10/7/16: FLU VACCINES: A Friend Suffers Misery After a Shot; I Launch an Investigation

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I was going to get my 92-year-old mother vaccinated against the flu this week until I heard from my 73-year-old friend “Rebecca” that she became very ill after receiving her seasonal shot.

Like Mom, Rebecca gets annual influenza vaccinations and has never had an adverse reaction. Not only did she experience nausea, vomiting, a sore throat, and chills, but she suffered intense pain at her injection site for days—also a first.

You can’t get the flu from a vaccine, but sometimes your reaction to the “cure” can rival the virus for misery.

Typically, I defer to my local pharmacist, whom I have known for years and respect and trust, on flu vaccines. “Linda” comes out to the car to give Mom her shot, saving us the wear-and-tear of wheelchair transport. This year, however, because of Rebecca’s response, I decided to study up before I talk to her.

Linda gave Rebecca her flu shot.

According to a recent New England Journal of Medicine article on influenza vaccination and the U.S. Centers for Disease Control and Prevention’s website, there are 11 different influenza vaccines available in the United States. Two of them are designed specifically for immune-weakened elders, whom the CDC and all public-health agencies consider anyone 65 and older, even though the health disparities among 65-, 75-, 85-, and 95-year-olds are vast.* And, I discovered, one of the two over-65 vaccines, which have “kickers” to boost immunization, is NEW this year.

A-HA! Never go with anything new from a pharmaceutical company unless you have no other choice. My late genius clinical-pharmacologist father, who discovered his share of new drugs, taught me that. Wait until millions of others have tried it first. Clinical trials enroll only thousands, at most. Until a drug—or vaccine—reaches millions, you won’t know how it will adversely affect people.

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CDC Vaccine Recommendations

Of the 11 available influenza vaccines, 10 are delivered by injection, i.e., by shot. Of those, nine are intramuscular, and the 10th is intradermal. Intradermal injections go in only under the skin, not into the muscle.

These vaccines differ by components, preparation, and manufacturer, the heavy hitters in the vaccine industry being Sanofi Pasteur and Novartis (Seqirus). The 11th vaccine is administered by nasal spray.

For the 2016-17 season, the CDC recommends all 10 flu shots, nine of which are inactivated influenza vaccines (IIV), and the other of which is a recombinant influenza vaccine (RIV). The CDC, which relies upon its Advisory Committee on Immunization Practices (ACIP) for expertise, does not recommend one specific flu vaccine over another, although many of them have age indications and have not been FDA-approved for young children. Fluzone intradermal, for example, is an IIV4 manufactured by Sanofi Pasteur that the U.S. Food & Drug Admin. has approved only for people between ages 18 and 64 because of its lesser intensity.

This flu season the CDC decided not to endorse the nasal-spray vaccine, an Astra Zeneca product that is a relatively new live attenuated influenza vaccine (LAIV) called FluMist, because of “troubling results of recent effectiveness studies,” according to Dr. John J. Treanor of the University of Rochester medical school in the 9/29/16 NEJM article, “Influenza Vaccination,” at http://www.nejm.org/doi/full/10.1056/NEJMcp1512870?query=aging-geriatrics.

If you’d like to read the details underlying the CDC’s decision to withdraw its support from FluMist, as well as its review of the other flu vaccines, see http://www.cdc.gov/mmwr/volumes/65/rr/rr6505a1.htm?s_cid=rr6505a1_w#B1_down.

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Vaccine Basics

The vaccines that immunize you from viruses come from the viruses themselves. (If you don’t know the story of how the smallpox vaccine, the first-ever vaccine, was discovered, look it up!) The first flu vaccine, an IIV3, was marketed in 1977.

All of the current inactivated influenza vaccines are produced in a growth of flu viruses subtypes A and B in embryonated hen’s eggs, hence the concern about delivering them to people who have an egg allergy.

The IIV3s have three viral components: (A)H1N1 virus, (A)H3N2 virus, and an influenza B virus, either By or Bv. The IIV4s contain the two A viruses and both of the influenza B viruses, and, thus, are formulated from four components. The former are known as trivalent (three) formulations, the latter as quadrivalent (four) formations. FluMist debuted as a trivalent formulation and is now quadrivalent (LAIV4).

I could tell you the preparation/manufacturing steps whereby an inactivated virus vaccine results from a laboratory growth, but I’d have to extensively quote Dr. Treanor’s New England Journal of Medicine article, which you can read on your own if you’re interested. I think it’s more useful to know that, according to the CDC, direct evidence of enhanced protection from an IIV4, as compared with an IIV3, is lacking.

Another fundamental of vaccines is that the ability of a particular vaccine to immunize you and, therefore, to prevent the flu, varies from year to year depending on how the vaccine matches up against the circulating viruses. Public-health networks in the United States and elsewhere monitor the effectiveness of each year’s vaccines. As you no doubt have learned, sometimes the efficacy percentage dips: A significant percentage of immunized people still get the flu.

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Vaccines for Elders

The two influenza vaccines designed for people 65 and over are Fluzone high dose, a dose-intensive IIV3 made by Sanofi Pasteur, and FLUAD™, a new IIV3 with adjuvant made by Seqirus. Older people are presumed, collectively, to have more chronic medical conditions that put them at a higher risk of severe flu illness than do those who are younger, but they nonetheless may opt for a standard-dose IIV3, of which there are two. There also are three standard-dose IIV4s.

Fluzone high dose contains four times the amount of antigen contained in a standard-dose injection. Antigens are target substances on viruses, bacteria, and other foreign invaders outside of your cells that prompt your body to make antibodies. The added antigen in Fluzone high dose is designed to trigger a stronger immune response. Whether it actually leads to greater protection than a standard-dose flu vaccine is a topic of ongoing research. From what I’ve read, the boost in effectiveness is not that great.

FLUAD, which the FDA approved in November 2015, is the first adjuvanted seasonal flu vaccine ever marketed in this country. It received initial approval in Italy in 1997. FLUAD stands for flu vaccine with adjuvant.

An adjuvant, as you might surmise, is an ingredient added to a vaccine to create a stronger immune response. The standard-dose FLUAD, which has a milky white appearance, contains MF59 adjuvant, an oil-in-water emulsion of squalene oil. (See the CDC link above for more details. I stopped with squalene oil.) According to the CDC, no studies have been done yet comparing the effectiveness of FLUAD with Fluzone high dose.

The package insert for FLUAD, which the FDA provides online, reports on a multicenter study of adverse reactions to FLUAD by 3,545 recipients ages 65 to 97, who live in the USA, Panama, Colombia, or the Philippines. Their mean age (average) was 72.

Twenty-five percent of the FLUAD recipients suffered injection-site pain, but only 0.3 percent overall had pain severe enough to interfere with normal daily activities, like Rebecca did. Fourteen-point-seven percent of the recipients had myalgia (muscle pain), and 13.3 percent experienced fatigue. Other percentages by symptom included: 13.2, headache; 8.5, arthralgia (joint pain); 6.7, chills; 4.8, diarrhea; 3.6, fever; nausea, 2.9; and 1.4, vomiting.

Researchers compared the adverse reactions in the FLUAD treatment group with the adverse reactions among a group of 3,537 recipients, ages 65-to-97, who took Agriflu, a standard-dose IIV4, instead. I think it would have been more instructive to compare the FLUAD group with a Fluzone-high dose group, but that comparison is lacking.

A far greater percentage of FLUAD recipients suffered pain and tenderness at their injection sites than the percentage of Agriflu recipients who did. In fact, the percentage of FLUAD group members who experienced a specific adverse reaction was greater than the percentage of Agriflu group members for every symptom, except vomiting. The package insert does not break down the adverse reactions by the age, health status, or any other pertinent characteristic of the recipients. This information may have been in the FDA application, but I doubt it.

Remember, these are just thousands of people, not millions.

My mother lives at home, not in a nursing home or other chronic-care facility, and is not exposed to many people. She has never had a problem with a flu vaccine—no allergic or adverse reactions. I would be heartsick if she suffered extreme pain or became ill after receiving one. I see now that I have been neglectful in not recording the type of vaccine that she has received, so I would have a history to consult.

I can see no reason why anyone would risk a FLUAD vaccine, despite its apparent success in other parts of the world, but I’ll be sure to ask Linda if she knows of any advantages and if she gave Rebecca a FLUAD shot. I’ll let you know what she says. My hunch is her answer will have more to do with vaccine economics than with vaccine safety. (I was wrong. See my followup on 10/11/16 at http://www.facebook.com/anngsjoerdsmaauthor/.)

Ann, 10/7/16

*I discuss the progressive immune deterioration that occurs with aging—also known as immune senescence—in “The Aging Body” chapter of my book, Our Parents in Crisis: Confronting Medial Errors, Ageist Doctors, and Other Healthcare Failings. According to my Merck Manual of Geriatrics, “Immune senescence leads to an appropriate, inefficient, and sometimes detrimental immune response.” But everyone is different. The healthier and more physically fit an elder is, the better his or her aged immune system will perform.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

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