Andrew Leubitz, DO, MBA
Good Samaritan Hospital Medical Center

Influenza in the Emergency Department:

It happens at least once per shift, sometimes it seems like every other patient presents this way… a new patient pops up on the board, a 20 or 30-something year old who’s chief compliant is “everything hurts.” It’s January and you already have a good idea of what’s going on.  “Doc I feel terrible, it started all of the sudden a 3 days ago. I have a fever, chills, I’m nauseous… I just feel miserable.” Casting a wide differential, you order labs, start IV fluids. Of course, your flu swab comes back positive. When you inquire about vaccination status, “I don’t believe in getting the flu shot, it never works. Just a way for big pharma to get rich…” You have to fight the urge to argue with him because you have 10 other patients to see and you just finished talking to a anti-vaxxer mom, without success, about the importance of antibiotics for her child’s complicated pneumonia.. His labs, chest x-ray, come back normal, the power of normal saline and ondansetron win again and he is feeling better. As you prepare to discharge him with a diagnosis of influenza A, he asks for a prescription for “The tamiflu pill I saw on TV, and an antibiotic.” You explain antibiotics are ineffective for the flu, and he is outside the window for Tamiflu.  You encourage hydration and rest, prescribe oral ondansetron for his nausea. As he is leaving he asks for a work note for the next couple days.

This cycle of influenza in otherwise healthy people had me thinking over this flu season.  Influenza can affect people in a wide spectrum and there is definitely a time and patient populations where hospital treatment for influenza is appropriate, however I cannot help but to think, “Why are all of these people not getting the flu shot.” With the focus of the anti-vaxxer movement becoming popularized by a subset of people who transformed legitimate personal questions of vaccination hesitancy, into a malignant form of one of the worst public health debacles in the 21st century. It seems that we are so busy fighting for people to just simply get their children the vaccinations they need, that we do not have the mental energy to argue with them when talking about their reasons not to get their annual influenza vaccination.  My question is simply Why not? and What would the next flu season look like if heard immunity took place and we had a majority of people vaccinated against the next strain of influenza.

The Stats:

Come late October, early November, Emergency Department’s across the country prepare themselves, we know that with winter, ‘Influenza is coming.’ The true incidence of influenza cases reported annually is difficult to calculate due to the wide spectrum of disease, reporting models, and number of patients who seek medical care, however the CDC does a reliable estimate of the burden of influenza in the population.  In the 2017-2018 season, an estimated 48.8 million people, about 15% of the population, in the United States contracted influenza, 22.7 million went to a health care provider, 959,000 were hospitalized and 79,416 died from complications due to influenza, including 618 pediatric patients.1

Most people who contract the flu know it.  They feel miserable. The have the classic fever, chills, body aches, and there is not enough chicken noodle soup in the world to warm them up.  That might be rough enough on a patient alone, but according to NIOSH, in the United States alone, employees miss approximately 17 million work days and over $7 billion a year due to influenza.2 Surprisingly, only an estimate of a mere 37.1% of adults received the influenza vaccination annually, half of what the Healthy People 2020 model states is needed for effective prevention of the flu.3  The goal of a 70% US adult vaccination rate estimates a reduction of roughly 2 million cases of influenza annually.3

What is it about the influenza vaccination that so many people just cannot seem to get on board with?

Flu Vaccination:

The influenza virus is an 8-segmented, single stranded RNA orthomyxovirus, containing two major surface glycoproteins, hemagglutinin (HA) and neuraminidase (NA).3 This “Step-1” science jargon is extremely important and is what separates the flu shot from vaccinations like the MMR or Tdap vaccinations.  The fact that the virus is a segmented virus is why we have to keep tell our patients to get an annual ‘flu shot’ because those segments are constantly changing and certain strains will hit different geographic areas harder and at different times of the 16-week average influenza season.5

In order for vaccination producers to make the ‘right vaccination’ and enough supply, data is constantly collected and reviewed by the WHO and the FDA who decide, based on surveillance data, which mix of three or four influenza viruses subtypes are likely to be most prevalent for the next year. The WHO relies on influenza research from 5 WHO centers located in Atlanta, London, Melbourne, Tokyo, and Beijing.  In February, each year, the WHO takes the data and reports a recommendation for specific viruses for inclusion, then each country makes their final recommendations. In the United States, the FDA’s advisory committee makes the final decision- manufactures have approximately 6-months to ramp up vaccination production, be it in chicken eggs or in cell cultures.6

Marketing of the Flu Vaccination:

To many patients, it sounds like through our best efforts, we are still playing a game of ‘whack a mole’ with influenza every year.  Unlike other pediatric vaccinations, the effectiveness of the seasonal influenza vaccination fluctuates yearly. From a mere10% effectiveness in 2004-05 to 60% in the 2010-11 season. 7   With these statistics in mind, our patients, who expects a magic pill to cure their disease, it is no wonder that people are skeptical of getting an annual shot that may or may not actually help them prevent the flu. Why go through the hassle?

It is simply very hard to prove a negative and to change the minds of a concrete thinking patient who says to you, and these are real things patients have said to me, “Vaccines contain aborted fetuses., Vaccines do not work., Vaccines can cause paralysis., And of course, I don’t want to hurt my child with a shot.”

It has been 100 years since the 1918 Spanish Flu pandemic, which affected one third of the global population, killing 20-50 million people including approximately 675,000 Americans.8,9 So many people forget how catastrophic influenza can be.

While I do not have the answer to the question of why the flu vaccination is deemed less important than others, one theory is found in an economics 101 book. In our efforts to make the flu shot more widely available, by having it advertised everywhere from your primary care doctor’s office, to the corner drug store, the grocery store, and even in the office breakroom, we as the public health community, have lowered its value in the perceptions of our patients.  This is known as the scarcity principle- low supply equals higher demand, and the reverse, high supply, lower demand and thus a perception of less importance. It is possible that the solution to make this life saving public health miracle more available, has actually hurt its own cause?

On a side note but related economic interest, the 2019-2020 cost per influenza vaccination is between $16-24, and it is usually free to the patient depending on their insurance.9

An Update in Treatment for Influenza:

For years, oseltamivir, or the brand name, “Tamiflu” a neuraminidase inhibitor and approved by the FDA in 1999, was the only game in town.  In a 2014 systematic review of the drug, in adults, the drug reduced time of symptoms by an average of 16.7 hours and in children, it reduced the time of symptoms by an average of 29 hours.10  The limitations unfortunately are that it is only shown to be meaningfully effective if taking within the first 48 hours of symptoms. However, there was a concern for many patients with significant side effects of increased nausea, vomiting, headaches, and neuropsychiatric symptoms. 10,11 The price of the drug is also not in the generic $4 list that we try to use with antibiotics if we can, because, like it or not, for our patients, price is often the limiting factor on whether the pick up their prescription.  Per GoodRx, the price of oseltamivir ranges from $48.88-126.74 depending on retailer, insurance, and coupon code.

The new kid in town, Baloxavir Marboxil is in its phase 3 trail, or CAPSTONE-1 trail and was recently featured in the New England Journal of Medicine.  The trail is showing that the viral count of influenza in the baloxavir population went to zero approximately 48 hours faster when compared to the oseltamivir population.  Additionally, symptomatic relief of influenza was decreased by about 24 hours in the baloxavir group compared to the standard oseltamivir group.12 It will be interesting to see hope the third phase of the trail turns out and if the side effect profile can be improved.  

Final Thoughts:

Influenza will continue to be a headline disease in the Emergency Department come every winter. While it is appropriate for most patients to be discharged with a prescription for a day or two of rest and their grandmother’s chicken noodle soup, there is a significant number of patients who antiviral therapy is appropriate and should be discussed with shared medical decision making.  

The current and upcoming influenza antivirals on the market are far from perfect, guidelines are changing but currently it is still recommended that only those presenting within 48 hours should be prescribed the drugs and even then, they still have significant side-effect profiles.

The best thing we can do for our patients is to try and encourage disease prevention with vaccinations.  Whether that be working with public health departments to push for vaccination programs, administration of the flu vaccination in the ED in the months leading up to flu season, or just talking about disease prevention in the discharge instructions can all be potential plans to help alleviate the burden of disease from influenza on your community and Emergency Department come next flu season.

Figure 1: Seasonal Influenza Vaccine Effectiveness, 2004-2018, Centers for Disease Control and Prevention

Citations:

  1. “Influenza (Flu).” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 18 Dec. 2018, www.cdc.gov/flu/about/burden/2017-2018.htm#table1.
  2. “CDC – Seasonal Influenza (Flu) in the Workplace – NIOSH Activities – NIOSH Workplace Safety and Health Topic.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, www.cdc.gov/niosh/topics/flu/activities.html.
  3. “2 Million More Flu Cases Could Be Avoided by Hitting National Target.” Healio, April 17, 2018. www.healio.com/infectious-disease/influenza/news/online/{afee050d-cae8-4c61-ae78-8d357b760f32}/2-million-more-flu-cases-could-be-avoided-by-hitting-national-target.
  4. Gao, Qinshan, et al. “A Seven-Segmented Influenza A Virus Expressing the Influenza C Virus Glycoprotein HEF.” Journal of Virology, American Society for Microbiology Journals, 1 July 2008, jvi.asm.org/content/82/13/6419.
  5.  “Influenza Picking Up Speed Across US.” Medscape, 31 Dec. 2018, www.medscape.com/viewarticle/907108?nlid=126950_1361&src=WNL_mdplsnews_190104_mscpedit_emed&uac=214678BR&spon=45&impID=1852145&faf=1.
  6. “Influenza (Flu).” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 4 Sept. 2018, www.cdc.gov/flu/about/season/vaccine-selection.htm.
  7. “Influenza (Flu).” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 8 Mar. 2019, www.cdc.gov/flu/professionals/vaccination/effectiveness-studies.htm.
  8. “Spanish Flu.” History.com, A&E Television Networks, 12 Oct. 2010, www.history.com/topics/world-war-i/1918-flu-pandemic.
  9. “Remembering the 1918 Influenza Pandemic | Features | CDC.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, www.cdc.gov/features/1918-flu-pandemic/index.html.
  10. “Vaccines for Children Program (VFC).” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 1 Mar. 2019, www.cdc.gov/vaccines/programs/vfc/awardees/vaccine-management/price-list/index.html.
  11.  Jefferson T et al. Oseltamivir for Influenza in Adults and Children: Systematic Review of Clinical Study Reports and Summary of Regulatory Comments. BMJ 2014. PMID: 24811411
  12. Rezaie, Salim. “The Tamiflu Debacle.” REBEL EM – Emergency Medicine Blog, 24 Oct. 2018, rebelem.com/the-tamiflu-debacle/.
  13. “Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents | NEJM.” New England Journal of Medicine, www.nejm.org/doi/full/10.1056/NEJMoa1716197.