Even garden-variety influenza kills — every year between 12,000 and 79,000 people die from flu in the United States alone. But flu's victims are typically the very young and the elderly, creating a U shape when fatalities broken down by age are charted on the X and Y axes of a graph.
The fatality chart for the 1918 pandemic had a distinctive W shape, with the inner peak capturing the deaths of young adults in their late 20s — a population that typically bounces back quickly from illness.
Why?
Michael Worobey, department head of ecology and evolutionary biology, pulls out slides of human tissue at the University of Arizona. Mamta Popat for STAT Pulling on little threads Worobey has a penchant for finding things others might assume are lost to the sands of time.
He specializes in the origins of pathogens. A few years ago, he and some colleagues garnered major headlines with the publication of a scientific paper showing that a French Canadian flight attendant named Gaetan Dugas — who had been labeled as Patient Zero in the narratives that emerged from the early days of the AIDS epidemic in the United States — was not the person who brought the virus to North America.
Worobey and his team have developed techniques for mining old medical samples for evidence of infections. To explore the Patient Zero mystery, they excavated stored blood samples and pulled out enough genetic material to sequence the HIV virus that eventually took Dugas' life. They then compared it to viral sequences retrieved from blood samples taken from gay men in New York and San Francisco before the existence of AIDS was known.
In the case of the 1918 flu, Worobey is convinced the virus responsible for the pandemic could not have jumped into humans from another host in 1918, a theory that stems from the virus's explosive behavior once it started transmitting among people. He has already conducted research analyzing eight genes of the virus that points to a two-stage emergence of this virus.
"It was like this little thread that I kept pulling and pulling and pulling and more of this story unfolded," Worobey told STAT in a recent interview.
Capt. William Rolland Courtesy Jim and Fiona Cox He believes a flu virus with an H1 hemagglutinin — the surface protein that gives a flu virus the H portion of its name — likely started circulating among people in the late 1890s or early 1900s and later swapped genes with a avian flu virus to form the H1N1 virus known to have caused the 1918 pandemic.
He also thinks the pandemic H1N1 virus had been sickening people for a few years before 1918, which is not the current view of history.
But how to test the theory?
In his research, Ferguson, the Australian historian, had come across a couple of journal articles published in The Lancet in 1917. One was the account from Rolland and two colleagues about an epidemic at a British military hospital in France. The second was from Dr. Adolphe Abrahams, who wrote to report similar illnesses at a military hospital at Aldershot, southwest of London.
Rolland's Lancet article piqued Worobey's curiosity. "Purulent Bronchitis: A study of cases occurring amongst the British troops at a base in France," as it was titled, described an outbreak of severe respiratory illness at the military hospital at Étaples, in northwestern France.
"Patients suffering from this unusually fatal disease present a symptom complex so distinctive as to constitute a definite clinical entity," they wrote in the journal article. Many of the men developed cyanosis — bluish skin resulting from a lack of oxygen.
Cyanosis was also widely remarked in reports of patients suffering from the Spanish flu. And a number of scientists and historians have speculated over the years that the outbreak at Étaples in the winter of 1916-1917 was actually part of the pandemic.
Worobey noticed Rolland was identified as a pathologist. Pathologists take and keep tissue samples for teaching purposes, he knew. Were Rolland's samples preserved and, if so, where might they be?
That's when Worobey turned to Google. He found Rolland's obituary and noted he had a son, Charles. More digging turned up the son's obituary. The warmth and affection in the account of Charles Rolland's life made Worobey suspect the writer was a relative.
Worobey was on a roll.
"It was about 2 o'clock in the morning at this point and my wife got up to get a drink and said … 'Go to bed, you weirdo,'" he recalled. "And I was like, 'No, no, I'm making progress.'"
Within four hours or so of when he started his search, Worobey had found an email address for Cox, who had written the obituary. By the time Worobey's laptop flipped shut for the night, he felt a bit like a cyber stalker.
In England, Cox was startled to receive the email from a stranger asking three questions. Had he written Charles Rolland's obituary? Was Charles Rolland the son of Dr. William Rolland, who had written an article in The Lancet in 1917? And were there any pathology specimens of Rolland's still in existence?
"It was an extraordinary email to receive," said Cox, who is married to Charles Rolland's daughter, Fiona. "And I think to his astonishment and mine, I was able to answer yes, yes, and yes.''
The answer to the last question might well have been no. William Rolland's widow was not one for hanging on to memorabilia, Cox said; she did not like clutter. But Charles Rolland had rescued the pathology slide collection from his father's office after his death, and later gave the collection to Cox.
After a dinner in London, and later a visit with Jim and Fiona Cox at their home in the town of Keswick, the couple agreed to let Worobey work with 10 slides in the collection that date back to the respiratory patients at Étaples.
"It was miraculous that these ones were preserved because … these [military] hospitals were decommissioned within weeks of the end of the war," Worobey said.
Study of the Rolland samples could prove that the Spanish flu pandemic didn't actually begin in 1918 and didn't begin in Kansas. The virus that infected Rolland's soldiers in early 1917, in other words, might have been among the earliest signs of the pandemic.
Historian Barry said he hopes Worobey's search turns up some evidence, but he's not convinced, noting that back in 1918 the Étaples outbreak was well-known, but felt to be unrelated to the Spanish flu.
If Worobey finds that's not the case, William Rolland's pathology slides will rewrite influenza history. Even if they show that the soldiers were infected with a precursor H1 virus, our understanding of what happened in the lead-up to the Spanish flu will change.
"It would be really interesting to me if this horrible virus was really circulating under the radar for so long before the fall of 1918 when it really had its peak effects," said Worobey. "It would tell us that there's a whole lot we have to learn about the forces that keep pandemic viruses simmering at a low level before they explode."
The late pathologist Dr. William Rolland's teaching collection included human tissue slides from France in 1917. Jim Cox A theory of the case There is one other mystery Worobey hopes to crack — the reason for the W-shaped death curve. He already has a theory.
When it comes to flu, there is increasing evidence that the body's immune system responds best to the virus it first encounters in childhood. The phenomenon is called imprinting. The less related a later virus is from the one that caused that first infection, the less effective the immune response will be in fighting it.
Three decades before the 1918 Spanish flu, the world was hit by a pandemic caused by an H3N8 virus. That virus was likely to have shared no genes with the 1918 virus; furthermore, the viruses in those two pandemics belong to different sides of the influenza virus family tree, meaning that the antibodies generated by the H3 exposures wouldn't even offer modest "cross-protection" against the virus in the Spanish flu pandemic.
In presentations Worobey gives and papers he's published exploring the issue, he shows a graphic that makes a compelling case: The people who were born shortly after 1889 were in their late 20s in 1918. They were the people who died in unexpected numbers from the Spanish flu.
People just a little younger than the worst hit seemed to weather the storm more easily, leading Worobey to believe they may have been exposed to an earlier iteration of the Spanish flu virus.
Figuring out which flu viruses were circulating before 1918 should help explain the unusual pattern of severe infections caused by the Spanish flu, and it may also further bolster the imprinting theory.
Might the miraculously conserved Rolland slides deliver up a century-old flu virus? Worobey is trying to keep his expectations in check.
"In all likelihood, we'll just get no result at all. That's something to keep in perspective," he admitted. " But if we did find something, whatever we found relative to flu would be really interesting and informative."
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