Volunteers are sought for yellow fever vaccine study

[00:00:00] Amber Smith: Upstate Medical University in Syracuse, New York invites you to be The Informed Patient with experts from Central New York's only academic medical center. I'm your host, Amber Smith. Today, we're focusing on the development of a potential new vaccine for yellow fever. My guest is Dr. Chris Paolino, who is an assistant professor of medicine and of microbiology and immunology at Upstate. He's also the principal investigator of this vaccine trial. Thanks for making time to talk with me, Dr. Paolino.

[00:00:29] Kris Paolino, MD: Not a problem. Thank you for having me.

[00:00:31] Host Amber Smith: I'd like to start by having you tell us about yellow fever and why it's a disease that travelers to Africa and South America have been recommended to be vaccinated against.

[00:00:41] Kris Paolino, MD: So yellow fever is something that's, been around for centuries.

[00:00:45] Kris Paolino, MD: We actually used to have yellow fever outbreaks in the United States way back when and the problem with the infection is there is no real treatment for it. If you get it you kind of have to get supported through the infection and, given the fact that it does have high case fatality rates that can be really devastating. And what often happens is, you'll get infections. And then, if you're in an area where the mosquito is able to transmit it, you can get large outbreaks, and it can spread very quickly.

[00:01:15] Host Amber Smith: So it can be deadly?

[00:01:17] Kris Paolino, MD: Absolutely. Yeah. Even with supportive care, people do die of this infection. And most of the data that's out there would indicate that about 50% of people who get infected with this will, will not make it through.

[00:01:30] Host Amber Smith: Now, is it only transmitted through the bite of a mosquito or can an infected person spread it to another person?

[00:01:37] Kris Paolino, MD: This is technically a viral hemorrhagic fever. So, you think about things like Ebola virus and how that can be transmitted from person to person. With yellow fever, it really needs to be spread by the mosquito.

[00:01:48] Kris Paolino, MD: So there is unlikely a chance that you'd have a person to person transmission. I'm sure there are some very, very rare case reports where that's a possibility, probably more so from a needle stick injury. But for the most part, that's, it's not how it's transmitted. It has to be in a mosquito.

[00:02:04] Host Amber Smith: So you mentioned that we've had yellow fever in the United States, but long ago. Is there any evidence of it being found in mosquitoes in New York state, anytime in the near past?

[00:02:15] Kris Paolino, MD: No, no, in fact the mosquito that carries yellow fever, which is typically the aedes aegypti mosquito, isn't really found here in New York state.

[00:02:25] Kris Paolino, MD: There are some references of aedes albopictus, which is a similar type of mosquito being right on our doorstep that potentially could carry yellow fever, but nothing that's been indicated that we have a threat looming in our region.

[00:02:40] Host Amber Smith: Now from time to time, we have had an issue with West Nile virus in mosquitoes around here.

[00:02:45] Host Amber Smith: It is that related to yellow fever in any way?

[00:02:50] Kris Paolino, MD: It is distantly related. Both yellow fever and West Nile fever are flaviviruses. So from that standpoint, they are related. Now, the mosquitoes that spread each are different. So you have the aedes aegypti for yellow fever, which we don't really have here.

[00:03:05] Kris Paolino, MD: And then we have Culex species mosquitoes, which are more bird mosquitoes that will spread West Nile virus. So that's kind of why we see the idea of these dead crows signifying a West Nile outbreak in our region because those mosquitoes are going to attack birds as well as, you know, potentially humans.

[00:03:26] Host Amber Smith: Now, getting back to yellow fever, is feve the main symptom of this disease? Is that why it's called yellow fever?

[00:03:33] Kris Paolino, MD: Yeah. So, if fever is in the name, you know, you're going to have it, but it's not the only thing that you worry about. Generally with yellow fever, you're going to have two phases of illness. There's going to be this acute phase where people are going to have this kind of flu-like illness that can be pretty severe. You can bad headaches. You can have muscle aches, flu like symptoms in general, as I said. And then there's this toxic phase that can develop. And that's where people really go downhill.

[00:03:59] Kris Paolino, MD: Generally they go into multiorgan failure. Kidneys shut down. So a sign of that would be maybe not urinating as much. Generally people will turn yellow and they'll become jaundiced, which is the other part of the name. And then on top of that, because the liver is affected there's generally a lot of bleeding that can occur so people can have bleeding, pretty much from anywhere, bruising under the skin. and it can get pretty severe, pretty quickly.

[00:04:24] Host Amber Smith: If a doctor suspects that someone may have yellow fever, is there a test available to confirm it?

[00:04:31] Kris Paolino, MD: Yeah, there's a couple of tests. Classically we use antibody response. So you can do serologic testing that can test for yellow fever. That may or may not be helpful if somebody has a really severe disease, really with any kind of viral infection, you may not mount an antibody response. So you may get a false negative. In addition to that, there are some places where you can send the samples off to and do PCR testing to look for the actual genetic material in the person's bloodstream. So, for example, the CDC would be a place that I would reach out to you if I had a suspicion of yellow fever and needed to have blood sent off for PCR testing.

[00:05:08] Host Amber Smith: Now, as I understand it, a vaccine for yellow fever has been in use for several decades. So what's new about what you're studying?

[00:05:17] Kris Paolino, MD: So to go back a step just to that old vaccine, this vaccine is probably one of the most successful vaccines in the history of man. And I say that because it's generally a single shot, and the data in the past that indicated that we needed to do a 10-year booster. Most of the data that we're seeing coming out now has actually eliminated the need for that in most place because, we have people who are 30, 40, 50 years out from vaccination who still have good protective antibodies.

[00:05:47] Kris Paolino, MD: So, it's a good vaccine. There's nothing has really changed from that standpoint. The problem, it is the way that it's manufactured and the fact that it requires an egg-based manufacturing process. It slows things down quite a bit. And when you have big outbreaks, like we've seen in sub-Saharan Africa and the past several years, and you need to use millions upon tens of millions of doses to try to curb the effects of the outbreak these resources were dwindled pretty readily. So it got to the point where they were so desperate, they were actually using fractionated doses of that vaccine to try to protect people, basically taking instead of a full dose, a full vial for the vaccine, using that in multiple people in smaller doses to try to provide some form of immunity to protect people.

[00:06:37] Kris Paolino, MD: So that, that issue, that shortage really kind of raised the eyebrows of a lot of the public health officials, and we realized we need an effective vaccine that we can rapidly make and get out in this situation that we have another one of these outbreaks, and we have these outbreaks pretty frequently in, in Africa, especially.

[00:06:56] Kris Paolino, MD: So that's where this new vaccine comes into play. It's very similar to the old one. It's a live attenuated vaccine. It's a single dose. The way that they make it, though, is different. Instead of using eggs, they use a cell culture.

[00:07:09] Host Amber Smith: You're listening to Upstate's The Informed Patient podcast. I'm your host, Amber Smith talking with Dr. Christopher Paolino. He's an assistant professor of medicine and of microbiology and immunology at upstate and he's recruiting volunteers for a new clinical trial for a yellow fever vaccine at Upstate's center for global health.

[00:07:33] Amber Smith: So I want to have you tell us about the goals of your study and how it's set up to work.

[00:07:39] Kris Paolino, MD: Sure. So the goals of this study are really to compare the immune response to this newer vaccine, to the, the standard age old vaccine that we've been using for forever. That, in addition to looking at the safety of the two, just to make sure that there's no significant differences in either of those just based on the fact that we're producing it differently. So that's the main focus.

[00:08:04] Host Amber Smith: So how many people are you recruiting, and what ages and genders?

[00:08:08] Kris Paolino, MD: Yep. So, we are supposed to recruit up to 57 people here at our site. That could be potentially less. It could be potentially more. We're looking for 18- to 60-year-olds in a variety of different genders, as well as races.

[00:08:24] Kris Paolino, MD: Anybody who would be of interest of participating in this study would be welcome. We do do a pretty extensive screening of their health to determine whether or not it would be appropriate for them to be in this study. So, a couple of things that would probably prevent somebody from participating would include pregnancy or lactating, if somebody has any kind of severe immunodeficiencies or any kind of immune modulating drugs that they're taking, so anything that could affect their ability to mount an immune response, and then anybody with any kind of other severe or significant medical disorders that-- in the eyes of the investigators, myself and my colleagues included-- may make it somewhat unsafe for them to be in this study.

[00:09:05] Host Amber Smith: Now, are you looking for people who've already been vaccinated for yellow fever, or if they might've already had yellow fever?

[00:09:13] Kris Paolino, MD: So for this particular study, we are looking for people who are not yellow fever vaccinated and have not been receiving any vaccines for other types of flaviviruses as well. So that's the the cutoff. We're not looking for people who have had it before to see if it boosts or anything like that. We're looking for people who have not had any prior exposure to yellow fever in any.

[00:09:36] Host Amber Smith: Now in terms of what's going to be required of the volunteers, will everybody, will all of the participants receive one of the vaccinations against yellow fever?

[00:09:45] Kris Paolino, MD: Yep. It's a randomized trial. And you'll either get the standard vaccine that is FDA approved or you'll get this newer vaccine, and we'll compare the two that way. As far as kind of study visits and things like that, it'll be a one-time injection for both. And then there'll be several visits up through six months. I think it's a total of up to five visits, depending on where people are enrolled in what cohort we're looking at in terms of early phase versus later, and then there are going to be annual visits every year, starting at 12 months. So there'll be up to potentially 10 visits for this yellow fever vaccine, although I think our site is only doing 900.

[00:10:25] Host Amber Smith: Now the visits take place at your office at Upstate?

[00:10:29] Kris Paolino, MD: Yeah. So we have a research clinic. It's the global health research unit over on the fourth floor of the north building at the Community campus. We've been here since last November, I believe. And we basically just do clinical trials out of this site.

[00:10:44] Host Amber Smith: Now once the volunteers have the vaccine, are they then at one of these appointments going to be exposed to yellow fever?

[00:10:53] Kris Paolino, MD: No, no, no. So you're alluding to challenge studies generally with a challenge study you're not going to be doing a challenge of the virus or the bacteria that you're testing the vaccine against, unless you have really good treatment for that or if there is some kind of alternative, like a really weakened strain of that infection of some sort. But in this study, we are not doing anything like that. Just vaccine, and then observe.

[00:11:19] Host Amber Smith: How do you tell whether it's working for this person? Do you test their blood at the regular intervals?

[00:11:26] Kris Paolino, MD: Yeah. So we'll have blood work that will be done. And during that blood work, we'll take a look at their immune response to the vaccine to see how high their antibodies against yellow fever have gotten.

[00:11:37] Host Amber Smith: What do you say about the risks to the volunteers? What do they need to know before they sign up?

[00:11:44] Kris Paolino, MD: With the standard yellow fever vaccine, which is really what we have most of our information about there are some risks associated with it as a live attenuated vaccine.

[00:11:53] Kris Paolino, MD: The risks are generally highest and people who are quite young, less than five years old, older, generally over the age of 65 or even older than that, or people who have any kind of significant medical disorders that would inhibit their immune response. If somebody had some problem with their immunity of some sort or had some thymus problems -- that's another specific thing for the yellow fever vaccine -- we wouldn't enroll any of those individuals into the study from that standpoint, just from a safety perspective. There are some risks associated with these vaccines in very, very rare cases, people who are not at those high risk groups can potentially have almost like an infection from the virus itself, since this is a live attenuated vaccine. But it's something that I have not seen in practice in the 10, 11 years that I've been an infectious disease physician. It's quite rare for that to happen, and that's what we generally tell people.

[00:12:48] Host Amber Smith: So what is the best way for someone who's interested to learn more?

[00:12:52] Kris Paolino, MD: Probably the easiest way would be to call our recruitment line, which is 315-464-9869. You can also visit us at our website and we also have a Facebook account as well. So if you were to search "global health SUNY Upstate," I'm sure you'll probably find us on there.

[00:13:10] Host Amber Smith: Now in the meantime for people who travel to areas with a threat of yellow fever transmission, they're still being recommended to get the traditional vaccine, is that right?

[00:13:20] Kris Paolino, MD: Correct.

[00:13:21] Host Amber Smith: And do you have any other advice to reduce the risk of getting bitten by a mosquito when you're traveling?

[00:13:29] Kris Paolino, MD: With yellow fever in particular, the mosquitoes, the aedes aegypti, they generally will bite in the mid- to late afternoons. That's kind of their high peak. And so if I were going into the Amazonian basin or an area in sub-Saharan Africa, where there was a high level of yellow fever, I would use some kind of DEET-containing bug spray, generally something about 25% DEET or greater. And I would use that at frequent intervals, especially in that afternoon period.

[00:13:59] Kris Paolino, MD: People talk a lot about bed nets. That's not going to prevent you from getting yellow fever because the mosquitoes that bite you at night are generally going to be the Anopheles mosquitoes that spread malaria, which is why malaria and bed nets kind of go together. But it's not going to do anything for yellow fever.

[00:14:14] Host Amber Smith: Well, I thank you for making time to tell us about this yellow fever vaccine trial. And I hope anyone who's interested in volunteering makes a call to (315) 464-9869 for more information. My guest has been Dr. Kris Paolino from Upstate's Center for Global Health. He's an assistant professor of medicine and of microbiology and immunology at Upstate. I'm Amber Smith for Upstate's The Informed Patient podcast, thanking you for listening.