Wisconsin Public Television University Place Wednesday Nite at the Lab  Tony Goldberg, "Health and Disease in the People, Primates, and the Livestock of Western Uganda: Insights from the Kibale EcoHealth Project"  October 13, 2010 UP 499   cc >> Tom Zinnen: Welcome everybody to Wednesday Nite at the Lab. I'm Tom Zinnen. I work here at the University of Wisconsin-Madison Biotechnology Center. I also work for UW-Extension Cooperative Extension, and on behalf of Wisconsin Public Television and the Wisconsin Alumni Association, welcome to Wednesday Nite at the Lab. We do this every Wednesday night, 50 times a year. Tonight's speaker is Tony Goldberg, who is a professor of epidemiology here at the University of Wisconsin-Madison. He started off with a bachelor's of arts and biology and English in 1990 from Amherst College, got his PhD in anthropology in '96 from Harvard and then got a masters in epidemiology in 2000 at the University of Illinois, and also the same year, 2000, got a doctor of veterinary medicine from the University of Illinois. Busy year, 2000. His training spans the biological, medical and social sciences which helps explain why his laboratory engages in cross-disciplinary research. In addition to his professional interests, he enjoys the outdoors such as hiking, biking, canoeing, fishing and skiing, as well as literature, music, theatre and a diversity of other cultural activities. 

All of which, as he notes, are readily available in and around the wonderful city of Madison, Wisconsin. I would second that motion. He is going to give his full title tonight but I think this is going to be an amazing saga of science from a whole range of social, anthropological, biological, the whole gamut. It's the kind of spectrum of science that's a delight to have here at Wednesday Nite at the Lab. Please join me in welcoming Tony Goldberg to Wednesday Nite at the Lab. [APPLAUSE]  >> Tony Goldberg: Thank you very much, Tom. And thank you everybody for coming out on the end of such a beautiful day. The title of my talk tonight is Health and Disease in the People, Primates and Livestock of Western Uganda: Insights from the Kibale EcoHealth Project. I'll explain that in a moment. Right now. 

The Kibale EcoHealth Project, this is our logo, this is a project that I started in 2004, and as you can see from the logo it has something to do with monkeys, people, livestock and how they are interconnected. And our goals are to understand how these species interact in nature and how that affects their health. And we're particularly interested in the types of changes that are going on to the tropical forests where these species interact. We want to understand how people are affecting the interactions between these species and how we might improve human health and animal health and primate conservation by reducing such things as disease transmission. The place I'm going to talk about is Kibale National Park. This is a relatively small national park in western Uganda near the foothills of the Rwenzori Mountains, also known as the mountains of the moon. And it's a famous site. It's very biodiverse. Over 30 years of primate research has happened there. And it also has one of the highest human population growth rates in all of sub-Saharan Africa. 

So it's got high biodiversity and a lot of people at the same time. This is a map that was published two years ago by a colleague of mine, Peter Daszak, and he's attempted here to make a global map of the risk of what he calls an EID event. EID stands for emerging infectious disease. We live, as you may have noticed, in the age of emerging infectious diseases. Swine flu, SARS, Ebola, bird flu, these are on the news on a daily basis. So this was an attempt to say where in the world should we be most worried about new diseases emerging. And whether or not you agree that there is, in fact, a hot spot here in Atlanta or New York or Chicago, it's clear that Uganda is red and a lot of sub-Saharan Africa and southeast Asia are red, indicating that these are areas where we should pay attention if we're interested in predicting and preventing emerging infectious diseases. So this is what Kibale National Park Uganda looks like. It's a beautiful rain forest. It's a tourist site. 

You can go there. It's got mature trees, beautiful evergreen or semi-deciduous forest and it's just a lovely place to walk around. Here's some more pictures. Unlike a wet, hot, sticky, tropical forest you might imagine, this is a high altitude forest or a medium altitude forest. So it's dry. Not unlike walking through the woods here in Wisconsin at certain times of year with streams and beautiful trees and running water. And it's full of interesting creatures. Here's some flowers, butterflies, it's famous for its butterflies, amphibians, other insects. And here's one of my students holding the infamous up to three-foot long iridescent blue Kibale forest earthworm. So all sorts of fun things. 

There are more creatures. I have colleagues who study fish and mammals and insects like this well-hidden caterpillar, frogs and chameleons. So it's what you might expect for an equatorial tropical African forest. And, of course, primates, which is why it's famous. This is a photo of, this is a slide showing photos of the 12 nonhuman primates that live in Kibale National Park and the one human primate, humans. That's my field assistant, Annette, posing for that photo, showing this is a very diverse primate community. Now we know something about primates and disease already. We know that pathogens that are shared between primates, people and domestic animals are threats to global health. So on the left here I have a list of pathogens that we know can be transmitted from primates to people. These are the zoonotic pathogens. 

And there are some big ones in here. HIV, for example, the virus that causes AIDS, started out as a simian immunodeficiency virus of chimpanzees that was passed to humans maybe about a hundred years ago. Then we have other nasty agents in here like Ebola, anthrax, tuberculosis, yellow fever, all of which have links to primates. But we shouldn't forget that there are human pathogens that can go the other way and threaten apes and primates and their conservation status. Like Polio, for example, ripped through the famous chimpanzees of Gombe National Park Tanzania that Jane Goodall has been studying for over 40 years at one point. Then there's accounts of Sarcoptes scabiei, the mange mite that causes sarcoptic mange, and several other nasty pathogens that can go from people to wild primates. So it's a problem in both directions. Why? Well, one reason is that we are primates, at least most of my friends are primates, we share similar physiologies, and we've co-evolved for millions of years. But that's not the full story. More importantly, I think, is the fact that recently we've been altering the habitats in which primates live. 

We've been disturbing them by deforestation, by encroachment, by hunting. And that's very evident in Kibale. This is a satellite image on the left of Kibale National Park. And you'll see that the dark part in the middle, this kind of kidney bean-shaped thing, is the national park and there's not much of a border between the park and what's outside of it. So here, again, we have a photo of the inside of the park, but if the look outside the park what you see is tea plantations and small scale agriculture. And if you go beyond the borders of the park, which are protected by Ugandan law, you will find a series of these fragments of remnant forests. These are patches of forest that persist in low lying, wet valley bottoms or steep hillsides where people can't farm. And in these patches of forest you will find monkeys living there, trapped, unable to leave, and people and their animals living around these environments using these fragments for water collection, collection of forest products, making charcoal. So these areas, these forest fragments are hot spots for human/primate interaction and conflict. And we know that this type of forest fragmentation is an issue for primates and people. 

We know that for primates it alters their behavior, their ecology, their demographics. It increases habitat overlap between primates and people and it reduces biodiversity of plants, invertebrates and vertebrates. So here, again, are the 12 nonhuman primates that you would find on a good day walking through Kibale National Park, but if you go into one of these highly degraded forest fragments, you would see only these three because none of the others can make it in those very compromised environments. So our general approach is to combine disciplines. Sometimes we're primatologists, we watch the primates and record what they're doing. Sometimes we're health professionals who survey the local human population to ask questions about their health and their land use patterns. Sometimes we're geographers and we look at the landscape through remote imagery like satellite images and try to make sense of it. And sometimes we're molecular biologists and we collect data on the pathogens that are circulating in this system to try to understand how they're moving among these species in this environment. And I'll give you a highlight of some of our results to date. So the first major trend in the study area is that the primates living in these forest fragments, the ones that are trapped there, are going extinct. 

Here we have a graph for a particular forest fragment of the number of red colobus in red, black and white colobus in black and red tail monkeys in blue over time. And you can see that the numbers of red colobus and black and white colobus went to zero within about two years of us beginning to observe them in this one particular location. And we know that that's a result of loss of habitat and other factors like hunting by dogs. So dogs roam around in these areas and can attack the monkeys. Now you might notice that the red tail monkeys do just fine because they just love to eat crops. They really enjoy eating corn and there's a lot of corn around here so they do just fine but the farmers don't like them. We've looked at a number of infectious diseases and this is a very typical pattern for what we see. Here I have a graph of red colobus, now this is an endangered primate species, and how many of them are infected with two protozoan parasites, giardia and cryptosporidium. You may be familiar with these ones if you've done any camping in Wisconsin, this is why you filter your water. If we look at these animals in the core protected undisturbed parts of the national park, we don't see these pathogens. 

If we look at these animals in the forest fragments outside of the park where they're interacting with people and livestock and are threatened and are being hunted by dogs, we see they have a relatively high infection rate with these pathogens. If we look at livestock living near them, we find that the livestock also carry these pathogens. This is suggestive but to really nail it down we need to go molecular. So here we show a kind of family tree of isolates of, in this case giardia, from different species in this area. And all I want you to see is that up here at the very top we have a cluster of giardia isolates from people and red colobus, implying that there's a human to monkey or maybe monkey to human, both directions, transmission cycle up here. But if you look down here to this part of the family tree, you'll see a separate transmission cycle between red colobus and goats and cows. So we have evidence of multiple transmission cycles of these types of pathogens. Some of them between people and monkeys, some of them between livestock and monkeys, which isn't surprising. We've made a lot of use of the common bacterium that everybody knows something about, E. coli. In its nastiest form causes food poisoning such as the 0157:H7 hamburger related outbreaks we always read about or sometimes vegetables. 

But we study kind of normal everyday benign E. coli, because it's all over the place, it's well studied, and we have plenty of genetic methods. We typical isolate it in our little field lab, and we do DNA fingerprinting and antibiotic resistance testing of bacteria that we collect from the people, the primates and the livestock to look at relationships. This was one of the first papers we published on the topic entitled patterns of gastrointestinal bacterial exchange between chimpanzees and humans involved in research and tourism in western Uganda. And what we did is we studied three populations. We studied people who actually work in the chimpanzee tourism industry. If you go to Uganda you can pay, I believe it's about a hundred dollars now for a really wonderful hour or two of chimp tracking. And you'll be led around by ranger guides who spend a lot of time following chimps, recording data on chimps and taking tourists there. So they have high levels of interaction with the chimps. We looked at them and we looked at people from local villages who don't interact with the chimps because they're not employed in research and tourism and we looked at the chimps themselves. And what we did is we took bacteria from the chimps, the people who work with the chimps and the people who don't work with the chimps, and we measured the genetic similarity between those populations of bacteria, and the thickness of these lines is related to the genetic closeness between those bacterial populations. 

So we see that people who are working with the chimps on a daily basis have bacteria that are much more genetically similar to the bacteria of the chimps than do people living in the local villages who don't interact with the chimps. Showing that there's something about being in the same environment with chimps that makes your bacterial flora more similar genetically to those of the chimps themselves. Interestingly, we decided to take a look at patterns of antibiotic resistance. Now antibiotic resistance, as you all know, is a global problem but you don't tend to think about it being a problem in remote areas like Uganda, but it is. And this is a list of the 11 or 12 antibiotics that are used commonly in people in Uganda, and the red colors are the ones where we see the most resistance in E. coli from people. And if you look down here at the chimps in green, we see pretty much exactly the same patterns of antibiotic resistance in bacteria from these chimps. Now I've gone to the local pharmacies on many occasions and I've never seen a chimp filling out a prescription. So the only way these chimps could be getting these antibiotic resistant bacteria, especially multi-antibiotic resistant bacteria, is by picking them up somehow from humans. Either directly or, more likely, through the environment such as through water or shared physical features of the environment. So a little more depth, I wanted to talk to you about three particular forest fragments that were the core of our study for many years. 

And they're shown here on this map next to the border of Kibale National Park. One of them is called Bugembe, and that one is in pretty good shape. People use it but not extensively. It's not that bad off. The second one is called Rurama, and people use it quite a bit and it's disappearing pretty fast. The third one is called Kiko, and that one is the one I showed you before where all the primates are extinct. That one was so disturbed when we were studying it, so degraded, that it's gone now. You walk through that area, you'd never know it was there. So we have kind of a gradient of disturbance. On the one end we have Kibale National Park which has no disturbance or very low. 

It's protected. But then we have what I call medium, high and very high disturbance. And what we did is we collected bacteria from people living near each of these forest fragments and also from the primates living in each of those forest fragments and we calculated how similar, genetically, the bacteria were between the people and the primates living in the same location. So here you see in Bugembe the primate bacteria weren't that similar to the human bacteria. In Rurama they were a little bit more similar. And in Kiko people had bacteria that was very similar genetically to the bacteria of the primates living in Kiko. And the interesting thing about that is that exactly parallels this gradient of ecological disturbance that I just mentioned to you. So the more disturbance, the higher the transmission rates we infer using these genetic techniques between people and primates in terms of their bacteria. Again implying that there's something about changes to the landscape that are facilitating this type of interaction. And we even were able to get fancier than that and ask for individual people, what is it that makes them more or less likely to have primate-like bacteria in them. 

Well, as in real estate, the most important thing is location, location, location, and I just showed you that. But also people who experience gastrointestinal symptoms, people who reported tending livestock or people who reported fetching water from an open well were more likely to have bacteria that were genetically similar to the bacteria of primates. So I'm not sure exactly what explains this, but at least it shows that there's certain things that individual people are doing that might influence their risk of exchanging microbes with wildlife such as primates. And again when we looked at antibiotic resistance we see a whoppingly high level of resistance in local people. This is just the percent of isolates of E. coli, resistant to at least one antibiotic, up to 80% of E. coli recovered from people are resistant to something. And then is drops off dramatically with lower levels of resistance in domestic animals, then in primates and fragments and we rarely see resistance in the primates living in these core undisturbed protected areas of the park. So one of my students, Innocent Rwego, replicated this work in the gorillas, the famous mountain gorillas of Bwindi National Park in southwest Uganda. You can go and visit them too. It's much more expensive. They're really beautiful animals. 

And he studied three populations of gorillas. Gorillas that are the subjects of tourism. These are the ones you visit. They live at the edge of the park. They interact with people and livestock quite a bit. He studied a population of gorillas that's only reserved for careful limited research. So they had some interaction with people but not much. And then he went right into the middle of the park and found a population of wild gorillas that really has no regular interaction with people except for the occasional student who might hike in there. And when he looked at levels of antibiotic resistance in the E. coli from those populations of gorillas and compared them to local people and livestock, it was pretty much as we predicted. People and livestock have relatively high percentages of bacteria that are resistance to at least one antibiotic. 

And as you go from tourism gorillas to research gorillas all the way to those wild ones that don't have much contact at all, the percentage of resistant bacterial isolates drops off almost in a linear fashion. So again we're finding evidence for this paradigm that ecological overlap is somehow leading to increased rates of transmission. And in this case because we're dealing with antibiotic resistance, we know the direction of transmission, this is probably from people and livestock to the wildlife rather than the reverse direction. So this all made us ask why are people in Uganda taking these antibiotics in the first place? And by far, the numbers aren't so important here, but by far experiencing gastrointestinal symptoms is the reason why. People who experience gastrointestinal symptoms are 30 times more likely to take medications such as antibiotics than people who don't. So this is how people are treating their GI symptoms which are pervasive in the area. So we asked, why are people experiencing gastrointestinal symptoms then? And we had this complicated statistical model where we put in all these factors we thought might be important: Age, sex, location. All these different things. None of it mattered. There were really only two things that mattered. 

The first one that came out in our statistical analysis I just told you was whether or not they took antibiotics. But the other factor that came out of this was whether or not they reported washing their hands before eating. So people who reported hand washing before eating were less likely to experience gastrointestinal symptoms. So all this work, I had to go all the way to Uganda, drag myself over there, study primates just to find out that hygiene is what's really important. So I didn't have to go that far I guess, but it's still nice to prove this. But we started to then ask, okay, we have all these antibiotics here across the top and we see in both Bwindi, where the gorillas are, and Kibale, where the chimps are, we see that different antibiotics are associated with different levels of resistance. Some, like ampicillin, have higher resistance. Some, like gentamicin or nalidixic acid, we find virtually no resistant isolate. Other ones that are commonly used for the treatment of malaria, for example tetracycline, have high levels of resistance. So what might explain this? We looked at a number of factors and, interestingly, the one that was most predictive was price. 

The cheap antibiotics are the ones associated with the most resistance, and the more expensive antibiotics are the ones associated with the least resistance. And in fact we found a statistically significant inflection point in this relationship at 2,000 Ugandan shillings. So after an antibiotic reaches a price of about 2,000 Ugandan shillings, the equivalent of about one US dollar, it suddenly doesn't have much resistance associated with it, probably because people can't afford it. So behind this whole trend of hand washing and disease transmission or microbial transmission from people to primates and conservation lies economics. And that made us very interested in what the people are doing and the human cultural practices in the area. And here I like to kind of tease my satellite imagery geographer friends because these are things you can't see from space. So here's a nice little story. We're out one day walking around these forest fragments. We always go out with our handheld GPS recorders and look at what's going on. And we saw a curious phenomenon on ears of corn planted at the edges of forest fragments. 

We found this brown stuff on them. And it turned out to be a noxious combination of sand, cattle dung and hot pepper. So obviously we had to ask people, why are you putting this on your maize? And it turns out they were doing it specifically to deter crop raiding by our friend the red tail monkey that I told you about. So these are the monkeys that just love corn and people hate the monkeys because they eat the corn. So they're using this type of chemical deterrent to try to get rid of the monkeys but there's cattle dung in here. So we were really intrigued by the fact that a human cultural practice that's born out of human/primate conflict might actually be increasing the risk of gastrointestinal disease transmission between livestock and primates and between people and livestock because people are ultimately going to eat this stuff too. So it's just an illustration of how complicated this system is and how human culture plays a big role. So a recently graduated student of mine, Sarah Paige, decided to look in very great depth at what people are actually thinking and believing and feeling about what's going on in this system. She conducted interviews targeting people who were representing diverse socioeconomic positions in the community. All the way from subsistence farmers to health professionals to local leaders. 

And rather than ask them kind of a fixed set of questions, she conducted semi-structured interviews that left their responses open. And she did this in-depth for a number of people in the local language and used methodology from the social science to try to understand what people are thinking. So I just wanted to give you some details of that. This is a demographic pyramid of our population just to show you that it's very skewed towards young people in both men and women. And this is probably a result of the AIDS pandemic. AIDS is endemic in this area so a lot of the adult population has been lost. So she began by asking people in the community just what do they know about zoonotic diseases, diseases that can be transmitted from animals to people, by asking can people share diseases with animals. Well, in these three forest fragments I told you about most people said yes, a lot of people said no and many people didn't know. When people said yes, they specified mainly food born diseases or agriculture related diseases. So brucellosis from unboiled milk which is a very important worldwide bacterial infection. 

Worms from pig feces and monkey feces. One gentleman thought about it for a moment and said, yes I think we can because we're all coughing and so are the goats. Well we spent a lot of time asking ourselves what in the world could this guy have been getting from the goats or the goats been getting from him until we figured it out. We were asking that particular question of that particular gentleman during the dry season and trucks drive down the road and kick up a whole bunch of dust. So he was coughing and the goats were coughing because of all the dust. So you have to be careful about how you interpret these results. So here's just some fun responses from Sarah's surveys that I think help kind of understand people's perceptions of health disease and wildlife in this area. So here this was an interview with two women, 25 and 65 years old, who are subsistence farmers, as most of the population is. People suffer from fever which is from animals, especially pigs. Even when you go to the pig sty without sandals or slippers, you can suffer from foot diseases or worms. 

Some knowledge about zoonotic disease. Here's from a health professional type. A 37-year-old man who is an enrolled nurse who owns a drug shop. Yes, primates can as well bring diseases to people because in this community we hear people telling us stories like two years back or three that a red colobus bit my two children and they died. Apart from we don't know if it's poison from their teeth or a disease from their blood but yes they also have diseases. So here we have a gentleman who's a health professional who is at least aware that wildlife can carry dangerous pathogens. Here's a 39-year-old woman subsistence farmer. Maybe I have drunk that water where monkeys have defecated or urinated because there are some times when we get confusing diseases and there are some times when we were given medicine that we should swallow. Because of drinking water which is unboiled we might have diseases from animals because the water sources are near the forest. There are even some times when we go to that forest and we step in that muddy water with no boots so I must be concerned maybe I'm getting those diseases from that fragment. 

So this woman is expressing some knowledge of the relationship between disease transmission between people and wildlife and the physical environment. So people are generally aware, but interestingly Sarah had to conclude as a summary of her findings that zoonotic disease was not a factor that local people considered to be a major health concern. If you ask people overall how does this stuff figure into our overall concerns about health, they referred to what are called structural barriers. Poverty, access to healthcare, access to education, improved transportation, improved water sources, the types of things that again relate back to hygiene. So are zoonotic diseases important or are they not important? Well, maybe they're not important in the lives of everyday people, but they're important globally. We here in Wisconsin remember the outbreak of monkey pox that occurred in our state a number of years ago. We decided to take a look in some of these same endangered primates for similar pathogens. And here's a case where we found evidence for a new pox virus. It's related to monkey pox but it's not monkey pox. It's also not small pox or not cow pox. 

We don't know what it is but they have it. We found evidence in these same monkeys for three new simian retroviruses, one of them a relative of the type of virus that causes HIV/AIDS. Are these passing to people? We don't know. But remember this is a population of people living in a rural setting where they interact frequently with wildlife, and many of them are immunocompromised because of poor nutrition or even HIV/AIDS. So we're concerned that people are not ranking infectious disease or zoonotic disease very highly in their own concerns about health, and yet we seem to have people interacting at a very high rate with wildlife that have a lot of pathogens that we don't know anything about. So that's where we are. This is very much a work in progress. I'm lucky to have a skilled team of field assistants who can help collect data even when I'm here in Wisconsin enjoying the lovely fall weather. But I guess if I had to impress anything upon you from our work it's that studying this system has made us realize that it's important to focus on the connections. The connections between people and wildlife and livestock because studying any one of these populations in isolation doesn't tell you very much. 

And that type of thinking, focusing on the connections in real ecological systems, leads to these new trendy fields of study that you may have heard about in the popular press. Terms like ecohealth, population medicine, conservation medicine, one medicine or one health. These are new paradigms that are emerging to capture the idea that people, animals and the physical environment are fundamentally connected. And that creates new opportunities for medical professionals, epidemiologists, biologists, ecologists and social scientists as I hope I've explained to you today. And I think those opportunities are particularly well represented here at University of Wisconsin-Madison. So I'm going to stop there with the science part of the talk except to say that obviously this work is very much a team effort and is supported by quite a number of funding agencies. And I'll just stop there to thank you and to apologize in advance if I've made any unwarranted leaps of faith. So thank you very much. [APPLAUSE]