#28 – Mumps: Why the Vaccine Is Faltering and Cases Are Rising

00:00:06: As mentioned the case fidelity rate, so number of people who die from it is relatively low.

00:00:12: But during their acute phase there can be a lot complications with infections in different organs.

00:00:46: Hello and welcome everybody to this episode of Virological.

00:00:49: This was recorded on August sixteenths of twenty-twenty six In New York.

00:00:55: Today we are going talk about virus that I personally find very interesting.

00:01:01: A little bit scared of it, and that's MAMS virus.

00:01:05: MAMs virus is a baromixovirus.

00:01:07: That means its related to viruses like measles but also baro-influenza virus And...a lot other different viruses including dangerous viruses Like NEPA virus.

00:01:19: This one may be less dangerous in terms of mortality In case fidelity rates But..its not nice virus either.

00:01:29: Like all baromixoviruses, this virus has a minus cent single-stranded RNA genome.

00:01:35: So basically one strand of RNA that has negative polarity.

00:01:41: The genome has about fifteen thousand base pairs or about fifteen thousands letters and it encodes for seven genes And these seven genes can produce nine different proteins.

00:01:55: The V-ray in itself is pleomorphic, which means it's irregular shaped.

00:02:01: It kind of looks actually all perimixoviruses to... ...kindof like a blob?

00:02:07: It's about hundred to six hundred nanometers in diameter So again not very regular shape.

00:02:13: if you look at the virus structure we have the genome there any genome on the inside that protected by the nuclear protein and associated with the polymerase, which is the L- and P-brotein together.

00:02:26: And this is packaged into a lipid envelope.

00:02:29: The Lipid Envelope is stabilized by matrix protein on inside... ...and in the Lipid envelope we have two proteins Two spike proteins One of them called HN Which stands for Hemagglutinin neuraminides And second one it's called F or fusion protein.

00:02:49: What do these proteins, too?

00:02:51: The HN protein binds to the receptor on the cell surface and the receptor in this case is Cialic Acid.

00:02:59: That's a sugar that's attached to proteins And it basically similar to what influenza viruses bind to.

00:03:06: they also bind to Ciali Acid.

00:03:09: Almost all cells have cialic acid on the surface... ...that becomes important later because I will tell you that this virus can infect cells throughout their body.

00:03:19: The second protein on the surface is the F-protein, and again this stands for fusion protein.

00:03:25: And once a particle bound to the cell's surface via the HN protein then the fusion protein inserts part of itself into the membrane of the host cells... ...and then fuses virus membrane in the host cell membrane.

00:03:43: That´s how genome gets inside our cells.

00:03:47: Mumps virus is genetically diverse, there are twelve genotypes.

00:03:52: They're named A to N if you count that it's not twelve.

00:03:57: I think E and M are missing.

00:03:59: they have been misclassified or removed And while the virus is generically diverse It isn't antigenically diverse.

00:04:09: There only one zero type.

00:04:11: That basically means There is a lot of cross-neutralization between the genotypes.

00:04:17: there's no drop in neutralization.

00:04:19: if you get, for example infected with one genotype then your serum neutralizes another Genotype as well As the genotype we got infected with.

00:04:29: so genetically diverse but antigenically not very diverse Mumps virus also has relatively low mutation rate.

00:04:39: Compared to other RNA viruses.

00:04:41: it does mutate and there might be even some antigenic diversity, we'll talk about that in the end but there's not a lot of it.

00:04:51: What is also important to keep in mind is that there are mums like viruses out there in other animals specifically fruit bats in Africa.

00:05:01: That has been more recently described suggests that maybe at some point even MAMS virus, which as you will see is an old human virus jumped from bats to humans in time.

00:05:17: Maybe it was the other way around who knows?

00:05:20: So historically the disease MAMs described very early.

00:05:28: I think first description comes from Chinese physicians about six hundred fifty BC.

00:05:35: Hippocrates also described an outbreak of four hundred ten

00:05:39: B.C.,

00:05:41: so quite old, quite early descriptions and that suggests the virus was in human population for a very long time.

00:05:50: The disease was first scientifically described by British physician Robert Hamilton And then there's also description.

00:06:00: it caused alot issues during World War I. It infected alot soldiers had a negative influence on troops.

00:06:09: And then in nineteen thirty-four mums was identified as viral disease by two gentlemen, Claude D Johnson and Ernest William Goodbasture who worked at Vanderbilt University in Nashville.

00:06:25: what they did is the collected saliva from people who have mums And they filtered in a way that would remove all bacteria.

00:06:36: So, basically then went on and infected Rhesus macaques with the material... ...and the Rhesous macaque got mumps!

00:06:46: That showed this was viral disease because it could pass through a filter which would remove bacteria.

00:06:54: so there wasn't a bacterial disease.

00:06:56: Then did something interesting.

00:06:58: They took materials from these rhesus macaques that had been infected And then with that material, in fact the children to show they would get mumps.

00:07:07: That was the case.

00:07:09: This was in nineteen thirty four.

00:07:11: Of course nowadays this will be completely unethical and nobody do it.

00:07:16: But back than people thought very differently about ethics of these experiments The virus is finally isolated in nineteen forty five Which led to vaccine development and we'll discuss later.

00:07:31: Historically kids would typically get infected with mumps between the ages of five and nine, then they usually will have protection for life.

00:07:43: And in the northern hemisphere these infections usually happened during winter or spring so there was a seasonality to it.

00:07:51: Historically at the case fatality rate – so the modality rate proportionate people who died from mumps were relatively low.

00:08:00: So mums is not a very deadly disease.

00:08:03: I think the historic case fertility rates before vaccination around zero point two to zero point zero three percent.

00:08:11: But as you will see, it's still not an ice disease while obviously It was shown that you can infect macaques with the virus.

00:08:19: Mums is usually human disease.

00:08:21: That means he doesn't have an animal reservoir just infects humans and As mentioned has probably been in the human population for a long time.

00:08:32: So how do people get infected?

00:08:34: Typically contact with respiratory secretions, respiratory droplets of an infected person.

00:08:43: they are not so the number that determines How many people and infected person will go on and infect if they're not vaccinated is four to seven.

00:08:55: In some cases it can go up to twelve.

00:08:58: So that's relatively infectious, it is not as bad as measles which has a very high R naught but its much more infectious than influenza virus for example.

00:09:06: Which has an r-naught of about one point five In terms of infections.

00:09:10: It also needs to be mentioned That people are usually infectious About seven days before they get symptoms And then another seven or eight days after symptom onset.

00:09:21: so People who don't have symptoms yet can transmit Mumps Virus To other people.

00:09:27: There are also asymptomatic cases.

00:09:29: about a third of the infections are asymptomatic, but they can also transmit the virus and pass it on.

00:09:36: Alright so what happens?

00:09:37: You get exposed to respiratory droplets, respiratory secretions.

00:09:42: for an infected person The virus lands in your upper respiratory tract And that's where the infection starts.

00:09:50: Then it starts to spread through the salivary glands Also through lymph nodes from there into blood.

00:09:58: We call that varemia when the virus spreads in our whole body.

00:10:02: And basically through this varemia, the virus is distributed throughout your whole body and it actually can infect a lot of tissues with a lot organs which could lead to complications you have for your mums.

00:10:16: The incubation time is around seven-to-twenty five days but usually it's sixteen or eighteen days so relatively long incubation period.

00:10:28: And then the disease itself comes in phases.

00:10:32: There's an early phase that usually come with mild fever, general malaise muscle pain a sore throat because you get virus replication and respiratory tract.

00:10:43: often people don't have any appetite or want to eat anything.

00:10:48: That is followed by early acute phase.

00:10:51: What happens there?

00:10:52: These symptoms continue specifically systemic symptoms like fever and people get barotitis.

00:11:02: So now what's Barotitis?

00:11:03: That is basically an inflammation of the barotid glands, which are special salivary glands.

00:11:10: They're basically on both sides of your face right in front of you ears And they kind go down below the jawbone... ...and that one of typical symptoms for mums as well.

00:11:23: And so you get this really, really big neck and basically a huge swollen face.

00:11:29: That's the typical sign of mumps.

00:11:31: Often one side swells before another site.

00:11:35: that is what typically is observed... ...and it actually also where name comes from.

00:11:41: I think its an old English word mump means something like grimace.. ..and that come form an old verb which mean to whine or to mutter like a beggar which is kind of the expression that people have when they have mumps.

00:11:55: Then often this resolves relatively quickly, the perioditis often has gone after two to three days and the whole disease often resolves within basically a few weeks.

00:12:09: as mentioned case fidelity rate.

00:12:12: so the number of people who die off it is relatively low but during their acute phase There can be a lot of complications with infections in different organs.

00:12:22: The virus, because its receptors it's basically on every cell and the body... ...can go to many different places.

00:12:30: And one complication is encephalitis.

00:12:33: That's rare but you can imagine that then this becomes a relatively severe disease.

00:12:39: Encephalytis is inflammation of brain Menomchiitis another complication Myocarditis, so inflammation of the heart.

00:12:51: Bancreatitis, information on the bancreas and that can also be quite problematic.

00:12:58: Nephritis or inflammation in the kidneys.

00:13:01: And then there's some interesting informations that could happen.

00:13:06: Ophritis for example.

00:13:08: So the ovaries can be inflamed because of infection.

00:13:14: Mastitis can happen, so that's inflammation and infection of the breast.

00:13:20: That happens in about thirty percent of both puberty female infected individuals.

00:13:26: but I think the most interesting symptom is orchidis And that happens in ten to forty percent of pubertal or post-pubertal males.

00:13:37: So it doesn't have mean kids But it happens in adults kids that go through puberty.

00:13:45: And, that's of course problematic.

00:13:48: so orchitis means inflammation and in this case infection of the testis.

00:13:54: That doesn't sound very nice.

00:13:56: usually only one testicle is affected sometimes both.

00:14:01: as I said about ten to forty percent of adult males who get mums will have Yeah, and basically the testicles just swell.

00:14:14: And this can have long-term effects on fertility.

00:14:18: Usually it doesn't lead to infertility but you can bleed too for example lower sperm count.

00:14:26: There are other Long term issues that come with mums.

00:14:30: One is deafness.

00:14:32: That happens in about four percent of people who get infected.

00:14:36: Persistent vertigo can be an issue and what also has been seen is onset of type one diabetes, and the virus can actually infect better cells which make insulin.

00:14:49: So there's a lot not so nice long term consequences that could happen with mumps infections.

00:14:56: Interestingly overall males are more affected by mumps infection than females.

00:15:03: The problem was also to know specific treatment once you have this infection basically write it out and hope that you get better, which is the case for majority of infections.

00:15:18: but it might be unblessed specifically if your an adult male.

00:15:24: Once you have been infected usually protected from disease or life reinfections I think maybe possible, I would need to look into that because there could be waning immunity but typically this very strong immunity induced by these infections and since the virus doesn't change so much.

00:15:46: The expectation is you will be protected from reinfection not just from disease.

00:15:53: But of course there's something you can do prevent getting infected with mumps virus and that's vaccines.

00:16:01: And so, vaccines were already developed in nineteen forty-eight initially as inactivated vaccine.

00:16:08: So basically the virus was isolated then grown Then chemically inactivate.

00:16:13: it used this vaccine.

00:16:14: The problem with that is only led to relatively short protection from disease.

00:16:22: But when the breakthrough came into nineteen sixties When a guy called Morris Hilleman A researcher who worked at Merck developed life attenuated vaccine, so basically a weakened virus strain.

00:16:36: Maurice Hilleman is legend.

00:16:38: he made or develop most of the vaccines that I used.

00:16:42: nowadays There's actually really good biography That was written about him and they highly recommended it.

00:16:49: It's entertaining And its super informative.

00:16:53: I'll post link to their book in there in the comment section.

00:16:59: And it's also interesting how this vaccine was developed, so Maurice Hilleman was a widow.

00:17:06: his wife died relatively early and he had her daughter and their daughters.

00:17:10: name was Gerald Lynn.

00:17:13: at some point you know.

00:17:14: He woke up in the morning.

00:17:16: then His daughter woke up.

00:17:18: she had mum symptoms.

00:17:21: So he said wait stay in bed I'll go quickly to the lab.

00:17:25: i will be back.

00:17:26: And so he went to the lab, basically got a culture dish and a swab came back.

00:17:32: Swapped her!

00:17:34: Basically took a virus isolate, went back to the Lab put that into Culture... ...and then went back home to take care of his daughter.

00:17:44: That's how this first vaccine strain was made.

00:17:46: It is actually called Cherylin.

00:17:48: after his daughter.

00:17:50: This virus was then grown on chicken cells and on monkey cells.

00:17:55: And what often happens?

00:17:56: if you grow these viruses that are typical human viruses on something like a chicken cell, initially the virus doesn't grow in this cells very well.

00:18:07: But then it mutates and it learns how to grow on chicken cells.

00:18:11: In that process, these viruses often lose their ability to grow very efficiently in human cells because they're now adapted into another species.

00:18:21: That exactly was done here.

00:18:23: so there's many passage as many growth cycles over time that were performed on chicken cells and then in the end, the virus was very weak in human cells but still growing enough to induce a good immune response.

00:18:39: And this became the first MAMS vaccine.

00:18:42: This was approved in nineteen sixty-seven.

00:18:45: In nineteen seventy one it was combined with the measles vaccine and the rubella vaccine into the MMR vaccine.

00:18:53: Over time The vaccine strains were improved.

00:18:56: The Gerald Lynn strain was improved too, I think there's a Gerald Lynn II strain.

00:19:00: then the rivet of the original strain.

00:19:05: other strains are developed and the MMR vaccine is initially given as one dose for Xen and in the nineteen eighties it has been given two doses because it was recognized that boosted dose was helpful to give more immunity not just for mumps but also for measles and rubella.

00:19:25: And out of the three vaccines in the MMR vaccine, mums is one that has the lowest efficacy.

00:19:34: It's not really low but it's lower than measles and rubella typically somewhere between seventy nine and ninety five percent because there are some waning immunity.

00:19:45: its' not as immunogenic as good as inducing immune responses.

00:19:52: Nevertheless, the vaccine was highly successful.

00:19:55: So when you look at the period of nineteen sixty eight so before basically Before that we've seen what's rolled out.

00:20:02: till nineteen eighty two There wasn't ninety seven percent reduction in measles cases in the United States.

00:20:11: if your compare nineteen sixty-eight with two thousand one there was a Nineteen ninety nine point nine percent reduction around the two thousands I think got close to a situation where mums could have been eradicated.

00:20:29: But since then things changed a little bit, one issue is that the MMR vaccine became controversial and there was a lot of hesitancy about using the MMR vaccine initially specifically in the UK.

00:20:45: so fewer people are getting.

00:20:47: that vaccine means that there are some people out here who have no immunity for mumps.

00:20:54: In addition to that, they're some waning immunity when you get the vaccine.

00:20:58: I told you the vaccine works well but it doesn't work super-well and so The immunity over time from the vaccine might actually drop a little bit.

00:21:10: And then There's also suspicion That the virus is evolving at Little bit can deal better with vaccine induced immunity.

00:21:17: So since the two thousand there is an increase in cases again.

00:21:23: They started already with a outbreak in the year of two thousand four, two thousand five in the UK where they had about fifty-five thousand cases of measles.

00:21:32: that was basically relatively young people who hadn't been vaccinated or have not been vaccinated twice.

00:21:41: There was a relatively large outbreak in two thousand thirteen in China with three hundred thousand cases and right now Typically there are between four hundred thousand and five hundred thousand cases of measles data.

00:21:55: And right now, there is approximately four hundred thousands to five-hundred thousand cases every year globally Of mums that are reported to the WHO.

00:22:05: If we look at

00:22:06: U.S.,

00:22:07: The numbers are relatively low Right Now.

00:22:10: Usually it's just a few hundred cases But again with dropping rates of MMR vaccination controversy about MMR again, I think it's just a matter of time until the case numbers go up as well.

00:22:26: So to summarize that mumps are virus that circulates in humans for quite some time or very long time already.

00:22:37: not a very deadly disease but can have very nasty symptoms including swelling.

00:22:46: It can also induce long-term issues like deafness and lower fertility, but there are good countermeasures.

00:22:55: There's a vaccine out there that protects well... ...but they might be rising case numbers for a number of reasons….

00:23:02: …but one of them certainly will be in hesitancy!

00:23:05: So thats it for this week.

00:23:06: as always if theres comments So that's it for this week.

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00:23:24: Thanks for listening And until next week Bye!

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