“The Most Important Diseases You’ve Never Heard Of”—Peter Jay Hotez, M.D., Ph.D.—National School of Tropical Medicine, Baylor College of Medicine

Richard Jacobs: Hello, this is Richard Jacobs with the future tech and future tech health podcast. I have Peter Jay Hotez, Dean for the National School of Tropical Medicine at Baylor College of medicine. We’re going to be talking about global health vaccinology specifically and neglected tropical disease control. So Peter, thanks for coming.

Peter Jay Hotez: Thanks for having me today.

Richard Jacobs: Why do you say that tropical diseases are neglected and how impactful are they on people?

Peter Jay Hotez: That’s a great question. We call them tropical diseases or now we call them neglected tropical diseases, which is a term we help coin in the early two thousand but the truth is they’re really diseases of extreme poverty. You ordinarily do not get a neglected tropical disease unless you live in extremely impoverished conditions where there’s environmental degradation and low poor quality housing, inadequate sanitation. So they’re really diseases of neglected populations who live in extreme poverty. Right now there are globally 750 million people who live below the World Bank poverty figure of a dollar 90 a day. And basically every one of them has at least one neglected tropical disease. And now we know there are about 5.3 million Americans living in that same level of poverty. They have neglected tropical diseases and they’re not only the diseases of the poorest countries of Africa and Asia and Latin America. We have NTDs, neglected tropical diseases right here in the US especially at Texas and the Gulf coast.

Richard Jacobs: So what are some of these diseases and what’s the impact in terms of mortality or sickness?

Peter Jay Hotez: So there are diseases I like to call them the most important diseases you’ve never heard of. They’re diseases like schistosomiasis and leishmaniasis and Chagas disease and hookworm. The point is these are not rare diseases that are incredibly common, affecting tens of millions or in some cases, hundreds of millions. It’s just that they affect the unseen poor and that’s why a lot of people have never heard of them. You know, everybody knows about AIDS and malaria and tuberculosis and but very few people know about these NTDs.

Richard Jacobs: And I guess the problem is if you were to develop drugs to treat these people, how would they afford them? And if you were to develop vaccines, that’s probably a better angle, right?

Peter Jay Hotez: Well, but even there, so I think you hit on it, right? So because these are the diseases of the poorest of the poor. They’re not really being worked on by the major pharmaceutical manufacturers. The major pharma companies are doing a few things for malaria and tuberculosis and of course AIDS, but not so much for neglected tropical diseases. So what happens is developing new interventions, new drugs, new vaccines, and new vector control technologies for insects all fall to the nonprofit sector. And so we’ve actually had to create a new type of organization to make those interventions. They’re called PDPs, product development partnerships. These are nonprofit organizations that use industry practices to make the drugs and vaccines that no one else will make. So in the case of drugs, one of the major ones is called DNDI the drugs for neglected disease initiative. They are an amazing organization based out of Geneva, Switzerland and they are taking these drugs on it for vaccines is our organization that the national school of tropical medicine at Baylor College of medicine through what’s called the Texas children’s hospital center for vaccine development is making those vaccines and advancing them through a clinical trial.

Richard Jacobs: Can you give a little bit of detail on some of the top tropical diseases that have been neglected? What do they do? What are they caused by? Who do they affect?

Peter Jay Hotez: Sure. So I’ll give you a good one. One’s called schistosomiasis. It’s a disease of almost 200 million people, 90% living in Sub-Saharan Africa. It’s a parasitic worm infection and you get infected with contaminated fresh water like Lake Victoria or Lake Malawi or in the Nile River. And the larval stages, they’re microscopic, have the ability to crawl through your skin and then they cause damage to your liver and testing’s depending on one species or the bladder and the female genital tract on another species. And it causes inflammation, it causes fibrosis, long-term organ damage. It also stunts childhood growth and interferes with child intellectual development as well. So these are particular problems of school-age children and adolescents, and it really robs kids of their childhood and adolescence. In the case of the one that affects the female genital tract, it causes a conditional female genital schistosomiasis, which is not the most common gynecologic condition on the African continent. And that’s actually a major co-factor in Africa’s AIDS epidemic. So there are very few people taking this on. The German Merck KGAA is now donating a drug for it. That’s just going to show you the lack of a market. So the drug companies taken out of the drug donation of a drug called praziquantel but the disease comes back and that’s why we’re developing a vaccine for this condition to prevent it from happening in the first place.

Richard Jacobs: Has this been around long enough to be, I mean, first of all, is it heritable from mother to child and has it been around to affect multiple generations and what’s been the effect of it on this population?

Peter Jay Hotez: Well, it certainly affects multiple generations, but not because it’s inherited. What happens is the larval stages of the parasite are ubiquitous in freshwater bodies of freshwater across Sub-Saharan Africa. So that people live in poverty depend on the river or the Lake to wash their clothes, to a bath. And so they’re continually getting infected. And so the idea is right now all we have is this drug being donated by the Merck KGAA, the German Merck to treat them but people get reinvested within weeks. So it’s the best we have and it’s really important that we give that mass treatment on a regular basis, but we’re hoping through the development of a vaccine, we can prevent that from happening.

Richard Jacobs: Has the vaccine been developed yet or not yet?

Peter Jay Hotez: So we’ve developed a vaccine that’s now started to just finish phase one clinical trials testing safety. And so far it appears to be safe. One of the problems that we have is getting to the goal line, getting to licensure. Because as a small nonprofit in Texas, at the Texas children’s center for vaccine development, we can go all the way from discovery through the scale of process development, pilot manufacturer, IND filing, investigational new drug filing with the FDA and that starting phase one. But then as you go through advanced clinical development, phase three trials and licensures, those trials get larger and more expensive. And right now we do not have the financing to see it all the way through. So there’s no roadmap here. I mean, people don’t develop vaccines in the nonprofit sector. So it’s kind of seeded the pants as we go and hope that we’ll continue to attract funding

Richard Jacobs: Other conditions that are very notable in terms of how many people they affect that you’re working on?

Peter Jay Hotez: Yeah. So we have another vaccine for Chagas disease which is a cause of debilitating heart disease across Latin America, especially in poor countries like Bolivia or in the poor parts of Southern Mexico or poor parts of Brazil, Northern Brazil, and Northern Argentina. But we’ve also not found the transmission of this disease in Texas. And the existing drug, which is called Benzmidazolam works in the early stages of the disease. But once it progresses beyond a certain point and heart disease begins, the drug does not work well. So we’re trying to make an amino therapy, a therapeutic vaccine for this and that we’re doing this through the support of the Carlos slim foundation, Mexico, but also the Clay Berg foundation, which is based in Texas as well as the Southwest electronic energy medical research Institute. So we kind of cobbled together our funding in order to make these things happen, are shipped to some ISS vaccine. Initially, the Gates foundation was helpful and now we’re been looking at the support of MIH and some internal funds from Texas children’s hospital. So this becomes a major issue in itself trying to piece together the support for our scientist. We’ve got an incredible group of scientists. My co-director is Dr. Mary Elena Patacki and together we’ve assembled an amazing team of scientists who are very committed to the mission, but it’s almost like a nonprofit pharmaceutical company. You need to put together the salaries and everything else to make it happen.

Richard Jacobs: Because some of these diseases, to affect so many people, are there carriers, are there people that are immune or the people that just somehow resistant to it?

Peter Jay Hotez: That’s actually a very profound question. The answer is yes and we took advantage of that fact to t design our vaccine. So what we’ve found this stopped so much me, it’s our colleagues. Jeff, Bethany and Alex Lucas. Jeff is at George Washington University and works in Brazil, administrates Brazil and Alex Lucas at James Cook University. They found in a population of people that seem to be naturally resistant to the infection for reasons that we don’t entirely understand. Those individuals developed antibodies to certain shifts, to some proteins. And we exploited that observation in order to help develop our current vaccine.

Richard Jacobs: Do you know if people develop immunity to it if they’ve been infected and then cleanser, then infected again? Do you have any people that had it multiple times?

Peter Jay Hotez: Well, some do, but most don’t. So most people don’t seem to develop protective immunity because these parasites have immune masking properties. So we looked at that. So a subset of that population, they looked at the subset of the population who is resistant and said, okay, well what is it about those resistant individuals that you didn’t see and the ones who continue to get it all the time. And the answer was those individuals make an antibody to our protein components used in the vaccine.

Richard Jacobs: Has anyone antagonized any parts of any of these parasites into a DNA? I know that happens with viruses sometimes, just wondering

Peter Jay Hotez: Not so much worm parasites is as far as we know. But not as far as I remember. These are worms. These are animals. So they’re not like viruses where the virus genes are getting into the host cell genes. So you wouldn’t ordinarily expect it to happen.

Richard Jacobs: Okay. I was just wondering, so how is the funding going to be achieved long-term? Is the big challenge getting a vaccine made at all or is the challenge once it’s made, getting it distributed affordably?

Peter Jay Hotez: Well, we’ve been at the shift to some ISS vaccine for 20 years and the hookworm vaccine for 30 years and now the Chagas disease vaccine for almost 10. And now we’ve gotten to it all the way through discovery and scale up and pilot manufacturer and IND filing and phase one clinical trials. One day I woke up and realized, hey, we just finished the easy part. So, now we’ve got to get it all the way through that pivotal clinical trial stag and licensure. So, vaccines are probably the toughest of all products in the pharmaceutical industry because they require years of safety testing and efficacy testing. And so hopefully we’ll continue to attract the support we need to get it all the way through the finish line.

Richard Jacobs: Is there a way to piggyback it on an existing vaccine that is given to a majority of people and let’s say Sub-Saharan Africa or a drug that they’re given for a disease like HIV, could you somehow piggyback and so it’s given at the same time as an adjunct.

Peter Jay Hotez: So you’re asking all the good questions that we’ve been asking. So I think so. And so for instance, one of the things that we made an observation from with a group at Yale with Dr. Amba and Alison Galvani is people who get just the semiosis are also more susceptible to malaria. So for instance, could we piggyback on GSKs effort to make a malaria vaccine and say, well, let’s give the two as a companion vaccine, let’s vaccinate against just the semiosis and malaria simultaneously. And I think that approach has a lot of merits because you don’t want to create a whole new health system just to give a new vaccine. You want to be able to exactly, as you say to piggyback onto existing interventions that were the lower the threshold. So I absolutely agree.

Richard Jacobs: May be the possibility of food they eat or something that they drink. Maybe a way for our field, but is there anything that you eat that’s grown that somehow could be altered to produce naturally the antibody that’s needed for what are these diseases?

Peter Jay Hotez: Yeah, there have been groups that have explored the possibility of edible vaccines or plant-based vaccines or genetically engineering, tropical fruits like bananas. That’s an interesting technology. The challenge comes in how you regulate that and how you manage for dose. Because let’s say you genetically engineer one of these vaccines into bananas, you don’t have to carefully regulate how those bananas are eaten and that sort of thing. So its sounds like a good idea. And I think that maybe where we moved to in the coming decades, but it’s not quite ready for prime time yet.

Richard Jacobs: I think so. Well, this is the noble work you’re doing. What do you expect is possible in the next 5 to 10 years? I know you’ve been at this a long time, but any breakthroughs coming?

Peter Jay Hotez: Well, I think right now there are vaccines, we’ve shown, they work in laboratory animal models, now we’re moving into phase one trials to show that they’re safe. And so far that’s looking really good. The question then becomes, does the vaccine actually work in people? And that’s the next big stage doing these proof of concept trials to show that they work as well and people as they do in laboratory animals and then through the final trials for licensure. So that’s kind of where we’re at right now. And unfortunately, we move at a fraction of the pace that industry will move at just because the funding is, it’s a patchwork of funding and trying to keep all the funding going and so you wind up moving a lot slower than you’d like to.

Richard Jacobs: Yeah, it makes sense.

Peter Jay Hotez: Yeah. I mean, as I like to say, people haven’t done this before, so there’s no roadmap here of how you develop a vaccine will nonprofit sector. And it’s not just the science, it’s coming up with innovative business models. So, I get a lot of young students that come to me and say they want to go into global health and sometimes they’re surprised or even disappointed when I tell them to go to business school because we need as much innovation in the business sector as we do in the science.
Richard Jacobs: That’s true.
Peter Jay Hotez: I think there’s an answer out there of how you work and create a business plan that actually can even generate revenue. I don’t have the skill set to figure it out and my team of scientists don’t. So we need smart people from business school to figure out how to get these global health technologies out there. My colleague Glenn Rockman heads a very innovative global health investment fund. Which now has a new name. It’ll come to me in a second. But maybe models like that might be the answer down the line. It’s now called Adjuvant Capital. So there are people out there trying to be really innovative and come up with new financial and business models, but we need more of them.

Richard Jacobs: Yeah. I wonder if getting it to be put into Coca-Cola for instance in those regions or a bottle of water might be the best way cause then it’s like a controllable dose per bottle and it’s probably pretty pervasive.

Peter Jay Hotez: Well, I don’t know by putting a Coca Cola per se, but the Coca Cola has the extraordinary distribution network. I mean, anywhere I’ve worked in low and middle-income countries, there’s Coca-Cola. So they’re definitely onto something in terms of how of their distribution network, could you tap into that potentially for vaccine delivery or other interventions. It’s maybe something worth exploring.

Richard Jacobs: Well, very good. What’s the best way for people to find out more than if they want to work in global health to get in touch? What are some resources for them?

Peter Jay Hotez: Well, there are a few things. One, you can go to our national school of tropical medicine, the Baylor College of medicine website. I also like to write books and I’ve written a book about the problem of neglected tropical diseases. It’s called forgotten people, forgotten diseases. It’s now in its second edition. My kids sometimes used to like to call it dad’s forgotten book on forgotten people with forgotten diseases, but it’s got to do the same and then I’ve got another more recent book called blue marble health, which looks at the surprising level of neglected tropical diseases among the poor living in wealthy countries, including 12 million Americans in the United States. And from that book called blue marble health published by Johns Hopkins university press, we’re starting to now work with Senator Cory Booker and who’s introducing legislation in the US Senate around this. And then lastly, we’ve got this other unexpected problem which we could do a whole separate podcast on, the rise of an anti-science movement in the United States and Europe and anti-vaccine movement that’s trying to discredit vaccines and make false assertions about them causing autism and other things. And I’ve written a book about that because I have a daughter with autism called vaccines did not cause Rachel’s autism, which was also published by Johns Hopkins university press.

Richard Jacobs: Okay. Peter, it’s been really great to talk to you. I’ll have to have you come back if you’re okay with that at some point. So thank you.

Peter Jay Hotez: Great. Thanks for giving attention to this issue.