Tropical diseases in the U.S. and prevention efforts

Host Amber Smith: Upstate Medical University in Syracuse, New York, invites you to be The Informed Patient, 播客中有来自纽约中部唯一的学术医疗中心的专家. I'm your host, Amber Smith.

It's important to be aware that some traditionally tropical diseases are being transmitted in the United States.

Today we'll talk about the Zika and dengue viruses with Dr. Stephen Thomas. He's professor and chair of microbiology and immunology at Upstate, and also the director of the Upstate Global Health Institute.

Welcome back to "The Informed Patient," Dr. Thomas.

Stephen Thomas, MD: Thank you, Amber. It's great to be back.

Host Amber Smith: Listeners may remember hearing from you frequently during the COVID pandemic, but you've worked extensively on vaccine development for other viruses, including Ebola and Zika. And before you came to Upstate, you spent 20 years in the U.S. Army Medical Corps at the Walter Reed Army Institute of Research.

在我们讨论登革热病毒之前，我想问一下寨卡病毒疫苗的进展情况. And can you first remind us what the Zika virus is?

Stephen Thomas, MD: Sure. The dengue viruses and Zika virus are in the same family, so they're called flaviviruses, and yellow fever is in that family, and West Nile virus, which we've had a history of in New York, is also in that family, as is Japanese encephalitis virus.

所以，正如你提到的，大多数都位于热带和亚热带气候. They're transmitted by mosquitoes. So Zika is transmitted by the Aedes aegypti mosquito, and that's the primary mosquito that transmits the dengue viruses.

Most people who get infected with Zika, they don't know it. Like a lot of viruses, people get infected, and they either don't get sick at all, 或者他们病得很轻，不会以任何方式打断他们的生活.

但也会有一定比例的人被感染，然后生病. They get fever and headache and muscle pain, and they get fatigue. 他们可能会出疹子，或者眼睛发红，发炎，充血. In a very small percentage of people, 他们可能会有一些非常严重的神经系统问题，这些问题可能是由感染引起的, 这是我们在拉丁美洲疫情爆发时看到的首批信号之一, back in, 2015, 2016. They can get something calledGuillain-Barré, which can be fatal. It can prevent you from being able to breathe on your own.

But the real public health burden of Zika were the infections that occurred in pregnant women who, they might not have become ill, but there was a relatively high rate of the fetus becoming infected and significantly damaged with -- it's a syndrome, so you can have multiple different types of findings, but they call it -- congenital Zika syndrome, one of which was microcephaly. 人们可能还记得看到过这些巴西孩子的照片, very small heads and deformed heads and, of course, brains that had significant problems as a result. So that's Zika, and that's why it's really so important to us.

Host Amber Smith: We still don't have a vaccine, right, for Zika?

Stephen Thomas, MD: You are correct. So, like many things, when there's a problem, and it's right in your face, and when there's a fire going on, everyone scrambles, and everyone starts looking for water and sand and things of that nature. And then, when the raging fire becomes a small, little thing, they all forget and move on to the next problem.

Stephen Thomas, MD: 全球科学界和全球医疗对策发展界, they were all rallied at one point, when this was all going on. I was still in the Department of Defense at that time, and we were very concerned because we have service members who deploy or are stationed all over the tropical and subtropical world, to include tens of thousands of women of childbearing age. 所以我们非常担心，想要开发一种疫苗.S. 美国国立卫生研究院(NIH)，许多制药公司也是如此. 我们进展得很快，很快就进入了人体测试. And it was because we had a lot of experience, similar experience, with other viruses that were like Zika. And we had technologies that were on the shelf that we could pull off those playbooks and modify them to meet the Zika need. But when things started to calm down, and the problems started to dissipate, then attentions went to other problems, and resources dried up, and things kind of paused.

Host Amber Smith: So is the work still being done to help pregnant women?

Stephen Thomas, MD: We had down in Brazil, in particular, thousands of children born to infected mothers and thousands of children who were affected either in very severe ways, like the way I mentioned, where it's clearly obvious, microcephaly is clearly obvious, but also in ways that were not obvious at the time of birth, but that have become obvious over time as the children have grown.

And so kids having significant neurologic problems or psychological problems, or they're having behavioral disorders or developmental delays or other issues that are not evident at the time, but they become evident over time. And so, the public health burden of Zika still very much exists in places that had large outbreaks. 所以他们仍然在与2015年的问题抗争，几乎是10年前的问题.

There is still, clearly, in places where Zika is possible, there's educational campaigns that go on, that talk to the risks of getting infected, especially if you're, pregnant.

I just came back from Thailand. I was in Thailand last week, up north, where they've had Zika before, and big, huge posters saying, "Look out for these mosquitoes and look out for Zika, especially if you're a woman of childbearing potential or pregnant."

And I have been to some meetings recently that have focused on Zika. So there is clearly attention coming back to Zika, that it is still a problem, it's still a problem that could explode at any moment, and we could run into the same issues we had a couple years ago, because we still don't have a specific treatment for Zika, and we still don't have a vaccine that can protect people, so the work that's being done is, some of the work, 这在实验室和动物研究中都有发生.

Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith.

I'm talking with Dr. Stephen Thomas. We talked about efforts to protect people from Zika virus, and now we're going to look at another mosquito-borne virus.

So let's talk about the efforts to create a dengue vaccine. You wrote about this recently for Forbes magazine. Can you remind us about what the dengue virus is?

Stephen Thomas, MD: Sure. There are four different dengue viruses, dengue 1, 2, 3 and 4. They're similar in many ways, but they're distinct enough that they get a different name for each of them. And they kind of behave differently. They behave differently in nature. They behave differently in mosquitoes. They behave differently in people.

And so, we need to develop treatments and prophylactics, like vaccines, for example, that can address each of the four different types of dengue virus.

近一个世纪以来，我们一直在努力研制登革热疫苗. 这始于20世纪初，人们意识到登革热是个问题. We had had very large outbreaks of dengue in the United States. Back in the late 1700s, 在特拉华河和费城沿岸有成千上万的人被感染. It was a known entity.

And groups, especially the Department of Defense, because we had such a bad experience during World War II in the Pacific, 国防部从50年代开始就一直致力于研制登革热疫苗.

Matter of fact, Albert Sabin, who became very famous because of the oral polio vaccine, 他是一名年轻的陆军军官，早在研究小儿麻痹症之前，他就在研究登革热, which is interesting.

But there are three vaccines that really in the last 10 to 15 years have either been licensed for use, or they are in advanced clinical development.

Sanofi Pasteur licensed the first vaccine, but the vaccine had a safety signal, especially in young children. 安全信号出现在以前从未感染过登革热的人群中. When they got vaccinated, they had an increased risk of having a severe outcome if they did get infected after vaccination. And so it has a very limited indication, in terms of who can get it and under what circumstances. And so, as I wrote in the piece, it's kind of died of market neglect. It just has not been picked up quite a bit.

And then the most recent vaccine to be licensed was made by a Japanese pharmaceutical company called Takeda. And that does not have the same issues as Sanofi, in terms of safety, but it does have issues of its own in that it works against dengue 1 and 2, it does not work against dengue 3, and we really don't know if it works against dengue 4. So even though I think, my personal opinion is, it can deliver a public health benefit, it's not going to be all things to all people.

然后是第三种疫苗，目前正在开发中，是由美国.S. NIH, and then it was licensed to a Brazilian company called Butantan. And it was also licensed to Merck, which is now (called) MSD. And the company in Brazil, they're in the middle of a five year, very, very large trial, over 16,000 people. 最初的结果也是积极的，因为它看起来非常安全. It seems to work against dengue 1 and 2, but we do not know if it works against dengue 3 or dengue 4, because there have not been enough dengue 3 or dengue 4 cases. 所以研究还在继续，希望我们能在某个时候得到这些信息.

But I think this is going to be one of those things where these vaccines are going to be able to deliver clinical benefit, but it's not going to be all things to all people. We're going to have to manage our expectations, and we're going to have to not let great be the enemy of good, and figure out how to best utilize these tools.

Host Amber Smith: So it sounds like as much as it would be ideal to have one vaccine that covered all four types of dengue, we may get four separate vaccines or fewer.

Stephen Thomas, MD: Yes. There are ministries of health and other public health authorities and regulatory authorities that make decisions of whether or not they're going to allow a country to license the vaccine and allow it to be marketed in that country.

他们必须做出风险收益的决定，只要他们是安全的，对吧? As long as they have proven that they can be safe, then they're going to have to think about, well, what viruses are most commonly being circulated in our community, or at least recently in our community, and which vaccine maybe is a better match for that.

And then there's also going to be practical considerations of how many doses of the vaccine is there? What kind of vaccine construct is it? Can it be used in pregnant people? Can it be used in immunocompromised people? What's the cost of the vaccine?

Like, all these kinds of things are going to play into it. 在美国唯一获得许可的疫苗是赛诺菲的疫苗. But it can be used in very, very limited people; 9 to 16 years of age was the original approval, and you've got to be tested before you can use it.

The Takeda vaccine, was under consideration by the FDA (Food and Drug Administration), but they pulled it from consideration after long discussions with the FDA and at least what the company had in the lay press, 他们被要求提供以前没有被要求的信息. 所以他们没有这些信息，所以他们停止了在美国申请执照.S. They may come back; who knows?

但我们现在有登革热，多年来，我们在美国有零星的登革热. So we've had outbreaks, which have sickened hundreds of people, in Key West (Florida) and Hawaii. We've had sporadic cases in Southern California, Arizona, Texas. 仅去年一年，我们在佛罗里达州就有近180例本地传播的登革热病例. So, if the susceptible people are there, if the mosquitoes are there, all you need is for the virus to be introduced, and the fire can start, and things can take off.

So dengue countermeasures really need to be on the forefront of public health officials' mind for the United States because it's not a matter of if, but when, and I can tell you, having seen firsthand Zika outbreaks and dengue outbreaks, they stress even the most advanced and well-resourced public health systems, and they can kill people. They kill about 40,000 people a year, mostly children. And so I think it's something we need to take seriously, now, at home.

Host Amber Smith: Is there more than one type of dengue circulating in Florida? Like the cases from last year, were they all one type of dengue?

Stephen Thomas, MD: Typically what you see is you either see a single type, which predominates, sometimes you see two types, which predominate. 你还必须区分，什么是本地的，什么是与旅行相关的. Because if you look at travel-related cases, from 2010 to 2023 in the United States, we had over 10,000 travel-related cases of dengue, in the United States, which means 10,000 opportunities for a virus to be introduced into a new place. At some point your number comes up, right? And it starts to be locally transmitted.

Host Amber Smith: So does this spread from person to person?

Stephen Thomas, MD: No, it requires a mosquito. That's what happens the vast majority of the time. So, for example, somebody goes on a cruise to the Caribbean, they go to Puerto Rico, they go wherever. They get infected, they come back home, the virus is replicating. They get off the plane, the mosquito feeds on them. Now the mosquito has virus in it, and then it goes to feed on another person. And as it's feeding on that person, the virus gets into that next person, and now that person's infected, and then another mosquito can come and feed. And, that's kind of the way that it plays out.

There are some very, very rare circumstances -- blood donation, organ donation, laboratory accidents, things of that nature -- but it's most predominantly with mosquito to human to mosquito to human.

Host Amber Smith: 人们在往返美国时是否进行过登革热或寨卡病毒的筛查.S.?

Stephen Thomas, MD: No. Ideally, if you were going somewhere that dengue has circulated, or Zika has circulated, or any of the other viruses that we talked about, you'd go get a pre-travel consultation from a clinician, and they would explain to you how to protect yourself and if there was a vaccine available or not, or if there were medications you could take, et cetera.

And, in the same way, if you came back and you were ill, I mean, I would highly encourage people, if you come back from a trip and you have a fever, 如果你从热带或亚热带地区回来后发烧, you should go to see a physician, because it could be something serious.

And then, during times when there are outbreaks, even if it's not in the U.S., if there are regional epidemics going on, or certainly a pandemic going on, then the FDA or others may decide to screen the blood supply. They might do that at that time, if it makes sense to do that.

But no, it's not routine that people would be screened. 这只是机场例行健康检查的一部分, then that's what they would do. And they don't do much of that now. 他们在其他国家这样做，因为他们不希望这些病毒被引入.

They may have thermal cameras set up and things of that nature, but not in this country right now that I'm aware of.

Host Amber Smith: So if somebody had dengue and survived and got well, 他们是否受到保护，不会再次感染登革热或其他类型的登革热?

Stephen Thomas, MD: The good news is that the vast, vast majority of people who get infected, they're going to have a mild to moderate form of the disease.

They're going to recover in about a week. They might have some prolonged period of fatigue and kind of the doldrums and not feel well for multiple weeks after that. But ultimately, everybody recovers, the vast majority of people recover. There are a small percentage of people who, if they have significant preexisting medical problems, that they can do poorly, and they can end up developing severe complications and die.

What's interesting with dengue, though, is, and it's something unique about dengue, is the people who end up doing poorly are most of the time people who are getting infected a second time with a different virus than they got infected with the first time. And it's usually when the time span between that first infection and second infection is 18 months or more. They call these secondary infections.

所以在继发性感染的人群中，大约5%的人会发展成严重的疾病. And severe disease is your blood vessels become leaky, and fluid that's in the blood vessels leaks out of the blood vessels. You can have problems with coagulation, so you can start to hemorrhage internally, like in the GI (gastrointestinal, or digestive) tract, for example. You can get buildup of fluid in your chest or in your abdomen. And all of this can contribute to developing shock. And what shock is, is when your organs are not getting enough blood, they're not getting enough oxygen, and then they start to shut down, and you go into something called multi-system organ failure, and that's what kills people. And that happens in about 5% of people that get these secondary infections; 5% doesn't sound like a lot, but they think on average, they estimate, there's about 400 million people a year who get infected and about a hundred million people a year who get sick.

It's the denominator that matters when you're talking about the percentages. And so, it does create, especially in low- and middle-income countries where dengue is endemic, it creates a huge resource issue, and it can create a huge public health issue, with hospitals just overflowing with patients during an epidemic. But in places that they know how to take care of dengue, the mortality rates can be less than 1%, well below 1%, but in places where they don't know how to take care of dengue, it can be as high as 20%, meaning one in five people will die.

And unfortunately, in 2023, there were thousands and thousands of deaths. And in 2024, we're also seeing deaths already. 上周我在泰国的一个年轻人，一个非常年轻的人死于登革热. So, it's a problem.

Host Amber Smith: 听起来，如果你能避免或尽量避免的话，你肯定不想得这种病.

Stephen Thomas, MD: You absolutely do.

And to your question, once you get infected with -- this is what we believe to be the case, based on decades of, research -- once you get infected with one dengue type, you should be immune to that dengue type, at least for decades. The dogma is for the rest of your life, but at least for decades, you should not be able to get infected with that type again.

And so in places where there is a lot of dengue, and where there are multiple types of dengue circulating over time, most people, by the time they're 20, 25, they've already been infected twice. 我们不会看到第三次或第四次感染导致问题. which kind of gives you targets, in terms of a vaccine, 你需要超过这个标准才能保护一个人的一生, and, through vaccination, advance them beyond that window of risk.

Host Amber Smith: So a vaccine would be one way to get at this. Is there any effort going into getting rid of the mosquitoes or making them where they can't transmit this?

Stephen Thomas, MD: 他们尝试了很多不同的方法来控制蚊子，控制它们的繁殖方式. They've actually become quite well domesticated. 它们喜欢住在人们的衣柜和房子里之类的地方, because they like to be near their food source. Spraying and all these other things, they just really haven't worked well, and they're really expensive, and you need a lot of expertise, and you need just tons of people to be able to consistently do this.

And so even in places that are highly well resourced and highly controlled, like Singapore, for example, 他们在哪里可以证明他们确实减少了蚊子的数量, it doesn't necessarily translate into less human disease. What has happened now, and there's a couple of groups that are taking different approaches, I'll just mention one of them, but there are these new, innovative ways of trying to address mosquito populations.

One of those ways is there is a bacteria that can infect mosquitoes. It's called Wolbachia. It can infect lots of different things, but it infects mosquitoes. It infects the mosquito that transmits dengue. 他们观察到，当蚊子感染了这种细菌, it cannot get infected with dengue virus. 这些受感染的蚊子会过度繁殖，把未感染的蚊子赶出去.

So what they have done is they have manufactured, in these farms, millions of infected mosquitoes that they can release, then, into these areas. They will outcompete the uninfected mosquitoes, 现在主要的蚊子种类无法被感染，也无法传播. And they've started doing those experiments and releases in different parts of the world over the last five years or so. The data's coming out, and it's pretty compelling, and I think it could definitely be one of the tools, along with vaccination, for example, one of the tools in the toolbox to try to do something about this.

I think there's other genetically modified mosquitoes, and other approaches, but what I would say is, they're innovative, there's potential there, and I'm very interested in seeing the information because it really seems like there's something there.

Host Amber Smith: Well, considering climate change, do you think that there'll be any sort of a vaccine available before dengue becomes more of a problem in the United States than it is already?

Stephen Thomas, MD: Well, I think it already is a problem, to be honest with you. You don't even have to talk about climate change, necessarily, because just think of the ingredients. What do you need? You need mosquitoes, you need a virus, and you need susceptible people. So the, vast majority of the population is susceptible because they've never been infected before. There are billions of travelers around the globe every single year, including the United States, so there's billions of opportunities to introduce viruses into the country.

And the mosquito is here. And what makes the mosquito be able to be here is, it's the right temperature, the right amount of moisture and the right duration of the right temperature. And so if the temperature's going up, 如果天气模式因为任何你认为的原因发生了变化, which we know that they are, then yeah, 它创造了一个机会，让登革热在美国成为一种地方病, like it was at one point in time. So I think the vaccine and the treatment discussion is now, it's not when the fire has gotten so far out of control.

But again, maybe Takeda will come back to the FDA. I have no idea. And maybe Merck's development of the NIH vaccine, 我认为所有的迹象都表明它有潜力成为一种非常好的疫苗, maybe they'll pursue licensure in the United States, and we'll have an option, even if it's not just here, it's an option for when you want to travel, when you want to go somewhere warm during the long Syracuse winters, because more than one traveler has come back to Syracuse with more than just a souvenir and a T-shirt. They've come back sick and end up needing to see the doctor, and it turns out that they have dengue. That is not a rare event. It happens all the time.

Host Amber Smith: Will the cold winters that we have in Central New York, will that protect us from getting these mosquitoes that are carrying dengue?

Stephen Thomas, MD: Well, it doesn't get cold enough in many parts of the Southern part of the country, where the mosquitoes would dissipate.

We do not have that mosquito up here. Different groups debate whether we do or we do not. I think the surveillance that the county has done over the last 10, 15, 20 years has shown that or has failed to show that that mosquito is up here. We've got ticks, we've got other problems of our own, but again, as it gets warmer, as the winters get warmer, as the winters get shorter, then there is the possibility for these mosquitoes to persist for longer durations of time and for their offspring to survive the winter. But the ecology plays a lot into this, and as that changes, then the calculus for human disease changes as well.

Host Amber Smith: Well, Dr. Thomas, once again, I appreciate you making time for this interview.

Thank you.

Stephen Thomas, MD: Thank you very much.

Host Amber Smith: My guest has been Dr. Stephen Thomas. He's professor and chair of microbiology and immunology at Upstate and also the director of the Upstate Global Health Institute.

"The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe.

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