Volunteers in Syracuse are helping in quest toward treatment for dengue virus

Host Amber Smith: Upstate Medical University in Syracuse, New York, invites you to be The Informed Patient, with the podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith.

About half of the world's population is at risk of becoming infected with dengue virus through a bite of an infected mosquito.

Researchers are trying to develop a vaccine or medications that would protect humans from this disease, and a trial related to that effort is underway at Upstate Medical University. Here to tell us more about that is Adam Waickman. He's an assistant professor of microbiology and immunology at Upstate, and much of his research is focused on viral pathogens.

Welcome to "The Informed Patient," Dr. Waickman.

Adam Waickman, PhD: Good afternoon, Amber. Pleasure to be here.

Host Amber Smith: I'd like to start with a description of the disease caused by the dengue virus. Is that dengue fever?

Adam Waickman, PhD: Correct, yes. So infection with dengue virus causes flu-like symptoms. You will get headache, fever, rash, eye pain. In fact, back before the causative agent of dengue fever was known, it was referred to as breakbone fever because the muscle pains and the bone pains associated with that infection can be so intense that that's the colloquial name that was given to this disease.

Host Amber Smith: So it's known to be painful.

Adam Waickman, PhD: Correct. So the bone pain and the headache and the rash and the muscle pain can be quite painful.

Host Amber Smith: A person would get this from the bite of an infected mosquito. Once the person's infected, can they spread it to other people?

Adam Waickman, PhD: Correct. The most common method of transmission, as you said, is when a mosquito feeds on someone who is ill, who has virus in their blood, and then that mosquito goes and flies away and feeds on someone who lives in the same household or lives in a neighboring household and then feeds again on someone who's not infected and then passes the virus to that person when the mosquito starts to feed and spits a little bit into the person to start that feeding process.

So it's very rare for someone to directly transmit the virus from one person to another. And most common method of transmission is from a mosquito.

Host Amber Smith: This dengue virus, isn't it mostly a tropical disease?

Adam Waickman, PhD: Correct. So most of the transmission of the virus is really limited and really driven by where the vector, the mosquito that can transmit the virus, can be found. And at this point, the Aedes aegypti and Aedes albopictus mosquitoes are found primarily, as you said, in the Tropics, so South America, South and Central America, Southeast Asia, Asia and parts of Africa.

But there are colonies of these mosquitoes that are found in the Southern and Southeastern United States, so Texas, Florida, Georgia. There are populations of these Aedes mosquitoes that can be found there, and there are periodic outbreaks of dengue in those areas. Small, but still present.

Host Amber Smith: I understand there are four different types of dengue. Can you tell us about the differences?

Adam Waickman, PhD: Correct, so there are four distinct, we call them serotypes of dengue, and this is really what makes dengue interesting and challenging from a virologic and an immunologic perspective.

So what we refer to when we refer to something as having a serotype, that means if you're infected with that serotype of dengue, generally you cannot be infected again with that serotype. However, you do not necessarily have protection against those other serotypes of dengue. So for example, if I was infected with dengue one, it is thought that I now have lifelong protection from dengue one. However, I am still susceptible to being infected with dengue two, three, or four at some later point in life. So this means that these are genetically, meaning the genome of these viruses are distinct, but also immunologically, meaning that the immune system can tell the difference between these serotypes of dengue.

Host Amber Smith: So how do you make a vaccine or a medication that'll take care of all four of them at once, or can you even do that?

Adam Waickman, PhD: So this has been the perennial challenge. This has been the massive lift that we have been trying to achieve as a vaccine and immunology community for the last 40 years.

Because you're right, we have to not only generate immunity against one virus, we have to generate immunity against four viruses simultaneously. And what makes this even more challenging, is that a unique feature of dengue virus is that, as I mentioned before, you can be infected with one virus, and be protected against infection from that same virus for life, but that infection with one serotype actually puts you at greater risk of severe disease if you're later infected with one of the other serotypes. So this has significant implications for vaccine development because if you do a poor job of generating immunity against one of these four or two of these four or three of these four serotypes, you may actually put someone at greater risk of developing disease than they would've been before.

Host Amber Smith: Would it be a medication you would take before you're infected, or would it be a medication that someone would take once they are already sick with the disease?

Adam Waickman, PhD: The hope for the vaccine community and the dengue community is to develop a safe and protective vaccine that can be provided before anyone is infected.

So, to prevent anyone from ever becoming infected and prevent them from developing symptoms and prevent them from being sick. That, as I said, is a high bar, but there are also efforts to try to develop drugs and other therapies that can be given if someone is exposed or early on, when someone is displaying early symptoms of dengue infection, to limit the disease and blunt the severity of the infection.

Ninety percent of dengue infections are asymptomatic, so Ninety percent of the time when someone is actually infected, they don't have any symptoms or very, very mild symptoms.

Of that, so let's say 400 million people are infected a year. Between 50 million and 100 million people become symptomatically ill every year. Of that 500,000, people may develop severe dengue. Of that, 20,000 to 70,000 die. So it's a very steep pyramid where the risk factors for moving from one category to another category are not well understood.

But again, having that preexisting immunity is one risk factor.

Host Amber Smith: Are there any dengue treatments that have been approved for use yet?

Adam Waickman, PhD: So there is currently one approved dengue vaccine, but it has restrictions on who can use it. So, as I mentioned, having one dengue infection can actually put you at risk of developing more severe disease should you become infected again.

So, the vaccine that is currently available, called Dengvaxia, is available and only licensed for use in people that have previously been exposed or have some amount of anti-dengue immunity. So what this vaccine can do is take someone who has some level of preexisting dengue immunity and boost it to a level where it's protective or mostly protective from infection, however It's not licensed to be used in someone who has no immunity, out of concern that you may put them into a window where they are at risk of developing more severe disease, should they become infected.

Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host, Amber Smith, and I'm talking with Adam Waickman. He's an assistant professor of microbiology and immunology at Upstate who researches viral pathogens, and he's involved with a clinical trial related to the dengue virus.

Now, you're involved in this dengue trial that's underway at Upstate, but it's not a vaccine trial. Can you explain to us what it is?

Adam Waickman, PhD: Yes. So, we have two programs that we are running here at Upstate, the first of which is that we have been involved in a consortium effort with a large group of partners, including U.S. Army and other academic institutions to develop what's called a dengue human challenge model, or for short, DHIM. And what this model seeks to do is to expose volunteers to a highly attenuated (weakened) strain of dengue that makes people a little bit sick. They get a fever, they get a rash, they have virus in circulation, but then it resolves very quickly in a very well understood way, and the goal with this is to develop a tool that we can then test vaccines and test drugs in a controlled fashion before we roll them out to large clinical trials out in the field, as it were.

Because one of the challenges, as you mentioned in your introduction, there are close to 400 million, 500 million infections a year. But it's really hard to know when and where that infection is going to occur. So it can be very hard to run a trial where we're trying to see if a drug or a vaccine prevents an infection.

So by having this controlled challenge model, we can very precisely know, "This is when we gave the drug," or "This is when we gave the vaccine," and then infect people in a controlled fashion with this attenuated virus to see does this drug, or does this vaccine, prevent disease or prevent infection.

Host Amber Smith: I've seen billboards recruiting people for this trial. How many people will be participating all told, and in Syracuse and other sites?

Adam Waickman, PhD: We're really just hitting our stride. So, we have, over the last eight years, infected close to 30 volunteers with these attenuated strains of dengue virus.

And right now we're running clinical trials where we're looking to recruit dozens of more volunteers. So this is a program that we're really excited about because we now have this incredibly powerful tool that we're hoping can help cure this disease that causes so much suffering, in predominantly children, around the world.

Host Amber Smith: What are the requirements to be able to participate, and are there any disqualifiers?

Adam Waickman, PhD: The main criteria for being able to participate in the study is that you have to be between 18 and 55 years of age at time of enrollment and not have any preexisting immunity to dengue itself, so you shouldn't have traveled to a dengue endemic area recently.

If you want more information about this study and see if you might be qualified for participating in this study, there can be more information found in the link below (in the posting for this interview on the website). Or you can call our lead recruiter for more information at 315-464-9869.

Host Amber Smith: What can participants expect? Because I'm curious how much time this will take, and where they have to go, and what the visits are like.

Adam Waickman, PhD: Everything is run out of our research unit at the Upstate Community (Hospital) campus (on Onondaga Hill). The first thing you would do is, you'd come in for a screening visit, where you'd meet the team, and we'd do some routine questions to get to know you and get to know your medical history and some blood work to be able to see, again, do you have the antibody profile that makes you eligible for this study? And also just some routine screening to make sure that you're healthy enough to participate in the study.

If you're enrolled in the study, the first two weeks of the study involve very frequent visits, where after infection, we'll have you come in and check in with the team, make sure that you're feeling OK. There's going to be blood draws for us to be able to follow how much virus is in your blood and how your immune system is responding to the infection. And also if you're taking a drug to limit the infection, this will be an opportunity for you to take that drug under the supervision of the study staff.

After that first two- or three-week intensive period, there's then going to be periodic follow-ups where, again, we're checking to see how you're doing and how your immune system has responded to the infection. And generally after a month, there's periodic follow-up. And most of these studies we close out after six months with just one final visit for us to be able to do a final check and see how your immune system responded to the infection, and at that point, that's it.

Host Amber Smith: So, participants, they're investing a little bit of their time in this. Do they get compensated?

Adam Waickman, PhD: Yes, there is financial compensation for participation in these studies. And again, more information about that can be found on the website linked below.

Host Amber Smith: So all of the participants will be injected with dengue, a watered down form of dengue?

Adam Waickman, PhD: Correct. So all participants in our challenge studies do receive an infection with the virus. If you're participating in a study where we're testing a vaccine or a drug, you may receive the vaccine, you may receive the drug, or you may receive a placebo, a control (a fake medication), for that.

Host Amber Smith: What are the risks to someone who have this injected into their body?

Adam Waickman, PhD: The risks are you do develop symptoms of a mild dengue infection. About half the volunteers that participate in these studies so far without any additional treatment, they have a headache, they have a fever, they'll develop a rash that will last three to five days, and they self-resolve and at this point, every volunteer that we've had involved in these studies, those symptoms have been treated with, rest and just over-the-counter painkillers.

Host Amber Smith: So, participants will have an immunity to dengue afterward? Is that right?

Adam Waickman, PhD: They will have generated an immune response to dengue, but we can't say that this is going to be a protective immune response against that serotype because the virus that we use for this challenge is very attenuated.

Again, we want this to be a safe, controlled experience, so we don't have the data to say that this infection is going to provide protective immunity, but it does certainly generate a very robust anti-dengue immune profile.

Host Amber Smith: Besides the compensation, what are the rewards for someone to be involved in this?

Adam Waickman, PhD: These studies that we're doing are designed to try to come up with a vaccine or come up with a drug that is going to be incredibly impactful for billions of people. There's, as we mentioned a couple times, there's 500 million infections a year, and again, most of the individuals that have symptomatic severe disease are children, in the Tropics and Subtropics around the world.

So our hope and one of our goals is to be able to develop a vaccine or develop a drug that is going to provide some relief and break this cycle where we have so many children, so many, people around the world getting sick from this disease. So by participating in this type of trial, you're providing an incredibly valuable service to the world community, trying to prevent and treat this very, very impactful disease.

Host Amber Smith: Does the information from your study get shared with researchers around the globe, in other countries where this is a bigger concern than it is here? How does that get shared?

Adam Waickman, PhD: All of our studies that we run here are published in peer-review journals, and as part of that process, the underlying data generated from the trial are made publicly available, so researchers from around the world can see what happened in our study.

And also we have extensive collaborations with groups from around the world in dengue endemic areas, where we're working with them to identify the questions and identify the tools that we can use to help best answer the questions that are impacting their communities.

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

Adam Waickman, PhD: It's been my pleasure. Thank you so much.

Host Amber Smith: I want to let listeners know again, the phone number to call for more information is 315-464-9869. My guest has been Adam Waickman, an assistant professor of microbiology and immunology at Upstate who's involved in research into the dengue virus. "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.

Find our archive of previous episodes at upstate.edu/informed. This is your host, Amber Smith, thanking you for listening.