ISSUE REPORT Germs Go Global: WHY EMERGING INFECTIOUS DISEASES ARE A THREAT TO AMERICA OCTOBER 2008 PREVENTING EPIDEMICS. PROTECTING PEOPLE. Trust for America’s Health is TFAH BOARD OF DIRECTORS Kimberly Elliott, MA a non-profit, non-partisan Deputy Director organization dedicated Lowell Weicker, Jr. Trust for America’s Health to saving lives and making President Former 3-term U.S. Senator and Governor Lynora Williams, MA disease prevention a of Connecticut Consultant, and national priority. Principal, Lyric Editorial Services This issue brief is supported Cynthia M. Harris, PhD, DABT by a grant from the de Vice President CONTRIBUTORS Beaumont Foundation. Director and Associate Professor Institute of Public Health, Florida A & M Laura Segal, MA The opinions expressed are University Director of Public Affairs those of the authors and do Trust for America’s Health not necessarily reflect the Margaret A. Hamburg, MD Secretary Serena Vinter, MHS views of the Foundation. Senior Research Associate Senior Scientist TFAH wishes to express Nuclear Threat Initiative (NTI) Trust for America’s Health special appreciation to the U.S. Centers for Disease Patricia Baumann, MS, JD PEER REVIEWERS Control and Prevention and Treasurer TFAH thanks the reviewers for their time, expertise, to the National Institute of President and CEO and insights. The opinions expressed in this report do Allergy and Infectious Bauman Foundation not necessarily represent the views of these individuals Diseases for expert review Gail Christopher, DN or the organizations with which they are affiliated. and helpful suggestions. Vice President for Health Edward A. Belongia, MD WK Kellogg Foundation Director, Epidemiology Research Center John W. Everets Marshfield Clinic Research Foundation David Fleming, MD Luciana L. Borio, MD Director of Public Health Senior Associate Seattle King County, Washington Center for Biosecurity University of Pittsburgh Medical Center Arthur Garson, Jr., MD, MPH Executive Vice President and Provost and the Robert J. Guidos, JD Robert C. Taylor Professor of Health Science and Director, Public Policy & Government Relations Public Policy Infectious Diseases Society of America University of Virginia James Hughes, MD Robert T. Harris, MD Professor of Medicine and Public Health Former Chief Medical Officer and Senior Vice School of Medicine; Rollins School of President for Healthcare Public Health; Emory University, and BlueCross BlueShield of North Carolina Former Director National Centers of Infectious Diseases; U.S. Alonzo Plough, MA, MPH, PhD Centers for Disease Control and Prevention Vice President of Program, Planning and Evaluation The California Endowment Kathleen F. Gensheimer, MD, MPH State Epidemiologist Theodore Spencer Maine Department of Health and Project Manager Human Services National Resources Defense Council James Lawler, MD, MPH, FACP REPORT AUTHORS CDR MC U.S. Navy; Chief Medical Officer Integrated Research Facility at Fort Detrick Margaret A. Hamburg, MD Division of Clinical Research, National Senior Scientist Institute of Allergy and Infectious Diseases; Nuclear Threat Initiative (NTI) National Institutes of Health Jeffrey Levi, PhD Ruth Lynfield, MD Executive Director State Epidemiologist Trust for America’s Health, and Minnesota Department of Health Associate Professor in the Department of Health Policy The George Washington University School Michael Mair, MPH of Public Health and Health Services Associate Center for Biosecurity University of Pittsburgh Medical Center Germs Go Global: WHY EMERGING INFECTIOUS DISEASES ARE A THREAT TO AMERICA An Issue Brief from Trust for America’s Health Funded by a Grant from the de Beaumont Foundation “ THE HEALTH OF U.S. CITIZENS IS INEXTRICABLY LINKED TO THE HEALTH OF OTHER PEOPLE IN OTHER PARTS OF THE WORLD: MICROORGANISMS CAN AND DO CROSS BORDERS EASILY AND OFTEN WITHOUT RECOGNITION. ” 1 -- SCIENCE OVERVIEW Despite remarkable breakthroughs in medical impact Americans, with far-reaching conse- research and advancements in immunization quences for the U.S. public health system, the and treatments during the 20th century, delivery of medical care, and the economy. infectious diseases are undergoing a global According to a National Intelligence Estimate, resurgence that threaten everyone’s health. “newly emerging and re-emerging infectious diseases, many of which are likely to continue Worldwide, infectious diseases are the leading to originate overseas, will continue to kill at killer of children and adolescents, and are least 170,000 Americans annually. Many more one of the leading causes of death for adults. could perish during a severe influenza pan- The range of infectious threats includes: demic or yet-unknown disease.”2 I The emergence of new infectious diseases, Intelligence analysts argue that “newly severe acute respiratory syndrome (SARS) emerging and re-emerging infectious dis- and the H5N1 avian influenza virus; eases will pose a rising global health threat I The resurgence of known infectious dis- and will complicate U.S. and global security eases, such as measles and pertussis over the next 20 years. These diseases will (whooping cough); endanger U.S. citizens at home and abroad, threaten U.S. armed forces deployed over- I The persistence and spread of certain seas, and exacerbate social and political “neglected” infectious diseases, like instability in key countries and regions in dengue fever; which the U.S. has significant interests.”3 I The potential deliberate use of deadly Federal support for identifying, preventing, bioterrorism agents, such as smallpox containing, and treating emerging infectious virus or anthrax; and diseases varies widely. The U.S. government has I The growing rise and spread of antimicro- invested significantly in the pursuit of drugs bial resistance has led to the development and vaccines that could counter an intentional of resistant pathogens and allowed many biological attack. For example, the Strategic diseases formerly treatable with drugs, like National Stockpile (SNS) has enough smallpox tuberculosis (TB) and malaria to resurge vaccine to protect every man, woman, and child and take hold with new vigor. in America and over 41 million treatment regi- mens for anthrax.4 Along with vaccine manu- The impact of emerging infectious diseases in facturers, the federal government has invested developing countries is well known and well heavily in developing new vaccine technologies documented. But these diseases can also 1 for influenza and vaccines that are effective tackling polio in this country during the last against the H5N1 avian influenza virus. In the century. Americans need and deserve a past few years, stockpiles of antiviral medica- national game plan to protect them from tions and vaccines that may be deployed dur- the wide range of infectious diseases that ing a pandemic flu outbreak have been added threaten their well-being. to the SNS. Policymakers must start thinking of U.S. On the other hand, many other emerging and contributions to prevent, treat, and cure re-emerging diseases have received far less emerging infectious diseases as a national attention. In the U.S., the private sector health imperative rather than as interna- research and development pipeline for most tional good-will gestures. Leaders also must emerging infectious diseases is stagnant or non- recognize that efforts to address biodefense existent. Lack of action is fostered by a com- and emerging infections are mutually sup- mon view that many of these diseases are limit- portive and that compartmentalizing these ed to the developing world, and that vaccine efforts is arbitrary and counterproductive. development and treatment options are not The response to emerging, re-emerging, seen as profitable for U.S. pharmaceutical and deliberately-introduced infectious dis- firms. Companies have found that the market eases requires a well-funded federal effort; for new antibiotics, medications, and vaccines coordination with international initiatives; for many infectious diseases is not as profitable and incentives that stimulate breakthroughs as developing drugs to treat chronic conditions in research, surveillance, next-generation like high cholesterol. Therefore, diagnostics diagnostics, treatments, and vaccines. and treatment are outdated for infectious dis- This issue brief examines what is currently eases like TB and Staphylococcus aureus (often known about a range of emerging infectious referred to as “staph”). According to the U.S. diseases and why they are potential threats Food and Drug Administration (FDA), “devel- to Americans. It also reviews the tools -- sur- oping products targeted for ... less common dis- veillance, diagnostics, vaccines, and thera- eases, prevalent third world diseases, preven- peutics -- that exist or are in development tion indications, or individualized therapy is and explores government incentives for becoming increasingly challenging.”5 enhancing them. Finally, it recommends The U.S. government should lead efforts to increased action to protect the nation from detect and conquer emerging infectious dis- deadly and debilitating infectious diseases. eases with the same energy it devoted to Scanning electron micrograph of HIV-1 budding from cultured lymphocyte. 2 U.S. INVESTMENTS IN INFECTIOUS DISEASE CONTROL IN OTHER COUNTRIES PAY OFF The U.S. cannot protect the health of its citizens without addressing infectious disease prob- lems that are occurring elsewhere in the world. Helping other countries to control disease outbreaks prevents those diseases from spreading to the U.S., saving lives and dollars. Smallpox The global eradication of smallpox in 1980, with support from the U.S. Department of Health and Human Services and the U.S. Agency for International Development proved to be a pru- dent economic investment for the nation’s health. In 1968, the U.S. spent $92.8 million on smallpox vaccinations and revaccinations for Americans, or about $6.50 per vaccination.6 The U.S. spent a total of $32 million over a 10-year period in the global campaign to eradicate smallpox -- the first and only infectious disease to be eradicated through human intervention.7 For all developed countries, the economic benefits of contributing to the WHO global small- pox eradication program were substantial because costs associated with smallpox vaccine preparation and administration, medical care, and quarantine were eliminated. The U.S., the largest donor to the WHO effort, is estimated to save the total of all its contributions to the smallpox eradication effort every 26 days.8 Over time, these savings are impressive. According to a General Accounting Office (GAO) report, Infectious Diseases: Soundness of World Health Organization Estimates for Eradication or Elimination, the cumulative savings from smallpox eradication for the U.S. was $17 billion through April 1998.9 TB A study published in the New England Journal of Medicine in September 2005 found that U.S.- funded efforts to expand TB control programs in Mexico, Haiti, and the Dominican Republic could reduce TB-related morbidity and mortality among migrants to the U.S. and produce net cost savings for the federal government.10 The research team predicted the number of cases, deaths and costs using the traditional U.S. approach of screening immigrants and refugees for TB using chest X-rays obtained before or on arrival and subsequent treatment when detect- ed, with expected outcomes if the U.S.-funded TB diagnosis and treatment programs in the home country. Particularly striking were the findings regarding Mexico, which is the single largest source of immigrants to the U.S. The study found that if the U.S. government spent $35 million to strengthen Mexican TB control, there would be a net savings of $108 million for the federal government over 20 years.11 The study also predicted that there would be 2,591 fewer TB cases in the U.S., and 349 fewer TB-related deaths over the same time period, than if the current approach were con- tinued. And these figures do not even account for the fact that preventing these cases will prevent transmission of TB from immigrants to other U.S. citizens. Similar U.S. government assistance for TB control in Haiti and the Dominican Republic would also lead to long-term savings. A $9.4 million investment to expand TB diagnosis and treat- ment programs in these Caribbean nations would result in a net saving for the U.S. of $20 million over a 20-year period.12 3 1. WHAT ARE EMERGING AND RE-EMERGING INFECTIOUS DISEASES? In 1992, the Institute of Medicine (IOM) experts. For example, in the past 2 issued a landmark report, Emerging Infections: decades, countries in the Americas, Microbial Threats to Health in the United States, Southeast Asia, and Western Pacific have which defined the concept of emerging and witnessed a resurgence of dengue fever re-emerging infections. It identified factors and its most serious manifestation, dengue contributing to disease emergence and re- haemorrhagic fever.18 This past year, Brazil emergence, and emphasized current and reported its first outbreak of yellow fever in future challenges posed by infectious dis- urban areas since the 1940s.19 eases. The report broadly defined emerging Malaria, nearly eliminated in the U.S., is ram- infections as new, re-emerging, or drug-resist- pant in developing countries, particularly in ant infections whose incidence in humans sub-Saharan Africa and South Asia. In 2003, has increased within the past 2 decades or the most recent year for which there are reli- whose incidence threatens to increase in the able data, there were 408 million malaria near future.13 Recognition of an emerging cases worldwide and 1.2 million deaths. No disease occurs when the disease is identified deaths were reported in the U.S., although in humans or another species for the first there have been sporadic cases reported.20 time or because links between an infectious agent and a chronic disease or a syndrome More than one-third of the global popula- have only recently been identified.14 tion is infected with TB and TB disease remains one of the world’s leading causes of In 1994, the U.S. Centers for Disease Control disease and death. In 2006, there were 14.4 and Prevention (CDC) issued a strategic million people living with active TB world- plan emphasizing surveillance, research, wide and approximately 2 million people and prevention activities necessary to main- die from the disease annually. The U.S. tain a strong defense against infectious dis- accounted for 9,842 of those cases in 2006.21 eases that affect, or threaten to affect, the public’s health. It has become a roadmap for TB disease is usually treated with a regimen of governmental infectious disease prevention drugs taken for 6 months to 2 years depend- and control. Plan updates and progress ing on the type of infection. It is imperative reports have been issued periodically.15 that people who have TB disease finish the course of medicine, and take the drugs exact- HIV/AIDS is an example of an emerging ly as prescribed. If they stop taking the drugs infectious disease that sparked a worldwide too soon or do not take the drugs correctly, pandemic. Globally, in 2007, nearly 33 mil- they can become ill again and the infection lion people were reported to be living with may become more drug resistant.22 HIV.16 More than 980,000 cases of AIDS have been reported in the U.S. since it was first There is a growing concern among public reported in this country in 1981. Many more health officials about a continuum of drug- Americans are infected with the virus but do resistant TB infections, which means that the not have disease manifestations. Nearly 30 TB bacteria can no longer be killed by com- years after emerging as a deadly infectious monly used antibiotics. As a result, the drug- disease, there is still no vaccine or cure for resistant forms of the disease are more diffi- HIV. While a combination of pharmaceuti- cult to treat than ordinary TB and require as cal interventions, when used correctly, can much as 2 years of multidrug treatment, or mitigate the effects of the disease and allow more in extreme cases.23 those infected to live many years with HIV, its Recently, several U.S. states experienced cost to society -- in terms of health care costs measles outbreaks, which is particularly and quality of life -- is enormous. troubling because transmission of the dis- Other new diseases recognized in the past ease was thought to be largely eliminated few decades include SARS, hepatitis C, thanks to immunization. More than 130 H5N1 avian influenza viruses, Lyme disease, cases have been reported in the U.S. so far and Legionnaire’s disease.17 this year, which constitutes the largest num- ber since 2001. At least 15 patients, includ- Re-emerging or resurging infectious dis- ing 4 children have been hospitalized. In eases are also of growing concern to health 4 the decade before the measles vaccination cant cause of vaccine-preventable death program began, an estimated 3-4 million among children. In 2005, 311,000 children persons in the U.S. were infected each year. under age 5 died from the disease globally.25 Of these, 400-500 died, 48,000 were hospi- Additional information on several of the talized, and another 1,000 developed chron- world’s deadliest infectious diseases can be ic disability from measles encephalitis.24 found in Appendix A. Descriptions of ani- Worldwide, 20 million cases of measles still mal-borne and foodborne diseases can be occur each year, and the disease is a signifi- found in Appendix B. TABLE 1: Leading Infectious Causes of Death Worldwide, 2002 Cause Rank Estimated Number of Deaths Respiratory infections 1 3,871,000 HIV/AIDS 2 2,866,000 Diarrheal diseases 3 2,001,000 Tuberculosis 4 1,644,000 Malaria 5 1,224,000 Measles 6 645,000 Pertussis 7 285,000 Tetanus 8 282,000 Meningitis 9 173,000 Syphilis 10 167,000 Source: WHO 2004 World Health Report The potential deliberate use of pathogens tion in the future because of availability; as agents of bioterrorism is of special con- ease of production and dissemination; and cern in the post-9/11 world. CDC classifies potential for high morbidity and mortality biological agents that could be used for an rates and major health impact. Hantavirus intentional bioattack into 3 categories. is an example of a Category C agent.26 I Category A, or “High-Priority Agents,” is Developing effective medical countermea- considered the most dangerous and sures against deliberately emerging diseases includes: Anthrax, botulism, plague, has become a national priority. Congress smallpox, tularemia, and viral hemor- and the Bush Administration have taken rhagic fevers ( e.g., Ebola, Marburg). measures to encourage the stockpiling of vaccines and medications to counter delib- I Category B, or “Second-highest Priority erately emerging infectious diseases. Project Agents,” includes food safety threats (e.g., BioShield and the Biomedical Advanced Salmonella and E. coli), ricin toxin, Typhus Research and Development Authority fever, and viral encephalitis, among others. (BARDA) were created to stimulate private I Category C, or “Third-highest Priority sector investment with direct federal sup- Agents” include emerging pathogens that port for product development. could be engineered for mass dissemina- 5 ANTHRAX AS A BIOLOGICAL WEAPON Anthrax is a potentially lethal infection caused by the bacterium Bacillus anthracis. Outside of a host, this bacterium normally resides as a spore -- a hardy, dormant cell that may become active (germinate) in the right conditions. Anthrax generally affects large grazing animals, but it can also infect humans who handle products of infected animals. However, deliberate expo- sure to aerosolized anthrax spores also is a highly effective means of transmission.27 That is why anthrax is considered by many to be the ideal bioweapon. It is extremely stable and can be stored almost indefinitely as a dry powder. The costs of producing anthrax mate- rial are relatively low and knowledge about production is widely available and does not require high degrees of technology. According to the U.S. Department of Defense (DOD), anthrax is easy to weaponize and can be loaded, in a freeze-dried condition, in munitions or disseminated as an aerosol with crude sprayers.28 Currently, detection of this silent, invisible killer is limited. In 1999, CDC classified anthrax as a Category A bioterrorism agent, which means it poses the highest level of threat to national security. However, unlike some other Category A agents (e.g. smallpox), anthrax does not spread from person to person, thus limit- ing the risk to those directly exposed in an attack.29 Historically, numerous nations have experimented with anthrax as a biological weapon, includ- ing the U.S. offensive biological weapons program that was disbanded in 1969.30 The worst documented outbreak of inhalation anthrax in humans occurred in Russia in 1979, when anthrax spores were accidentally released from a military biological weapons facility near the town of Sverdlovsk, killing at least 66 people. In the fall of 2001, lethal anthrax bacteria were spread deliberately through the U.S. Postal Service. Seventeen people became ill, and 5 died. SMALLPOX AND BIOTERRORISM Although the World Health Organization (WHO) declared that smallpox was eradicated in 1980, this contagious and deadly infectious disease caused by the Variola major virus, remains high on the list of possible bioterror threats. The last naturally occurring case of smallpox was reported in 1977. Currently, there is no evi- dence of naturally occurring smallpox transmission anywhere in the world. Although a world- wide immunization program eradicated smallpox disease decades ago, small quantities of smallpox virus officially still exist in research laboratories in Atlanta, Georgia, and in Novosibirsk, Russia.31 There is a fear there may be other unknown sources of smallpox virus that could fall into the hands of terrorists. In January 2003, the Bush Administration declared smallpox the “number one bio-threat fac- ing the country” and made planning for an attack a top priority.32 The Administration launched a national smallpox vaccination initiative with the goal of immunizing 500,000 health care workers in 30 days and 10 million emergency response personnel within a year. Immunization rates fell well-below that target level with approximately 40,000 people actually vaccinated. The plan faced obstacles, including unexpected side effects, worker compensation issues, and liability concerns that precluded its full implementation.33 6 NEGLECTED TROPICAL DISEASES Recently, neglected tropical diseases have garnered increasing international attention. The leaders of Canada, France, Germany, Italy, Japan, Russia, the United Kingdom, and the U.S. met at the G8 Summit in Japan in July 2008. Japan’s Prime Minister, Yasuo Fukuda, summa- rized their position on neglected tropical diseases: “We ... agreed to support the control or elimination of neglected tropical diseases (NTDs) to reach at least 75 percent of the people with NTDs. We also discussed the timeframe to provide US$ 60 billion to fight infectious diseases and strengthen health, and agreed to do so over 5 years, while some countries will provide additional resources for health systems including water.”34 Health officials estimate that one billion people -- one sixth of the world’s population -- suffer from one or more neglected tropical disease. Extreme poverty, war and civil conflicts, and natural disasters aggravate conditions that are conducive to the spread of these diseases. Lack of comprehensive surveillance, unreliable statistics, and the diseases’ obscure names con- tribute to their low profile and status among global public health priorities. WHO considers the following to be neglected tropical diseases: Buruli ulcer, dengue/dengue haemorrhagic fever, dracunculiasis (guinea-worm disease), fascioliasis, human African try- panosomiasis (sleeping sickness), leishmaniasis, leprosy, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases, trachoma, and yaws.35 2. FACTORS CONTRIBUTING TO THE EMERGENCE OF INFECTIOUS DISEASES Emerging and re-emerging infectious dis- complacency ... Infectious diseases unknown eases pose serious threats to the health of in this country just a decade ago, such as West the American people. In 2003, the IOM Nile encephalitis and hantavirus pulmonary issued Microbial Threats to Health: Emergence, syndrome, have emerged to kill hundreds of Detection, and Response, an important follow Americans -- and the long-term consequences up to the 1992 IOM report on emerging for survivors of the initial illnesses are as yet infectious diseases. The 2003 IOM report unknown. Other known diseases, including assessed the threats of emerging infectious measles, multidrug-resistant tuberculosis, and diseases to the U.S. and warned: even malaria, have been imported and trans- mitted within the United States in the last 10 “While dramatic advances in science and med- years... Compounding the threat posed by icine have enabled us to make great strides in these infectious diseases is the continuing our struggle to prevent and control infectious increase in antimicrobial resistance.”36 diseases, we cannot fall prey to an illusory TABLE II: FACTORS OF EMERGENCE I Microbial adaptation and change I International travel and commerce (i.e., drug resistance) I Technology and industry I Human susceptibility to infection I Breakdown of public health measures I Climate and weather I Poverty and social inequality I Changing ecosystems I War and famine I Human demographics and behavior I Lack of political will I Economic development and land use I Intent to harm Source: 2003 IOM Report: Microbial Threats to Health: Emergence, Detection, and Response. 7 Antimicrobial (Drug) Resistance “ IN THEIR ONGOING WAR AGAINST ANTIBIOTICS, THE BACTERIA SEEM TO BE WINNING, AND THE DRUG PIPELINE IS VERGING ON EMPTY...THE LAST DECADE HAS SEEN THE INEXORABLE PROLIFERATION OF A HOST OF ANTIBIOTIC-RESISTANT BACTERIA, OR BAD BUGS, NOT JUST MRSA BUT OTHER INSIDIOUS PLAYERS AS WELL. ” 37 -- SCIENCE Antimicrobial resistance is a serious patient that can identify infectious agents, poor infec- safety and public health issue. According to the tion control in health care and community set- National Institute of Allergy and Infectious tings, and poor hand hygiene. The use of Diseases (NIAID), “antimicrobial drug resist- antibiotics in agriculture and aquaculture also ance is the ability of a microbe to grow in the contributes significantly to antimicrobial presence of a chemical that would normally kill resistance.40 Preventing infection and decreas- it or limit its growth.”38 Disease-causing ing inappropriate antibiotic use are important microbes that have become hard to treat with strategies for controlling resistance. antibiotic drugs include E. coli, Salmonella, Staphylococcus aureus, and those causing TB, gonorrhea, and malaria, among others. People Difference Between Non-Drug Resistant infected with antimicrobial-resistant organisms And Drug Resistant Bacteria are more likely to have longer hospital stays and may require more complicated treatment. A class of drug resistant bacteria known as “gram-negative” is particularly hard to treat. One strain, acinetobacter baumannii, has threatened the lives, limbs, and organs of hundreds of U.S. forces fighting in Iraq and Afghanistan. According to DOD documents, more than 250 patients at U.S. military hos- pitals were infected with a highly resistant strain of acinetobacter between 2003 and 2005, with 7 deaths as of June 2006, linked to acinetobacter-related complications.39 Antimicrobial resistance is exacerbated by the overuse and misuse of antibiotics in people Source: National Institute of Allergy and Infectious and animals, the lack of rapid diagnostic tests Diseases, www.niaid.nih.gov 2005 colorized scanning electron micrograph (SEM) depicts numerous clumps of methicillin- resistant Staphylococcus aureus (MRSA) bacteria. Methicillin- resistant Staphylococcus aureus infections, e.g., bloodstream, pneumonia, bone infections, occur most frequently among persons in hospitals and health- care facilities, including nursing homes, and dialysis centers. 8 MRSA Methicillin-resistant Staphylococcus aureus (MRSA) infection is caused by Staphylococcus aureus bacterium. Often called “staph,” this organism is a common cause of serious skin, soft tissue, and bloodstream infections. The advent of antibiotics revolutionized the treatment of staph infections, greatly reducing morbidity and mortality. MRSA is a strain of staph that is resistant to broad-spectrum antibiotics commonly used to treat it. MRSA is a growing cause of fatal staph infections,41 causing potentially life-threatening infections in bones, joints, surgical wounds, the bloodstream, heart valves, and lungs.42 In the past, most invasive MRSA infections occurred in hospitals or other health care settings, such as nursing homes and dialysis centers. This is known as health care-associated MRSA, or HA- MRSA. Older adults and people with weakened immune systems are at most risk of HA-MRSA.43 More recently, community-associated MRSA, or CA-MRSA, has become increasingly responsible for serious skin and soft tissue infections and for a serious form of pneumonia among previously healthy persons.44 The deaths of 2 previously healthy school children in October 2007 -- one in Virginia and the other in New York -- have significantly increased public awareness about this serious public health concern. CA-MRSA rates continue to rise at an alarming rate, now accounting for more than half of community-acquired staff infections in many communities.45 Both HA- and CA-MRSA infections are painful, difficult to treat, and cost the U.S. health care system many billions of dollars annually. While both types of MRSA still respond to a few medications, intravenous vancomycin is the mainstay for treating severe MRSA infections and there are growing concerns that this medication may be losing its effectiveness. Some U.S. hospitals report seeing strains of MRSA that are less easily killed by vancomycin, and 7 cases of complete resistance were reported in this country between 2000-2006.46 Globalization Globalization, the worldwide movement Lower cost and efficient means of interna- toward economic, financial, trade, and com- tional transportation allow people to travel munications integration, has impacted pub- to more remote places and potential expo- lic health significantly. Technology and eco- sure to more infectious diseases. And the nomic interdependence allow diseases to close proximity of passengers on passenger spread globally at rapid speeds. Experts planes, trains, and cruise ships over the believe that the increase in international course of many hours puts people at risk for travel and commerce, including the increas- higher levels of exposure. If a person con- ingly global nature of food handling, pro- tracts a disease abroad, their symptoms may cessing, and sales contribute to the spread not emerge until they return home, having of emerging infectious diseases.47 Increased exposed others to the infection during their global trade has also brought more and travels. In addition, planes and ships can more people into contact with zoonosis -- themselves become breeding grounds for diseases that originated in animals before infectious diseases. jumping to humans. For example, in 2003, The 2002-2003 SARS outbreak spread quickly the monkeypox virus entered the U.S. around the globe due to international travel. through imported Gambian giant rats sold SARS is caused by a new strain of coronavirus, in the nation’s under-regulated exotic pet the same family of viruses that frequently trade. The rats infected pet prairie dogs, cause the common cold. This contagious and which passed the virus along to humans.48 sometimes fatal respiratory illness first International smuggling of birds, brought appeared in China in November 2002. Within into the U.S. without undergoing inspection 6 weeks, SARS had spread worldwide, trans- and/or quarantine, is of particular concern mitted around the globe by unsuspecting trav- to public health experts who worry that it elers. According to CDC, 8,098 people were may be a pathway for the H5N1 “bird flu” infected and 774 died of the disease.49 virus to enter the country. 9 SARS represented the first severe, newly ruption and economic losses. Schools, hos- emergent infectious disease of the 21st cen- pitals, and some borders were closed and tury.50 It illustrated just how quickly infec- thousands of people were placed in quaran- tion can spread in a highly mobile and inter- tine. International travel to affected areas connected world. SARS was contained and fell sharply by 50 - 70 percent. Hotel occu- controlled because public health authorities pancy dropped by more than 60 percent. in the communities most affected mounted Businesses, particularly in tourism-related a rapid and effective response. areas, failed. According to a study by Morgan Stanley, the Asia-Pacific region’s economy SARS also demonstrated the economic con- lost nearly $40 billion due to SARS.51 The sequences of an emerging infectious disease World Bank found that the East Asian in closely interdependent and highly mobile region’s GDP fell by 2 percent in the second world. Apart from the direct costs of inten- quarter of 2003.52 Toronto experienced a sive medical care and disease control inter- 13.4 percent drop in tourism in 2003.53 ventions, SARS caused widespread social dis- 10 Environmental Factors Geophysical phenomena such as shifts in temperature, wind, and rainfall patterns can precipitate the appearance of new diseases in new places. Weather and climate affect dif- ferent diseases in different ways. For exam- ple, diseases transmitted by mosquitoes, such as dengue fever, Rift Valley fever, and yellow fever are associated with warm weather (addi- tional information on these diseases can be found in Appendix B) and experts believe that an El Niño occurrence (a fluctuation of the ocean-atmosphere system in the tropical Pacific having important consequences for weather around the globe), may be a factor in the resurgence of malaria and cholera.54 On the other hand, influenza becomes epi- demic primarily during cool weather. Meningococcal meningitis is associated with dry environments, while cryptosporidiosis outbreaks are associated with heavy rainfall, which can overwhelm sewage treatment plants or cause lakes, rivers and streams to become contaminated by runoff which con- tains waste from infected animals. Climate changes in North America are believed to be responsible for the growing populations of 2 new species of mosquitoes, including Asian tiger mosquitoes, in the continental U.S. These insects, which are believed to be successful bearers, or “vec- tors,” of diseases like LaCrosse encephalitis, yellow fever, dengue fever, and West Nile virus, now infest more than 30 states.55 Large scale climatic change may also have an effect on the timing of migration of wild birds, which in turn can impact the move- rates of deforestation have grown signifi- ment of other species such as ticks and lice. cantly since the beginning of the 20th cen- Wild birds are important to public health tury. Driven by rapidly increasing human because they can be infected by a number of population numbers, large areas of tropical microbes that can then be transmitted to and temperate forests, as well as prairies, humans. In addition, birds migrating across grasslands, and wetlands, have been con- national and intercontinental borders can verted to agricultural and ranching uses. become long-range carriers of any bacteria, The result has been an upsurge of certain virus, parasite, or drug-resistant organism infectious diseases, as the relationships they harbor.56 Wild birds are believed to be between humans and disease vectors (carri- key to the rapid spread of West Nile virus ers) shift. Deforestation, with subsequent across the entire country just 3 years after the changes in land use and human settlement first case was identified in New York in 1999. patterns, has coincided with increased Similarly, migratory birds are being closely malaria prevalence in Africa, Asia, and Latin observed by human health and veterinary America.58 Conversely, reforestation in the health officials as they monitor the spread of Northeastern and the upper Midwest the H5N1 avian influenza virus worldwide.57 regions of the U.S. has promoted an Deforestation and reforestation also can be increase in the population of the white- factors in the spread and prevalence of cer- tailed deer, an important host for the ticks tain emerging infectious diseases. Globally, that carry Lyme disease.59 11 Social Inequities, Geopolitical Events, and Human Behavior A number of societal factors contribute to with diarrhea, can lead to malnutrition in the emergence and re-emergence of infec- young children, so that diarrheal illness is tious disease. Poverty, lack of access to health both a cause and an effect of malnutrition.61 care, poor sanitation, unsafe water, and a lack War and civil strife generally result in a of proper hygiene all contribute to the breakdown of domestic stability, food and expanding impact of infectious diseases. water shortages, and destruction of the Overcrowded and poor living conditions medical infrastructure, including existing make people living in poverty especially vul- vaccination programs. Refugee camps often nerable to communicable diseases such as TB are crowded and dirty, with little or no and cholera. Limited access to health care access to medical care or protection from and medicine can render otherwise treatable disease transmission.62 conditions such as malaria and TB fatal for High-risk behaviors continue to be an those living in poverty. Urban decay and important factor in the transmission of squalid living conditions and the presence of some infectious diseases. Sexual behavior vermin also contribute to the spread of infec- and use of intravenous drugs continue to be tions, such as plague. Meanwhile, contami- primary modes of HIV transmission, and nated water and inadequate sewage treatment public health efforts over the last few systems in impoverished nations contribute to decades have demonstrated how difficult the spread of infectious diseases like cholera.60 such behaviors are to change. In developing Poor nutrition and compromised immune nations, ignorance of preventive measures systems are also key risk factors for several and the absence of social agencies to teach major diseases including lower respiratory the avoidance of risky behaviors exacerbate infections, TB, and measles. There is the problem. Once diagnosed with a partic- increasing evidence that suggests that mal- ular disease, failure to comply with pre- nutrition is the underlying reason for scribed treatment regimens is another fac- increased susceptibility to infectious dis- tor of transmission. The emergence of drug- eases especially in children. At the same resistant TB can be attributed in large part time, infections, especially those associated to poor patient compliance with therapy.63 PARASITIC DISEASES AND POVERTY IN THE U.S. Parasitic diseases are rare in the U.S. However, these diseases have been found in certain low- income communities. Researchers find at-risk populations to include “people of color living in the Mississippi Delta and elsewhere in the American South, in disadvantaged urban areas, and in the U.S.-Mexico borderlands, as well as in certain immigrant populations and disadvantaged white populations living in Appalachia.”64 Natural disasters, compounded by poverty, can also lead to spikes in these diseases, as was the case post-Hurricane Katrina along the Gulf Coast. Some of the top exiting parasitic threats currently in the U.S. include: I Ascariasis -- the most common worm infection in humans. It is caused by a parasitic worm that lives in the intestine, and infected just under 4 million people in 1974 according to the last survey, in the South and Appalachia. I Toxocariasis -- a roundworm parasite transmitted in dog droppings. It has the potential to cause intestinal illness and blindness, according to the CDC, and infect up to 14 percent of the U.S. population. So far, this parasite has infected up to 2.8 million poor black children in inner cities, the South and Appalachia.65 I Strongyloidiasis -- caused by a threadworm that lives throughout the body and can cause hyper-immune reactions, and infects 68,000 to 100,000 people each year. I Cysticercosis -- associated with the pork tapeworm. I Giardiasis -- diarrheal illness caused by a one-celled parasite. Not all of these diseases are life-threatening, but they can lead to symptoms and complications that make the lives of people in poverty even harder. Chronic conditions that can develop from these diseases include asthma, epilepsy, diarrhea, fever and heart disease, which can adversely affect child development and hearing, as well as professional and financial stability. 12 3. IMPACT OF EMERGING INFECTIOUS DISEASES AT HOME Emerging infectious diseases already pose a are increasingly commonplace. And, the U.S. domestic health crisis. has experienced its first deliberate and lethal attack using a biological agent as a weapon. West Nile virus is now endemic in the U.S. American troops are returning from Iraq and Emerging and re-emerging infectious dis- Afghanistan with highly drug resistant bacte- eases pose risks for all Americans. For exam- rial infections. Increasingly, locker rooms ple, if a severe infuenza outbreak were to and gymnasiums are sources of staph infec- occur, the U.S. government estimates that as tions. A heretofore unknown pathogen -- many as 90 million Americans could become SARS -- emerged, causing illness, death, and sick and 2 million might die.66 The conse- economic mayhem. Public health officials quences of a bioterror attack involving small- remain on high alert for the first sign that the pox or anthrax are almost unfathomable. deadly H5N1 avian influenza virus has While U.S. public health officials must be breached U.S. borders. An American citizen prepared for such scenarios, they remain thought to have XDR-TB exposed the vul- hypothetical. There are, however, a number nerability of the U.S. public health system. of emerging and re-emerging infections that Deadly foodborne disease outbreaks from are real threats to the health of Americans as domestic and imported agricultural products well as the U.S. economy today. High Prevalence Rates and High Costs There are 1.2 million people living with of the American Medical Association estimated HIV/AIDS in the U.S., including more than that MRSA infects more than 94,000 people 440,000 with AIDS.67 There are an estimated and kills nearly 19,000 annually nationwide.73 56,300 new cases of HIV diagnosed in this That makes it the sixth leading cause of death country every year.68 Nearly 566,000 in the U.S. MRSA-specific studies suggest that Americans have died of AIDS since 1981.69 the additional cost of treating an antibiotic- African Americans accounted for 49 percent resistant staph infection versus one that is not of new HIV infections diagnosed in the U.S. resistant range from a minimum of $3,000 to in 2006, although they comprise only 13.8 more than $35,000 per case. In 2005, such percent of the population. The HIV infec- infections cost the health care system tion rate among African Americans is 7 (patients and hospitals) an extra $830 million times higher than the rate among whites. to $9.7 billion, before taking into account The infection rate among Latinos is 3 times indirect costs related to patient pain, illness, higher than the rate among whites.70 and time spent in the hospital.74 As devastating as the health consequences of Hepatitis C is a liver disease caused by HCV this infectious disease may be, the costs of treat- and is transmitted through blood or other ing HIV/AIDS are equally staggering. The body fluids. These infections sometimes result annual per-patient medical expenses associated in an acute illness, but most often become a with doctor appointments, laboratory tests, and chronic condition that can lead to cirrhosis of drugs to prevent or treat HIV-related oppor- the liver and liver cancer. tunistic infections average from $18,000 - In 2006, there were an estimated 19,000 new $20,000, with even higher costs for those with hepatitis C virus infections in the U.S. and an more advanced HIV-related illness. These costs estimated 3.2 million Americans have chronic do not include those related to lost productivity. hepatitis C virus infection. Approximately 8,000- The costs to the American taxpayer are also 10,000 people die every year from hepatitis C high. In Fiscal Year 2007, total federal spending related liver disease.75 It is the leading cause of on HIV/AIDS-related medical care, research, cirrhosis and liver cancer and the most com- prevention, and other activities in the U.S. was mon reason for liver transplantation in the U. S. $23.3 billion.71 Additionally, during the same According to the American Liver Foundation, time period, the share of state-Medicaid spend- medical expenditures for people with hepati- ing on AIDS was estimated to be $5.5 billion tis C are estimated to be $15 billion annually. and states reported spending $294 million on The projected direct and indirect costs of their AIDS Drug Assistance Programs.72 hepatitis C will be $85 billion for the years The MRSA numbers are alarming too. A 2007 2010-2019, as the number of people chroni- CDC-supported study published in the Journal cally infected will likely continue to increase.76 13 HEPATITIS C OUTBREAK IN LAS VEGAS In February 2008, CDC investigators responded to a request from the Nevada health officials to help investigate 3 cases of hepatitis C (HCV) in people who had undergone procedures at the same Las Vegas endoscopy clinic. Three additional cases were identified later. During the investigation of the clinic, where routine colonoscopies were performed, health officials found that the re-use of syringes was the likely cause of transmission. Forty-thousand people were then notified that they might have been exposed to HIV and HCV, in what a federal health official called the largest notification of its kind in U.S. history.77 The clinic was subsequently shut down by city officials. Infections Making a Comeback In addition to emerging infections, Americans tions occurred among immigrants, refugees, also are increasingly at risk from re-emerging and foreign visitors, compared with a little infectious diseases. For example, after seeing a more than 4 percent of U.S.-born residents decline in TB cases in the U.S. over the last with active TB infection.79 decade, this contagious airborne disease Additional information on latent TB and could be on an upswing active TB infection can be found in Of particular concern is the number of cases Appendix A. of drug-resistant TB found in foreign-born Other infectious diseases, once thought to be individuals now residing in the U.S. According under control, have experienced recent out- to a study conducted by CDC researchers, 57 breaks in the U.S. They include pertussis percent of all TB cases in the U.S. were among (especially among adolescents), mumps, and foreign-born individuals in 2006.78 Approx- measles, all of which are vaccine-preventable. imately 10 percent of drug-resistant TB infec- AN INTERNATIONAL TB SCARE The threats posed by XDR-TB garnered public attention in May 2007, when Andrew Speaker, a U.S. citizen with drug-resistant tuberculosis, led public health officials on a trans-Atlantic chase. The incident began when Speaker flew to Europe on a commercial airline for his wedding and honeymoon. He was aware that he had an active case of drug-resistant TB, but it was not until he was out of the U.S. that tests suggested he had XDR-TB. CDC officials tracked Speaker down in Rome and asked him to turn himself into Italian health officials. Instead, he and his wife flew commercially to Prague, then on to Montreal, and drove by car back into the U.S. Speaker claims he took these actions because CDC indicated that he would be held in Italian quarantine for up to 2 years. Out of concern that Speaker could have infected fellow travelers with the disease, health offi- cials advised anyone who flew with him on the trans-Atlantic flights to be tested. Subsequently, Speaker was treated at the National Jewish Medical and Research Center in Denver, where it was announced that Speaker’s earlier diagnosis was incorrect and that he instead had the more treatable MDR-TB. CDC later confirmed this diagnosis. The incident raised serious questions about the effectiveness and timeliness of TB testing, U.S. border security, and the practicality of international restrictions on travel by people with infec- tious diseases. A Congressional investigation into the incident found significant security gaps, heightening concern about vulnerability to potential cases of pandemic influenza or smallpox. 14 DENGUE FEVER NIPPING AT OUR BORDERS Dengue fever is a flu-like illness that can be painful and debilitating and is sometimes referred to as “break bone” fever that is transmitted by mosquitoes. The more severe dengue hemorrhagic fever and dengue shock syndromes can be fatal.80 Most common in tropical and subtropical regions, public health experts believe that dengue is one of the world’s most important re-emerging diseases. Worldwide, 50 to 100 million cases of dengue infection occur each year. This includes 100 to 200 cases in the U.S., mostly in peo- ple who have recently traveled abroad. Many more cases likely go unreported because some health care providers do not recognize the disease. Mosquitoes that can transmit the illness have been found in 36 U.S. states and are of particu- lar concern along the U.S.-Mexico border and in Puerto Rico.81 In 2001, there was a dengue fever epidemic in Hawaii that sickened at least 120 people.82 Food-Related Infectious Diseases on the Rise “ FOODBORNE ILLNESSES ARE DEFINED AS DISEASES, USUALLY EITHER INFECTIOUS OR TOXIC IN NATURE, CAUSED BY AGENTS THAT ENTER THE BODY THROUGH THE INGESTION OF FOOD. EVERY PERSON IS AT RISK OF FOODBORNE ILLNESS. ” 83 -- WORLD HEALTH ORGANIZATION Infectious diseases transmitted by foods an outbreak of bloody diarrhea traced to have become a major public health concern hamburgers from a fast-food chain.86 in recent years. It seems that hardly a Cyclospora emerged in 1992 as a foodborne month goes by without the report of a food- pathogen, and was later traced to outbreaks borne illness outbreak in the U.S. in the U.S. from imported Guatemalan rasp- berries.87 In March 2008, melons imported Approximately 76 million Americans -- nearly from Honduras caused Salmonella infections one-quarter of the U.S. population -- are sick- in 16 states; and beginning in April 2008, a ened by foodborne disease each year. Of these, Salmonella outbreak, thought to be associat- an estimated 325,000 are hospitalized and ed with jalapeño and Serrano peppers 5,000 die. Medical costs and lost productivity imported from Mexico, sickened at least due to foodborne illnesses are estimated to 1,400 Americans in 43 states.88 In 2007, the cost $44 billion annually.84 Major outbreaks can U.S. Department of Agriculture issued 20 also contribute to significant economic losses separate meat recalls due to potential E. coli in the agriculture and food retail industries.85 contamination, and in February 2008, the Several new foodborne pathogens have department issued its largest beef recall in emerged over the last few decades. E. coli history -- 143 million pounds of beef -- from O157:H7 was first identified in 1982 during a California meatpacking company.89 “I, for the life of me, cannot understand why the terrorists have not attacked our food supply, because it is so easy to do.” -- FORMER U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES SECRETARY, TOMMY THOMPSON, DECEMBER 2004. Agroterrorism is the “deliberate introduction of an animal or plant disease with the goal of generating fear, causing economic losses, and/or undermining stability.”90 The deliberate contamination of our nation’s food supply is a serious threat that could have a quick, widespread impact. In January 2004, the Bush Administration responded to this very real threat with Homeland Security Presidential Directive/HSPD- 9, “Defense of United States Agriculture and Food.”91 This directive calls for a coordinated national approach to countering threats to the food supply. 15 4. THE NEED TO IMPROVE INFECTIOUS DISEASE PREVENTION Scientists worldwide -- government and aca- and should, improve and expand its diagnos- demic, together with their industry partners tic and disease surveillance capabilities, and and international collaborators -- have made dramatically increase its investment in devel- great strides in understanding emerging and oping new treatments and vaccines. Scientists re-emerging infectious diseases. Many of also need to better understand mechanisms these discoveries have resulted in novel diag- of drug resistance and develop new ways to nostics, anti-infective therapy, and vaccines. circumvent this growing public health threat. Yet, much remains to be done. The U.S. can, Surveillance Disease surveillance is defined as the “system- 2008 multi-state foodborne outbreak, which atic collection and analysis of data and the pro- initially implicated tomatoes before identify- vision of information which leads to action to ing the source as peppers. Or consider the prevent and control a disease, usually of an possibility of a domestic outbreak of a new infectious nature.”92 The primary purpose of strain of influenza virus. disease surveillance is to predict, observe, and That is why CDC should make it a priority to minimize harm caused by outbreaks, pan- ensure that every state and local health depart- demics, and pandemic situations, as well as to ment in the U.S. is part of a 21st-century dis- better understand what factors might con- ease surveillance system that is interoperable tribute to the spread of the disease. In the among jurisdictions and agencies to ensure U.S., state and local health departments, in rapid information sharing. Surveillance sys- collaboration with CDC, are responsible for tems should be able to detect and characterize disease surveillance. The National Electronic known infectious disease outbreaks, new syn- Disease Surveillance System (NEDSS), a com- dromes (e.g., SARS in 2003), or a bioterrorist ponent of the Public Health Information attack. Plans should ensure adequate labora- Network (PHIN), is a CDC-led initiative that tory surveillance of influenza and other infec- was developed to integrate and standardize tious diseases, as well as testing for pathogens the tracking of infectious diseases at the local such as E. coli and XDR-TB. level. Additionally, BioSense, another compo- nent of PHIN, collects syndromic surveillance, Furthermore, CDC should consider how like patients’ symptoms, quantities and types health information technology (HIT) can be of prescriptions, and emergency room visits to mobilized far more effectively to improve sur- alert health officials to possible disease out- veillance capability and overall public health breaks or health emergencies. preparedness. When coordinated, HIT sys- tems can facilitate data exchange among The U.S. government also implements or par- public health partners and facilitate the man- ticipates in more than 25 specialized systems agement of data from health care delivery for monitoring diseases. The networks include facilities, laboratories, and health agencies. the Global Emerging Infectious Diseases Sentinel Network, also known as GeoSentinel; At the same time the U.S. needs to be a EMERGEncy ID NET; the Foodborne Dis- leader in efforts designed to accurately eases Active Surveillance Network (FoodNet); assess the burden of infectious diseases in the Active Bacterial Core Surveillance System; developing countries, detect the emergence the National Respiratory and Enteric Virus of new microbial threats, and direct global Surveillance System; the National Tuber- prevention and control efforts. The culosis Genotyping and Sur veillance Network; nation’s endorsement and subsequent com- and the National Influenza Surveillance pliance with the 2005 revisions to the Systems, among others. International Health Regulations (IHR), which encourage nations to work together Despite this proliferation of networks, the to take preventive measures against, as well overall system of disease surveillance in the as detect, report on, and respond to, public U.S. has not developed into a robust, coor- health emergencies of international con- dinated capability. Consider for example, cern, is a step in the right direction. the delay in identifying the source of the 16 Most traditional global disease surveillance infectious disease threats. Many public health programs target only specific diseases (e.g., officials support expansion of these existing influenza or polio) and the infrastructure systems because infectious diseases -- often of and support is relatively weak for the more animal origin -- are a major cause of morbid- difficult task of tracking emerging and re- ity and mortality in poorer populations, and emerging infectious diseases. This is espe- such environments frequently serve as incu- cially true in developing countries, where bators for emerging pathogens.93 scarce human and material resources may The U.S. should enhance its commitment to not support even routine surveillance tasks, the 2005 IHR revisions by increasing support such as the recording of births and deaths. for CDC’s Coordinating Office for Global Recent international initiatives to expand Health, including expanding the number of capacity for the detection and surveillance of its Global Disease Detection Centers. HIV/AIDS and avian influenza have not Similarly, DOD and NIH should expand and been broadened to enable a look at all major increase overseas program sites and research. INTERNATIONAL HEALTH REGULATIONS (2005) The International Health Regulations (2005) (IHR) govern the roles of WHO and 194 nations (Member States) with respect to disease outbreaks and other public health events with inter- national impact. The regulations update the previous version of the IHR, which was adopted in 1969. They are designed to prevent and protect against the international spread of diseases while minimizing interference with world travel and trade. The revised IHR, which became effective in 2007, gives WHO clearer authority to recommend to its Member States measures that will help contain the international spread of disease, including public health actions at ports, airports, and land borders, and on means of transport that involve international travel. The revised regulations include a list of 4 diseases -- smallpox, polio, SARS, and human cases of new subtypes of human influenza -- that Member States must immediately report to WHO. The U.S. government began complying with the revised IHR on July 18, 2007.94 Diagnostics New rapid diagnostic tests are needed across A focus on point-of-care testing is particu- the spectrum of emerging infectious dis- larly important. Developments in nanotech- eases. Many existing diagnostic tools are nology have the potential to improve sensi- outdated and difficult to use. For example, tivity and specificity of point-of-care, hand- the standard test for diagnosing active TB in held diagnostics over time and at a potential most of the world is smear microscopy, gen- cost-savings over current technology. This erally of s sputum sample. Quality samples type of diagnostic tool would be particularly are hard to obtain; moreover, this test is over useful during an influenza pandemic. 100 years old and is only 50 percent accu- The next generation of effective diagnostic rate, and cannot determine drug suscepti- tools needs to be made available worldwide bility. Failure to quickly and accurately for use by a workforce that has been ade- detect infections, such as TB, can be deadly quately trained in their use. Also, given that and costly. There is more opportunity for an 35 of the most recent emerging diseases, infection to spread that longer that it goes including avian influenza, monkeypox, West undetected. In addition, the infection is Nile Virus and SARS, have been zoonotic more likely to be treated with a broad spec- (animal-borne) in origin,96 updated diag- trum drug, which increases the risk for nostic tools to improve disease detection in resistance and adverse outcomes. animals should also be a priority. 17 CLINICAL TRIALS FOR NEW ANTIBIOTICS ARE CHALLENGING A clinical trial is the scientifically controlled study of the safety and effectiveness of a drug or vaccine, using consenting human subjects. Clinical trials for new antibiotics are complicated and time consuming. Finding enough patients to enroll in clinical trials of new drugs to treat resistant pathogens is not easy. For many resistant pathogens, there are no rapid diagnostic tests available to help researchers to identify patients who would be eligible for their studies. By contrast, when enrolling patients in a clinical trial to test a new cancer drug, researchers know from the start whether a specific patient has the specific type of cancer they are targeting. With antibiotic clinical trials, that is not necessarily the case. As one industry consultant explained, in order to test a drug that is intended to treat resistant strains, “You have to wait for epidemics to break out in hospital wards, and you can’t predict when that will happen. It may take 5 years to complete a clinical study.”97 That is one of the reasons that the need for new rapid diagnostics to detect drug resistant bacteria infections is particularly acute. Treatment While dramatic advances in science and action, with no cross-resistance with other medicine have enabled scientists, medical antibiotics). In 2002, among 89 new medi- practitioners, and public health officials to cines emerging on the market, none was an make great strides in the struggle to control antibiotic.”99 This trajectory needs to change. and treat infectious diseases, there is a sig- The development of new, improved thera- nificant amount of research, development, pies to treat drug resistant bacterial infec- and testing that remains to be done. tions, as well as for influenza and other virus- Once considered “miracle drugs,” antibi- es is essential. According to FDA, because of otics successfully treat a range of bacterial rising costs, innovators often concentrate infections, such as strep throat, ear infec- their efforts on products with potentially tions, urinary tract infections, and pul- high market return. Developing counter- monary infections. However, overconfi- measures and medicines targeted for impor- dence in existing antibiotics, over-reliance tant public health needs (e.g., drug resist- on them, disincentives for industry to devel- ance, counterterrorism), less common dis- op new antibiotics (because a drug that takes eases, diseases prevalent in the developing decades to develop might be useful clinically world, or individualized therapy is becoming for only a few years), lack of sufficient diag- increasingly challenging.100 That is why addi- nostic tools, and competition from more tional incentives may be necessary to foster highly profitable opportunities for pharma- the development of treatment medications ceutical development and sale of medicines for those diseases that do not represent large to treat chronic diseases, has resulted in a lag market opportunities but have high rates of in the production of new classes of antibi- morbidity and mortality. The threat of cer- otics. According to the Infectious Diseases tain drug resistance and viruses as agents of Society of America, “the end result of the biological terrorism emphasizes the decline in antibiotic discovery research is increased need for the development of new that U.S. Food and Drug Administration counter-measures, as well as broad-spectrum (FDA) is approving few new antibiotics. antibiotics, antivirals, and immunomodula- Since 1998, only 12 new antibiotics have tors, especially for those agents for which been approved, 2 of which are truly novel there are no vaccines.101 (i.e., defined as having a new target of 18 Vaccines The success of vaccines in preventing infec- production methods and a pricing structure tious diseases has been profound. The that may not adequately compensate indus- childhood diseases of diphtheria, tetanus, try for development costs in the years imme- and polio are relatively rare in the devel- diately following licensure.102 oped world and are controlled in many Cultural obstacles, religious and ethical con- developing countries. Smallpox, one of the cerns, and misinformation about the safety most horrific killers in human history, was and efficacy of vaccines can impact market eradicated through the employment of an size and increase the likelihood of vaccine- effective vaccine. However, despite some preventable diseases in those who are not progress and the dedication of scientists immunized. For example, of the 95 patients worldwide, there still are no highly effective who contracted measles during the 2008 vaccines available to prevent 3 of the world’s outbreak in the U.S. and were eligible for largest killers: HIV/AIDS, TB, and malaria. vaccination (over 12 months of age), 63 And, a large proportion of the world’s chil- were unvaccinated because of their or their dren do not have access to currently-avail- parents’ philosophical or religious beliefs.103 able, highly effective vaccines. The U.S. must continue to modernize its As science and medicine progress, sometimes approach to vaccine production and delivery, at lightening speed, opportunities for major increase domestic capacity to manufacture breakthroughs in vaccine development are vaccines, and recognize that it has a responsi- very promising. Scientists have made signifi- bility to help assure that all the people of the cant advances in genomics, immunology, and world have access to vaccines. This is both a biotechnology, including discoveries in moral responsibility and a practical necessity; reverse genetics methods for faster develop- in a highly interdependent world, mitigating ment of influenza vaccines and for new vac- the impact of any infectious disease pandem- cines such as Gardasil and Cervarix, which ic requires that all corners of the globe are protect against certain types of the human protected equally. As part of this effort, the papillomavirus (HPV) infection that can cause U.S. government must coordinate activities cervical cancer in girls and young women. between the public and private sectors, and Vaccine development and production is with academia. To effectively harness the sci- complex and is dictated by a set of variables, entific expertise potentially available for this including the translation of basic research endeavor, vaccine development and modern- into the development of effective vaccines, ization efforts must be open and transparent regulatory requirements, liability concerns, to ensure that experts from government, and market forces, which include market industry, and academia from around the disincentives for developing new vaccine world have access to vital information. New Technology Geographers are contributing to the fight surface temperature patterns in the Indian against emerging infectious diseases by and Pacific oceans, scientists now believe turning satellite imaging and global posi- they have found a way to predict outbreaks tioning systems into tools to help prevent up to 5 months in advance. By predicting infection. In the early 2000s, scientists pre- the likely onset of an outbreak, the geogra- dicted an outbreak of the mosquito-borne phers prompted local public health officials Rift Valley fever in Kenya by using these to implement prevention strategies.104 devices. Scientists at the Goddard Earth Hantavirus outbreaks in the U.S. Southwest Sciences and Technology Center and at the could also be monitored in this way. The virus Walter Reed Army Institute of Research is carried by deer mice and can kill people have discovered that outbreaks of Rift Valley who have been exposed to it. Like Rift Valley fever follow sudden floods triggered by El fever, Hantavirus is correlated with rainfall, so Niño and a similar (yet lesser-known) cli- the same kind of bioclimatic rhythms can be mate disturbance called the “Indian Ocean used to predict an outbreak.105 Dipole.” Using weather satellites to track sea 19 5. FINANCIAL INCENTIVES ARE CRITICAL If the demand for new diagnostics, therapeu- date drugs. But these are still few for each tics and vaccines to combat emerging infec- disease, and success may rest on the fate of tions is so urgent, why has industry not one or 2 products. New types of products answered the call? The answer requires a clos- also require new delivery systems (e.g., “gene er look at market forces and business strategy. gun” system for administering DNA vac- cines) and new production systems (e.g., The development of new medical technolo- cell-based production systems for influenza gies is a long and expensive process. vaccine) that carry their own development Pharmaceutical industry standards for new risks and costs. Finally, many emerging dis- drug development are a good example. eases are currently uncommon in the U.S. or These standards predict, on average, a 10-year are treated with short-course therapy, thus development period from drug discovery to creating a small market for their sales. licensure at a price tag around $1 billion.106 A significant proportion of the time and fund- When a large pharmaceutical or biotechnolo- ing required comes in advanced develop- gy company is faced with the choice of pursu- ment. In addition, the expected failure rate is ing a new drug for TB or the next multi-billion high; only 10 percent of candidate drugs in dollar statin, shareholders are much less inter- Phase I trials ever make it to licensure.107 ested in altruism than in a wise investment that minimizes opportunity costs. As a result, In order to maintain profitability in a highly a significant proportion of product develop- competitive market, pharmaceutical and ment for biodefense or emerging infectious biotechnology companies must minimize diseases rests with small companies. Many of the risk of development while maximizing these are supported by venture capital, and the reward (profit) potential for products. they lack institutional experience of carrying a Risk is minimized by spreading it among product from discovery to licensure. multiple drug candidates, pursuing class analogs similar to already successful prod- Advocates, policymakers, pharmaceutical ucts, and utilizing existing and proven sys- companies, and researchers debate ways in tems for developing and manufacturing. which research and development of vaccines, Reward is maximized by targeting diseases treatments and diagnostic tools can be accel- with proven high returns. Generally drugs erated, but most agree that a combination of treating chronic and highly prevalent dis- initiatives is needed to fight emerging infec- eases create the best sales opportunities. tious diseases. No one-size-fits-all approach will spur adequate investment in biomedical Unfortunately, most countermeasures for research and development on emerging emerging infectious diseases present an infectious diseases. Different medications, unfavorable risk-reward balance for industry. vaccines, diagnostic tools, and surveillance NIAID funding has strengthened the aca- systems have different market potential and demic research base for emerging infectious require varying levels of up-front investment. diseases and has produced promising candi- Public-Private Partnerships Public-private partnerships are proving to strains, be compatible with antiretroviral be effective in the search for new vaccines therapies for those HIV-TB patients current- and drugs. Treatments for dengue fever, ly on such therapies, and improve treatment malaria, and MDR-TB are under develop- of latent infection.109 The GAVI Alliance’s ment through the Novartis Institute for (formerly the Global Alliance for Vaccines) Tropical Diseases, a public-private partner- Accelerated Development and Introduction ship involving the Swiss-based Novartis phar- Plans (ADIPs) have promoted research and maceutical company and the Singapore “negotiation with the pharmaceutical and Economic Development Board.108 Working public health sectors to achieve rapid, suc- with public and private research laborato- cessful introduction of the pneumococcal ries worldwide, the Global Alliance for TB and rotavirus vaccines.”110 Proponents of Drug Development is committed to acceler- public-private partnership urge greater sup- ating the discovery and development of new port of initiatives that involve small-scale TB drugs that will shorten treatment, be commercial endeavors. effective against susceptible and resistant 20 A massive infusion of philanthropic funds is Global Fund to Fight AIDS, Malaria and also stimulating investment in research and Tuberculosis. Former President Bill Clinton is development for vaccines and medicines, pro- supporting the Sabin Vaccine Institute’s “Stop fessional training, and public education Neglected Tropical Disease Campaign.”111 efforts. The Bill and Melinda Gates British Prime Minister Gordon Brown recent- Foundation is spearheading large global ly committed his nation to buying 20 million health initiatives, including support for the mosquito nets for malaria-ravaged nations. U.S. Government Programs to Spur Investment The U.S. government has several measures may be able to take advantage of existing pro- already in place to encourage private sector grams that are well established. For instance, investment for the development of vaccines, the far-reaching global HIV vaccine trial infra- medicines and diagnostics. In addition to the structure may be a useful model for testing specific measures described below, researchers tuberculosis treatments or vaccines. Orphan Drug Act The Orphan Drug Act (P.L. 97-414, as amend- For the purposes of the Act, an “orphan ed) includes various incentives that have stim- drug” is one that would treat or prevent a rare ulated a considerable amount of interest in disease or condition that affects fewer than the development of orphan drug and biolog- 200,000 persons in the U.S., or that may affect ical products. The incentives include tax more than 200,000 persons in the U.S., but credits for clinical research undertaken by a for which there is no reasonable expectation sponsor to generate required data for mar- that the cost of developing and producing the keting approval, and 7 years of marketing drug would be recovered from its U.S. sales.112 exclusivity for a designated drug or biological product approved by FDA. Project BioShield and BARDA In 2004, Congress passed the Project fessionals are working together to meet the BioShield Act to jump-start the nation’s abili- threat of bioterrorism -- we’re making the ty to develop, purchase, and deploy cutting- American people more secure.”113 edge countermeasures against a bioterrorism In 2006, Congress enacted the Pandemic and attack. The law also granted the federal gov- All-Hazards Preparedness Act (PAHPA), which ernment new authority to expedite research in part, directed HHS to establish the Biomed- and development on the most promising and ical Advanced Research and Development time-sensitive medicines to defend against Authority, or BARDA, and authorized funding bioterror. Congress authorized $5.6 billion of advanced development of medical counter- for Project BioShield over 10 years so that the measures, such as vaccines, drugs, and diag- government could purchase and stockpile nostic tools for public health emergencies vaccines and drugs to fight anthrax, small- affecting national security.114 pox, and other potential agents of bioterror. However, funding for Project BioShield has BARDA is the umbrella organization within been significantly lower than the level the Office of the Assistant Secretary for authorized. For example, the program was Preparedness and Response at HHS that pro- authorized at $1.07 billion for Fiscal Years vides an integrated, systematic approach to 2006-08, but received an appropriation of the development and purchase of the med- only $102 million in Fiscal Year 2008. ical countermeasures, treatments, and diag- nostic tools for public health medical emer- In signing the bill into law, President Bush gencies. Upon its creation, BARDA assumed acknowledged the vital role that the private responsibility for 2 existing separate, but sector plays in biodefense efforts by taking complementary projects: The Public Health risks to bring new treatments to the market. Emergency Medical Countermeasures Enter- He said, “By acting as a willing buyer for the prise (PHEMCE) and Project BioShield. best new medical technologies, the govern- ment ensures that our drug stockpile There is some expectation among remains safe, effective, and advanced. The researchers and government officials that federal government and our medical pro- the establishment of BARDA and its over- 21 sight of Project BioShield may improve the such a dedicated mechanism could allow chances of success during the development countermeasures to further mature through phase of countermeasures. According to the development process longer before the Congressional Research Service, “one of competing for a Project BioShield contract. BARDA’s roles is to support the advanced This could reduce the risk that a counter- research and development of promising measure will fail while under a Project countermeasures. In theory, funding this BioShield contract.”115 part of the development process through Priority Review Voucher for Neglected Tropical Diseases In September 2007, Congress approved an owner of the voucher can sell it to another amendment sponsored by Senators Sam company on the open market.117 New drugs Brownback (R-KS) and Sherrod Brown (D- or treatments for neglected tropical diseases OH) to the Food and Drug Administration may also qualify for market exclusivity and Revitalization Act, which created a transfer- tax credits under the Orphan Drug Act. able voucher to “encourage treatments for Unlike many other incentive mechanisms, tropical diseases.”116 The amendment allows the voucher program does not require any the sponsor of a newly approved drug or up-front financial outlays by governments or vaccine, which prevents or treats an eligible donors, and no budgetary provisions are tropical or neglected disease, to receive a required. However, some worry that while priority review voucher, which can then be developing new drugs and treatments is a cru- applied to another product. cial step to alleviating the burden of tropical Priority review reduces the time it takes FDA diseases, the voucher program does not guar- to assess a product submitted for approval antee that producers will make new treat- from an average of 18 months to “no ments available in sufficient quantities or at longer” than 6 months. The company prices that will be affordable to individuals.118 obtaining the voucher can use it for anoth- Vouchers, which are not universally support- er human drug submission, affording an ed by medical experts or the pharmaceutical opportunity to get that product to market industry, could be worth as much as $500 mil- many months sooner. Alternatively, the lion according to some estimates.119 Strategies to Address Antimicrobial Resistance (STAAR) Act Introduced in 2007 by Senators Sherrod HHS agencies as well as across multiple fed- Brown (D-OH) and Orrin Hatch (R-UT) eral departments, including Agriculture, and Representatives Jim Matheson (D-UT) Veterans Affairs, Labor, and Defense, as well and Michael Ferguson (R-NJ), the STAAR as the Environmental Protection Agency. Act is designed to enhance the U.S. ability to The STAAR Act would also provide new respond to the antimicrobial resistance opportunities to address the global antimi- problem. The bill would provide compre- crobial resistance problem. The STAAR Act hensive strategies to strengthen federal includes a comprehensive set of specific antimicrobial resistance surveillance, pre- actions to avoid a public health crisis that is vention and control, and research efforts. taking and/or debilitating the lives of hun- The legislation would authorize new fund- dreds of thousands of Americans annually.120 ing and strengthen coordination within 22 6. RECOMMENDATIONS The magnitude and urgency of addressing ration, and coordination with industry, aca- emerging and resurging diseases demand demia, private organizations, and founda- renewed attention, dedication, and sus- tions. Additional investments should take tained resources to ensure the health and the form of financial and technical assis- safety of the nation and of the world. tance, operational research, enhanced sur- veillance, and efforts to share both knowl- U.S. policy makers must abandon a point of edge and best public health practices across view that emerging infectious diseases in the national boundaries. The U.S. should exert developing world are a back-burner con- its leadership in setting global goals for cern for Americans. And the nation’s com- elimination or eradication of diseases where mitment to eliminating these diseases, or this is possible, such as malaria and tubercu- mitigating their impact on global mortality losis. In addition, the President should and morbidity, can no longer be based on appoint a distinguished public health offi- international goodwill alone. Emerging and cial to a new high-level position responsible re-emerging diseases, especially those relat- for coordinating the U.S. effort and for serv- ed to potential bioterror threats, are a mat- ing as a point of contact for public, private, ter of national security. and public-private efforts. Trust for America’s Health (TFAH) recom- mends the following actions, many of which 3. The U.S. should enhance its leadership mirror those made by the Board on Global role in promoting the implementation Health and the IOM in their 2003 report, of a comprehensive system of surveil- Microbial Threats to Health: Emergence, lance for global infectious diseases that Detection, and Response.121 builds on the current global capacity of infectious disease monitoring. 1. U.S. federal, state, and local govern- This multinational effort will require region- ments should allocate the necessary al and global coordination, expertise, and resources to build and sustain the financial resources from participating nation’s public health capacity to nations. A comprehensive system is needed respond to emerging diseases that are to accurately assess the burden of infectious naturally occurring or intentional. diseases in developing countries, detect the The nation’s public health capacity must be emergence of new threats, and direct pre- enhanced to respond quickly to emerging vention and control efforts. Sustainable disease threats and to monitor infectious progress in these efforts will require health disease trends. Prevention and control agencies to broaden partnerships to include capacity should be expanded at the local, philanthropic foundations and international state, and national levels and be executed by institutions such as the World Bank and the an adequately trained and competent work- United Nations. At the same time, infectious force. Examples include enhancing surveil- disease surveillance systems in developed lance (medical, veterinary, and entomologi- nations will require sustained investments to cal [related to insects]); augmenting labora- strengthen their capacity and make them tory facilities; building epidemiological, sta- more effective, accurate, and timely. tistical, and communication skills among the workforce; and implementing informa- 4. The U.S. government should develop a tion and logistical systems to ensure the comprehensive, multi-year, government- rapid utility and sharing of information wide research agenda for emerging infec- among the public, industry, health care tious disease prevention and control in facilities, and all levels of government. collaboration with state and local public health partners, academia, and industry. 2. The U.S. should further its leadership This agenda should be designed to investi- role in enhancing the global capacity to gate the role of genetic, biological, social, respond, control, and eliminate infec- economic, political, ecological, and physical tious disease threats. environmental factors in the emergence of The U.S. should continue efforts to coordi- infectious diseases in the U.S. and through- nate with key international agencies such as out the world. This agenda should also WHO, with active communication, collabo- include the development and assessment of 23 public health measures to address emerging longing the use of existing pesticides is and re-emerging diseases, including the paramount in the absence of vaccines to intentional use of biological agents. The prevent most vector-borne diseases. research agenda should be flexible enough to permit rapid assessment of new and 5. The U.S. government, professional emerging threats, and should be rigorously health organizations, academia, health reevaluated every 5 years to ensure that it is care delivery systems, and industry addressing areas of highest priority. should expand efforts to decrease the inappropriate use of antimicrobials in Components of the research agenda should human medicine, agriculture and include: aquaculture through: I A national vaccine strategy for protecting I Expanded outreach and better education the U.S. population from emerging and of health care providers, veterinarians, re-emerging infectious diseases. The fed- drug dispensers, the food industry, and the eral government should explore innova- general public on the inherent dangers tive mechanisms, such as cooperative associated with the inappropriate use of agreements between government and antimicrobials. industry or consortia of government, industry, and academia, to accelerate I Increased use of diagnostic tests, as well research and development efforts. as the development and use of rapid diagnostic tests, to determine the nature I A national strategy for developing new of the infection and drug sensitivity, antimicrobials, as well as producing an thereby ensuring a more appropriate use adequate supply of approved antimicro- of antibiotics. bials. This strategy should include plans for stockpiling and distributing antibi- 6. The U.S. government should work otics, antivirals, and antitoxins for natu- with academia, private organizations, rally occurring or intentionally intro- and foundations to recruit, retain, and duced disease threats. train public health professionals I A national strategy to better understand the capable of identifying, verifying, mechanisms of antibiotic resistance and to preventing, controlling, and treating develop and evaluate interventions to pre- emerging infectious diseases. vent and control resistance in human, ani- I Training should combine field and labo- mal and agricultural environments. ratory approaches to infectious disease prevention, diagnosis, and control. I A national strategy for developing new Federal agencies should develop these rapid, cost-effective sensitive diagnostics programs in close collaboration with state to identify targeted pathogens, ensure and local public health partners and aca- appropriate use of existing antimicrobials demic centers and should include an edu- in the clinical setting, and reduce the cost cational, hands-on experience at state of clinical trials for new antimicrobials and local public health departments. thereby serving as an incentive for greater industry research and development. 7. The U.S. government should support Development of rapid, point-of-care diag- intensified public health education nostic tests for TB, including drug-resist- efforts to prevent the spread of ant TB; health care associated bacterial infectious diseases. infections; and various strains of the influenza virus, should be priorities. I The U.S. should launch public education campaigns on hand hygiene and cough eti- I Research on innovative systems of surveil- quette, as well as the importance of com- lance that capitalize on advances in health plying with the recommended schedule of information technology. Integration of elec- childhood and adult vaccines, including tronic medical records into public health seasonal influenza vaccines. Additionally, surveillance systems should be pursued. disseminating information to the general I Research on vector control. The develop- public about the appropriate use of antibi- ment of safe and effective pesticides and otics should be a priority for the nation’s repellents, as well as strategies for pro- public health departments. 24 8. The U.S. Congress should: investment in TB research could have a I Amend the Orphan Drug Act to explicitly significant impact on disease control address infectious diseases like MRSA, or and mitigation globally, including vac- create a parallel incentive system to cine development. address the unique concerns in this area. I Enhance appropriations for ongoing emer- Specially tailored incentives are needed to ging infectious disease programs at NIH, spur the development of new antimicro- CDC, DOD, the Department of Agriculture, bials, vaccines, and diagnostics. and the Department of Homeland Security. I Fully fund BARDA, which was authorized I Increase appropriations for global surveil- at $1.07 billion for Fiscal Years 2006-08, lance efforts, including an increase in fund- but was funded in Fiscal Year 2008 at ing to $45 million for the CDC’s Global $102.1 million. Disease Detection program, which was I Enact the Strategies to Address Antimicro- funded at $31 million in Fiscal Year 2008. bial Resistance (STAAR) Act to strengthen I In light of the threat emerging and re- the U.S. response to the increasing antimi- emerging diseases pose to Americans, crobial resistance crisis through enhanced Congress should fully fund CDC’s pro- coordination, leadership, research, pre- grams to support state and local public vention and control, and surveillance. health departments’ all-hazards pre- I Request a professional judgment budget paredness activities. At a minimum, fund- for a comprehensive, multi-year, govern- ing should be restored to the Fiscal Year ment-wide research agenda for emerg- 2005 level of $919 million. In Fiscal Year ing infectious disease prevention and 2008, programs to upgrade the capacity control and fully fund it. For example, of state and local public health depart- according to the professional judgment ments were funded at $746 million. of senior NIH researchers, a $50 million Colorized transmission electron micrograph of Avian influenza A H5N1 viruses (seen in gold) grown in MDCK cells (seen in green). 25 APPENDIX A: THE WORLD’S DEADLIEST INFECTIOUS DISEASES Many of the global efforts to reduce the bur- lion or more illnesses a year and at least 6 mil- den of infectious diseases are concentrated on lion deaths.122 Also, hepatitis C (HCV) infec- HIV/AIDS, TB, and malaria. Combined, these tions are pervasive worldwide -- an estimated 3 diseases account for approximately 500 mil- 200 million people have the virus. Human Immunodeficiency Virus (HIV) Acquired Immunodeficiency Syndrome (AIDS) AIDS is a chronic, life-threatening condition for stemming the spread of HIV is to focus caused by the human immunodeficiency on prevention, treatment, and education. virus (HIV). By damaging or destroying the The U.S. commitment to the global battle cells of the body’s immune system, HIV against HIV/AIDS has been impressive. In interferes with the ability to effectively fight 2003, President Bush launched the off viruses, bacteria, and fungi that cause President’s Emergency Plan for AIDS Relief disease. This makes individuals with HIV (PEPFAR), committing $15 billion over 5 more susceptible to certain types of cancers years to combat global HIV/AIDS -- the and to opportunistic infections that the largest international health initiative in his- body would normally resist, such as pneu- tory to fight a single disease. In July 2008, monia, TB, and meningitis.123 The virus the U.S. Congress reauthorized PEPFAR itself is known as HIV. The term acquired and increased its funding level to $39 billion immunodeficiency syndrome (AIDS) is used over the next 5 years.126 In addition, the new to mean the later stages of an HIV infection. law provides funding to fight the diseases An individual can become infected with that complicate HIV/AIDS. It commits $4 HIV in several ways, including unprotected billion to fight tuberculosis -- which is the sex; transfusion of infected blood; transmis- leading killer of Africans living with HIV -- sion through needle sharing or accidental and pledges an additional $5 billion to com- needle sticks; re-use of syringes in a medical bat malaria. setting, especially where the medical infra- According to the White House, PEPFAR has structure is lacking; or transmission from already helped bring life-saving treatments to mother to child during pregnancy, delivery, millions of people worldwide. For example, or through breast feeding. In rare cases, the at of the end of Fiscal Year 2007, PEPFAR was virus may be transmitted through organ or supporting life-saving antiretroviral treat- tissue transplants or unsterilized dental or ment for approximately 1.7 million people surgical equipment.124 living with HIV/AIDS in the 15 focus coun- In the nearly 3 decades since the first tries in Sub-Saharan Africa, Asia, and the reports of the disease, AIDS has become a Caribbean. When the President announced global pandemic. Worldwide, an estimated PEPFAR in 2003, only 50,000 people in all of 38.6 million people are living with HIV, sub-Saharan Africa were receiving treatment. nearly half of them women and girls PEPFAR has also supported treatment and between the ages of 15 and 24. And though care for nearly 7 million people, including the spread of the virus has slowed in some millions of orphans and vulnerable children. countries, it has escalated or remained At the signing of the PEPFAR reauthoriza- steady in others. In 2007, more than 2.7 mil- tion, President Bush observed that the initia- lion people were newly infected with HIV; tive had allowed nearly 200,000 children in 25 million have died of AIDS since the pan- Africa to be born HIV-free.127 demic began, 2 million in 2007 alone.125 There are 1.2 million people living with Despite improved treatments and better HIV/AIDS in the U.S., including more than access to care for people in the hardest-hit 440,000 with AIDS.128 There are an estimat- parts of the world, most experts agree that ed 56,300 new cases of HIV diagnosed in the pandemic is still in the early stages. With this country every year.129 Nearly 566,000 a vaccine probably years away, the best hope Americans have died of AIDS since 1981.130 26 Hepatitis C (HCV) Hepatitis C is a contagious liver disease that I Sharing needles, syringes, or other equip- ranges in severity from a mild illness lasting a ment to inject drugs. few weeks to a serious, lifelong illness. It results I Exposure to needle stick injuries in from infection with the hepatitis C virus healthcare settings. (HCV), which is spread primarily through contact with the blood of an infected person. I Exposure to unclean tattooing or body- Hepatitis C can be either “acute” or “chronic.” piercing instruments. Acute hepatitis C virus infection is a short- I Being born to a mother who has hepatitis C. term illness that occurs within the first 6 Less commonly, a person can also get hepa- months after someone is exposed to the hep- titis C virus infection through: atitis C virus. Approximately 75 to 85 percent of people who become infected with hepati- I Sharing personal care items that may have tis C virus develop chronic infection. come in contact with another person’s blood, such as razors or toothbrushes. Chronic hepatitis C virus infection is a long- term illness that occurs when the hepatitis C I Having sexual contact with a person virus remains in a person’s body. HCV can infected with the hepatitis C virus.131 last a lifetime and lead to serious liver prob- Globally, 200 million people, or more than 3 lems, including cirrhosis (scarring of the percent of the world’s population are infect- liver) or liver cancer. ed with HCV.132 CDC estimates that 3.2 mil- People can become infected with the hepa- lion Americans have chronic HCV infection, titis C virus by: and approximately 10,000 die each year from HCV liver disease.133 Malaria Although malaria has been virtually elimi- A malaria infection is generally character- nated in developed nations with temperate ized by recurrent attacks, each of which has climates, it is still prevalent in tropical and 3 stages -- chills, followed by fever, and then subtropical countries in Africa, Asia, the sweating. Along with chills, the person is Middle East, South America, and Central likely to have headache, malaise, fatigue, America. Evolving strains of drug-resistant muscular pains, occasional nausea, vomit- parasites and insecticide-resistant mosqui- ing, and diarrhea. Within an hour or 2 of toes continue to make this emerging infec- the initial symptoms, the body temperature tious disease a global health threat. rises, and the skin feels hot and dry. Subsequently, as the body temperature falls, Malaria is caused by a single-celled parasite a drenching sweat begins.135 from the genus Plasmodium and is typically transmitted to humans by mosquitoes. Malaria Doctors can treat malaria effectively with can also be transmitted through blood trans- several medications, which are known col- fusions, organ transplants, or contaminated lectively as “antimalarial drugs.” However, needles or syringes. “Congenital” malaria there is increasing worry about drug-resist- refers to the transmission from a mother to ant parasites that have rendered some of her fetus before or during childbirth.134 these medicines ineffective. QUICK FACTS ON MALARIA I More than 40 percent of the world’s pop- I Approximately 300-500 million cases of ulation lives in areas where there is a risk clinical malaria occur each year. of contracting malaria. I Malaria accounts for at least $12 billion in I A child dies of malaria every 30 seconds. economic losses each year in Africa, and a reduction in annual economic growth esti- I More than one million people die of malaria mated at 1.3 percent. every year, mostly infants, young children, and pregnant women; most of them live in Africa. Source: World Health Organization 27 Tuberculosis (TB) Tuberculosis has plagued mankind for cen- People with weakened or compromised turies. Today, despite advances in treatment, immune systems - - individuals with HIV dis- TB is a global pandemic, fueled by the ease, those receiving chemotherapy, preg- spread of HIV/AIDS, poverty, a lack of nant women - - are at a much greater risk for health services, and the emergence of drug- developing active TB disease. When these resistant strains of the bacterium that causes people breathe in TB bacteria, the bacteria the disease.136 settle in the lungs and start growing because the individual’s immune system cannot fight Every year, about 9 million people develop the bacteria. In these people, TB disease active TB disease, and TB kills nearly 2 mil- may develop within days or weeks after the lion people worldwide. The infection is infection. In 2006, CDC reported 9,842 common - - about one-third of the human cases of active TB in the U.S.141 population is infected with TB, with one new infection occurring every second.137 The most common method for detecting TB infection is a tuberculin skin test, which TB is a contagious airborne disease caused is performed by injecting a small amount of by infection with Mycobacterium tuberculosis. tuberculin antigen under the skin in the TB typically affects the lungs; however it also lower part of the arm. A person given the may affect any other organ of the body, such tuberculin skin test must return within 48 to as the brain, the kidneys, or the spine. 72 hours to have a trained health care pro- There is a difference between latent TB fessional look for a reaction on the arm. A infection and active TB disease, which positive tuberculin skin test only indicates makes people sick and can be spread to oth- that a person has been infected with TB ers. One-third of the world’s population has germs. It does not confirm that the individ- the TB bacterium in their bodies, and they ual has progressed to active TB disease. The are considered to have a TB infection. presence of symptoms and additional tests, Those who do not get sick are known to such as a chest x-ray and a sample of spu- have latent TB infection, which is not conta- tum, are needed to determine whether the gious. TB bacteria can remain in this dor- individual has active TB disease.142 mant state for months, years, and even TB disease usually can be cured with prompt decades without increasing in number and and appropriate treatment, but it remains a without making the person sick. Most peo- major cause of death and disability in the ple with latent TB infection will test positive world. It is usually treated with a regimen of on the tuberculin skin test, or their chest X- drugs taken for 6 months to 2 years depend- ray will show signs of latent TB, but will not ing on the type of infection. It is imperative develop active TB disease, may never get that people who have TB disease finish the sick, may never show any symptoms, and medicine, and take the drugs exactly as pre- may never spread the bacteria to others.138 scribed. If they stop taking the drugs too However, approximately one in 10 people soon or do not take the drugs correctly, they infected with TB bacteria develop active TB can become ill again and the infection may disease. When an individual develops active become more drug resistant.143 TB, it means the TB bacteria are multiplying Public health officials are particularly con- and attacking the lung(s) or other parts of cerned about 2 forms of TB disease that are the body. Symptoms of active disease include drug resistant. According to NIAID, mul- cough, loss of weight and appetite, fever, tidrug-Resistant Tuberculosis (MDR-TB) is a chills, and night sweats as well as symptoms form of drug-resistant TB in which the TB bac- from the specific organ or system that is teria can no longer be killed by at least the 2 affected; for example, coughing up blood or best antibiotics, isoniazid (INH) and rifampin sputum in TB of the lungs or bone pain if the (RIF), commonly used to cure TB. As a result, bacteria have invaded the bones.139 TB germs this form of the disease is more difficult to treat spread when a person infected with active TB than ordinary TB and requires up to 2 years of disease in the lungs or throat coughs or multidrug treatment. Extensively drug-resist- sneezes.140 People with active TB disease are ant tuberculosis (XDR-TB) is a less common most likely to spread it to people they spend form of multidrug-resistant TB in which the time with every day. This includes family TB bacteria have changed enough to circum- members, friends, and coworkers. 28 vent not only INH and RIF, but also most of the Susceptibility testing for TB is time-consum- alternative drugs used against MDR-TB. These ing, resource-intensive, and not well-validat- second-line drugs include any fluoro- ed. Few laboratories are able to conduct the quinolone, and at least one of the other 3 tests, which dramatically complicates the injectable anti-TB drugs: amikacin, kanamycin, ability of public health officials to deter- or capreomycin. As a result, XDR-TB generally mine whether a patient is infected with the needs at least 2 years of extensive drug treat- standard variety TB, MDR-TB, or XDR-TB. ment and is very challenging to treat.144 MILLENNIUM DECLARATION AND MILLENNIUM DEVELOPMENT GOALS Since their adoption by 189 nations in September 2000, the Millennium Declaration and the Millennium Development Goals (MDGs) have become a universal framework for develop- ment and a means for developing countries and their development partners to work together in pursuit of shared commitments to reduce poverty and hunger, and to tackle major health issues, gender inequality, lack of education, lack of access to clean water and environmental degradation. Together, the 8 MDGs represents a compact that recognizes the contribution that developed countries can make through trade, development assistance, debt relief, access to essential medicines, and technology transfer. Goal 6 is directly related to infectious diseases. The following lists the targeted outcomes for the goal and how progress will be measured. GOAL 6: Combat HIV/AIDS, Malaria & Other Diseases Target 6A: By 2015, halt and begin to reverse the spread of HIV/AIDS. I HIV prevalence among population aged 15-24 years I Condom use at last high-risk sexual encounter I Proportion of population aged 15-24 years with comprehensive correct knowledge of HIV/AIDS I Ratio of school attendance of orphans to school attendance of non-orphans aged 10-14 years Target 6B: Achieve, by 2010, universal access to treatment for HIV/AIDS for all those who need it. I Proportion of population with advanced HIV infection with access to antiretroviral drugs Target 6C: By 2015, halt and begin to reverse the incidence of malaria and other major diseases. I Incidence and death rates associated with malaria I Proportion of children under 5 sleeping under insecticide-treated bednets I Proportion of children under 5 with fever who are treated with appropriate anti-malarial drugs I Incidence, prevalence, and death rates associated with tuberculosis I Proportion of tuberculosis cases detected and cured under directly observed treatment short course Source: United Nations Development Programme. 29 APPENDIX B: EMERGING INFECTIOUS DISEASE THREATS TO THE U.S. ANIMAL-BORNE DISEASES Bolstering defenses against emerging human gence of zoonotic diseases worldwide can be infections of animal origin, also known as attributed to population displacement, zoonoses or zoonotic diseases, is crucial to urbanization and crowding, deforestation, improving global public health. More than 35 of and globalization of the food supply.146 the most recent emerging diseases, including The following are descriptions of emerging H5N1 avian influenza, monkeypox, West Nile or re-emerging zoonotic diseases that are virus, and SARS, have been zoonotic in origin.145 endangering or may endanger the health of The link between animal and human health Americans. CDC, NIAID, and WHO have is not novel and has been studied for cen- thorough and accessible information on the turies. In 1967, a landmark study undertaken symptoms, transmission, treatments (if any), by the United Nation’s Food and Agriculture and epidemiology of these and many other Organization and WHO documented more animal-borne diseases, including yellow than 150 zoonotic diseases. By 2000, more fever, hantaviruses, Japanese encephalitis than 200 diseases occurring in humans were virus, and rabies. Anthrax and SARS, which known to be transmitted through animals. are described in earlier sections, also are Experts believe that the increased emer- considered zoonotic diseases. Avian Influenza in Humans Most Americans have had some experience H5N1 virus mutates into a form that can with seasonal influenza, a respiratory illness spread more easily from person to person. The that strikes annually. Seasonal flu is not a grimmest scenario would be a global outbreak benign illness -- it kills an average of 36,000 to rival the flu pandemic of 1918 and 1919, and hospitalizes over 200,000 people in the which claimed millions of lives worldwide. U.S. every year.147 Most experts generally Because the H5N1 virus does not commonly regard it as a manageable public health infect humans, there is little or no immune problem, since many people have some protection against it in the human population. form of immunity, and a new vaccine is avail- At present, 2 antiviral medicines used to treat able each year. seasonal influenza -- oseltamivir (Tamiflu) and Fears about pandemic influenza have intensi- zanamivir (Relenza) -- may be treatment fied in recent years with the emergence of a options should an H5N1 or another influenza deadly strain of avian (bird) influenza. Avian virus spark a pandemic.150 However, there influenza is an infection caused by avian remains uncertainty about their utility in a influenza (flu) viruses. One such virus, influen- pandemic: Access may be limited, resistance za A, subtype H5N1, has scientists and public may develop, and additional barriers may pre- health officials especially concerned. H5N1 vent the rapid administration after the onset originated in Asia, but has spread through of symptoms necessary for optimal benefit. Europe, Africa, and the Middle East, with cases In April 2007, FDA approved the first human in birds reported as far north as England and vaccine to prevent infection from one strain of human cases reported as far south as Nigeria. H5N1 bird flu virus. This vaccine is not avail- H5N1 has led to the deaths of hundreds of able to the public, but the U.S. government is millions of wild and domestic birds and as of stockpiling it and may distribute it if it is close- August 15, 2008, 243 human fatalities.148 ly matched to the influenza virus that sparks Currently, however, bird flu remains diffi- the next pandemic. Additional research and cult for humans to contract. Most people clinical trials are being supported by NIAID who have developed symptoms have had and vaccine manufacturers, including studies close contact with sick birds, though in a few on the use of an adjuvant -- something that cases, bird flu has been transmitted from helps a vaccine provoke stronger immunity in one person to another.149 the human body -- in candidate H5N1 vac- cines.151 Adjuvants also are important because Health officials are concerned that a major they can extend the available vaccine supply. bird flu outbreak could occur in humans if the 30 H5N1 viruses, however, are not the only viruses and avian H7N2, H7N3, and H9N2, pandemic influenza threat. Other influenza highlighting the need for continued vigi- A viruses that have jumped from animals to lance in monitoring for influenza viruses cause illness in people include swine H1N1 with the potential to cause a pandemic. Lyme Disease Lyme disease (borreliosis) is the most prevalent system. About 10 to 20 percent of untreated tick-borne infectious disease in the U.S. The people develop chronic arthritis.155 disease is caused by a spiral-shaped bacteri- Lyme disease can also affect the nervous sys- um, Borrelia burgdorferi, and transmitted to tem, causing such symptoms as stiff neck, Bell’s humans by the bite of the black-legged tick. palsy, and numbness in the limbs. Less com- Typical symptoms include fever, headache, monly, untreated people can develop heart fatigue, and a characteristic skin rash. The problems, hepatitis, and severe fatigue.156 telltale rash starts as a small red spot at the site of the tick bite and expands over time, form- According to CDC, in 2006, there were 19,931 ing a circular or oval-shaped rash. cases of Lyme disease reported in the U.S., yield- ing a national average of 8.2 cases per 100,000 As infection spreads, rashes can appear at persons. In the 10 states where Lyme disease is different sites on the body. It is often accom- most common, the average was 30.2 cases per panied by symptoms such as fever, 100,000 persons.157 The disease continues to headache, stiff neck, body aches, and spread geographically and increases in intensity fatigue. If left untreated, infection can in areas in which it had already been found. spread to joints, the heart, and the nervous Rift Valley Fever Rift Valley Fever (RVF) is a serious, fever- tissues of infected animals. Individuals with causing viral disease that affects domestic RVF typically have either no symptoms or a animals (such as cattle, buffalo, sheep, and mild illness associated with fever and liver goats) and humans. RVF is most commonly abnormalities. Patients who develop symp- associated with mosquito-borne epidemics toms usually experience fever, generalized during periods of unusually heavy rainfall. weakness, back pain, dizziness, and extreme Generally found in regions of eastern and weight loss at the onset of the illness. However, southern Africa where sheep and cattle are in some patients the illness can progress to raised, a RVF outbreak was reported in Saudi hemorrhagic fever (which can lead to shock Arabia in 2000 and subsequently in Yemen. or hemorrhage), encephalitis (inflammation of the brain, which can lead to headaches, Bites from infected mosquitoes are generally coma, or seizures), or ocular disease (includ- the means of transmission of RVF to humans, ing blindness). Typically, patients recover with- although people can also get the disease if in 2 days to one week after onset of illness.158 they are exposed to the blood, body fluids, or This is a transmission electron micrograph (TEM) of the West Nile virus (WNV). 31 West Nile Virus West Nile Virus (WNV) first emerged in the mation of the brain and spinal cord.159 In Western Hemisphere in 1999 in the New 2007, CDC reported 3,630 cases of WNV in York City area and spread rapidly through- the U.S. and 124 deaths from the disease.160 out the U.S. The virus is transmitted to Licensed WNV vaccines exist for horses, but humans by mosquitoes. there are no specific vaccines or treatments In general, most human infections are mild, for human WNV disease. According to causing fever, headache, and body aches, NIAID, “Faced with a potentially deadly ill- often accompanied by a skin rash and ness spreading quickly across the U.S., sci- swollen lymph glands. If the virus crosses the entists and public health officials have accel- blood-brain barrier, however, it can cause life- erated research on developing tools to pre- threatening conditions that include inflam- vent and treat WNV disease.”161 THE ONE HEALTH INITIATIVE The One Health Initiative, designed to foster greater collaboration between physicians and veterinarians, is a direct response to increasing concerns about the threat of emerging dis- eases worldwide and the significant threats such outbreaks pose to the health of humans and domesticated animals. Created in July 2007, a major goal of One Health is the integration of educational systems within and among medical schools, veterinary schools, and schools of public health. The cross-disciplinary project will promote increased research on cross-species disease transmission and the integration of human, veterinary, and wildlife disease surveillance and control systems. The initiative also will encourage comparative research on diseases affecting both humans and animals, including diabetes, cancer, autoimmune disorders, and obesity.162 FOODBORNE ILLNESSES Foodborne disease is caused by consuming have contaminated the food, for example, poi- contaminated foods or beverages. According sonous mushrooms. These different diseases to CDC, more than 250 different foodborne have various symptoms, and although they are diseases have been identified.163 Most of these often referred to as “food poisoning,” there is diseases are infections, caused by a variety of not a single “syndrome” that constitutes food- bacteria, viruses, and parasites that can be borne illness. However, nausea, vomiting, foodborne. Other diseases are poisonings, abdominal cramps, and diarrhea are common caused by harmful toxins or chemicals that symptoms in many foodborne illnesses.164 Botulism Botulinum toxins are the most poisonous sub- within 18 to 36 hours after eating contami- stances known to humans. They are derived nated food, but can occur in as few as 6 hours from bacteria called Clostridium botulinum. or as long as 10 days afterward.167 The toxins affect the nerves and, if untreated, Of particular concern to public health officials can cause paralysis and respiratory failure. are ongoing attempts by a number of coun- Exposure to the toxins can be fatal.165 tries to develop these toxins into bioweapons. Foodborne botulism is caused by eating foods This poses a major threat because of its lethal- that contain botulism toxin. Although deadly, ity and relative ease of production. botulism is not contagious.166 Signs and symp- A supply of antitoxin against botulism is main- toms include difficulty swallowing or speak- tained by CDC. The antitoxin is effective in ing, facial weakness, double vision, trouble reducing the severity of symptoms if adminis- breathing, nausea, vomiting and abdominal tered early in the course of the disease.168 cramps and paralysis. Symptoms usually begin 32 E. coli O157:H7 The Escherichia coli (E. coli) group of bacteria with E. coli infections develop a potentially life- includes numerous strains and most are threatening complication known as hemolytic harmless. However, in 1982, scientists identi- uremic syndrome (HUS). Symptoms include fied the first harmful foodborne strain of E. decreased frequency of urination, extreme coli in the U.S. -- O157:H7, which lives in the fatigue, and pallor. People with HUS should intestines of ruminants, sheds in their feces, be hospitalized because their kidneys may stop and is a leading cause of foodborne illness in working and they may develop other serious this country. Most often, people are exposed problems. Most persons with HUS recover to the E. coli bacteria through food or water, within a few weeks, but some suffer permanent especially from undercooked ground beef damage or die.170 and contaminated raw vegetables or unpas- For most people with an E. coli infection, the teurized apple cider. In the U.S., about best treatment option is to rest and drink 75,000 people each year become ill after plenty of fluids to help with dehydration and being infected with E. coli O157:H7.169 fatigue. People are advised to avoid taking The main symptoms of E. coli O157:H7 are anti-diarrheal medications, which can slow diarrhea, which may range from mild and the digestive system down, making it more watery to severe and bloody, and abdominal difficult to get rid of the toxins. According to cramping, pain, or tenderness. Some people CDC, antibiotics should not be used to treat also may have a low-grade fever and others this infection. There is no evidence that treat- experience nausea or vomiting. Approximately ment with antibiotics is helpful, and taking 5 to 10 percent of people who are diagnosed antibiotics may increase the risk of HUS.171 Salmonella Salmonellosis, or Salmonella infection, is one avoid circulatory collapse. Life-threatening of the most common bacterial infections of complications may also develop should the the intestinal tract. Salmonella typically live in infection spread beyond the intestines. In the intestines of animals and humans and most otherwise healthy people, diarrhea and are shed through feces, where the bacteria abdominal pains subside within several days remain highly contagious. Humans become to 2 weeks without specific treatment. infected most frequently through the inges- An antibiotic-resistant strain of S. typhimuri- tion of contaminated food sources, such as um, first found in the United Kingdom and poultry, meat, raw dairy products, and chick- then in the U.S., poses a major public health en eggs. Salmonella can survive for months in threat because it is resistant to several antibi- water, ice, sewage, and frozen meat.172 otics normally used to treat people with Typically, people with Salmonella infection Salmonella disease.174 develop diarrhea, fever and abdominal Salmonella may occur in small, contained cramps within 12 to 72 hours. Signs and outbreaks in the general population or in symptoms of Salmonella infection generally large outbreaks in hospitals, restaurants, or last 4 to 7 days. Most healthy people recover institutions housing children or the elderly. without specific treatment.173 Every year, CDC receives reports of 40,000 In some cases, diarrhea can cause severe fluid cases of Salmonellosis in the U.S.175 loss, requiring prompt medical attention to 33 ENDNOTES 13 Lederberg, J., R. E. Shope, Oaks S.C., and the Committee on Emerging Microbial Threats to Health, Institute of Medicine, eds. Emerging 1 Berkelman, R.L., R.T. Bryan, M.T. Osterholm, Infections: Microbial Threats to Health in the United J.W. LeDuc, J.M. Hughes. “Infectious Disease States. Washington, D.C.: The National Surveillance: A Crumbling Foundation.” Science Academies Press, 1992. 264, no. 5157 (April 15, 1994): 369. 14 Ibid. 2 Gordon, D. 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Rappuoli, and M. Buckley. Vaccine Congress. Washington, D.C.: Congressional Development: Current Status and Future Trends. Research Service, March 8, 2007. Washington, D.C.: American Academy of 116 Specifically, the legislation lists the following as Microbiology, 2005: 6. diseases: tuberculosis, malaria, blinding tra- 103 U.S. Centers for Disease Control and Prevention. choma, buruli, ucler, cholera, dengue/ “Most U. S. Measles Cases Reported since 1996, dengue, haemorrhagic fever, Dracunculiasis Many Unvaccinated because of Philosophical (guinea worm disease) Fascioliasis, Human Beliefs.” U.S. Department of Health and Human African trypanosomiasis, Leishmaniasis, Services. <http://www.cdc.gov/vaccines/vpd Leprosy, Lymphatic filariasis, Onchocerciasis, vac/measles/default.htm> (accessed August 21, Schistosomiasis, Soil transmitted helmithiasis, 2008). Yaws; or any other disease for which there is 104 Miller, K. “Rift Valley Fever.” Science @ NASA, no significant market in developed nations April 17, 2002. http://www.science.nasa.gov/ and disproportionately affects poor and mar- headlines/y2002/17apr_rvf.htm (accessed ginalized populations. May 18, 2008). 117 International AIDS Vaccine Initiative. “U.S. 105 Ibid. FDA Priority Review Vouchers: An Effective Incentive to Develop Drugs and Vaccines for 106 Matheny, J., M. Mair, A. Mulcahy, and B.T. Neglected Diseases?” https://www.iavi.org/ Smith. “Incentives for Biodefense file.cfm?fid=47963 (accessed June 18, 2008). Countermeasure Development.” Biosecurity and Bioterrorism 5, no. 3. 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President Bush Signs Project 38 BioShield Act of 2004. Washington, D.C.: The 124 Mayo Clinic. “HIV/AIDS.” 135 National Institute of Allergy and Infectious http://www.mayoclinic.com/health/hiv- Diseases. “Malaria: Symptoms.” U.S. aids/DS00005/DSECTION=causes (accessed Department of Health and Human Services. July 22, 2008). http://www3.niaid.nih.gov/topics/Malaria/u 125 UNAIDS. “2008 Report on the global AIDS nderstandingMalaria/transmission.htm epidemic.” Joint United Nations Programme (accessed June 16, 2008). on HIV/AIDS. http://data.unaids.org/pub/ 136 Ibid GlobalReport/2008/jc1510_2008_global_rep 137 Mayo Clinic. “Tuberculosis: Introduction.” ort_pp29_62_en.pdfIbid. (accessed July 30, http://www.mayoclinic.com/health/tuberculo 2008). sis/DS00372/DSECTION=1 (accessed June 126 The White House. President Bush Signs H.R. 17, 2008) 5501, the Tom Lantos and Henry J. Hyde United 138 National Institute of Allergy and Infectious States Global Leadership Against HIV/AIDS, Diseases. “Tuberculosis (TB): Detailed Tuberculosis and Malaria Reauthorization Act of Description of TB.” U.S. Department of 2008. Washington, D.C.: The White House, Health and Human Services. July 30, 2008. http://www.whitehouse.gov/ http://www3.niaid.nih.gov/topics/tuberculosi news/releases/2008/07/20080730-12.html s/Understanding/description.htm (accessed (accessed July 31, 2008). June 17, 2008). 127 Ibid. 139 Ibid. 128 U.S. Centers for Disease Control and Preven- 140 National Institute of Allergy and Infectious tion. HIV/AIDS Surveillance Report, 2006. Volume Diseases. “Tuberculosis (TB): Overview.” U.S. 18. Atlanta: U.S. Department of Health and Department of Health and Human Services. Human Services, 2008. http://www.cdc.gov/ http://www3.niaid.nih.gov/topics/tuberculosi hiv/topics/surveillance/resources/reports/ s/Understanding/overview.htm (accessed (accessed August 13, 2008). June 17, 2008). 129 U.S. Centers for Disease Control and 141 National Institute of Allergy and Infectious Prevention. “Estimates of New HIV Infections Diseases. “Tuberculosis (TB): Overview.” U.S. in the United States.” U.S. Department of Department of Health and Human Services. Health and Human Services. August 2008. http://www3.niaid.nih.gov/topics/tuberculosi http://www.cdc.gov/hiv/topics/surveillance/ s/Understanding/overview.htm (accessed resources/factsheets/incidence.htm June 17, 2008). (accessed August 22, 2008). 142 U.S. Centers for Disease Control and Preven- 130 U.S. Centers for Disease Control and Preven- tion. “Tuberculosis: General Information.” tion. HIV/AIDS Surveillance Report, 2006. U.S. Department of Health and Human Volume 18. Atlanta: U.S. Department of Health Services. http://www.cdc.gov/tb/pubs/ and Human Services, 2008. tbfactsheets/tb.htm (accessed June 17, 2008). http://www.cdc.gov/hiv/topics/surveillance/r esources/reports/ (accessed August 13, 2008). 143 Ibid. 131 U.S. Centers for Disease Control and 144 National Institute of Allergy and Infectious Prevention. “Hepatitis C Information for the Diseases. “Tuberculosis (TB): Detailed Public.” U.S. Department of Health and Description of TB.” U.S. Department of Human Services. http://www.cdc.gov/ Health and Human Services. hepatitis/C/cFAQ.htm#cFAQ04 (accessed http://www3.niaid.nih.gov/topics/tuberculosi August 14, 2008). s/Understanding/description.htm (accessed June 17, 2008). 132 The C. Everett Koop Institute at Dartmouth Medical School. Hepatitis C: An Epidemic 145 Ellis, K. “One Health Initiative Will Unite for Anyone. Hanover, NH: The Trustees of Veterinary, Human Medicine: Experts Urge Dartmouth College, 2008. Collaboration Between Veterinarians, http://www.epidemic.org/theFacts/theEpide Physicians in Wake Of Emerging Zoonotic mic/worldPrevalence/ (accessed July 7, 2008). Diseases, Potential Epidemics.” Infectious Disease News. February 2008. 133 U.S. Centers for Disease Control and Preven- http://www.infectiousdiseasenews.com/20080 tion. “Hepatitis C Information for the Public.” 2/veterinary.asp (Accessed July 15, 2008). U.S. Department of Health and Human Services. http://www.cdc.gov/hepatitis/C/ 146 Ibid. cFAQ.htm#cFAQ04 (accessed August 14, 2008). 147 U.S. Centers for Disease Control and 134 National Institute of Allergy and Infectious Prevention. “Influenza: Questions and Diseases. “Malaria: Transmission.” U.S. Answers: The Disease.” U.S. Department of Department of Health and Human Services. Health and Human Services. http://www3.niaid.nih.gov/topics/Malaria/u http://www.cdc.gov/flu/about/qa/disease.ht nderstandingMalaria/transmission.htm m 8 July 2007. (accessed June 16, 2008). (accessed June 16, 2008). 39 148 World Health Organization. “Cumulative 161 National Institute of Allergy and Infectious Number of Confirmed Human Cases of Avian Diseases. “West Nile Virus: Research.” U.S. Influenza A/(H5N1) Reported to WHO.” Department of Health and Human Services. http://www.who.int/csr/disease/avian_influe http://www3.niaid.nih.gov/topics/westNile/u nza/country/cases_table_2008_05_28/en/ind nderstanding/reserach.htm (accessed June ex.html (accessed June 16, 2008). 17, 2008). 149 U.S. Centers for Disease Control and 162 Ellis, K. “One Health Initiative Will Unite Prevention. “Questions and Answers About Veterinary, Human Medicine: Experts Urge Avian Influenza (Bird Flu) and Avian Collaboration Between Veterinarians, Influenza A (H5N1) Virus.” U.S. Department Physicians in Wake Of Emerging Zoonotic of Health and Human Services. Diseases, Potential Epidemics.” Infectious http://www.cdc.gov/flu/avian/gen- Disease News. February 2008. info/qa.htm. 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June 12, 2008). http://www3.niaid.nih.gov/healthscience/hea 153 Ibid. lthtopics/botulism/cause.htm (accessed June 17, 2008). 154 Effler, P., L. Pang, P. Kitsutani, V. Vorndam, M. Nakata, T. Ayers, et. al. “Dengue Fever, Hawaii, 166 U.S. Centers for Disease Control and 2001-2002.” Emerging Infectious Diseases [ser- Prevention. “Facts about Botulism.” U.S. ial on the Internet], May 2005. Department of Health and Human Services. http://www.cdc.gov/ncidod/EID/vol11no05/ http://www.bt.cdc.gov/agent/botulism/factsh 04-1063.htm. (accessed June 12, 2008). eet.asp (accessed June 17, 2008). 155 National Institute of Allergy and Infectious 167 Ibid. Diseases. “Lyme Disease.” U.S. Department of 168 Ibid. Health and Human Services. 169 U.S. Centers for Disease Control and http://www3.niaid.nih.gov/topics/lymeDiseas Prevention. “Escherichia coli O157:H7.” U.S. e/understanding/intro.htm (accessed June Department of Health and Human Services. 16, 2008). http://www.cdc.gov/NCIDOD/DBMD/diseas 156 Ibid. einfo/escherichiacoli_g.htm#What%20is%20 157 Ibid. Escherichia%20coli%20O157:H7 (accessed June 16, 2008). 158 U.S. Centers for Disease Control and Prevention. “Questions and Answers about 170 Ibid. Rift Valley Fever.” U.S. Department of Health 171 Ibid. and Human Services. http://www.cdc.gov/ 172 Mayo Clinic. “Salmonella Infection.” ncidod/dvrd/spb/mnpages/dispages/rv http://www.mayoclinic.com/health/salmonell f/rvf_qa.htm (accessed July 22, 2008). a/DS00926 (accessed June 17, 2008). 159 National Institute of Allergy and Infectious 173 Ibid. Diseases. “West Nile Virus: Symptoms.” U.S. Department of Health and Human Services. 174 National Institute of Allergy and Infectious http://www3.niaid.nih.gov/topics/westNile/ Diseases. “Salmonellas: Cause.” U.S. understanding/symptoms.htm (accessed June Department of Health and Human Services. 17, 2008). http://www3.niaid.nih.gov/healthscience/hea lthtopics/salmonellosis/Cause.htm (accessed 160 U.S. Centers of Disease Control and June 17, 2008). Prevention. “2007 West Nile Virus Activity in the United States.” U.S. Department of Health 175 National Institute of Allergy and Infectious and Human Services. http://www.cdc.gov/ Diseases. “Salmonellas: Overview.” U.S. ncidod/dvbid/westnile/surv&controlCaseCou Department of health and Human Services. nt07_detailed.htm (accessed August 13, 2008). http://www3.niaid.nih.gov/healthscience/hea lthtopics/ salmonellosis/Overview.htm (accessed June 17, 2008). 40 1730 M Street, NW, Suite 900 Washington, DC 20036 (t) 202-223-9870 (f) 202-223-9871