Influenza

Question 1

Why should we be careful not to treat colds with antibiotics?

Answer 1

Colds will be beaten by the immune system within a few days. By giving antibiotics this is just allowing any bacteria in the system to become familiar and therefore evolve and become resistant to the drug.

Note: we are now entering a period where we must come up with new drugs as we are running out of antibiotics that people aren’t resistant to due to mis-prescirbing.

Question 2

What even is flu and how is it transmitted?

Answer 2

The flu (Influenza) is a contagious virus that affects the respiratory tract.

It is transmitted via droplets (eg when someone sneezes or coughs and a droplet lands on your mouth of nose). Hence because it is spread in this way it is important to stay away from people with the flu.

Question 3

What does it mean by saying that flu is ‘Ubiquitous’?

Answer 3

It is found everywhere and affects many people every year (espesh winter).

Question 4

What are orthomyxoviridae?

Answer 4

A family of RNA viruses that include Influence A B and C.

Question 5

How is C different from Influenza A and B?

Answer 5

Influenca A and B cause seasonal outbreaks of flu but C does not.
Influenza C only causes a mild cold.

Question 6

What is the structure of the influenza virus?

Answer 6

The influenza virion (as the infectious particle is called) is roughly spherical. It is an enveloped virus – that is, the outer layer is a lipid membrane which is taken from the host cell in which the virus multiplies. Inserted into the lipid membrane are ‘spikes’, which are proteins – actually glycoproteins, because they consist of protein linked to sugars – known as HA (hemagglutinin) and NA (neuraminidase). These are the proteins that determine the subtype of influenza virus (A/H1N1, for example). We’ll discuss later how the HA and NA are given subtype numbers. The HA and NA are important in the immune response against the virus; antibodies (proteins made by us to combat infection) against these spikes may protect against infection. The NA protein is the target of the antiviral drugs Relenza and Tamiflu. Also embedded in the lipid membrane is the M2 protein, which is the target of the antiviral adamantanes – amantadine and rimantadine.

Question 7

How are subtypes of influenza viruses determined?

Answer 7

By the type of glycoproteins on the surface (haemaglutinin and neurominidase)
There are 15 different HA subtypes and 9 different NA subtypes. Many different combinations of HA
and NA proteins are possible.

Question 8

What is the difference between influenza “type”, “subtypes” and “strains”?

Answer 8

Type = Influenza A, B or C

Subtype = only influenza A can be broken down into subtypes and this is determined by the type of Hameoglutinin and Neurominidase on the viral surface. Influenza B and C both only have one subtype and hence are not classified in this way

Strain = different strains appear in the Influenza B virus and the different subtypes of Influenza A. This is due to antigenic drift (a slow change or adaptation of what the virus presents on its cells surface - therefore as new strains appear the cells cannot recognise the antigens on the virus.

Question 9

What do each of the Influenza viruses infect?

Answer 9

A = birds (and humans which are an accidental host)
B = only humans
C = humans and pigs

Question 10

How is Influenza A and B named?

Answer 10

A = example
A/H1N1/New Zealand/2016

B = example
B/New Zealand/2016

Question 11

What is the difference between an epidemic and a pandemic and why does only Influenza A cause pandemics?

Answer 11

Epidemic = a disease that spreads rapidly among many people in a community at the same time. (eg within 2 weeks)

Pandemic = a global disease outbreak. (en epidemic that spreads globally) It is determined by how the disease spreads, not how many deaths it causes.

When a new influenza A virus emerges, a flu pandemic can occur. Because the virus is new, the human population has little to no immunity against it. The virus spreads quickly from person-to-person worldwide. Influenza B dosent have any subtypes and so it cannot cause a pandemic.

Question 12

What is hemaglutinin/what does it allow the Influenza virus to do?

Answer 12

It is a glycoprotein found on the surface of the virus that allows it to bind to cells with sialic acid on the membrane (eg cells in the upper respiratory tract) and allows their entry into the cell.

Question 13

What is neuraminidase/what does it allow the influenza virus to do?

Answer 13

A glycoprotein enzyme found on the surface of the virus that cleaves Hemaglutinin from the sialic acid to allow the virus to exit the cell and move to invade and replicate in another cell.

Question 14

What is the M2 protein found on the surface of Influenza cells?

Answer 14

It is an ion channel

Question 15

What does it mean by Influenza being “seasonal”?

Answer 15

The Influenza virus only circulates in winter (in temperate zones of the world) and so people will only be diagnosed with flu during 6-8 weeks of the year.

This illness generally lasts for 5-6 days and is an infection of the respiratory epithelium.

Question 16

If someone said they had the flu in the summer, would that be true?

Answer 16

No, influenza is seasonal so unless they just got off a plane from somewhere else in the world, the Influenza virus wouldnt be circulating in NZ summer.

Question 17

The recovery to seasonal flu is by the bodies immune system and once the body has been infected once it is immune to that virus. So how can someone be infected with flu a few years later?

Answer 17

Due to antigenic drift: (minor changes in the antigens)

This process occurs continuously in Influenza A and B

The virus (in particular the hemaglutinin) evolves over many years and after considerable mutation the immune system will no longer recognise it and the antibodies (IgA - which protects mucous membranes) will not bind to them therefore allowing entry of the virus particles into the cell. (this is called a new strain)

However closely related strains may still be recognised and partially blocked by the immune system. (resulting in minor illness/mild symptoms)

Question 18

On average how often will a child and how often will an adult be infected with Influenza?

Answer 18

Child = 3rd-4th winter
Adult = every 10th winter 

(because a childs immune system hasnt been exposed to as many antigens)

Question 19

When are the symptoms at their worst/when do people feel their worst after infection of Influenza?

Answer 19

About day 2 after infection. This is because this is when the spread of the virus in the body is at its peak and also at this stage the lymphocytes are releasing their cytokines which cause the symptoms of flu.

Question 20

What is a popular drug used to lessen the symptoms of flu?

Answer 20

A neurominidase inhibitor. This will mean the virus particles arent cleaved from the sialic acid on their exit and so they will remain stuck to the cell they are in and will be unable to spread to other cells.

eg Oseltamivir

Question 21

What is the difference between antigenic drift and shift?

Answer 21

How Influenza Viruses Change: Drift and Shift
Influenza viruses can change in two different ways.

One type is called “antigenic drift,” which occurs through small changes in the virus that happen
continually over time. Antigenic drift produces new virus strains that may not be recognized by antibodies
to earlier influenza strains. This process works as follows: a person infected with a particular flu virus strain
develops antibody against that virus. As newer virus strains appear, the antibodies against the older
strains no longer recognize the “newer” virus, and infection with a new strain can occur. This is one of the
main reasons why people can get the flu more than one time. In most years, one or two of the three virus
strains in the influenza vaccine are updated to keep up with the changes in the circulating flu viruses. For
this reason, people who want to be immunized against influenza need to receive a flu vaccination every
year.

The other type of change is called “antigenic shift.” Antigenic shift is an abrupt, major change in the
influenza A viruses, resulting in a new influenza virus that can infect humans and has a hemagglutinin
protein or hemagglutinin and neuraminidase protein combination that has not been seen in humans for
many years. Antigenic shift results in a new influenza A subtype. If a new subtype of influenza A virus is
introduced into the human population, if most people have little or no protection against the new virus, and
if the virus can spread easily from person to person, a pandemic (worldwide spread) may occur (see
Influenza Pandemics).

Influenza viruses are changing by antigenic drift all the time, but antigenic shift happens only occasionally.
Influenza type A viruses undergo both kinds of changes; influenza type B viruses change only by the more
gradual process of antigenic drift.

Question 22

What does efficacy mean?

Answer 22

The ability to produce a desired result.

Question 23

Why is it necessary to get an annual flu vaccine?

Answer 23

Due to antigenic drift the strain that prevails in each seasonal epidemic of the flu may change. Therefore WHO monitors what strain is infecting people each year and update the vaccine accordingly.

Question 24

What is the current vaccine available?

Answer 24

A trivalent vaccine -

This contains antigen from AH1N1, AH3N2 and an Influenza B virus.

Question 25

What are the two main types of flu vaccines and how are they made?

Answer 25

Trivalent vaccine and Live attenuated vaccine (LAIV)

Trivalent vaccine:

• Most popular
• Given intramuscularily (generally in the deltoid)
• The virus is cultured in chicken eggs and is inactivated by formaldehyde (no active virus in the vaccine). It is then purified and then ‘split’ with detergent which seperates off all of the viral RNA so that you are only left with the viral Hemaglutinin in the injection

LAIV:

• this works well but is less common as it contains the live virus (however this is attenuated meaning that it is such a small dose it wont cause infection).
• It is cold adapted meaning it is only activated in cold temperatures
• It is not killed by formaldehyde and is not split by detergent but it is purified.
• this is delivered as a nasal spray

Question 26

What is the efficacy of the flu vaccine?

Answer 26

About 80-90% effective

Question 27

How does antigenic shift cause pandemics of flu?

Answer 27

Antigenic shift is where there is an abrupt introduction of a new H or N. This can occur if another Influenza A virus leaps from a bird species for example to infect humans (bird flu eg swine flu).

Because these H and N surface proteins have not circulated in humans before then noone is immune. (currently everyone should be immune to AH1N1 and AH3N2).

NOTE: Having had a certain strain of Influenza A before (eg a strain of H1N1) can mean you are partially immune to another strain eg H1N1. But if there are major differences in the H or N glycoproteins then the antibodies to the other H and N will provide no protection.