The real and terrible consequence could be seen on CT scans, MRIs and ultrasounds. Those tiny heads contain shrunken brains. Sometimes just the funnel 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?
Jeez.
Yeah, it was really intense, but that's also the reality. Yeah, Itzica, it's dang.
Yeah, it's awful, It's really awful.
Yeah.
So that firsthand, that really horrible, sad description is from a book called Zeka by Donald Neil.
Okay, well, hi, hi, we always managed to start on really great notes.
I mean, this podcast, what's this podcast about?
Oh?
Yes, yeah, I'm Aaron Welsh and I'm Erin Almond Updyke and this is this podcast will kill You And today we're talking about none other than zeca 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 zekea is, let's arm ourselves with a stiff drink. Let's do that or a placey berita. So it's quarantining time.
I believe it is definitely quarantine 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 zeka is transmitted by the tiger mosquito, and in part because one of the symptoms is conjunctividis a haha, pany as heck today erin 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 as the non alcoholic version our placey ba Rita 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 Zica. I want to hear about this is. 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 zica, which is exciting. And what I think is so interesting and I can't wait aron 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 zeica virus because I don't even know that I heard of it before, like twenty fifteen.
No, yeah, 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 zica is just brand spanking new.
Yeah.
I mean, it's still happening, right, But I don't want to steal your thunder of oh the history though you Let's just talk about the virus itself and how it makes you sick. Okay, So Zeca virus is a virus that very obvious it is. You know, we could go crazy, you know, call something Zeka virus and have it be a No, it's a virus. It's in the family Flavivii. Day and so perhaps some really deep listeners or recent binge listeners might remember another disease we've covered that's in
this same family. Aaron, do you remember this.
Is gonna be embarrassing? Is it yellow fever?
It's a yellow fever?
Okay, good, thank great, Yes, 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 Dangay, Japanese encephalitis, West Nile, 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. Zeka happens to be transmitted by the same mosquitoes that transmit yellow fever and Dangay virus and chicken gunya.
But those are all different stories. And that's eighties a jypdi and eighties albapictus, 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 bitters. 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 biers, so they'll bite you all day long. They're not like other mosquitoes that will only bite at like dawn or dusk.
Or crepuscular one of my favorite words.
It's a good word. And so diseases that are spread by these mosquitoes, like yellow fever dangay zica, 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. It's these diseases aren't going to stop being an issue anytime soon.
And urbanization and change and clear the things, 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 ZEKA 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 born disease because It really adds a whole nother layer of complexity to control efforts, right, which are already really difficult when you're dealing with vector born diseases.
Yeah, I can't believe how long it lives.
I've read something about someone who it was circulating. They found traces of the virus in their semen sixty two 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 sixty two 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 zica can be transmitted, and that's vertically. So vertical transmission is from mother to baby, and so in this case, Zica 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 zica could be transmitted this way until very recently, and as far as I know, it's not that common for mosquito or vector born diseases to be able to cross the placenta.
Yeah, I don't think so.
Yeah, but it's not it's not that out there. Just in terms of a biology perspective, there's a number of viruses and bacteria that can that can cross the placenta. So those are all the ways that you can get infected with ZICCA.
Fantastic.
So the question is what happens once you get in affected?
Yeah?
Yeah, so okay, So the most 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 fourteen 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 how much how long it was feeding on you? Yeah, it's all this, 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 zecavirus compared to other flavaviruses, Like most of the time, if you're going to have someymptoms with ZICA, you'll probably have a rash. Also conjunctivitis, hence the.
Name of our quarantine pink guy.
Pink iy raise your head if you had pink eye as a kid. Who didn't, Oh yeah, everyone did, right, It wasn't 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 flavaviruses, malaise, 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 eighty percent of people who are infected with zeca virus don't ever develop any symptoms.
That's yeah, I've 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 eighty percent of people never showing symptoms ooof 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 mosquito born 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 zecavirus infects your specific cells and causes damage we don't entirely know. So we don't know the exact path of physiology of zica virus yet.
That it makes it a little bit harder to target and its acts differently or it's suspected to act differently than other flavaviruses.
I don't know the answer to that question, okay, But Zica 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 Zica, you'll probably find Zeca 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 Zeca virus particles.
I have a question about bodily fluids. Okay. Do boogers and snot count totes? Yeah? Okay?
And so on top of this sort of general nondescript symptoms, there are a number of different complications that can arise as a result of Zica infection. So there's an increased risk for future neurologic complications like gion beret syndrome, myelitis, general nerve issues, and also things like meningitis are possible as a result of Zeica virus infection. Right, But the biggest complication that we mentioned in our first hand account
and that people has probably become. The most famous is that five to fifteen percent of infants born to pregnant women who are infected with ZICA during their pregnancy have
evidence of complications directly related to Zica virus infection. These complications include intra uterine 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 ZICA. The exact mechanism of how this happens is not clear.
Are their thoughts as to what it might be well.
So shortly after the connections between zecavirus and microcephaly were sort of brought to light, there was a lot of pushback because it's only five to fifteen percent 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 ZEKA 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 Zica 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's effects 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 Zica can be transmitted sexually, that's a pretty sinister picture of a disease. Yet me, it's pretty depressing. That's all I've got. That's zeka 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 twenty sixteen, nonet even heard of it? Is it brand new?
Well? The Romans called it just kidding, Okay. I feel like we all know the history of Zica, 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 twenty fifteen and twenty sixteen, 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 Gamboa about the danger of Zica 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 sam Blos, there was an outbreak of zica declared there like that was oh Zeca and plam Blas, And I was like, oh, okay, at least it's mild, you know, something like that stupid that I was thinking.
Oh yeah, that's I was the same way. I was like, man, maybe I should just try and get Zeka now. So then 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 US now, they test you for zica and they call you if it's positive. And mine was negative. So I didn't get zica.
Okay, so you never got zeka.
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, Zeka 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, 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.
Yeah.
Even though the first time that many of us heard the word zica was probably in twenty fifteen in connection with the words Microcephae and Brazil.
The Zeica virus had.
Actually been known for almost seventy years.
Amazing. I didn't know it was seventy years. I knew it was a long time, but dang.
Yeah, oh it's really Yeah.
Did you come across the meeting of Zica and any of your readings?
No? Okay, My favorite.
Part it actually means overgrown what and is Yeah, So it's taken from Zeica forest and Uganda, which is close to and Tebbi, where the Rockefeller found established its virus research Institute in the nineteen thirties. The swampy hot Zekea forest was the perfect place to accomplish some of the goals the research institute had laid out, including understanding mesquito ecology, exploring which animals are susceptible to different viruses, and the big one, discovering new viruses.
And this is a common theme in so 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 books. 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 alife.
Right, My God has 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. Yeah, one day, April nineteenth, nineteen forty seven, to be exact, because you know how I like to be exact, of course, a monkey with the charming name of Rees's seven sixty six was observed to have a high fever one hundred and four degrees fahrenheit forty degrees celsius now that I'm in Finland.
But 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 Reese's seven sixty six 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 Riese's seven sixty six.
Man, that just sounds like because so you can have coinfections. It 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, for sure.
Yeah, I don't know if.
I would have had the patience to be in microbiologists back then.
I don't even have the patients for it now. Yeah, fair point, Fair points why I do this podcast instead.
Uh.
Finally, they would test this new mosquito derived slurry on a monkey that had recovered from an infection with the original virus. Huh yeah, full circle, and the results of those experiments confirmed their hunch the virus was mosquito born transmitted specifically by the species, in this case eighties Africanus. But still they didn't know whether this was a new
virus or one that was already known. Since it was nineteen forty seven, 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 nineteen forty seven to two thousand and seven, sixty years.
Nineteen forty seven, they discover it, They're like, cool, we got a new virus. Nobody cares to two thousand and seven. Tell me what happened?
Well, I should have maybe kept going, Sorry, just keep going. From nineteen forty seven to two thousand and seven, sixty years, only fourteen cases of active human infections with CICCA were described. Fourteen so in sixty years.
And were those all in Uganda?
No, So they were in various places. Sometimes they were specified, sometimes that they weren't so, but they weren't necessarily all from Uganda. So it includes this list includes a ten year old girl from Africa whose home country was not specified, who had a fever and headache and antibodies against CICCA. And then there was a researcher who decided to inject himself with the Eastern Nigeria strain of ZICA, so he got a head Yeah. I think he was like, oh,
it's mild. I want to be the first one to describe this about myself, jeez.
Whatever. And there were some other people here.
And there, all in Africa.
Yeah, So most of these Zega cases were detected in Africa, but at some point in the nineteen sixties, the virus moved to Asia, popping up in Malaysia, Pakistan, and Indonesia. In the late sixties and seventies, Okay, and then Zeka began to pick up steam. Yes, here's where we get rolling. In two thousand and seven, 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
dengay but was much milder. This infection was also accompanied by a rash, and test for dengay came back negative. This sudden outbreak prompted a physician working at the yapp 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. Ye.
Sample after sample came back positive for ZICA, which was bizarre. In the sixty years of zeica history, at that point, the virus had never been responsible for a large outbreak.
It was barely.
Recognized to be a disease causing pathogen in humans.
Right, it's just like, oh, yes, 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 seventy three percent of YAPS seven thousand inhabitants became infected with ZICA over a five month period. Whoa who seventy three percent and they.
Like, seventy three percent had symptomatic illness.
No, so seventy three percent was was estimated based on those who did have symptomatic illness. Interesting, So this is this is based on the twenty symptom twenty percent symptoms, eighty percent asymptomatic.
Okay, breakdown wow though, seventy three percent yeah. Oh and then just like that it faded away, gone. So nineteen forty seven, pops up, Nobody cares. Nobody cares. Two thousand and seven, 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 it 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 ZICCA would be recognized, the virus made its second dramatic appearance again in a Pacific island group, this time in
French Polynesia in October. In twenty thirteen, six years and a few months after the YAP outbreak had ended, alert went out about a bunch of people with rashes, fevers, bloodshot eyes, swollen joints, with most of these cases occurring on Tahiti. Again, Dangay was the primary suspect, and that in itself was worrying. The first time you get dan gay 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 danngae hamorrhagic fever or Danngae shock syndrome, which can kill you much more easily.
Yeah.
So if this was a new type of dengay that the island group hadn't seen before, that was very concerning.
Yeah.
But again tests for Dangae came back negative, and again the true culprit was found to be zekavirus. As with the app outbreak, a large proportion of the population of Tahiti became infected with ZEKA, 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 zica was not as benign as
it seemed. Here and there, a person infected with ZICA would show up to the hospital a couple weeks after their illness and report with partial paralysis. These cases were determined to be Giambarret syndrome, and the link to ZICA
was pretty clear, at least statistically. Where in previous years there would be three to five cases of giambarre, now there were dozens and the only thing that seemed to be different was the Zeka 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 Zeica.
Rumors.
Trying really hard to work a Fleetwood mac joke and to hear, but I cannot find anything. I can never I never came up with anything.
You could have just started singing instead. Go on, give it to me just a little.
Maybe, 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 zekeavirus was giambarre. No reports of microcephaly had been made, and as with the YAP outbreak, the virus burned through the population. This time, only sixty six percent of the population of around two hundred and fifty thousand people oh was infected.
Six of two, or sixty six percent NBD, just a.
Few thousand people, No big deal.
Handful really really, and then it seemed to disappear. In Following this large scale outbreak, Zeka showed up on other islands in the Pacific throughout twenty fourteen, including Rapanui 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 Zica still wasn't considered
much of a threat. The next time Zico would make front page news, it would do so in a big, big way, in 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 twenty fifteen, where as Zeka epidemic was raging. Although later molecular tests would show that the virus had been circulating in Brazil at least since twenty fourteen, the epidemic wasn't recognized until May twenty fifteen, 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 when? It could have been a lot of different sources, but it seems likely that it was that it came over at some point during this something called the VA world Sprints VA world Sprints, which is this outrigger canoe races held in Rio in August twenty fourteen, and so this is a month after the World Cup that had many participants from the Pacific Islands where there had been cases of zeka.
So another theory is that it was introduced during the FIFA Confederations Cup, which is a pre World Cup.
Match thing that is that was played thing.
I don't know, some like big time football people are going to be like, it's not a match thing, Aaron.
It could 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 twenty thirteen, and so that would mark a slightly earlier origin.
Would that also be even earlier than the French Polynesia outbreak?
It would, But there have 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 mirrord that of Yap and French Polynesia, mostly mild infections with very few people needing hospitalization, and
a heightened incidents of Giambarre. But this epidemic was different than those other ones in a couple of key ways, one expected and the other a complete surprise. First, ZEKEA 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 Zica that has been conspicuously absent from.
The history so far microcephaly. You got it.
In October twenty fifteen, five months after Ezeka 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 zekavvirus and microcephaly, based
purely on the shared epidemiological patterns of the two. Both ZICA and microcephally were highest in the northeastern part of Brazil, and the delay between the ZICA outbreak and the microcephaly made sense given a prenatal exposure, and in November of twenty fifteen, Brazil declared a state of emergency as the number of diagnoses of microcephaly climbed past twenty seven hundred.
Some obstetricians and even public health officials were advising women not to get pregnant, which was unheard of, 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 zicca, 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 demonstrate the link between microcephaly and ZICA, which naturally led to speculation. And I'm sure you remember some of the other rumors about what was causing the increase in microcephally genetically modified mosquitoes to fight dangay, chemical larvacide and
drinking water that was intended to kill mosquito larvae. Yeah, the rubella vaccine. Ooh, I didn't hear that one. Yeah, because apparently rubella can cause microcephale.
Yeah, it can cause a lot of fetal defects in 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 anti vaxxs to be logical or fact based in any.
Of their Sorry.
Maybe another one was that there was no actual increase in microcephale cases at all, but that Brazil hadn't been keeping track of the case as 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 microcephale had actually been decreased. Ooh, but for most of the cases that were microcephae as a result of ZICA.
They were not on the borderline, so it wouldn't have mattered.
Yeah.
And then there was the apparent absence of microcephale outbreaks in places where ZEKA 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 twenty fifteen and early twenty sixteen, none of them calling themselves rumors, of course, more like could franken mosquitoes be responsible for the increase microcephaly?
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 frank and mosquitoes could be responsible, you know, And it takes phrases like could indicate as yes, definitely.
It does this.
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. Yeah, for instance, if there is a paper in a scientific journal that said, this finding is highly suggestive of a causative link between zica and microcephaly, that sounds that might sound fairly uncertain, or at least more uncertain compared to zica causes microcephale.
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, 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 zica and microcephale 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 zica and microcephally 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 ZICA articles freely accessible during the duration of the emergency.
On February first, twenty sixteen, the WHO declared a public health emergency of international concern over the possibility that zica caused microcephaly, which was very carefully worded the possibility, but not more than two months later, the wording of the WHO Zeca report changed to quote. Based on observational, cohort and case control studies, there is strong scientific consensus that Zeca virus is a cause of GBS microcephalye and other
neurological disorders GBS meaning gambarre. Scientists looked back at places that had ZEKA 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 ZICA 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 born virus and a horrible, horrible neurological disorders was unprecedented in medicine. If most of the world had had its head turned toward Brazil during late twenty fifteen, its eyes were starting to wander in the early months of twenty sixteen as the virus made its way throughout other parts of South America and up
through Central America. Even before the link between Zica 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 zica. And as the sexual transmission aspect of zica 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 yeah, etc.
Use safe sex practices and blah blah blah.
Yeah.
Of course there was a lot of fear about bringing the virus to the US 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 thirty five percent of women had access to birth control
at the time time that this book was written. So in twenty sixteen, other places fared barely better fifty percent, sixty percent. And what about women who can't delay pregnancy by a couple of years due to biological reasons, or they just don't What about too or they don't want to? Yeah, 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 did said wait two years, wait six months, whatever. Most instead recommended protective measures such as mosquito nets, bugspray, 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 healthcare, access to birth control, access to these protective bugnets, these 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 US, 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 rs, 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, Yeah, admits these Zica was continuing to spread and spread and spread, and panic reached an all time high during the lead up to the twenty sixteen Olympics in Rio. Yeah, and the final tallly of cases of zica and cases of microcephaly reported for those attending the games was zero.
H yeah, so zero very anticlimactic.
Great, yeah, but well, make make no mistake. Zica was still an ongoing problem in Rio during this time, particularly in poor areas with little infrastructure and no access to healthcare.
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. So I feel like we should just jump straight into it. Aaron tell me about you can know? Is there a vaccine?
Let's do it.
Okay. PAHO, which is the Pan American Health Organization during like from twenty fifteen all the way through twenty seventeen, 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 octocthonous cases. That's a new VOCA word. I love that sorta word, autocthinus. Aaron 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 you.
So basically it means arising from the same location exactly.
Yeah, So octogulinist cases of transmission in the US are cases that weren't imported from somewhere else. There are cases that were transmitted in the US. So the number of octopolinist cases as well as the number of imported cases. But what I find gobsmacking about the pah.
Good word, great word.
The most recent update that pa Hoo has about the number of cumulative cases of zecavirus was last updated January fourth, twenty eighteen.
So a year 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 twenty eighteen, the countries that have been hardest hit by far in terms of the total number of cases are Brazil and Puerto Rico. Over one hundred and thirty seven thousand total cases in Brazil ill and over forty thousand 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 twenty sixteen twenty seventeen or twenty seventeen to twenty that's.
Twenty sixteen twenty seventeen, so we don't have numbers from twenty eighteen yet. And what's also important to point out, and I do want to make this important because it's important in epidemology 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 one hundred thousand people. Yeah, So in that case, it's actually some of the Caribbean islands, for example Curasow, which had over two thousand confirmed cases, but the incident's rate is over four thousand cases per one hundred thousand people.
Oh my gosh.
And in Brazil the case rate is still extremely high, one hundred and seventy six cases per one hundred thousand people in Brazil.
Wow.
Yeah, that's that's really high. That's really high. Puerto Rico, the incident's rate was over one thousand cases per one hundred thousand people from twenty sixteen to twenty seventeen. So for comparison, in the US, in that time period, there were two hundred and twenty seven confirmed octogthonous transmission cases. That means people who acquired zeke infection in the United States two hundred and twenty seven. That's a incidance rate of point zero six cases per one hundred thousand people.
So overall, across all the countries in the Americas that have been affected, there have been over two hundred and twenty three thousand confirmed cases and five hundred and eighty thousand suspected cases. Is three thousand, seven and twenty cases of confirmed congenital ZEKA Syndromeugh. Yeah, it only had twenty 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 ZICA is happening. So I actually was checking pro med and there was an outbreak of ZICA going on in India very recently.
Okay, and do we know what strain that is or 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 zica is on everybody's radar. We should have a vaccine for it, right, just like after the a bullet 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 zica virus is that it's such a beautiful example of a disease that we have known about for seventy 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.
Eighteen ninety three, Thank you, wasn't it really?
No, I don't have no idea, but it was a long time ago.
Right, it's 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 zeica. It's not that we didn't have any animal models. It's not 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 nineteen forty seven first discovered strain
of Zeca 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 zeka. Wow, it is so cool.
So is there 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 zica, 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 ZICA on fetuses is really really important, right, And
so they've done a lot of that. They've infected pregnant monkeys with ZICA 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 ZECA 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 ZEKA 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 gion beret. This also allows for the study of antibody therapy, antiviral therapy, and vaccine developments. Aha, so let's talk about it. There are vaccines in development, including at least several all DNA vaccines.
Oh fav 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 zica.
Which also makes sense.
I mean, it was it does, a very mild infection that no one knew had this under its right up its sleeve.
So I think an important contrast to make here is that with ebola. Before the twenty fourteen 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 zica. 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 zecavirus. 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 Zeka 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 maime them.
So you just give importance 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, Yeah, so it's just
trying to see if it's a 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 incidents 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 a thick hole. 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 their vaccines don't kill anybody. And that's what's happening with Zeka 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 a I think probably very exciting time to work in the ZEKA field.
Yeah, I can imagine.
So I have a question, Okay, only five to fifteen percent of women who are infected with ZECA while pregnant have an adverse outcome, right, are there any other outcomes associated with the ninety five to eighty five percent of women who are not, so something like are there developmental disorders in otherwise, you know, 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 microcephaly was a thing associated with ZICA 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 study 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 sika. 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 follow Zeka over the next few decades.
Yeah, absolutely, yeah, uh sourceness. Yeah.
I have some papers that I will put on the website. And I also, as I mentioned earlier, the book Zeka by Donald McNeil, which was written in twenty sixteen 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 dot 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 yeah, and thank you dearest listeners, listeners to our ramblings.
We love you, Yes we do. It's the best.
It is, Okay, until next time, wash your hands, you filthy animals. U.