Monday, November 2, 2009

Swine Flu Anxiety

While in the midst of an epidemic, a great deal of anxiety arises in the population.

Anxiety can lead to an exaggerated or inaccurate perception of risk, particularly when the mass anxiety is spread in the media, such as via front-page accounts of unexpected deaths.

In approaching any type of anxiety, I think it is important to know exactly what the risks are.

So, for example, it would be dishonest to tell an airplane-phobic person that air travel is perfectly safe. It isn't: there is about a 1 in 1 million chance of the plane crashing. (In a future post, I'd like to present my analysis of the statistics, and also show that the average spontaneous death rate in the population, for a person beyond young adulthood, exceeds the death rate from flying in an airplane--therefore I could claim--flippantly--that flying is statistically a "life-prolonging activity" for most travelers).

The current flu epidemic is clearly a serious matter. There definitely is a risk of death for those infected.

Estimates I've seen of the mortality rate vary, but the prevailing opinion seems to be that it is less than 0.1% (1 in 1000) for those infected.

This is not particularly different from the mortality rate of ordinary seasonal flu.

HOWEVER, the significant difference in this epidemic is the mortality rate by age. It is clearly true that swine flu has a higher mortality rate for healthy young adults--probably at least triple-- compared to seasonal flu.

Therefore, we are seeing more young, healthy adults die of flu this year. The total numbers are very low, but are much higher than in other years. The reason the overall mortality rate is the same is that fewer elderly individuals are dying of swine flu, most likely because of heightened immunity in that population due to exposure to a similar virus decades ago.

The CDC site shows that in a cohort of 268 people who died from swine flu early in the epidemic, 39% were in the 25-49 age group, and 25% were in the 50-64 age group. This is very different from seasonal influenza, in which about 90% of the deaths are in the over 65 age group. Here's a link to a pertinent page from their site:

Here's another important page from the CDC:

Based on the table shown on this page, here are estimated risks of death for individuals infected with H1N1, stratified by age:
0-17 age group: between 1 in 10 000 and 1 in 20 000.
18-64 age group: between 1 in 2400 and 1 in 6000.
65+ age group: between 1 in 2300 and 1 in 6800.

I found a table of age-standardized "excess deaths" due to pneumonia and influenza in Italy between 1969-2001. ( Based on this table, and assuming that only 10% of the population is infected during typical seasonal flu years, here is a very rough estimate of the risks of death by age for seasonal flu:
0-44 age group: 1 in 100 000
45-64 age group: 1 in 20 000
65+ age group: 1 in 750

The above data show that H1N1 influenza has a substantially higher death rate for those under 65 compared to seasonal flu, but as you can see the chances of dying if you catch the flu are still quite low, regardless of your age.

The risk of flu vaccines appears to be extremely low.
There is a substantial risk of contracting flu without the vaccine.
There is a low but non-zero risk of severe illness or death if you contract the flu.
The risk of a severe adverse reaction to the vaccine is much lower than the risk of a severe adverse effect from the flu itself.
The vaccine is likely to reduce the risk of contracting the flu by at least 90%.
Therefore, the benefit:risk ratio regarding the flu vaccine is very favourable. Here are references:

So, my recommendations regarding swine flu anxiety are to be informed about the most accurate facts available:

1) the risk of death or severe illness remains low, for anyone infected

2) but the risk of a healthy young adult becoming severely ill or dying is relatively higher compared to seasonal flu

3) public health measures, such as very careful hygiene and mass vaccinations, are likely to save many lives (this is true of seasonal flu as well). Statistically, you as an individual are unlikely to contract severe flu illness. Hygiene and vaccine recommendations are more likely to be part of reducing the spread of flu in the population: therefore such recommendations, if you follow them, are statistically more likely to spare severe disease in someone else, rather than yourself. That is, if you receive a vaccination, that vaccination is more likely to save someone else's life rather than your own, since the average active case of flu is likely to spread to about 2 other people, even if the case is mild.

4) Therefore, I encourage following hygiene protocols and receiving the vaccine when it becomes available. It may spare you severe illness, and it has an even higher likelihood of being an altruistic act, which spares other people severe illness. Prompt use of anti-influenza medications such as Tamiflu are likely to further reduce the risk of severe complications, and most likely will further reduce the risk of contagion.

Altruistic acts, such as getting vaccinated or washing your hands, are psychologically healthy (this is my justification for posting something about influenza in a psychiatry blog!).

*It may be important to keep in mind, for the sake of perspective, that automobile accidents, for example, claim about 600 000 lives per year among young, healthy adults. In Canada alone, there are about 1000 deaths of young, healthy adults per year due to car accidents. (reference: Another altruistic act of very practical importance is to slow down on the road!

A good article in the November 10, 2009 edition of CMAJ (p. 667-668) presents evidence that handwashing is not actually likely to be very effective in reducing the spread of influenza. Microbiologist Dr. Donald Low argues that hand hygiene has not been proven to reduce influenza spread, and that the influenza virus is primarily spread by fine droplets from coughing, which then have to be inhaled deeply. He points out that receptors for the influenza virus are located farther back in the respiratory tract, hence cannot be easily infected by touching mouth or eyes with hands, etc.
Here is an excellent article on the subject:

His evidence-based position is that the N95 mask is the best mechanical way to prevent infection if you are near an infected person. Other than that, the best practice to prevent contagion would be to contain any coughing or sneezing, to stay away from other people if you are coughing, and to avoid close proximity with those who are infected, if possible.

Meanwhile, it is undoubtedly true that good handwashing practices do reduce the spread of the common cold and other infectious diseases. So all the handwashing and hand-sanitizing stations you see all over the place remain a good idea -- it's just that handwashing might not actually protect you very much from contracting influenza, compared to other measures.


Anonymous said...

Very interesting analysis.

This may be a dumb question, but does getting a vaccine mean you will not get the flu virus in you at all, or that if you get the virus inside you your body has the means to quickly fight it off.

If the latter...isn't it still possible to pass it to, and subsequently harm, someone else who isn't vaccinated?

GK said...

An immunologist or infectious disease specialist could give a more authoritative answer, but here is my nutshell response to your question:

Immunity results in your body quickly "digesting" the relevant pathogen, in this case influenza viruses. There are also various locations of immune response, some of which prevent viral entry to deeper structures of the body, and some of which take care of any pathogens which make it past the first barrier. So there is a reduced likelihood of the flu virus "getting into you", but even if some viruses do make it inside, your body would quickly "fight them off."

In an immunized individual exposed to the infection, flu viruses would not have a chance to complete their life cycles within the body, and would not have a chance to multiply and spread. Even if the immunization is not perfectly effective, and an immunized person still gets the flu, it is probable that there would be reduced viral populations, and reduced risk of contagion.

Therefore, if you are vaccinated, there is a substantially reduced risk of subsequently harming someone else who isn't vaccinated, unless you are simply a mechanical vector (i.e. you have some flu viruses on unwashed hands which you picked up from a doorknob, etc., or if someone else has sneezed on your coat, etc. and you end up spreading the virus that way).

Anonymous said...

What a great entry. Thank you so so much for this!!

Anonymous said...

Part 1

I have been wanted to write some more information on H1N1 vaccine for people who are interesting in the vaccine, the virus and immunology in general. I have taken a few courses in this area, have interest, and have access to scientific literature but I am by no means an expert. I have tried to collect and organize credible information in this piece ranging from Internet sources and published journals to course notes and acquired knowledge and am confident that the majority of the information presented is credible.

I do not claim authorship or ownership of these ideas and/or studies… hence the anonymous nature of this information.

These types of viruses are RNA viruses from the Orthomyxovirida family and are usually the most virulent. Influenza type A has the most antigenic shift and drift. Antigenic drift is the accumulation of different RNA mutations. Antigenic shift or re-assortment occurs when two different strains of influenza combine to form a new strain subtype.

Symptoms include fever, muscle pains, severe weakness, nausea and vomiting.
These viruses are highly contagious acute respiratory diseases transmitted via saliva, blood…etc.

H1N1 falls in this category.

It was influenza of the H1N1 subtype that caused the Spanish Flu in 1918-20, which killed up to 40-100milion people. Approximately 500 million people were infected which was equivalent to about 1/3 of the population at that time. The infection rate was about 50% and was particularly rare because if affected young adults (20-40 years old). Normally the Influenza virus affects the very young, the very old, or the immunologically suppressed individual. This is the same trend we are seeing with 2009 H1N1.

Please keep in mind that the high number of deaths occurred in 1918-20. Since then our knowledge in virology and infectious disease has increased tremendously in parallel to the advancement of modern technology (i.e. electron microscopes). Just to give you a time reference, it wasn’t until 1935 that the first virus structure was crystallized and observed through an electron microscope.

The genome is composed of eight segments of single-stranded RNA which contain genetic elements form North American Swine Influenza, North American Avian Influenza, Human Influenza and a Eurasian Swine Influenza

This virus is “decorated” with two surface glycoproteins called HA, due to its hemagglutinin activity, and NA, due to it’s to neuraminidase activity. Therefore H1N1 virus has the first classified hemagglutinin protein (H1) and the first classified neuraminidase protein (N1).
When dealing with the H1N1 virus and vaccine production, an emphasis has been placed on the HA component as a target for vaccination. There are two main functions of HA. The first is to bind to sialic- acid (a specific chemical structure containing nitrogen and oxygen atoms) containing receptors present on upper respiratory tract cells, allowing virus entry. Sialic- acid containing receptors are also present on human erythrocytes, called red blood cells (RBCs), and leads to hemagglutination (clumping of RBCs). This relationship can be used to determine viral concentrations in blood samples using Viral Hemagglutination Assay.

The second function of HA to facilitate the fusion of the host (in this case human) endosomal membrane with the viral membrane. Basically, when the virus binds to the outside of a human cell, the human cell membrane will, invaginate, encompass and ingest the virus. This process is called endocytosis and results in the virus being surrounded by an intact “bubble” of human membrane (endosomal membrane) while inside the human cell. However HA will disrupt this “bubble” of human membrane and the virus membrane, to allow the internal components of the virus to infiltrate the inside of the human cell. Once the internal components of the virus enter the inside of a human cell, the virus takes over the cell and the cellular machinery in order to replicate itself.

Anonymous said...

Part 2

As GK alluded to, there are numerous anatomical (skin and mucous membranes) and physiological (temperature, pH, and chemical mediators) barriers to virus entry. These will not be discussed but if anyone is interested I will be happy to provide more information.

I am going to focus on cell mediated (mainly B-cells and T-cells) adaptive immunity, or the specific immune response to the entry of a specific virus/ antigen into the body. (This means the innate (anatomical and physiological barriers) have failed, which would happen if you had a laceration in your skin, for example.)

1) Upon the first exposure to an antigen or virus, a B cell is “activated” by the presentation of an antigen (i.e. the HA epitope) on the surface on an antigen presenting cell (i.e. dendritic cells).

Antigen presenting cells are kind of like the “Cookie Monster” from Sesame Street or “Pac Man.” Antigen presenting cells are cells that phagocytose (which is just a subtype of endocytosis) viruses and degrade them into pieces. These pieces can then bind to a Major Histocompatibility Complex (MHC) to be displayed on the surface of the antigen-presenting cell. In other words, antigen presenting cells display what types of material they been “degrading and digesting” to other immune cells. If the material is foreign to the body, this will mount an immune response, if not, there will be no response.

The B-cell is activated by this antigen presentation and by other co-stimulatory signals (specifically cytokines which are chemical messengers) coming from other immune cells (specifically T-helper cells). This activation results in a couple of immunological events discussed below.

2) After the activation step the B-cell creates an antibody for the specific antigen and then undergoes massive replication.

2A) Some of these B-cells turn into plasma cells, which create and secrete anti-bodies (or specific proteins that recognize the epitope of the virus). (Note: this epitope is the same epitope that was presented by the antigen-presenting cell.) The main function of an antibody is to “tag” foreign material, such as viruses in the body, and act as a signal to other immune cells to destroy the foreign material it is bound to.

After a B-cell has produced and secreted antibodies it will usually die. However, a few of these plasma cells are “long lived” and can be stored in our bone marrow.

2B) On the other hand some of these replicating B-cells turn into memory B-cells. These cells do not produce antibodies but can recognize the same viral epitopes. This becomes very important in a subsequent exposure of the body to the virus.

They also contain the information relevant to produce the specific anti-body that was used in the prior exposure to eradicate the virus. These cells remain in circulation for long periods of time. However not all last a lifetime and therefore “booster” vaccinations are given.

From this information, if the virus invades again, memory B-cells replicate into more plasma cells and more memory cells at an increased rate. The response is so fast that many times an individual will not experience viral symptoms. The magnitude of the response is also more robust. The concentration of antibodies is higher in the second response than the first response.

To give a general comparison it takes about 10 days after antigen exposure to reach maximum antibody concentration for the first exposure but only about 5 days to reach maximum antibody concentration for the second exposure. (Note that the maximum antibody concentration for the second exposure is about 2 times greater than the maximum antibody concentration of the first exposure and I am referring to these concentrations above. It takes less than 5 days, during the second exposure, to reach the maximum concentration of antibodies produced in first exposure.)

This difference is mainly due to the “lag time” the body needs to create antibodies that are specific to the virus, during the first exposure.

Anonymous said...

Part 3-
Differences in antibody concentration and time to reach maximum antibody concentration put an individual at risk for developing viral symptoms. In some individuals these symptoms can progress rapidly and severely.

In short, the main purpose of vaccination is to expose the immune system to viral components of the specific virus, for which you want to develop immunity towards.

The influenza vaccine is an inactivated virus. It is “killed” via the use of heat or chemicals (such as formaldehyde).

Advantages of this type of vaccine:
-It is safe, stable and easy to store.

Disadvantages of this type of vaccine:
-The virus cannot replicate. This leads to a shorter immune response and often requires boosters. This may also decrease the cell-mediated response (i.e. the B and T cell response).
-There are dangers associated with manufacturing because live pathogens must be handled.
-If the virus is denatured by heat, sometimes epitopes are destroyed. (However the H1N1 vaccine was not produced in this way).
-The vaccine must be administered via injection, which may be inconvenient.

Two Kinds- A and B

A) Produced by GlaxoSmithKline- called Arepanrix
(AS03‐adjuvanted H1N1 pandemic influenza vaccine)

(I heard from someone who attended an AAPS (American Association of Pharmaceutical Scientists) conference that GSK is one of the few pharmaceutical companies that have survived the economic crisis in the past few years…. I wonder why.)

It has two components:

A1) Antigen component (as a suspension)

This consists of the H1N1 immunizing antigen, based on the influenza virus strain A, found in California in July 2009. This is the officially recommended strain by the WHO for the manufacture of vaccines during the current influenza pandemic.

The H1N1 antigen is an inactivated, purified, detergent split, monovalent virus propagated in eggs.

Basically the federal government or regulating body prepares a virus reference stock to manufacturers who then incorporate the HA and NA genetic components (which will be transcribed and translated into the HA and NA epitopes) into a different high yielding virus strains. Because wild-type flu viruses grow poorly, genetic material from the reference stock is re-assorted into a more stable, faster growing, and higher yielding virus strain. This is done by injecting both different virus strains into egg cells and allowing the virus to replicate and re-arrange genetic material so that you end up with numerous hybrids of both viruses. (People with egg allergies should be very cautious when getting vaccinations due to the possible presence of residual egg proteins.

The virus that has genes for the HA and NA markers of the H1N1 (i.e. H1N1 epitopes) flu virus and genes for the internal proteins of the high-yield donor virus will be selected for through the use of selective antibodies and selective yield rates. (Antibodies selectively bind to different surface markers and therefore allow the researcher to determine what viral HA and NA surface markers are present and the faster replicating viruses will have the internal proteins of the donor strain.)

More information:

Once this live virus is selected, it is purified and inactivated (or killed by heat or chemicals, such at formaldehyde). The H1N1 vaccine is a split virus vaccine. This means the selected virus was exposed to organic solvents and detergents leaving only the viral structural proteins (i.e.: HA and NA) and portions of the viral membrane. These are the viral parts for which your body makes specific antibodies.

In this way the vaccine is enriched with HA and NA and contain merely residual internal structural proteins of the donor virus.

Anonymous said...

Part 4-

The actual component of this vaccine only has the haemagglutinin (HA) component specific for the H1N1 virus in any measurable amount. This vaccine is called mono- or uni-valent because it only provides protection from one virus strain unlike other vaccines (called di- tri- poly- or multivalent) which can provide protect again numerous viruses, due to numerous HA and/or NA components from different viruses. However, it is thought that the most robust immune response is established through monovalent vaccines.

More information:
Guidance Document on the Use of Pandemic Influenza A (H1N1) 2009 Inactivated Monovalent Vaccine:

A2) An adjuvant

Adjuvants are substances, when mixed with the antigen and injected with it, enhances the immunogenicity of that antigen and therefore increases the ability to evoke a specific immune response.

A commonly used antigen is Freund’s water-in oil adjuvant, which is basically an oil and water emulsion with (complete) or without (incomplete) the killed antigen. Therefore, this would be classified as a complete adjuvant vaccine.

The purpose of an adjuvant is to enhance the immune response while using a significantly lower antigen dose. It may also broaden the immune response and provide some cross protection again virus drift. It also decreases the use of antigen preserving agents like (Thimerosal—discussed below)

It is also cheaper and easier for companies to produce more vaccines from the same amount of stock virus therefore making more money and profit. After all vaccine profits are HUGE! Apparently it will be costing the government about 400 million dollars just to purchase enough vaccinations for Canada.

B) The second version of the vaccine is the non-adjuvanted formulation also produced by GSK. It is very similar to the one described above.

Both formulations are produced in a similar manner to the production of seasonal vaccine.

Other ingredients: Thimerosal (preservative), Squalene (naturally occurring oil), DL-α-tocopherol (vitamin E oil), Polysorbate 80 (nonionic surfactant and emulsifier often used in foods) and trace amounts of egg proteins, formaldehyde, sodium deoxycholoate and sucrose.

A note on Formaldehyde:

Formaldehyde is used to kill the virus and most of the residual amount is extracted or filtered out. The amount that is left is less than the amount that is naturally occurring in our bodies. One source I found says that the amount of formaldehyde in five scheduled vaccinations is less than that made by a 12-pound infant make in one day. Also the formaldehyde in vaccines (given intramuscularly) usually cross-link with proteins before it can enter the blood stream.

Here I would like to invoke the words of Paracelsus, referred to as the father of toxicology. He said:
"All things are poison and nothing is without poison, only the dose permits something not to be poisonous."

More information on Formaldehyde:

Anonymous said...

Part 5 (The last part)

A note on Squalene:

Squalene was suspected for causing health problems in Gulf War Veterans who received an anthrax vaccine with Squalene. One report suggested that individuals developed squalene antibodies, which subsequently caused disabilities. However there was no Squalene in the vaccine and the claims have now been refuted.

Squalene is used in many commercial products and cosmetics.

More information on Squalene:

A note on Thimerosal:

Thimerosal is used as a preservative in vaccines.
Thimerosal is a mercury-containing organic compound (an organomercurial). Because it contains mercury a controversy developed around the correlation between Thimerosal exposure and the development of autism. However, most of the research looking at this correlation arose from epidemiological studies, which can be misleading and confusing due to numerous confounding variables.

Different organomercurial substances can be metabolized into ethyl mercury or methyl mercury. Methyl mercury is the substance related to more severe health implications. However, Thimerosal is metabolized into ethyl mercury, which is rarely associated with health problems and better handled by the body.

Two of the results I found on Thimerosal and autism:

When a suspected link between autism and mercury arose around 1999-2000, there was a lot of effort to either completely eliminate or decrease the amount of Thimerosal in vaccines.

At this time the amount of Thimerosal in the adjuvant vaccine is 5 micrograms and 50 micrograms in the non-adjuvant vaccine. BOTH amounts remain within the daily limit recommended for environmental exposure to mercury. Both of which are less than that found in a can of tuna.

However, if there is still concern about this issue it may be useful evaluate susceptibility to autism in your child.

Children who are genetically or biologically susceptible may react differently to different environmental toxins.

At the same time you also have to weigh these effects and the effects of contracting the H1N1 virus.

A good discussion with a family physician may be the best way to evaluate the data so you can make an informed decision.

Here are just a few sources on Thimerosal and H1N1 vaccine:


Indirect protection by vaccinating one group to reduce exposure to another group is called HERD PROTECTION (as was indicated by GK).

An example of this would be to vaccinate school children.
School children are constant introducers of the virus into the household and should be considered as targets for the vaccine as they have the most impact on the community.

Although cute, cuddly, warm, delightful, beautiful gifts…young children are incubuses of viral plague! Watch out!


(P.S. I did this in a word document and had to send it in pieces. It is supposed to be read from part 1 continuously to part 5)

GK said...

Well, "Anonymous," thank you for the essay; you obviously have a good fund of knowledge to share, and your comments themselves are altruistic, articulate acts, of benefit to others as well as to yourself. Keep it up!