Fall has started and along with it comes several long-anticipated events like football season, changing weather, and Thanksgiving. But there’s something else associated with this time of year that no one is looking forward to–flu season. Despite being seemingly innocuous, the flu is one of the greatest scourges in the history of mankind and is still a potent killer. It has also given rise to a billion dollar vaccine industry bent on stopping it.

Read on to find out more about the history of the flu, the flu vaccine, and the business that it has spawned.

The History of the Flu

Human beings have been victims of the flu or influenza for as many as 6,000 years. While no precise date is readily available, it is believed that once humans started to domesticate animals they also started acquiring the flu from them, as many animal species carry flu strains. The name “influenza” originated in eighteenth century Italy where its outbreak was blamed on poor air quality.

Although the existence of the flu has been known for centuries, it is only within the last hundred years that it has been clearly identified. In 1918, a veterinarian actually discovered that a disease found in pigs was similar to one found in humans. In 1928 other researchers proved, through experiments on pigs as well, that the mysterious killer influenza was actually caused by a virus. Still, it was not until 1933 that scientists finally identified the specific virus that caused influenza.

The video below gives an overview of the history of the flu:

Types of Flu

Although the flu is commonly referred to as a monolithic thing, it is actually a combination of related viruses. There are two main types of flu virus: H-types and N-types. These letters correspond with genetic markers for two glycoproteins, hemagglutinin (H) and neuraminidase (N), which are the antigens the host of the virus develops an immunity to. Along with these are three major strains: A, B, and C. The A strain is the one that causes major outbreaks that lead to widespread deaths. There is also a D strain, which primarily infects cattle and is not known to harm humans.

The reason why the flu is so deadly is because of its genetic makeup. Since the genetic code of the influenza virus is made of RNA and not DNA, the viruses replicate very quickly and are more prone to mutations. Thus, viruses can change numerous times before a human, for example, can even build up an immunity to the original virus. This is done through two processes. The first is called antigenic drift, and it occurs when mutations change the virus over time eventually making it so immune systems can no longer recognize it. The second is called antigenetic shift, which involves a dramatic change in the composition of the virus, like combining with an animal subtype, which is often the process that leads to pandemics.

The flu generally hits elderly people, those with asthma, pregnant women, and children the hardest. For anyone who has had the flu before, the symptoms are familiar: fever, chills, coughing, sore throat, achiness, headaches, fatigue, vomiting, and diarrhea. The virus is usually transmitted through the air via respiratory droplets, but can also move through physical contact. Some people who get the flu are asymptomatic meaning, while they have the flu, they do not experience the typical symptoms, yet can still get others sick. The flu also triggers several related complications including, pneumonia and sinus and ear infections. It can worsen existing medical conditions such as chronic pulmonary diseases, or cause heart inflammation.

Deadliest Strains

While the flu is perceived as commonplace and not particularly dangerous today, it is still one of the deadliest viruses in human history. During the 16th and 18th centuries, there were a number of massive and deadly outbreaks. Since 1900 there have been four major flu pandemics. The Asian flu lasted from 1957-1958 and killed one to four million people. The Hong Kong flu circulated from 1967-1968 and killed one million people. The third was the Swine flu, or H1N1, which broke out in 2009. The greatest outbreak by far, though, was the Spanish flu that broke out in 1918, right on the heels of World War I. The epidemic killed as many as 50 million people worldwide, more than the war itself.

The accompanying video looks at the deadly 1918 pandemic:

Aside from these major outbreaks, the flu remains a virulent threat. Although it is hard to pinpoint exactly how many people die each year from the flu, the CDC estimates that more than 55,000 people died from influenza and pneumonia in 2015. But that is an estimate and the numbers often vary. An earlier estimate for the flu alone, by the CDC, put the yearly average somewhere between 23,000 and 33,000. The discrepancy is caused by outliers in yearly totals and different strains that respond to the flu vaccine differently.

The Flu Vaccine

If someone catches the flu there is little that can be done for them. Infected people can take over-the-counter remedies and in certain cases can even be prescribed antiviral medications, although many strains of the virus have grown immune to such treatments. Generally, the only way to consistently ward off the flu is by trying to prevent it in the first place with a flu vaccine.

Developing the flu shot has been a long process and one that is still in progress. The first step was on the heels of two important discoveries–scientists managed to grow the flu virus in eggs for the first time in 1931 and were able to isolate the virus itself in 1933. While Louis Pasteur was the first to actually attempt to make a flu vaccine, it was a Soviet researcher in 1936 who developed the first prototype. While this vaccine was used in the former USSR for 50 more years, it had the drawback of using a live strain of the flu.

However, scientists quickly overcame this by finding a new source of the dead, “inactivated” virus to use in vaccines instead. In 1940 a new problem arose as a second strain of the flu was discovered, leading to the bivalent vaccine in 1942, which targeted one A and B strain. The next major step in the development process occurred in 2007 when the source of the virus for vaccines moved from hen eggs to cell cultures, making reproduction and sterilization easier.

On top of the bivalent vaccine, trivalent and quadrivalent vaccines were developed, containing multiple A and B strains. Vaccines typically change each year because the virus itself mutates from season to season, often making old vaccines ineffective. Strains of the virus are actually monitored all year long, with the Northern Hemisphere monitoring what is circulating in the South and vice versa. When the prevailing strains are identified, a vaccine is tailored to them. Additional vaccines with other strains can also be created in emergencies. This system came about as a result of a WHO recommendation in 1973. Since 1999 WHO has issued two sets of vaccine recommendations each year, one for the Northern Hemisphere in February and one for the Southern Hemisphere in September.

The video below explains how the flu shot works:

The Business Side

Developing a flu vaccine and then redeveloping it each year to fight the different strains of the flu virus has been a long and arduous task. An estimated 171 to 179 million doses of the vaccine were created for the United States in 2015 alone. That amounts to a $1.61 billion industry in the United States and roughly a $4 billion one worldwide.

With an industry this large, it is fair to ask whether the pursuit of profits has overwhelmed the pursuit of health. Roughly 44 percent of Americans received the vaccine in 2015 and the shot is considered the best way to fight the flu. But because of the difficulty of matching the vaccine to the dominant strains, it is only 50 to 60 percent effective. Furthermore, there are different types of vaccines sold depending on how many strains the shot will protect against.

Conclusion

Each year, millions of people are infected with the flu and thousands or even tens of thousands die. It took centuries to identify the virus and much of what we know about the virus was discovered in the last hundred years. Given the nature of the virus and the rate at which it mutates, vaccines often have a hard time keeping up. The international community has developed a sophisticated monitoring system to identify and track new strains of the virus to ensure that vaccines are as effective as possible. But because of the frequent changes, new vaccines must be developed each year, prompting the development of a substantial industry.

Resources

CDC: Deaths and Mortality

CDC: Seasonal Influenza, More Information

WHO: Influenza: Surveillance and Monitoring

NPR: How Many People Die From Flu Each Year? Depends How You Slice The Data

Medical Ecology: Influenza

CNN: Getting a Flu Shot? It may be Better to Wait

The History of Vaccines: Influenza

Medscape: The Evolving History of Influenza Viruses and Influenza Vaccines

CNBC: The $1.6 billion Business of the Flu

Flucelvax: History of the Flu Virus and Influenza Vaccination

Michael Sliwinski

Michael Sliwinski (@MoneyMike4289) is a 2011 graduate of Ohio University in Athens with a Bachelor’s in History, as well as a 2014 graduate of the University of Georgia with a Master’s in International Policy. In his free time he enjoys writing, reading, and outdoor activites, particularly basketball. Contact Michael at staff@LawStreetMedia.com.

The post Feeling Okay? The History of the Flu and Flu Vaccines appeared first on Law Street.

Start saving up your sick days. The Centers for Disease Control and Prevention (CDC) says that the upcoming flu season could be severe. The agency expects influenza A (H3N2) to dominate this year. H3N2 causes more hospitalizations and deaths than other flu types and has mutated since this year’s vaccine was created. Is it time for a quarantine? Probably not. But even if you’re vaccinated, you could be purchasing more tissues than usual from now until March as flu season peaks. I’ll break down what you need to know below.

How bad will it be?

Here’s some perspective: last year’s vaccine was only about 50-55 percent effective and experts estimate we won’t even reach those levels this year.

Here’s why

• Ninety-one percent of recent samples are influenza A (H3N2), an influenza (flu) subtype that typically causes more hospitalizations and deaths than other subtypes. (Don’t worry, I’ll explain subtypes later!)

• Over half of these samples don’t match this year’s vaccine because they’re drift variants; they’ve “drifted” to become structurally different from the H3N2 virus used to create this year’s vaccine. The drift could make this season’s vaccine less potent but it’s certainly not useless. In past flu seasons where influenza A (H3N2) drifted, vaccines were about 40 percent effective in stopping the virus. The vaccine still protects against other flu subtypes that haven’t drifted, like influenza A (H1N1) a.k.a the “swine flu.”

So, what is the flu anyway?

The flu we’re talking about should not be confused with the stomach flu, which is really just slang for gastroenteritis. It’s also not a blanket term for any ailment. You only have the flu if you’ve been infected with the flu virus.

A true flu is a viral infection that preys on your nose, throat, and lungs. The flu sees these mucous membranes as ideal ports of entry. Even innocently rubbing your eyes invites the flu into your body. Once the flu gets in, it causes an infection that leaves your respiratory system hampered and makes you feel generally miserable–sneezing, coughing, weak, and sluggish.

This video from Health 360 explains the flu virus and how it invades your body.

Flu Mechanics

Google a picture of a flu virus and you’ll see a circle covered in spikes, kind of like a balding koosh ball. Just like the koosh ball’s rubber fingers make the toy easier to catch, the flu virus’ spikes make the infection easier to catch. The flu virus would be nothing without its spikes.

The viral protein hemagglutinin (H) makes up most of the virus’ spikes. Hemagglutinin causes red blood cells to stick together (hema is heme molecules found in red blood and agglutinate means to stick together). Hemagglutinin enables the virus to attach to a host cell. Viruses can only spread if they hijack a host cell and replicate within it, so you can see why hemagglutinin’s role in host cell attachment is of the utmost importance…to a virus.

The viral protein neuraminidase (N) makes up the rest of the virus’ spikes. After the virus has infected a host cell and replicated itself, neuraminidase (N) allows the replicated virus to escape the host and infect other cells.

So hemagglutinin (H) assists in infecting the host cell and neuraminidase (N) helps the replicated virus proliferate. They work together to infiltrate as many immune systems as possible. Different subtypes of these viral proteins–Hs and Ns–are behind all of the confusing names for different flu viruses like H3N2, H1N1, etc. Let’s end that confusion once and for all.

H?N?: Naming flu types and subtypes

Three types of flu affect humans: A, B, and C.

• Influenza A: Infects both animals and humans and is usually responsible for large epidemics because of its ability to change.
• Influenza B: Infects only humans and is typically less severe than influenza A.
• Influenza C: Infects humans but is the least severe of all the types.

The ABC’s are the least of your worries in understanding flu names. Naming the flu gets complicated when we look at all of the subtypes of the viral proteins (spikes), hemagglutinin (H), and neuraminidase (N) that we just learned about above.

There are 16 possible subtypes of H and nine subtypes of N that can recombine to form 144 different subtypes of the flu virus that are named based on which H and N subtypes they contain. The influenza A virus dominating this year is named H3N2 because it has the viral protein subtypes H3 and N2 decorating its surface.

Viral proteins also come into play when we’re looking at how this year’s vaccine ended up being mismatched with this year’s dominant flu. Even among the 144 different subtypes, something called antigenic drift can cause different strains to form. The drift changes the structure of the viral proteins H and N to be different enough to befuddle your immune system, but not different enough for separate classification.

For example, this year’s dominant strain of influenza A (H3N2) drifted antigenically from the strain used to create the vaccine. So even if you’re vaccinated, your immune system might respond differently if you’re exposed to the newly drifted virus.

The Drifts and Shifts of the Flu

The flu virus has a sneaky habit of changing and tricking the immune system into letting it pass. The change happens through antigenic drift or antigenic shift. The preceding “antigenic” refers to antigens, which trigger your immune response. So the drifts and shifts produce a virus strain with altered antigens that your immune system will respond to differently. The antigens in this case are the viral proteins H and N. Your immune system responds to the shape of H and N subtypes you were vaccinated with. If those shapes change enough, you could have a problem.

Antigenic Drift

Antigenic drift happens when small changes naturally accumulate over time as a virus copies itself. At first, the drifted virus will be antigenically similar enough that a vaccinated immune system can recognize it. But small changes can compound over time so the shapes of the proteins drift enough that even a vaccinated immune system can’t recognize the drifted virus.

Think of a close friend getting a radically different haircut. She’s the same person, but at first glance you might not realize it because she looks completely different. If a virus drifts enough to create an antigenically different strain, the immune system might not be able to recognize and bind to the new shape of the viral proteins.

The flu drifts adeptly so we need to create a new vaccine every year. Drift is also why you’ll probably get the flu more than once in your life.

Antigenic Shift

An antigenic shift causes fast changes that make completely new H and N viral proteins. The virus is so altered that humans have no immunity to it, even if they were vaccinated. This happens when viruses shift from animal populations to infect humans.

Antigenic shift occurs rarely, but it can be devastating. Pandemics and epidemics like the 2009 H1N1 flu pandemic often happen when a flu virus shifts suddenly. Flu viruses usually shift to humans from domestic pigs and poultry. Don’t worry, this year’s dominant influenza A (H3N2) has only drifted not shifted.

Making a Vaccine

Since it takes so long to develop the vaccine, experts have to pick the virus strain they’ll use months in advance. There’s always a good chance the virus will drift in the interim as it has this year.

Private companies make flu vaccines but are subject to FDA safety and efficacy requirements. The FDA has approved three flu vaccines: egg-based, cell-based, and recombinant flu vaccines. The processes vary, but here are the basic steps:

• The CDC or other Influenza Collaborating Center provides the vaccine manufacturer with the vaccine viruses chosen.
• The viruses replicate in a controlled environment.
• The viruses are extracted from their growth host (eggs or cells).
• The manufacturer kills the virus and purifies the viral antigen to produce a vaccine that will not make people who take it sick.
• The manufacturer tests the vaccine before it goes to market.

Historyofvaccines.org has a great animated walk-through of the process. Check it out here.

Then what?

When you get your vaccine–the flu shot–it kind of tricks your body. Immunity builds when you’re exposed to a pathogen, such as a virus. In most cases you have to get sick to build this immunity. When your immune system fights off a virus once, it keeps a memory of the virus in case it returns.

A vaccination gives you the benefits of exposure and immunity building without making you suffer through the actual illness by exposing you to a harmless version of a pathogen. It won’t make you sick, but your immune system responds like a feisty dog that barks at anyone who knocks on your door. The overprotectiveness eventually pays off. If a harmful version of the virus tries to take you down, your immune system will have an immune memory to use in the fight.

That sounds OK, why doesn’t everyone do it?

There’s just something inherently scary and untrustworthy about getting injections. People come up with many fears and excuses for not getting vaccinated. Take a look at the video below.

And the list continues with NPR’s 32 Myths About The Flu Vaccine You Don’t Need To Fear. The good news? Most fears and excuses for not getting vaccinated are unfounded. The bad news? People don’t care if their fears are unsubstantiated.

Researchers have found that foiling flu vaccine myths doesn’t increase a skeptic’s intent to get a vaccine. It actually reduces it. The study suggests that explaining the facts about vaccines might remind people of why they were fearful of getting them in the first place or even give them new information to worry about. This only solidifies their anti-vaccination stance.

So what are we doing about this flu mess?

The CDC maintains that a flu shot is still the best way to protect yourself, but it also urges doctors to prescribe antivirals to people coming in with flu-like symptoms or those at high risk such as children, pregnant women, and adults 65 and older. Antivirals work best within 48 hours of flu symptom appearance, so most doctors will not wait for a positive test to prescribe them.

Is antiviral resistance a problem?

With doctors prescribing medication without lab test confirmation of the ailment, you might be wondering if antiviral resistance is a concern. Yes, it’s actually an inherent problem since the rapid replication process of viruses leads to mutations that can evade antivirals as well as immune systems and vaccines. Some strains of influenza have already become resistant to drugs that have been on the market for a while like oseltamivir, amantadine,  and rimantadine.

What are the benefits?

Results from past flu seasons and the 2009 H1N1 flu pandemic show that these drugs can reduce potentially devastating effects of influenza. Clinical trials and observation show reductions in symptoms, complications, and deaths from influenza with antiviral use.

All Things Considered, It’s Not So Bad

With its fast and unpredictable changes and complicated subtypes, the flu presents a formidable enemy for modern medicine. Flu shots and antivirals aren’t the perfect weapons, but they’re more effective than entering the battle unarmed. So how bad is this flu season going to be? Probably worse than last year’s, but a pandemic doesn’t seem likely.

Resources

Primary

CDC: Early Data Suggest Potentially Severe Flu Season

CDC: Health Advisory Regarding the Potential for Circulation of Drifted Influenza A (H3N2) Viruses

CDC: Types of Influenza Virus

CDC: How the Flu Virus Can Change: “Drift” and “Shift”

CDC: How Influenza (Flu) Vaccines Are Made

NIH: New Vaccine Technologies

Additional

Mayo Clinic: Influenza Treatments and Drugs

Synapse: “Flu” – Recombinant Genes on the Loose!

Science Daily: Correcting Myths About the Flu Vaccine: Effective?

Virology: Structure of Influenza Virus

Ashley Bell

Ashley Bell communicates about health and wellness every day as a non-profit Program Manager. She has a Bachelor’s degree in Business and Economics from the College of William and Mary, and loves to investigate what changes in healthy policy and research might mean for the future. Contact Ashley at staff@LawStreetMedia.com.

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