To me, flu season is a lot like Christmas; there's a defined time period when we expect it to occur, yet it seems to appear earlier and earlier every year. While we often hear of exaggerations from weather forecasters about "the worst storm ever," and stock market prognosticators who project that "we're all doomed," the fact of the matter is that the flu season really did start early last year, and the U.S. Department of Health is warning that it may start early again this year.

Washington state Gov. Jay Inslee getting a flu shot. Source: Jay Inslee, Flickr.

With that in mind, I've outlined some of the key questions on this year's upcoming flu season and what you should know as a possible flu patient and as an investor in the companies involved in making flu vaccines and medications.

Why should I care about the flu?
The primary reason is that according to CDC statistics, the flu and pneumonia combined in 2010 to be the ninth leading cause of death in the United States! You may feel invincible to the effects of the flu, but it can pose a marked risk to the elderly and those in society with compromised immune systems from a primary or secondary disease.

How do researchers determine which strain will be prevalent in the upcoming year?
Now here is where most people fall off the "give me a flu shot" bandwagon and jump aboard the skeptics' train. Researchers, including those at the CDC, use the best information available to them from existing viruses and circulating viruses from the previous year to take their best guess at what viruses will be circulating in the upcoming year. Is it a perfect science? Absolutely not! The CDC will constantly monitor existing viruses for mutations and will study the vaccine effectiveness, or VE, of a current year's therapies relative to a strain to determine whether changes in strain resistance should be made. 

So, is it even worth getting a flu shot?
Based on statistical data, the answer is empirically yes. Last year's cumulative flu vaccines provided a VE estimate of 56% across all age groups. I know that sounds really low, but understand that a flu vaccine isn't necessarily designed to keep you from getting the flu so much as it's designed to keep you from getting severe versions of the flu. The ultimate goal of the flu vaccine is to keep you out of the hospital and from developing serious complications from the illness.

Which age group does the flu shot benefit the most?
Ready for some irony here? Flu shots are actually most effective at, and are geared toward, protecting healthy young adults. Doesn't make a lot of sense initially, does it? The reason researchers want to see this age group get their flu shots is that it frees up our hospitals to take care of the elderly, which is the age group at the highest risk of having serious complications from the flu. Although only 9% of people older than 65 demonstrated VE with last year's vaccine for the H3N2 virus, it is nonetheless a 9% reduction in potential hospitalizations, which is no small figure.

Is getting a flu shot going to give me the flu?
Researchers use inactive strains of the flu to develop the vaccine, which your body's autoimmune system will recognize as foreign and then adapt to defend itself against the active strain in the future. So the idea that you'll get the flu from a flu shot is a common myth.

Have influenza medications improved recently?
This is a transformative time among certain vaccine options, because we're starting to see the emergence of quadrivalent vaccines. In previous years, vaccine makers developed trivalent formulations that focused on preventing both type A influenza viruses and one type B influenza virus that was expected to be more prevalent in the upcoming year. Unfortunately, there was still enough of the minority type B influenza in circulation each year that quite a few people still became ill. Thus, we have the new quadrivalent vaccines, which target all four strains for a bigger level of protection than before. The downside, of course, is that quadrivalent vaccines are more costly than trivalent vaccines.

What strains are this year's flu vaccines protecting against?
With the CDC still basing its flu decisions on the assumption that most manufacturers will use it to create a trivalent vaccine, the strains they'll be combatting are the H1N1 virus, H3N2 virus (both influenza type A strains), and the Massachusetts/2/2012 virus in the type B strain.

OK, so what are my flu vaccine/medication options?
There are quite a few versions of the flu vaccine available that can be given as a shot or nasal spray, as well as medications to minimize the symptoms should you contract a strain of the influenza virus.

  • FluMist: Developed by MedImmune, which is a subsidiary of AstraZeneca (AZN 0.83%), FluMist is the only FDA-approved nasal spray. It's approved to treat children and adults between ages 2 and 49. This is the first year some of the FluMist vaccines will come in a quadrivalent form, similar to quite a few of the vaccines I'll be discussing in a moment. From a convenience factor, FluMist seems like it'd be a winner, but sales of the drug have been uninspiring at an estimated $162 million last year, according to FierceVaccines, because of its higher cost relative to its injected peers. Although insurers are beginning to cover FluMist, many consumers are simply opting for the cheaper shot from one of its competitors instead.
  • Fluarix and FluLaval Quadrivalent: Perhaps one of the more exciting new vaccines developed by GlaxoSmithKline (GSK -0.03%), Fluarix was the first intramuscular quadrivalent vaccine approved in the U.S., in December 2012, so it essentially set the standard. All told, Glaxo is expected to supply 10 million doses of Fluarix quadrivalent this year, as well as 22 million to 24 million doses of its trivalent vaccine. Fluarix is approved for treatment in those age 3 and up. FluLaval was the second-best grossing vaccine during last year's flu season (an estimated $375 million in sales), even though it's approved to treat only adults, age 18 and up. Similar to Fluarix, FluLaval will also be available in a quadrivalent form for the 2013-2014 flu season.
  • Fluzone: Developed by Sanofi (SNY 0.52%), Fluzone is by and far the most successful flu vaccine by sales, bringing in an estimated $1.25 billion last year alone. Part of that has to do with its vaccination approval range, which begins in patients as young as 6 months old. Sanofi also developed an intradermal patch with a needle that's 90% shorter than traditional needles, which allows for the vaccine to be injected directly into the skin instead of the patients' muscle, thus reducing injection-site discomfort. And if that doesn't give Fluzone a big enough advantage, it also comes in six separate dosages, adding to its acclaim. Like its peers, Sanofi, too, will be launching a quadrivalent version of its Fluzone vaccine this year.
  • Fluvirin and Flucelvax: Novartis' (NVS -1.02%) Fluvirin was a big winner last year, selling an estimated $359 million in flu vaccines (third best among flu vaccines), and seeing a sizable increase over the 2011-2012 flu season. Novartis began shipping its vaccine in the U.S. just one month ago and plans to ship a minimum of 30 million doses this year (which is expected, since it shipped 36 million last year). Fluvirin is the more popular of the two, given that it's approved for children as young as 4, while Flucelvax is approved only for adults, 18 and older.
  • Tamiflu: Originally developed by Gilead Sciences but licensed globally to Roche (RHHBY -0.18%), Tamiflu is a medication designed to reduce the severity of the flu should you contract it. Since it's on the "essential medications" list of numerous governments around the world, Roche has racked up sizable sales for Tamiflu, but it's also come under fire within the past year for not disclosing safety data on the medication. It's also currently being investigated by the European Medicines Agency
  • Relenza: Also developed by GlaxoSmithKline, Relenza is a medication given to patients who have contracted the flu that works by stopping the influenza virus from replicating in your body. It's not a substitute for the flu vaccine but could theoretically stop you from contracting the virus if you took it just before the point of where you would have contracted the virus. It's approved in children ages 7 and up, but has been used as a flu-prevention tool in children as young as 5. 

I have money and I want to invest in flu vaccine makers. What's my best bet?
Because the flu virus changes each year, one company could be wildly successful one year and fall flat on its face the next, so investing becomes a bit tricky.

One thing for certain is that Roche's Tamiflu doesn't appear like a safe bet, with its safety and efficacy in question overseas. AstraZeneca's FluMist also isn't very inspiring, with its higher costs consistently driving patients to cheaper options.

That really leaves Novartis, Sanofi, and GlaxoSmithKline as the investable options in this space. Glaxo is obviously intriguing for becoming the first quadrivalent vaccine to reach approval. However, since other vaccine makers will also have quadrivalent vaccines on the market this year, that advantage quickly evaporated. I believe Sanofi still remains the most intriguing way to play flu season. Sanofi's Fluzone has the widest vaccination range when it comes to age, comes in more dosages than its peers, and even has a transdermal patch that cancels out the need to ever use AstraZeneca's FluMist, since it drastically reduces injection-site pain.

Foolish roundup
I hope this gives you a better understanding of what flu season entails, what you can expect this season, and what your best investment opportunities might be in this space. With less than half of Americans getting a flu shot annually, there is a wide moat of opportunity for growth in this sector, so I think it bears your full attention as a patient and investor moving forward.