This Podcast Will Kill You - Ep 24 Zika: Rumors and Rumours

Episode Date: April 16, 2019

Zika virus may not have as long and storied a history as many diseases we've covered, but in a short time it has managed to make a big impression. Today we'll talk about how Zika wriggled its way out of obscurity and cover its journey from a mosquito's mouth straight to our newspaper headlines. From the first discovery of the virus in a Ugandan jungle, to the heartbreaking effects only recently discovered, to the future of Zika research and vaccine development, we'll fill you in on everything you want to know and then some. See omnystudio.com/listener for privacy information.

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cybersecurity and expert partnership, Comcast Business is powering the engine of modern business. Powering possibilities. Restrictions apply. The real and terrible consequence could be seen on CT scans, MRIs, and ultrasounds. Those tiny heads contain shrunken brains. Sometimes just the frontal lobes, the seat of decision-making, of speech, of intelligence, of humor, were atrophied, showing abnormally large, dark ventricles, the hollow internal spaces that are supposed to appear smaller and smaller as the brain grows. Sometimes all that was left was the bulb above the brain stem, where the most basic functions, like breathing and digestion, reside. Around it would be blank space filled with cerebrospinal fluid. Usually the skull had not completely collapsed,

but neither had it pushed out to its full size by the growing brain. And the brain would be smooth, looking more like a small liver, with none of the deep folds and fissures that every growing brain should develop as it folds in upon itself to pack more thinking power into a small space. That smooth brain baby might be more than comatose. Maybe it could breathe, could blink, could digest, could live. But maybe that baby could not chew food, or see the spoon or the breast coming toward its mouth. Certainly it would never walk,

probably never crawl, or maybe would never do more than roll from side to side, unable to control its contorted arms and legs enough to even turn over. Hospital hallways, doctors remembered in Brazil, were lined with mothers who resembled ghosts. They were in shock, mute, expressionless, bleak. Some were just teenagers. Some had ridden buses for hours and were too poor to buy food, as the hours waiting to be seen stretched on, and there were so many of them. One mother looked up from her son's face to ask, Doctor, his head is going to grow, right? Yeah, it was really intense.

But that's also the reality. Yeah, Zika. It's, dang. Yeah. It's awful. It's really awful. Yeah. So that first.

hand that really horrible sad description is from a book called Zika by Donald McNeil. Okay. Well, hi. Hi. We always managed to start on really great notes. I mean, this podcast. What's this podcast about? Oh, yes. I'm Aaron Welsh. And I'm Aaron Alman Updike. And this is, this podcast will kill you. And today we're talking about none other than Zika virus. Heavy. Yeah.

Well, they all kind of are, really. It's true. Okay. Well, so before we move on to hear more about just how awful Zika is, let's arm ourselves with a stiff drink. Let's do that. Or a placebo-rita. So it's quarantini time, I believe.

It is definitely quarantini time. So this week we're drinking the pink eye of the tiger. And why is it called that? Well, in part, as we'll discuss in the biology, because Zika is transmitted by the tiger mosquito. And in part because one of the symptoms is conjunctivitis. Ah ha, ha, ha. We're puny as heck today, Aaron. Just wonderful.

So what is in pink eye of the tiger? Okay, so it is a little bit of raspberry sorbet, a little bit of mango and passion fruit infused vodka. Thanks to my brother Josh, who can't hear this, but I'll thank him anyways for that gift. And then you top it up with some champagne. Yum. Yeah, it's actually quite delicious. And as always, we'll post the recipe for our quarantini, as well, well as the non-alcoholic version are placebo-rida on all of our social media channels. So

TPWKY on Twitter. And this podcast will kill you on Facebook and Instagram as well as our website. Cool. I want to hear about Zika. I want to hear about this is a bizarre little virus. It's very bizarre and it's new for many of us. So let's get into it. I'm excited to tell you about the biology. So we've actually gotten a fair number of requests for Zika, which is exciting. And what I think is so interesting, and I can't wait, Aaron, to hear about the history of it is that if we had talked about, I mean, if we had started this podcast a few years ago, I don't even think we would have proposed doing Zika virus because I don't even know that I heard of it before like 2015. No, definitely not. It was not on almost anyone's radar. Yeah.

So it's in that way, it's really exciting because so much of Zika is just brand spanking new. Yeah, I mean, it's still happening. Right. But I don't want to steal your thunder about the history. You won't. Let's just talk about the virus itself and how it makes you sick. Okay. So Zika virus is a virus.

Is it? Is it? It is. You know, we could go crazy. you know, call something Zika virus and have it be a, no, it's a virus. It's in the family Flavaviridae, and so perhaps some really deep listeners or recent binge listeners might remember another disease we've covered that's in this same family. Erin, do you remember? This is going to be embarrassing.

Is it yellow fever? It's a yellow fever. Okay, good. Thank great job. I was like, the amount of stuff I can forget is impressive. Oh, same. But you got it right. It's related to yellow fever, also to dengue, Japanese encephalitis, West Nile, a bunch of other viruses. So it's an RNA virus. And like all of those other viruses that I mentioned, it's transmitted by mosquitoes. Zika happens to be transmitted by the same mosquitoes that transmit yellow fever and dengue virus and chicken guinea. But those are all different stories. And that's 80s Egypti and 80s Alis. So that's the yellow fever mosquito and the tiger mosquito, both of which, if you live in a

place where they exist, then you've definitely noticed them because they're gnarly biters. They bite humans like prolifically. They love humans and they bite hard and it hurts and they're big and black with white stripes on their legs. Oh yeah. And they bite often. They bite often. And they also are like daytime biters. So they'll bite you all day long. They're not like, other mosquitoes that will only bite at like dawn or dusk or acular. It's one of my favorite words. It's a good word. And so diseases that are spread by these mosquitoes like yellow fever, dange, Zika,

they're especially difficult problems to deal with, in part because of how well adapted these two species of mosquito are to the urban and peri-urban environment and how much they love humans and the environments that we create for them. So it's really fun. When you combine that with climate change and how they're expanding their range, these diseases aren't going to stop being an issue anytime soon. And urbanization and land use change and clear cutting forests.

All the things. It's just so fun. Good news from our corner, everyone. Right? Job security. Okay. So one of the things, though, although Zika is, transmitted primarily by mosquitoes, one of the things that we discovered relatively early on during

the most recent outbreak that's pretty novel and very scary is that it can also be transmitted sexually. Oh, yeah. So the virus somehow seems to be able to live in, especially the male reproductive tract. I don't know exactly where. I don't think we know as science exactly where in the reproductive tract of humans. It happens to live, but it can live there and be transmitted weeks or even months after a person was infected. And most of the cases of sexual transmission have been from symptomatic people, and usually it's transmitted via semen, but you can also transmit it to your partner even if you've been asymptomatic, which is really scary because it means that you could potentially be a carrier, never know that you're infected, and then end up transmitting it to a

partner. Yeah. And this is, yeah, it's something that's pretty novel and quite frankly scary in looking at something that's normally a vector-borne disease, because it really adds a whole other layer of complexity to control efforts, which are already really difficult when you're dealing with vector-borne diseases. Yeah. I can't believe how long it lives. I read something about a about someone who it was circulating, they found traces of the virus in their semen 62 days after exposure or something like that or after first being positive. And the thing is that since we don't know, like there's so much that we don't know about this virus, we don't know, like, is 62 days the average or is that the maximum, right? We don't know. Or is that just like maybe on the low end,

maybe it could live for six months or a year? Who knows? We don't know at this point. Oh, man. And there's one other way. that Zika can be transmitted, and that's vertically. So vertical transmission is from mother to baby. And so in this case, Zika can actually cross the placenta and be transmitted to the fetus during gestation. And while this is not uncommon for viruses in general, there's a number of infections, viral and bacterial that can cross the placenta. It wasn't known at all that Zika could be transmitted this way until very recently. And as far as I know, it's not that common for mosquito or vector-borne diseases to be able to cross the placenta.

Yeah, I don't think so. Yeah. But it's not that out there just in terms of a biology perspective. There's a number of viruses and bacteria that can cross the placenta. So those are all the ways that you can get infected with Zika. Fantastic. So the question is what happens once you get infected? Yeah.

Yeah. So, okay. So the most common. common way that you get infected, right, is via mosquito. So if you get bitten with an infected mosquito, the incubation period, which is, again, the time from when the mosquito bites you and dumps a bunch of virus into your bloodstream until the time that you show symptoms, that time period is usually between three and 14 days. So usually within two weeks, you'll start to show symptoms. It's, again, a long span. It's a pretty long span, yeah. But again, that has to do in part with just your

immune system and then in part with how many viruses was the mosquito infected with and blah, blah, blah, blah. How long it was feeding on you. Yeah, all those things. All the things. So the symptoms in this case are actually very mild. Fever, rash. And the rash is one of the features that seems pretty prominent in Zika virus compared to other flava viruses. Like most of the time if you're going to have symptoms with Zika, you'll probably have a rash.

also conjunctivitis, hence the name of our quarantini. Pink eye. Pink eye. Raise your hand if you had pink eye as a kid. Who didn't? Oh yeah. Everyone did, right? We weren't just filthy.

I don't know. Let us know, people. Okay. So those are really common. Also, muscle and joint pain, and that's something that's really common with a lot of flavaviviruses. Malays, headache. These are all things that are pretty typical if you get any kind of viral infection. and they're also very nondescript, which you can imagine makes it very difficult to diagnose.

Yep, right? Sure does. And symptoms are pretty self-limited. They usually only last between two and seven days. So we're talking like the flu length, but not even as severe as the flu probably. Right. But what's really important is that up to 80% of people who are infected with Zika virus don't ever develop any symptoms. That's, yeah, I read that. That's amazing. Yeah. Yeah. And it means that, I mean, it just makes it so, so difficult to try and get a handle on how many people have been infected and everything. Because if you've got 80% of people never showing symptoms, oof, it makes it tough.

And so in general, this infection happens in a very similar way as any other flava virus or really any other virus or misdemeanor. Bored virus, and that is the virus gets into your skin because the mosquito pokes a hole in it. It goes into your lymph nodes and then into your bloodstream, and it replicates, and it invades cells. So how exactly Zika virus infects your specific cells and causes damage? We don't entirely know. So we don't know the exact path of physiology of Zika virus yet, which means that it makes it a little bit harder to target. And it's

acts differently, or it's suspected to act differently than other flabaviruses? I don't know the answer to that question. Okay. But Zika virus particles can be found in almost every bodily fluid that we have tested so far. So if you test the blood of someone who's been infected with Zika, you'll probably find Zika virus. If you test their semen, if you test vaginal secretions, if you test their eye fluid, if you test their saliva, if you test almost any bodily fluid or almost any organ, you'll probably find Zika virus particles. I have a question about bodily fluids. Okay. Do boogers and snot count?

Tots. Yeah. Okay. And so on top of the sort of general nondescripts, symptoms, there are a number of different complications that can arise as a result of Zika infection. So there's an increased risk for future neurologic complications like Gian Burey syndrome, myelitis, general nerve issues, and also things like meningitis are possible as a result of Zika virus infection. Right. But the biggest complication that we mentioned in our firsthand account and that people, it has probably become the most famous is that five to 15% of infants born to pregnant women who are

infected with Zika during their pregnancy have evidence of complications directly related to Zika virus infection. These complications include intrauterine growth restriction, which means the baby's not able to grow as big as it should, early pregnancy loss, also known as spontaneous abortion, and microcephaly, which is a small brain that's inadequately developed and in some cases can be incompatible with life. So this is sort of the most extreme complication and the most devastating complication that has come from Zika. The exact mechanism of how this happens is not clear. Are there thoughts as to what it might be? Well, so shortly after the connections between Zika virus and microcephaly were sort of brought to light, there was a lot of pushback because it's only 5 to 15% of cases, and that seems pretty low.

And in some areas, the baseline levels of microcephaly weren't necessarily known at the time. But since then, multiple different animal models have shown that Zika is capable of crossing the placenta and in mouse models, can cause fetal defects. I believe in monkey models, non-human primate models as well. So at this point, the link is pretty clear. But we don't really know exactly what is happening. Besides that, Zika is able to invade across the placenta and then infect the fetus. Okay.

Yeah. You might have said this, but I don't remember any trimester. Is it any trimester for infection that's dangerous? Great question. So the number or the percentage of birth defects is highest in women infected during the first trimester, but it is possible to end up having a baby born with congenital malformation if you're infected at any point in the pregnancy. Okay. But what I think is scary is that when you combine this complication with the fact that Zika can be transmitted sexually, that's a pretty sinister picture of a disease. Yeah. It's pretty depressing.

That's all I've got. That's Zika virus. It's a scary and really tragic one. It really is. It really is. Yeah. So what the heck, Aaron? What's going on?

How do we get here? Where did this thing come from? How did it just pop up in 2016? No one even heard of it. Is it brand new? Well, the Romans called it. No, just kidding. Okay.

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and 365-day returns, now available in Canada too. That's Q-U-I-N-C-E dot com slash this podcast to get free shipping and 365-day returns. Quince.com slash this podcast. I feel like we all know the history of Zika, or at least a big part of it. I mean, we've,

we've lived it more or less, like we've been there for it. Maybe not in the epicenter, but we remember the headlines at least. And I can remember the panic and headlines of 2015 and 2016, and I'm sure you do too. I was living in Panama for much of the peak of media hysteria. And I remember all sorts of rumors just among, you know, in, in Guamboa about the danger of Zika and how pregnant female researchers weren't going to be allowed to conduct research in Panama. And I think that the week I was visiting San Blas, there was an outbreak of Zika declared there. Like that was, oh, Zika and San Blas. And I was like, well, okay. At least it's mild, you know, or something like that stupid that I was thinking. Oh, yeah. I was the same way. I was like, man,

maybe I should just try and get Zika now, so then I've had it. Yeah. I mean, I really wonder if we tested antibodies, whether we would have been show exposure. Actually, I was tested because if you give blood in the U.S. now, they test you for Zika, and they call you if it's positive, and mine was negative. So I didn't get Zika. Oh, okay. So you never got Zika.

Yeah. So for every disease or topic that we cover, I try to ask myself the question, what does this specific disease or outbreak teach us? about epidemic response or the nature of disease or often humanity itself. And I think in this way, Zika is one of the first epidemics to show us how fast information and especially misinformation can spread. In many ways, though, that just kind of shows us how little things change. Rumors and conspiracies thrive during epidemics.

Someone's always wanting to go against, quote, conventional wisdom. sometimes they're right, most times they're not. And it just moves at a faster pace and with a higher turnover in this internet age. Yeah, thanks Twitter. As age of Twitter. And so does the virus itself, thanks to global travel. Even though the first time that many of us heard the word Zika was probably in 2015, in connection with the words microcephaly and Brazil,

the Zika virus had actually been known for almost 70 years. That's amazing. I didn't know it was 70 years. I knew it was a long time, but dang. Yeah. That's a long time. Yeah. Did you come across the meeting of Zika in any of your readings?

No. Okay. My favorite part. It actually means overgrown. What? And is, yeah. So it's taken from Zika for us in you guys. which is close to Anteby, where the Rockefeller Foundation established its Virus Research Institute

in the 1930s. The swampy hot Zika forest was the perfect place to accomplish some of the goals the research institute had laid out, including understanding mosquito ecology, exploring which animals are susceptible to different viruses, and the big one, discovering new viruses. And this is a common theme in so much. many early, quote, global health institutes, the primary focus was research, not intervention. That brings with it a whole other set of issues about the ethics of early global health research. But anyway, so to conduct this research, scientists suspended cages containing sentinel monkeys of various

species in the forest can't be. Then they would pull them down occasionally for inspection and temperature taking. Sounds like a really wonderful way to live a life, right? Oh my God, how sad. To be a monkey in the forest so you can like see your friends and you're in a cage your whole life. Well, and some weren't from Uganda. Some were from various Asian countries, so extra cool. Even better. One day, April 19th, 1947, to be exact, because you know how I like to be Exactly. Of course. A monkey with the charming name of Reza 766 was observed to have a high fever, 104 degrees Fahrenheit, 40 degrees Celsius now that I'm in Finland. Blood was drawn and processed, and in it scientists found what they called a filterable transmissible agent, which back then

often meant it was a virus, something they couldn't easily culture. But this still left many questions. First, was it a new virus, meaning undiscovered? And was it mosquito-born? To answer the second question, they had to collect many mosquitoes from the same areas that Rees' 766 had been kept, and then test whether these mosquitoes carried anything resembling this virus, which meant grinding up and filtering the mosquitoes and injecting the slurry into the mice or monkeys they had on hand. And then comparing that to the infection caused by the filterable transmissible agent that had originally come from Reese's 766. Man, that just sounds like,

you can have co-infections. This sounds like a messy way to try and figure out what's going on. I think they just didn't know any other better way to do it. Oh, yeah, for sure. Yeah, like, what else are you going to do? I don't know if I would have had the patients

to be in microbiologists back then or virologists. I don't even have the patients for it now. Yeah. Fair point. Fair points. Why I'd do this podcast instead. Finally, they would test this new mosquito-derived slurry on a monkey that had recovered from an infection with the original virus. Yeah, full circle.

And the results of those experiments confirmed their hunch. The virus was mosquito-borne, transmitted specifically by the species, in this case, 80s Africanus. But still, they didn't know whether this was a new virus or one that was already known. Since it was 1947, they couldn't test for specific genetic material, but they could see whether the virus could be neutralized by antibodies against known viruses. And they found, as you can guess, that this was a brand new virus. So they named it Zika, because why wouldn't you name it after a geographical place? Just kidding. And then it all but dropped off the face of the earth.

Yeah. From 1947 to 2007, 60 years. 1947, they discover it. They're like, cool, we got a new virus. Nobody cares. 2007, tell me what happened. Well, I should have maybe kept going. Oh, sorry.

Just keep going on. From 1947 to 2007, 60 years, only 14 cases of. of active human infections with Sika were described. 14. So in 60 years. And were those all in Uganda? No. So they were in various places.

Sometimes they were specified. Sometimes they weren't. So they weren't necessarily all from Uganda. Okay. So this list includes a 10-year-old girl from Africa whose home country was not specified, who had a fever and headache and antibodies against Sika. And then there was a research. who decided to inject himself with the eastern Nigeria strain of Zika.

So he got ahead. Yeah. I think he was like, oh, it's mild. I want to be the first one to describe this about myself. Oh, geez. Whatever. And there were some other people here and there. All in Africa?

Yeah. So most of these Zika cases were detected in Africa. But at some point in the 1960s, the virus moved to Asia, popping up in Malaysia, Pakistan, and Indonesia in the late 60s and 70s. Okay. And then Zika began to pick up steam. Yes. Here's where we get rolling.

In 2007, a bunch of people on Yap, which is an island in the Caroline Islands group in the Western Pacific, started showing symptoms of something that resembled dengue, but was much milder. This infection was also accompanied by a rash, and tests for dengue came back negative. This sudden outbreak prompted a physician working at the Yap Department of Health Services to reach out to the CDC for help. The CDC deployed some EIS agents and they began the hunt. Oh, our dream, my dream.

My dream, too. Sample after sample came back positive for Zika, which was bizarre. In the 60 years of Zika history at that point, the virus had never been responsible for a large outbreak. Like, it was barely recognized to be a disease causing pathogen in humans. Right. It's just like, oh, yeah, it's like four people have gotten sick. Like, they had a headache. Yeah.

Yeah. And when I say a large outbreak, I mean that an estimated 73% of Yap's 7,000 inhabitants became infected with Zika over a five-month period. Whoa. 73%. And they, like, 73%... Had symptomatic illness? No.

So 73% was estimated based on those who did have symptomatic illness. Interesting. So this is based on the 20% symptoms, 80% asymptomatic breakdown. Wow, though, 73%. Yeah. Wooey. And then, just like that, it faded away. 2007, gone.

So 1947 pops up. Nobody cares. Nobody cares. 2007. What's going on? Then nobody cares. Yeah, basically. Because of the mildness of symptoms, if you were even unlucky enough to have symptoms, the hospitals and clinics weren't overwhelmed by people seeking treatment. And so, yeah, it just showed up. It spread through the population like wildfire, and it disappeared without seeming to leave any substantial damage in its wake at first. But before the aftershocks of Zika would be recognized, the virus made its second dramatic appearance again in a Pacific Island group, this time in French Polynesia. In October in 2013, six years and a few months after the Yap outbreak had ended, alerts went out about a bunch of people with rashes, fevers, bloodshot eyes, swollen joints, with most of these cases occurring on Tahiti. Again, dengue was the primary suspect, and that in itself was worrying. The first time you get dengue can be excruciating.

They don't call it breakbone fever for nothing. But if you are exposed to a different stereotype, you can actually get something called dengue hemorrhagic fever or dengue shock syndrome, which can kill you much more easily. So if this was a new type of dengue that the island group hadn't seen before, that was very concerning. Yeah. But again, test for dengue came back negative. And again, the true culprit was found to be Zika virus. As with the Yap outbreak, a large proportion of the population of Tahiti became infected with Zika, with the majority of infections being asymptomatic, and the cases that were symptomatic tended to be, again, mild, rarely requiring hospitalization. But then something started happening.

The first indication that Zika was not as benign as it seemed. Here and there, a person infected with Zika would show up to the hospital a couple weeks after their illness and report with partial paralysis. These cases were determined to be Guillambore syndrome, and the link to Zika was pretty clear, at least statistically, where in previous years there would be three to five cases of Guamarei. Now there were dozens. Dang. And the only thing that seemed to be different was the Zika outbreak. But that didn't stop the rumors, of course, that the cases of paralysis were caused by something else, like pesticides, for example. Always blame it on the pesticides.

Always. The easiest thing to blame it on. And that's, yeah, I mean, sometimes it is pesticides. But that's something that we see pop up time and time again in the history of Zika, rumors. I was trying really hard to work a Fleetwood Mac joke into here, but I cannot find anything. I could never come up with anything. You could have just started singing instead. Go on, give it to me, just a little.

Maybe I'll make a fake album cover. Anyway. Rumors. Rumors. At least in the months after the outbreak, it appeared that the only serious possible outcome of infection with the Zika virus was Guillambore. no reports of microcephaly had been made. And as with the Yap outbreak, the virus burned through the population.

This time, only 66% of the population of around 250,000 people was infected. Only 60% of 250,000. Yeah, no big deal. NBD. Just a few thousand people. No big deal. A handful, really. Really?

And then it seemed to disappear. In following this large-scale outbreak, Zika showed up on other islands in the Pacific throughout 2014, including Rappanui, also known as Easter Island, and the Cook Islands. But these outbreaks didn't get as many headlines as the one on Yap. And in French Polynesia, largely because the population wasn't as big, and also probably because Zika still wasn't considered much of a threat. The next time Zika would make front-page news, it would do so in a big, big way, an international way, and it would stay there for months, if not years.

Yeah. Let's continue our journey across the Pacific, jumping across South America and landing all the way over on the Atlantic coast of Brazil, May 2015, where a Zika epidemic was raging. Although later molecular tests would show that the virus had been circulating in Brazil at least since 2014, the epidemic wasn't recognized until May 2015, probably for many reasons, including mosquito population dynamics and the natural epidemic growth of this population. During the middle of the Brazil outbreak,

there was a lot of discussion as to where did this come from, where did this come from? It could have been a lot of different sources, but it seems likely that it was, that it came over at some point during the something called the VAA World Sprints, VAA World Sprints, which is this outrigger canoe races held in Rio in August 2014.

And so this is a month after the World Cup that had many participants from the Pacific Islands where there had been cases of Zika. So another theory is that it was introduced during the FIFA Confederation's Cup, which is a pre-World Cup match thing. Match thing. Yeah, I don't know.

Some big-time football people are going to be like, it's not a match thing. Erin. Listen, it can be a match thing if I wanted to be a match thing. Obviously not sports fanatics over here. That match thing was played in June 2013, and so that would mark a slightly earlier origin. Yeah. Would that also be even earlier than the French Polynesia outbreak? It would, but there has also been indications that the virus was present in Haiti and some other Caribbean islands before, or at least at the same time as the French Polynesia. Huh, interesting.

So up to this point, we had seen how the virus could act on relatively small islands, but how would it behave when it got to a country with some very high population densities and then spread to the rest of the continent? Because mosquitoes don't exactly acknowledge political boundaries. At first, the epidemic mirrored that of Yap and French Polynesia, mostly mild infections with very few people needing hospitalization and a heightened incidence of Guillaumbara. But this epidemic was different than those other ones in a couple of key ways. One expected and the other a complete surprise.

First, Zika didn't burn through the population like it did in the island outbreaks, but rather established more of a permanent transmission zone, which was somewhat expected given that the much larger population meant a constant supply of susceptible people, and a much, much larger geographic area meant more places to spread. And at this point, you can probably guess what the surprise difference was in this outbreak, because there's one essential thing about Zika that has been conspicuously absent from the history so far. Microcephaly. You got it.

Yeah. In October 2015, five months after a Zika epidemic had been confirmed, doctors in the northeastern city of Recife, noticed that they were delivering an unusually high number of infants with microcephaly. And a few of these doctors suggested that there was a link between the Zika virus and microcephaly, based purely on the shared epidemiological patterns of the two. Both Zika and microcephaly were highest in the northeastern part of Brazil, and the delay between the Zika outbreak and the microcephaly made sense, given a prenatal exposure. And in November of 2015, Brazil declared a state of emergency as the number of diagnoses,

as the number of diagnoses of microcephaly climbed past 2,700. Some obstetricians and even public health officials were advising women not to get pregnant, which was unheard of. Yeah. And it shows how dramatic the uptick and microcephaly was during this time and also serves as a bit of a preview for the many debates that would be held on the international stage about Zika, its effects, and recommendations for those in endemic areas.

At the time when the state of emergency was declared, there was, as of yet, no definite pathophysiological evidence, no lab studies on animal models, no meta-analysis that clearly demonstrated the link between microcephaly and Zika, which naturally led to speculation. And I'm sure you remember some of the other rumors about what was causing the increase in microcephaly, genetically modified mosquitoes to fight dengue, chemical larvae, and drinking water that was intended to kill mosquito larvae. Yeah. The Rubella vaccine. Oh, I didn't hear that one.

Yeah, because apparently rubella can cause microcephaly. Yeah, it can cause a lot of fetal defects if a pregnant woman gets infected, but also pregnant women don't receive the MMR vaccine, which contains Rubella, because it's a live vaccine. Well, we've never known antivactors to be logical or fact based in any of there. Sorry, maybe. Another one was that there was no actual increase in microcephaly cases at all, but that Brazil hadn't been keeping track of the cases well, or they had changed the definition so that a larger skull circumference would be classified as microcephalic.

Side note, it was actually the reverse. So the upper limit of what was considered microcephaly had actually been decreased. Oh. Yeah. But for most of the cases that were microcephaly as a result of Zika, they were not on the borderline. Right. So it wouldn't have mattered.

Yeah. And then there was the apparent absence of microcephaly outbreaks in places where Zika was endemic, such as parts of Africa and Asia. But that could be explained by early exposure and subsequent lifetime immunity, which also explains why we hadn't really seen a big outbreak. It probably has just been there circulating for a long time. It seemed like every time one rumor was discounted, another popped up into its place.

I remember these rumors making the rounds during late 2015 and early 2016. None of them calling themselves rumors, of course. More like, could Frankenmuskitos be responsible for the increase in microcephaly? Like BuzzFeed headlines kind of thing. Right. Well, and then the article that goes with that headline just wildly speculates, and it's not actually asking that question. It's more like Frankenmiscitos could be responsible, you know.

And it takes phrases like could indicate as yes, definitely it does this. Right. And this is where the very real disconnect between how science is written about for academic journals and how science is written about for newspapers becomes very apparent. Oh, God, yeah. For instance, if there is a paper in a scientific journal that said, this finding is highly suggestive of a causative link between Zika and microcephaly, that sounds, that might sound very,

uncertain, or at least more uncertain, compared to Zika causes microcephaly. I just feel like what you said sounded so certain. I was like, wow, were there papers that said that back then? Because to me, that sounds like really, but that's because I read scientific papers. You read these papers. And it is, I mean, all of the wording is incredibly cautious, because that's how science is done. Very, very rarely is anything ever proven. Instead, hyper, hypotheses are supported. Every now and then, rarely, a theory will be developed, and that's about the closest thing we have to anything being proven. And this is one of the reasons that the link between Zika and microcephaly seem to take a while to become fully established. There cannot be

jumping to conclusions. Each piece of evidence has to be carefully measured and weighed, especially when lives are on the line. All things considered, the link between Zika and microcephaly took not very long at all to be established, thanks in part to a policy of freely publishing data that many researchers took part in, as well as a pledge to make Zika articles freely accessible during the duration of the emergency. On February 1st, 2016, the WHO declared a public health emergency of international concern over the possibility that Zika caused microcephaly, which was very carefully worded, the possibility. But not more than two months later, the wording of the WHA's Zika report changed to, quote, based on observational cohort and case control studies, there is

strong scientific consensus that Zika virus is a cause of GBS, microcephaly, and other neurological disorders. GBS meaning Giambore. Scientists looked back at places that had Zika outbreaks before, like French Polynesia and Yap, and found clusters of microcephaly. They did lab experiments showing that the virus injected into a mouse at any stage of pregnancy could be deadly to the fetus. And they had case control studies in which they followed women who had tested positive for Zika infection during pregnancy through the time they had given birth. There was no one study that showed this definitive link. It was many small ones, because that's how science is done. And this link, like you mentioned, between a mosquito-borne virus and a horrible neurological disorders was unprecedented in medicine.

If most of the world had had its head turned toward Brazil during late 2015, its eyes were starting to wander in the early months of 2016 as the virus made its way throughout other parts of South America and up through Central America. Even before the link between Zika and microcephaly had been established, even before the WHO had declared its first global emergency, countries were issuing travel advisories for its citizens. If you are pregnant or thinking of becoming pregnant, you shouldn't travel to X or Y country where there is an ongoing outbreak of Zika. And as the sexual transmission aspect of Zika became apparent, that was incorporated into the warning. It became more wide. It wasn't just towards pregnant women. It was also about if you have been to a country, you should consider this and etc.

You should use safe sex practices and blah, blah, blah. Yeah. Of course, there was a lot of fear. bringing the virus to the U.S., because the mosquito vector is present there. But what about warnings or advice for the people living in those epidemic regions? What should they be told about Zika? As I mentioned earlier, some public health officials and physicians were advising their patients to wait to get pregnant, but there had been no formal statement to that effect from governments

early on. And should there be? This was a big debate among reproductive health and infectious disease specialists and was reported to be causing quite a rift within organizations like the CDC. What role, what right does the government have to make these recommendations to women about what they should or shouldn't do with their bodies and when? Access to birth control wasn't possible for many. In some places, most of the women in these countries.

For married women in Guatemala, Bolivia, and Haiti, less than 35 percent of women had access to birth control at the time that this book was written. So in 2016. Other places fared barely better, 50%, 60%. And what about women who can't delay pregnancy by a couple of years due to biological reasons? Or they just don't want to. Or they don't want to. Yeah.

And what about the dark history of forced birth control that has lingered in some places, sterilization programs for convicted people? Ultimately, most countries didn't recommend waiting to get pregnant, although some said wait two years, wait six months, whatever. Most instead recommended protective measures such as mosquito nets, bug spray, and screens. But this brought to light the really important issue of access that I, in reading this book, didn't feel like it got enough attention or coverage. Access to accurate information, access to health care, access to birth control, access to these protective bug nets, these mosquitoes.

these mosquito sprays, access to the things that would allow you to protect yourself and your family and to make an informed decision. I remember when they were talking about making those recommendations and in some areas making them, like just telling women, you can't get pregnant, don't get pregnant, and just being so infuriated at that idea because it is often so difficult to get birth control. I mean, even in the U.S., it's often very difficult to get birth control, you know. Yeah. Oh, it was just so infuriating. Even if these recommendations had been made, because even if it was just these,

these governments saying you should wait to get pregnant, then it's almost like they're washing their hands. Yeah. Of things because it's like, well, then if you got pregnant, you went against our recommendation, so there's nothing we can do for you. Instead of the fact that it's like, well, it wasn't exactly a choice for me, perhaps, that I, you know, all of these different aspects. Amidst these debates, Zika was continuing to spread and spread and spread. And panic reached an all-time high during the lead-up to the 2016 Olympics in Rio. Yep.

And the final tally of cases of Zika and cases of microcephaly reported for those attending the games was zero. Oh. Yeah, so zero. Very anticlimactic. Great, though. But, well, make no mistake, Zika was still an ongoing problem in Rio during this time, particularly in poor areas with little infrastructure and no access to health care. Just not amongst people who were at the Olympics. Who could afford to travel to the Olympics and spray themselves with bug spray or whatever else?

I think that this so far in our podcast is the closest the history has gotten to the epidemiology. Yes. So I feel like we should just jump straight into it. Erin, tell me about Zika now. Is there a vaccine? Let's do it. Anyone who works long hours knows the routine. Wash, sanitize, repeat.

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first car? The one you wish you'd never sold, but now, you finally get the chance to take back home for good this time. Shop eBay for millions of fines, each with a story. eBay, things people love. Okay, Pahoe, which is the Pan American Health Organization, during, like from 2015 all the way through 2017 had lists that were updated several times a month of the cumulative case reports from every country across the Americas that included the number of octokthenus cases. That's a new vocab word. I love that word too. It's such a good word.

Attoctthenus. Erin, tell us what it means. Basically, it means, are you telling, are you asking me or are you asking you? Oh, good question. I'm asking you. I know sometimes you talk to yourself. I do. So basically it means arising from the.

the same location. Exactly. Yeah. So octagonist cases of transmission in the U.S. are cases that weren't imported from somewhere else. They're cases that were transmitted in the U.S. So the number of octahlinous cases as well as the number of imported cases. But what I find gobsmacking about the Pahoe, good word. Great word. The most recent update that Pahoe has about the number of cumulative cases of Zika virus was last updated January 4th, 28. So a year ago. We'll see if this changes by the time we release this episode. But as of recording, the data that I have is from one year ago.

Okay. So as of January 2018, the countries that have been hardest hit by far in terms of the total number of cases are Brazil and Puerto Rico, over 137,000 total cases in Brazil and over 40,000 in Puerto Rico. And that's just confirmed cases. That doesn't include many, many more suspected cases. Is that number total or is that just for 2016 and 2017 or 2017? That's 2016-2017. So we don't have numbers from 2018 yet. And what's also important to point out, and I do want to make this important because

it's important in epidemiology in general, but it's super important in this case, is that those are the largest number of cases overall. So while Brazil had the largest number of cases, it's a massive country, right? So in epidemiology, we don't really look at raw numbers that often we usually use incidence rate rather than straight numbers to get a sense of how many people are affected based on the population's size. So we look at the number of cases per 100,000 people. Yeah. So in that case, it's actually some of the Caribbean islands, for example, Kurosau, which had over 2,000 confirmed cases, but the incidence rate, is over 4,000 cases per 100,000 people.

Oh, my gosh. And in Brazil, the case rate is still extremely high, 176 cases per 100,000 people in Brazil. Wow. Yeah. That's really high. It's really high. Puerto Rico, the incidence rate was over 1,000 cases per 100,000 people from 2016

and 2017. Oh, my God. So for comparison, in the U.S. in that time period, there were 227, confirmed octahthenous transmission cases. That means people who acquired Zika infection in the United States, 227. That's a incidence rate of 0.06 cases per 100,000 people. So overall, across all the countries in the Americas that have been affected, there have been over 223,000 confirmed cases and 580,000 suspected cases.

Wow. as well as 3,720 cases of confirmed congenital Zika syndrome. Ugh. Yeah. It only had 20 deaths listed, but I'm not sure that that counts fetal deaths or early pregnancy loss. I don't believe that it does, but I'm not positive. Okay.

So, and I will say that this is not the only place that Zika is happening. So I actually was checking ProMed and there was an outbreak of Zika going on in India, very recently. Okay. And do we know what strain that is? I have absolutely no idea because I didn't go further down that rabbit hole. It's a great question, though. Okay. So now the question is, what are we doing about it? Now that Zika is on everybody's radar, we should have a vaccine for it, right? Just like after the Ebola outbreak, we had a vaccine, right? Right? Oh, yeah. Yeah. No. Well, we do now, though. Well, let's talk about why.

So one of the things I think that I was so excited to talk about Zika virus is that it's such a beautiful example of a disease that we have known about for 70 years. That's a long time. And yet we know so little about this disease. Yeah. One of the reasons is, in our scurvy episode, you touched briefly on the idea of developing animal models, right? which is a really important part of studying diseases that infect humans. And I don't remember the exact year that you said the guy came up with the guinea pig as the model. 1893.

Thank you. Wasn't it really? No. I don't have no idea. But it was a long time ago, right? It was a very long time ago. And that's what allowed us to hone in on and figure out what exactly was happening with scurvy. Well, with Zika, it's not that we didn't have any animal models.

that they didn't exist at all, but two things. One, very few good animal models actually did exist. And number two, the ones that did exist were made from very, very old strains, like the 1947 first discovered strain of Zika virus. And viruses evolve. They change. So it's important to have animal models that actually reflect the viruses that are circulating in the population. And it has only been in the last three or four years that you can find a ton of papers where people are literally developing animal models to study Zika. Wow. It is so cool.

So is there a candidate animal model now? There are several. And so I'll post some of those. There's actually a really nice review that goes through all of the research that's been done currently and what the most promising animal models are. And so mostly it's mice and non-human primates. So those are the two biggest ones. And makes sense. Right. They're just kind of some of the biggest in general. But what's really important is developing this non-human primate model, though, because the effects of Zika, like mouse placentas aren't equivalent to human placentas. And mouse fetal development is nothing like, well, not nothing like, but very dissimilar to human fetal. development. So developing these non-human primate models in order to study the effects of Zika on fetuses is really, really important. Right. And so they've done a lot of that. They've infected pregnant monkeys with Zika and found their fetuses to have reduced growth of the fetal brain,

white matter deficiency, axonal damage, which means damage to the axons, which are like the long spindly bits of your neurons, and more. And they've been able to detect Zika virus in all different kinds of placental tissue and fetal tissue. Wow. Yeah. So these links are very clear, even though we don't know the exact pathophysiology of like how exactly is Zika infecting this cell and then what is it doing within that cell. We know that it's infecting the fetus. It's infecting the fetus brain and it's causing this damage. And development of these animal models allows us to get a better understanding not just of that pathophysiology so that someday we will know exactly how it's causing disease. We can also study the mechanisms by which it's able to be sexually transmitted.

Yeah. We can study the mechanisms by which it can cause Gian Bray. This also allows for the study of antibody therapy, antiviral therapy, and vaccine development. Uh-huh. So let's talk about it. There are vaccines in development, including at least several DNA vaccines. Oh, my fave. Your fave. However, it's many, many years away before we'll see any real action from that most likely. That makes sense.

It makes sense because prior to these most recent outbreaks, nobody was paying attention to Zika. which also makes sense. I mean, it was a very mild infection that no one knew had this under its up its sleeve. So I think an important contrast to make here is that with Ebola before the 2014 outbreak, there had been a lot of funding to study Ebola, and there had been vaccines that were in development, but funding for those had often dried up. And so while they had been started down the long road of vaccine development, they hadn't made it all the way. With Zika, people have been starting completely from scratch.

So the World Health Organization has a pretty awesome, actually. I can't believe I just found out about this. They have a vaccine development tracker, and I'll definitely put a link to it on our website. But on this, you can see the status of vaccine development for a whole number of different diseases, including Zika virus. So there are, yeah, it's very cool. There are a lot of different groups that are working on it,

and you can see exactly what phase they're in. So at this point, basically all of the Zika vaccines are in phase one trials. There's two that are in phase two trials. Okay. Phase one is essentially just making sure that this vaccine is safe and not going to kill people or maim them. So you just give... Important? It's really important.

You just give the vaccine to a small number of people, probably in various dosages, and you're just trying to make sure that it doesn't make anybody sick or cause any serious adverse reactions. phase two is when you actually try and see if it works, which is harder to do. It's not testing it against anything else. That's phase three where you have like controls, right? So it's just trying to see if it's effective at all. And this is hard for, well, it's hard for vaccines in general, but it's really hard for diseases that have low incidence. Because if you're never exposed to a disease, you can't really, really test if it works.

but we also can't give people diseases. That's not ethical. So what you can do is test for an immune response. So you can give people a vaccine and then you can test their blood after a certain period of time to make sure that they're actually making antibodies against the vaccine components. So cool. So that's the stage that two of the vaccines are in, but most of them are still just in phase one where they're just trying to make sure that they're a vaccine. vaccines don't kill anybody. Hmm.

And that's what's happening with Zika research. That's pretty cool. It's pretty cool. It's been very quickly added to the WHO's list of priority diseases. So, yeah, it's, I think, probably very exciting time to work in the Zika field. Yeah, I can imagine. So I have a question. Okay.

Only 5 to 15% of women who. who are infected with Zika while pregnant have an adverse outcome. Right. Are there any other outcomes associated with the 95 to 85% of women who are not? So something like are there developmental disorders in otherwise physically healthy children? Are there anything that's diagnosed at a higher rate? Anything like that? It's a good question.

And I don't think that we know yet at this point. Because remember that since the first time that we found out that even Microsoft Cephaly was a thing associated with Zika was just two years ago. But some of those kids, presumably from like the Yap outbreak or the French Polynesia would be Right. But that would mean that people would have to be doing studies on those people now. And I don't know that they are. So I would guess that I know that in Brazil there are definitely longitudinal studies that

are being done and are probably following up on those exact outcomes. But I don't know if people have looked back to see in older kids if there's any. other effects. I'm not sure. It's a really good question, though, because it definitely, you know, seems possible. Right. Yeah. That's Zika. Wow. It's a scarier one than I gave it credit for when I first heard about it. That's for sure. Oh, yeah. It's a scary one. It's a sad one. And it's definitely present tense, future tense verbs apply here. Yeah, absolutely. It will be very interesting. I think to see if there is continued cases and continued sort of epidemics of microcephaly or in the Americas, or if this becomes like it perhaps was in Africa just sort of an endemic disease that people get exposed to in childhood,

and then we no longer see it as affecting pregnant women because women have been exposed to it when they're younger. It's going to be really interesting to like follow Zika over the next few decades. Yeah, absolutely. Yeah. Sources? Yeah. I have some papers that I will put on the website. And I also, as I mentioned earlier, the book Zika by Donald McNeil, which was written in 2016 before the Olympics, right on the heels of that first or of the big Brazil outbreak.

Cool. I have a number of articles. The one I do want to shout out that I thought was super interesting was by Thomas Morrison and Michael Diamond. That is a summary of animal models. We will, as always, link to all of the articles and books that we used in this episode on our website. That's this podcast will kill you.com slash episodes. So you can find all of our sources from every episode there. And.

And thanks to Bloodmobile for providing the music for this episode and all of our episodes. Love you. And thank you, dearest listeners, for listening to our ramblings. We love you. Yes, we do. It's the best. It is. Okay.

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