Influenza: Past, Present and Future

It was a pandemic unlike any other. The 1918-19 influenza outbreak at the end of World War I killed more people than the Great War itself, claiming the lives of as many as 50 million men, women and children. The Spanish flu has been called the most devastating epidemic in recorded world history, with more people dying of influenza in a single year than in four years of the black death bubonic plague.¹ A global disaster of this magnitude is hard to imagine today, especially when so many people view the flu as little more than a very bad cold. History, unfortunately, contradicts that cavalier point of view. And when it comes to flu, experts believe history may have a tendency to repeat itself.

Understanding Influenza

Influenza, commonly known as the flu, is actually a general name given to any one of a number of viruses that can cause serious illness. There are three types of the flu: influenza A, B and C — each one with its own viral strain that replicates and changes independently from the other types. Seasonal strains of human influenza change constantly, which is why people can catch the flu multiple times.It is also why the flu shot is the only vaccination that is continually updated; influenza is a rare type of virus that is constantly mutating.

Each year, a certain strain becomes prevalent and strikes, typically between the months of October and March, a time period now referred to as flu season. When a flu outbreak occurs in one country or region, it is referred to as an epidemic, whereas outbreaks around the world are called pandemics. Because of the global nature of our world today and the speed and frequency of international air travel, the likelihood of another great pandemic is not farfetched; a flu strain that originates in China, for example, could land in New York in less than a day’s time, infecting everyone en route.

Large-scale events that create a draw for tourists are a concern for those who study flu outbreaks. A recent report suggests that the 2012 Summer Olympic Games pose an extreme threat for a serious flu outbreak within the United Kingdom as an extra 5.3 million tourists descend upon the area. The report, which was conducted by global risk research firm Maplecroft, revealed that such a large influx of visitors during the summer months coupled with an increase in the use of public transportation will exacerbate the already significant risk to this particular region of the world.²

A Viral Link to the Past

The flu virus mutates and changes each year, but many researchers believe the specific strain that wreaked worldwide havoc in the mid-1900s may have birthed a viral dynasty with ramifications that can still be seen today. According to scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, it may even be linked to the now infamous H1N1 outbreak of 2009. In an article published online by the New England Journal of Medicine, authors Anthony S. Fauci, MD, Jeffery K. Taubenberger, MD, PhD, and David M. Morens, MD, argue that we have lived in an influenza pandemic era since 1918, and they go on to describe how the H1N1 virus that circled the globe in 2009 was merely another manifestation of the same viral family that killed millions nearly a century ago.³ “The 1918-1919 influenza pandemic was a defining event in the history of public health,” said Dr. Fauci, director of NIAID and a co-author of the study. “The legacy of that pandemic lives on in many ways, including the fact that the descendants of the 1918 virus have continued to circulate for nine decades.”⁴

The study went on to explain that all flu viruses have eight genes, including two that are coded to produce the proteins hemagglutinin (H) and neuraminidase (N) that allow the virus to enter a host cell and spread from cell to cell. There are 16 H subtypes and nine N subtypes, making 144 possible HN combinations. But only three — H1N1, H2N2 and H3N2 — observed to date are fully adapted for infecting humans. Other combinations such as the H5N1 bird flu virus have only occasionally infected small numbers of humans. “The eight influenza genes can be thought of as players on a team: Certain combinations of players may arise through chance and endow the virus with new abilities, such as the ability to infect a new type of host,” said study co-author David Morens. “That is likely what caused the 1918 pandemic.”

The Fight Against Flu

From a public health perspective, the flu has become easier to manage in recent decades. Improved healthcare conditions, greater understanding of the virus itself, more sophisticated means of communicating the risks of flu and, of course, the creation of the flu vaccine all have contributed to this achievement.

The influenza virus was first identified in the early 1930s, and scientists developed a working vaccine by the 1940s, which was used on soldiers during World War II. At the time of the great pandemic during the first World War, the flu virus and its means of transmission were not familiar to the medical community, and there was no such thing as a vaccine. By 1957, the time of the next major flu outbreak, doctors had developed an arsenal of vaccines and were able to alert the public to the risks of not being vaccinated. Casualties were still high — 70,000 people in the U.S. alone.⁵

The next large flu outbreak in 1968 was known as the Hong Kong flu. Thanks to ample supplies of vaccines and public compliance to get vaccinated, only 34,000 people died in the U.S. as a result.⁶ These declining mortality rates may have contributed to the growing public sentiment that the flu is not that deadly, but the appearance of several new flu strains in recent years — including the H5N1 “avian flu” strain in the late 1990s — illustrates the challenges faced annually by researchers trying to track, contain and develop vaccines for the ever-changing virus known as influenza.

An Evolving Challenge

Because of the evolving nature of the flu, developing an effective vaccine each year is no small task. Each year, a global network of scientists are tasked with surveying flu virus mutations and making vaccine recommendations.

The World Health Organization (WHO) holds two vaccine strategy meetings annually, one for the Northern Hemisphere (in February) and one for the Southern Hemisphere (in September). As soon as the organization announces which influenza subtypes should be targeted by the vaccine, medical labs go to work developing strain-specific vaccines. As one might imagine, production schedules are tight and leave little room for error — the FDA must approve the vaccine by the spring, the vaccine must be in production by August and be ready to be administered in September through December, giving people enough time to develop immunity before flu season is in full swing.

Today’s influenza vaccine contains three strains of the virus, as determined by the World Health Organization (WHO), and researchers labor to stay one step ahead of the constantly mutating bug. For the 2012-13 flu season, the vaccine was reformulated with two new flu strains.⁷ Each year, public service campaigns encourage people to get vaccinated; current Centers for Disease Control and Prevention (CDC) guidelines advise everyone 6 months of age and older to get a flu vaccine annually.

When you consider how far we’ve come from the fearful days when flu was an indiscriminate killer and no protection existed, it seems odd that each year tens of thousands of people still die from flu-related complications in the U.S. While there may be many extenuating reasons for these statistics, the sad fact remains that many people still avoid getting a flu vaccine. Studies show young healthy adults are chief among the population groups who skip immunization because they feel they are not at high risk, they think that the vaccine doesn’t work, and/or they believe that getting the flu vaccine will make them sick. Clearly, more education, communication and effort are needed to help dispel some of these common myths surrounding flu vaccination to ensure pandemic history does not repeat itself.

The 1970s Swine Flu Scare

The ability of a virus to breed panic was perfectly illustrated when the emergence of a flu-like illness at Fort Dix, N.J., in the late 1970s became public knowledge. Federal researchers isolated a flu virus with the same H1N1 antigenic signature as the Spanish flu. Thirteen soldiers became seriously ill, and one young man died.

While hindsight is 20/20, at the time of the outbreak, the CDC recommended a massive vaccination campaign in an effort to protect the American public. The effort was initially successful, and within 10 weeks, 40 million Americans were inoculated. Unfortunately, public health officials had little time to revel in the achievement, as reports of temporary paralysis and death linked to the vaccine began to emerge. By January 1977, more than 500 cases of Guillain-Barré syndrome were counted, along with 25 deaths.⁸

To add insult to injury, the potentially deadly pandemic never really materialized, and the public backlash against government-recommended flu vaccines created skepticism about flu vaccine efficacy that continues to this day.

Pandemic Predictions: Fact or Science Fiction?

For years, infectious disease experts have warned of an influenza virus that could infect 40 percent of the world’s population. Some now believe that the H5N1 virus, also known as the avian flu, could become that deadly strain.The catastrophe such a pandemic could pose has been compared to the 1918-19 Spanish flu, with the possibility of H5N1 being even more lethal.

Since it was discovered in China in 1997, the H5N1 has mutated, becoming stronger and more deadly. But whether the relentless virus ever becomes capable of being transmitted from human to human on a wide scale remains to be seen.⁹ The fear of this unknown creates much unease among those whose job is to predict pandemic outbreaks.

The threat of bioterrorism is also a concern, with many in the scientific community wanting to limit the release of information garnered from studies about H5N1, lest it fall into the wrong hands. In a correspondence addressing the topic earlier this year, Michael Osterholm, director of the Center for Infectious Disease Research and Policy, which studies bioterrorism threat, stated that even if H5N1 was not spread in human populations, a terrorist group might try to infect pigs, devastating local livestock industries because people would fear infection from eating them (despite the fact that viruses are not transmitted this way). 10 “I can’t think of a worse scenario than having H5N1 virus circulating widely in swine with a critical reassortment likely to occur and human transmission not far off,” Osterholm said.

Developing countermeasures to hold back the flu is an even more complicated challenge to today’s scientists than it was to their predecessors. Much is dependent on our current strategies and continued vigilance against the virus that has the potential to bring about global disaster.³