Measles


How to structure your Report

Divide up your research to answer the following questions:

Virology and Immunology

  1. What is the Measles Virus

  2. How does the Measles Virus infect the human body

  3. What is the immune response

  4. How does the immune response and the Virus manifest as illness

  5. Why don't you get sick a second time

  6. How does the Vaccine work

Epidemiology

  1. Who, Where, When, Why

  2. Reproductive number, Mortality, Morbidity

  3. Government Response

Sociology

  1. Anti-Vax movement - what evidence do they base their claims on

  2. Anti-anti-Vax

You

  1. Your position, with a recommendation for action

References

These are the Best Three References for this Internal Assessment

Click on the Youtube clip on the right of the screen to below to get the best overview of Measles available on Youtube (1). Click on the link to the left of the screen to get a written overview of Measles from Nature Reviews, Disease Primers (2). Its called a primer because it primes your knowledge.

It is important for this research assessment that you use Vancouver referencing, as seen in this paragraph. Nowadays, most references will include an Available from link to a website (3). Remember to only include references that you actually use in the body of your article. The numbers used at the end of a sentence refer to the number in your reference list. The reader can then go to that reference link, click or copy it, then they can delve deeper and learn more. You can also find webpages or apps that will create the citation for you once they have the url, just click past all of the advertisements (4, 5).

References

  1. Kurzgesagt - In a Nutshell. Measles Explained - Vaccinate or Not? [cited 18/06/2021]. Available from: https://www.youtube.com/watch?v=y0opgc1WoS4

  2. Rota PA, Moss WJ, Takeda M. et al. Measles [Internet]. Nature News. Nature Publishing Group; 2016 [cited 2021 Jun 17]. Available from: https://www.nature.com/articles/nrdp201649

  3. Laksono BM, de Vries RD, McQuaid S, Duprex WP, de Swart RL. Measles Virus Host Invasion and Pathogenesis [Internet]. Viruses. MDPI; 2016 [cited 2021Jun18]. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997572/

  4. The University of Auckland. ReferenCite - Quick©ite - Vancouver - Webpage [Internet]. Cite.auckland.ac.nz. 2021 [cited 17 June 2021]. Available from: https://www.cite.auckland.ac.nz/2_6_5.html

  5. Save Time and Improve your Marks with CiteThisForMe, The No. 1 Citation Tool [Internet]. Cite This For Me. 2021 [cited 17 June 2021]. Available from: https://www.citethisforme.com/vancouver

  6. Choose your source [Internet]. Citation Machine, a Chegg service. [cited 2021Jun17]. Available from: https://www.citationmachine.net/vancouver

Virology and Immunology

Question 1 and 2: What is the Measles Virus and How does it infect the body

The Measles virus is an RNA virus that infects humans

As a virus, it can not replicate without a host

The key host cells are immune cells and epithelial cells

  • Epithelial cells are the outside cells of the body, they are skin cells, but are also found lining the gastrointestinal tract and the lungs

As an RNA virus, Measles does not need to enter the nucleus of a cell. Rather, it simply needs to get in

This video shows a Virus, but not Measles. However, it shows the roll of the Viral Surface Proteins, also known as Spike proteins

Measles has two spike proteins

  1. Hemagglutinin - binds to SLAM

  2. Fusion protein - allows the virus membrane to merge with the host cell membrane

On the diagram above

(a) - The virus assembled

(b) - the individual proteins of the virus - note the color matching and the letters next to the names. Also see that there are 6 proteins.

(c) shows the genes on the RNA - there are 6 genes coding for 6 proteins. As shown in (b) the 6 proteins have letters next to the words, these correlate for the genes in the RNA - so Matrix protein is M gene

  • note that the Phosphoprotein is made from 3 smaller proteins (polypeptides) joining together. This is shown on the gene as P, V and C.

  • In the Live virus, the gene for C is missing - so it has a very hard time replicating

Notice the SLAM receptor - this is the Signalling Lymphocyte Activation Factor, this receptor allows the Lymphocytes to signal each other to increase their activity, however, the Measles virus has evolved so that its Hemagglutinin protein will bind to SLAM

The steps involved in entering a cell are as follows:

  1. virus is floating in the liquid outside of the cells

  2. Hemagglutinin binds to a receptor (SLAM (CD150) or Nectin-4)

  3. Hemagglutinin holds the MV in place while the Fusion Protein fuses the virus membrane with the cell membrane

  4. The RNA contents and RNA polymerase spill into the cytoplasm of the cell

  5. RNA replication and Protein synthesis can begin

What happens next?

  1. New virus RNA is made by RNA polymerase

  2. New virus protein is made by ribosomes in the Endoplasmic reticulum

  3. New virus proteins are modified in the Golgi

  4. Virus proteins and RNA assemble near cell membrane

  5. Virus buds off from the cell membrane (lysogenic budding)

  6. When levels of Virus production by the cell are high, other functions of the cell are decommissioned, causing the cell to die

The Measles Virus (MV) consists of the following parts

  1. RNA - the genetic instructions for making more MV

  2. Hemagglutinin - this is a protein that sticks out from the MV capsule, like a big Key, it will bind to any 'locks' that match it (also spelt Haemagglutinin) It is one of the two spike proteins

  3. Fusion protein - this allows the MV into a cell once Hemagglutinin has bound it to a cell. This is the other spike protein

  4. The virus also has a protein coat underneath its phospholipid bilayer (cell membrane) called the Matrix protein

  5. There are also two other proteins called: Phosphoprotein and Large protein - these work together to replicate the RNA once in a cell - they work together to from the RNA-dependent RNA polymerase - this is found in viruses and is used once inside a host cell to make copies of the RNA. The phosphoprotein gene consists of three parts: P, V and C. the C part is missing in the recombinant live virus vaccine, so the virus, though still 'alive' can not replicate well, this gives more time for the immune systems B cells to figure out how to make antibodies against it

Measles Virus (MeV) replication cycle is shown below. In order to infect a cell, MeV binds to its entry receptors on the cell surface (SLAM) (1) and initiates the virus-cell membrane fusion using the Fusion protein (2). Virus and cell membranes fusion leads to genome delivery into the cytoplasm (3).

Viral RNA is transcribed in mRNA (4) by RNA dependent RNA polymerase. This is further translated into viral proteins (5). Viral glycoproteins maturate during their transport to the cell surface (6). The replication of positive stranded anti-genomic RNA starts in the cytoplasm (7) and serves as a template for synthesis of new negative stranded genomic RNA (8).

Viral proteins assemble at the cell surface, leading either to budding of new virions (9) or cell-to-cell fusion (10).

The haemagglutinin (H) protein binds to the SLAM receptor at the cell surface, allowing the triggering of fusion (F) which reaches a stable conformation. Then, Fusion protein (F) anchors in the target cell membrane, F undergoes shape changes bringing the two membranes close enough to merge and form a pore throughout which the viral RNA is delivered to the cytoplasm.

At step 6 above, the viral proteins are in the cell membrane, here is a chance for the antigen to be presented to T-cells, that will then kill this cell. Notice also the cell to cell spreading

The image below shows the structure of the virus, along with its replication and budding in an immune cell. Note that CD150 is the same as SLAM - its the same receptor but with two different names (Cluster of Differentiation 150)

The Youtube clip below outlines Viral replication in a human cell - However, the virus is not measles, rather it is a DNA virus, so it is slightly different, but the general process is similar - click on the 'watch on YouTube' link

Question 3: The Immune Response

Police officer

Does the day to day work

Macrophage

Detectives

Search for clues for hard to fight cases

Dendritic cells

Armed Offender Squad

Kill the offender that the detectives tell it to kill

T-Cells (Thymus Lymphocyte Cells)

Drone Operator

Drones find and crash into the offender or the places where the offender is hiding

Drone Operator = B-Cells (Bone lymphocyte Cells)

Drones = Antibodies

Below is a really good clip covering some of the key players in the immune system - if you only watch one clip, watch this one

The Key players in the Immune Response to Measles are:

  1. Macrophages

  2. Dendritic Cells

  3. T - Cells

  4. B - Cells

Macrophage chasing then phagocytosing a bacteria

A series of Youtube clips showing the activity of the immune system, you'll have to open each on Youtube due to their privacy settings.

Macrophages

  • The police on patrol

  • Mainly eat Bacteria (phagocytosis)

  • Innate immune system - always ready and looking for action

  • Can eat viruses, but have a harder time finding them as they are so small

Dendritic Cells

  • The Detectives - take clues

  • Link Innate and Adaptive Immune system

  • Innate means always ready, adaptive means it changes to new problems

  • Take antigens to the T and B cells

T-Cells

  • Armed Offenders Squad snipers

  • Adaptive immune system - needs to be told what to hunt

  • Once armed with the clue (antigen), they will make a receptor that is the opposite shape to the antigen, they then leave the thymus and will kill any cells that it meets that have the antigen

B-Cells

  • Drone Operators

  • Adaptive immune system - needs to be told what antibodies to make

  • Antibodies made via guess and check - so it takes time - the closer an existing antibody is to matching with the new antigen, the shorter the time taken for guess and check

  • Stay in the Bone marrow, but make antibodies that will bind to the antigen

  • Antibodies = drones

    • stick to the antigens stopping them from working

    • flag the antigen so that it can be spotted by the macrophages for phagocytosis and destruction

SLAM - Signaling Lymphocyte Activation Molecule

  • this is used by Macrophages and Dendritic cells to tell the Lymphocytes (T and B Cells) to that they need to increase their level of activation

Question 4: How does the immune response and the Virus manifest as illness

The measles virus enters the body through the lungs

It then uses the SLAM receptor on Macrophages and Dendritic cells to enter the immune cells and start replicating

The Dendritic cells take some of the Measles virus antigens to the Thymus and to the Bone Marrow, for the T-cells and B-cells. Unfortunately it is also carrying live virus inside of it

The virus bursts out of the Dendritic cells in the Thymus and the Bone Marrow and starts to infect the T-cells and B-cells

As the infection overwhelms individual cells, they die

Because the T-cells and B-cells are dying - antibody and adaptive immune memory of old illnesses like chicken pox decreases, as the cells that made the antibodies for chicken pox die as well, along with cells that made antibodies for the flu, the cold, and cells that had the memory of various bacteria. This 'immune amnesia, makes it a lot easier for the person to get sick with something else at the same time. They are also more likely to get sick with something that they were previously immune to if they are exposed within the few months after recovering from measles

Ultimately, enough of the Measles Virus antigens are presented to the remaining B-cells for the correct antibody to finally be made and the war starts to tip in favor of the human.

Once an antibody is stuck on the outside of the virus, it can no longer enter cells

Also, if an antibody sticks to an infected cell, then it will be targeted for destruction by the Macrophages

T-cells also figure out what the antigen looks like, and whenever they find the antigen on the outside of an infected cell, they kill the cell

Ultimately the person recovers

Question 4.2. Symptoms

The symptoms of Measles include a Fever, a Cough and a Rash

  1. Fever

    1. A Fever is caused by a signal from your immune cells to your brain. The brain will increase your body temperature from the normal 37.5 degrees celcius to 39 degrees. It does this by instructing the cells of the body to burn more fuel, whilst also surpressing your cooling responses. The brain will also tell you that you feel cold, although you are actually hotter than normal. So your behavoral response will be to wrap up warm and hop into bed.

    2. Tiredness - the immune system will also tell your brain to make you sleepy - this is so that you are less likely to go to people and catch other illnesses from them, you are also less likely to go hunting and get cuts with more bacteria. Because you are tired, you'll stay in bed, allowing the immune system to just combat the current enemy. It also allows your body to maintain an energy focus on keeping you feverish. Rather than running and hunting and all of the body responses this requires, your body is focused on lying in bed and fighting the infection

  2. Cough

    1. Because the infection started in the lungs, this is where a lot of the action is taking place. As immune cells flood the area, they cause more liquid to enter the aveoli, or air-sacks. This liquide will capture any bacteria, dust and viruses. This liquid needs to leave the lungs, so you cough it up then you usually swallow the liquid mucus.

  3. Rash

    1. Not only can the Hemagglutinin spike protein on the Measles virus enter immune cells via binding to SLAM, it can also bind to Nectin- 4. Nectin 4 is found on the surface of epithelial cells. Epithelial cells are the 'outside' cells. So, they are found in your lungs and nose. Your mouth and digestive track. And your skin.

    2. Infected Dendritic cells and T cells accidently take the virus to near the epithelial cells. The virus then buds out of the Dendritic cells and T cells and binds to the Nectin-4 receptor, its Fusion protein then binds to the cell membrane. The two membranes merge and the virus enters the cell.

    3. The healthy immune cells detect the measles virus antigen on the membrane of the epithelial cells and try to kill these cells - though they are not very good at finding the right cells at first.

    4. As the healthy immune cells search for the infected cells the blood capillaries near the epithelium swell up to let more immune cells in. This also lets more red blood cells in. This causes the skin inside the mouth first, to become blotchy with a bumpy rash. This then spreads to the face and eventually to the whole body.

Pathology of measles. Measles Virus starts its infection via SLAM entry into Macrophages and Dendritic Cells in the lung.

After initial replication in regional lymph nodes, Measles Virus enters the bloodstream and subsequently spreads to all lymphoid organs, such as the spleen, thymus, appendix, tonsil, and lymph nodes, throughout the body.

When the Measles Virus infection of the lymphoid organs reaches its peak, Measles Virus -infected immune cells transfer Measles Virus to epithelial cells. Measles Virus uses Nectin-4 found on epithelial cells as a receptor to bind to.

Question 5: Why don't you catch the measles virus again? - Immunity

Ultimately Once a person has had the measles, they will never get it again, as they will always have some T-cells that are looking for the Measles antigen. They will also have some B-cells that will produce small amounts of the anti-measles Antibody.

If the measles virus is detected by the body again, the Antigen Presenting Cells (APC) that are the Dendritic cells will present the antigen to the T-cells and B-cells. Because the the B-cell are already making the correct antibody for this antigen, they will quickly ramp up production of this antibody to stop the Measles virus from spreading. While the T-cells will quickly divide, creating an Armed offender squad that will kill any infected cells


Question 6: How does the Vaccine work?

The measles vaccine was created over 50 years ago. You can see a video discussing its creation and showing the lead Scientist in the clip to the below

The measles vaccine contains a live virus. This live measles virus is a little bit different. It still has hemagglutinin and fusion spike proteins. So it still has what the immune system will notice as antigens. Indeed it is these spike proteins that the immune system will create antibodies against, thus giving you immunity. So why do you not get sick from this live virus (not you can still get a little bit sick, with a short fever and a bit of a run down feeling. Sometimes even a slight, temporary rash. But all of these weak measles symptoms are because you have a weakened measles virus, and they all disappear as your antibody production ramps up. But, why don't you get sick?

The reasons is the RNA dependent RNA polymerase.

In all of the measles vaccines, including the common Edmonston-Enders Strain or Attenuvax used in MMR combination vaccine, there are small changes (attenuations) or mutations in all of the genes.

All of the vaccines have a changes (mutations) in the P/V/C genes that make up the RNA dependent RNA polymerase.

'Amino acid substitutions detected in the P gene included a change shared by all of the vaccines at position 225' (1)

The RNA dependent RNA polymerase still works, but it is much, much slower. Because it is so much slower at making the RNA for the virus, your immune system has more of a chance of making the antibodies soon enough to stop the virus from spreading.

Its like fighting the zombies from Walking dead, rather than the zombies from I am Legend. Slower is easier to fight

Because the recombinant or attenuated measles vaccine is still a live vaccine, it can not be given to people who are immuno-compromised. As they will still not be able to make enough antibodies, so they will actually develop measles. To keep these people safe, we need heard immunity, where 93% of the population is immunized.


  1. Parks C, Lerch R, Walpita P, Wang H, Sidhu M, Udem S. Comparison of Predicted Amino Acid Sequences of Measles Virus Strains in the Edmonston Vaccine Lineage. Journal of Virology. 2001;75(2):910-920. Accessible via: 10.1128/JVI.75.2.910-920.2001



Look at the incredible effectiveness of the Measles vaccine. From a rolling average of half a million people contracting Measles per year in the USA, the cases dropped to a few thousand within the first couple of years of the roll out of the vaccine. It continued to drop to near zero.

Notice also the smaller graph, showing the recent rise in Measles, why is this?

Not seeing anything above? Reauthenticate

Epidemiology

Question 7, 8 and 9

Question 7 - Who, when, where, why

The most common demographic affected by measles are children under the age of 10.

Under the age of 1, the children are protected by antibodies passed through breast milk. After 1 they are usually eating solid foods.

The kids are in playschool, daycare and kindergarten. Then they go to primary school. In these environments large numbers of children interact and can easily pass the virus amongst each other


Question 8 - Reproductive number, Mortality and Morbidity

Measles has an R value of 12, this means that for every person that catches measles, they will pass it on to 12 other people

Question 9 - Government Response

  1. Free MMR vaccine

  2. Lock down of schools when a case is detected - as seen at Manurewa High School



Question 10: The Anti-Vax movement

People are naturally cautious about injecting things into their bodies and the bodies of their children

If a child develops an illness, we look for causes. If the cause is ourselves, we don't like that, so we find external agents to blame.

There is a rise in the levels of autism worldwide. Currently the thinking is that this is due to earlier and more sensitive detection of autism symptoms than their used to be.

In the case of the Anti-vax movement, a Doctor that was paid to find a link so that pharmaceutical companies could be sued. However, it turns out that his link was fraudulent. Nonetheless, the doubt that he has caused in the minds of parents has resulted in thousands of children not being immunized. This has caused a rise in the cases of measles.

The 60 minutes YouTube clip below is a very, very good resource for supporting the Anti-Vax movement. - Watch it!


Remember for Excellence

Report comprehensively involves: refining a given or agreed question or purpose identifying multiple links between the biological ideas that are related to the question or purpose collecting and processing primary or secondary data and/or information from a range of sources evaluating sources of information/data in respect to the question or purpose identifying at least two different points of view supported by evidence taking and justifying a position on the issue with a recommendation for action presenting findings.

The original article by Dr Wakefield (no longer a doctor as was struck off the medical register due to fraud)

Wakefield’s article linking MMR vaccine and autism was fraudulentClear evidence of falsification of data should now close the door on this damaging vaccine scare “Science is at once the most questioning and . . . sceptical of activities and also the most trusting,” said Arnold Relman, former editor of the New England Journal of Medicine , in 1989. “It is intensely sceptical about the possibility of error, but totally trusting about the possibility of fraud.”1 Never has this been truer than of the 1998 Lancet paper that implied a link between the measles, mumps, and rubella (MMR) vaccine and a “new syndrome” of autism and bowel disease.⇓ Authored by Andrew Wakefield and 12 others, the paper’s scientific limitations were clear when it appeared in 1998.2 3 As the ensuing vaccine scare took off, critics quickly pointed out that the paper was a small case series with no controls, linked three common conditions, and relied on parental recall and beliefs.4 Over the following decade, epidemiological studies consistently found no evidence of a link between the MMR vaccine and autism.5 6 7 8 By the time the paper was finally retracted 12 years later,9 after forensic dissection at the General Medical Council’s (GMC) longest ever fitness to practise hearing,10 few people could deny that it was fatally flawed both scientifically and ethically. But it has taken the diligent scepticism of one man, standing outside medicine and science, to show that the paper was in fact an elaborate fraud. In a series of articles starting this week, and seven years after first looking into the MMR scare, journalist Brian Deer now shows the extent of Wakefield’s fraud and how it was perpetrated (doi:10.1136/bmj.c5347). Drawing on interviews, documents, and data made public at the GMC hearings, Deer shows how Wakefield altered …

Autism

Autism is a range of disorders that range from barely noticeable to significant.

They come above due to the development of the brain. And they affect communication and social skills (1).

https://www.cdc.gov/ncbddd/autism/facts.html

1. Basics About Autism Spectrum Disorder (ASD) | NCBDDD | CDC [Internet]. Centers for Disease Control and Prevention. 2021 [cited 20 June 2021]. Available from: https://www.cdc.gov/ncbddd/autism/facts.html

The leading risk factors for the diagnosis of Autism are as follows:

  1. Better detection

    1. The tools to diagnose Autism are more sensitive and are used in schools rather than being left to just the most extreme cases

  2. Genetics

    1. Genetic predisposition to developing Autism - a family history of autism spectrum disorders increases the risk

  3. Older parents

    1. Maternal age strongly correlates with risk

    2. Paternal age also correlates with risk

  4. Unknown environmental factor

    1. it is likely that their is a third player in the environment, what this is though is currently unknown.

Question 11: Anti - Anti-Vax movement (aka Pro-Vax)

The clips below show that damage that the Anti-vax movement has caused

Many news agency's have moved towards counteracting the anti-vaccine propaganda. This could be seen as their social conscience. This is also seen in Facebook, as Facebook is now actively targeting fake news.

However, like all organisations, money comes first. So, should a Fake news story generate clicks, then they could still push it. So always be suspicious.

Some of the international Science push back against the anti-vax movement

Newshubs reporting into the Antivax Propaganda pamphlet

You

Question 12: Your Opinion, Your Recommendation

What is your position, your opinion.

What is your recommendation

Should the Measles Vaccine be part of New Zealands National Immunization Schedule?

Yes/ No - Why?????? (back up your opinion by referring to your earlier research)


Let me know if there is anything else to be added to this web-page to help people with their Internal assessment. Cheers, Mr Cowley.