 I'd like to ask everyone to get to their seats and we'll get started momentarily. Good afternoon and welcome to CSIS. Thank you all for joining us this afternoon. I'm Steve Morrison from CSIS, the Global Health Policy Center. This is part of our regular speaker series and we're thrilled today to be hosting Peter Small, who for the last six years has been the senior program officer and team leader for tuberculosis at the Bill and Melinda Gates Foundation. We spoke with Peter, Charles Freeman, and I visited with him way back in September and put on the table the idea that we were hoping he would come to CSIS and speak specifically about drug resistance to tuberculosis. And he kindly has agreed to do that, so welcome Peter and thank you very much for taking time out of your schedule to come and be with us here. Peter's been in the lead at the foundation in developing its tuberculosis strategy, building core partnerships, hiring and managing the TB team, and serving as the foundation's voice on tuberculosis. He received his undergraduate degree from Princeton University, medical degree from University of Florida, and did his postgraduate training in internal medicine at UCSF and infectious diseases at Stanford University where he also served on faculty before joining the Bill and Melinda Gates Foundation. He's arguably among America's foremost experts on tuberculosis. He's published more than 100 articles and chapters and a number of landmark studies in the key journals and has been a leading strategist as well on how to bring forward a more effective international mobilization politically and institutionally to bring forward the global TB agenda. So with that, thank you so much Peter for being with us. Welcome, the floor is yours. We'll follow in this presentation with some comments and questions. Thank you. Hearing that introduction, I'm reminded of the fact that I actually in medical school never learned about the two diseases that dominated my professional life. In 1981, HIV was unknown and tuberculosis was thought to have been conquered. The myth that tuberculosis was a disease of antiquity was dispelled for me during my medical training at San Francisco General Hospital where I was treating increasing numbers of immigrants and AIDS patients with tuberculosis. But the full consequences of this misconception and the decades of neglect that that has spawned became apparent to me in 1990 when I was working at Muhenbilly Hospital in Dar es Salaam, Tanzania. This was my first exposure to the real world in which TB and HIV collude to overwhelm underfunded medical systems. And Muhenbilly Hospital at that time was Tanzania's largest hospital. It was a teaching hospital with about 3,000 beds and an average census that was almost twice that. So on the ward that I worked in, we had TB patients and AIDS patients sharing beds shoulder to shoulder in the same beds. And I have to say that as a clinician, I'll never forget the patients who died because of the things that I did. But there's something particularly haunting about the people who died because of what we didn't do in that hospital. What we didn't do in that hospital was pay attention to interrupting TB transmission and protecting those patients from getting infected while they were in the hospital. It was partly because we had lousy tools. We still have lousy tools today and I'll get to that. But by the time we knew a patient had tuberculosis, they'd already infected probably a dozen other people in the hospital. And I don't know for sure, but I suspect that many of those AIDS patients who got infected with tuberculosis in that hospital on my watch subsequently died for lack of therapy. I returned to the United States to complete my subspecialty training at Stanford University Medical Center. I was very enthusiastic at that time about the use of high-tech molecular bacterial DNA fingerprinting as a way of tracking who was infecting who in the city of San Francisco. It was a truly exhilarating time for me. I was publishing in the New England Journal of Medicine on an annual basis and generating data about what was going on and what was fueling this resurgence of TB that I think helped the TB control program in San Francisco to control the situation. However, with time it became increasingly clear to me that the real TB problem was not in the United States and that the world was only going to go so far in controlling TB with the lousy tools that we currently rely on. I think we're all fortunate whether we know it or not that Bill and Melinda Gates are an incredible couple who have a profound belief in the power of science and technology to solve big problems. I, for one, am incredibly fortunate that six years ago Helene Gale recruited me to Seattle to design and implement a TB program for the Gates Foundation and it was in the early months when I was in Seattle that Bill and Melinda fully realized and I think we're completely shocked to realize that a global epidemic that was killing somebody every 22nd had as its primary intervention tools the diagnostic test that was 125 years old, a vaccine that was 80 years old and drugs that hadn't changed for 40 years. The UN has now committed more than $875 million of their money to rectify that situation and increasingly I'm getting nervous to think that all of those investments will have no impact if we don't get these tools out there. Thus it's really, I totally appreciate the opportunity to come and talk to this crowd. I'm told that you understand political will and resource mobilization. In fact, as I was packing for this trip I asked my wife, I said, Delaney, can you believe that I'm flying across the country to talk to a room full of people in the hopes of a TB nerd somehow helping to close a billion dollar a year funding app? I mean, in your wildest dreams did you ever think that I would be doing this? And she said, Peter, you've never been in my wildest dreams. So with that send off on the plane, I put together a talk in which I'll briefly expand on the TB problem but spend most of my time describing the new tools and the innovations that are coming down the pipeline and some of the encouraging signs that increasing political leadership, not just among traditional donors but also from the emerging economy to have high rates of drug resistant TB may finally be rallied to combat this disease. You know, my medical school teachers were not alone in thinking that tuberculosis was a thing of the past and yet just because TB isn't making headlines it doesn't mean that it has gone away. Globally, tuberculosis remains a huge problem and has the potential to get worse. Next week the World Health Organization will release their new report and this year the actual number of TB cases will once again have increased this time to 9.3 million cases and this year the number of TB deaths will once again have increased this time to 1.8 million deaths placing TB just behind AIDS in global fatalities. Now tuberculosis is a bacterial disease. It causes pneumonia. When someone with that pneumonia coughs, the pathogen turns them into little atomizers, little perfume bottles around, just spreading through the air, infectious particles which if somebody has the bad judgment to inhale will create an infection and in many cases that infection will be controlled and the people will become latently infected. In fact, a third of the world is latently infected and lives in this tenuous balance between a pathogen and their immune system. How many people in this room know their tuberculin status, whether their skin test is positive or not? That's good. I won't ask who is infected but I'm going to just guess off the bat that looking at the demographics it's about 20 or 25%. There are about 15 million latently infected people in the United States and at any point any one of them can reactivate and spread disease to others. But this issue about the central role of the immune system in checking TB is most dramatic in sub-Saharan Africa where the convergence of the HIV and TB epidemics have totally changed the disease. Rather than people getting inhaling, getting infected and staving off disease in the absence of an immune system or in the presence of a decimated immune system they inhale the bacteria, they get sick and without treatment they promptly die. And this is really what is fueling the TB epidemic throughout sub-Saharan Africa and many other places in the world. Each year 1.4 million HIV infected people will develop TB and 456,000 in the most recent data died from it. This makes tuberculosis the leading cause of death amongst people with HIV. Shocking to me that while we can prolong a life with antiretroviral therapies we still are incapable of saving a life with $14 worth of drugs. It's particularly tragic from a public health perspective because TB control is one of the most cost-effective public health interventions. $14 can save a life and stop the spread of the disease. It really works well when it's done perfectly and yet it is really hard to do perfectly with those antiquated and inadequate tools. When it's done imperfectly treatment of tuberculosis rather than curing patients turns them into chronic secretors of drug resistant TB. And drug resistant TB is really a very significant threat because what we're talking about is an airborne epidemic of an increasingly untreatable disease. Last year there were half a million cases of multi-drug resistant TB. These are patients who are resistant to the standard antibiotics that are used. And if those patients are treated inappropriately and to treat them you need 12 to 18 months of therapy and if you don't do that right then they will become resistant to more antibiotics so-called extensively drug resistant tuberculosis for whom treatment options are severely limited. Now to adequately address tuberculosis in the context of these new challenges of HIV and MDR the TB community needs to embrace an entirely novel concept and that concept is innovation. The TB community is incredibly disciplined in execution but has really not taken on the challenge of innovation and without innovation we are not going to make progress. I would point to USAID as being innovative. 75% of the USAID money is spent at the country level helping countries respond to the needs that they're perceiving on the ground. For example in Tanzania evaluating the nature of the drug resistance problem and figuring out how to use both the existing and the new technology as it comes online. The primary focus of the Gates Foundation TB program is innovation mostly centered to date on technologies namely new diagnostic tests new drugs and new vaccines. The majority of our investments in these activities are with the so-called public-private partnerships or the product development partnerships. These are non-profit organizations who use the best practices of industry to develop the tools that the world needs and these investments are made by the Gates family not with an eye on the dollars made but rather in terms of the life saved. These organizations partner with for-profit sector in terms of gaining access to know-how and to intellectual property to accelerate the development of these tools and we desperately need these new tools in particular diagnostics is the current test I mentioned is 125 years old I didn't mention the fact that it misses half the cases. The most commonly used test for drug resistance takes two months to get results back to the patient. In the context of HIV that just is filed in the chart because the patient is usually dead by then. Unfortunately we are making great progress in the development of new diagnostic tests better and faster liquid cultures are available they've been endorsed by the World Health Organization and they are being rolled out by programs such as Unitate and PEPFAR. Through one of our product development partnerships FIND the Foundation for Innovative New Diagnostics molecular diagnostics are becoming available which will allow you to know within hours and not months whether patient has drug resistant TB. We need to move rapidly to get these tests from licensure into the field and in particularly in the context of drug resistance because you cannot confront drug resistance if you don't know that it's out there. What's most important exciting to me is the prospect that in 2012 industry will have for us some really transformational rapid diagnostic tests which will be much easier to use and put the power of knowledge into the hands of the practitioner at the health care centers. We also desperately need new drugs. Current first line drugs are cheap they've got that going for them $14 for six months of pills I think that's what I spend in a week and a half on my Zyrtec but they've not really changed in 40 years and they require multiple drugs for a minimum of six months because of this many patients don't complete their therapy and that's part of what is spawning this epidemic of drug resistant TB. Again fortunately we are making great progress in the development of new TB drugs. A four month treatment regime is in a phase three trial by one of our grantees the Global Alliance for TB Drug Development and a number of pharmaceutical companies have gotten fully engaged and there are now three new drug candidates for which there are exciting phase two trial results. My expectation is that in the year 2016 or 2017 we'll have a regime that will work to treat these drug resistant cases. And finally we desperately need new vaccines the current TB vaccine was invented before the car and it has had little or no impact on the epidemic in adults. An effective vaccine is the ultimate game changer in the fight against tuberculosis and again fortunately we are making great progress. Five years ago there was virtually nothing going on in terms of a coordinated process to develop TB vaccines. Today there are six vaccines that are either in or will soon begin human trials. Any one of these has the potential to be the vaccine that we need to protect people from tuberculosis and I'm optimistic that around 2016 we may have an improved vaccine license for tuberculosis. Every bit as exciting as the technical progress for me are the signs that there is increasing political commitment and action to combat tuberculosis. In particular two upcoming meetings by Brazil and China have the potential to galvanize increased global action against tuberculosis. President Lula will open the Stop TB Partners Forum in Rio on March 23rd and at the beginning of April the Vice Premier of China the Director General of the World Health Organization and Bill Gates will open a meeting in Beijing. The meeting in Beijing is hosting the Ministers of Health from the 27 countries who have the highest burden of drug-resistant TB. China is also showing some initiative in that they have ensured that MDR-TB has been inserted onto the World Health Assembly agenda for this year. In addition to these meetings there are early signs of new political leadership on tuberculosis from high burdened emerging economies. China, India, Brazil, South Africa throw in a couple of others and suddenly you have half the world's tuberculosis and more than half the world's drug-resistant TB. These countries who are increasingly vocal leaders on trade, politics and health and science are showing some genuine leadership in confronting their own tuberculosis problem. If they do this I think it will have broad and global impact. In addition to the obvious commitment that Brazil and China are showing, India has a burgeoning pharmaceutical industry which is already making the existing drugs for much of the world. South Africa where TB and HIV in combination is a huge problem is increasingly vocal on tuberculosis and is home to some of the most critical clinical trial that are now underway in terms of vaccines, drugs and diagnostics. I think as it evolves, emerging economy leadership on TB can further catalyze a global response in the established global health paradigm rich countries come up with solutions and pay for it for the rest of the world. For tuberculosis, emerging economies can complement and expand on this important work and over the long term if the emerging economies take care of their own problems it will free up the resources from the rich world to focus on the truly needy regions. Now if the emerging economies do show leadership it will also free up the rich world to do what we do best. And I think one example of this is that with the increase in funding on USAID and PEPFAR they are now reaching out and providing technical assistance to assess the MDR situation in these overwhelmed countries and to help them to understand what the appropriate response is. For countries who don't yet have an MDR program they're providing technical assistance to prevent it and for those that already have a problem on how to treat it. But none of these plans that are being hatched will have any impact without money. And it's clear that a lack of funding for TB contributed to the resurgence of tuberculosis between 1985 and 1992 in this country. That combined with the general neglect of our public health system in New York City resulted in an epidemic of drug resistant TB there that cost more than a billion dollars for the city alone to clean up. Partly in response to this the U.S. government in 1992 instituted the Federal TB Task Force Action Plan on TB which has decreased the incidence of MDR TB domestically by 75% down from 485 cases in 1993 to only 119 cases in 2007. The U.S. should be commended for increasing TB funding since the year 2000 but there's still far more that needs to be done. The 2009 budget that Congress recently passed includes in the State Department and Foreign Operations $162 million for TB which is a nine and a half million dollar increase over the prior year. USAID has increased its funding for TB from $22 million in 2000 to $93 million in 2005. In 2008 the NIH spent about $160 million on TB and the recent $48 million reauthorization for PEPFAR includes $4 billion for TB treatment and prevention over the next five years. I think that if all of these monies are well spent and wrapped up together that it provides an opportunity for the new administration to build on a very solid commitment and become a global leader on tuberculosis. The Global Fund has helped to mobilize the global resources. Around 7, about 14% of the funding went to TB. To date the Global Fund has treated 4.6 million cases of tuberculosis but it needs to continue to do much more if we're going to continue to have progress in the context of these challenges of HIV and MDR. To give you some sense of the magnitude of the gap the STOP-TB partnership has a global plan. It's a bit of a business plan for the world in terms of what the response needs to be what it will cost and what the implications will be if they do. In that there's a funding gap of $31 billion including $22 billion for implementation and $9 billion for tools over the next decade. Let me end with a few thoughts about the future. Over history, TB has thrived in the context of poverty and social unrest and the economic downturn that we're in right now presents a really serious challenge to continuing the momentum that we've gained over the last decade. And I think it may become the Mycobacteria's best ally. Despite all our progress today, someone still dies of tuberculosis every 20 seconds and drug resistance is spreading. With the economic crisis, TB has poised to become an even greater threat. I think now more than ever the world needs to pull together to expand our efforts on TB. We need to continue to build on the existent momentum of the meeting in Rio, in Beijing, the G20, the World Health Assembly, and the Pacific Health Summit, which will be in Seattle in June. But most exciting to me is the possibility that the high burden emerging economy leadership could accelerate access to existing TB tools and the development of new, more effective technologies. As the emerging economies address their own TB problems, they can have this global impact. And their biotechnology and pharmaceutical companies can use TB to apply their competitive advantage in new ways to diseases that are much less competitive than the cardiovascular and neurologic realms in which they're currently competing. At the same time, China, India, Brazil, and other emerging economies have a strong interest in engaging and supporting less developed countries through partnerships and twinning programs. These countries can share innovative TB tools, particularly with Sub-Saharan Africa. Finally, and I think most importantly for this group, the U.S. has to continue to support the TB programs. As the Andrews speaker case highlighted, in this globalized world, MDR-TV anywhere is MDR-TV everywhere. We've seen what happens when we ignore tuberculosis in New York City, but we've also seen what happens when the U.S. commits to having an impact on global health. PEPFAR and the President's Malaria Initiative have helped millions of people and has become a source of national pride. I think that now is the time for this country to apply the same level of commitment to tuberculosis. Thank you. Thank you very much, Peter. Let me put just a couple of quick questions out and ask you to respond to those, and then we'll invite our audience to step forward some comments and questions. The picture you paint is of a shift of consciousness among the major emerging economies towards greater leadership. Awareness of this factor of TB and XDR-MDR-TV is requiring a higher level of attention and effort. Is that something that you're reasonably confident is going to be durable through this period? There's this broader question around how the global economic crisis is going to impact these emerging economies. Will they stunt their demand growth? Will they change their budget processes internally? Will they change their diplomatic strategies outside their borders? Will they become founders? They aspire to be leaders. They're taking a greater stake in multilateral institutions and the like. They've pulled the global fund in on many different ways. So as we look forward in this really unprecedented crisis-driven setting, how do you see the TB agenda without knowing? But how would you expect to see how that agenda would be upon in a period where there's greater uncertainty, a certain level of triage and fear and insecurity around this? And we know historically that in similar, severe downturns that health budgets take a big hit. Education budgets, social services take a big hit. That's one question. The other is around the U.S. foreign policy. We know that now we're moving towards a period of re-engagement with South Africa, for instance. We have a new administration. We've had a pretty grim period in terms of our bilateral linkages. Now we have a new foreign, a new health minister, Barbara Hogan. We're going to have a transition of power looking forward. If you could say a bit more about South Africa and what you see as the prospects there, because within U.S. foreign policy in this administration, the South African relationship is figuring as one of the priorities looking forward. And TB, prospectively, and HIV may occupy a significant place. So if you could just comment on those two issues. Yeah, well, let me start by coming clean about what I am and what I'm not. My training is in epidemiology. And I think what we're looking at is perhaps an early trend from the perspective of tuberculosis. This general sense with these meetings, the promises that our leaders are making. And so I'm not saying that this is a fact. I'm saying that this may be an early trend that we're picking up. I've been wrong before in my epidemiology. So I also, though, to say what I'm not, I'm not an economist. And so I really kind of came here hoping to hear some discussion from you folks about what you think of this idea. And in particular, what do you think of the economic situation? I will say that everything that happens in tuberculosis happens in slow motion and over the long haul. And so we're not talking about what's going on in the next six months or even the next couple of years. I think what we're looking for is something that will, if it happens, occur over the next decade and that in a decade from now, looking back, that there will have been an inflection point and we may be there now. I'm optimistic in the long term for a couple of reasons. I would say first and foremost is that it is clearly in the best interest of these countries to address this problem. In contrast to some of the other issues which they're struggling with, they themselves bear the brunt of this problem. And as the World Bank analysis has shown, investing in TV control is an incredibly good investment. The return on investment is on the order of 15 to 1. So I think that there are very selfish reasons why these countries will do so. And not just the countries, but I also suspect that the industries within those countries will come to think of the fact that there are 10 million cases in the world and that a third of the world is infected with this germ as an opportunity and that perhaps in the process of developing a drug which can be used for active disease, if a company stumbles over a drug that can be used to treat latent infection, that is a huge global market. So I'm optimistic but I'm not the right one to answer the question. Nor am I really that familiar with South Africa, so you're probably starting to wonder why I'm here. I have been very impressed with the tuberculosis situation in South Africa. The rates of TB there defy what I as an academic modeler could ever get my computer to generate. I mean it's just phenomenal how bad the tuberculosis situation is and inexplicable. I mean part of it is neglect. The question that the country has profoundly neglected their TB situation and for a country like that to deny that there's a link between TB and HIV is only going to have them fighting with one or two hands behind their back. But I am incredibly optimistic by the political changes as I understand them and Barbara Hogan, one of her first public speeches which was at the AIDS vaccine conference, came out very clearly stating that TB and HIV was going to be a priority for her. So South Africa impresses me with the magnitude of their problem but also with the political sea change that I think we're seeing. Thank you very much. I'd like to invite three or four folks to offer comments and questions. We have microphones. Please just stand up and identify yourself. Yes, Lisa? Hi Peter, thanks very much. Lisa Cardi from CSIS. Two related questions. First is in the global TB plan which I believe is a $50 billion plan as you said there's a number of actions enumerated. I wonder if you could comment on what you think the technical capacities are at the country level to actually deliver on that plan and whether there are things within the current architecture around TB whether it be the Green Light Committee or something else that needs to be adjusted or ramped up. That's the first question. And second question, there's an ongoing big debate about health systems in general and how to sell health systems intersect with vertically targeted programs or diagonal or horizontal. What's your view informal or otherwise on the adequacy of health systems to now support a very broad and rapid global scale up on TB? Thank you. Do we have other comments or questions just now? Right here? Kristi Lubinsky, IDSA. Thank you very much for a wonderful talk. I guess I just wanted to follow up on your remarks about the President's Malaria Initiative and PEPFAR and some of us have been thinking in our advocacy about TB that it might be worthwhile to try to persuade the Obama Administration to embrace tuberculosis in the form of some kind of a presidential initiative. It does seem if you just look at the data and you look at the relative spending levels that there's no doubt that that kind of level of presidential commitment has made a real difference both in terms of coordination across government as well as in terms of absolute dollars being spent on the problem. And we have quite a fragmented response, albeit robust in its various departments in the U.S. government, it's still quite fragmented. You have research going on in three places and programming and so on. So I just wonder what your thoughts are about that, again, as a way perhaps to get the TB community of something concrete to rally around as well as a mechanism to really try to bring TB funding and some of these important interventions to the field and through phase three trials, all of which are going to be challenged under current U.S. funding levels. Thanks. Brenda? Yes. I was just wondering, listening to you say that the WHO is about to come out with a report next week announcing another increase in the number of people infected with TB around the world. So I guess my question is having sort of followed this for the last decade or so is when we're going to turn the corner on those kinds of reports. It makes it very difficult to do my job. As a reporter, it's sort of like if nothing changes, there's nothing to report. And when somebody is going to roll out some of these new technologies of which we know some things about diagnostics, whether some of the money that's rolling around that's out there is going to be invested in getting these into countries and whether the countries are capable of using them, whether they have the infrastructure to be able to use them. I realize I'm packing a lot of things in here, but I guess I want to know what sense there is going to be of some real serious change, or whether we're going to have to wait until 2016 when all of those wonderful things you talked about will be rolled out. So, what? I just wanted to add to the way you from IDSA. Please. The Mabardo Open New Services has a project Bileshield program and then an pandemic food program and they're attempting to have one portfolio effort with DOD and NIAID and HHS, USAID, potentially here. If the Obama administration can get through the economic situation and then propose something like, was in the last, you know, the Bileshield program and the big boost that NIAID got back in 2002 following the anthrax attacks and to have a coordinated approach. And, you know, that seems to be maybe the type of thing that they could rally around. I was just wondering what your thoughts are about that. The second question is, do you see that there's money available for the more costly phase three trials of vaccines that need to be conducted after phase two? Okay, well, a lot of questions. See if I can remember them all. I think that the global human capacity, manpower issue is a massive problem and it's not restricted to tuberculosis, obviously. It cuts across all diseases. Where I am optimistic about tuberculosis it is in the basic intervention programs are very well defined, that manpower needs are clear and the value for that investment is an obvious one. So, while clearly there's not enough manpower to execute the plan of the TB community or any community that I'm aware of, I am optimistic that you can make a very coherent argument for doing so. I think that this issue of health systems and the vertical horizontal debate which seems to be such an obsession of policy people, in my limited experience it goes away on the ground where you may be the tuberculosis person but your clinic is in fact providing care at the health center level for a whole spectrum of diseases. I sometimes feel as though this argument about the vertical versus horizontal and ultimately we kind of settling on the diagonal is a little bit of, it gets tedious I think. And the issue of whether these systems will be able to roll out new technology is a problem however that terrifies me. Because the time that we're going to turn the corner is going to be when we fully implement what we can do today and when we start to experiment on large scale with other interventions. And if we just look at the malaria field for a moment, they're way ahead of us. They have a rapid diagnostic test. In fact there are 60 of them that you can buy. And yet the WHO has recently evaluated these and roughly two thirds of them are no better than a coin toss. So how do you roll out a new diagnostic test when there is in fact no regulatory framework? Are we going to assume as we roll out these new diagnostic tests that the manufacturers will only make and sell quality products that every country will have its own stringent regulatory body that the WHO is going to pre-qualify every manufacturer in the world? I mean I don't know which of those thoughts is more ludicrous really. So I do think that now is the time to start thinking about those issues. Start using incremental increases in the health system as it exists to deliver today's products in a continuous process that segues into the delivery of innovative tools as they become available. And in so doing it's a much more holistic problem than dots versus innovation. I think there's no question that the United States doesn't get appropriate credit for what we are doing in tuberculosis. USAID has done an incredible amount of work in Eastern Europe on drug resistant tuberculosis and no one in America knows it. It seems like a pretty well kept secret to me and any effort to both amplify and give credit for the work that we are doing as well as to bring in new resources and as you point out increasing efficiency. The WHO report that's coming out it's like the last 13 reports there. It's a book full of numbers. As a TV nerd I myself find that interesting and exciting in and of itself but I understand that your world's different and just having the ability to know how many people between the age of 16 and 25 had extra pulmonary TB and Rwanda last year has no value really until you can translate that into a message that the world buys into and I don't know what the message of this year's report is. The facts speak for themselves at some level. It is true. It's very much the half full, half empty and the WHO and the Stop TB Partnership in particular have been tone deaf to anything but the half full message and the fact is that I was involved in tuberculosis for a dozen years before it struck me that while TB rates are going down, which is all I ever read in the headlines, the actual numbers, the only thing we really care about are going up every year. So somehow there's a very mixed message there. There are a lot of success stories and I think that that's the bottom line is that while we may be looking at an overall picture which is half full and half empty, there are innumerable success stories that show that when there is the political will and when there is the commitment that lives can be saved with the tools we have and that the progress will be accelerated in the future and in fact the mechanism for rolling those new tools out is not known but this is where the experimentation and the innovation is in my mind most exciting. So if you look at, for example, what Unitate is doing with the Global Lab Initiative and some of the things that the World Bank is talking about doing in terms of rolling out laboratory systems so that our patients will finally know. I mean diagnostics is the most empowering thing. It gives a patient the ability to demand the treatment they need. It gives the healthcare provider the ability to do the right thing and it gives the whole system the chance to actually even make some money in the process in terms of making this something that is self-sustaining and so I think that without there are stories out there to be told. I don't think it's buried in the World Health Report. And then finally in terms of the TB vaccine situation and just advocacy in general for tuberculosis, it's been interesting to me how tuberculosis advocacy, while tuberculosis has been smoldering with subtle changes that the U.S. attention to it has had several bumps and with each bump it has kind of quietly complacently slipped back to baseline. The bump of drug resistant TB in New York City they got a lot of attention. It certainly ratcheted up investment in the research that probably led to the vaccines that your groups are working with in some way or another. That the push then just fell back and actually it was Andrew Speaker who did more for raising awareness about tuberculosis than any $30 million campaign that we could ever fund. But then again it seems as though we've fallen back into a sense of complacency and I don't know really how with this sort of rolling thunder in the distance that could come out at these large global meetings that gets translated into a message that continues. Clearly part of that message has to be that in product development and vaccines are not alone in this but in all product development the easy part are the early parts. That's and the big expense comes in the later trials. And if we look at the global budget for R&D in the last year for which data were available it's about if I'm remembering correctly $410 million. What is that all about? $410 million the whole world is spending on basic and apply drugs, diagnostics and vaccines less than half a billion dollars. We've been through numbers of exercises to say what should that number be but no matter how you approach it whether you start by getting some advocates in a room or whether you start by getting some people together to build that number from the bottom up and say well this vaccine trial is going to be here at this point it's going to cost this much. It's grossly underfunded and that's got to be part of the message. About a third of the funding is going to drugs right now. Actually a lot of that coming from industry. I believe the vaccine number is on the order percent of that. Most of that's coming from governments actually and the challenge with the vaccines with the diagnostic before you start to produce a diagnostic you have a pretty good sense it's going to work because that's just the way the industry is. Drugs tend to die early in the development process before you've invested a lot of money. The huge challenge in vaccines is going to be that you don't know until the end of the trial whether it worked or not and so I think that the issue of phase 3 funding for all products is a critical one but for vaccines in particular. Next round right here. Please identify yourself. I'm John Voss with Results. Just maybe a quick answer actually to Ms. Wilson's question about sort of what the headline might be my understanding is one of the data points in addition to sort of incidents and deaths is a pretty serious revision so hopefully we'll write that headline for you and that'll be an easy story to write. I want to just maybe make a point and ask a question I think you've laid out several of the sort of compelling components of the case for expanded U.S. leadership in TB. I just wanted to maybe add another one and get your thoughts on that and that is we've talked about subterrain Africa you talked about emerging economies. It seems there's also a set of countries where the U.S. has a very real strategic security interest which is coincident with huge TV burden and also particularly high rates of drug-resistant TV so Afghanistan, Pakistan, but also then the sort of other stands in terms of a former Soviet state so we'll just be curious to hear your thoughts about the TV situation in those countries and how the U.S. might direct some of the frankly massive amounts of foreign assistance that are being poured into those countries to strengthen health systems and address the real problems of people living there. Do I have any other comments or questions just now? Yes, Joel? Joel Spicer, World Bank. One quick comment on South Africa having come back recently from Swaziland and Lesotho I was led to see that no matter what Swaziland and Lesotho do to try and fight MDR, they'll never be able to get a lock on it because most of the cases are imported through minors working in South Africa. So when we talk about South Africa, I think one excellent opportunity for regional leadership on what is clearly a global public goods issue would be for South Africa to play more of a role there in controlling it from a regional point of view supporting countries around it. In terms of the financial crisis it's clear that with insufficient funding for health anyway that the money we have for health has to be spent better. So when I think about the millions and the blood, sweat and tears going into HIV AIDS which by my calculations is between 500 and 1000 bucks to get someone on antiretrovirals. You think about how quickly that is wasted when the person gets infected and dies with TB in a couple weeks in some cases with MDR. It makes me wonder if we're doing enough to wake up our brothers and sisters who are fighting and pulling the wagon on the HIV AIDS side do they get it enough that the people they are trying to protect and the dollars that they are throwing at the problem are actually being eroded by something that's relatively cost effective to address. My personal feeling is no they are not awake enough we see a lot of policy statements but when it comes right down to it at the ground the HIV side is not screening for TB there is not an awareness of this there is no isolation control isolation facilities for people that are treated and it goes on. So what can we do to wake them up is my question. So in terms of writing Brenda's story which I would never really try and do knowing how well she does it but I wouldn't, I don't actually think that the HIV, I would be cautious with the HIV numbers because that's really a reporting artifact. The number of cases didn't just double in the world and I think we have to maintain a degree of care. It's one thing to say it's a big problem but the fact that the numbers have increased because they are actually getting real data is more a statement about the need for real data than it is about the trend. I do also think that maybe it's a slight attention deficit issue on my side but I'm tired of the doom and gloom because it's not where I see the world right now I mean we've known this problem has been out there for a long time and the real story is the optimism which is not in my mind a confabulated story. I mean it's that if you actually go and you look at those countries who are doing a good job their TB rates are coming down. If you look at those countries that have good TB programs they don't have drug resistance. If you look at those countries who have drug resistance who are starting to take care of it patients are living who would have died and then if you combine that with this very real sea change that we've seen in industry engagement in tuberculosis products you know six years ago there was just very little going on and and now there are five major companies involved in vaccines. There are these three drugs that are incredibly exciting. I mean phase two studies are not a drug. I mean at first to admit that but the idea that you could take a couple of these pills these chemicals mix them in a fixed-dose combination and provide that as first line therapy means that MDRTB is a historical oddity because these would be two molecules the world has never seen before. You could shut down every TB diagnosed every drug susceptibility lab except for the research laboratories and then if we could ensure that they are delivered as fixed-dose combinations and well-controlled programs and really defend against drug resistance you know this is an incredible vision and those are the stories that I'm most interested to be honest I don't know anything about the part of the world that you're asking about so I'm going to actually see if anyone in the audience wants to talk about security and TB it's certainly not something I'm Gene Bonventree just retired from the Department of Defense with the local health policy center the only thing I've heard about TB in relation to security is the risk of multiple drug resistance and SDRTB in prison systems and this is particularly a problem in Russia and some of Eastern Europe where entry into the prison system essentially is a death sentence for whatever for whatever you're arrested for and how that upsets the balance of stability and security inside Russia remains to be seen and there are no effective ways inside Russia to deal with that I'm not sure it will take the epidemiologist and the security folks talking at the same table and trying to come to a common language I don't know if we're going to be there Hi, I'm Charlotte Calvin I've related to that one of the things I'm interested in in your thoughts are in this very same region when we talk about innovation and the tools we have countries that still rely primarily on chest x-ray that aren't even doing smell microscopy culture which less rapid agriculture DNA testing not only do we have an extra barrier there that we don't even face in places like sub-Saharan Africa where smell microscopy is more widely used so I would be curious to hear your thoughts on as we talk about this innovation there are some countries that are really important security wise and that we need to get the techniques out there that are going to be a little bit more behind in terms of being willing to accept and innovate do you have any thoughts on how you can move that forward actually you know Christy so over there Christy Hansie from USID has been thinking quite a bit about this issue of how to roll out innovation as best I can tell there's nobody who adopts anything they adapt everything so the question is how do you adapt in different settings thanks for putting me on the spot Peter in response I think specifically for Eastern Europe and just responding to that not to the overall issue of adopting new tools which is another hour's discussion but in Eastern Europe my understanding is that there's a real hesitancy to use because it is such a unsophisticated disgusting technology that they're not very interested in using and it's really a technology that's for Africa my sense is that if new diagnostic technologies that are much more sophisticated were made available they would be rather rapid adopters of the new technologies so I don't think it's a matter of necessarily at this stage of the game saying we've got to get them on to get them using spudos so that then we can introduce other tools they're going to be the ones that jump I think on the new tools very quickly Peter may I ask a couple questions one the around Russia we have a I realize you're a little reluctant to talk about some specific countries but in the case of Russia you've got this recalcitrance and an outlier factor and yet we're now in a period where there's at least a reappraisal around the bilateral relationship we're holding a consultation with a number of Russian health experts here in Washington in early April which I mean early May which I take is a pretty significant shift in the willingness to engage on these matters do you see my questions do you sense that there's within the community of folks that work officially and unofficially on these issues that there's some rethinking going on the second question has to do with the inability of TV to acquire a dramatic face for an American policy maker it's not it's not something that seems to have the same kind of of compelling personality as HIV I mean it doesn't have the same potency of threat it's not it's seen as a more diffused problem whether incorrectly or incorrectly it's one that as you say there are a little bump ups but it doesn't graduate into something that is seen and understood and exactly what is it endemically about this where you have this vagueness around the personality of something that is so important and the tolerance of an obsolete technology across the board when you talk about the need for patients and a long term time perspective on the development of new diagnostics vaccines and therapies when you pointed out just how antiquated those are I find that very compelling persuasive that it's going to take a while to overcome that because we permitted this obsolescence to to exist and to deepen but I don't understand why that why that would be such a historical experience it wasn't just us it's a global phenomenon so how did we find ourselves in that fix yeah which is to touch briefly on the on the Russia issue I early on Paul Farmer and Jim Kim partners in health working in Tomsk I think showed that there is a way to engage in that country and in particular their efforts in Tomsk which was you know it was a long hard slog at the beginning but it has now become a regional center for excellence and is really looked at as as lead innovators I think that that may be the model for working forward in those settings you know the the fact that tuberculosis is such a underappreciated problem is something that I've never understood I've probably heard 30 different explanations and but I had an experience just in March I was in Inner Mongolia and we were we were starting to scope out some of the drug resistant situation and opportunities there and it was really shocking to me because you know I think part of it is when we think about the success of Tomsk has been incredible but I don't think that when people think of drug resistant TB and they think of a cacetic tattooed prisoner in a Russian system that it has actually captures the real magnitude of the issue because for me the TB issue is about protecting our children from the future and this was driven home to me because we were visiting a man who had been really dragged into poverty because of the having had three courses of therapy and he failed his third course of therapy and the medical system had assumed at this point that he had drug resistant TB and essentially abandoned him nothing more we can do go home the community that he lived in a small community had basically ostracized him they understood enough about airborne contagions we know that if the health system had no time for this guy that the kids certainly shouldn't be playing there and we went into the man's house and as we were talking to him I looked in the back room and I saw his white breastfeeding a small child and kids clothes over in the corner and I realized that this is actually the face of MDR TB MDR TB was going to kill this man and the only legacy that his children were going to have was infection untreatable organism and that it's really you know that to understand that the real threat of drug resistant TB is providing a better future for those children and thousands there are half a million cases and how many children are being affected by those half million cases and what their life is going to be like well there's one scenario where their life is going to be fine in 2017 we have a new combination of drugs and when they're sick they get treated it's a good thing and another they grow up without a dad and without a future and when they're sick they too will slowly pass away I actually feel like as a community we've not done a good job of telling the stories when you go to these communities and you talk to the healthcare providers they get it they don't want to talk about pandemic flu they want to talk about what to do with this waiting room full of what to do about any other comments or questions yes my name is my area that I work with path I just want to add the problem of MDR in all the Central Asian countries and it's actually about the need to mobilize other organizations you know beyond the health organizations because in this context a lot of MDR is transmitted for migrant workers so it takes involving for example the international labor organization or international migrant organizations to actually buy into this initiative of controlling tuberculosis because otherwise I guess that it's very important to bring it to the table other opportunities beyond rapid diagnostics because a lot of people don't have access to them just leaves us to where we start off so I think that it's something that the WHO and other institutions have promoted is like private public partnerships and in terms of tuberculosis we have to look also into this other sectors to bring and involve and you know in conversations in a table so that they can contribute somehow to the fight against this epidemics and also about prisoners you know they go back to the communities like we all know and we've been hearing about and actually in those communities like you say they have their children so also involving as it has been done lately the penitentiary and ministers of justice ministers of law so I think you know a very comprehensive approach to bringing other organizations in Africa like the minors you know industries and everything to buy into this and invest in this you know I think that it has to be a kind of like you say holistic approach but also taken into account other aspects beyond the biomedical of tuberculosis I think we'll close on that Peter maybe offer some closing remarks you know I I agree with everything that Myra said I think that we are in the next six months faced with a critical moment in time for tuberculosis where the stakes have been raised the potential is there for upping our game to match that that the issue of HIV and the issue of MDR in particular have the potential to float all of the boats in this point in time and for example I think you can change the economics I mean if right now we can be complacent about treatment of drug susceptible TB but in the context of the cost of treating that case if it's drug resistant that the public health system have to look at TB control with it with an understanding of MDR and with a whole different economic perspective and I think the same is true in the private sector and vaccines in particular you know one of the reasons that vaccines have had problems getting traction is that it's a treatable disease you get TB you get treated but that's no longer true when we're talking about a world in which there is MDR and XDR TB then the market for a TB vaccine goes beyond the truly poor to the entire world and some of the analyses that I've seen suggest that now you're talking about gross sales of $10 a year if the world were really concerned about drug resistance and really had a vaccine that could prevent that that's an opportunity for funding phase 3 trials in my opinion and throughout all of this I feel as though that now is a time in the next 6 months in which we really have to seize the urgency and try and make some real sustainable progress