I am delighted to introduce our Jefferson Fellow, Dr. Bruce Conn, who has been in my office this past year where he has advised us and shared his experience in parasitology and entomology, working on neglected tropical diseases and other infectious diseases, as well as the rest of his knowledge and expertise and keeping us on the straight and narrow in our office. So we appreciate that.
At the State Department, Dr. Conn also serves as an advisor on the development of the Centers of Excellence for Health as part of the President’s New Beginnings speech in Cairo and works on the U.N.-led Towards a Safer World Project, which I think he will continue with after he leaves us. Dr. Conn is a Professor of Biology and Dean of the School of Mathematical and Natural Sciences at Berry College in Mount Berry, Georgia. He’s also an Associate in Invertebrate Zoology at the Museum of Comparative Zoology at Harvard University. His research on parasitic diseases and biological invasions include international collaborations in Poland, Canada, Ireland, Spain and Australia, as well as the Czech Republic where he was a Fulbright Senior Specialist. Dr. Conn earned a Bachelor’s degree from Lee University, a Master’s from Morehead State University, and his Ph.D. from the University of Cincinnati. He has authored more than 300 scholarly publications, including a textbook, Atlas of Invertebrate Reproduction and Development, which was awarded national honors in biomedical publishing by the Association of American Publishers. Today he is going to speak about neglected diseases, emerging infections, and America’s global health century, so over to you, Dr. Conn.
Bruce Conn:
Great, I want to say, first of all, thank you all for coming, but I also want to say “Thank you” to anyone involved with the Jefferson Science Program, which has been a wonderful program for me. I certainly have learned a lot. I feel like I’ve gone back to college after many years out in the teaching role myself. I also want to thank Catherine, not only for a very generous introduction, but also for a great learning experience; not only to her, but to all of my colleagues in the Office of International Health and Biodefense. I don’t think they’ll ever know how much I have learned from this experience and continue to learn.
Well let me get right on with the talk. What I want to do, first of all, is I always like to start with a very happy note, something that makes everyone feel good and the only thing more beautiful than a human child is a lot of human children, especially interacting with each other, playing together, smiling and being healthy. So I just wanted to start off with that and these children will come back again over the course of my comments. What I want to do though, now, is I want to lapse back into the old professorial role. You know, the old time when you had to go and sit in the seat and watch the PowerPoint, listen to the historical presentation leading up to the rest of the topic. Well I’m a biologist, I’ve been a denizen of the Ivory Tower for the last 30 years so I can’t break habits very well, but in this case I do believe that a historical perspective is very critical.
This is a very important time in American diplomacy and American foreign policy as it relates to health. Of course the U.S. Global Health Initiative is the thing that’s on everyone’s mind right now and we are making a major commitment to visualizing health issues as being not specific to any particular country, but being global in character. Well that’s a very good thing to do, but this is not a new aspect of our foreign policy. We have had health and disease issues as a major part of American foreign policy for the last 100 years. Different people would probably put the date at a little different spot, but I actually put the date when foreign policy actually began to engage in health-related issues as a major point of U.S. foreign policy, about 1911, about 100 years ago.
But in order to understand that, you need to understand a little bit of a historical perspective before that, and we’ll start with 1880 when Alphonse Laveran, who was a military officer in France in the French military, first discovered that the malaria parasite occurred in human blood, was actually a living organism that occurred in human blood. Now, up until then, malaria had been known, of course, for many centuries -- actually many millennia, in various forms, as a disease syndrome that has certain types of characteristics. But this was the first time that it was actually tied to a particular organism. It didn’t take much time after that until Sir Ronald Ross discovered that malaria, in fact, was transmitted by mosquitoes. This was a mind-boggling discovery because it was the first time w actually began to see that diseases of humans were not simply diseases of humans. They were sometimes things that were far more complex and involved other organisms.
That, of course, led to a number of things, not only that Ross was awarded the Nobel Prize in Physiology and Medicine in 1902, but it really brought about a new revolution in our entire approach to health and the understanding of diseases. It also, as part of this revolution, led to the establishment of many organizations. First of all in 1899, the London School of Hygiene and Tropical Medicine was founded, incidentally by Sir Patrick Manson. Those of you who are very familiar with neglected tropical diseases, and schistosomiasis in particular, know the name schistosoma mansoni named after Patrick Manson. In 1903 the American Society of Tropical Medicine and Hygiene was founded because the Americans didn’t want to stay too far behind the Europeans in this respect, and then in 1907 the Royal Society of Tropical Medicine and Hygiene was founded. In 1914, then, the Journal of Parasitology was founded in the United States by a group that continues to study parasitic diseases today.
What I have highlighted in yellow, though, and something very critical to my comments, is hygiene and medicine. In all of these societies and now in the journals that are still produced by these societies, hygiene and medicine are seen as being alongside one another as partners in attacking these diseases and confronting these diseases. Medicine alone, in other words, will not do it. Hygiene alone will not do it. The two must be done in companionship with one another.
Well what was going on in 1911, 100 years ago, that I think was so important? Well most of you are familiar with the whole story of the Panama Canal Zone. You may be familiar with William Gorgas, who later would become the Surgeon General of the United States, another military officer, and by the way, much of our foreign policy in terms of disease control and management was conducted by the military at that time in the United States as well as in Britain, France and in other places. But it was in 1911 that Gorgas was preparing to announce that malaria had been completely eliminated from Havana, Cuba as a human disease problem. This was on the tail of having already had successful campaigns against both malaria and yellow fever in the earlier part of the century. What I wanted to say though, is what drove Gorgas to get involved in this particular type of thing? What led him to look at disease transmission by a mosquito? Of course he became familiar with the work of Ross and others, but also it is very important that Gorgas, who was actually from Alabama, spent much of his childhood on the Cumberland Plateau, a higher altitude area in Tennessee, and in fact he lived on the campus of the University of the South in Sewanee Tennessee. There is, if you go to the chapel there, there is a nice stained glass window dedicated to him. It’s interesting; it has him dressed up in fancy attire holding his syringe. In reality, this is a depiction that is not historically accurate. He spent most of his time, as you saw in the photograph before, sort of in rumpled clothing, wading through nasty places in Panama and in Havana, Cuba and trying to combat mosquitoes, not necessarily treating people even though he was a medical officer himself.
Why was he, though, in Tennessee? Why was he in Tennessee along with his family? It’s because they were establishing the university up there, the University of the South. Why establish it on a mountaintop in Tennessee? Well because at that time, we tend to forget, at that time most of the coastal plain of Alabama, Mississippi, Georgia, South Carolina and on, was infested with mosquitoes which were carrying yellow fever, malaria, all of these other maladies. In fact, many may not recall this from history, but in the late 1800’s, one out of every eight citizens of Memphis, Tennessee died of yellow fever, here in our own country. Malaria was widespread as far north as Boston, even Montreal, and we still dealt with it as a major problem in this country and so the university was actually placed there, as were summer homes of many of the affluent from the American South, because it was in a malaria-free zone. If you go up there still and see places like the University of the South and Monteagle Assembly, those had their foundation as a place to get away from these terrible diseases of the summertime.
A similar thing was taking place at the same time in the Adirondacks and the Catskills of New York state, where wealthy families like the Rockefellers and many others had their homes, once again, to escape the deadly diseases of summer that, at the time when they established the camps, did not fully understand. In other words, they didn’t know they were escaping mosquitoes, they just knew that down in the lowlands that were hot and moist they tended to get more sickness in the summer than in the higher, cooler areas.
So that’s what took Gorgas there and that’s what, ultimately, if you read the biographical information on him, sort of led him to have the passion he had for eliminating some of these diseases. But what he did is he stimulated then, with his successes, a several-decade period of other scientists in the United States attacking these diseases in various ways. We saw light at the end of the tunnel. We saw that there was some hope there, because these diseases that had plagued mankind for hundreds of years. Now we could see what they were, what caused them, what carried them and so forth, and there was great optimism. So there was a period of several decades of very ambitious groups of people who took expeditions to many parts of the tropics.
One of the most important in this period was Richard P. Strong, who was at Harvard University, but who also had been an Army officer prior to that and, in fact, had great fame in various situations in the Philippines combating pneumonic plaque, in the Serbian region combating typhus, and also in Britain during World War I combating typhus. So he then went through a period of several decades on these expeditions and published a lot of his work, in fact did the seminal work in infectious diseases, what have now become known as the neglected tropical diseases, onchocerciasis, leishmaniasis, schistosomiasis and others throughout the world.
Strong was influential enough that he worked in rather influential circles, including those of Franklin D. Roosevelt, and at the end of this several-decade period, it was becoming very apparent to Roosevelt and to others in the political scene in the United States in Washington and elsewhere that in fact, attacking these diseases was going to be a very important part, and continue to be a very important part, of American foreign policy both for the military but also for the civilian leadership. But read this. This is a statement of the National Institute of Health in 1940 where Strong reported on the President’s words and says that in this speech he “emphasized that the United States was less than a day by plane from the jungle type of yellow fever of South America, less than two days from the sleeping sickness of Equatorial Africa, less than three days from cholera and bubonic plague -- Hence, the world has now become so inter-related and apparently so small, that our medical and sanitary responsibilities, regarding tropical diseases have greatly increased.” It’s really interesting looking at this in the 1940s, when we realized that airplane travel back then was not a whole lot compared to today. Two days ago I flew from Brussels to New York in barely more than six hours. We can now be halfway around the world in less than 24 hours, along with our diseases, along with the mosquitoes or the bad bug that stowed away in our suitcase. So clearly, if this was apparent to FDR way back then, it certainly is apparent to us today.
Roosevelt became, of course, a big champion of this and many other things and emphasized in this speech that I referred to, that “the ramparts we watch must be civilian in addition to military” and he was referring to these tropical diseases in this discussion. He also was affected by his own past, his own experiences. Here are two pictures of Roosevelt. Interestingly, the one on the left is before he contracted polio, which he contracted as an adult, which made him confined to a wheelchair. But before he got polio, he also spent his summers in a summer camp environment on Campobello Island in the frigid waters of the Bay of Fundy in Canada, just off the coast of Maine. After polio, of course, you see a picture of him leading America from the White House in a wheelchair, but with a passion for trying to deal with these terrible diseases that caused so much pain.
Well let’s move ahead for 40 years, we had -- or 30 years. We had 30 years, then, of extensive development of things like pesticides to control mosquitoes and other insects, we had a wonderful development of many chemotherapeutic agents, drugs. We had the wonderful development of a number of vaccines and so forth. We were really making major progress against infectious diseases. In fact, many at that time during this period by about 1971 thought that infectious diseases were going to become something of the past. We basically had come to ignore malaria, we had rid the United States of this, and we were just tempted to consider it something tropical that we would deal with occasionally, perhaps, but not necessarily as one of our primary objectives. We thought tuberculosis was a thing of the past. This is the time, by the way, when I’m finishing high school. I’m going off to college. There was a very rosy picture being painted for me. Tuberculosis is a thing of the past; drugs have taken care of that. AIDS? There was no AIDS at the time. Well, I shouldn’t say there was no AIDS, at least we didn’t know about AIDS at that point. It had not been discovered or described from humans. It had not come onto the scene. How little we knew, how little we expected the next few decades that were to come.
So the next 30 years, by 2001, malaria is making periodic reappearances in the United States. Tuberculosis has come back in the form of drug-resistant forms, which now are very, very difficult to treat and still just as deadly. AIDS has come to dominate the public health scene both in the U.S. and globally, and it’s something that we’ve only been dealing with for a few years, so clearly the picture has changed again.
By 2011, where we are now, malaria, tuberculosis, and AIDS of course are the big three that we regard as major problems in the U.S. Global Health Initiative. We have other diseases, like dengue virus, that are spreading both in space and time, becoming less and less seasonal, and occurring in more parts of the world than ever has occurred before. And then we have the -- I have termed, or others have termed -- the “Great Neglected Diseases” that have continued unabated or have re-emerged, and I’ll come back to the idea of “Great Neglected Diseases” versus “Neglected Tropical Diseases” in just a bit. Basically the “Great Neglected Diseases” were discussed in the early 80s, especially by the Rockefeller Foundation and others, and included things like malaria, that now are no longer regarded as being as neglected as they were then.
So we come to the question, “Are these diseases we’re dealing with old and neglected or are they new and emerging? Or is there overlap between the two?” Another way of looking at it is “Are they new and emerging, or are they old and re-emerging -- not just neglected, perhaps re-emerging from places where they had formerly been set aside?” Well one of the things we need to do in answering this is say what are the diseases that are neglected. Now I know I’m speaking to a more general audience here. You’ve heard of neglected tropical diseases, you’re probably wondering exactly what that means, and it may comfort you to know that nobody knows exactly what it means and we all have discussions about exactly which organisms or which diseases to include. According to the primary emphases at this point in time, of the U.S. Global Health Initiative, we are looking at 13 primary diseases. The Neglected Tropical Diseases Global Health Network, which is the primary advocacy organization, NGO, that deals with neglected tropical diseases, they pretty much follow after what is currently being done in a pragmatic sense by the Global Health Initiative, and recognize these 13. But if you go to the National Institute of Health’s website, you’ll find that there are 15 listed, for whatever reason. If you go to the World Health Organization’s site, they also list neglected tropical diseases, but they mention 17-20, depending on what you count or what you clump together.
The earlier great neglected diseases that I’ve based my course on -- I actually established a course that I’ve now taught at three different universities, called “The Great Neglected Diseases in the mid-1980s”. There were 20 of those, but again as I said, they included malaria and a couple of other things. If you look at the Public Library of Science, Neglected Tropical Diseases journal, which is probably the most definitive scientific treatment of these things, they recognize 40 diseases that they normally will take under consideration in their editorial policy of what to publish in terms of diseases. So you can see there’s quite a bit of variation and this will be in flux for some time.
One of the things, though, that I want to point out about all of these neglected diseases is that most of them are what we call eukaryotic. Eukaryotic basically means genetically very complex. That means most of them, not all, but most of them are non-viral. Most of them are non-bacterial. Viral and bacterial organisms have a relatively simple genome. They are genetically quite simple compared to eukaryotic organisms. It’s very important to realize that a malaria parasite, though it is quite small, small enough to be inside your red blood cell, is genetically almost as complex as we are. And certainly, some of the other things that we deal with, some of these large worms, the soil-transmitted helminthes you may see discussed, the schistosomes. These are large, multi-cellular organisms, and again, their genetic complexity certainly rivals human genetic complexity, and so when you start talking about attacking them or engaging them, you have to realize you’re up against a very serious enemy.
We’re very familiar with viruses, especially what are called the epidemic viruses that we gained so much against in the last century. I include in these, not influenza --I’m not going to talk about influenza today because it’s a very different sort of beast, but viruses like smallpox, measles, mumps, rubella, these are organisms that we’ve had great success with in terms of development of vaccines, in fact eradicating smallpox and taking major strides against many of these others. But in -- Crawford, a British microbiologist or virologist treatment in her book, The Invisible Enemy, published in 2000, she looked at the characteristics of these viruses. I then, when I was making my presidential address to the American Society of Parasitologists a couple of years ago, contrasted those viral infections that we’ve been so consumed with over recent decades with some of these neglected tropical diseases, these eukaryotic complex parasites and here’s how they differ, something we need to keep in mind.
The epidemic viruses that I mentioned, for example, only infect humans. Again, remember I’m not talking about influenza and some others. There are other viruses that do infect other animals, but most of these epidemic viruses infect only humans, whereas most of the neglected tropical diseases infect animal vectors and/or reservoirs. Typically the epidemic viruses will only infect someone one time and then there’s some level of lasting immunity. That’s not true of most of these neglected diseases. If you’re treated once, you go back out in the environment you become infected again. There is no lasting immunity, which of course would make vaccine development much more difficult. Do-able, something we’re striving for, but certainly more complex in many respects.
The epidemic viruses typically do not establish chronic infections, they’re usually very acute diseases whereas the neglected tropical diseases typically do establish long, chronic infections, typically with very high morbidity or prevalence but typically a fairly small mortality rate. Usually the epidemic viruses are transmitted person to person, whereas the other neglected tropical diseases typically do not go from one person to another. They are transmitted through an environmental mediary or through another organism, especially an insect vector or a snail or something like that.
Well let’s look at a few of these. Malaria, of course, is the big one and I’m not going to say a whole lot about each of these. I’m going to throw up these beautiful but complex graphics that are made available through the Centers for Disease Control. I want to throw it up though, just to remind you of the complexity and to make a few points. Malaria, of course, again is very complex, has a very complex life cycle, living not only in the liver at times and also in the blood of the human host, but also in the mosquito host. If you look down at the lower left, you see this exflagellation process, which basically is this. The malaria parasite is so complex that it -- although it undergoes asexual division and reproduction in the human host, it later, in the mosquito, actually goes through a process of developing sperm and egg-like structures and undergoing a regular fertilization process, a regular sexual reproduction to further amplify its genetic variability.
A lot of things, though, that are not often discussed about malaria. One that we need to keep in mind is that even though malaria is not typically regarded as zoonotic. Zoonotic, meaning “diseases that are shared between humans and animals.” Malaria is not typically regarded in that way because if mostly affects only humans, but historically that has not been the case, and perhaps in the future it will not be the case. One of the things I’m proud of, Steven Rich, who’s a professor now at the University of Massachusetts, was one of my first students when I was at St. Lawrence University, one of the first students to take my “Great Neglected Diseases” course. He went off and has made a career studying malaria and other things, and in fact, recently his published work doing very extensive genomic analysis that has demonstrated quite conclusively that malaria, as it occurs in humans, was originally a parasite of non-human primates and emerged from that to infect humans. Sounds like a familiar story, doesn’t it?
And so at one time, at least historically, perhaps up to 30,000 years ago, we did get it from other animals. But also we have now, even though there are three or four, depending on how you look at it, primary human malarial parasites, different species, all of which by the way cause different kinds of symptoms, different types of virulence in the human host. There is also a fifth, plasmodium knowlesi, which is currently shared. It’s primarily considered to be a disease, of course, of primates but also there are human infections and there’s always the chance that any of these human parasites could adapt progressively into being a human parasite, something we should always keep in mind. And, in fact, that’s sort of the underlying statement of this entire presentation, that these are living, breathing, adapting, changing, evolving organisms. They are not simply things to be defeated. They are things that are constantly going to be on the move.
Chagas’ disease, one of the neglected tropical diseases, a very important one. This is one that is found in the Americas. It’s related to African sleeping sickness disease but has very different clinical consequences, very different epidemiological consequences. It’s generally thought of as a vector-transmitted disease, transmitted by bugs. It’s also thought of as being a South American or Central American thing, but actually it’s increasingly becoming a problem in the United States. Depending on the estimates that you look at, we now probably have, according to some estimates, up to 300,000 infected people in the United States, most of these having immigrated from Central and South America. Most of these are not reported cases. Of course the number of reported cases would be a very small fraction of that, so these are just estimates. But one of the things that’s important to recognize is that even though you may read well there’s not a major concern for emergence of Chagas’ disease in the United States because we don’t have the competent bug vectors here, we do have bug vectors that can transmit it but they’re not as well-suited as those that are found farther south. It’s important to realize that one of the primary modes of transmission of Chagas’ disease is transplacental, from mother to unborn child. It also is shown -- in fact the vector-borne disease arbitrary at Berry College, where I work, is actually publishing papers now on the propensity of the American-isolated strains, mostly taken from American wildlife, to infect placental cells. That’s a much better efficiency of infecting placental cells than other strains. And there’s some thought that the primary form of transmission in the United States terrain right now may be transplacental, not vector-borne. So keep your eyes open for that. Something else to sort of show how complex the situation may be.
Leishmaniasis. This is something important to point out, because in trying to clump all these neglected diseases together, we fail to mention one critical point and that is that many of these diseases, perhaps most of these diseases, are not single diseases. Leishmaniasis is not a single disease. We clump all these together out of convenience, but really there are perhaps 20 different species of leishmania that infect humans. And those, they are transmitted not just by the sandfly, as it is often stated, but of numerous species of sandflies with different behavioral, physiological, and other characteristics. They occur in different environments. They have different clinical pictures. There are three primary clinical forms of leishmaniasis. Again, very different diseases. They share in common that they live inside the macrophages of your body, the very cells that you send to destroy pathogens. They actually seduce those cells into engulfing them and then they live there off of those cells, cause the damage there. But they can do that either deep in your viscera, in your internal organs, in visceral leishmaniasis. They can do it in your skin in cutaneous leishmaniasis. They can do it in the mucocutaneous membrane, the mucus membranes of the nasal passages, the mouth and so forth, as mucocutaneous leishmaniasis. None of these are very easily treatable. None of these have had successful vaccines consistently developed against them, but again, the main point here is this is not one disease, this is several, at least three if not more than three, diseases. And so if you were to go back to that list of how many neglected diseases are there, well really you can see already that the list grows much, much longer.
A similar thing is true with schistosomiasis. Schistosomiasis is called “blood fluke disease”. It’s caused by a worm that lives actually inside your blood vessels, mating, laying eggs. You can see the male and female wrapped together in a permanent copulatory state there on the lower right. The important thing though, is that after they have sexual reproduction they’re producing eggs which ultimately cause the greatest disease. These eggs go throughout the body, destroying tissue as they go, resulting in extreme fibrosis and so on. But schistosomiasis is not one disease. Schistosomiasis is at least three diseases. There are actually more species that infect humans, three primary ones, and I’ll talk to you a little bit about those to show that in fact these really should be classified as very different types of diseases, not just all one thing.
They have some epidemiological as well as clinical differences and you can see this on the far left. The far left shows all the different snails. All of these are transmitted by snails, aquatic snails. The snails, however, are releasing the infective stages of these parasites and you don’t even have to drink the water. All you have to do is be in contact with the water and these things are able to penetrate directly through the skin. But the snails are quite different from one another and that results in these different epidemiological characteristics and why I say you can’t call this one disease. Schistosoma mansoni, for example, named after Patrick Manson, is in Africa and the Americas, as opposed to schistosoma haematobium, Africa and the Middle East, Asia for schistosoma japonicum. So biogeographically these are very different.
Clinically, they are extremely different. Schistosoma mansoni mostly causes problems in the intestine and the liver. Schistosoma haematobium mostly causes problems in the urinary tract and the reproductive tract. Schistosoma japonicum, the intestine and the liver, but also because of the nature of its eggs relative to the other two types, ends up causing severe complications in places like the lungs and the brain. So again, very different clinically. Epidemiologically, all transmitted by snails, but mansoni is transmitted by snails that live primarily in slower moving waters, the biomphalaria snail, it’s called. The bulinus snails that transmit schistosoma haematobium tend to occur also in slow but sometimes somewhat faster moving waters. Schistosoma japonicum snails, oncomelania, they actually are more amphibious. They are able to engage in longer periods outside of the water or in damp meadows and so on, and of course set up different problems there. So if you’re trying to control the diseases simply by treating water, it’s not necessarily as successful with the schistosoma japonicum because it may not be in the water as frequently.
What about reservoir hosts? Well with schistosoma mansoni there are very few host species beyond humans. There are some, in fact some indications are that there are many and maybe more than we have accounted for in different geographical localities, especially of Africa. Schistosoma haematobium mostly is a human parasite. It will infect certain other primates and so on, but schistosoma japonicum infects a lot of different animals, domesticated livestock as well as wildlife, and as a result is more difficult to control in that respect.
Okay, what about schistosomiasis? Is it an emerging disease or is it neglected? Well, probably both. It depends on where you’re looking. This is information that just came out, by the way, about two days ago in an analysis that was put out by ProMed Database group that some of you may be familiar with that you can get access to. It estimates -- now these are not clinically reported cases, which would be again, a very small fraction. But they estimate that in 1921 there were probably 25,000 to 30,000 people infected with schistosomes in the Philippines. By 1948, that number had grown to an estimated 300,000. By 2002, an estimated 800,000. Now even though it has gone down since then because of more active campaigns to control this, the point is this would appear to be not just neglected by actually an emerging disease if you’re looking again at the long emergence over time. But also, again, remember we’re not talking about diseases that tend to occur quickly and acutely and cataclysmically. These are slowly progressing diseases. These are the tortoises of diseases, whereas influenza may be the hare. Which should we fear most? Well, perhaps we need to fear both for different ways and then we need to adopt different measures for dealing with the two.
Okay, now let’s get to one that’s of special interest to me and I told you the children would be back. I didn’t tell you I was going to be bringing them back in such an unhappy circumstance. In the pictures they’re still smiling, the reality is much more grim. In 2011, here we are. Diarrhea still ranks second only to various types of respiratory diseases as the number one killers in the world. Somewhere in the world, this is by World Health Organization’s statistics, somewhere in the world a child will die of diarrhea of some sort every 24 seconds. Think about that. There are ten children figured here. Within the next couple of slides that I show, all ten of them would be dead. A rather grim thing to think about. Is diarrhea one disease? Oh, clearly not. Diarrhea is many, many diseases. We hear a lot about things like cholera in Haiti and so on, but there are many other diarrheal diseases that also cause tremendous morbidity, significant mortality.
One that’s clearly an emerging disease and yet is also now regarded as a neglected disease in other respects is cryptosporidiosis. Interestingly, it’s a biological relative of malaria, of the plasmodium parasites, same group of organisms. It also goes through an alternation of sexual and asexual life, except that instead of infecting blood cells and liver cells, it infects cells that lie in the intestine. It’s now recognized as one of the most common and most widespread diarrheal pathogens in the world, and we really don’t know a lot about how many people are affected because we haven’t studied it that well, because in fact, the first human case was only described in 1976. So this has not been with us long, at least in our minds. Now we knew the species, or at least some species of cryptosporidium to occur since the early 1900s, we just didn’t know that they affected humans. There are several species, some of them are zoonotic, others apparently are not. The genomic complexity of this group is just extreme. It’s sort of like thinking you have one parasite and you open the window and if you were to see the genomic analyses of cryptosporidium now, there may be scores of species out there, all doing different things in different animals, potentially making their way into human bodies at different rates and with different consequences, a very complex situation. They’re not easily killed by chlorination. They can make it through a lot of filtration systems. There’s no good vaccine. There’s no treatment. So do we only worry about those in tropical countries, poorly developed, poor sanitation? Not at all.
In fact, one of the biggest outbreaks on record occurred in Milwaukee, Wisconsin in 1993. Not only a sophisticated city with very sophisticated sewage and water treatment system, but a city in a very northern environment. If you’ve been around Milwaukee you know it’s covered with snow and ice much of the year there on Lake Michigan. So it’s not tropical at all and not underdeveloped at all, and yet in 1993 the water treatment system was overrun. An estimated 400,000 people were sickened by this parasite, one out of every three people in the Milwaukee area. 100 people died of this, mostly elderly or people who were immunosuppressed for one reason or another. We still don’t know exactly what was going on there, but we think that it was probably a zoonotic situation associated with the cattle there in the Wisconsin dairy industry and also an occurrence of different rain events followed by dry events and so forth, but again, we don’t really know exactly what caused this to happen. But if it could happen in a very modern, sophisticated city like Milwaukee, certainly it could occur, and probably does occur, in many other places in the world where it is not recorded as such.
One of the problems with not knowing what caused the outbreak is we have failed to look at cryptosporidiosis as well as many of these other diseases, perhaps most of these other diseases. We have failed to look at these in the proper way, I believe. For one thing, we look at them too much as diseases and I would argue they’re not diseases. Cryptosporidium is not a disease, it’s an organism. It’s out there living its life just like we’re living our lives. It just happens that its life involves living inside of us from time to time and until we start looking at it in that way, we’re going to have a hard time really understanding how to predict the outbreaks and how to control them.
So some of the things that we’re doing, just to make a little bit of a touch, I had to give a little plug for some of the research we’re doing in my laboratory since I am an academic after all. One of the things we’re doing is we’re trying to look at Lake Ontario. We are surveying about 300 sites across the Great Lakes and the St. Lawrence River, counting the numbers of cryptosporidium infectious agents that are found there, trying to understand where they are, and perhaps trying to understand why they are in some places rather than the other. I won’t bother with this. This is cryptosporidium as well as some other water-borne diarrheal pathogens that we’re dealing with, so don’t worry about reading the labels. I know you can’t. But look at the columns there. The columns basically show the numbers of parasites relative to one another in these different locations and all of those flat ones over on the left are near Toronto Harbor, whereas the ones over on the right are farther along toward the east on Lake Ontario and down the St. Lawrence River. So we know there are distributional differences, we just don’t understand what they are. We need to look not at clinical laboratory data from infected humans, we need to look at the environment. What is the environment doing? What is it telling us? So we look at the hydrology of Lake Ontario. We look at the wind patterns as shown on this slide. This is just one, as an example to show that NOAA takes care to produce. We believe that some of the answer to why you have less in Toronto than in Kingston, let’s say Ontario, to the east has to do with the bathymetry of the lake, the hydrography, the surface current patterns, and so forth but we’re still studying that. The point is, we have to understand that this is part of a complex environment. It’s not just a human clinical problem.
There are other things going on. We’re looking at flies and how flies are used to transmit these. One of the neglected diseases being focused on in the Global Health Initiative among the neglected tropical diseases is blinding trachoma that has fly transmission as a major part of how it is spread from one person to another. But that also occurs with a lot of other parasites, and we’re showing here cryptosporidium and giardia, two diarrheal parasites that are transmitted looking here at various types of livestock as well as wild animals. We’re trying to understand how these different animals maintain these populations, how they may be moved around by flies, and how they may ultimately then end up inside human bodies.
Another very important one that people don’t think of much. Dung beetles. Who knows about a dung beetle? I mean, you know, boring little things unless you’re an entomologist like me and then you know they’re fascinating creatures. The important thing is that any time any animal defecates on the ground, anywhere in the world, whether it’s an elephant in Africa or a wild turkey in Tennessee, anytime that it defecates within minutes, literally within minutes, half or more than half of the fecal material is transported underneath the ground by these dung beetles. They are extremely abundant everywhere and they go virtually unnoticed by the average person. But if they’re burying all this fecal material, they’re also burying all of these pathogens that come out with the fecal material. The thing is, nobody has really looked at that yet, in terms of what implications, if you’re taking all of the infectious material in a pastural land, near Milwaukee for example, and you’re burying it -- these beetles are burying it within a matter of minutes -- what implication does that have for the epidemiology, the chances that a sudden rainfall at a particular time of the year might overwhelm the water systems and result in a hundred people dying and 400,000 people being sick? We don’t know the answer to that, because again, we haven’t been looking at the entire environment. We haven’t understood things like dung beetles as being a critical part of this.
So what’s the biological bottom line? Again, I’ve already said it, these are not simply diseases of humans. We’ve got to stop looking at them as diseases of humans. That may be the reason that we want to study them, but if we stop there and then we approach them only as diseases of humans, we’re going to fail, I believe. They’re genetically sophisticated, adaptable, natural components of the same highly complex ecosystem of which humans are also just one component and we’ve got to approach this from that standpoint.
So finally, where does biology meet diplomacy and foreign policy on all this? Where have we come to now after a year? Partly we go back to Gorgas’ days in 1911. We start looking not only at people being sick, but also at mosquitoes and where the mosquitoes live in drainage ditches and how those drainage ditches are configured and things of that sort. We look at dung beetles, though. We look at water flow patterns in lakes and rivers and so on.
I wanted to make an analogy again to something we’ve learned -- I think we hear about in the military campaigns going on right now, for example, in Afghanistan. Campaigns against terrorism and counterinsurgencies. One of the things that has been learned is just because you have bigger, better, more powerful weapons doesn’t mean that you’re going to win a war. You also have to understand the people, you have to understand the culture, you have to understand the behaviors. That has become very apparent, for example, in Afghanistan as we’ve seen lately. Well we are at war with these diseases and we have to understand the same thing about them and the same way that people in different countries come with different cultures and different patterns and so forth. All of these ecosystems are differently designed and we’ve got to understand each ecosystem in its complexity and we’ve got to approach the disease -- not the disease -- the organism we would like to control from that standpoint. To do that then, we must change. We must end-manage the natural ecosystems as well as the human behaviors when we interact with those systems. So in the end, why do we do it all and what do we have to thank for this? Well I’ll let the last picture say it all for us. And with that, I will be happy to take questions.
[applause]
Male Speaker:
Thank you, it was really well presented. I have a question. I served in Rwanda and there was a great deal of effort through the PEPFAR program to work on AIDS, but in Rwanda the biggest single economic medical problem is malaria. How much does politics get into it? How much can we influence this? What do you think?
Bruce Conn:
Well, I think that -- for one thing, I think that we already are influencing it quite a bit. Of course, as you mentioned PEPFAR, we have made a major emphasis of AIDS, something that needs to be done, because it has such terrible effects across the world. But I think one of the real signs that the United States is serious about engaging the entire globe to improve human health, is seeing in effect that malaria has taken on -- as I mentioned, in the 1980s malaria was considered one of the neglected diseases. We no longer classify it as that partly because the United States and others have placed it higher on the list. Not just because it’s re-emerging or it’s become a bigger problem, but out of the recognition that it is such a significant problem in most parts of the world and that we cannot -- just like we can’t isolate ourselves from Rwanda or the rest of the world in a political sense, we can’t in a biological sense either. We have to approach all of these diseases as diseases of all of humanity. And I think we’re doing that. I think the statements that are being made out of Washington are clearly doing that. I hope that what has been done for malaria will now extend increasingly to many of the neglected tropical diseases and other diseases which, while they’re at least on the radar screen now, they’re still a small blip on the radar screen. There are still neglected tropical diseases, for example, that are still only about one percent of the overall Global Health Initiative budget. So I think we’re learning and we’re progressing. We still have a ways to go.
Male Speaker:
What I was thinking of, Bruce, was along those lines was, you know, you talk about eradication of malaria here in the United States, so I mean has somebody been able to plot economic development along with increased use of pesticides and insecticides to eradicate malaria? It would seem that they would go hand in hand, even including deforestation, which would help so could you tell us something about the correlation of economic development and the disappearance here. Are there any good studies?
Bruce Conn:
Well, you know, certainly eliminating diseases like malaria would increase economic development. But having the diseases in the first place of course, will suppress economic development and so it’s a very difficult thing to approach. In the United States -- one of the important things I think to remember about controlling or eradicating malaria from the United States is that, for one thing, I’ve mentioned that all these diseases are not single diseases. They are several. There are four major plasmodium species that affect humans and the United States never had the most devastating, the most virulent one, plasmodium falciparum. We have imported, occasionally, with people who have come in sick, but it has never been locally transmitted here to a large degree. We mostly have had plasmodium vivax, which although it causes tremendous disease, it’s not as difficult, as virulent, as deadly as plasmodium falciparum.
But also, the name “neglected tropical disease” is a little bit false, as I mentioned, in terms of the geographical distribution, but for the most part it’s not false. Most of these things are organisms adapted to tropical environments, so since the United States in the mainland has not got any actually tropical types of settings, I guess it’s fair to say that malaria, relative to sub-Saharan African countries, malaria just barely had a toe-hold here. So in some ways it was easier to eliminate it from the United States than it would be -- or from Western Europe where it was also a problem many years ago. It was easier to eliminate from those locations than it has been in other areas.
But in terms of economic development. Economic development typically brings clean water, sewage treatment, water treatment. It brings better housing for people so that they’re not exposed to vectors and other things. It brings easier access to good and regular medical care, so again, clearly to attack these diseases we have to work on increasing the level of development of the countries where they occur.
Female Speaker:
Yes, if I could add a positive note. I’m on detail at State from the National Science Foundation, and the good news is that the National Science Foundation has partnered with NIH for at least the last 10 years to run a competition called “The Ecology of Infectious Disease” where NSF brings all that expertise on ecology and critters together with the disease expertise. Many of these projects, in fact, are international and have international collaborators. So, the good news is that our government has kind of recognized some of this, the bad news is the climate change now promises to change many of those relationships. Do you know -- can you speak to climate change and how that might be influencing some of these diseases?
Bruce Conn:
Well, I am happy to address it, of course climate change is a difficult subject but all these subjects are difficult. Clearly climate change will change radically the distribution of all these diseases, because again, they are living organisms. A lot of times when people ask me whether climate change will have an effect on disease, I say -- my answer is “Do polar bears live in the Arctic?” In other words, these are living organisms. Yes, they have certain types of environments, temperature, rainfall patterns, everything else. Certain types of environments where they prefer to live and where they flourish most extensively. And so yes, changing climate will affect these things, but the reason I don’t think of that as -- even though I think it is a problem, I think whether it’s climate change or something else, these organisms will continue to evolve and adapt and to seek new places to live and to have their own offspring. So I applaud the NSF’s approach to this. I think that it’s the way to go.
I also, if I could put in a plug for the State Department and USAID, I will say that really because of the complexity of this, because it has economic, cultural, other elements to it besides just the scientific and the medical, I think that organizations like the State Department and USAID are ideally suited for dealing with these issues, for bringing together the expertise not only of different federal agencies of the United States government, but from comparable agencies and ministries and other governments. And I think one more of the things that has excited me in my year of being here is I’m seeing that occurring to a greater and greater degree as things go along, and so it does bring me a lot of optimism and hope that we will be integrating more of our work over the years.
Male Speaker:
Hello, thanks again. It’s always a pleasure to hear from somebody who is so passionate and knowledgeable about their subject. One thing that I was surprised about when I was traveling throughout Southeast Asia, even as shortly as six, seven years ago, is I came across lepers. Where does leprosy fall into all of this and what are the chances of that being eradicated? Secondly, I’d like to ask --I've read some articles about phages as being a therapeutic tool, or maybe something that could be used on some of these diseases and would like to hear your comments about that.
Bruce Conn:
Okay. Leprosy, of course, has been a major problem for a long time, although I should hasten to mention that most of us heard of leprosy from biblical readings from years back and it’s important to point out that when those were written, they may have referred to things also like leishmaniasis and other skin afflictions because there was no discrimination there between bacterial and other things. Nevertheless, we know that leprosy has been among us for millennia, for as long as we have recorded history, and it remains a major problem in many areas, but one that is being dealt with. Leprosy has always been one of, for the last four decades especially, one of the primary diseases that various philanthropies and governments have been attacking. Leprosy is currently a major target within the Global Health Initiative, with the idea of trying to eliminate leprosy as a major human problem and so, in terms of its prioritization I think it’s still up there and that should give us some hope.
The question with phages -- there are lots of new things being explored. A lot of new molecular techniques, a lot of new techniques that attempt not only to develop immunity for example in humans, but immunity in insects to keep them from getting diseases. There are also efforts to look at ways that we can infect the various types of parasites, so if you have a bacterial phase it can actually infect pathogenic bacteria. That might be a good way of controlling that. You know, I think with all of these new techniques I think we need to proceed cautiously but optimistically, that we are continuing to develop newer and newer arsenals. What we shouldn’t do is think that we’re ever going to find the magic golden answer or the silver bullet, if you will. I think this is a permanent fight. We’re going to be constantly working on new ways to treat organisms that will continue to find ways of resisting our treatments. That’s not pessimism, that’s just a realistic attitude, but I think we’re getting better at doing this as we go along.
Male Speaker:
Is there a civil engineering response?
Bruce Conn:
Well [laughs] I’m actually glad you mentioned that. Is there a civil engineering response? Clearly there is a role for civil engineering in this and civil engineering, like medicine or anything else, can help or it can hurt. But this is why we have to look at each situation differently and try to determine what is best in any particular situation to deal with the disease situation that occurs there. For example, how can civil engineering projects hurt? One of the reasons I showed you the data for the Philippines -- if you’ve followed North African situation over the last several decades, things like development of the canal projects in Sudan, the Aswan High Dam in Egypt, various types of irrigation projects, you know that many times the development of some of these water-control projects have actually caused an increase in the occurrence and distribution of diseases like schistosomiasis. And so it’s very important to look carefully at the situation before you begin to develop various types of engineering projects. But on the other hand, the power for us to deal with diseases by developing better sewage treatment, by developing better irrigation systems when we need them, safer irrigation systems by developing better water treatment systems, there’s no better way, I think, of controlling the disease than to make sure people have clean water to drink and a good way of sanitizing their sewage material so that it does not come back into the environment. Most of these diseases that we’re talking about are spread -- or many of them, the soil-transmitted helminths, schistosomiasis, many of the others are transmitted by fecal contamination and if we can control that, mostly through civil engineering projects, I believe, and other even -- not necessarily big grand projects, but minor scale village level, even individual household level projects -- I think that we can control a lot of the sickness.
I don’t see anyone else moving toward the microphone, so I will simply say thank you very much for being very attentive and I’ll be happy to chat with you after this is over, or you can email me, but I love the conversation and thank you so much for being a part.
