100 years after Spanish flu, researchers look for new pandemic protections

October 12, 2018

When health officials formulate a vaccine each flu season, which runs October through May in the United States, they choose virus strains to include based on versions that have recently circulated around the world.

The U.S. Centers for Disease Control and Prevention and agencies like it can draw upon a global flu surveillance system involving more than 100 member states -- a tool that wasn’t available in 1918, when an influenza pandemic sickened more than a third of the world’s population and killed at least 50 million people, possibly up to 100 million.

Around 5,000 people are believed to have died in Pittsburgh, with another 2,000 deaths in Westmoreland County.

The intervening century has brought increased knowledge about the flu virus -- first isolated in the 1930s -- as well as vaccines to provide immunity against many known strains. There also have been advances in preparing for and responding to flu infections, including development of antiviral drugs to treat the disease.

Modern researchers are exploring yet other approaches for providing better protection against flu strains.

“We have better hospital facilities that can support people who get sick with influenza,” said Dr. David Wyszomierski, a physician with Excela Latrobe Pediatrics who participated in a lecture series last year at Westmoreland County Community College on influenza concerns past and present. “We have more rapid means of diagnosis that will tell us what strains are going around. The CDC keeps track of what is circulating.”

But predictions of seasonal flu varieties are imperfect, since strains continue to evolve and sometimes jump the species barrier between animals and humans.

Likewise, the CDC cautions, it’s impossible to predict when the next pandemic will occur.

Wyszomierski noted health officials have been monitoring so-called bird flu viruses in recent years that have been transmitted from wild birds to domestic birds and then to humans, mostly in Asia. Migratory birds naturally host and spread a variety of flu viruses.

“They’ve only infected a few human beings, and they’re not transmissible from person to person,” Wyszomierski said. “If such a flu virus attains the ability to be transmissible from human to human, it could cause a worldwide epidemic.”

Though rare and infrequent, flu epidemics morph into pandemics that spread around the world, infecting and killing on a large scale. Researchers believe such influenza epidemics date back to the Middle Ages, if not earlier.

Aside from 1918′s deadliest outbreak, other known flu pandemics in recorded history struck in 1889, 1957, 1968 and 1977 -- the last believed to have originated from a flu strain not seen since the 1950s that escaped a Chinese lab that was likely working on a vaccine.

The most recent flu pandemic that affected the United States was a new H1N1 virus, which was detected in April 2009 in California, a month after first appearing in Mexico. The letters refer to types of proteins in the virus that are key to creating effective vaccines.

The H1N1 strain struck the world in 1918 and has spawned viral descendants over the decades since. The 2009 virus was “another genetic product in the still-growing family tree of this remarkable 1918 virus,” researchers noted in an article published by The New England Journal of Medicine.

The 2009 virus didn’t have as severe an impact as the one in 1918, which claimed nearly 700,000 lives in the United States. According to the CDC, the worldwide 2009 outbreak resulted in 2,125 confirmed U.S. deaths, including 344 children.

Health officials quickly found antiviral drugs -- which didn’t exist a century ago when scientists were not yet aware of viruses or how to treat them -- that could be used to treat the 2009 illness until a vaccine was ready for distribution that October.

Researchers determined the 2009 virus contained genetic material derived from human, avian and swine viruses from various continents. That virus has now become one of the regular seasonal varieties that can be addressed with a vaccine.

The 1918 flu may have lessened the blow of the 2009 pandemic, according to Seema Lakdawala, an assistant professor of microbiology and molecular genetics who heads a flu research lab at the University of Pittsburgh.

“The 2009 H1 protein is very similar to the H1 for 1918,” Lakdawala said. “People who had been born before 1957, who had seen the similar H1, were protected from the 2009 pandemic,” having built up immunity to the similar viral component.

Searching for answers

The extreme virulence of the 1918 flu long puzzled officials, but researchers have found some clues.

In 2005, CDC microbiologist Terrence Tumpey became the first researcher to reconstruct and study the 1918 flu virus, applying reverse genetics to preserved lung tissue from victims of the pandemic.

His work revealed that two types of genes in the 1918 virus were “essential for maximal replication and virulence,” Tumpey said in an interview published on the CDC website. “With these data in hand, some scientists felt that these virus genes could be a potential target for a new generation of anti-influenza A drug development.”

Of the four basic types of influenza viruses, the A type is most commonly associated with cross-species infection and pandemics.

Lakdawala also has been working on methods to interfere with the ability of a flu virus to spread among humans.

“We focus on human seasonal viruses,” she said. “We mutate it and try to lose its ability to transmit through the air.”

Formerly associated with the National Institutes of Health, Lakdawala operated her Pittsburgh lab for three years. But she’s been researching flu transmission since 2009.

“We’ve learned so much in the past 10 years,” she said. “Before, we had only one lab at the CDC looking at how flu transmission occurs through the air. Now multiple labs across the globe are studying it.”

Lakdawala stressed the importance of ventilation to exchange the air inside a building and to help disperse airborne flu viruses expelled by someone infected with the illness. Just as important is frequently wiping down touched surfaces such as door knobs and elevator buttons, where viruses can be present, she said.

Research has revealed that flu viruses can remain stable in the air for at least an hour, and for up to 16 hours when present in mucus on certain surfaces, according to an article published by Lakdawala and colleague Linsey Marr, a professor at Virginia Tech.

According to Wyszomierski, medical centers in the United States and Great Britain are working to develop a longer-lasting, universal vaccine against seasonal flu strains that could be effective for five years or more between doses.

Until that breakthrough occurs, he said, “It’s always best to follow the direction of the CDC and get the flu vaccine every year.”

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