remedy for dengue fever

>> hello. welcome, everyone. i appreciate the opportunity this afternoon to introduce a wonderful colleague, peter hotez. before i do, i wanted to announce that there will be a reception after the lecture

today, sponsored by the faes, which i think is a wonderful thing to allow us to have as time to interact with peter, and it will be in the library across the hall. so i hope many of you who have an opportunity can spent a -- spend a few moments talking

to peter about some of the fascinating work that he presents today. i'd like to start out by saying that peter is probably one of the world's most renowned experts in tropical diseases. he is recognized internationally as a clinician and investigator

of neglected tropical diseases, and spends a huge effort in vaccine development. he studies diseases that include hookworm, shifto so miceis, shag as and malaria, among others, and these diseases effect the lives of millions of individuals and mainly children and

departments worldwide. this is a critical public health importance and summery related to the mission of nih he heads texas children hospital at baylor college of medicine and serves as the founding deb of medicine of tropical medicine at baylor and serves as the chief

of new tropical diseases in the baylor department of pediatrics. and he also holds endowed chair of texas children's hospital. he has been involved with the innovative partnership that is dedicated to controlling the spread of these neglected tropical diseases in developing

nations. he got his ph.d. in biochemical parasighatology frerockefeller universitiy and went on to get his medical degree from cornell. he completed a pediatric residency as mgh and did postdoc training at yale.

and then he joined the yale faculty as an assistant professor. he achieved associate professor before moving to george washington university as professor and chair in 2000 and we interacted with him in that position at george washington.

but he was wood away by baylor and is now seattleed in quite well. he authored more than 240 original papers and wrote in textbooks. he has been invited speaker at many events both nationally and internationally.

and he is the member of the national institute of medicine national academy. he also serves as president -- i'm very pleased and proud to have the opportunity to present peter today and he will be speaking to us on the elimination of ntds

through antipoverty vaccines. peter, thank you very much for coming. [ applause ] >> thank you very much for inviting me to speak to you this afternoon. it's always an honor to be here at nih.

i never miss a chance to come up here to get rejuvenated. something very special happened today with the postdoctoral fellows from niaid and something i can't remember what happened last, when i got a free lunch. then i tried to tell how special this really is and it could be

years before it happens again. it's good, wonderful to be here. i have been in houston 9 months and one of the ways i was able to go is i convinced my wife, we moved in august, not the best time to move to houston. i tried to convince my wife the summers in dc are just as bad as

they for houston. not quite. so it's especially for the -- this is my second day i have been here and it's been glorious weather. thank you very much. so i'm going to give you an overview talk about the problem

of neglected tropical diseases and why you should care about these conditions. so -- and to give you thought about where we are going in terms of thinking about a large global overview for eliminating many of the neglected tropical diseases.

and this is the group that we are particularly concerned about. and a subject of concern of many of the institutes of nih, not just the fogarty international center. this has now prevaded the culture of the institute, which

is so nice to see. there is 1 1/2 billion people in the world who live on no money, who live below the world bank poverty figure of $1.25 a day. many of you are aware of the goals established in 2000 by kofi annan and the secretary general of the u.n. to list the

bottom bill om billion out of poverty -- what is interesting about these is that they are now 12 years into them and they are still around with us. unlike so many documents. this is stuck. there is one that specifically addresses infectious diseases to

combat hiv-aides and malaria and other diseases. the nih is responsible in a big way between stepping up research on aids and malaria as well as a lot of other diseases. and the u.s. government, in general, stepped up through pepfar, the president's

emergency plan for aids relief, now funded almost to 7 or 8 billion dollars annually. with the exception of the intramural and extramural research at nih, a lot of major governments from the ga and g20 countries do not know much about some of the other diseases and

the ones we will be addressing today are what we call the neglected tropical diseases. there is the mtds and -- ntds. it's a concept we wrote about in 2005 and 2006 to reflect the fact that there is a lot of commonalty between this group of

predominantly paracytic infections that are going to list for you in order. so these are the most prevalent infections of poor people. 1.4 billion people are infected. all the bottom billion have one or more of these neglected tropical diseases.

i'm going to rank them in terms of most common infections of poor people based on our studies as well as the new information that dr. simon berker developed at the school of hygiene and tropical medicine. this is the most common infection of poor people, round

worm and ser iceis, a lot of these are wormy deceases -- diseases. hook work, 690 million people. this little boy has hook work and he has a big descended belly. he has worms in his intestinal tract but not just the fact that

he has a big belly, he is stopted for height and weight and does poorly on tests of cognition, intelligence, and this now we know is because he is infected with one or more of these neglected tropical diseases, as car iceis and hookworm.

4 un40 million with shiftosomiasis. 115 million with lymphatic filariasis. and so on. and the consequences of this, in addition to the health effects is now accumulated a lot of evidence to suggest these are

not only occurring in the setting of poverty but the 17 major ntd u.s. is defined by the world health organization and also calls poverty. they can cause poverty because they reduce productive capacity and make people too sick to go to work every day.

i'll show you an example of that impairing intellectual and physical development in children. as well. this concept that the ntds are in poverty and they are caused by poverty and trap about a billion in poverty.

here is a wormy curve generated by us and when you live in the endemic area, you're looking at the intestinal worms as well as other types and it's children that have the largest number of worms. and there is a period of worminess during life of a

villain where you harbor large numbers of worms between the age of 4 and 5 and 15. it is the most common infection of children in the world and we don't even have our arms around why it is that children have larger numbers of worms than adults.

is it some type of acquired immunity, behavior, exposure? we are still in the dark about this. you have a situation where you have a big belly and these are the worms from that one child from paraguay. you wouldn't see this in older

adults and individuals. we don't know the basis of it. and the point being, that the fact that children have so many worms, especially the intestinal warms n-this particular case, goes beyond the immediate health effects we have known about since medical school.

and among this period of observation of the more worms you have, the greater your loss of intelligence shown on the y axis. it's showing you here you have negative worm burden, moderate, heavy, and this is loss of intelligence.

so i like to tell my neurology colleagues and psychiatry colleagues, here is the world's leading psychiatric disturbance. and it really isn't a single published paper on the mechanism. and presumably there is some kind of interplay with nutrition

but beyond that, it's really not well established. y know in the case of hook worms that iron deficiency may be related to environment needed for the biosynthesis. but we don't know the basis for it. we also don't know why it causes

physical growth retardation as here you have hiv on the x axis and weight on the y axis and a growth curve following children along the third, tenth or 25th percentile and here is a child with flatline growth after getting rid of the worms and then there is impressive

catch-up growth. so it's leading to intellectual disturbances and we have very little information mechanisms to account for this. an enormous amount of research problems we can address with and now, university of chicago has shown on the right, hookworm

infection in childhood leads to a 40% reduction of future wage earnings. who knows why. maybe because of the intellectual and cognitive deficits. that's the most likely reason but it's a reoccurring theme of

ntds causing poverty not just occurring poverty. big impact on productive health, this is the study in brookeer at the hygiene medicine at the word bank showing an estimated 7 million pregnant women in sub-saharan women with hook worms associated with disease

birth weight, increased perinatal child mortality and increased child mortality and the big problem you get with hook worms is profound anemia where the adults have the infections and you can see in pregnancy, this is not only infections during childbirth.

as my obstetrics colleagues tem -- tell me, it's not just it's the delivery of bleeding more than women in the united states, it's just to they are starting because of severe hookworm infection and other and with that in mind, there is increasing recognition with

ntds not occurring in isolation but there is co-morbid effects and other infections and a good example is malaria. this is a study we did showing that if you looked at sub-saharan africa, in the green are areas of africa where you have both hookworm and malaria

predominantly malaria occurring exactly at the same time. what this practically means perhaps is that peel are polyparavideo tiesed. they don't just have malaria or hook worms, they often have both together. on the right, you can seat

consequences of having these co-infections that the hemoglobin concentration on the y axis and i'm showing you studies from enia, northwest tans tanzania, what happens if you have neither infection trucks malaria alone or hookworm alone or both together.

you can see the bottom falls out when you have infections together and anemia is in children and pregnant women as so that really adds. the term i use is the perfect storm of co-infections. there is also increasingly recognition that these are

important co-factors in africa's aids epidemic. there is a disease called urinary tract shiftosomiasis. it's caused by -- and we have known for generations that the spine-shaped eggs when they get into the bladder will cause irritation, ulcers and

inflammation so that they are responsible for blood appearing in the urine, a condition that is a common disease. maybe as many as 400 million people are infected. 90% in africa. if you go into endemic village and ask kids to void in a cup

and then hold up their urine, kids are doing large percentage of children in sub-saharan africa have blood in their urine. for decades we ignored the fact that we should be doing copescopic examinations on the conditions and now there is

recognition that the 75% of them have those same eggs or lesions in their bladder and on their cervix and uterus and lower genital tract and it's a condition of female euro genital i'm of i'm show youing studies done by jennifer at cornell. this is throughout mow zam beak

marks lawy, tanzania. and associated infertility and pain with sexual intercourse and stigma and abdominal pain. and these gran lomas are rich in cd4 positive cells and all of the things that we have been working on for years and years when people bother to look, in

zimbabwe these lesions are associated with 3-fold increase in hiv aids transmission and initance media fourfold increase in horizontal transmission. you can see overlap between these two conditions call considerations suggest there may be as many as 100 million girls

and women with female euro genital schistosomiasis. this could be the most common gynecological problem in sub-saharan africa. it's grossly unstudied. another key point i'd like to make is when you think about ntds, we are focused on

sub-saharan africa and poorest points of south asia. increasingly, poverty seems to be the overwhelming determinant of neglected tropical diseases. show me poverty and i'll show you neglect the tropical i want to take you to the western hemisphere in latinlatin

american and caribbean regions, that's what i mean by lac. populations of 578 million, 48 million live on less than a dollar a day and another 99 million live on less than two dollars a day. sometimes we call that the bottom 100 million living in our

own backyard. and some studies we did a while back, the adjusted life here suggests that the loss from neglected tropical diseases is up there with hiv/aids or tb, more than malaria. so there really is a fourth leg to this aids, tb and malaria we

see a mantra really with hpv, malaria and neglected tropical here are the major neglected tropical diseases in the caribbean region. some are not unique to the region. hook worms, and as crisis and shag sas a unique one.

and again, this is a map of poverty nelatin america. between southern mexico and central america, poor parts in bolivia and paraguay and northern argentina andandies and columbia and these are the regions where we need to look for ntds.

poverty is not exclusive to you have a lot in our own backyard. we can look at human development indexes in some latin american countries andey we can see they are equivalent to many african countries as well. the other point about poverty

nelatin america is even wealthy countries have intense pockets of poverty and people are at risk for neglected tropical 11 million people in mexico live in extreme poverty, 10% of the population. 46% lived in some level of poverty and it's particularly

concentrated in place where is we are working quite a bit now in southern mexico and up in uke tan as well. and if we can even take that one match further, we have poor people in the united states. who knew? child poverty rates approaches

50% in these counties along the southern border. so in south texas, the counties in red, parts of the panhandle, high rates of poverty. what about neglected tropical diseases there? so we recently came out with this paper looking at the

neglected tropical diseases occurring in both texas and mexico and this is a list of diseases that we found quite a bit of and i want to talk to you about chagas disease and shift i cirrhosis and dengue and library man iceis and leprosy. my colleague estimates that

there may be as many as 267,000 cases of chagas disease in texas. it is highly endemic among the dogs in south texas. 11% of dogs are infected with chagas disease. we have the kissing bug vectors there, we have the poverty

conditions and so he is constructed a snapshot of where it will occur. so i think an important question we want to answer over the coming months and years, what percentage of these 267,000 cases are actually result of endemic transmission of the

disease within texas? you have to be very careful when you talk about these diseases. there is an anti-immigrant mentality through many parts of our country and every time i talk about it, the anti-immigrant blogs light up and say, you should build the

wall higher and we are trying to make the case that you could build a wall as high as you want but there is transmission of these diseases, if we have poverty and the right climate conditions, we have to really give serious thought to investigating these diseases

just like we would any other developing country. you have to think about it here at home as well. neurocystic psychosis we are seeing leading cause of epilepsy. a nice paper in discover magazine where they interviewed

dr. ted nash about the problem of cystopsychosis here and clearly a huge problem and we are seeing this disease show in our doorstep. toxo car iceis. it's a dog worm. the full-blown syndrome is fairly rare.

but we are seeing a form of the disease that is called toxocariasis, and we also see a lot of wheezing and there are studies in europe showing the tox cara larvae, these paracytic larvae are a cause of asthma in europe. the question is now, the cdc has

shown that 21% sayo prevalence among african americans with poverty being the risk factor, what is the role of the covert toxo care infection. we have dengue in western florida caused by dengue type 1. we have known we have dengue type two in brownsville, texas.

kristi murray, a new faculty member has been looking retrospectively at stored serum samples for the past 10 years and she has uncovered pretty good evidence, a paper under review, that we had dengue outbreaks in houston during may and june every year possibly for

the last nine years. so we have transmission. when you look at it all, chagas disease, cystosaricoseis, dengue, there is -- these are not even rare diseases. these are common diseases and if these were occurring among wealthy people in the suburbs,

we would never tolerate it. but because they are attacking poor people living in extreme poverty, especially people of color, they are forgotten diseases among forgotten people. one of the things we have done now at the hospital, a public hospital at texas medical

center, it's extraordinarily well run public hospital, we created a tropical medicine clinic where patients from the area come every friday morning and the things that we are seeing on a weekly basis, leach niceis, chagas disease, shifto saricoseis, regularly.

with some of it, in transmission in texas we think it will be very interesting. now we have a new diploma in tropical medicine, as well as tropical diseases, we have now created this new national school of tropical medicine we are hoping to offer it once in the

summer and once again in the winter. i'm showing you houston. there is downtown houston and this is not another city. this is the texas medical center, which some people say is the largest medical center in the world.

it's really a medical city of 100,000 -- 96,000 employees. they have their own police force. it's just an amazing place. and it's a great opportunity to now take all of that and really concentrate global health activity in one area through

this national tropical medicine. very much modeled on the liverpool london school of hygiene, tropical medicine, but we adopted a new world theme for our logo rather than the egyptian theme of the liverpool school and london school. this is the mayan jaguar.

so now that's the overview of the burden of disease caused by i wanted to update ow what is happening in terms of global control efforts to control or eliminate these diseases. the first thing i want to tell but is this concept of mass drug administration which is

blanketing large populations with single dose annually of a drug to reduce the burden of these diseases. it was the concept not discovered by steven hawk ins but some people credit his father with potentially discovering this.

he was working with a disease heavily investigated here by aimy and tom, lymphatic flurriesis where he was able to show if he could give a single dose of -- dec, it reduced the number of circulating microfilaria, required for transmission of the infection

and picked up by mosquitoes and able to provide evidence that you could village it in around brazil, that i could eliminate the disease as a public health problem by treating our entire villages at the same time. and even took it a step further showing you could mix the

medicine up in the cooking salt people are salting their foods, and buildup the medicine and we read about this in the w.h.o. in 1967 which led by chinese pair sightologists during the cultural rev exclusion this went to the attention of chairman now and the chinese scaled it up as

only the chinese could by medicating the entire salt supply of eastern china with this becoming the first country to eliminate the disease as a public health problem. so w.h.o. began looking at how to franchise this. this shows that through mass

drug administration you could reduce the prevalence of these diseases either through once a year administration or through medicating the salt. we can't use it in africa because it causes a severe toxic reaction known asthma jotty reaction in cases with river

blindness, which is co-endemic. but merck came through with ivermectin. so now you have a box of 1000 tablets costs 4 dollars. so whereas in africa we are using ivermectin which is free. you are factoring out the costs of the drugs a is was exciting

is the ceo of pfizer said, if merck and company will donate something, i better donate something too and he donated zig row max, which i'm sure many of you have taken in your z packs for upper respiratory infections and it works for tricoma and this is the result of

administration in egypt. so a few years back, we undertook this exercise with the w.h.o. and with david at the liverpool school of tropical medicine and others including eric to, sketch out a map of the world for where these neglected tropical diseases, these seven

most common ones that could be targeted through mass drug administration, meaning as caar iceis, trick riceis, hookworm, schistosomiasis and oncoser iceis and trachoma. and eliminating lymphatic through mass drug administration reaching 50% of the populations

at risk. in sudan people are polyparasa tiesed. they may have shifto so miceis and river blindness and hookworm and perhaps we should bundle itinal a package. this targets the intestinal worms and every mec 10 targets

the flair yarr worms and then zig row max sarcoma -- you could give all at the same time. and you could target all 7 neglected tropical diseases at once. and we you now providing proof of concept to do this as little as 50 cents a person per year.

the most common infections of these diseases knocking them down and eliminating lymphatic file iceis or river blindness or trachoma for 50 cents a person per year. we projected this integration, combining mass drug administration would be to a

26-47% reduction in cost savings and sure enough, the carter center, frank richards and others published -- you got about a 41% reduction in costs by combining these medicines into a package that can be given spades apart. usai does. now backed this

concept really nicely and it began in the bush administration and expanding in the obama administration where i'm showing you the funding in millions of dollars. this is the funding for integrated ntd control since 2006.

and up to 89 million dollars annually. that may not sound like a lot, but because the costs are so modest, we can make a very big impact on these diseases through national programs of integrated neglected tropical disease control.

we still have a ways to go. one of the big problems we nais doing there is in order to develop algorithms for treat width different medicine, we need to have good mapping data on where these diseases are and this is just to show you where we're at.

this is a paper done by the tropical institute, looking at schistosomiasis and you see this big hole in the democratic republic of congo. it's dark in terms of data collection as well. so we have big gaps in our data. it's not that schistosomiasis is

not there, it's that nobody is looking because of the complexities of working in conflict and post-conflict countries. same with central african republic as well. we are also working on version 2.owe now as integrated ntd

control, we need to really start thinking about how to link this with the president's malaria initiative and pepfar. going to reduce euro genital schistosomiasis, will we have a big impact? should we be including ntd control in the president's

malaria initiative? we think we should. this is going to be a important new trend in the coming year. those ever you who are scientists or might be thinking, my god, when we talk about treating literally hundreds of millions of preme, aspiring to

get all the bottom billion on these wholistic drugs and others, we are concerned about emerging drug resistence. and the answer so far is, there is not a lot of evidence for emerging drug resistence against these pathogens. not a lot of people are looking

as well and our status of biomarkers is quite inadequate. but what we are concerned about is for instance, one of them, single dose benz zol, what i'm showing you is a forest plot showing improvement effective anemia on hookworm when you useal bend zol because it's to

the right of the middle line here. but it's showing that it may have no impact. a new metanalysis published in jama about four years old is shown as 15% cure rate from benz midda zol. it's been difficult to persuade

congress or global health policy people. the gates foundation gets it but not too many others, that you can't -- it's not either-or. it's not just mass drug administration. you have to continually invest in research and development for

new and better controls. and this is a paper that i wrote a couple of years ago, 2011, saying that we -- to offer the concept for many of the neglected tropical diseases, we need to think about developing new vaccines. it's not enough just to give the

medicine. so we need to been vaccinating in order to prevent reinfections as a potential elimination strategy. and to be as provocative as i could to get people to notice it, we call them the antipoverty vaccines because they are

vaccines that not only impact global health but improving educational outcomes and improving poverty outcomes for all the reasons i showed but in the beginning. so, back in august, the best time of year to move to houston, we moved our laboratory to this

building over here. this is enormous research tower that is called the sabin center, named after the great pediatrician at texas children's hospital. this is our portfolio of vaccine that we now have under development.

and i don't have too much time to go into detail but i'll tell you about a few briefly. we have a human hookworm vaccine that has a component now in phase i clinical trials. and that is being led by david demerc who is formerly at niaid and now with vaccine institute.

shift miceis vaccine complete manufacturer and will lead to start clinical trials. chagas vaccine as well as a brand new sars vaccine. so hookworm vaccine is supported by the bill and melinda gates foundation and the dutch ministry of foreign affairs.

shifto spiceis vaccine is supported partly by niaid where we got together a consortium of private individuals and the chagas vaccine supported with the local institute in houston together with the institute of health and niaid is supporting the new sars vaccine.

and we are doing this at the vaccine institute, as an organization that some may not be familiar with. it's the type of organization which is sometimes known as the pdp, product development partnership, which are essentially nonprofit

organizations that use industry practices to develop stuff to, develop products, whether it's diagnostics, therapeutic products which mean storm molecule drugs, microbiosides or vaccines to target neglected diseases to include aids, qb, malaria and diarrhea and

respiratory diseases. our sweet spot are vaccines, crossing over here with ntds whichwhich were our major focus is currently. so our hookworm vaccine, our goal is to reduce 80% of moderate and heavy hookworm infections which will cause worm

burden reduction, egg reduction and blood loss reduction, anemia and malnutrition. and thereby dose sparing as drug sparing, to prevent ongoing use of the drug to delay or forestall emerging drug resistence. many may not be familiar with

hook worms. the major gene species responsible for 85% of the global hookworm infections is a helmuth parasite a center meet long that fastens into the intestine and then causes blood loss and then the blood comes out the other end.

so it can produce anemia and illness. we spent now decades trying to develop strategies for vaccinating. we don't have -- we could do a whole hour just on how you make a vaccine for something like remember, this is a worm.

animal about a center meter in length. we have really been focusing in collaboration with dr. alex lucas and jeff bethany and others, the gut of the worm. what happens is that as the worm feeds on blood, we have been able to show that the worm grows

is particularly focused on investing hemoglobin. i know you're not used to looking at cat scans of worms. shire section of a hookworm that has been probed with an antibody against enzymes used to degrade hemoglobin. along the membrane of the gut,

possibly tethered by sequences are enzymes involved in hemoglobin digestion including protease, cp3 and another that breaks down the hemoglobin into smaller bits that are then absorbed by a amino acid transporter and then the parasite has to do something.

in the case of ma layer yeah, it polymerizes it into -- in the case of hook worms they deal with binding it up to especially modified group of transferase which is homodimer and has low peroxidase function but specifically bound to heme. so, through the years, we have

identified two molecules for purposes of vaccine development. one is transferase to elicit neutralizing antibodies. the continent of australia here is a protease but the protease has been modified through mutagenesis to residues through alanins so it can enact and

keeps this tertiary confirmation and we have been able to show this is high levels of antibody and the antibodies are ingested by the worm and the antibodies neutralizes blood feeding and then inhibits the ability of the worm to survive. it's a very novel mechanism and

how you use the immune response to attack animal. and here is our clinical development plan which includes phase i studies in adults and then combining to the and ultimately established proof of concept for protection. we are now seriously looking at

the possibility of doing some challenge studies in vaccinated human volunteers. the challenge of hookworm larvae. this was pioneered back in 1980s as niaid in this concept of doing infctions with hook warm larvae pioneered by frank

gottesman and also involved actually placing hookworm larvae and people to look at self infection. we have been asked to develop a challenge model in order to make all of this run faster and our modler that is we have been working with have been able to

identify some real advantages of using hookworm vaccine rather than getting this reinfection we are seeing withal benda zol that over time, that could lead to elimination of the disease what do we need using the mass drug administration approach and folding in new tools, new

controls so that in the case of lymphatic floor iceis, our thinking is that for hookworm, the mda, mass drug administration itself will not be sufficient. we'll need to fold in our vaccine and then there are stud these bruce lee and his

colleagues have done at the university of pittsburgh to do modeling looking at the impact of reduction over a period of 20 years with drug treatment alone versus adding the vaccine and having a big improvement. alex lucas who was with us and now has his own group at james

cook university has been working taking advantage of completed genome project supported by niaid, to identify this very exciting antigen on schistosomiasis which when you put formulated advent such as alum, you could get very high levels of antibody that seems to

result in high levels of worm killing around 50%. and alex has done nice rnai studies. we can't get it to work in parasitic nematodes but he is getting it to work in shiftasomes and using this molecule.

so now we can show high levels of protection in laboratory mice that we have just, threw a number of different sources of support, we have now finished manufacturing and advancing to clinical trials. global access plan for how we are going to get these vaccines

disseminated to the world's poorest people, has a heavy reliance working as developing countries and manufacturers. so one of the great things about it, if you look at the countries if latin america where vaccines are made, brazil, cuba, and mexico, it's that public sector,

they are run by the federal government, oftentimes in the ministry of health in the case of the group in the state of south paul oh, their group is public health. and we're looking now at developing the manufacturing on a large scale the hookworm

vaccine jointly and their biologic manufacturing arm known as map deanose and shift osmesis vaccine jointly. and here the vaccines are getting tested and incredible prevalence of hook worms, 68% and shifts spiceis, 45%. brazil is innovative developing

india and indneedsia and tie wean make vaccines and we don't know of a single sub-saharan country that makes vaccines. with all the chagas disease we are seeing, you have very interesting problems. through a genome project, number of promising antigens have been

developed, including one developed in eric's laboratory. two antigens known as tc24 and tsa1 and now we are looking at scaling up these antigens for a chagas vaccine i'll tell you so chagas vaccine, i'm relatively new to the field. we only have been working in it

for a couple of years. and i have just gotten fascinated by this disease. because it's high prevalence, 10 million cases of chagas disease. i don't think anybody really knows. some people say there may be 6 million cases in mexico alone.

including the 200,000 plus cases in texas and the united states. and of those 10 million people, roughly two-3 million, 20-30% will go on to develop shi gaza cardiomyopathy linked to arithnyia, heart failure and sudden death. the current numbers are 20,000

deaths occurring annual frethis condition but some people feel the numbers are higher. 11% of pregnant women in latin america are positive for chagas disease and this transmission 5-10% and transfusion-associated cases. now based on all of that, back

when i was at yale, i had a pediatric aids clinic and found a lot about pediatric aids and the transfusion association, disease and chronic infection and chagas disease, medicine do not work very well, especially as soon as you develop heart symptoms.

high toxicity causes patients who abandon treatment indicating pregnancy. this reminds me of in 1990y when i had a pediatric aids clinic it reminds me of the aids epidemic. so i thought, chagas disease, hiv in the america's and i since realized that you can't compare

anything to hiv/aids without creating a firestorm. so this one just came out last week. and we have now broken -- we had this ability to give article-specific metrics for our plus ntd papers and the most we ever had was around 20,000 hits.

downloads of a manuscript which occurred over a period of 4-5 years. we have now had 30,000 downloads in the first week of publishing this paper. that's the good news. but unfortunately, a lot of the news bureaus kind of took it

over the top. and were a little too literal in what we meant by hiv/aids thinking that there mab a person to person transmission, which there is not, which is it about to overtake new york city and boston, which it's not. so, i learned an important

lesson and how you use the term, hiv/aids in any kind of comparison. but i don't want to take away from the fact that this is a horrific problem of 10 million cases and so they call it the new american hiv/aids. what i really meant this is a

problem of comparable to the magnitude in the first part of latin america and has a lot of similarities with respect to the maternal child impact and transfusion associated cases. so we are very interested in developing -- this is a therapeutic vaccine.

and the idea here is because the lack of efficacy for current medications and seropositive adults, the drug didn't eradicate the parasite. it has a lot of in tellerence and unacceptable side effects -- in tollerrence.

so 12% of patients have to spend their therapy. it causes weight loss we are looking at these together as a therapeutic vaccine to take people who have seroconverted and prevent or delay the onset of chagas cardiomyopathy, which would be possibly targeted for

adults and children. and we are doing this serosupport from the carlos ministry of health and the southwest electric energy medical research institute and the idea would be that we would do just like we are doing the hookworm vaccine, with the

brazilian, we're doing the chagas vaccine with the mexicans. including the public sector vaccine manufacturers in mexico, known as beer max. it's exciting. one of the things we are having or going to struggle with is

there is strong evidence that the vaccine protection appears to be cd8 positive cells inside ctls not antibodies so the problem that we are going to face is, how do you produce strong ctl responses in cd8 positive cells to produce antigens high levels of

interferon gamma and cd8 positive responses which has been shown as a dna vaccines to reduce pair cite sigh teamia and decrease parasite burden in the heart and increase survival and decrease inflammation. how do you produce those effects because we think dna vaccines

often are not shown a great track record. so in humans, we are looking at the possibility now of co-formulating our vaccine antigens into nanoparticles. one of the things we learned coming to houston is that rice university has some of the best

nanoparticle institutes in the country and they are our neighbors. we are working very closely with them. michael has been looking at repackaging the nanoparticles we are going to use elimination of a high prevalence of neglected

tropical diseases and we think that will be through urgent needs to scale up on mass drug administration and getting other countries involves and covering all of these. but again continuing to make new drugs, diagnostics and insect sides and vaccines and today we

spoke about the vaccine piece the others are of course equally important. thank you to ni aia and to nih to fogarty international center where i'm a member of the advisory council. so nida provided a decade of support for the human vaccine.

and supported the schistosomiasis vaccine and 30 years of mentoring ever signs my md-ph.d. days, i always come here for whenever i had tough intellectual scientific problems as well as emotional support when you are doing something like vaccines for neglected

this has always been a source of great comfort and learning. and i want to thank you for that opportunity. >> thank you for that great talk. you referred to how most individuals with these infections are polyparasi tiesed

and talked about bundling therapeutics. premature probable tow talk about bundling vaccines for these individuals, but i wonder how much forethought is put into vaccine development when considering that some of these individuals with all these

different types of paracytic infections as well as viral infection and bacterial infections, may have immunologic interaction between the pathogens and how that might effect vaccine development? >> so it's a great question. and i can't give full justice to

it now but because of time. but one of the things we agree. we are looking at bundling, for instance, if i had a crystal ball, i'd love to seat day where you could bundle hookworm and shift miceis vaccines because they are coin demmics. the others when you think about

the time of delivery, we most likely will integrate our tropical disease vaccines in the health system where kids are getting vaccinated around the same time. maybe when they are given measles ack scenes. we think potential they could be

a very good time rather than trying to reinvent the health system and then you have to do all the immunological studies ahead of that. >> very nice talk, peter. i'm curious haw you're getting around the complications of the area we saw in the first trials

of the hookworm vaccine because of the induction ever ige and mechanisms of resistence. >> thank you for that question. so i doesn't have time to go into it but this is not our first generation of hookworm vaccines. the first one is one where we

worked on our lab and first discovered by john, at the time a postdoc in my lab and worked on for 25 years and we watched it crash and burn one day all suddenly when we immunized people in the endemic area and three of them developed generalides certificate caria

and 30% of the endemic population in brazil as living in the endemic area developed ige antibodies to those antigens naturally and then administered the vaccine, we were crosslinking that igm and causing generalize said i caria. so that is a sobering lesson.

we look now for levels of prevaccination, ign endemic communities and the reason part of the selection criteria to you for all of our helmuth antigens is no ige in the endemic area. so there doesn't appear to be an ige in gst1 and shove enough so far no problems with respect to

hert caria. why do some some antigens have high levels of ige and others have none? it's interesting that the ones we looked at that have ige are mostly the third-stage infected lafferal antigens but the hookworm antigens don't seem to

have that problem. so we are trying to sort that out. the same with shifto. alex lucas is now looking at protein arrays and making ige chips to look at all the different antigens and some that are being talked about have high

levels of ige and the question is would that be a show-stopper for advancing into clinical >> i just want to thank you again for a wonderful talk and thank you for coming. and to remind the audience we will have a reception sponsored by faes in the library so please

join us and get all your questions that you wouldn't ask now to peter. so thank you again peter for >> thank you.