 because we can't even say it's Riley, who's a professor and chair of the infectious disease and vaccinology division at UC Berkeley. I was interested in reading his bio, I guess, because I didn't know that he trained at Stanford. That's his ID fellow. Right, no, I did, yes. But actually started off, did his residency at Columbia, was an EIS officer at CDC, then came to Stanford to do his ID fellowship, and then as faculty at Cornell, until he, actually for quite some time, you were at Cornell. About seven years, yeah. He transferred to UC Berkeley as the professor and chair of the division there. It gives me great pleasure to actually meet Lee for the first time, even though we share a center, a global health equity, I'm part of the consortium for Global Health Equity Scholar Program in Slum Health. And so, Lee, for the talk to us a little bit about, I'm asking some of the disparities in Slum Health. It's very important to look forward to it. Thank you, great. So it's a real pleasure to be back where I spent many years of my life. I was actually as an undergrad as well, so I spent a lot of time here. I was with Gary Skulnik, who's my mentor. Let me just stick this up. There's no, okay, it's okay, I'll just use this. And so, as Michelle mentioned, we have this consortium that focuses on this new theme of some of the things that we do, it's called Slum Health. It's a consortium that comprises of UC Berkeley, Stanford, Yale, and Florida International University. And I'll mention this at the end because some of you may be potentially interested in participating in this program. But so, as Michelle mentioned, I did EIS after my residency and then I came here to do molecular biology, basic pathogenesis training. And so I combined my basic pathogenesis training, bacterial pathogenesis training, with my epidemiology training to do what we call molecular epidemiology and that's one of the courses that I teach. And I'm always looking for new ways to apply this discipline of molecular epidemiology to address important clinical as well as public health programs. So I thought I'd share it with you, one of the things that we've been doing here. So, how many of you have been to India? So you know, India, so this is actually when you go, this is Chennai, when you go from the airport into the city at night, this is what you will see. You'll see the billboards here like this and you'll think that India is represented by what's depicted in the billboards. But if you go to this, if you cross this bridge in the middle of the day, this is what you'll see. And this is a part of India, which is actually a very large part of India, that you don't really see unless you're there in the daytime. And you know, in the US, we had just talked about, you know, the so-called 1% versus 90%. This is a population that's not represented by either 1% or 99% because they don't really officially exist. And about one billion people in the world who live in these kind of communities. And the health impact of what this population contributes to the formal health sector is something that we have to deal with. I mean, all of you in this room, at some point it's gonna be dealing with this one way or the other. And we don't talk about this. And so that's what I wanna talk about and share with you. So here is a cover of a magazine from Brazil. And you see this? I mean, you see, what's wrong with this picture? You have this fence here. This is stopped working. Is there a, neither? It's okay. You see this fence on this side of the fence. You see this apartment building with a swimming pool in each porch, okay? With a tennis court and swimming pools. And on this side, you have these kind of housing. And of course, people who live on this side of the fence will, of course, contract those types of diseases, infectious diseases, okay? And so will the people on this side of the fence. But on this side of the fence, you see these other diseases that you will never see on the other side. Leptosporosis, meningitis, all the hepatitis, vaccine-previvalent disease, multidriaguses, TB, and rheumatic heart disease. And I'm actually gonna talk about two diseases today. Leptosporosis and rheumatic heart disease. Because these are probably diseases that you've probably never seen unless you've worked in places like this. How many of you have worked in places like this? Okay, so you know that, okay? Most of you have, good? And I just wanna start by showing the contrast of the way people live in this community. So you have this side here, this kind of community that's called the favela. And then you have these high-rises here. And the high-rises, of course, surrounded by walls and gates. And the people who live here probably never venture into this kind of community. But people who live here will work in these kind of residential units as servants and cooks and et cetera. So you do have this kind of intermingling. Here is another situation in Mumbai, India. So this is Taj Palace, the most exclusive hotel in Mumbai, probably in India. And you heard about this terrorist attack in that hotel several years ago. But if you walk maybe just 10 minutes this way, you'll come to this type of settlement. And it's actually called fisherman's slump. That's the official name for this community, just 10 minutes away by walking. And I took this picture in Chennai because it actually represents sort of the three stages of sort of these, what I call slum development. So here you see these makeshift houses in the front. And then the one in these concrete buildings in the middle represent the sort of the government programs, the sort of projects that we call projects in the US that they built for these populations. But in the back, you see yet sort of another type of housing. So you see the three levels of housing there. And the disparity across these three type of populations, populations who live in these types of buildings are just enormous, okay? And so you know about the genie coefficient, right? You've heard of genie coefficient. So this is the measure of the difference in the highest income earning segment of society and lowest income segment of society. So if you have a genie coefficient of zero, that means everybody in that society makes the same amount of money. And if you have genie coefficient of 100, then only one person makes all the money in that community, okay? So the lower the number, the more equal, the distribution of income. And so if you look at the two members of the BRICS countries, Brazil and South Africa, they were there, but the other two members of the BRICS countries, China, Russia, they're in there actually more equal than all of the BRICS countries. And look where U.S. is, it's right here, okay? Oh, great, thank you. Okay, thank you. So U.S. is here, and you know yesterday we had an election, right? And we almost went this way, in terms of the number. We may still go this way, but maybe not as fast. U.S. used to be much lower in terms of the genie coefficient. So how many of you speak other languages? TG, one of the African director, Jodhupati. Guess I can't do it, Turkish. This means it happened overnight. What about Ashway, what about Bariadas? You know that, some of you, many of you probably speak Spanish, no? Okay, so you know what Bariadas is, Kampung, Muduku, Bidonville, okay? So these are what slums are referred to in these countries, and they were depicted here in all these terms. We call them, in the U.S., slum, Shenandoah and Ghetto, Square, neighborhood, et cetera. And so in 2003, the United Nations Human Sentiments Program published this report called The Challenge of Slums. How many of you have actually seen this? Okay, so you guys are all involved in health, and this is probably one of the most important documents on health that I think I've ever been published. Reports the sort of the characteristics and the social demographic characteristics of one billion people in the world who live in these conditions. There's very detailed statistics of this, okay? So in fact, there's the operational definition of slums. These are human settlements with unilateral access to safe water, unilateral access to sanitation of the infrastructure, poor structure, quality of housing, overcrowding, insecure residential status. And so if you use this definition, right now about one third of the people in the world live in these conditions. This is the reality right now. And then it's estimated to go up to two billion by year 2030, so that's only 20 years from now, less than 20 years. And so this is gonna happen long before impact of things like global warming. You know, global warming, the impact of that on populations not gonna probably happen till for 50 more years. But the same thing that the global warming is predicting on the population distribution is gonna happen much earlier just because of this urbanization issue, which is something that's not addressed. And it was nowhere in any of the presidential campaign discussions. So right now already 43% of the combined urban populations in developing countries live in these conditions. And the least developing countries already have close to 78% limits. So already this is the norm of the existence of large proportion of the world's population. And so this report discussed demographic, spatial, economic, legal, and social indicators, one billion people. They also discusses life expectancy under five mortality, slum upgrading programs, poverty reduction programs. What do you think is missing from this report? Health burden measures. Okay, there's nothing about health burden. These are very difficult to measure in these kind of communities. Many of these people who were born there, their births are not necessarily recorded. If they die, their deaths are not recorded. They don't officially exist. They don't just say they can't go to school, they can't do anything. And so we get these kind of data from things like national mortality registry, hospital discharge diagnosis, health insurance database, demographic and health surveys, multiple indicator cluster, WHO surveys. But there's information disparity in these communities. We can get these things. This is where we get things like dalleys and all these information burdens of disease. So in 2000, UN actually, as part of the Millennium Declaration said, this significant improvement in the lives of at least 100 million slum dwellers by year 2020. And that's great because this is the first time an international organization even used the word slums and recognized the existence of this population. The problem is that urban population growth is 70 million per year. So this is just a drop in the bucket, 100 million by year 2020. So let me not tell you with this background. Let me just tell you what we do in Brazil. So a lot of our projects done in Brazil. How many of you have been there? Okay, so you know. And so one of the things that we're doing is just something we started. You know Rio de Janeiro is hosting the next World Cup and the Olympics. So the Brazilian government decided to just to be respected by the world, try to, they started these programs to upgrade all these slums in the city of Rio as well as Sao Paulo and other cities. So what we decided to do was to really try to assess the impact of these slum upgrading problems on certain types of health outcomes. So I sent a student there, an epidemiology student there last summer to kind of get baseline data before these upgrading programs start. And we're gonna do this after these of course implement it and see what happens, okay? And so these are some of the baseline data that Robbie Snyder got. And so we're gonna assess five diseases, three infectious and two chronic, non-communicable. And we're gonna develop what's called the new slum specific metrics, calculate dallas. You know dallas, right? These are disability life years lost. So this is a way to quantitative disease burden, okay? And so for instance, tuberculosis has a numerical attachment, dallas. In the low and the middle income countries is about 35 million and 87,000, that's a dallas. But if you look at TB in high income countries the number is 219,000. So there's a difference of more than 35 million, okay? But if you look at the slums versus non-slums in those low and middle income countries we're gonna also see a difference, okay? And we wanna measure this what's called the Dali Gap and then see if the slum upgrading program will decrease the gap. So that's just a real quantitative way to assess disease burden. So we're just getting that started. And then Brazil itself uses a definition of slum. They call it aglomerados subnumais. And it's a very similar definition that the UN uses. So these are settlements consisting of at least 51 houses, illegal occupation of the land and illegal property construction, possessing at least one of the following characteristics, urbanization outside of existing standards, which is indicated here, and then lacking essential public services and invaded land, irregular illegal lots are clandestinely occupied in a recent period. So this is a part of Rio de Janeiro. And this is the Lagos, right? This is Ipanema where everybody goes and this is Copacabana. And these pink areas are the sort of slum communities. So the Brazilian government has actually done a very extensive census of these communities and we're gonna actually measure things like income, age, all the demographics. And just to show you the age pyramid. And you can see just within the same city, the difference in the age pyramid structure. You see how where the bulge is in the slum community versus non-slum community. So the bulge is much lower here. So this already influences the kind of health problems that we're gonna see, just the difference in age structure. And if you look at the Gini Coevision itself that I just mentioned a few minutes ago, in the slum communities, it's actually quite equal. It's the most equal segment of Rio de Janeiro. Because everybody's poor, equally poor. For many years, we've been studying leprosy and tuberculosis and rheumatic heart disease in Salvador, Brazil, up in the north, northern part of Brazil. In fact, when I was at Cornell, I had an infectious disease fellow who worked with Albert Coe and I sent them down to Brazil. He's American and he stayed in Brazil for 15 years working on leprosy. Now he's one of the world's well-known researcher on leprosy. So I'm gonna tell you a little bit of what he's done. He's now a member of this consortium at Yale. He's a Yale PI for this consortium. So that's where Salvador is. And this is what it looks like. How many of you have been there? You guys, you know, this is the fortunate novel where they are one of the, maybe the opening ceremony of the World Cup will take place, we'll see. But we work in one of the community, slum community called Pau de Lima, which is near the airport. So in this community, in late 1950s, this is what it looked like. No housing, nothing there. And then by mid-1970s, you begin to see formal settlements outside of this demarcated area. And then by late 1980s, you begin to see these informal settlements and by early 2000s, they're just completely occupied. So this is the community that we've been working for the last 10 years or so. And they close up, this is what it looks like. So you can imagine, this is kind of located in a valley and during the rainy season, everything gets flooded. You can see the water mark going up. So people have to walk through these flooded areas. And when they do that, the water there, the rainwater is contaminated with rat urine. Okay, so you walk through there and the spiral key, let the spiral back there, we're forth right through the skin. How many of you have actually seen a case of leptosporosis? Okay, good. So you know this. So they're forth through the skin, enter the bloodstream, dismain all over the body, go to your liver and your kidneys and you have a kidney shutdown. And then you have ichterous here. We call it conjunctival suffusion. It's a combination of ichterous and the dilatation of the conjunctival vessels. This is a man with an undergoing peritoneal dialysis. It's getting the shutdown. And this is a sort of a relatively unusual manifestation of leptosporosis, pulmonary hemorrhage. Very high mortality associated with this. And what's interesting in Brazil, we've been doing this for close to that more than 10 years. Early on, we never saw these pulmonary hemorrhage cases. And then sometime about four years ago, we began to see these pulmonary hemorrhage cases. We don't know why. You know, nothing's changed in terms of the host, the community. But we think maybe there was a change in this train of leptospira over time. And we've sequenced the whole genome of the strains isolated from the pulmonary hemorrhage cases and in the earlier cases, we're trying to characterize what's contributing to this new manifestation of this disease. So that's one of the so-called molecular epidemiology project that we do. And this is how you get the infection. You see how in this case, is the woman who is doing this? Because we've actually shown that despite the similar level of the exposure, meaning if you do serology, they have a similar prevalence of evidence of infection. But it's the young adult males who develop the severe manifestation of this disease. For some reason, we don't know why. We don't know why this is so. The woman don't seem to get the very severe manifestation. And this is one of the reasons why the government, when we published on this, the first publication we had on this was looking at risk factors for mortality. And the government paid attention to this because this was a disease that was predominantly affecting young adult males which are the sort of main income earners of these communities. Before this, we used to do diarrheal disease projects. And no matter what we published, nobody paid any attention because kids don't really contribute that much to these communities. And so this is one of the things that we learned in the process of doing this kind of work abroad that even though let's spiral itself is not like AIDS, malaria, TB, working on this project really had an impact because after the publication, instead of getting kicked out from Brazil, the government in Brazil actually contacted us and wanted to set up a similar type of surveillance system in other parts of Brazil, okay? And it's a very simple solution. I mean, you just have to close these sewages, put it in piped water, and that not only had an impact on leprosy, but also had an impact on other diseases associated with water, such as diarrheal diseases and many other types of diseases. So that's why we call the Gandhi's salt march approach to research. You can think about that a little bit. So this is what we do. We map these places and do this and this is just showing you the association of rainfall, okay? With the number of cases. It always follows these heavy rainfalls, okay? And then one of the molecular epidemiology projects we did, this was done by one of my peers, students who went down to work with Albert. So there are a lot of animals in these communities, goats, dogs, opossums, and we don't exactly know which animals urine was contributing to the spread of this. And we found this fire from all these different animals, but it's the ones from the rats that had the same identical genotype as those that we found from primates. And there were certain types of rats, ratas norvegicus that carried these organisms. So again, this is just a very quick illustration of how molecular techniques can sort of contribute to understanding the dynamics of disease transmission in these communities. And ultimately, so one of the problems that we discovered was that these epidemics of this process always occur during the rainy season, okay? So what else occurs do you think during the rainy season in these type of places? For those of you who went to Brazil, what happens during the rainy season? Dengue, exactly. You have the mosquito population and you get dengue, okay? And the initial manifestations of dengue are indistinguishable from those of leptosporosis. You get high fever, myalgia, headache, et cetera. With dengue, there's no treatment, just supportive care. With leptosporosis, you have to start antibiotics right away, okay? If you wait too long, there's nothing you can do. All those people who came into the emergency room, okay, in those early pictures with kidney failure, died no matter what we did. Maybe 15% of them died no matter what we did. So we needed to develop a test that can rapidly distinguish dengue from leptosporosis. So Albuco came to my lab, he made a genomic library from one of the leptospirals, and then cloned the genes and expressed all these proteins, and we found several sets of proteins that were recognized by anisera in these P8 patients that could rapidly distinguish dengue from leptosporosis cases. And ultimately, this was developed into a kind of a pregnancy type lateral flow assay, and this is being now developed by a company in New York in collaboration with the Brazilian government. And one of the things that we also did was instead of giving all the rights, the licensing rights in American company, we coordinated that with the Brazilian company, so they had the patent rights. Okay, so the Brazilian can set these products, instead of having an American company sell it at a much higher cost. So these are the kind of things that we try to incorporate into our research projects. So this is Albuco here, who this is his team. In Brazil, he actually includes the people who live in these slums as part of the research team, and that's what enables us to go into these communities. And this is Mitomaya Galvão, who is the director of Osvaldo Cruz Foundation in Pio Cruz, and he actually comes to these surveys sometimes, and he's very well accepted by this community because when he was a medical student, he lived here. He's from a very poor family in southern part of Bahia, the state of Bahia. And so the people in this community know, so that's what enables us to work in these types of communities. So these are some things on the side. Okay, so let me just, the reason I'm hurrying a little bit is I have to go back to Stamford Berkeley to give a lecture at two, so I'll try to give a little time at the end for discussion. Okay, so, automatic heart disease, how many of you have actually seen a case of automatic heart disease? I have never seen one until I went to Brazil. You know, this is something that happens in my parents' generation, right? In my parents' generation, anybody who has a heart murmur has probably had an automatic heart disease, but this is a disease that you hardly ever see. How many of you have a pediatrician? 280,000 in the UK this year, about 20,000 that varies in incidence, low incidence in Cuba to about 78 for 1,000 in Samoa. It's responsible up to 65% of hospitalization for cardiovascular disease in developing countries. And in China, it's the leading cause of valvular damage that needs surgery. And prevalence is significantly higher in kids living in urban slums. So, you know that this is an immunologically mediated chronic complication group-based strep infection, right? And it results from repeated episodes of acuromatic fever and or gas infections. And WHO, the traditional observation made by WHO, is the prevalence peaks around the age 24, 35, so young adult age. But recent studies from Brazil suggest that this actually peaks much earlier. So there were two studies done by a cardiologist in Salvador, Brazil. His first study showed the mean age was 12 years, mean age later, nine years. So these are the kids who are actually requiring valvular replacement with artificial valves. And because they're getting their valves to be placed so early in their life, they may have to get them replaced again when they're in their 30s or in their early 40s because these valves don't last that long. So Brazil spends more than $50 million a year taking care of these people with these valvular disease when for less than a million dollars a year just give simple penicillin, ampicillin, they can prevent this. So this is one of the reasons this happens is because these kids live in these slumps. And so traditionally again, there's been this association with certain genotypes with certain manifestations such as pharyngeal skin infections of both. But this is actually being challenged by studies coming from Australia by a group, a caretas group where they have shown no association with any genotypes with the clinical outcomes. And then in the past, people used to talk about rheumatogenic strains, I guess, but in the southern hemisphere countries, there's no association with any specific EMM type. So the epidemiology of the disease appears to be really changing. And so these are what we're doing. We wanted to sort of assess the disease prevalence, RHD prevalence, develop simpler diagnostic or prognostic tests. And then the questions we had, the hypothesis we had were these were some of the risk factors that we had considered. Is it access to healthcare services? Maybe they're not getting the penicillin when the kids develop pharyngeitis. Or maybe it's a difference in circulating strains of group A strip. Maybe there are indeed specific clones that trigger this response. Or maybe there are other differences in biological factors. It turns out strip organisms make all kinds of super antigens. There are at least right now 11 super antigens that are expressed by group A strip. But our hypothesis initially focused on this. We think that it's the diversity of these strains that contribute to trigger this. And I don't know if you know, but strip organisms, they undergo a lot of horizontal exchange of genetic materials. They're very notorious for horizontal exchange of genetic materials. So we think that this will ultimately trigger all kinds of diversity in the strains that circulate in the community. It may ultimately trigger this immune response. So let me just provide evidence that that's what we see. So we do multi-local sequence typing. This is a sort of a new way of typing the organisms. And most common EM types reported in the world in the literature are EM 12 and one. And higher diversity EM types are observed among gas high system African Pacific regions compared to high income countries. This is sort of the paper that came out in Lancet. So you see these EM type, EMM 1, EMM 12, EMM 28, et cetera. I don't know if you can see from back there. The ones that are in red are those that are included in this vaccine that's being undergoing clinical trial right now. And obviously they chose the EMM types that are gonna be represented by the common EMM types in developed countries, high income countries, right? So this is a high income country. But if you look at the EMM type distribution in African countries, you see that, yes, you have EMM 12 here, but this is EM 75, okay? And the EMM 1 is that way down here. And if you look at the Pacific countries, only EMM 1, EMM 1 is way down here. EMM 12 is not even represented. So if this vaccine became available, you'll be, yes, it'll be probably effective in developed countries, partly effective, maybe in Africa, but not in Asia, specific, okay? So what we did was we started this project looking at three outpatient clinics. This was done by Sarah Tartoff, who was a PhD student who spent two years there. And two of the clinics that we looked at were those serving slum residents and one served privately insured residents. This was done between April and October, 2008. We looked at kids between the ages of three and 15. Cases are defined as those with chief complain of sore throat and controls with children with other complaints who came to these clinics but not admitted. And so this is some Marcos, one of the slum clinics. This is near the slum that we work in. Quinto Centro is the other slum community. And then this is the private clinic. We had 624 cases and 1,500 controlled children. We found 529 strep isolates, group A through G. 253 of these were gas. We found 128 from cases and 125 from controls, okay? So controls, people, kids without sore throat also had gas asymptomatically. Among the cases, 23 were from the slum clinics, 17 were from non-slum clinics. So gas clearly is associated with herenitis, okay? So we just proved what's already known. But what was surprising was when we did the genotype analysis, this is what we found. So if you look at the George Valente, which is the private clinic, you see the diversity index, symptoms of diversity, it's 92, okay? But if you look at Quinto Centro and ESM, it was 0.96. And if you look at the Lancet study from Stier, look at this, high-income countries, 92, okay? And African Pacific region. So in the same city, the genotypic diversity of the kids who live in the slums resemble more of those people who live in Africa, kids who live in Africa and Pacific. Or as the kids who went to the private clinic, okay, had diversity that would resemble those found in kids who live in high-income countries. So if this vaccine became available in Salvador, it's only gonna help these kids, but not these kids. So this is very surprising because, you know, I've been talking about disparity of income, socioeconomic status, structure of housing. But disparity exists even at this biology level, okay? And so, again, this is something that's revealed by molecular epidemiology studies. So this is, so you see this, these EM-12 and one, just like in high-income countries. And here, EM-12 is here, but EM-1 is way down here. And then here, EM-12 is here, EM-1 is here, okay? So this was the difference in the occurrence of EM-1 between the private clinics and slum clinics is quite significant. So, so I've been talking about different types of disparity in slums, socioeconomic, environment and ecologic, legal, inflammation disparity, and then finally, biologic disparity. And so where do we go from here? I don't think we can, you know, come here and to wait for things like alleviation of poverty and disparity and you know what, we've been talking about this for hundreds of years. We already know this. It's boring to talk about these things. We know that. And we can't wait for social capital development, technology transfer, US millennium goals. We need ACT now to formally recognize the existence of these populations. Okay, that's number one. And then assess burden of disease in this population, develop new metrics. We don't have the metrics right now to assess disease burden in these communities. And then conduct research and report financing international journals, provide data for national government and identify and implement novel interventions specifically designed for slums. So that's what we're trying to do with this consortium that Michelle mentioned at the beginning. So we have this consortium called Global Health Equity Scholars Program that's funded by Fogarty. And we have, as I mentioned, Stanford, Berkeley, Yale and Florida International University. We have 12 sites right now around the world where we can go and we're going to use this open to postdocs, residents, PhD students who finished their qualifying exam and medical students in their third or fourth year. And they can spend anywhere from eight months to 11 months in these places, fully funded. The fellows get paid very well actually, including research money. And residents actually will be considered as postdocs in this case. But residents have trouble spending, I guess, eight months. So that may not be quite feasible, but we might be able to be flexible about this. So just contact Michelle about this here or us in Berkeley. But we're going to kind of really bring to attention to the world, especially the Americans of this issue. I think that really needs lots of attention. And so this is the team that's been doing all the work. And hopefully you can participate with us. So I'll stop here. So we don't know yet because they're just starting these upgrading problems. But in Salvador, because of our work, I suppose they've been doing some, the city of Salvador's been doing some upgrading problems. So they put in pipe water, they sort of removed trash and things like that. And that actually had an impact transiently. Then the infrastructure kind of started deteriorating again. And so we're back to where we worked maybe 10 years ago, but, it's not just implementing these upgrading. They have to be sustained somehow. And so that's one of the things that we're struggling with. How do you sustain these things once they are implemented? What's going to happen after the Olympics? So they work up, can they sustain these things? What sort of hypothesis do you have about why the wetwear, pretty mealogy patterns and the plums more closely match after they've done it in their neighborhood? That's a good question. I think it's just crowding. There's more opportunity for these kids to be recurrently infected because of all the crowding. So they get infected with multiple different genotypes over time and after a while it triggers this autoimmune response of these genetic heart disease. That's just a hypothesis. But clearly shown that there's diversity of these traits. So we're doing a study to just really assess how often these kids develop heregitis and then also do an echo survey in school kids to see what the real prevalence of rheumatic heart disease is. And so those are ongoing projects, okay? And since we have such a wide gene coefficient in the United States, we see this crowding. Why do you think rheumatic heart disease has disappeared? I think it's, that's a good question. So last, there was actually an outbreak of rheumatic heart disease. Yeah, I think it also, Utah too. And there was a, there were some so-called rheumatogenic strains identified, but those have disappeared. They really sort of, so, you know, I think maybe there are certain rheumatogenic strains that maybe at least as recognized in temperate zones, but they've really, I think, disappeared and they've been replaced by new genotypes and that may be one of the reasons. But you know, in Americans they're always exposed to antibiotics. You know, we have easy access to antibiotics, antibiotics in the food that we eat, those food that you just ate there. So I think they're probably selecting for maybe the non rheumatogenic strains. I don't know, I'm just hand-weighting. But it's true, we don't really see this disease in the U.S. anymore, okay? Okay, thank you. The preceding program is copyrighted by the Board of Trustees of the Leland-Stanford Junior University. Please visit us at med.stanford.edu.