Mercy Family Practice SC

Influenza

Table of Contents

Introduction

Influenza during the 2015-2016 season came late, and was not as severe as in previous years. This suggests that the addition of H1N1 to the current flu vaccination has worked. Back in 2009, there was a severe outbreak of influenza that came early in the third week of October 2009. In 2009, H1N1 was not included in the flu vaccine. Over subsequent years, the peak has come later and the height of the curve has diminished, indicating that we have gotten more successful at treating Influenza A & B through immunization.[1]

Cost of an Injection

At our clinic, we obtain the quadrivalent influenza vaccine for the wholesale cost of $19.33. We charge $20.00 to cover the cost of shipping. In addition, there is an administrative cost of $26.00 which is often reduced based on insurance coverage. If you take the number of deaths without vaccination (47,851) and subtract the number of deaths at 4 months lead time with vaccination (34,481), you have a difference of 13,370.[2] If you divide the total population (47,851 + 34,481) by the difference (13,370) you have the number needed to treat (NNT), which is 6.16. In other words, you need to immunize 6 people to prevent one death. If you take a conservative cost of around $25 per immunization and multiply by 6.16, you have $153.95. In other words, society has to spend $154 to save a life. By all measures, this is considered cost effective. Therefore, all patients who want a vaccination for influenza A & B should get the quadrivalent vaccination.

Table 1, Influenza Vaccines

VaccineNameManufacturerSourceComponent
Trivalent AdjuvantFluadSeqirusEggH1 H3 Bv
Trivalent HDFluzone HDSanofi PasteurEggH1 H3 Bv
TrivalentAfluriaSeqirusEggH1 H3 Bv
Trivalent SDFluvirinSequirusEggH1 H3 Bv
Quadrvalent recombinantFlublokProtein SciencesHA recombinant proteinH1 H3 Bv
QuadrivalentFlucelvaxSeqirusCell cultureH1 H3 Bv By
Quadrivalent Intra dermalFluzone intra dermalSanofi PasteurEggH1 H3 Bv By
Quadrivalent Live AttenuatedFluMistAstra ZenecaEggH1 H3 Bv By
QuadrivalentFluarixGSKEggH1 H3 Bv By
QuadrivalentFluLavalID BiomedicalEggH1 H3 Bv By
QuadrivalentFluzoneSanofi PasteurEggH1 H3 Bv By

All the above are Standard-Dose unless indicated. HD is High-Dose. At Mercy Family Practice we have Quadrivalent Flucelvax and Fluzone. H1 & H3 are Hemagglutinin antigens, Bv is Hepatitis B Victoria strain, and By is Hepatitis Yamagata strain. Taken from Treanor [6]

Effectiveness of the Influenza Vaccine

The effectiveness from year to year has varied from as low as 30% and as high as 80%, with an average effectiveness ratio of 56%. In recent years, it has been near the 80% mark.[2] The addition of the H1N1 component has increased the effectiveness significantly. The current antigens H1N1 an H3N2 cross react with other antigens and confer immunity to other strains of influenza A. The quadrivalent vaccine includes two strains of Influenza B: Victoria and Yamagata. This makes the current quadrivalent vaccine highly effective.

Timing of the Influenza Vaccine

It is always difficult to know from year to year when the peak will be. In most years it is between the last week of December (week 52) and the first week of March. In generally, you need 4 weeks for your immune system to activate the memory T cells in your bone marrow. The recommendation is to get the flu shot in the last week of September or the first week of October. This will afford you protection from November through March.

Source of Influenza

The first pandemic of influenza was in 1918-1919 just after the outbreak of World War I when it killed approximately 75 million people worldwide. Even today it sill causes about 500,000 deaths worldwide per year.[3] Between 1990 and 1999, there were an average of 36,000 deaths per year in the United States attributed to influenza.[4]

Influenza A is categorized by two antigens: H and N. These antigens are combined, and several common variants are found in nature: H1N1, H3N2, H2N2, N7N9, H10N8, etc. The first two are used in the current quadrivalent influenza vaccine. “H” stands for Hemaglutanin and “N” stands for Neuraminidase. H1N1 caused the pandemic bird flu of 2009. Approximately once or twice a decade, there is a major mutation which causes this combination to change. The CDC in Atlanta is charged with identifying the most common antigens in the United States, and preparing the antigens for the next influenza season. It takes approximately 9 months to produce a new strain of vaccine. In China, many of the peasants live with their chickens and pigs. In the process of slaughtering them and bringing them to market, the humans are cross contaminated with the influenza virus. From there it spreads human to human who often hop on an intercontinental air flight and bring it to the united states. Once in the US and Mexico, the virus can then spread to contaminate poultry and pig populations.

Table 2, The Initial Year of Occurrence for Select Influenza A antigens

StrainYearSourceLocation
H1N1*1918,2009pig (swine)Spanish flu, Swine flu
H2N21889,1956bird (avian)Russian flu, Asian flu
H2N21968bird (avian)Hong Kong flu, China, now extinct
H2N32006pig (swine)US
H3N1pig (swine)
H3N2*1968pig (swine)Fujian flu, China
H5N12003bird (avian)China
H7N11999,2013bird (avian)Bird flu, Italy
H7N22002bird (avian)China
H7N32011bird (avian)Zhejiang, China
H7N72003bird (avian)Netherlands
H7N92013bird (avian)Shanghai & Anhui, China
H9N22013bird (avian)Beijing, China
H10N72004bird (avian)Egypt

* combinations found in the current quadrivalent influenza vaccine

Gillian-Barre Syndrome

In 1976 there were an extremely small percentage of individuals who reacted adversely to influenza vaccination. This included angioedema, anaphylaxis, narcolepsy and Gillian-Barre syndrome. By far the one that got the most attention was the latter. The incidence of all cases was 0.001%, or once case in 1000, and not all cases were severe.[2] Those individuals who develop Gillian-Barre had an ascending paralysis that often creeps up from the extremities to the diaphragm. If it reaches the diaphragm, patients become paralyzed and end up in the ICU on a ventilator. Most cases are reversible, but this often takes several weeks to months to resolve. Of course, 1976 was a very long time ago, and the type of formulation used back then is quite different from the one used today. Techniques are much more refined. There have been no associated cases of Gillian-Barre associated with influenza vaccination in the modern era.

Herd Immunity

If at least 85% of a population is immunized, then this will infer protection against those who cannot be immunized. It is as if an army of protection individuals surround the one who is vulnerable. This is very much true when it comes to Influenza vaccine. If someone sneezes within 15 feet of you, and they are infected with influenza, the virus is suspended in the water droplets and can may their way to your airway. You breath this in and become infected. If those aerosolized air droplets fall upon a counter surface, or if you touch a door knob with an infected hand, it has been shown to stay in place for up to several hours. On porous surfaces such as plastic, the virus can survive in microscopic crevices for up to two days. This is what makes influenza so contagious. Furthermore, the antivirals used to treat influenza are now less effective as the virus learns to become resistant. This makes vaccination the best defense against the infection. Here, prevention is far better than treatment.

High Dose Influenza Vaccine

It has been shown that high-dose (HD) trivalent influenza vaccine improves the antibody response in adults over the age of 65.[5] The standard-dose group had an incidence of 1.4% influenza and the high-dose group had 1.9%. This difference is so small that the number needed to treat (NNT) to avoid one case of influenza would be 438. The wholesale cost of the standard dose is 12.54 and that of the high-dose is 31.91. Given this price difference, it would cost $8,484 to prevent a single case of influenza, and if you have a mortality rate of 10%, this would make the cost of saving a life over $84,000. These values increase once you add in administrative costs.

Due to cost, in 2016-17 Mercy Family Practice has elected to no order the high-dose trivalent influenza vaccine. If you choose to have HD version, you should check with local pharmacies to see if they carry this version.

Nasal Version of Influenza Vaccine

The nasal version of the influenza vaccine is an attenuated virus. It should not be given to people with compromised immune systems, such as those who may be taking chemotherapy. It causes limited replication of the virus in the nasal passages and upper airway and infers an immune response against influenza.

The efficacy is just not there. This year (2016) for the first time it is no longer recommended to use this vaccine.

Egg Allergy

As noted in table 1, if you have an egg allergy, you can get around this by taking the vaccine grown on mammalian cell culture, called Flucelvax from Seqirus. The wholesale cost is around $19.50 which is only slightly above the cost of the egg-grown vaccine which is around $13.50. After an administrative fee, this will come to about $22.00.

Antiviral Therapy

If you contract influenza you may take an antiviral. It should be started within 48 hours from the onset of symptoms. It is even effective if taken as late as 5 days after the start of infection. Meta analysis using 90 observational studies shows that Tamiflu (oseltamivir) is the most effective. The World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) both recommend starting antivirals as soon as possible. They have been shown to reduce hospitalizations and death.[7] If there is an outbreak in a nursing home, often Tamiflu may be used as a prophylactic dosing.

Now there are Tamiflu-resistant strains of H1N1. This is particularly worrisome. There is ongoing testing of a new formulation of zanamivir which has to be given intravenously. It is only available under compationate use. In the meantime, there is ongoing work to find medications that can inhibit the hemagglutinin M gene.

Other antivirals are in use, which include Relanza (zanamivir), which is used as an inhaler, and Rapivab (peramivir) which is administered intravenously. It has been discovered that 0.8% of the isoates of H1N1 and H3N2 are resistant to Tamiflu and Rapivab.[1] If antiviral follow the way of antibiotics, this will only become a growing trend over time. This makes the preventative use of vaccines that more appealing.

Figures

Figure 1, The Peak Incident of Influenza in 2015-2016

Graph of Influenxa Peak
Note: week #10 corresponds to the first week of March 2016. The tall gray shaded area represents Influenza A type H1N1, the most prevalent type. high resolution

Figure 2, The Spread of Influenza A N7N9 from Animal to Human

Image of Animal to Human Transmission
Note: a new strain of Inflenza A, type N7N9 forms through mutation. Humans come in contact with the host animal, a bird in this case. It is then transmitted to the human host. H is for Hemagglutinin and N is for Neuraminidase. high resolution

References

  1. Davlin, Stacy L, et al, Influenza Activity United States, 2015-16 Season and Composition of the 2016-17 Influenza Vaccine, Morbidity and Mortality Weekly Report, June 10, 2016, vol 65(22), pp 21-27.
  2. Khazeni, Nayer, et al, Health and Economic Benefits of Early Vaccination and Nonpharmaceutical Interventions for a Human Influenza A (H7N9) Pandemic, a Modeling Study, Annals of Internal Medicine, 2014; 160: pp 684-694.
  3. Fineberg, Harvey V, Pandemic Preparedness and Response — Lessons from the H1N1 Influenza of 2009, New England Journal of Medicine, 2014, vol 370, pp 1335-42.
  4. DiazGranados, Carols A, et al, New England Journal of Medicine, 2014, vol 371, pp. 635-45.
  5. DiazGranados, Carlos A, et al, Efficacy of High-Dose versus Standard-Dose Influenza Vaccine in Older Adults, New England Journal of Medicine, 2014, 371, pp 635-645.
  6. # Treanor, John J MD, Influenza Vaccination, New England Journal of Medicine, 2016, 375, pp 1261-1268.
  7. Bresee, Joseph MD, Frederick G Hayden MD, Epidemic Influenza — Responding to the Expected but Unpredictable, New England Journal of Medicine, Feb 14, 2013, 368(7) pp 589-592.

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