#2 – Measles: How Vaccine Gaps Lead to Outbreaks

00:00:06: None of the studies that were done subsequently found an association between MMR and Autism.

00:00:12: And in a way, doing these studies is great because it proves again... ...that the vaccine is safe and there's no issue.

00:00:33: Birological with Florian Kremer.

00:00:46: Hello and welcome to this week episode of Biro logical.

00:00:50: This episode was recorded on January nineteenth twenty-twenty six in Vienna Austria.

00:00:57: So today we're going to talk about measles virus.

00:01:00: Measles virus is part of the orthomyxovirus family and part of genus mobili viruses.

00:01:08: it has a number of close relatives that are animal viruses.

00:01:11: so measles is strictly human virus.

00:01:14: but there's very similar animal viruses, those include rindabest virus which used to affect cattle but was actually eradicated and also Canaan distemper virus which can be a problem in dogs or other animals.

00:01:30: It's also more distantly related to very dangerous viruses like Nipah Viruses, Handra Viruses but also to other common human pathogens such as Mumps Virus and RSV.

00:01:41: The virus has single stranded negatively polarized RNA genome.

00:01:46: it has a coding capacity of about sixteen thousand basebears approximately and the virus is about hundred to two-hundred fifty nanometers in diameter.

00:01:56: It's pleomorphic, which means it doesn't have a very well defined shape so its kind of roundish but not very nicely round.

00:02:08: that's true.

00:02:08: actually for most Paramix viruses they kinda look pretty ugly.

00:02:11: honestly They don't have regular shapes.

00:02:15: They look like an ugly blob of a virus, so you can hear I'm not big fan the shape and structure of Biramexoviruses.

00:02:23: When we look into how its structure looks it's built.

00:02:27: We have genome on inside that is protected by nuclear protein.

00:02:32: There are polymerase associated to the genome and phosphobrotein and then the particle is stabilized on an inside biometrics protein, Then we have a lipid envelope.

00:02:42: And two spike proteins in that envelope.

00:02:45: One of them called hemagglutinin That's used by the virus to bind cells.

00:02:52: A second one called f-protein or fusion protein responsible for fusing the viral membrane with cell membrane which allows release of the viral genome into the cell and starts infection.

00:03:07: Death.

00:03:07: protein binds to protein receptors on our cells, the number of them.

00:03:12: You don't have to remember that but one is CD-forty six.

00:03:16: another one is cd hundred fifty and nectin involved in binding.

00:03:21: so we see pining into a protein receptor not sugar receptors.

00:03:25: like with many other viruses influenza for example binds to a sugar as a receptor, sugar on cell surface.

00:03:33: this more like SARS-CoV-II which also binds to proteins.

00:03:37: measles virus is genetically diverse, there are different genotypes and that makes it actually relatively easy to track outbreaks, investigate outbreaks and see where these viruses came from.

00:03:49: And how outbreak are connected with each other?

00:03:51: That's important.

00:03:52: we'll get that later on when you talk about measles free status granted by the WHO in countries.

00:03:58: As I mentioned this is a human virus.

00:04:00: it really only circulates in humans.

00:04:03: You can experimentally infect non-human primates or monkeys but typically they're only found in humans and it's just transmitted via the air, either by aerosols.

00:04:14: So these are very tiny droplets that stick in the air for a long time or by respiratory droplets.

00:04:21: larger respiratory droplets usually fall to ground quicker.

00:04:26: Missiles virus is very infectious.

00:04:29: we have previously discussed this R-NOT or basic reproductive number which specifies how many people an infected person infects And for measles this R-naught is eleven to eighteen, so a person infected with measles infects about eleven to eighty new susceptible people.

00:04:49: Of course if people surrounding an infected person are vaccinated they're protected and won't get infected but still the virus very infectious.

00:04:58: If there's non-protected, non-vaccinated people around will likely be infected.

00:05:03: The virus known as long time in humans.

00:05:07: It has likely a common ancestor with this render best virus that I mentioned.

00:05:13: And the idea is, it jumped... The common ancestor of measles and render best viruses jumped into humans or started to infect humans maybe around four hundred BC to five hundred AD.

00:05:27: That's the estimate.

00:05:31: The idea is that this ancestral measles version already had similar symptoms to today's measles virus.

00:05:37: And the disease was already described in ancient Persia by Muhammed Zakaria Arazi, who was a philosopher and physician... ...and he could already differentiate between measles box- and chicken boxes just based on their symptoms.

00:05:54: That was approximately nine hundred eighty.

00:05:57: And so the idea is that there was a complete separation from this common ancestor with Rinderbestvirus around thousand one hundred to thousand two hundred AD and From then on we can probably talk about proper measles in humans.

00:06:13: The virus itself was isolated in nineteen fifty four by John Andersen, Thomas Biebels at Boston Children's Hospital form a thirteen year old boy called David Edmondson and keep that name in mind, we'll get back to it later when you talk about vaccines.

00:06:30: And John Enders was also involved with the discovery of isolation and cultivation of polio virus... ...and he got a Nobel Prize for that I think as well in the same year in nineteen fifty four.

00:06:41: So how do you get infected?

00:06:43: I mentioned earlier that the virus is spread by aerosols and droplets, so basically the infection starts via inhalation.

00:06:49: And the lung is getting infected.

00:06:52: from the lung the virus reaches local lymph nodes.

00:06:55: there it starts to replicate quite rapidly.

00:06:59: After approximately seven days after the infection started we see first varimia.

00:07:05: Varimia means the virus spreading through blood And this is usually when first symptoms occur.

00:07:13: These first symptoms are often respiratory symptoms, sniffles, cough, bronchitis... ...often also conic divide so eye infection and then fever.

00:07:24: Then around day twelve to thirteen after the initial infection we see a second viremia And that triggers this typical rash you see with needles.

00:07:35: This rash often starts behind the ears and then spreads throughout the body, which is also associated with a second fever wave.

00:07:43: Then four to five days after symptom onset typically the infection starts to resolve if it's mild case.

00:07:54: So when are people infectious?

00:07:56: About four days before the onset of the rash to four days after the rash is gone.

00:08:03: And of course, this is problematic because that means an infected person can already pass on infection before it's clear that the infection is measles right?

00:08:12: Typically people understand they have measles when their rash starts and they can spread the virus beforehand.

00:08:20: then thats good for the virus.

00:08:25: relatively unspecific symptoms, you don't think about this and then you spread the infection.

00:08:30: Typically the disease is more severe in adults than in kids but of course most adults are actually immune because either they were infected in childhood or most of them were vaccinated.

00:08:42: when we look at kids about two-thirds But about one sort of the cases come with complications.

00:08:51: This could be a diet is media, diarrhea for example but in five percent of the case we see pneumonia.

00:08:59: so off course diverse replicates in the lungs or that lung is involved and depending on you know where the case happens which country which area what they have status of the kid.

00:09:10: this would.

00:09:11: living standards are if how to nutrition statuses the mortality rates can be relatively high.

00:09:20: They're typically described as one to five hundred, two-one thousand for measles but there are studies that out there they'll also see one to three hundred thirty fatality rate and immune suppressed individuals.

00:09:34: this can be much higher upto thirty percent.

00:09:37: The situation is different between high income countries low and middle income countries Depending on the outbreak.

00:09:45: and again, setting case fatality rates or mortality rate in low-income countries can be up to twenty five percent.

00:09:53: This actually also tracks with historical mortality rates... ...in the US and Europe.

00:09:59: so you know back before health care improved Before nutrition improved before hygiene improve then so forth.

00:10:07: The cases for that relates in Europe but in the u.s.. We're pretty high too.

00:10:12: There can be also rare side effects with measles, one of them is meningitis.

00:10:18: And if that occurs the case for deliderates even in high-income countries ten to twenty percent and kids that survive often have long term issues.

00:10:28: Then there's a relatively scary disease called subacute sclerosing benenophilitis or SSBE.

00:10:37: That sounds bad actually is pretty bad.

00:10:40: What happens here, you have virus replication and inflammation in the brain.

00:10:45: that also leads to scarring of the brain.

00:10:48: it's a very slow progressing disease can be pretty deadly.

00:10:56: so typically if kids under the age five are getting infected with measles two to six out ten thousand kits develop this SSBE.

00:11:07: When kids get infected under the age of one year, this rate can be up to one-to six hundred according to a study in California.

00:11:16: So what happens here is that you know Kids got regular measles infection and the virus stays in their brain And doesn't do much damage there almost like it's dormant.

00:11:30: Last up to ten years and then symptoms start typically seizures paralysis dementia.

00:11:38: This moves very slowly, but the problem is the case fatality rate for SSPE about ninety five percent.

00:11:44: So unfortunately it's a very tragic situation.

00:11:48: basically you know The kid already had measles survived was uncomplicated and then years later, unfortunately the virus starts to become active again.

00:11:59: It causes this very severe disease And it's interesting because similar cases are also described for other paramexor viruses.

00:12:08: For example one such case is described for handra virus in Australia where a man also got infected with handrovirus, survived the infection.

00:12:17: But then later the virus started to replicate again in that brain and the person died.

00:12:22: Unfortunately there are also indirect issues with measles.

00:12:25: Measles virus infects memory B and D cells so these are part of their adaptive immune system And they can also persist in these cells for upto six months.

00:12:37: That affects immune memory basically kills off immune memory And this immune amnesia can last over months.

00:12:47: What happens there is that if these memory B and D cells disappear or are non-functional anymore, kids get very susceptible to other infections typically viruses or bacteria.

00:13:01: that would just cause mild infections usually, but all of a sudden kids can have very severe infections with viruses like adenovirus which is relatively harmless for healthy kids and these infections can end fatal as well.

00:13:16: There's actually a very good paper by Michael Mena and up Osterhaus And I'll provide the link to that paper so people can look it up.

00:13:24: But many people don't know about this indirect effects that can be pretty problematic too.

00:13:30: Just a little bit of trivia here, Roald Dahl the writer.

00:13:35: his daughter died off measles when she was seven years old and I think before the vaccine was available.

00:13:43: he later on really helped to promote measles vaccination due to such tragic cases.

00:13:49: The interesting thing with measles is people who survive measles infections which is the majority of infected individuals develop pretty strong immunity, and that typically leads to herd immunity in a population.

00:14:02: And there have been studies that determined for measles virus to kind-of stay circulating in their populations or stay alive it needs at least the population size of two hundred fifty thousand to five hundred thousand individuals.

00:14:17: And that was determined when island populations or indigenous tribes were studied, where the virus made into that population.

00:14:26: and if The virus just burned through the population but then couldn't infect anybody anymore and basically disappeared.

00:14:35: But if the population size was big enough, there were always kids that were born who were susceptible so the virus stayed in their populations.

00:14:44: But that's also interesting.

00:14:46: and this point starts potential measles elimination if you have a good vaccine, very high coverage.

00:14:53: Because of course measles doesn't circulate in animals there is no animal reservoir.

00:14:57: so once it gone into human population It would really be eliminated eradicated.

00:15:03: Unfortunately we are still pretty far away from them.

00:15:08: actually We're moving to the wrong direction.

00:15:11: So if you look historically, when we go back to the year two thousand there was an estimated eight hundred thousand measles deaths globally per a year.

00:15:20: Since then there's been lot of work in terms of vaccination campaigns and that really reduced number cases globally And I think the estimate for twenty-two is about one hundred thousand.

00:15:38: You find these cases around the world.

00:15:41: Africa is most affected by measles, but basically you have outbreaks on all continents.

00:15:47: Of course many countries also eliminated measles circulation through rigorous vaccination campaigns and high vaccination rates.

00:15:56: And when a country eliminates measles circulations it can get measles free status from the WHO.

00:16:04: That doesn't mean that There are no measles cases at all in that country.

00:16:07: It just means there is not constant circulation and you have to prove it.

00:16:11: so if a country has outbreaks, can be proven these outbreaks aren't connected or they're from introductions outside of other countries then this isn't the problem because you can do that through sequencing the virus and tracing them back.

00:16:24: That's why this diversity in genotypes makes it easy for us to trace the virus.

00:16:32: But if it turns out that the virus is circulating constantly in a country, then you lose that measles free status and Canada just lost this status.

00:16:42: In twenty-twenty five.

00:16:44: The US for example still has it.

00:16:46: I don't know how long but we'll see.

00:16:49: I mentioned that there's a lot of measles cases in Africa, for example.

00:16:53: But we see measles come up quite a bit also in North America and Europe.

00:17:00: just the few numbers were two thousand twenty five here.

00:17:03: Mexico had around six thousand.

00:17:05: measles case is in two thousand Twenty-five.

00:17:08: Canada had five thousand four hundred in two thousand twenty-five and as I said lost the measles free status.

00:17:15: The US had two thousand two hundred cases about two thousand to one hundred cases in twenty, twenty five with three deaths And about eleven percent of the infected individuals have been hospitalized according to the CDC.

00:17:31: so that's highly problematic.

00:17:33: but we also see a lot.

00:17:35: Romania for example had about eight thousand cases.

00:17:38: Last year Germany had two hundred fifty, France at the eight hundred.

00:17:43: so there's an increase in many western countries including North America and Europe.

00:17:49: that of course has to do with basically lower vaccination rates.

00:17:55: if you have gaps in vaccination then there will be increases in measles and we'll start to circulate again.

00:18:03: as I mentioned Missiles can be prevented by vaccination and there's a very well-established, effective and safe vaccine.

00:18:13: This vaccine was developed based on the virus that John Anders isolated in nineteen fifty four from this kid at Munston.

00:18:22: so the vaccine strain is also called after it.

00:18:28: What happened back then was that John Enders besaged the virus, which just means he cultivated it over and over again in the laboratory first on human cells.

00:18:38: And then in chicken cells... So what happens when you do that with a virus?

00:18:42: When you switch species of the cell growing on initially typically the virus doesn't grow well on these new cells initially.

00:18:51: so measles is a human virus.

00:18:54: It's not equipped for growing on chicken cells right.

00:18:57: But if you do that over and over, then it starts to mutate.

00:19:05: It optimizes its growth on chicken cells.

00:19:08: And what often happens in the process of adaptation... ...to a new cell or species is that the virus loses their ability to efficiently grow and replicate in human cells.

00:19:24: That weakens them in humans.

00:19:28: We call that attenuation.

00:19:30: And thats how classically these life-attenuated vaccines were made and so this was also the case for measles, it's a very classical way of making vaccine strains, of attenuating them or weakening them... ...and the strain developed is called Edmonton B Strain.

00:19:49: There was used as a vaccine but wasn't attenuated enough until in nineteen sixty eight new strain was developed and introduced that was even weaker, further attenuated and it's done by Maurice Hilleman.

00:20:03: Maurice Hillerman is a real pioneer in terms of vaccine development.

00:20:08: he developed many vaccines we are using nowadays.

00:20:12: He had an interesting life.

00:20:14: there is really good book about him.

00:20:17: I'll leave the link to this book.

00:20:21: From that strand at Hillemann developed.

00:20:23: basically three strains were derived, the Edmondson-Sagreb strain, the Marathen strain and the Swart strain.

00:20:30: And those are basically vaccine strands.

00:20:32: they're still used nowadays.

00:20:34: in nineteen seventy one.

00:20:36: this measles vaccine was combined with the mumps and rubella vaccines which also life had denuated.

00:20:42: weakened to vaccines.

00:20:50: This vaccine was super effective and in the US, for example is led to a drastic reduction of measles cases.

00:20:59: It had an efficacy of about ninety-three percent against measles.

00:21:04: but because measles are so infectious it still caused cases at very low level even after that vaccination started And so the idea was to give a second dose of the vaccine.

00:21:17: Initially, only one dose was given and if you gave it a second-dose you get an efficacy of ninety seven percent... ...and that's really enough to stop measles virus circulation.

00:21:28: in the United States The estimates are this vaccine prevented about fifty seven million measles deaths between year two thousand so that's a huge number of lives saved.

00:21:44: Typically this vaccine is given at the twelve months of age, before that.

00:21:48: typically babies are protected by antibodies to take out from their mothers through the placenta because these maternal antibodies and if you give the vaccine earlier than twelve months often it doesn't work well because of course these antibodies also kill off the vaccine strain and then doesn't replicate, you don't get a good immune response.

00:22:12: So typically it's only given at twelve months of age And the second dose is often between fifteen to eighteen months.

00:22:19: The recommendations differ little bit among countries but that kind in general the scare do.

00:22:26: The vaccine, because it's a live virus vaccine can have side effects.

00:22:30: It can cause fever or a mild rash but these side-effects are actually relatively rare and its super safe vaccine.

00:22:38: However ,because of the live virus it cannot be used in people who has issues with their immune system Cannot use in pregnant women for example whoever downregulated or some aspects down regulated immune systems.

00:22:51: You can also not use it in immune compromised individuals and people with untreated HIV because, in these cases could replicate better to some damage even though its a weakened vaccine.

00:23:04: But again the very successful vaccine saved many-many lives.

00:23:09: We have problem with this vaccine.

00:23:10: This has do more perception than was the vaccine itself And that goes back to nineteen ninety eight.

00:23:17: In nineteen ninety-eight British doctor Andrew Wakefield published a paper in the Lancet.

00:23:24: So, The Lancet is actually pretty good medical journal but sometimes even they make mistakes.

00:23:30: and so this Andrew Wakefeld publishes study that he had done on twelve kids That have what he described as Autistic and Oracleitis basically intestinal inflammation plus autism.

00:23:45: And He said there are hints that this is connected with the MMR vaccine.

00:23:52: Actually, going through that paper and what followed... And the investigation that followed and so on and so forth warrants its own episode.

00:24:00: I'll keep it brief today to keep it short.

00:24:03: basically The study was nonsense in a scientific sense And in the year of two thousand four it was partially retracted, so taking back basically and two thousand ten.

00:24:15: It was completely retracted.

00:24:17: there were relatively intense investigations or what happened then they turned out that this Andrew Wakefield had massive conflicts of interest.

00:24:26: He was paid to do that study but he didn't disclose that.

00:24:30: I think There Was also a lack of ethical approval To Do The Study which is not good?

00:24:34: Then In the end he lost his medical license in the UK.

00:24:38: So basically, it didn't make any sense and the data wasn't really supporting what they claim was.

00:24:46: But of course there were a lot reports in media that fueled skepticism about the MMR vaccine... ...and fears of parents that the vaccine would cause autism if they get their kids vaccinated.

00:24:57: And this impacted quite a bit on vaccination rates right?

00:25:01: Vaccination rates went down because of death.

00:25:04: That is one of the reasons why we have this current increase in measles cases, specifically in western countries.

00:25:11: Of course initially it was taking very serious right?

00:25:14: So if you see a study like that and there might be an association... You have to look into that!

00:25:19: It may be true so its important to investigate that.

00:25:23: And they were actually large number of follow-up studies quite big follow up studies Quite expensive Follow Up Studies.

00:25:31: One example is a two thousand twelve Cochrane study that included analysis of about fourteen point five million kids and they didn't find any association between MMR and autism.

00:25:44: None of the studies were done subsequently found in an association with MMR or autism, but doing these studies was great because it proves again that the vaccine is safe and there's no issue.

00:25:57: But you end up with one study, with twelve kids... ...with massive conflict of interest involved on one side….

00:26:05: …and a large number of studies was millions of kids in good-study designs on the other side….

00:26:11: And people still believe what Andrew Wakefield published back then and don't vaccinate their kids!

00:26:16: So the problem really it once fake information is out.. ..and once conspiracy theories are out It's really hard to counter them.

00:26:25: Even if you have hard data that says it is not the case, right?

00:26:29: People just start to believe these things and its' really hard get this out of their minds.

00:26:34: So Just To Summarize The Situation With Measles Measle Is A Problematic Disease With Rising Case Numbers Mostly Fueled By Vaccine Skepticism And False Information.

00:26:46: Its a big problem and will be an even bigger problem in coming years.

00:26:51: This Actually Sad Because This is a virus that's restricted to humans.

00:26:57: We have very good vaccine and we could eradicate it, get rid of it in the human population but unfortunately are going into completely wrong direction right now.

00:27:08: So this is end today episode.

00:27:10: as always if you have comments suggestions or questions please write an email to virological at podcastworks.com.

00:27:19: Thanks for listening!

00:27:23: Bye!

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