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 You are in: Bureaus/Offices Reporting Directly to the Secretary > Policy Planning Staff > Secretary's Open Forum > Proceedings > 2001 - 2002

A Conference on Global Infectious Disease and U.S. Foreign Policy

Dr. Norman P. Neureiter, Science and Technology Advisor to the Secretary of State
Dr. John R. La Montagne, National Institutes of Health; Dr. Kenneth Shine, Institute of Medicine; Dr. Barry Bloom, Harvard University; Senator Bill Frist (R-TN)
Remarks to the Open Forum
Washington, DC
November 2, 2001

Opening Remarks by Alan Lang, Chairman of the Open Forum

Dr. Norman P. Neureiter: Thanks so much, Alan. Ladies and gentlemen, welcome to the Department of State. I have to extend apologies on behalf of the Secretary. He's greatly disappointed to miss the beginning of this conference. This is an issue on which he personally feels extremely strongly.

I must confess I feel a little bit like that obscure and long-since forgotten basketball player who was once asked to sub for Michael Jordan, but I hope you can understand those feelings.

On behalf of the Secretary, let me echo Alan's thanks to our sponsors, the National Academies, the Association of Microbiology, the Infectious Disease Society of America, and particularly Alan Lang, chairman of the Secretary's Open Forum. There's a lot of hard work that has gone into putting this program together.

I want to especially single out our good friend and colleague, Dr. Kenneth Shine, President of the Institute of Medicine, for the time that he and the National Academies have devoted to this conference, and, particularly, in providing the best scientific and technical underpinnings for these discussions.

When planning began for this conference several months ago, one of our goals was to convey a sense of urgency to the American public about infectious disease as a foreign policy issue and a national security issue. I am going to say that again: infectious disease is a foreign policy issue and a national security concern for the United States of America and for all of the countries of the world.

After September 11, and now with the anthrax mailings, I don't think any of you need much more convincing on that issue. In fact, just three days ago, Secretary Powell held a town meeting in this building to talk to our employees about the bio-terrorist threat we face right here at State, and in our embassies and consulates abroad. He also talked about what we are doing to protect our people. And, as you know, we still don't know where that anthrax is coming from, and we don't know who is doing it. But we must respond to this kind of threat in ways that sometimes go well beyond the spheres of just public health and medicine. Those are the special measures needed to respond to bio-terrorism.

But in a broader sense, the threat posed by infectious disease in a world that is globalizing, fast-moving and interdependent, requires a comprehensive, a relentless and a swift response. And a swift response is needed regardless of whether that infection is deliberately spread by domestic or foreign terrorists, or whether it is naturally occurring, such as with HIV/AIDS, TB or malaria. And it is critical decision-makers base their policies on solid science. That's a message that we are trying very hard to communicate throughout this department and throughout the government. We must make our decisions based on solid science. And citizens must have accurate and timely information on which to base their own decisions regarding their health and that of their families.

The anthrax threat has suddenly drawn public attention to the complex challenge of dealing with infectious disease. But a host of government agencies have been working for many years to try to prepare for outbreaks of disease, regardless of their cause, and these include the State Department, AID, CIA, DOD, the Department of Agriculture, the White House Office of Science and Technology Policies, and those multiple units of the Department of Health and Human Services, such as the Centers for Disease Control and Prevention, NIH, FDA and so on.

Most recently, of course, you know that the President has created the new Office of Homeland Security, headed by former Governor Tom Ridge, and he is charged with helping the nation leverage and focus its strengths on this critical effort. Countering the threat posed by infectious disease requires unprecedented cooperation and concerted action at all levels of government -- local, state, national -- but also on an international basis as well. It requires an entirely new level of information-sharing and coordination on a global basis, across many fields of expertise and responsibility. And it demands an unprecedented degree of public-private partnership. You are going to hear that word a lot, "public-private partnership." And the wide diversity of participants here today at this meeting reflects both the scope of concern and of the needed response. We have here members of the foreign policy community, the public health community, academia, scientists, medical personnel, representatives of NGOs and also the media. And, by the way, the media play a very critical role in this whole process.

The headlines about anthrax and the new urgency concerning bio-terrorism must not, however, deflect the world's attention from the lethal and growing threat to vast populations posed by HIV/AIDS, TB and malaria. Just as the whole world is responding to the attacks of 9/11, so too must the international community marshal its forces and resources against these terrible diseases. The long-term dangers absolutely must not be ignored.

Already these killers have taken the lives of tens of millions. They can devastate communities, they can cripple economies, they can decimate countries, they can destabilize regions and unchecked perhaps engulf entire continents. Every day HIV/AIDS alone kills over 8,000 people; 22 million have died from it since 1980; 38 million are infected and will die within seven years. And that's why President Bush has taken a leadership role in the world community and is working closely with UN Secretary General Kofi Annan to bring sustained and focused international effort to bear against the HIV/AIDS pandemic, and other infectious diseases.

The Secretary has asked me to assure you that while the global campaign against terrorism is a matter of the highest priority to the United States, the terrorists have not hijacked American foreign policy, nor have they lessened our determination to fight the continuing battle against infectious disease. This administration is just as strongly committed today to a comprehensive, intensive and effective global response to HIV/AIDS, TB and malaria as it was before 9/11.

The President has put the full strength of his Cabinet behind his effort. He has named Secretary of Health and Human Services Tommy Thompson and Secretary Powell to serve as co-chairs of a special task force to make sure that our domestic and international actions are both comprehensive and well coordinated.

The President has also announced an initial pledge of $200 million to jump-start a new public-private partnership, the Global Fund to Combat HIV/AIDS, TB and Malaria. And we hope that this seed money will help generate billions more from donors all over the world.

Just this week in this building, at the U.S.-Africa Trade and Investment Forum, the President declared that he's ready to commit more resources to the Global Fund once it demonstrates success. That will be a key challenge for the managers of this fund.

Infectious disease is a global concern, demands a global response, and so we must build a worldwide network of networks to focus on prevention and tracking of infectious disease, and to increase the effectiveness of our responses. The nations of the world must be in concert. We can stem the tide of these frightful scourges if we work together, if we adopt an integrated approach--an approach that emphasizes prevention, prevention, prevention; an approach that also includes treatment of the sick, care for AIDS orphans, measures to stop mother-to-child transmission of the virus, affordable drugs, effective delivery systems, training of medical professionals. And, of course, our approach must also include research into vaccines and a possible cure.

In conclusion, I want to assure you that the United States is committed to leading the global campaign against terrorism. We are equally determined to work at the forefront of the worldwide fight against HIV/AIDS and other infectious diseases. The United States and the international community must not, and we will not, let terrorists or microbes destroy the immense promise that this century holds for humankind.

Now, what I have just read were mainly remarks prepared for the Secretary. But I was so moved by something that he personally said when he was talking about his trip to Africa that I am going to read just one additional paragraph from his own words. "Ladies and gentlemen, when I travel, whether here at home or abroad, I look to meet with young people, as I did when I visited Africa this spring. I talked to young Africans about their countries and what their world could be like in 20 years time. I spoke to them about seizing the incredible opportunities of this age, of growing political and economic freedom and technological advance. And those energetic, enterprising young men and women gave me many reasons to hold high hopes for their countries. Yet I have to tell you it was sobering indeed to realize that many of those bright young people with whom I was meeting will not make it, even to middle age. Ladies and gentlemen, that's our challenge. Thank you. (Applause.)

Dr. Kenneth Shine: Good morning, I'm Ken Shine. I serve as president of the Institute of Medicine, and I am the Oprah Winfrey of today's events. I want to thank the Department of State, the American Society of Microbiology -- I hope Gail Cassel is here someplace -- and the Infectious Disease Society for co-sponsoring this event and helping us organize it.

A couple of years ago, with a generous gift from Bill Golden, the National Research Council, including the Academy of Sciences and Engineering and the Institute of Medicine, undertook a study of the role of science and technology in international relations. The report of that study was extremely well received by the Department of State. One of the principal recommendations was that there ought to be in the department a science advisor, and he's sitting right there. But the notion that there needed to be a key presence within the department focused on science and technology, in addition to those who worked on the diplomatic and foreign relations side, was critical.

Science and technology offers enormous opportunities as we pursue international relations. Clearly as we talk with other countries, their potential for advancement when they are looking for development depends on science and technology. And it often means making the right choices. Do you build a hospital to do bypass surgery, or do you provide medications to control blood pressure and prevent heart attack? It involves situations in which developed countries have major interests in trade which if properly developed can advance science and technology for themselves and for the rest of the world.

Science and technology offers another very, very important element. It's the opportunity for scientists to talk to each other. The communications between the science and technology communities around the world is not only important in terms of its effect on science; it is one of the most democratizing activities that can take place. Clearly science thrives on openness, on communications, on truth, on trying to understand what is reality as well as we can understand it. Those shared values are critically important. Those values are critical when we deal with all of our colleagues throughout the world. From time to time America has not had the best reputation in terms of its relationships with other countries. But I submit to you health is one of those areas in which no matter what the relations may be, common attempts to improve health, to allow children to develop and grow, mothers to survive childbirth, and young people to live in an environment in which they can anticipate getting an education, planning for the future -- those kinds of developments are shared by the people in all countries of the world. We need to take advantage of that opportunity, not only because it will lead to better health, but because it will lead to better communications, better understanding, and because it in fact promotes democracy in that the principles, the very principles that make for good science and make for good technology are also principles that are part of democracy.

Infectious diseases are clearly a global health issue. Not so long ago a plane arrived in Los Angeles from Peru with 75 individuals on it who had cholera. The capacity to respond to that and to prevent the spread of cholera was extremely important to the people in the city of Los Angeles.

One of my favorite examples was the development of trichinosis among an Orthodox Jewish family on Long Island. Those of you who know about trichinosis know that it is spread primarily through pork, and these people never ate pork. It turned out they had a Guatemalan maid who helped them cook, and she had gotten such a large burden of trichina when she got back to Guatemala that she was able to infect the food in the kitchen of this family.

As a physician, it is not at all uncommon for me to see individuals who have been to other parts of the world, presenting with shaking chills, and to find that they not only have malaria, but they have malaria that is resistant to the common anti-malarial drugs.

In his comments on behalf of the secretary, Norm talked about young people in Africa. As a scientist and physician, I can tell you that for a number of areas of science where we had established relationships over the years, there's nobody to talk to. We have worked in countries and problems on improving food production and agriculture, and the outstanding scientists and a whole generation are gone. We have worked in South Africa and related countries on issues related to health and vaccine development, and a whole generation is gone. It is an extraordinary experience to recognize that you once had a scientific collaboration with outstanding individuals and find they have gone. It makes it extraordinarily real when you try to communicate with a colleague and find out that he or she is gone. So that for science and technology solving the problems associated with global infection are absolutely critical.

Now, the relationship between health and policy is an essential relationship. In many parts of the world governments are struggling with their budgets. We happen to be struggling ourselves. And we are worrying about the cost of antibiotics. And yet if you look around the world, the cost of antibiotics is in fact an overwhelming obstacle to the availability to treat large numbers of patients. What people often fail to understand is that we can deliver free antibiotics -- free antiretroviral -- to many parts of the world, and the infrastructure for delivering those drugs is not present. The distribution systems, the role of health professionals, many of whom incidentally in parts of the world have in fact been infected themselves by HIV. So that when the World Bank or the IMF or the State Department or any international organization looks at these issues, it can't be just about price; it also has to be about process, it has to be about delivery. And that means looking much more broadly than, Can I get a particular drug delivered at a particular price?

The policies that are carried out in order to be economical often are costly. It's one thing to invent a new drug to treat malaria. It's another to use it as a single drug therapy, because the possibilities of resistance when you use a single drug rise very rapidly. Those of you who followed the HIV epidemic know that in the early days there were substantial problems because we had effective agents, but patients became resistant very rapidly, because we were using one drug. Now we have triple therapy, and that has had an enormous difference. But governments, ministries in trying to save money, in many cases will introduce the newest drug one by one. That's a clear example of where understanding the science is critical to the policy.

For a long time economists have argued that economic development produced better health, and surely it does. Economic development that can produce roads or clean water, proper housing -- all of these improve health. But in the last decade or so, the evidence has accumulated that better health enhances economic development. If you don't have a healthy population, they don't work very effectively. And what's even more important, and I think more subtle in terms of its invidious effect, if you don't believe that you are likely to live a full life, than why should you spend a lot of time getting an education? Why should you spend a lot of time learning how to do science and technology? Why should you invest a huge amount of resources in structures, in infrastructure, whether they are irrigation ditches or bridges or road or universities, if you don't think you are going to live to the extent that you are going to benefit from those?

The culture and attitudes of societies where poor health reigns is dramatically impacted by that view, and it has negative effects in terms of economic development. So that the relationship between economics and health is clearly a two-way relationship, and it emphasizes again that in our international relationships we can't only look at the economics of what happens in the relationships between countries; we must also look at what happens in terms of their health.

Finally, it is clear that the spectrum of bio-terrorism has engaged us over the last several weeks in this country to an extraordinary extent. I say "spectrum" -- I would emphasize to you that a number of us who have been working in this area for a long time have predicted that the biological problem would not be a big catastrophic event of the kind that occurs with explosives or with the kinds of things that happened in New York, but rather they would be the kind of thing we are seeing; namely, if you will, low-impact events occurring in such a way that they scare the hell out of everybody. And what we are seeing with anthrax is a classic example of what we might see in terms of a number of other biological agents. And what have we learned from that? We've learned what we have been talking about for the last decade and a half is true: that effective responses to biological agents introduced by terrorists are essentially the same responses as made to any new and emerging infection. You have to have systems of surveillance, detection, rapid abilities to respond and abilities to recover. And in the discussions today I think you will find repeatedly that the public health model, which is of prevention, surveillance, response and recovery -- that model is central to much of what we do in infectious disease for all infectious diseases. And having that model in place and working effectively will be useful in every country, not only to deal with the usual and customary infections, but also to deal with bio-terrorism when it occurs.

This is not a meeting about bio-terrorism. This afternoon we will have some discussions about that. I hope in the morning what you will have is an opportunity to get a broader insight into a number of the truly important infections around the world, and you will see some figures which are astounding in terms of the millions of people who are affected by these other infections.

This is not to downgrade the importance of bio-terrorism. But I think in the course of the day the message should be clear that on an international scale, if we understand how to deal with infectious disease, including new and emerging infections and antibiotic resistance, we will have in place the best possible mechanisms for dealing with bio-terrorism. And the reality is that when the current wave of concern subsides, and it is, quote, "business as usual," only if we go back to a system in which the public health infrastructure is strong, the health professional infrastructure, the public education infrastructure is strong in dealing with new and emerging infections, we will be in a position to respond quickly if in fact there is another problem associated with bio-terrorism.

It's my privilege then to introduce our first speaker this morning. We will have presentations by each speakers with an opportunity for questions after each presentation. We will take one break in the morning. At lunch time you are invited across the street. For a variety of reasons, it turns out that the afternoon session is best held in the auditorium of the National Academy. But all you have to do is go across C Street. There will be box lunches available in the atrium there, so we will go across, have a box lunch, and reconvene at one o'clock in the auditorium of the National Academies. But our business here will begin with a presentation by John La Montagne. John La Montagne is deputy director of the National Institute of Allergy and Infectious Disease at the NIH. Originally we had planned that Tony Fauci would give this presentation. You may have noticed he has been busy lately. He is in my view clearly an extraordinarily articulate individual with regard to explaining the current dilemmas to the American public. But John is no slouch. (Laughter.) He has had a remarkable career. John started out working in the influenza program. He was director of the AIDS program. He is deputy of the institute which Tony is responsible for. And we have had the good fortune of working with John on many, many projects related to new and emerging infections. So it's my pleasure to introduce John La Montagne.

Dr. John R. La Montagne: Ken, thank you very much for those kind remarks.

Before I begin, I just wanted to repeat that Tony is very, very sorry that he could not make this presentation himself. These are issues that he feels very passionately about, and was actually looking forward to making this talk. But he is testifying in Congress this morning, and is just simply unable to come. So he wanted me to make sure that you understood that other business was calling him, and he needed to tend to that and sends his apologies for not being here.

Thank you again, Ken, and distinguished colleagues. The institute, the NIAID, which is one of the components of the National Institutes of Health, is the institute charged with responsibility in the area of infectious disease and immunology. If I could have the first slide, it gives you an idea of what I think motivates us at the institute in terms of our interest in global health research. And fundamentally we believe this is a very important issue for four reasons. There are of course the humanitarian concerns that we all have. We want to relieve pain and suffering to the extent that we can around the world. Domestic health problems are related in many ways to what happens overseas. There is a trend in the globalization of health problems, which I will describe in a little bit more detail with some of the examples I will cite later on. And also we recognize, as was pointed out by Dr. Neureiter and others, that there is a link between economic development and political stability and health. And we believe that improving health around the world will in fact improve political stability and hasten democratization and all of the issues that we feel are very, very important.

Let me just start off with the United States. This is a timeline of the last century, and it's interesting because it shows you the impact of a variety of different interventions on mortality over the last century. I should point out that the leading cause of death, if I remember correctly, in the 1900s in the United States was tuberculosis. You see early in the century chlorine was introduced as a method of purifying water. We had a major, major problem, as we all know in the early 20th century with the influenza pandemic which occurred in 1917 and 1918, and was the only significant alteration in what appears to be an inexorable downward trend in mortality over the last century. However, if you look towards the end of this timeline you will notice that the curve is starting to go up again, and this is almost certainly due, in the opinion of some, to the impact of HIV/AIDS on our population.

Now, historically also in the U.S. -- and the next slide shows you a quote from the U.S. surgeon general, William Stewart, in 1967, which was interesting because he proposed that in 1967 the war against infectious disease with the advent of antibiotics and the broad use of vaccines had been won essentially, and that we needed now to pay attention to other health issues which were of importance, such as chronic diseases.

But if you look at the statistics -- if I could have the next slide -- and this is a pie diagram which basically shows you what the leading causes of death globally are for -- leading causes of death around the world for individuals under 45 years of age. And you will notice that infectious diseases represents about half of that total; injuries about a fifth of it; and non-communicable diseases again about a fifth.

The next pie diagram shows you an even more disturbing statistic, which is the impact of death on individuals under five years of age, where almost two thirds of the deaths that occur in this population are attributable to infectious diseases, truly an enormous and difficult problem.

Now, it isn't just simply mortality that affects individuals. Mortality isn't just one of the outcomes. If you look at the next slide you can see that in terms of disability adjusted life years, a measure of long-term impact of these problems on individuals who survive, infectious and parasitic diseases probably account for 30 percent of the total global burden of disability-adjusted life years -- a very, very impressive statistic.

Now, it has also become apparent -- from the next slide this shows you another important recent -- relatively recent -- discovery in the area of infectious diseases, and that is that many infectious diseases are actually causes of other problems, particularly malignancies. This slide illustrates that about one out of every six cancers around the world is probably attributable -- and this number may actually be increasing as we learn more and more about these problems -- to infectious agents, the leading ones being papilloma hepatitis viruses and the helicobacter pylori. Where stomach cancers are attributable to helicobacter, liver cancers primary hepatital cellular carcinoma is a very, very common complication of hepatitis B infection. And human papilloma virus, which is a very, very common problem, leading cancer of women around the world, which is cervical cancer. So we can appreciate that infectious diseases have not only an acute impact on the population, as I illustrated with that timeline of events in the United States, but also there is a longer-term burden which is associated with cancer. In the hepatitis B area, I should point out that it has now been documented or demonstrated in some populations that the use of the hepatitis B vaccine actually reduces the rate of hepatital cellular carcinoma in populations at risk.

But my task is really to talk about emerging and reemerging infectious diseases, and to focus on this problem to try to illustrate for you the impact of the three major ones, but also to try to describe for you two things. One is the variety and diversity of these problems as they are emerging; and, second, to try to give you a sense of how important we believe these are in the context of international activities.

We have used the definition that the Institute of Medicine applied for emerging infectious diseases, which is shown for you on this slide. And in that outstanding report that they produced, I think -- Ken, isn't it true that that was probably the most popular-selling report that you guys had produced in a long time? That identified seven causes of emergence, and they are listed for you on this slide. Certain human demographics and behavior represent one significant factor. Technology and industry also is an important factor in the emergence of infection. Economic development and land use is a third factor. We all know about international travel and commerce. Dr. Shine gave you an anecdote about the impact that malaria has or cholera in that particular instance. Microbial adaptation and change is one that we appreciate more and more every day, and this is a real factor in the lifestyle of microbes, and we need to appreciate and deal with it. Also, importantly, it is the fact that public health is not often given the emphasis that it requires to maintain the vigilant stance that is required to keep infectious diseases under control. And there are ecologic and other environmental factors that contribute to the emergence of these infections.

On the next slide we have shown you -- I am projecting a map of the world which is incomplete, and I will admit that it's incomplete. But it gives you an idea of where emerging infectious diseases have appeared over the last 10 years actually -- 10, 15 years. And you can see that there is no -- these are occurring around the world. It is not something that occurs only in Africa or only in South America or only in Asia. We have quite a few of them occurring in the United States. Lyme disease, for example, is something that basically erupted in our own back yard. Hepatitis C is another problem that has emerged over the last year. The hantavirus infections, Ebola which occurred in Africa, the nipah and Hindra viruses which are currently causing us to examine them in closer detail in Southeast Asia, and the H5N 1 avian influenza epidemic that occurred in -- or outbreak that occurred in Hong Kong three years ago.

But let me begin by talking about HIV/AIDS. And I am going to have to go through these very, very quickly, and I hope you'll understand. This is a dated slide. It's 1999, but I think the impact is sadly not much changed since that time. And one can appreciate from this that HIV/AIDS, a truly emerging infectious disease, has emerged and is now a tremendous cause of death and disease around the world, particularly in Africa where it has caused significant problems and is now moving into Southeast Asia. But truly it is affecting all countries around the world. I would just illustrated the rapidity with which this happened in sub-Saharan Africa. And you can see that in a very, very short period of time the infection rates and the disease rates associated with HIV and AIDS have expanded broadly in the region. And this is a source of very much concern for the world as a whole.

Tuberculosis is an ancient adversary. It's been in the human population for many, many hundreds of years. And, as I mentioned, in the United States was if, not the leading cause of death at the beginning of the 20th century, certainly one of them. Nonetheless, in the United States we tend to believe that tuberculosis is not a real big problem. Well, it is. We still have about 18,000 new cases a year. We have probably 10 or 15 million people that are currently infected that could reactivate -- about 10 percent of those I believe reactivate or can reactivate per year -- not 10 percent, but 10 percent of the 15 million through their lifetime will reactivate, I believe is the proper way of expressing that.

But globally the impact of tuberculosis is enormous. There are perhaps two billion people -- that's 30 to 40 percent of the population of the earth is infected. There are eight million new cases each year. There are perhaps two million deaths each year. Tuberculosis is a leading cause of death associated with HIV infection in sub-Saharan Africa and in Asia where these background infections are quite prevalent.

The therapy for tuberculosis is a long therapy. Six months of drugs therapy may be required. And drug-resistant strains are spreading, so that the tools we have to control this infection are being limited by drug resistance. There is a vaccine which is widely used around the world. It is effective in preventing disseminated tuberculosis in children, but is not very effective, if it is effective at all, against pulmonary TB, and it is not recommended for use in the United States.

Now, as I mentioned just a moment ago, HIV and TB are related. It is probably the leading cause of death among HIV-infected individuals. Tuberculosis is more aggressive in these people, sadly, because of their weakened immune state. So it is probably responsible for up to a third of all the cases -- all the deaths that occur in HIV-infected individuals.

And this active TB which occurs in these individuals may actually spread to non-HIV-infected persons.

Now, the NIH in collaboration with our colleagues at the Centers for Disease Control and Prevention and the Food and Drug Administration and our colleagues in academia have been working hard to try to develop new and more effective vaccines for tuberculosis, and we have launched into a 20-year program to try to do this. It's going to engage the skills of all of the individuals listed on this slide and many, many more for this to happen. And I am pleased to report that I think this interaction is a very, very positive one, particularly with our colleagues at USAID and in other groups that are interested in international health issues.

Malaria, the third of the large problems that I want to talk to you briefly about, and then go on to a description of some of the other emerging diseases that are affecting us. Malaria is truly an enormous problem. As this slide shows, about every 20 seconds to 30 seconds, a child dies of malaria. There may be half a billion people infected with the disease, and the death estimates. There are one and a half to 2.7 deaths annually, but that may be an underestimate. Malaria is distributed, as you can see, broadly around the equator around the world. But many people may not appreciate the fact that in the United States we have the vectors right there. Malaria used to be transmitted quite readily in this location where we are speaking right now. There was a warning that I saw, a poster issued by the New York City police department in 1904 warning people not to walk around Central Park because of the risk of malaria during the summer.

So the vectors for this, the mosquito vector for this diseases exists broadly around the world, and there is the capacity or potential at least that this problem could become bigger. And in fact we are starting to see some evidence of that, not only in the sense of multiple drug-resistant parasites and insecticide-resistant vectors, but also in the spread of the disease particularly into central and southern North America, Mexico in particular. So we have a tremendous problem ahead with malaria.

Now, it has a very large economic impact. It's expected to be -- it was expected in the year 2000 to be greater than $3.5 billion. The cost of malaria in terms of productivity is really hard to underestimate, because it impacts so broadly in the population, particularly in Africa. But if you are facing a problem in which 20 to 40 percent of all of your out-patient visits are due to malaria, and 15 percent of inpatient visits might be due to malaria, which is a common descriptor of malaria in sub-Saharan Africa, you can appreciate readily that this is a problem that is of tremendous proportions.

It is also a deterrent to tourism, foreign trade, international activities of all sorts. And just to remind you about the impact of malaria in the United States, we recently had a couple of cases in a boys camp in New York in which some children acquired malaria, having never left the United States.

But our problems aren't limited just to malaria, tuberculosis, HIV. There are others that are also concerning us. And let me go through some of these quickly. Dengue Fever is one of them. This is a disease transmitted by mosquitoes, a viral infection that is spreading inexorably and seemingly rapidly around the equatorial belt and into the temperate zones where the mosquitoes exist. And you can see from this chart, this histogram, that the average number of cases has increased dramatically since the 1950s.

Now, dengue in the United States, just to show you that we need to add now another arrow to this map. Recently there has been sustained transmission of dengue in the Hawaiian Islands, where the Island of Maui and Oahu have both experienced significant dengue outbreaks.

Influenza, my own nemesis, and the reason that I came to the NIH in 1976 at the time of the famous swine flu program, is a persistent and consistent and difficult adversary. This slide basically just shows you some recent scientific information about this problem, because there's been a lot of interest in trying to identify the reasons for the high virulence of the pandemic of 1918. And part of this has been a retrospective look at genes recovered from autopsy specimens and other sources to try to determine through genetic sequencing what might be the properties associated with this virus that made it such a difficult and virulent agent. But we have had some recent examples that are worthy of note. And let me spend just a minute or two on the Asian flu outbreak which occurred in Hong Kong in 1999. This was an outbreak of a virus that was a pathogen of chickens and other domesticated birds. Its source was probably from migratory birds that were in the region. It caused about 40 cases I believe in Hong Kong, with a fairly high mortality rate of about 20 percent. There were some concerns that as this virus transmitted within the human population it would acquire the properties that would make it truly transmissible more easily within the human population and cause perhaps a full epidemic of this disease. And I think it is to the great and everlasting credit of the Hong Kong health department that they took the significant step of basically eliminating the source of the infection by killing the birds that were infected in that municipality. And I think we really do owe them a tremendous debt of gratitude. But it was an effort that required a lot of collaborative research activities, and this slide basically illustrates the fact that we work closely with the CDC and with FDA and USDA on all of these issues.

West Nile virus -- something that has been in the news lately in the United States, although it seemed to have vanished from notice. But we are still paying attention to it. It was introduced in the U.S. in 1999. The virus is very rapidly spread throughout the Eastern part of the United States, and as of early September was as far west as Indiana and as far south and west as Louisiana and Florida. It is causing significant problems in horses, where the mortality rate is quite high. But we have the vector to transmit this virus is quite present in the United States, and there is no reason to expect that it will be contained any time soon.

I mentioned nipah earlier, and I this is a virus that has emerged in Southeast Asia. There was a recent report of additional cases due to this virus apparently in Northeast India, but it emerged in Malaysia, and it is quite an interesting perimysial virus. It is related in many ways to and very similar to viruses such as the measles virus, so it apparently has the capacity to spread quite rapidly into humans. It is probably a bat virus that somehow got into pigs in the region, and from pigs into humans. It causes encephalitis, and has a high mortality rate.

Bacterial agents have not been immune from this reemergence phenomenon, and this story out of UPI last year basically illustrates the problem that we have had with one Escherichia coli strain, 0157, whose spread has been rapidly facilitated by I think changes in the way people prepare and consume food. These bacteria are quite interesting. They do cause a serious problem, particularly in children, and they can be associated with significant long-term morbidity and mortality. There was a very large outbreak of this in Japan in 1995.

I think you can skip the next slide. And let me talk about some of the problems that are perhaps more contemporary in our interests, and that is the concern over bio-terrorist release of an agent and the attendant problems that might cause. These are some now ancient but rather prescient headlines. We have been working on this problem for a long time. It's not something that has been new. We have focused our efforts on the three agents that you see listed on the left-hand part of the slide. We have been focusing particularly in the area of vaccines, anti-microbial research, genomics and diagnostic development.

Now, I want to get into anti-microbial drug resistance as the next area of emergence. And I apologize again for going through this very quickly, but I am trying to cover a lot of territory here. There are significant human pathogens with significant antibiotic resistance. This slide lists five of them, but there are many others that we could talk about. Some on typhi, the cause of typhoid fever, and dysentery is another one.

But we have been trying to develop programs, research efforts and programs to try to address this problem more systematically. And we think it is a four-pronged approach that is required. We need to have good surveillance, we need to promote the rationale use of antimicrobials, and we need to have effective infection control programs. But we also need to have an assertive and aggressive, basic and applied research program that looks at microbial pathogenesis, that looks at improving diagnosis, that does develop vaccines, because vaccines are an effective way of eliminating antimicrobial resistance, and that identifies new drugs and novel therapeutic targets.

The next slide shows you the three accepted targets that currently are being used for antimicrobial drug development. Most of the drugs that are -- in fact, I think almost all of them -- currently fit into one of these three categories. That is, drugs that inhibit the synthesis of the cell wall, those that affect the synthesis of proteins, and those that affect DNA replications and repair.

We have, however, learned through our microbial genomic sequencing activities that there are likely other targets that could be very effective for inhibiting essential activities of microbes. So I think that the genomic revolution, which is hitting not just the research on humans, but also the microbiological world, will reveal many, many new avenues of intervention.

I mentioned vaccine research, because I think that vaccines offer the best solution to the anti-microbial resistance problem. By preventing the disease, you prevent the use of the anti-microbial agent. And we have been I think fortunate over the last 20 years to have developed some very, very effective and new vaccines that are eliminating many or mitigating this problem to some extent.

Let me mention some of this just quickly. These are four vaccines that have been developed by in large part not just by the NIAID -- we played a significant role in this -- but we worked with our partners in academia and the private sector and the public health community to get this done. For hepatitis B, haemophilus influenza type B meningitis, cellular pertussis and the pneumococcal conjugate vaccine we worked very closely with the U.S. Agency for International Development in getting the first pneumococcal conjugate developed, a seven-valiant vaccine. These vaccines have enormous potential to prevent deaths and diseases and disability around the world.

Let me illustrate that with just haemophilus influenza. For many of those not familiar with this disease, this bacterium causes meningitis. It was the leading cause of bacterial meningitis in the United States up until about 1985 or so, when these vaccines started to be introduced and used in the United States. And about 40 percent of the isolates at the time I believe were resistant to ampicillin, the standard of therapy. The vaccine has been extremely effective -- not only in the United States, which you can see in the bottom left-hand panel, but around the world. The wide deployment of this vaccine by the Pan American Health Organization in the Americas has almost eliminated this disease as a problem in this continent. And I think it illustrates the tremendous power that vaccines have to improve the life and health of the population.

I have a couple of slides on microbial genomics, but I think I have talked about this enough, so let me just skip, because I am running out of time here just very briefly to indicate to you that we believe that through the use of microbial genomics we can expand greatly our ability to develop vaccines and therapeutics and diagnostic tests. And we are working quite diligently to try to improve the information around the world in terms of the genomic sequences of important microbial organisms.

This slide illustrates some of the organisms that we have sequenced, but the list is now much longer. This slide is dated. Now over 20 bacteria have been sequenced. And this cartoon basically illustrates how we believe this can be applied. The pace at which this is occurring is actually breath-taking. You can now sequence bacteria, genomic sequences which may be as large as five million bases of nucleotides in as little as a week's time. So this is becoming a technology that is not only fast, but very accurate, and gives incredibly important information that can be useful to the research and public health communities as they try to address these problems.

Now, all of that being said gives you a sense of the impact that infectious diseases have on the health of communities around the world. Why then is infectious disease a concern in terms of the social and economic development around the world? Well, that's a question that I think many of us would answer by saying that controlling these infections will improve the health of the people in those communities, and will improve their prospects for development and to live the kinds of lives that are free of distress and disease.

There have been many reports the Institute of Medicine has issued. The Institute of Medicine in 1997 issued a report on America's vital interest in global health, a view that we certainly believe is important. Two years ago there was an intelligence estimate that the global infectious disease threat and its implications for the United States -- this is a very widely read document and quite interesting that it does describe the kinds of impacts that these infectious diseases can have around the world. We have seen this more recently with HIV/AIDS, where many have been concerned about the impact that AIDS is having in its uncontrolled spread around the world, and whether or not this infection can in fact lead to destabilizing politically countries where the infection is out of control.

This is one of the reasons why we believe that in the next century, this century, the 21st century, the life sciences will play a dominant role in interactions among countries -- not only because of our joint concern for improving global health, but because we are increasingly interdependent economically, and because none of this can happen in an arena in which political instability is occurring. So we need to strengthen our efforts, keep our momentum sustained, go into a lot of partnerships around the world, and we try to do that very much as frequently as we can. We have developed very positive interactions with colleagues around the world -- in Africa, in Asia, in Europe, South America, to try to deal with these problems. We do believe that their solution is going to require a comprehensive approach. It's not simply research; it's research in connection with prevention efforts, with development efforts of all types, with education and other activities. They are all interdigitated and will be required. But we believe, as was mentioned earlier by Dr. Shine on the importance of building research capacity and health care infrastructures around the world. This is going to be the way in which the modern miracles that are coming out of the research engine that exists in biomedical science will be deployed and implemented. And in order to do that I think we need to try to get over what Jeff Sachs calls the technology divide, where there is an increasing concern that some regions of the world are being left behind in their ability to exploit this rapidly-developing revolution not only in biomedical research but in communications and in other areas of everyday life. Global health is an interconnected problem is a problem for all of us, and I think we welcome very much this meeting and this forum for the discussion of this very, very important topic. So thank you. (Applause.)

Dr. Kenneth Shine: We have got a few moments for some questions, if anyone wants to raise any issues for John. I should emphasize to you that one of the things that we hope will come out of this meeting will be an opportunity for you to identify places for getting additional information, so that you can get timely, specific information. NIAID and John and his colleagues are a good example. Over here please.


Question:
I am with the Mariah Fund. And I wanted to ask you, given the many things you have said about the dangers of communicable diseases, and particularly the scourge of AIDS, why it is that more emphasis is not being put on research to develop a woman-controlled agent to protect against the spread of HIV, such as microbicides that are being researched. But it's very, very difficult to get the attention. I have been to many sessions on AIDS, and the idea isn't even mentioned. And yet women are the fastest-growing newly-affected populations in Africa who are contracting the disease.

Dr. La Montagne: That's an excellent question, and I must say that it is an area that we have been quite concerned about and are trying to support as much as we can.

The technical problems associated with the development of topical microbicides for that use are significant, however. And I think that that's kind of where the problem is currently. The NIAID spends $20 to 30 million a year in this area alone. But I think it's going to require some conceptual breakthroughs in terms of not only the agents themselves, because the I think the program has been bedeviled by the fact that people are trying to apply topical antiseptic agents, some of which are quite irritating, for general and repeated use in areas where irritation, as we have learned in the area of HIV/AIDS, can be quite problematic and in fact enhance infectivity, not reduce it. So I think we have a tremendous challenge, and I can assure you that we are trying to do as much as we can.

Dr. Shine: I would just make a couple of observations. First, we talked generally about problems with the infrastructure for public health. In my view the erosion of mosquito abatement programs in many parts of the country have in fact provided the opportunity for agents like West Nile to become problems. And at a time when we all felt safe it was felt that it was not necessarily worthwhile spending money on mosquito abatement. But we learned the hard way that we can't do that.

Moreover, in many parts of the world, and certainly where malaria is endemic, the single most useful preventative intervention we have short of a vaccine again has to do with mosquito control and protecting people from mosquitoes. So these things are very closely related to very common kinds of issues in the public health.

John gave you an example of e. coli. That epidemic had to do with the failure of the water supply and the failure to protect the water supply. And again, to the extent that we stop paying attention to water supplies throughout the world invariably it produces some kind of a problem.

I think the other point that needs to be emphasized is in the 21st century we still have a problem with sex. Sex bothers us. The notion of sexually-transmitted diseases, of acknowledging the importance of sexual transmission, whether it's heterosexual or homosexual or whatever, is very painful. And if you look around the world, the capacity to deal with HIV has often been confounded by the difficulty we have of recognizing that sex has got something to do with it, and that you don't need to be embarrassed about it; that in fact one needs to be able to address that in a formative way. And by sex I mean in the broadest sense. And I think the question that was raised about HIV microbicides is central to another major issue which has to do with health. In most parts of the world women are in fact the principal health givers -- they are in this country, as well as in other parts of the world. Moreover, in terms of sexually-transmitted diseases, they are in fact the individuals who are often put in dependent situations with loss of control of the circumstances in which even protected sex can take place.

So the institute did a study several years ago called "In Her Lifetime," which was the life cycle of women in Africa. And our principal message was that a major public health strategy is the education of, the empowerment of women, particularly in parts of the world in which health problems are a major issue.

In India there are some very interesting experiments going on, supported by a private foundation, in which they have put terminals to connect to the Internet in isolated villages. The requirement to get the computers is you have to in the village create a room which will be effective for housing those computers, and you have to provide people who will use the computers. Most of the people who use the computers are the women in the village. The top priority for the use of the computer is about weather and market prices for crops. The second highest use is women's health and pediatric health. So there is a huge untapped opportunity to get information to people around the world. And I think we have to focus particularly on the importance of women in this regard.

Any other -- one last question, or otherwise we will move on. John, thank you very much.

And now it's my privilege to introduce Barry Bloom. Barry R. Bloom, PhD, is the dean of the faculty and professor of immunology and infectious disease at the Harvard School of Public Health. He is a truly extraordinary individual. He is a fundamental scientist. He was a Hughes investigator. And not too often do they take those people out of the laboratory and make them deans. As a matter of fact, however, he has combined his basic laboratory interest with an extraordinary contribution in international health, chairing World Health Organization committees working on WHO/ UNAIDS vaccine advisory committee and on the national AIDS Vaccine Research Committee. He is certainly a person for all years and all problems, and we are looking forward to his comments about some of the broader implications of infectious disease, particularly in the political and economic environment. Barry?

Dr. Bloom: It's a tremendous privilege for me to be able to address a group like this. I share John La Montagne's view that if the last century was the century of physics, between the genome and anthrax in a very short time, we have to really think of the impact of biology health demands in poor countries, and put them in a quite different context than we have ever had before.

I presume they really tried to get a real economist to do this, and they were smart enough not to do so. So I am not averse to risk, and here we go.

If I have the first slide, I would like to talk about three things really -- something about the global burden of disease, some of which you have heard from John; something about the economics of the diseases, and something about the intervention, and then get the privilege in this audience of making some suggestions about policies, some of which are imminent, some of which are long-term needs.

Next slide please. As I understand it, the impacts of diseases on economics can be reduced to three very general categories. One is the reduction in life expectancy and productivity due to early death or chronic illness. And as simple as that sounds, that is the most profound impact in terms of power to effect the economy.

The second are more indirect effects to business infrastructure investment, social cooperation, and ultimately political stability. And finally there's the impact on parental investments in children and the future, what Gary Becker the economist called the "quantity-quality takeoff." Next slide please. And that's illustrated by something you all know, but the closeness of that curve is quite impressive with infant mortality on the bottom axis and fertility rates. The paradoxical fact is that the higher the infant mortality, the more kids people have, and can't take care of and can't provide educations for, which leads to a vicious long-term cycle of increased poverty.

Next slide please. There are a couple of metrics. Up until 1995-1994, WHO would only count mortality as a measure of health, because it was the only thing one could get reasonably accurate numbers for. There's a lot of impact on the economy from disabling conditions and diseases, and that led to the development actually at my School of Public Health by Chris Murray of a metric called Disability Adjusted Life Years, which figures in years of healthy life loss to a variety of disabilities, added to a total period of life loss to premature death. And from that one can come up with very crude figures, which economists are now trying to do, by multiplying the years of life loss and what that implies, times the per capita income or a multiple thereof, in terms of productivity to get an assessment of the aggregate economic loss caused by any one disease.

You are going to see some numbers that I think the most interesting fact of which is they will disagree at almost every level with John La Montagne's numbers. And the reason is not that his are better or mine are better. It's one of the great lacks or paucities for policy planning or economics is we don't have data particularly from developing countries on the actual numbers of disease burdens and lots of other things that I will mention.

But, nonetheless, if I could go back to that slide please. It's two general point on the value of life to an economy. And I cite a not-yet-published WHO macroeconomics report that brought seven working groups, a slew of economists from around the world, to begin to start to look at what you need to estimate the values of investments in health in straight economic terms. That every 10 percent increase in life expectancy at birth is associated in countries with about a 0.3 to 0.4 percent per year annual growth. The average growth of an ordinary country, is about 2.3 percent annually. It can go up or down depending on the economics of the world at that time. These are very significant contributions. And the difference in annual growth accounted for by life expectancy, if you just do that difference between a rich and a developing country, it would be about 1.6 percent, which is huge, so that if one could really extend life and productivity there would be tremendous economic gains. Next please. Thank you.

So let's look at the burden of infectious diseases, but in a context. And it's a context in which a billion people live on less than a dollar a day, in which 44 poor countries with a per capita income of less than $500 a year have an average health expenditure of about $12 per person per year, and none of them comes anywhere close to 5 percent of GDP able to be spent on health. In that context, a third of all causes of death in the world is due to infectious diseases; almost half, 41 percent, of the burden of disease, the lost years of life plus death, is infectious diseases. But if you look at Africa and Asia, it's 68 percent of deaths and 37 percent of deaths in Southeast Asia, and the burdens would be proportionately higher in terms of healthy years of life lost.

And again the data are very weak, so we do the best we can with the data that are available.

Next slide please. Starting with tuberculosis, which is the disease I work on, it's huge. It's 8.4 million cases worldwide; 2 million deaths -- 98 percent of those are in developing countries. And 80 percent, which gives us some focus for targeting programs -- are in 23 high-burden countries. A third of patients in consecutive autopsies in Africa the cause of death, attributable cause of death in a third of AIDS patients has been TB. And, as you will see, multi-drug resistant TB is emerging and is present now, according to WHO, in 72 countries.

Next slide please. These are the top 23 countries that really need to do better for TB, and there are a variety of reasons. WHO has recommended a program of DOTS -- directly-observed therapy with short-course chemotherapy. We have some countries, like Mozambique, that don't do anything; others in the second list that are trying to do something and have a very poor treatment outcome, and probably because they are not using Directly-Observed Treatment, where people know that others -- village workers watch people take the pills. Then we have other countries that do have DOTS, but they do it poorly. Amazingly enough, Brazil and India where the case detection rates are so low that even if they do good treatment, it has negligible impact. And then you see the remaining countries. They move up and down the list. But the bottom line is that the cure rate should be 80 percent or higher, and the detection rate should be 70 percent or higher if we are going to make a dent.

Next slide please. TB and AIDS no longer exist as independent separable biomedical problems. The overlap, particularly in Africa, and increasing in Asia, is tremendous. This is the number of people with tuberculosis in Malawi, Zambia, South Africa, Uganda and Ivory Coast who are also HIV-positive. It is in essence the signal disease that tips off people there is an immunodeficiency, and that leads to the reactivation of TB.

Next slide please. These are figures from WHO, which say that ostensibly 60 countries say they are doing Directly-Observed Treatment, but in fact they are reaching only 23 percent of infected cases. That's not an adequate amount of supervised treatment to be sure that we are going to have an impact. The average cure rate is in fact 80 percent under DOTS, and in the rest of the world is 60 percent. And there's a great adage in the field of TB: There's only one thing worse than no TB program, and that's a bad TB program, because that's where drug resistance and chronic carriers come from that causes a lot of trouble.

Next slide please. MDR-TB, multi-drug resistant TB, resistant to the two major drugs, very difficult to treat, costs in the U.S. for MDR is a quarter of a million dollars per patient, and the cure rates even here are not terribly high.

If you look at where this is emerging, it's Estonia, it's China, it's Russia, it's Peru -- everywhere where there is a bad TB program with access to drugs -- will have increasing drug resistance. That is moving across from Eastern Europe to Western Europe, Netherlands, Denmark have increases in MDR. And it will come here unless something is done.

Next slide, please. One of the things when I said we don't have data that would be very important for policy and economic projections would be what would happen if we had a vaccine, if we had a better set of drugs that worked in one month and not six months? Almost impossible to get data like that, or even scientists to speculate on that for the big diseases. This is an old model, done again by Chris Murray, who is now at WHO. And basically it says that if we do what we are doing now at the same rate we are doing it for TB in the blue line, it is going to take one very long time to make a dent in the epidemiology of this disease. If we had in red a drug combination that would only have to be given one month, where compliance would be high, cost for treatment low, you would have a very significant short-term effect. And in the purple, if you had a vaccine that was even 50 percent effective, in the long run you would have a profound effect, but it would take 15 years till it took the new cohort of kids that were going to become susceptible and protect them, so you would have a big lag on the outcome.

Next slide please. The economics as I understand it for TB come out to be very straightforward. For about eight-point-some million people who are sick from TB, there's a loss of 30 percent income. There are two million deaths. Cost of treatment is about $4 billion dollars. Total cost of TB annually is on the order of $16 billion. WHO estimates that to reduce by 50 percent the number of deaths from tuberculosis would cost about $900 million a year. And if one did this for a decade, the return on that investment of $9 billion would be 22 million cures, 16 million deaths averted, and a net economic return of $6 billion. This turns out to be a remarkably good investment. And if we had better tools that worked for shorter times, or a vaccine, there would be greater returns and less investment.

Next slide, please. You've heard about malaria. It's very hard to know what the actual data are on incidence of malaria -- somewhere between four and nine hundred million febrile infections -- a relatively low death rate, a high burden of illness rate. But we do know that of the death rate, about three quarters of that is in African children. Only 20 percent of these patients come to the attention of the health care system. Pregnant women are at high risk of dying, and they are at high risk of giving low birth weight birth kids. Children are shown now to have cognitive damage and anemia in all the people which has a big impact not measurable yet on productivity. And what we do know is that at least in places like Kenya families can spend up to 25 percent of disposable income on drugs for treatment, most of which drugs are absolutely totally useless. And so when we say there's no markets in a developing country, that is in a sense true. But if the little markets that were there went to drugs that were effective, they would spend no less and would get much greater health benefit.

Next slide, please. Ah, you are going to have trouble seeing that slide. (Laughter.) No, it's coming. It took 40 years before malaria became resistant to quinine, 16 years to become resistant to chloroquine, six years to fansidar, four years to mefloquine and six months to -- there is it -- atavoquone. Not only is there resistance to almost all the drugs available for malaria, but it's increasing at a rate, particularly in the Thai-Cambodia Golden Triangle region, that we can't keep up with. And there are virtually no major drug companies that find enough return to invest in malaria drugs. Very serious problem.

Next slide, please. There are treatments. They are not terrific, but they have a big impact. And as Ken mentioned, there is the potential for impregnated bed nets. Spraying is more expensive. Chemoprophylaxis for kids with rather inexpensive drugs and case management. The fact of the matter is these are very cheap interventions to save a life. They are too high a cost for most very poor countries to implement, and that's a global problem.

Next slide, please. If we look at the burden -- Jeff Sachs has done this comparison -- these are associations, not predictions. If you look at the countries that had high incidence of malaria, their income levels turn out to be only a third of those without malaria. Thirty-one countries with intense malaria grew at 1.3 percent less per year than those without. If you just take the aggregate loss, it's $73 billion. And that's greater than 15 percent for 25 countries of their entire GDP over a period of 15 years.

What it says is if there were only a 10 percent reduction in malaria, countries would have a 0.3 percent higher growth rate. And, as you know, it isn't just malaria, it's malaria in a geologic, in a geographic, in a climatic context that makes it possible. But, nonetheless, these interventions would have a very significant impact on growth of many of the poorest countries.

Next slide, please. AIDS you have heard about before. My numbers are again a little different than John's, but they are all horrible, and they are getting worse.

Next slide, please. The distribution you have seen before.

Next slide, please. The worrisome part of this curve is the red line -- besides the fact that we know in Africa, in sub-Saharan Africa, the rates have gone up staggeringly high. But mercifully they appear to be tapering off. But the epidemic is beginning now in South and Southeast Asia. Nobody really knows. I could not find a single epidemiologic modeler who would present -- allow me to present a model that they believe we have enough data. When testing for HIV seroprevalence in sub-Saharan Africa is only 11 percent, these would be just wild guesses. And yet there's no greater urgency for data for decision-making than to know how this epidemic will evolve.

Next slide, please. There are success stories. Brazil, we had a meeting at Harvard about two weeks ago -- quite staggeringly impressive results. Since 1997 when they put in chemotherapy, antiretroviral therapy for HIV, mortality dropped by 50 percent -- prevalence over what was predicted dropped by 50 percent. Opportunistic infections dropped by 70 percent. Economically, most importantly, hospitalizations dropped by 80 percent. Drug costs dropped by 50 percent. And in that four-year period there was a net saving of $700 million. Now, there is a peculiarly important number on this chart, and that's the second one. The GDP per capita in Brazil is $6,625. They had the money to make it a national commitment to buy antiretroviral. They had eight companies that produced them, and the government gives them out free to the people who need them when they are symptomatic, which is 100,000 a year.

Next slide, please. If you look at success stories in Africa that I am aware of, and in Asia, Thailand, Uganda and Senegal, there are some keys. One is the support of the government -- the commitment of the prime minister as head of the national committee, high condom use among the highest risk groups, which is where you have to target programs,; extensive media campaign; involvement of universities; and prevention even in primary schools. These are characteristics of places that have made a dent.

Next slide please. This is an important slide, and a shocking slide, as you will see momentarily. The purple line is the projection given the rates of spread of HIV predicted by a very good epidemiological modeling group in Thailand had there been no intervention or change in behavior. The yellow line were the actual data in Thailand. So that starting at the beginning of the epidemic with a massive national effort and huge amount of money from internal sources, they changed the course of the epidemic in an unbelievably dramatic way.

Next slide, please. From those data, for example, as condom use goes up, HIV cases as a surrogate for HIV short-term goes down very dramatically.

Next slide please. I would ask you only to look at the bottom part, because what you see is Thai data in the top curve, showing a precipitous drop in incidence, the new cases per year. But the staggering thing is for every case that you had they will persist, they will be potential transmitters, and they will hang on as prevalence. You can drop incidence -- there's a very long lag before you drop prevalence.

Next slide, please. And what that says is even in a country like Thailand, which has done terrifically, if they drop their guard, if condom use drops from 85 to 60 percent, the epidemic will take off again. That's again a modeling study by the working group in Thailand.

Next slide, please. I focused -- and I focus here -- on the need to start interventions early. What we learned from Thailand and the other countries is if there is an effort made very early, the impact can be attenuated. These are data on Thailand and South Africa, and what you will see is between 1990 and '91, the prevalence rates were almost identical. Next slide, please. But in Thailand there was a massive effort to do this. In South Africa there really was not. And you will hear from William Makgoba, and I hope he proves me wrong on that, but the fact of the matter is the economics are different, the cultures are different, the biology, the viruses are different. Nonetheless, what it says is that if you get in early you have a fighting chance, and if you don't it's much harder.

Next slide please. That tells us that there are risks out there we should be thinking about. And as I look at the data on Africa, as certainly my school did, we felt that Nigeria, with 113 million people but a national rate that is low is a place that ought to have investments to do prevention, because the numbers are low enough. One could have a really good impact like Thailand, Uganda and Senegal. And if it does get out of hand, as it is in Botswana, we really don't know yet how to make that turn around. So I just point that out as the kind of predictions that the epidemiology can make for policy and priorities.

Next slide, please. My colleagues at BU and the Center for International Health have, I think supported by USAID, done some important studies in companies to look at the economic cost and benefit to investing in AIDS treatment in companies. This is in South Africa, the different kinds of companies that they've looked at. The assumptions are reasonable. They start at treatment at seven years. The survival time with treatment is extended by five years. Treatment begins in year six for the males at most risk.

And the bottom line is two things. First of all the returns are good. For the cost of $600 a year per treatment, there are tremendously strong returns, as you see. But they are not equally distributed across the work force. There's a greater return obviously for high-level managers for most companies than for unskilled laborers and workers, which in some cases could have a negative economic value. When we think of treatment, we have to think of the equity issues involved and the disincentives to treating everybody. And this is one example of that, and the first that I am aware of.

Next slide, please. What would happen if we had a vaccine. I couldn't get anybody truly to model it. There's a recent abstract that says that a 50 percent effective vaccine -- and I think on the first couple rounds it would be unrealistic to expect greater than that -- one could still have with very high coverage a very major impact on HIV infections and prevalence. With a poor vaccine and reasonable coverage you would still have an impact.

In another study in 1995 one of the great epidemiological modelers asked the question, What do you have to do to get R0 less than one? R0 is the so-called reproductive rate. It's how many secondary cases come from a single index case. And if it becomes less than one, sooner or later the epidemic will die out. That's the number we have to shoot for from a public health point of view. And his calculation is that if one had a 75 percent vaccine with even 50 percent coverage, one would be able to turn the course of the epidemic. The higher the coverage, the more the effectiveness, the more rapidly that would occur. But it is not impossible, even without a perfect vaccine, a non-measles-polio 99 percent efficacy vaccine one could have a huge impact.

Next slide, please. The economic burden as calculated by WHO is that there are about in sub-Saharan Africa 72 million disability adjusted life years lost. If you take a death at about 34 life years, because people die so young, and a DALY is valued at just the per capita income, it would be about a 12 percent gain in GDP, or put it this way -- an aggregate loss for that number of people afflicted of that amount. And if you do it as economists would do it in the U.S., you would value a life as about three times the per capita annual income, then that turns out to be a giant percentage of the GDP loss that is going to occur in Africa.

Next slide, please. Another way of calculating independently -- David Bloom is an economist at our place who has reanalyzed the Thai data, and it comes out with rough ranges such that if you can look at returns on the preventions made by Thailand, if the benefits include only averting medical expenses, the gain is about 12 to 33 percent. If, too, you throw in income losses, it goes up to 37 to 55 percent. And if you put in a statistical life -- that is, all of the economic value from an individual who is saved for that length of time, almost a half a lifetime, the returns are staggeringly high. No other investments that I know of would you do very much better than that.

Next slide, please. As Ken mentioned, the model we have traditionally worked under is that the market will take care of health; economic growth implies good health. We know only looking at prevention and public health in this country people that aren't sick saved.

And next slide please. We have also learned, I hope from the studies, of a really exciting new generation of health economists that are interested as a challenging issue that health has a big impact on economic growth.

Next slide, please. What the keys to successful health initiatives from a number of economists and my own reading, good governance from Robert Barrows' work turns out to be the number one category that he would list. You have got to have research and evidence-based decisions which means you have to have information and data. You have to target interventions to high-risk groups for any of these diseases. You have to recognize the key role of women in health, both as women and as mothers of kids and the next generation. You have to encourage community involvement, which we don't always do very well. Clearly business has a major role to play, and we have not as scientists at least often reached out to them. And that's an important set of connections to be made. And they have to set examples, particularly in AIDS, that it can be done in some countries -- partnerships with governments, NGOs and ODAs.

But the bottom line of the macroeconomic report at WHO is there have to be adequate resources. The difference between Brazil and many other sub-Saharan African countries is Brazil has the resources. And without that you can't do it.

Next slide, please. We had a meeting at Harvard about a month ago -- very concerned about whether there was appropriate agenda at the Global Fund for AIDS and Health, and if there were such an agenda that dealt with the problems, how would we think about that fund being used to help health? And we came up with a series of principles, sent that to Kofi Annan and to Dr. Kyonga, and hope it's helpful. But I wanted to share some of the thoughts. There's a group of people from industry, NGOs, developing countries, academics. Our view is that you can't do prevention for very much longer if the only outcome of finding that someone is positive is stigmatization and ostracization. You have to provide some treatment.

Effective TB treatment is the best public health intervention. It stops transmission by itself in a month. STD treatments we now know reduce HIV as well as STD transmission. Treatment there makes sense. We know that antiretrovirals, wherever they have been used, increase voluntary counseling and testing, particularly in Brazil, diminish maternal-child transmission, improve survival of mothers. And now there's absolutely incontrovertible data in discordant couples that by dropping the viral load in one partner that markedly blocks transmission of the virus to the other in a conjugal situation, such that if one generalizes from that, dropping viral loads drops the probability of transmission. That's the public health goal. And antiretrovirals I really think have to be contemplated.

The key operating principles are going to play out slowly. I don't think you can spend the world's resources on every country in the world and get much in return. I think that our feeling was you have to start with those countries that have a plan and a commitment -- NGOs, communities -- not just governments -- and select the best and see if you can use drugs in a poor country context. You have to have a transparent process with really independent review. You have to have monitor able health outcomes, and they have to be scientifically rigorous. We can afford the equipment and the technology to learn whether AIDS drugs or vaccines are working or not.

We suggest that the drugs not be -- that money not be given to the poorest countries necessarily to buy drugs which require combinations, very important synergies in pharmacokinetics, and disparities and adverse effect -- very tricky to do when you are matching generics and non-generics. We think that ought to occur as grants-in-kind from the global fund through companies that exist that can meet pre-qualification standards for quality, experience and capacity. We believe the only way you can get good and new and increasingly new drugs is to respect intellectual property. We think there have to be direct in-country grants to support the linkage of treatment and prevention, operational and lab research, surveillance for drug resistance and assessment of outcomes. And this has to be done in collaboration with communities and NGOs.

Next slide, please. The other view that the World Health Organization looks at is what would all this cost if we were to do it in the way that would really make a difference? And I start with this, which is their data on what we are talking about for the lesser-developed countries and other low-income countries. It's a lot of people in there. It's over two billion people. The per capita incomes -- I put this on there to show you when you ask the question, Can they get good governments, can they clean up their act, can they drop corruption? Yes, they could do all of that and still not have the money to make a significant impact on their health. And that's the bottom line of the macroeconomics report.

Next slide, please. This is what they recommend as a minimal health package, and I think most of us would agree it's minimum: childhood immunization to very high levels; tuberculosis treatment, as you saw before to drop the disease by 50 percent in a decade; malaria prevention; HIV prevention and treatment including opportunistic infections, STDs, and using antiretrovirals; integrated management of fevers and respiratory infections; maternal mortality prevention; antenatal care, vitamin A and micronutrients; and smoking prevention, which is not to be left out of any list.

Next slide, please. What's it really cost? Well, the cost is $30, $34, and the numbers keep changing in the drafts -- $34 per person. The domestic resources available in those countries by the year 2007, assuming they put through a 1 percent increase now and a 1 percent increase later in the GDP spent on health from themselves -- their contribution maximally would be $11 or $18 dollars per person. That means the world at large, if it wants to do this program, is going to have to contribute to narrow that gap, both in dollars for treatment and these programs, and also for public goods for research and development to help do this.

Next slide, please. They turned out to be significant costs. People may faint here to see numbers like this, but we've never asked for big numbers in health, and I think the Macroeconomics Committee of WHO is really trying to say this is what it would cost to keep this world a much healthier place, particularly in the poorest countries.

The total cost, internal country contribution and external, would be $27 billion. I point out the total overseas development assistance in the world right now is only $53 billion. You'd save a lot of life years. You'd avert a lot of deaths. And Jeff Sachs calculates that you would return $182 billion if you assume each life can be valued at 1XGDP, or $545 billion, which is a huge amount, if they had a value of three incomes for every life saved.

I've come to the end of my talk. But this is an opportunity to make one overarching reflection, because this may be the moment and the only shot I will ever get to do this. Fifty-six years ago the United States made what I believe to be the most important foreign policy initiative, certainly in the century. It was called the Marshall Plan. I would have hoped that certainly without bio-terrorism that we could have a Powell Plan. And the Powell Plan would be a declaration of war on disease and hunger in poor countries, a commitment of the United States investments in health, nutrition and education in poor countries. And it would do for this country a lot -- and the world. It would save millions of lives. It would improve economic development in the poorest countries. It would hopefully inoculate foreign policy against its vulnerability to anti-American attack and not caring. It would protect America's health from the emerging threats that John spoke about, and hopefully change the U.S. image from self-interests to human interests. Thank you very much. (Applause.)

Dr. Shine: Are there questions for Dr. Bloom? Do you want to -- up in the back, Dr. Spelanski.

Question: Yes, hi. I'm from the Institute of Medicine. I have a question about the figures that you show about the vaccine. I've seen a lot of models about HIV vaccines and the different proportions of success, depending upon the efficacy. We have enough problems in this country with vaccines that have to do with communicable diseases, like respiratory infections. How do you account for a vaccine where human behavior is the main vehicle of spread, and if you have a vaccine that's anything less than 100 percent effective, how do you model in the change of behaviors that may revert to the kind of behaviors that spread this disease based on people having false security of an effective vaccine?

Dr. Bloom: It's a very good question, and I just -- on the good side, it is certainly an issue that the modelers have worried about. And you can model what percentage of every high-risk group stays in a vaccine trials, changes behavior in any manner, shape or form. It's model able. The answer is we don't have a vaccine good enough to know whether there would be a change in behavior. And I think in the phase one trials in San Francisco that I am aware of, there was not a great deal of evidence to say that they didn't understand that it was a trial, that the vaccine was not a guaranteed protection, and the change on behavior was very small -- much less than had been dire predictions. The impact in the developing country context is unclear.

Question: I'm from the Fogarty Center. I have a question for Dr. Bloom related to investments in research and capacity strengthening as a portion of the Powell Plan. You gave certainly a number of figures. Dr. La Montagne spoke about the importance of research and training. I'd like to know what type of guidance you'd give to the organizations and the countries as they march forward with implementing in regard to what percent of that investment should be accorded to capacity strengthening and research done locally.

Dr. Bloom: Thank you for that question. A couple of points. First, if one just takes overseas development assistance loans from the Bank and IMF to countries, I know very specific cases in which there was a component of a loan which was called assessment which was partially capacity building, partially R&D on operational research. And they have not always flown. That has been given sort of the lowest priority in overseas development assistance.

The 1996 ad hoc committee on the role of research and development done jointly between the Bank and WHO, recognized a couple things. First, there are very few health institutions in developing countries that have been created in the last two decades, and most of the institutions that are there are either falling behind or need scientific and technical assistance. Secondly, there's a huge brain drain in developing countries. When capacity is trained in the U.S. and Europe, very often the people stay, and that's partly because they don't have institutions from which they can be productive to return.

Of the $25 billion that you saw in my list, WHO recommends that $3 billion of that be global public goods which include some capacity building, also R&D on the needs of the poorest countries. And that would be something on the order of one-eighth to one-ninth of the package for health. It has to be there. The estimate that they would like to see is something like 5 percent of the funds in countries to go to operational research and capacity building and training.

Dr. Shine: Thank you, Barry. We are going to take a 15-minute break. I hope you'll come back promptly, because we want to start with Senator Frist's presentation very promptly in 15 minutes.

(Break.)

Dr. Shine: I've had the privilege throughout my career of working closely with cardiac surgeons. But to get one in the Senate, I mean that's really neat. Bill Frist has been a United States senator representing the state of Tennessee since he was first elected on November 8th, 1994. He became the first practicing physician elected to the Senate since 1928. He has had a very distinguished career in practice, on the faculty of Vanderbilt. He helped develop the Vanderbilt Transplant Center. He has written scholarly work on both surgery and transplantation. I think what has struck me more than anything else in watching his career in the Senate is the breadth and scope of his interests in terms of issues related to health in all of its aspects. I mean, he is a cardiac surgeon who worries about prevention, who worries about public health, who worries about issues related to access to health care and so forth. He has been very concerned about issues related to research, both in the areas of biomedical research, and had a great deal to do with the focus of the Agency for Health Care Research and Quality to focus its activities on quality of health care in America. So the fact that he has a substantial interest in issues of global health represents one more aspect of what I think is a rather remarkable vision. And it is my privilege to present to you the honorable senator from the state of Tennessee, Bill Frist. (Applause.)

Senator Frist: Thank you. Ken, thank you. And indeed as a United States senator, but much more importantly as someone who has spent his entire adult life in the field of health care and medicine, I sit here today and people say a politician sitting here for three hours, listening and paying attention, politicians are supposed to come and spend 20 minutes, give their talk and leave, go to the next event. But it's a real privilege for me to be able to sit on this panel, really in this audience, and listen and learn, to pay respect to the vision of someone having a conference like this, to be able to in my own mind applaud Secretary Powell in his efforts to bring us together, to have in really ways a discussion, even though a lot of it is presentation going forward, because all of us come with our own different views and our own different experiences, and it's rare to have such a wonderful collection of people. But we are immediately injecting our own experiences on what we are seeing. So in a way it is a discussion as we go forward.

So it's been a real privilege for me to be able to be here this morning, the entirety of the morning, and to listen and to learn, because when I have the opportunity to talk to the President of the United States, or we look at the global fund, or as a ranking member on the Africa Committee on Foreign Relations, it gives me the opportunity to take what I learned and inject it into those discussions, so that we all really are working together with a common goal.

All of us -- each one of you in the room draw upon your past experiences, and I do exactly the same thing. As a physician we were trained to listen, to make a diagnosis on as much information is out there, to act, to treat, and then be held accountable for that treatment. And all of us in essence do the same thing here. And we are at that point where, yes, we need to value information. We need to pull that information together. And now what's alive today is that assimilation of that data, the decision-making and then acting on what we learned. And the wonderful slides that Dr. Bloom showed, which kind of pull us into the future with the uncertainty of data which is primitive by many regards, but being pulled into the future and setting policy as we come together to address these issues, to me, is so exciting.

Before coming to the United States Senate I transplanted hearts and lungs. Again, it's not that too dissimilar in that you are giving people in pretty much hopeless situations that have 100 percent chance of dying within six months or eight months -- you are giving them a chance by interjecting with action. But that's not quite enough, because I give all of these patients when I transplant their hearts immunosuppressive drugs. It drives their immune system down, and that introduces a new set of problems, and that problem is what we are talking about today. It's infections. And it's the infections that rear their head at any point in time. The operation takes for me to zip these hearts in -- it's about five hours -- and that's what people see on TV, and they see the cooler going around in the middle of the night. It's what happens after that that really is what is important. It's every time an infection comes up you knock it down. If resistance develops, you move into a different direction. And, again, that slide we just saw, these shortening periods of resistance developing.

What do we do to prevent resistant microorganisms from emerging? And our overall success depends on how good we are in treating that infection. And in a patient after a dramatic heart transplant, if an infection sets in, what happens? The patient drops out of school, if they are a student -- so they don't get an education. If they are working, because they have that good heart and they get an infection, all of a sudden they leave work. Because all of a sudden they can't be out and associate very well with people, they don't become the parent that they really want to be. Their overall family becomes less secure. They no longer can participate on that school board or whatever, as you drop down to the, say, communities in Africa, a level, a tribal concern over education. They no longer can participate in that regard. You lose relationships with other people. Your own structure in life deteriorates, and then the relationships around you deteriorate. Normal structure dissolves. That's the micro of what Dr. Bloom just presented to you, the macro, the big figures.

Now, that's what I saw when I addressed infections every day. And you can see all of a sudden it's not that dissimilar when we talk about this very rich matrix, this interrelationship between our fight globally, not just an individual person, but globally with disease, and the impact that it has on the big macro numbers of GDP, of employment, of what it does to the vitality of a country, and indeed what it does to the security of that country, especially in light of what we see going on today with coalition building, with all of us trying to work together to fight terrorism. So even though we are not talking about the terrorism, bio-terrorism this morning, you will a little bit this afternoon. And if I have time I'll comment a little bit on that. It's all part of one big picture as far as I am concerned.

Those immunosuppressive agents that I give, I have to give, I do give to all of my patients. It keeps that heart pumping away so it doesn't have what was called rejection. It is not too dissimilar to the poverty, to the starvation that we have out there today. It is not too dissimilar to the lack of political will, all of which allows these things that we don't like to pop up. Not too different than a blind eye to other nations from the standpoint of the United States. So with appropriate action, I think security can be achieved, whether it's with that patient with the new heart fighting those infections or for the nation who really does have the will -- not just the United States, not just donor nations -- but the nation that is sitting back that has either emerging infectious diseases or infectious diseases very well established.

Foreign Relations -- I do serve as chairman or now ranking member, formerly chairman of the African Affairs Subcommittee. I began this calendar year on that subcommittee with a real commitment to make HIV/AIDS, malaria, tuberculosis, the emerging infectious diseases, the established infectious diseases, a very important part of that subcommittee. And I can tell you, working hand in hand, Democrat and Republican, you are going to see the Foreign Relations Committee in the United States Senate focused on the sorts of issues that we are talking about today. Just watch it. I promise you it's both occurring -- it started about a year and a half ago -- and it's going to occur even more as we go forward.

HIV/AIDS -- not long ago -- again, personal experience. This was about 20 years ago or so I was a third-year resident, and HIV/AIDS -- I didn't even think about it then. As you know, we are sort of at this 20-year period. It was really about three years after that that as a resident all of a sudden things were revolutionized. Even when we first sort of heard about HIV/AIDS we sort of thought it was going to be just a narrow population. We did have to change our behavior in terms of how we treated blood. All of a sudden blood became a toxic chemical where before blood was essentially sterile, and we didn't mind getting it on our gloves or on our hands. We just didn't even think about it. Behavior in the dentist chair changed with gloves and masks coming down in a rapid fashion. But even then in the mid 1980s or late 1980s we had no earthly, earthly idea that what you have just seen on the slides by the two previous presenters would have taken place -- not in this country, but much less around the world -- the worst public health crisis in 600, 700 years. A lot of people don't realize it of course today, so we have to educate those people. But even then 15 years ago, 12 years ago, very few people would have predicted it.

The statistics we have been through already this morning, again sort of taking the big statistics and pulling them down. Right here at home it's about every 13 minutes, as all of you know, that an American becomes infected with AIDS. And over that same 13 minutes, stepping back globally, about 72 people die somewhere in the world, the figure of three million people a year. Again, we have gone through in the previous speakers' presentation -- twice that number will be infected. And of those infected, again 70 percent are in Africa. But, once again, when you look at other nations -- when you look at India, when you look at Russia -- 70 percent may be in Africa, but when we look to those curves emerging elsewhere, we all know that this is around the world.

My example of the transplant patient, of the instability that comes and relates to that position person obviously is happening in Africa. I have the opportunity of doing -- not as a United States senator, but as a surgeon -- operating every year in some country in Africa. For the last several years I have been going to the southern Sudan. And the southern Sudan has been fascinating for me. I helped get a little hospital started there about three years ago -- very unstable environment when I first went in. Now with that hospital there, people have come together, there is commercial activity around it. The area is still bombed -- it was bombed about 43 times in the last year there. But after about a year and a half the hospital that we set up was insufficient. Why? Because of tuberculosis, HIV/AIDS, the relationship again which Dr. Bloom mentioned, is so integrally related that we had to open up another hospital -- has 50 beds -- about two or three miles away where patients come and the various Africans come to be treated for six months at a time. So this whole emerging interrelationship between tuberculosis becomes very real to me.

The good news, again, is that we do know a lot about how to reverse what has gone on today. The slide and the story that Dr. Bloom told about Brazil -- dramatic. It drives home to me and reinforces what we have seen in the other countries that he mentioned, with Uganda, Thailand, Senegal -- all who have had remarkable successes.

I will say that it does come down to community-based organizations, religious, secular, both, that the linchpin of success, at least what I viewed as I worked on the ground each year in the African nations, again as a physician, seeing patients one on one, treating, doing general surgery there -- what I see is the community-based organizations. And, again, I am going to continue to emphasize that, because as you know, whatever money we allocate here, whether it's in Washington or from a global fund -- unless we get it down to where the ideas have worked, where they are working, where they can be delivered, it is too often wasted.

Prevention and treatment. It's been mentioned. I am going to have to reinforce that, because as a physician you take prevention, but nothing in health as a physician or as a public health official can stand on prevention alone. And therefore you have to have treatment. Prevention, behavioral treatment -- again, we went through it earlier today -- is the key. We know that. It still has to be the linchpin. But treatment is an important part of the mix.

Pharmaceutical companies have stood up. And there are a lot of people who are very angry at the pharmaceutical companies, and say, You are going to do more, and they are going to keep beating them until they do more -- and it takes some of that beating to get them to where we are today. But pharmaceutical companies have sent a message of hope. And, again, we haven't used hope that much this morning so far, so I am going to use that word a little bit more. But the pharmaceutical companies have done, I believe, a reasonable job in slashing those prices. An article in today's newspaper talked about some progress being made in terms of patents and the approach to patents. And more can be done. And people will after I say this will say, Yes, but that's not enough. But it is moving in the right direction. Other treatment regimens we know must be addressed, because they ultimately may make a bigger difference in the actual treatments as we go forward.

Hope or the treatment component as we go through prevention and diagnosis and treatment, where we've really lagged -- you could spend all your money on treatment, but you have got to have some treatment in there to build up that hope, to bring people in to be tested, to give them an incentive to change behavior. That linkage between prevention, diagnosis and treatment has got to be there. With scarce resources -- and they are scarce -- I am not sure we are going to get $27 billion -- that need -- the need can be identified, but we do have to make decisions to allocate what we can get as we make our case as we go forward.

Access -- access to treatment and drugs. Again, the case has already been made for the opportunistic infections themselves. You learn very quickly if you are on the ground taking care of patients that it is tuberculosis -- the slide's exactly right -- that you have to set up a tuberculosis hospital next to your other hospital. But also in your treatment that is what people are dying of in terms of tuberculosis. So, again, when we think treatment, it doesn't have to be just the big antiretroviral guns which are so effective in this country, but again it's treatment of those opportunistic infections, the emergence of tuberculosis, the resistant strains of tuberculosis, the more virulent strains of tuberculosis have already been mentioned.

Finally, in support of our health care delivery systems, you have got to have a system. And if there is one thing, again bringing the linkage back to what we have all been focused on in many ways, that is the bio-terrorism today, I don't stand up and make a talk without stressing the importance of our United States public health infrastructure. Again, it comes down to surveillance and communications and the diagnosis and the treatment, the rapid response and the consequence management. It's a model that is proven, as we talked about this morning, and it is a global model. And this gives us an opportunity to link what we see together, to what we are seeing today. What we are experiencing as we talk about anthrax and plague and tularemia and smallpox. Because without that public health infrastructure of surveillance -- nothing else is going to work. And we can throw money -- as much money at bio-terrorism as we want to, but if you can't answer the question if there is a bio-terrorist attack right now in this room who you are going to call, where are you going to go, who are they going to talk to, what the response is going to be -- the system is not going to work. That surveillance applies to what we are seeing today in the United States, and what the world has known for a long time. So now is the time to make our case.

So how do we do all this? The price-tag -- again, I don't want to repeat the data. We have seen the figures just presented, and I immediately sent a note over saying I need copies of every one of those slides as we go through. And it is true. We have seen the data that comes out of the United Nations, the figures of three to five billion dollars annually. What does that really do? It's the figure we all use, because the U.N. came up with these numbers, and it's a good start. But all we know, that doesn't include the treatment end of it really in essence at all. It just sort of gets us up to a base line itself. But that's enough to scare people. It does make the statement, whether you use three to five or you use over a 7- or 5- or 6- or 7-year period of $27 billion, governments have got to be involved. The foundations are terribly important. They are quick, they are responsive. Without it the stimulus may not be there. Within two months you can have something done. But when we are talking about figures that big, we do have to have governments involved on a global scale. But there are great opportunities for those public-private partnerships which I am sure we will be talking about a little later as we go through today.

The United States of America -- I spend a lot of time talking and traveling around the world and talking about the United States of America. We have a lot to be proud of in terms of where we have been, and I know where we are going. The United States indeed has been on the forefront of the AIDS fight for over 20 years. People will say, yes, but it's not enough. Let me just step back. We have spent more than any other country on research. We have spent more than any other country on treatment. We have spent more than any other country on public community. We have spent more than any other country on the global problem. And U.S. foundations, who have stepped up -- and you know you can just run through the list -- and many are represented in the room today -- because of their speed, their efficiency, their targeting, know which buttons to push, their money gets leveraged tremendously. They have contributed much more than many, many countries around the world. And others are doing their part. We have got the United Nations, we have got various governments, we have got the World Bank, we have got world leaders, we have got the secretary general, we have got Secretary Powell, Jim Wolfensohn, people -- all these world leaders are really for not the first time, but together collectively for the first time over the last 18 months have focused on the issue. Opportunity -- and that's why hope for me personally, and the coming together like today where we can pull together ideas and move ahead and come out with a Powell Plan or a Powell Doctrine. We need to hear those sorts of ideas put forward, because that sort of leadership to me is what public service is all about, is what being a senator is all about -- is putting the vision out there and pulling people along using information, using the data as we go forward.

Policymaking -- and again we haven't talked a lot about policymaking. One of the principles that I use in terms of policymaking is I step back and look at the data and look at all the hard work, whether it's from NGOs, whether it's from people on the ground, whether it's the doctors or physicians or the research community or various governments. Number one, we absolutely must ask political leaders, religious leaders, business leaders of the world to unite -- to unite and join that international commitment to halt the spread of HIV/AIDS. If you don't ask, you don't get. People aren't just going to come naturally to the issue. You have got to look the religious leaders in the eye. You have got to look the business leaders in the eye. And you have got to pull them together and be committed.

Number two, we must, I believe, and we talked some about it, embrace the international fund for HIV/AIDS, TB and malaria -- TB and malaria -- keep them all together, and in truth those three are surrogates for all the other things we are involved in broadly.

It is not an American fund, nor should it be. The President just two or three days ago, I guess here, said we are committed -- you demonstrate that the principles are right, that you are going to work hard, that you are going to stay focused, that you are going to do good, and we will be there with increasing resources over time. But it is not an American fund, and if it becomes an American fund it is not going to work. It is not a United Nations fund. And again, as we go through the organization, I think we need to make it clear it is not a U.N. fund. Indeed, it's a new way of doing business. And I didn't go to the Harvard conference, but I know a lot of people went to the Harvard conference. And the idea of thinking through what is a new way of doing business and what are those principles, and let's begin to articulate those, is the right direction, because we have no true model upon which to base this fund.

Last month -- as of last month -- I am not sure it is today -- 26 countries, 1.5 billion to the fund -- a long way to go. A good start. Again, we have got to set it. This new way of doing business in the direction.

Number three, coalitions. It's exciting to me. You will see that I will talk a lot about -- and it really comes down to the public-private partnerships idea. But you need the very best in communications. You need the very best in our academic institutions, the people who are out there thinking the issues all the time. The foundations, another partner that I have spoken to, the corporations -- sometimes people beat corporate America down and say, come on, you are just out to rape the world. In truth, they want to be -- and we need to reach out and take the very best of them and make them part of this overall coalition.

Scientific institutions. Obviously the NGOs -- and some of you represent NGOs in the room -- that's who I do my medical mission work, which is a little outside of medicine, a little bit outside of the Senate -- actually way outside the Senate -- (laughter) -- as I go through. But the NGOs have got to be partners. It's those community-based programs that are the front line. The front line in bio-terrorism today is not the United States government. The front line in bio-terrorism today is who you call when you get in trouble, when the threat is there, the NGOs that are on the ground today delivering that service.

Number four, and it really is an extension of that -- I think the non-governmental and community-based organizations alone need to have that appropriate emphasis, in part because if we just step back and say, Okay, they need to be a part of the coalition, I don't think the money is going to ever get down to them quickly enough. And so this whole idea of getting the funds to them quickly, efficiently, is an important I believe fourth point in the policymaking arena.

International research efforts is number five for me. And it's international research efforts on disease affecting developing countries. And I mentioned this relationship earlier in my analogy to patients of poverty, of nutrition. We saw it presented a different way when you break it down to developing countries and developed countries. We need to focus that international research effort at that relationship of malaria, TB -- TB's relationship with HIV. All of this needs to be reinforced by the best scientific work that we have in the United States. This can lead to real benefits in the developing world. We need to keep it at a cost that they can afford, and that mind-set is different. We know that. We can fund this research in many different ways.

Number six should focus on prevention. And as soon as I say prevention -- because everybody knows that that's the linchpin of success -- I am going to go back to what I said earlier: we need to focus on prevention, but not forget care and treatment. These care and treatment options do need to involve low-cost pharmaceuticals, enhanced care delivery systems. But it's that linkage. Don't forget the linkage.

And number seven, I put -- again, it comes from personal experience, because I go to Kenya outside Nairobi -- and I would encourage all of you to go to these camps of orphanages of children. It is was a little bit like Secretary Powell's remarks that you weren't supposed to give that you gave -- they weren't in his written remarks. When you look at the children, and you look at the orphans -- the whole story is told. There is a doughnut that is being lost from our society, this hole, and it's gotten bigger and bigger and bigger, and you have the children that are left. Some because their parents died of HIV/AIDS, and they are simply orphans; and some because they are HIV-positive because of the mother-to-child transmission which was mentioned earlier. Attention to the orphans I think is important as we go forward, as we understand the effects that we have on society. It opens up vistas. It opens up an understanding. And therefore in the legislation that I have written in the United States Senate -- it is now law of the land -- our global health threats and emergencies act currently or the bill that we passed two years ago -- you will see there is a whole section in there on orphans. And I think it's important because the comfort and the care and the treatment and the concern to me is very important.

I think I'll turn to questions. Let me, because that touches the policy and sort of my philosophy. So I think in the United States Senate you will see, as I mentioned the Foreign Relations Committee focus very much on this relationship, in part security, in part health, in part economic as we go forward. We will be doing some hearings in either late January or early February that we did have scheduled for a few weeks ago on that very issue at the full committee level in Foreign Relations.

What we see here isn't that different to what we have seen in bio-terrorism in the last several days. I mentioned the surveillance and the public health infrastructure. The emerging public health threats that are international are domestic. Germs know no boundaries. The principle is basically the same.

I had the opportunity before coming to the United States Senate to do the transplants, but to be a trauma surgeon, where I took care of gunshot wounds, took care of crush injuries and mass casualty. When I came to Washington, my mind-set, as I was making this adjustment from physician life every day getting up at 5:30 in the morning, and operating from 6:30, and the usual physician life of sort of going, taking care of patients all day, coming here -- I did ask when I got here, What about mass casualties? What do you have happen in Washington, D.C.? -- and convened a conference at the Capitol, and we pulled together the EMS people and the SWAT teams and the doctors and the emergency -- and it was clear to me that in truth America has not thought enough about terrorism in this country and mass casualty and the like. The following year I began hearings with Senator Kennedy, who he and I have been very interested in this, on anti-microbial resistance and emerging threats -- much of the data that you are all familiar with. That expanded because in part my interest on Foreign Relations to a group of bills coming out of the Foreign Relations Committee on global threats -- again linking the public health threats with the global threats.

Domestically, Senator Kennedy and I wrote a bill called the Public Health Threats and Emergencies Act, that passed about six months ago. People said, How did you know this was coming? Well, we didn't know it was coming, obviously when it was coming -- but we knew that it was important to have a structure in place for domestic terrorism, for surveillance, for prevention, for preparedness and for consequence management. Again you can see it's a pretty similar model to what we are actually developing globally that we are beginning to articulate I think in a more refined way over the last two or three years.

That bill was not really funded very much over the last six months, but we -- Senator Kennedy and I went to the Appropriations Committee about three weeks ago, asked for $1.4 billion for right now in order to increase our funding for this Public Health Threats and Emergencies. It wasn't really in response to September the 11th, because we had already written the bill; it just hadn't been funded. And I believe we will obtain that funding in the next couple of weeks.

We will be introducing a bill next week that is sort of a second phase of this bill. It's an authorization bill that again will look at the various dimensions that parallel what we are talking very much about today. We will add a food safety component of that bill. We will address agriculture to a certain extent, and we will address mainly state and local preparedness. Hospitals -- right now, one out of five hospitals have a bio-terrorism plan, and it should be five out of five -- about six or seven thousand hospitals in the country -- 5,000 don't have a bio-terrorism plan. So if something happens to you, there is no plan to take care of you. Now, there will be hopefully over the next couple of months.

Summary on the bio-terrorism: We are not unprepared, but we clearly are under prepared. We have got a great system. The building blocks are out there -- just like all of you are building blocks as we address the issues on the global health issues. Now is the time to pull those building blocks together, the global issues for the topic of today, for domestic terrorism, bio-terrorism, germs, bacteria -- using them as weapons to kill -- all the building blocks are there from the surveillance standpoint, the prevention standpoint, the preparedness standpoint. We have got to pull those building blocks together in a more seamless fashion, and that's our challenge as we go forward.

The parallel again is represented by you. All of you are here today to pull together. We can't forget, whether it's in the domestic bio-terrorism, or whether it is in our offense that we are putting forward globally, that we are part of a greater world, that we are not alone in facing this threat, that we can't go alone in crafting those solutions and those answers. The war on bio-terrorism has to be a coalition effort, just like the war on the international health challenges have to be an international collaborative effort.

As Americans -- and I am continually amazed -- and in the United States Senate the one vantage point that you have is that you are able to interact with a lot of people in a lot of different ways, and people for the most part who are the smartest people in the world, another group of people who have the most common sense, another group of people who are most experienced -- none of those are in the Senate, by the way -- (laughter) -- but with that you do see the challenges that we have, and you see the tremendous resources that are out there today, if we are good enough to pull them together, to put them around a table, to pull out the best in each of those individuals. Our challenge is to create a better United States, a safer United States, and a better and a safer world.

I am very optimistic, and I think as you see the building blocks come together in our discussions, as you look at the policy objectives that we have, if you look at the goals out there that we can achieve, our own goals to meet those challenges -- you do a heart transplant, it takes five hours to do it, as I said, for the next 10 years, 15 years, 20 years or 30 years you are continually fighting to keep down those infections. I think we have sort of done the heart transplant; we have made the commitment. Now is the time for each and every day, for us to get up, to make sure that we beat down these infections, so that the individual patient can live the life with their family, with their community, with their state and with their nation. Thank you very much. (Applause.)

Dr. Shine: The senator timed himself very well, so that we have some time for questions, issues, slings, arrows, outrage. Yes, please identify yourself and ask your question.

Question: Yes, thank you. I am the deputy chief of mission from the Embassy from St. Vincent and the Grenadines. I wish to commend Senator Frist for such an interesting presentation. I would also like to take this opportunity to take advantage of his unique position as a medical doctor and a politician, and just to say that the problems have been diagnosed. Prescriptive measures have been identified and implemented. In short, you know, much has been done regarding this problem that we are trying to discuss today. But yet there is still a high correlation between the high incidence of diseases and the incidence of poverty. Why? Why haven't we in the underdeveloped world been able to achieve the types of successes that you in America and other developed countries have achieved?

Dr. Shine: That's an easy one, right? (Laughter.)

Senator Frist: That's easy, yeah. You know, first of all I can't answer the question of the why. And I think it's an important question, because as we develop initiatives to support, if we ignore the correlation -- I am going to say a correlation, because the causality I am not sure of. The causality was there one way or another, either from a health to poverty or poverty to health, it would be much easier. But the correlation is there, and the straight line can be drawn. And I think it's important for us to separate the two.

If we were able to focus on just raising poverty levels -- and you know you can start looking at what a government can do -- it can do debt relief, it can do grants, it can do infrastructure itself -- that is no guarantee that tuberculosis or malaria or HIV/AIDS would be any less. I don't think the data is sufficiently strong, even though the correlation is there.

If on the other hand we ignore nutrition, it's pretty clear -- nutritional relationship between disease, between causes of disease, is pretty strong. The correlation between nutrition and poverty is pretty strong. If you flip it around and you treat the disease itself, you treat -- you basically say, Okay, we are just going to pump money into antiretroviral or a treatment for HIV/AIDS, I am not sure, even if you had enough money, that that is going to work if you don't address the issues of poverty, of lifestyle, of the correlates of that with behavior, for example. I don't have the answer to the question of why. I think we need to further dissect it from a practical standpoint, because we have $27 billion. How are we going to really spend it? And I don't think the figure is obviously accurate if you really understand that relationship between poverty and education and nutrition and disease. It's obviously going to be much more than that.

Dr. Shine: Let me ask you a question of a slightly different kind. I think many of us believe that major investments in health, helping standards of living in parts of the world where terrorism arises, can be extremely valuable -- not necessarily because it's going to change the ideology of certain terrorists, but because it does change a climate for the rest of society, in terms of whether they look at terrorism as being a legitimate activity that they ought to support. So improving standards of living, health status and so forth become extremely valuable. At the same time, that leads one to focus efforts particularly on countries where there is that kind of an environment. And there has been a lot of discussions about Moslem countries, for example, or what's to do in Afghanistan. We are doing that in an international environment in which as you point out Africa continues to be an enormously difficult environment, and in which for example if you want to look at resistant tuberculosis Central Europe and Russia is clearly percolating huge amounts of it. My question is how do you as a policymaker think about how and in what way we ought to balance our investments? That is, how do we think about the necessity when you have such a disparate set of opportunities and responsibilities and a limited amount of resources -- how are we going to think about where we put the resources and the effort?

Senator Frist: Well, everybody would answer the question a little bit differently, and my bias again as I went through my seven points that now whenever you see me you know I am going to be running a piece of legislation down or how we spend money down these seven points. My bias and the challenge that we have as we look at terrorism is that I believe we have to have the recipient country or the recipient -- I don't want to say necessarily state -- but we have to have the leaders committed to licking this problem. And if we don't, and if we go to a country, basically even if the incident is like Russia, which is on a curve like that in terms of incidence of HIV/AIDS, or some of the countries in Sub-Saharan Africa where incidence is already high but may be flattening out, that unless we have the committed leadership at the top, and it doesn't necessarily have to be the President, but it has to be a figure that people look to, that when they say something they'll listen to, that they will learn from -- I don't think it's going to work. And it's a bias, and I am not sure if it's a fair bias. It means if you don't have that sort of leadership there, we have a real obligation to educate them, or through coalition-building put pressures on them. But as you look through the nations that have worked, the three that were discussed or Brazil, it took a national commitment, starting at the top. And in the nations where it hasn't worked it has leaders who are not there.

I don't want to overstate the leadership end of it, but to me not only what's important in America, but other countries, it's leadership. And when we are talking about changing behavior, when we are talking about using scarce resources, and literally taking it out of your military in order to put a dollar in to health treatment, if you don't have a leader in that country stating it, I just don't think it's going to work.

Dr. Shine: Laurie Garrett makes the very interesting point that the reasons that at least one of the African countries was so aggressive was that during the guerrilla phase of the combat the person who went on to become president had sent a number of key people off to Cuba to get military training, and when they got there it turned out three of the six of them were HIV-positive and he was so affected that when he became leadership he immediately provided the leadership. So that's anecdotal, but it is consistent with the leadership hypothesis.

Time for one or two more questions. I can't see you, but identify yourself.

Question: Thank you. I'm with the Student Global AIDS Campaign. Senator, I was extremely struck by your emphasis on coalition-building, but I was a little disappointed because students and young people were not included in that. And whereas students right now are the fastest growing group of people entering the AIDS movement, but also the group that is about to become NGO leaders and government leaders. And, unfortunately, young people are very marginalized within our government system. Recently at the United Nations Special Session on HIV/AIDS young people were not included on the official delegation, whereas young people were included on official delegations from many other countries. And the President Advisory Council on HIV/AIDS only has one youth representative. How can the consciousness level of involving young people and talking with young people be raised, instead of talking about young people? Thank you.

Senator Frist: Well, clearly your question -- the first part of your question answered the second, because we obviously are not doing as good a job as we should either in representation on official panels, maybe my remarks -- although I thought I did pretty good for young people -- (laughter) -- and the universities and the like. But clearly I need to articulate that, because you are exactly right, it is the younger generation. The younger generation is going to have the energy, is going to have the voice, is that next generation. And I think, as you pointed out, we need to articulate it better, we need to make sure there's better representation on the official panels. When I sort of more formally advise people on the Global HIV Fund and speak with people in the administration, I will do better there.

Dr. Shine: You might be interested to know that the first reports in this country of HIV were from my Department of Medicine at UCLA. And the reason that we were the first people to recognize it was a young medical intern who happened to admit two patients a month apart who were immuno-compromised. He couldn't figure out why. And he presented them to me on rounds, and I was supposed to know the answer. And I was very upset, because I couldn't figure out what was happening. He put together the first six cases. Other people got the credit, because they did the lymphocyte counts and all the rest of it. But he's an author on that paper that appeared in the New England Journal. So young people have lots to contribute. And I try to tell our interns and residents and students there's still new things to be discovered by young people, even in the clinic.

Senator Frist: You know, let me just say -- again, this comes from medical stuff -- we shouldn't be up here together -- too much medical things -- all -- if you look at what we have to do in terms of creativity, we really have to be thinking out of the box totally, and we really to need to have to capture both the creativity based on information that we have as we go forward. And there is no question to my mind -- and both of us have been involved in teaching residents. The hierarchy of medicine is that if you are at academic health centers, you are around people three years, six years, nine years, twelve years behind you all the time asking you questions, forcing you to think. That sort of creativity, thinking out of the box, in an age where assumptions had to be thrown out the door -- back in the early 1980s with HIV/AIDS, all the assumptions of who would be affected, how big it would be. They got just blown away. It happens today.

Four weeks ago, if you had asked me -- and I was in the middle of the command center in terms of this outbreak in the Hart Building the other day. Four weeks ago -- about four weeks ago I guess -- yeah, almost four weeks ago, if you had asked me, Is there any way somebody from handling a piece of mail could get inhalation anthrax, not just me, but every scientist in the world, every medical person, every public health official, would have said no, based on what we knew over several hundred years -- not that many cases, but several hundreds years. It is a time, whether it is addressing what we have to with infectious diseases around the world, or right here at home, that we need questioning minds thinking out of the box that are honest, that are direct, that are straightforward. And based on my experience, it's not a bunch of old politicians -- I'm not that old -- but not a bunch of old politicians who do it or a formal cardiologist, but it is the young people out there who are thinking creatively, not locked into a lot of the traditions that we have.

Dr. Shine: One last question over here. Please. Yes, sir.

Question: I am with CDC. I think all of the speakers this morning have done an excellent job of outlining the magnitude of the problem and the challenges that we face. And I wanted to be a little provocative and ask a couple of questions. One thing that seemed to be missing from the discussion was outlining the burden of vaccine-preventable diseases, which was much discussed over the last two or three years as being the fourth pillar of the global infectious disease threat, along with HIV/AIDS, TB and malaria. Vaccine-preventable diseases, for which these vaccines are currently available, cause as many as three million deaths per year. We are talking about measles, hepatitis B, pertussis, diphtheria, neonatal tetanus and tetanus. But this fourth pillar seems to have dropped off the radar screen. And keep in mind that vaccines for HIV/AIDS, TB and malaria are being touted as the ultimate solution to prevent these diseases. But the system for delivering these vaccines is in dire straits -- in Africa, in South Asia, in parts of the developing world where most of these infectious disease deaths are occurring. For example, measles is still killing nearly a million people, even though the vaccine costs 12 cents through UNICEF, and it's been available for almost 40 years.

So my questions are: Why isn't the unfinished agenda of vaccine-preventable disease prevention with existing vaccines being discussed? It's kind of like the surgeon general's comment in 1967 that almost people think that these diseases have already been conquered. They have in the United States, but not -- they are raging in the rest of the world. What about the inadequacies of the system to deliver vaccines in the developing world? And is it because these deaths occur mainly in young children rather than adults that there is less attention given to them?

Dr. Shine: Do you want to try that one? I have some responses to that, because they are all very legitimate issues. The fourth pillar has not dropped off the scene. I mean, Barry Bloom is a good example of someone who is extraordinarily active in this area. As you may or may not know, the Institute of Medicine in 1993 issued a report on the children's vaccine initiative, in which we said specifically that this country needed a national vaccine authority with the capacity to develop and support public-private relationships between both biotech and pharma to create cost-effective ways of both developing, producing and distributing vaccines for children, which includes measles -- tetanus is another example of a vaccine that we have a great deal of difficulty getting. We are revising that issue, and you will hear from us in the next couple of weeks about the whole issue of a national vaccine initiative, which I think bio-terrorism has raised to the surface. The issue will be not to let it stop with vaccines for terrorism, but to in fact use the interest in availability of vaccines as a way to reinvigorate the broad breadth of vaccines.

The second issue -- the second point I would make is that in March of this next year the Institute of Medicine is convening 37 academies of medicine in the world in Paris -- the French are hosting the meeting, and they are paying for it -- so that's why we are in Paris. The subject is new and emerging infections, and one of the principal subjects is the infrastructure for delivery. The subject is emerging infections and antibiotic resistance, and part of the subject of the program will be how do we create infrastructures to deliver vaccines. And in fact that part of the program will include many non-medical people who know about how to build infrastructure. So I think that both of these are critically important issues, and I think that we would like to work with a number of other organizations to try to strengthen things. We are running late. I am going to take the chair's prerogative to thank Senator Frist for a wonderful presentation, and to encourage him to continue his incredible efforts in this broad category of activities.



Released on December 24, 2002

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