 So thank you everyone for coming. My name is Todd Summers. I'm a senior advisor here at CSIS and the Global Health Policy Center. This is a Friday afternoon before the 4th of July week conversation with my friend and colleague Peter Small from the Gates Foundation. I spent a few years working at Gates and Peter was one of my colleagues and allies in that institution. And when I heard he was coming back through DC, I think he arrived on a red eye and he's leaving on a red eye so things have not changed too much. I thought it would be a great opportunity to check in with him and find out how things are going broadly with TB, R&D, and also more specifically what he picked up during his time in India. So this is intended to be a conversation, just a little bit on format. I've got a few questions in my pocket I'm going to use to start things off, but I'm really hoping that this will be interactive with you. So we'll have a couple people with microphones will be available in a few minutes for you to ask questions. We do webcast these so it's always helpful if you use the microphone so that people who are participating electronically can hear what's going on. And so Peter's mother can get a full recording of how he does today. Most importantly. So Peter, thank you and welcome to CSIS. Peter has been active in TB professionally. He's been very much involved in shaping the Gates Foundation's approach to TB. The last two years he's been in India and he's returning to Seattle this fall. So it's a great opportunity for us to hear from him what's new, what's happening in the TB research and development platform, what's exciting, what's coming at us that we ought to be gearing up for all those kinds of things. So let me kick off a little bit and just ask you if you can give us your sense of where you see the TB R&D system going right now. What's coming at us that's got you most excited? Are we going to have a vaccine next week? Do we have a new diagnostic? Have we got new treatments coming? You know, when I was reading some of the preparatory material for this meeting, I realized that the last vaccine we had was before my father was born and he's 83. The last TB drug we had was last year, but before that was when I was 13 and I'm over 50. So it feels like we're fighting this 21st century illness with a 19th century response. And I want to know what is it that's coming that's going to change that paradigm? Well, first of all, I thank all of you for coming and I hope the lunch justifies it. I would say the first thing that is changed is the fact that we're talking about it. You would not get this group together as recently as five or ten years ago. What we saw on TB&D was a complete inaction for decades. There were probably 40 years in which there was very little, arguably no progress because there was no effort. And I think what we've seen in the last decade is an acceleration that the very significant investments from the NIH and from pharmaceutical companies and from the Gates Foundation has created this sea change. And it's really changed what was a vicious cycle of neglect and despondency into one in which we're starting to see exciting new products. Some of those products are hitting the market, which are generating demand. And it's really been at the highest level a flip from a vicious to a virtuous cycle. The specific parts of that, I would say, are not surprisingly that diagnostics leading the way. We have now for the first time the capacity for untrained healthcare workers to definitively diagnose TB within two hours and know if it's drug resistant. And we're starting to see now you've been more than two and a half million of those tests run in the world. And there's tremendous receptivity amongst the consumers. In the drug space, you know, there have been two new licensed drugs. They've been shown to be effective. There's still some questions about safety. But they are actually just the front edge of a pipeline which I think is including other agents and importantly a whole new way of thinking about drug development which is to bring drug compounds together early. We know we're going to need multiple drugs to treat this. So rather than taking 15 years to figure out which drugs work and another 15 years to put them together, the whole process has been collapsed and including very significant involvement from regulators. So I'm super excited about the drug space as well. And I think that that concept that you could promptly diagnose and treat TB is a really promising one. I think the Holy Grail remains a vaccine. And it's unlikely in my mind having actually now lived and breathed in the epicenter of the epidemic that we do need a vaccine to finish the job. And the great thing is that we've completed a phase three trial. We've shown that we can get definitive answers and unfortunately that trial was ineffective. But I think that the vaccine pipeline is now something which we can, we know we can test. And do you think that there are more products coming down the line in terms of vaccines that are going to complement the one that showed no efficacy? I mean where, if we do need a vaccine to bring TB to an end, how long do you think that we're going to have to wait? So the bet that was made 10 years ago was that we had enough candidates so that if we pushed them into human trials we would get either a vaccine or a signal about what the immune response is that a vaccine is working. The pretty resounding negative results of that test, that trial has reiterated the importance of fundamental understanding. So I think what it's doing is it's sending many people further upstream to try and take a more fundamental science approach to understanding that. And you know the good news is in the last 10, 15 years there have been massive improvements in understanding immunology. This whole systems immunology is I think one that we're all very excited about. So while we're waiting for a vaccine we're dealing with treatments and clearly one of the challenges we've seen is that treatments are long term, they require patients to be engaged for months and sometimes years and we've seen a lot of resistance to those drugs in a variety of settings across the world. Anything new on the drug space is transformative or are we dealing with iterations here? Are we going to sort of slightly better dots? Are we talking about an era where we'll actually move beyond dots? You know I think when we start talking about what we're going to get out of a diagnostic and a drug you can't separate that from the systems into which they're going. And so clearly the four month quinolone based regime is an incremental improvement and we'll have a definitive answer on that fairly soon as to whether it's effective or not. I think where the transformation comes is when you're using truly new molecules. These are agents that attack bugs in ways that they've never seen before so that the so-called multi-drug resistant is essentially no different than susceptible TB because these are new agents, they work new ways. And there are a number of promising ones in the pipeline. Taking some of those and putting those together would mean that you have a new regimen which treats everyone, drug susceptible or drug resistance. And at least at the outset you don't even need to do susceptibility testing. I think that's the transformation. But the challenge in all of this is how do you actually put it into a system where those new drugs are getting to the people who need it and not being abused in a way such that you lose them to resistance rather quickly. So you make a case that the drugs are highly dependent on the system that's utilizing them and yet a lot of the problems that we're seeing are in countries that have challenges in terms of health systems or India where a substantial portion of patients actually seek their care through the private sector which is slightly regulated. Any thought around how you put those two together? Like how do we make sure that people get treated even when the systems of the countries in which they reside are not fully up to speed? Yeah, I think one of the really big challenges globally is private health care systems in some of these countries, they're unruly and unregulated and attempts to interact with them through regulation and badgering have largely failed. So what's exciting to me are some of the social franchising approaches and some of the interface agency approaches which actually approach the private sector on their terms rather than on the public health terms. Just say what are the incentives? What are your current incentives that have you doing the wrong thing and how can we tweak those incentives so that you'll do the right thing? Right now in many countries the private health care providers are incentivized to order tests and prescribe drugs. They're not incentivized to appropriately diagnose and treat TB. If you can somehow flip that incentive around in its most simple way you'd say I'll give you X rupees when you do the right thing and as long as X is more than doing the wrong thing then that would start to drive these people towards doing the right thing in the absence of regulation. So I had understood that the Gates Foundation was financing a sort of a new approach in China that was in some ways trying to address that very issue which is that TB clinics and TB doctors were often only partially paid for by the government so they had to go out and raise part of the salary and part of the budget and one of the ways they did that was sort of reimbursements from drug companies so the incentive was to write a lot of prescriptions but not necessarily to ensure full completion of treatment. So what's going on in China with that experiment? Could we learn anything about how to change these motivations? Yeah, so it's a really interesting story in China and I'm sort of loath to describe it here where there are so many China experts but as I understand that China has radically privatized their health system so in TB what that means is that when a patient has TB they either end up in the public CDC system or they end up in what are largely privatized hospital systems. What the Gates experiment is looking at in partnership with the government is putting right up at the front molecular drug resistance testing so that rather than patients who are drug susceptible going into the private health system and being over treated with fancy unnecessary drugs or drug resistant patients going into the public setting where they're under treated with standard for drug therapy at the very first encounter you say if this is a drug susceptible person they will go out to the public system and get the standard for drug dots and if they're drug resistant then they move into the hospital system where they get more complicated medications and treatments and actually the program started in 2009 we've seen a fairly significant increase in appropriate treatments decreases in diagnostic delays and importantly significant decreases in out of pocket payments ironically though if you squeeze these systems too hard so that no one's making any money off of doing the right thing then you find people abandoning TB all together and it's hard to even hire patients or doctors to work on the TB clinics and the hospital administrators are shutting down the TB wards and turning them into something that's more renumerative so once you start getting into this issue of incentives they're hard to fine tune and you can fall off the rail on either side Great, well I wanted to hear a little more about your experiences in India but I actually wanted to start the process for questions from the audience because I can go on all day long as most of you know over here we've got a microphone coming to you from the back that it's Gates Foundation DFID that there's some questioning about whether product development partnerships in that model can effectively bring new products, vaccines, diagnostics drugs to the market Is that observation correct? Is it generalizable? Why and what's your personal view about that? Yeah, so I have a strong view on this I actually think that product development partnerships have been transformational in bringing attention to diseases which would otherwise be neglected and have been neglected because there's simply no market for them I think they've been on a steep learning curve and you know looking back over the work that we've funded as I have had the opportunity to tell Bill and Melinda themselves I mean we're over budget, we're behind schedule and I think that those are always fun Those are not fun conversations but fundamentally I think if you look at things like the gene expert it would not have happened in the absence of find and now you know the fields moving and evolving and I think people are constantly trying different models but I'm quite certain that in the TB space the progress that we have seen would not have happened in the absence of PDPs And Peter I understand that one of the things that Gates as one of the major funders of a lot of these product development partnerships is actually looking to find more cross talk between them so they're not operating in isolation so that cohorts for example can be optimized clinical space, laboratory capacity they're not having a TB system and HIV system and even with HIV you have a vaccine system and a microbicide system how is that happening and is that being resistance or is that supported by the PDPs? Yeah so I have to say for the last two years which has been a dynamic period I've had my head deeply down in India so I'm not probably the right person to address that but my general sense is that forums such as product development forum are increasingly bringing these groups together and forcing that dialogue but I'm really not the person I have people in the room who are part of it who probably could address it So next question in the middle over here I'm Jeff Dow, I have two questions I'm using that for the webcast, thank you So my first question is where do you see the role of treating latent TB and do you think there's enough I'm from the malaria space personally and the influence of gates in that space has been I agree with you transformative but you compare total investment from the private sector in neglected diseases versus western diseases and there's still I think a disparity there and I'm wondering if you could comment on that So the first question is what do I think about treating latent infection Can you tell us what you mean by latent infection? So tuberculosis is like many infectious diseases you have to conceptually differentiate infection from disease So were I to have TB which I can tell you for a fact that's another story I don't have TB though I do have a cough You know, of a hundred people about 30 of you if we spend enough time together would get infected Now of that 30 only about three of you would move on or three to ten of you would move on to develop active disease So it's this conceptually differentiating infection and then this long period in which you're living with the germs in your body but suffering no real consequences from that and we think about a third of the world is living in that state from the state of actually being ill with it being symptomatic having fever, cough and being infectious to others since the epidemic is being driven by that latter group the public health response has been really focused on that in high burdened countries in lower burdened countries like the United States there's quite a strong emphasis on trying to find people who are latently infected and treating them with six to nine months of a single drug isonized or now the CDC has been doing some beautiful studies that show you can actually treat this with now as few as 12 doses but from a public health perspective in a high burdened country and I'll speak from the perspective of India because I know it best the magnitude of the challenge of just finding those people who have active disease promptly and treating them appropriately is so daunting that they frankly can't stretch themselves to even think about the others the one space where it kits some play is in the TV HIV world because with the confluence of TV and HIV the progression of the disease is so much greater that the juice is actually worth the squeeze I think for treatment of latent infection to become a higher public health priority you'll need a few things to happen the first is that if you had a marker not of who which third of the world is infected but which subset of that have incipient disease and you could target that group that would make a huge difference and I think that policy would be taken much quicker that requires some basic biology that NIH is now funding and biomarker work I think the second thing is if you had a drug which you could administer that didn't take six to nine months if you had a safe simple drug then that would also change the world's approach to treating latent infection but I will say that that drug would have to be a little bit less toxic than this glass of water in front of me because you're going to be giving it to a lot of healthy people many of whom won't benefit from it so it's a high bar to cross so you alluded to this I know there's a second question pending around funding levels but before we move to that one how much do we know about this trigger that moves someone from latent to active disease you know in many parts of the world people with TB are often people that are dealing with other difficult circumstances they're drug users, they're migrants, they're prisoners they're people that have a lot of stresses in their life do we know if there's any connection why is it that I have latent and somebody else gets active yeah we know scanty little about that and it speaks to the broader principle that in TB we have actually this thin veneer of science upon which we've been groping to try and get these new tools and I think we've been successful but this issue of latency becoming active disease is one in which there's a vast fund of ignorance I think there's been a really important transformation in that field which is to not sort of dichotomize the world into you're infected and I'm not and realize that there's a whole gradient you may have just a few bacteria I may have a bunch of bacteria but we're both latently infected and this has really profoundly advanced the approaches to understanding it and also to intervening so it's not the progress isn't being made it's just that we have a long way to go and you would think that might be one of the things that would be useful for vaccine developers to understand what it is that that's triggered and see if there's some way to engage to stop that progression yeah I mean you talked about polarization between the different PDPs but I think that bringing the scientific disciplines together in a synthetic way so that the same immunologic investigations that will tell you why someone is protected to help you make a vaccine could also tell you why someone is how to detect that someone is latently infected or not and perhaps even tell you what part of the immune system do you want your antibiotic to kind of nudge a little bit so they all converge in a way and it's kind of gratifying to see how in the same way that some of the PDPs are coming together and having conversations and increasingly basic sciences is really becoming a much more integrated field and do the HIV and the TB people talk I mean some of what you just said you could just strip out TB and put in HIV in terms of vaccine research how much connection obviously there's one is a bacteria, there's a virus and malaria, you've got a parasite but are there conversations between these different disease groups that should be happening Yeah, not enough Okay Questions I want to do a couple, we had a bunch of hands up so why don't we just do a few in a row and then you can remember them because you have photographic memories Good luck Yeah, hi, David Briden with Results on behalf of Stop To Be Partnership I just wanted to ask about USAID's role in the space of R&D in particular I'd love to get your perspective on that especially in light of the budget proposal from the President to cut USAID's money by 20% Would that have in your view a negative impact on the ability to pursue greater investment in R&D or to help countries roll out some of the new technologies that we're excited about and what's behind that proposal if you have any thoughts about that Yeah, let me just answer that question quickly because you know I think that TB is under resource there's no question about that I think that the space that USAID can occupy in R&D is in the operational research ends they actually have on the ground presence in many of the most heavily affected areas and so I think they have an incredible opportunity to help us not with just coming up with these tools but actually figuring out how to use them so I do think that increasing resources are critical Hello, I'm Shunvi Thimukherjee I'm an assistant professor at George Washington University Is it working? Can folks hear? I hear you but I don't think it's through the mic It says it's on So I I was just, and you just touched upon this in terms of answering that question about AID's role in operational research and you referred to it in terms of new developments of new technologies especially molecular types of drugs I find that we also have a vast amount of ignorance around many of the non-technical issues surrounding TV control and management and I have worked years ago with a program on understanding incentives and enablers for TV and it was very hard to figure out who would fund that kind of research so when we're talking about TV R&D what about the other kinds of R that can help inform how these technologies won't go to seed in 10 or 15 years I mean, I'll just answer that very personally because I I started in a lab looking at, well, I spent a decade as a doctor and then a decade as a scientist at Stanford and then a decade developing drugs and my two years in India have completely changed all of that in terms of your question I think it's a critical question and I don't have a good answer for it it is clear that all of these investments mean nothing until you get them out there to the people who need them and stitching all of that together is actually an incredible opportunity of I think the US government, frankly, because in a way this transition that we're at in TV control where we know that DOTS isn't going to finish the job but we are not exactly sure how to modernize it but we do know we have all the putty we need, we have the technologies we have the health systems we have experiences like what you've evidently contributed to in terms of how do you change provider behaviors and patient behaviors health seeking behaviors I was really thrilled to see the gene expert take a test turnaround time from six weeks to two hours until someone pointed out that actually there were seven months before the patient sought care and that the marginal impact was pretty trivial so you know somehow stringing this all together is a tough puzzle yeah yeah, yeah, no, and so you know how can you repeat the question that she wasn't on the mic yeah, so for my mother who's on sorry, I'm just a small the question was when I'd only test for resistance to one drug refamp and absolutely it's an incredibly imperfect breakthrough right, and that's the way it's going to happen we're not going to wake up one day with a point of care test that you dip in your urine and the one pill that you can get at the corner drug store, you know it's going to be a long slog of incremental improvement to help us with those incremental improvements, that's a huge frustration for a lot of us who would like to contribute yeah so let me answer for Peter and speak on behalf of the Gates Foundation two things I'm really ineligible to do one thing that's interesting is to see how the foundation has transformed even in the last couple of years hiring Chris Elias the former head of path whose focus was delivering technologies into the developing world and really expanding the footprint of the foundation and looking at the delivery space as it would call it is actually a big deal it is a major acknowledgement that developing new things is critical and that's probably still the foundation's core space, but if you don't pay attention to how you get those to the people that need them then they sit on shelves and the history is certainly replete with examples of that so I do think that that's important, I do also know that one of the things that Bill and Melinda have been very clear about is the foundation can't be financing the delivery of these things that is not in space that's governments, mostly development and country governments and our government to the extent that we can help but this connection between NIH and AID even here in DC is critical so we'll go on from there go ahead I'm a public health consultant there has been a renewal call for child survival so I wonder if you can comment on the magnitude of TB in children and who are some of the challenges you see in the field the biggest challenge with what we can say about TB in children is how little we can say about TB in children and I think we've suffered from this kind of I don't know what to call it a catch-22 or whatever chicken and egg thing it's actually very difficult to diagnose TB in children because we generally think of TB as pneumonia and we get pneumonia sample by having people cough and spit and you can't get 5 year olds and below to cough and spit so we've not been able to diagnose you've been around my nephew I'm sorry cough and spit in a cup on demand when not in the presence of Todd point taken so because we can't diagnose it the world has tended to assume it doesn't exist and because they assume it doesn't exist then they don't feel the need to invest in diagnosing it so we're in that kind of a catch-22 and I don't know what the way out is but I'm hopeful that some of the science that's been invested in in biomarkers will give us non-sputum based diagnostic tests and that'll be the critical breakthrough for pediatric TB when you can diagnose TB with a blood sample it'll be a lot easier to diagnose TB in kids but it is I believe it's one of the top 10 causes of child mortality so it's way high up in the list and one of our interns is doing some research on this very question it turns out that we don't really have any kind of pharmacokinetic studies on children so we basically use adult doses and divide by weight which is an interesting approach we don't really have any sense around how to do diagnosis you know so we're while we're dealing with adults in a 19th century approach it feels like we're going even farther back in history in dealing with kids even though it's a major cause of child mortality so an area of hopefully some increased attention next question and then we'll move out of this row we can pass the microphone around I'm gonna make a comment about poor yield in TB diagnosis I started doing autopsies on TB in 1980 in Kinshasa I spent five years at Perje Sita and that's when we discovered that TB was what was killing a third of the people I just have been working the last five years in Uganda in Kampala TB is still killing undiagnosed TB is still killing a third of the people who die in the hospital people don't like to think about dead bodies they don't look at what people die of and unless you do that you don't really know the real data verbal autopsies are not an autopsy and a pathologist point of view but I think and I just shared a paper with him it's in PLOS in Uganda and I think it's people would be shocked about how much TB disseminated TB is not even considered in the diagnosis in people with HIV in Africa so let me throw a question before you lose the microphone so since I don't really have any technical background I often answer technical questions interns ask me today like how good are these child mortality statistics anyway so I gave her an answer but I won't tell you what it was so tell me what's your answer well the answer we say is the verbal autopsy is an excellent tool for demographic data but a very poor tool for specific disease so when we say that TB is the number ten killer of children that's largely a guesstimate yes there have been a few studies of TB autopsies in children in South Africa and it's usually in children over two who are HIV positive who die of TB and under two it's more likely to be pneumocystis or bacteria thank you over here and then Steve Morrison gets to ask a question since he signs our paychecks I'd like to thank Peter again and I remember when I met you in Delhi I advocated for one of the diagnostic which applied signature mapping has developed the TBDX the microscopic diagnostic kit you see the expert is also if you compare the data you have to have a golden standard the microscopic validation so what do you think about this still why it's not people are adopting that technology because it minimized the time as well as the accuracy of the direction of best life is almost 99% one question and whatever you did in India is really a great contribution I recently visited Dr. Ashok Kumar and Chauhan they were mentioning about you and another thing is MDR TB cases are increasing it's because of the co-infection of HIV and TB or what is your opinion about that yeah so first of all I will say generically about any diagnostic tool that its impact is entirely dependent on the system in which you put it and how you and fundamentally no one in the world knows where the best place in either the diagnostic algorithm or in the health system to deploy any of the new tests we know enough to get started we know enough to try it here and there but it then has to be iterated and I think the same is going to be true the system that you and I have discussed previously which is sort of computer driven image analysis so in terms of what I've done in India I have to say it's been an incredible experience for me mind blowing in many ways but I don't really know what I've done but I do know what India has done in the last couple of years and the policy landscape has entirely changed so what they've done has been an ambitious strategic plan which calls for universal treatment, MDR and HIV included this is a remarkable advance over the we're going to find some percentage of the cases and cure some percentage of that and for a program the size of India to make that boldest statement was really I think very brave of them they've also been very frank about the problems they're going to face and I think that the some of the progress they've made in other policy spaces making TB reporting mandatory creating an electronic database that's web based, name based and allows or will allow when it's deployed tracking of cases and the making outlawing these worthless blood tests which are used in more than 90% of private labs so it's been phenomenal to watch the changes in India over the last couple of years so MDR we haven't spent much time talking about that we were just in some colleagues in Iowa in South Africa recently and we witnessed Gene Expert being deployed in Durban and Koreshia Krim's clinic there Brian Brink a friend of ours who is the medical director for Anglo one of the largest employers in Africa they deal a lot with TB obviously one of the things that he states over and over particularly global fund board meetings is that MDR is simply a sign of failed TB treatment that it's just simply poor TB treatment manifest rather than necessarily being connected to HIV because you obviously MDR where there isn't necessarily a lot of prevalence of HIV there has been this big question about whether or not given limited resources we should focus on MDR it is 10 to 20 times more expensive at least using the current drugs and the current protocols as opposed to putting the money into regular dots and regular TB treatment hopefully won't have to make that choice but I'm wondering if you give us your thoughts around MDR and also then what you saw in India they were dinged recently in a New York Times article to their approach to MDR any reaction there it is one of the highest number of MDR cases in the world in that country yeah so MDR is a huge problem I wouldn't minimize it for a minute it's a catastrophe for the individuals involved and it's a nightmare for the budgets India is spending about 45% of their budget on 3-4% of their patients that's just not sustainable and there's no reason why those and that's driven by the cost of these second-line drugs is that a market issue or is that the product is fundamentally more expensive it is a fundamentally more expensive product which is way exacerbated by an incredibly broken market so you know the global fund which has done a fantastic job really transformed in many ways the treatment of TB funds 80-90% of donor assistance they are really well situated to work with US government agencies to try and change that market dynamic and drive those prices down they're generic drugs they've been around for 40 years and and I think that that's a clear issue that will help with the deployment of diagnosis but I think if you look for example at the paper that was published out of China where they said look it's no longer just about compliance the cat is out of the bag and we're seeing primary drug resistance which means these are not people who start off drugs susceptible, don't take their medicine and become drug resistant these are the people who are drug resistant from the get-go and so what China is saying is look we need to diagnose and drug resistance at the first interaction and get people on the right treatment I think this is a big challenge but I think it's the tools are lining up the political will is lining up so it's a huge problem I wouldn't minimize it but there are days when I'm optimistic good to hear question over here sorry Dr. Morrison we have microphones down there Peter thank you so much for being with us today two quick things one is you've had a front row seat on the drama in India and you've talked a bit about it but it's also been prone to quite a bit of turmoil in convulsion the last two years and you talk about what's driving that and the second thing is what's the message to Congress or the executive agencies what the one or two top priorities should be in terms of US policy in the next five years on TV thank you yeah those are easy questions you know India is an amazingly vibrant place and while at the same time you're seeing this massive advancement in policy the day-to-day the execution against that policy is challenging all you have to do is read Betsy McKay and Geetanan's story in the Wall Street Journal to understand the flip side of the progress it's I don't I can't explain it those of you who read Indian literature will know Rohinton Mystery's book called Fine Balance and he refers to it as a fine balance between hope and despair I think all of us are trying to do hard things would see it that way if we're honest with ourselves difficult things are difficult at the end of the day I've been incredibly impressed by the technical people and their commitment to make things better and what I feel we as a global community have failed to do is to provide them the assistance that they need it's a booming economy or at least it was until recently but it started pretty low yes they're increasing their TV budget but they're still spending about $115 per patient puts them right on the bottom rung so they need resources we can't pretend that this is some bricks phenomena and they don't need assistance in the short term India will transition to a self sustained system but they need a lot of technical assistance in the interim and so how to provide that kind of technical assistance and the role of WHO and stop TV partnership USAID and others is something that merits very deep thought and I don't have any quick answers in terms of US policy I think the most important thing is that we as a country have to recognize that TV is and remains a huge problem and that TV anywhere is TV everywhere and that we're at this transition where we need to modernize interventions and we as a country have been pioneers in these innovations in getting the drugs the diagnostics in figuring out how to work in complicated systems and so I would say that now is actually the time when the US needs to actually redouble our effort when it's easy to say well we've been doing it for a long time let's back off I think that that would be a catastrophe Thanks Alicia where'd you go? Over here we'll pass around this column for a while and then we'll move over to the middle Hi thank you for being here today I'm Josh Glasser with the Department of State I was curious if you could talk a little bit about how the rapid and transformational changes in society in the environment in India are interacting with some of these biomedical and public health developments that you've been talking about Yeah so the environment of India is a place if we're talking about the physical environment living in Delhi quite close to an open sewer and having just spent a week in Leila Dak one of the most gorgeous pristine places I've ever been India's once again incredibly complicated and incredibly heterogeneous I think if we're talking about the human environment the big challenge that India epitomizes is urbanization dots has always been focused on the situation and I'm not sure anyone with the possible exception of New York City and that was done a different time in a different budget know how to control TB in the urban context where all of the environmental issues are colluding against you again the policy environment in India is quite encouraging because while they've had a national rural health mission for many years it's only in the last month that they've announced and launched a national urban health mission I think getting TB and other infectious diseases addressed and understanding the sort of unique characteristics and possibilities in urban settings is going to be one of the big challenges It's interesting to know sort of see the almost the opposite of China which sort of gave up doing a lot of rural health care and focused on urban health care and then realized a little bit late that they left too much off in terms of rural health care and now reinvesting in that area Other questions over here Thank you New Lamor with American Thoracic Society so we've talked a little about TB in children but then we also know that it's also a major killer in women and is actually one of the leading killers of women of reproductive age so I wonder what your perspective would be on you know why or how TB hasn't focused in the prioritization with maternal and child health issues Yeah, I think it's a great question There were an estimated 1.4 million deaths from TB in the last year and at least half a million of them were in women and that does make it one of the big killers I don't know I don't pose to understand much I certainly don't understand advocacy and how that link has failed to happen is mystifying and needs to be rectified I think the link to children is another one because it's not just disease it's the fact that when I'm a sensitive guy, but I don't cry a lot I was with Bill Gates in South Africa Did Bill make you cry? We're at the King George Hospital which is a five-story building just overflowing with drug-resisting cases and the pediatric ward just brought tears to my eyes these kids, one, two years old who were they had so few muscles they could hardly find they were getting these painful intramuscular injections and I realized that this is really what we're doing there are all these MDR orphans whose only legacy from their parents is that they are infected with germs which are multi-drug-resisting I think it's incredible how do we let this happen the whole idea of being TB-free on your fifth birthday is something which just needs to get some traction not necessarily disease-free but infection-free If I suspect the issue with women is connected to the comment you made earlier around latency and actually seeking care certainly I know more about the HIV space but women are often the last to seek care for themselves and put everybody else ahead of the line and sometimes that's by choice and sometimes it's not by choice they're sort of pushed to the back of the line so one of the challenges here is understanding how much of it is that sort of situational issue or discriminatory issue and how much biological is there any difference in terms of biological receptivity for women I'm going to go out on a limb and say I don't think so I think that pregnancy is a slightly immunosuppressing event and that there's some relationship here but for the most part my understanding is it's mostly environmental but I could be totally wrong on that So let's move up here to the front row and then we'll come over here and then we'll go to the middle Hi my name is Mandy and I work at Results with the Action Partnership and I'm so excited everyone's talking about women and children TB because three years ago when I started working on that issue I could barely get anyone to answer a question on it so my question is a bit more about what happened in India in January of 2012 with the emergence of what some call totally drug resistant TB that report came out and then there was contradictory reports from the Indian Government saying oh no it's not totally drug resistant it's just extra extensively resistant and then there was this WHO meeting where they had to figure out how resistant was this resistant strain and there was a pretty big contradiction between media reports and what the government was saying and there basically seems to remain that contradiction to this day so my question is when do we start freaking out because you're talking about a completely resistant strain I mean we're not coming up with antibiotics fast enough to outsmart the bacteria that we're dealing with so why aren't we being louder and freaking out about it yeah so I was around during all that time and it was interesting because it happened after an international meeting mission which had been to Mumbai and came back in Ken Castro from CDC said it's New York City all over again and Mumbai is a really special case in India in terms of our awareness of it. I hope it's genuinely a special case and it's not just the tip of a bigger iceberg but I think what you saw are kind of expected political responses so let's not talk about the problem let's talk about the name and things like that which this is to be expected there are two things one is I think actually the media attention was critical in pushing through that and getting to the heart of the game which was that the TV control program in Mumbai needed to be radically revamped the other thing which is more encouraging to me is that Mumbai is doing that so they've held meetings they've now launched a plan which is an integrated urban response that includes strengthening the public sector as well as the private sector bringing in IT and other things so you know if there's a silver lining to that cloud it's that it has precipitated a response and Mumbai is the right place to take it on because it's a relatively affluent city which can afford to try and do some new things and if those things are found to work then the question becomes how does the country scale them up and this is encouraging to see discussions between the World Bank and India about resources to do that. We're here. Thank you. Elena McKeon Catholic Relief Services I just want to comment a little bit about the women and for us what we have fun is lack of opportunities or misopportunity because the women are the ones who come every time the child is sick but the health system fails to ask if they have any symptoms. We did recent research in the Philippines and what we found is that the female patients were more likely to be asked to bring the contacts to the male patients. So there are some interesting information there to see what are the misopportunities the system is failing to ask the women but my question is can you make comments about the role of community in TV prevention and control? Yeah, only to say it's insufficient. It's a complicated chain of causality that starts with someone becoming infected or symptomatic or seeking care and getting the right care and it's unclear who holds the system accountable for that whole chain working and I think that one of the great things about the community is that they can have a really unique and proper impact at many of those stages where the traditional medicalized approaches have simply failed in it's been really interesting for me Todd mentioned the evolution of the Gates Foundation and one of the evolutions of the Avahan program has been to start off thinking of this as a fairly straight forward intervention and now it's a significant portion of what the foundation has been doing in India about HIV as community mobilization so it's something which again my time in India has really changed my mind on. It was interesting to see when they started it was Avahan as an HIV prevention program and they went in with a full set of slides from a well known consulting firm and found quickly that although Chevron didn't result in impact so they switched actually one of the areas one of the big things they were finding was a gender violence hotline that was intended to allow women an opportunity to engage some system to help them when they were suffering from gender violence and that actually turned out to be through a lot of studies one of the most effective HIV prevention interventions that they had but that certainly didn't show up on the original slide set so I think there is a lot of learning here I think Bill and Melinda have also spent a lot of time in India and they certainly heard from people and witnessed themselves that back to your point that technologies are important but it's a community that allows those things to make or break that supports the women to get in to get a diagnosis and to get treated all those things happen at the community level not so much at the research platform I would just add that I don't think that certainly in the TB space you'll see the foundation moving away from the promise of science and technology but rather expanding to incorporate the issues of delivery at the end of the day it's that integrated approach if you have a point of care test it makes all the other parts easier and so how one iterates that entire spectrum in integrated fashion is really I think where at least the TV program is going thanks other questions over here I'm Mary Doofish here with Samaritan's Purse thank you for your talk as with malaria drugs there is a certain amount that are not I don't know if you call them counterfeit or what is the right word to call them is this a problem with TB drugs and if so how big of a problem is in your experience well I think in the public health system it's not a problem but in the private sector drug control is an incredible issue and I don't know frankly how much drug resistance that we're seeing emerging in India or anywhere for that matter is due to patients being prescribed the wrong medicine for them being prescribed the right medicine but actually being given inferior quality or insufficient dosing how much of it is just that they are failing to adhere and so the most candid answer is that we don't know if you're ever in Delhi I would recommend that I can give you the coordinates of the drug market in Old Delhi where you see unlicensed medical practitioners wander around with burlap bags full of drugs that they're buying and reselling at times the increase in price and I don't know whether those drugs, whether it would be better from a public health perspective if they were all actually water or not but I can assure you it's a terrifying scene we did actually at CSIS we had a similar session to this a few weeks ago with the Institute of Medicine and the FDA the Institute of Medicine just did a report around fake and substandard medicines and TB drugs or anti TB drugs were cited as one of those where there is a lot of fake drugs going on but as you said depends on the system they are in the public system certainly in some places the Global Fund has struggled with that public sectors often have weak supply chains but they're definitely more robust often than the private sector which just seems in many of these countries to go without much regulation at all in that report they note that there have been connections made between the presence of fake or substandard TB drugs and the development of resistance but it feels more like supposition than actually the conclusion of research so it's more like there are fake drugs there is resistance so maybe there's a connection rather than evidence that shows that connection questions over here in the middle what is your opinion about targeting hawk spots is there an experience in India? this is during the last Global Fund Board meeting it was a week or so ago in Sri Lanka Mark Diable along with Lucika from Stop TB and Rob from WHO Malaria Program we're talking about this new super hotspot approach which I thought was interesting since our data are often so weak but there are apparently in some places good enough data to sort of drive down to a very micro level and focus your efforts there I think it's great I think that when we look to modernized dots we have only a limited number of opportunities but each of them are really quite powerful and one is to acknowledge that one size fits none and to really say that how do we target one area where things are being driven by the private sector differently than another where the epidemic is being driven by say HIV or MDR so I think that that's a critically important issue but I think you also have to put it in the context of we have to get away from being comfortable with uncertainty and demanding precision and quality so it's no longer a question of finding someone in whom you see a bacteria hoping it's drug susceptible and finding them for drugs and knowing two months later that you are right or wrong it's like we have to know the first touch with the right test that these are the people who need these drugs or those drugs and get them on them and I think the third one really speaks also to the point you raised which is that we can't we can't pretend anymore that we know what to do we certainly know enough to get started but if we're not learning in real time and getting smarter every day and that smartness it's a different smarts in one place than another we're simply not going to make progress yeah and just to add I think there's a lot of evidence where the data are only part of the picture and even when you have the data there are other factors that relate so when you have a country where the TB is hitting populations that are illegal or migrant or otherwise sort of ostracized having data that shows they're at risk doesn't seem to drive attention to their needs you know the hotspots approach which is certainly a data centric approach is still going to run into this resistance of sort of addressing people that have needs and sort of getting over the political or cultural issues and sort of keep them somehow from not getting served so it'll be an interesting challenge just to speak just a kind of quick personal anecdote when I moved to India I was shocked to hear that people who have protracted coughs are taking care and I wasn't quite sure how someone could be so stupid and then I have asthma so I after cold I took my usual 10 days of oral prednisone and the cough kind of went away but two weeks after that being an ID doc and having a persistent cough I figured well this must be a post viral bacterial infection so I found three days of withdrawal in my closet and I took that speaking of burlap bags and and being fundamentally human after that failed to work I just started chugging quietly cough medicine at work and one day my roommate my office mate busted me on and said you know Peter you're coughing a lot and you've been spending a lot of time in these hospitals and sometimes it's not just TV or XDR TV aren't you worried? and it hit me like a ton of bricks that if I had walked into my ID clinic at Stanford I would not let me finish a sentence before I put a mask on me and yet I've been like living with my family my young kids for six weeks coughing and I was a TV suspect and the amazing thing though which made this story really gratifying is that we have been working with CHI a gene expert through the private lab networks in India so there are now 13 laboratories and there are actually maybe 30 labs in the network so 30,000 collection sites 3,000 collection sites where you can go and get a gene expert and the prices guaranteed did not exceed a ceiling and so I went to one of those labs and I walked out 17 minutes later with a digital chest X-ray and a gene expert cooking and they SMS me later that just the next day and said I didn't have TV and you know it was it was really one of these things or you have XDRTB time to freak out well I actually was convinced that I had XDRTB my wife was a physician and is generally pretty good at talking me down was out of the country for the week and I was just my kids were like you know and when are you going to get that green expert and leaving notes do you have TV it became like a family drama anyhow so you know this whole issue about how you get people to seek care and you know when you find those hotspots you know what's different about asthmatic retired Stanford academics and you know the people the others out there and how do you get to all of them it's important In the back Kalisha can you both ask a question and we'll Yeah Ambassador Don Bandler in 1972 I decided that you know my wife and I should go to Nigeria and see what it looked like and the malaria was immediately whacked and you know we asked and what's going on and how and what can we do about it and there really wasn't much to say in their health universe so I don't know it was just we're still alive but it was it was very surprisingly to me that we didn't get the amount of the right kinds of drugs and really make a change I mean Nigeria is one of the countries that's also addressing a lot of the TB they have malaria widely they have a high utilization of the private sector and you know you were talking around diagnosis and sort of getting that you know initial point to be diagnosis and moving forward that clearly has been the effort with malaria but they have been really challenged Nigeria especially because so many people seek care through the private sector and getting the private sector to utilize a diagnostic before they give you the drug that they sell is a real challenge India the same so maybe you can comment a little bit around you know how you think there is an opportunity to utilize a private sector and you mentioned before incentives this is about making it as profitable for country companies to be able to diagnose effectively and how do you stop the profit from selling the drug that they don't need yes so the first thing that we've done which has been great fun is we've been few of us have been spending a lot of time with these private doctors just going out you know learning how their business model works and we're calling this the Freakonomics of TV Care because if I were poor and sick in India I would have really three options I can go to the public sector I can go to an unqualified private doctor I can go to a qualified doctor so just taking the unqualified private doctor because if I'm poor that's where I'll probably start because it's cheaper I would pay in year of the doctor I would pay you 30 rupees for the visit and think that wow I'm getting a lot of service for 30 rupees you would order 600 rupees of tests you'd order chest X-ray CED-ray and CBC that would be done on a form and when I took it to the lab your signature would ensure that 40% of that money came back to you and then you know if the drugs kick back is not so straightforward but what you realize is and then at a certain point if I'm not getting sick you don't want me around because that looks bad right and so then you will refer me to another doctor and at that point you'll actually get about 40% of the fee that I pay him kick back to you as well so when we start to see lots of referrals amongst the private sector you realize well it's an inevitable consequence of this business model so what we're doing it's kind of fun actually we're working with the Indian School of Business to actually model all of this and try and say like if these were shoes you're selling and you're trying to optimize this function then what would you change and we've stuck into this something which is in the National Strategic Plan it's a private provider interface agency without getting intended the technicalities of it it's basically it's a group who have separate relationships with the lab with the drugists and with the providers and they then would tweak that model by for instance paying you more money to do the right tests or helping you to get the sputum from your office to the right lab and these are models which are just being you know so we're doing two things we're working with academic modelers and then we're funding groups to actually go out and just make it work so we're going to see how these models equilibrate in the real world and how closely that tracks to what the analytics suggest and then we'll have the cross talk between them and so it's just an experiment but I think it's these kind of experiments where you start by putting yourself in the mindset because we fundamentally what we learned is if you're a doctor and I'm coughing I'm worth about 450 rupees if I have my little google glass is going to be starting to estimate when I'm talking to you how much I'm going to get out of this transaction and if I have TV you know I'm worth about 3000 rupees right now the the government of India has for 15 years said that if you will refer the patient to them and then complete treatment of them with the dots you'll get 250 rupees and they're not getting a lot of takers 3000 is more than 250 yes I'm Dr. Jennifer Platt with Wash Advocates Water and Sanitation Hygiene Advocates I'd like to follow up on the earlier question regarding the impact of the environment and you need to discuss the need to address urban situations of course safe sanitation and hygiene only exacerbate the spread when they aren't present I'd like to know if there are any examples of TB control efforts that are integrated to also address sanitation and hygiene otherwise we're missing a key opportunity to mitigate the spread yeah I'm not aware of any I think that TB being an airborne disease probably has slightly would have different implications in terms of water and sanitation than some of the more common enteric infections that I've become familiar with hygiene meaning like cough hygiene and so infection control is a really good point because we have not really good handle on how much TB is being transmitted in aggregate settings and what the potential impact would be of infection control so I could totally I do think this is one of the things that PEPFAR has looked at quite a bit with the CDC is how to understand basic steps that can take to reduce the likelihood that patients waiting for AIDS treatment are somehow then susceptible to the person sitting next to them who happens to also have TB again going back to South Africa we were in a very rural health clinic and they took this very simple step which is their waiting room was outside covered but open air and they had appointment slots so that people weren't sort of coming in the morning the entire day together so just trying to reduce the load and the actual patient count in the clinic was quite low you saw very few patients inside most of them are waiting outside they found that that alone had substantially reduced the morbidity of TB in that little clinic in Lumpopo province so I think that there is an effort to try to understand at least how in addressing AIDS treatment we're not exacerbating risk for TB and maybe more proactively how it is that we can use that opportunity to get people who have come in for HIV to address TB I do want to ask you some more about that but I want to come back to there were some more questions over here in the back and then over in the left and then Sharon Hi Jason Meisner with Relief International I wanted to touch more on HIV you have countries let's say like Burma where there's a high TB rate also high HIV rate particularly when the highest in Asia you also have a population living with both I was wondering if you know of any innovative approaches particularly for integrating both and the role humanitarian organizations can play with national health centers yeah so the the numbers would suggest that the two programs are increasingly playing well together that the numbers of TB patients who are being screened for HIV and HIV for TB are going up and I'm not actually familiar myself with which of those are really working well and which are not and what the common themes are that are emerging out of that I do know you know the blueprint for an AIDS free generation is I think a really landmark document in terms of the way it addresses TB HIV together and brings together funding streams in an important way the issue in Myanmar is a population that has higher rates of TB, higher rates of HIV they also have malaria and where Artemisum resistant malaria has been found so I think there is an understanding of how basic health system capacity is an issue rather than sort of addressing one of the diseases and also addressing a migrant population or workers are moving in and out of one area to do lumber or mineral extraction or other things so Steve Morrison and I and Tom Collison and others are actually going to Myanmar in a couple weeks and we're going to write a little CSIS report so hopefully we'll have something pretty to show you that gives you maybe a more definitive answer to the question you just asked over here Hi, Kate Doyle from PAP you've talked previously about what you think the role of communities is very important as well as how much you think new tools can be a game changer but can you comment on how prior to implementation you think communities can have an input in working with drug developers with PDPs on things like target product profiles and user acceptability Yeah I can say that it seems intuitively obvious they should be at the table and they should be involved I can say that I'm seeing more and more of that happening that affected communities are increasingly involved in those discussions I think what what we're also seeing is sort of formally treating those communities as recipients and thus finding preferences actually going out and doing the research as you would if they were rich Southern California housewives or something I think there's a lot of little things I've seen but it's actually not something I've had a lot of personal experience with I do recall an incident where I think you were actually with her where Melinda Gates was in Hainan province in southern China and went to a TV clinic and saw someone, a woman who was being treated with dots and in that case it was 32 tablets per treatment and came back quite ready to push the foundation to do a better job of understanding what it was like for her to have to go to a clinic every day and take 32 different pills and how could that possibly happen so maybe a little bit more awareness around some of the donors understanding what actual people need and are willing to take and how they take them has got to enter into the discussion here particularly when we're not going to have very short treatments or a vaccine that actually I remember that clearly because I thought I was showing her a really successful clinic they had lots of people there they were taking their drugs and she perceived it entirely differently and actually much more accurately so that's an impressive pill burden and why do they have such a long line they have to wait in every day Sharon Hi I think this is on Peter thank you for being here today one question bubbling up in the literature more and more these days our discussions of TB and diabetes coming in from India were obviously very large epidemics of both occurring I wonder if you could comment on the importance and then sort of posing the related question we all know how difficult it's been to deal with TB and HIV integration and what does that teach us or tell us as we think more broadly about diabetes and TB and some of the other things that we've been talking about here Yeah I think that not just diabetes but a spectrum of non-communicable diseases which is starting to get some a lot more traction and a lot more formal attention and it's going to bring up the same issues of how do these communities and service networks actually integrate I don't know whether we can expect them to accelerate their progress by learning from HIV or whether it's incumbent upon all communities to just relearn the same stuff so that's going to be probably the biggest challenge is ensuring that there's cross-learning and not relearning So it's 1.30 we will let our last question come from here and then we'll conclude I'll let you know what's coming forward to you from CSIS, a working group that Sharon is actually sharing I have the microphone, can I ask a question? Absolutely. Maybe two questions? Can you tell us who you are? Yeah, Tom Kenyon, CDC Thank you Peter for sharing your experience and all the foundations done for TB and other causes I wonder if you could come back to diagnostics talk about TB diagnostics in the context of broader infectious disease diagnostics and having a point of care technology that would address a battery of infectious diseases at the same time because I think in spite of the technology it remains elusive and it requires not only health-seeking behavior on the part of the patient, but as you showed amongst yourselves diagnostic-seeking behavior on the part of the clinician and can't we take the thinking out of it and make it more automated So for example, in a given community you knew the top five etiologies of lung disease or fatal infectious diseases and can include those in a package of technologies and use GeneXpert as the approach Is that feasible and how far away are we from that? Thank you The diagnostics industry is a platform industry and so right now GeneXpert for example has a TB cartridge and other cartridges as well they're not tuned for the needs of the local environment and so having a fever cartridge diarrhea cartridge and all the rest is a big push in a number of diagnostics initiatives but it also gets to the systems issue of I kind of grew up in the TB community and I always thought it was great it's like wow with this we can prove they don't have TB and send them on their way you know it's actually really ungratifying for the patient and so I think that there's not only you know it doesn't only make sense for the system to be able to say oh this wasn't TB it was something else it's actually going to really drive consumer behavior because what we, what I used to consider big win is like oh we sent them from the TB and said it's not TB he goes home and goes like I went to that place you know I waited all day they took my serum and they did nothing for me the good news is I don't have TB the bad news is I'm still dead which was true of my cough incidentally last question hi Alam Sabri the intern Todd mentioned earlier two things I remember from my medical training back in Morocco first treatment and diagnosis were definitely challenging but also factors highly associated with tuberculosis like malnutrition are these factors taken into consideration when tackling tuberculosis globally? I don't know how to answer that I think that the traditional approach to TB was to set up a clinic and wait for people to come in and diagnose them and treat them I think as we start to move towards the modern dots it's going to be targeted outreach and intervention and so malnourished diabetic populations obviously would have the target rich in a way but I there's so many of these things are co-linear the people who have diabetes the people who have malnutrition are poor and they live in a crowded area so in a sense they kind of wrap them up by focusing on them kind of synthetically and not say like oh let's go find the malnourished people and screen them but maybe there should be more of that we had a number of questions here around these cross connections a lot of discussion around understanding what patients need and want and how to ensure that they have the capacity to seek care certainly focus on the delivery side of things which is quite interesting and one by asking you if you don't mind fill out that little form on your chair and you can just leave it back on your chair it gives us a little bit of feedback as to whether or not this was a useful session for you we're also happy to take comments in other ways but this does it a little more systematically if you can join me in thanking Peter for participating today wish you all a happy 4th of July week