The Global Infectious Disease Threat and Its Implications for the United States

NIE 99-17D, January 2000

The Estimate was produced under the auspices of David F. Gordon, National Intelligence Officer for Economics and Global Issues. The primary drafters were Lt. Col. (Dr.) Don Noah of the Armed Forces Medical Intelligence Center and George Fidas of the NIC. The Estimate also benefited from a conference on infectious diseases held jointly with the State Department's Bureau of Intelligence and Research, and was reviewed by several prominent epidemiologists and other health experts in and outside the US Government. We hope that it will further inform the debate about this important subject.

John C. Gannon
Chairman, National Intelligence Council

Preface

The Global Infectious Disease Threat and Its Implications for the United States

I am pleased to share with you this unclassified version of a new National Intelligence Estimate on the reemergence of the threat from infectious diseases worldwide and its implications for the United States.

This report represents an important initiative on the part of the Intelligence Community to consider the national security dimension of a nontraditional threat. It responds to a growing concern by senior US leaders about the implications--in terms of health, economics, and national security--of the growing global infectious disease threat. The dramatic increase in drug-resistant microbes, combined with the lag in development of new antibiotics, the rise of megacities with severe health care deficiencies, environmental degradation, and the growing ease and frequency of cross-border movements of people and produce have greatly facilitated the spread of infectious diseases.

In June 1996, President Clinton issued a Presidential Decision Directive calling for a more focused US policy on infectious diseases. The State Department's Strategic Plan for International Affairs lists protecting human health and reducing the spread of infectious diseases as US strategic goals, and Secretary Albright in December 1999 announced the second of two major U.S. initiatives to combat HIV/AIDS. The unprecedented UN Security Council session devoted exclusively to the threat to Africa from HIV/AIDS in January 2000 is a measure of the international community's concern about the infectious disease threat.

As part of this new US Government effort, the National Intelligence Council produced this National Intelligence Estimate. It examines the most lethal diseases globally and by region; develops alternative scenarios about their future course; examines national and international capacities to deal with them; and assesses their national and global social, economic, political, and security impact. It then assesses the infectious disease threat from international sources to the United States; to US military personnel overseas; and to regions in which the United States has or may develop significant equities.

Key Judgments

The Global Infectious Disease Threat and Its Implications for the United States

New and reemerging infectious diseases will pose a rising global health threat and will complicate US and global security over the next 20 years. These diseases will endanger US citizens at home and abroad, threaten US armed forces deployed overseas, and exacerbate social and political instability in key countries and regions in which the United States has significant interests.

Infectious diseases are a leading cause of death, accounting for a quarter to a third of the estimated 54 million deaths worldwide in 1998. The spread of infectious diseases results as much from changes in human behavior--including lifestyles and land use patterns, increased trade and travel, and inappropriate use of antibiotic drugs--as from mutations in pathogens.

• Twenty well-known diseases--including tuberculosis (TB), malaria, and cholera--have reemerged or spread geographically since 1973, often in more virulent and drug-resistant forms.
• At least 30 previously unknown disease agents have been identified since 1973, including HIV, Ebola, hepatitis C, and Nipah virus, for which no cures are available.
• Of the seven biggest killers worldwide, TB, malaria, hepatitis, and, in particular, HIV/AIDS continue to surge, with HIV/AIDS and TB likely to account for the overwhelming majority of deaths from infectious diseases in developing countries by 2020. Acute lower respiratory infections--including pneumonia and influenza--as well as diarrheal diseases and measles, appear to have peaked at high incidence levels.

Impact Within the United States

Although the infectious disease threat in the United States remains relatively modest as compared to that of noninfectious diseases, the trend is up. Annual infectious disease-related death rates in the United States have nearly doubled to some 170,000 annually after reaching an historic low in 1980. Many infectious diseases--most recently, the West Nile virus--originate outside US borders and are introduced by international travelers, immigrants, returning US military personnel, or imported animals and foodstuffs. In the opinion of the US Institute of Medicine, the next major infectious disease threat to the United States may be, like HIV, a previously unrecognized pathogen. Barring that, the most dangerous known infectious diseases likely to threaten the United States over the next two decades will be HIV/AIDS, hepatitis C, TB, and new, more lethal variants of influenza. Hospital-acquired infections and foodborne illnesses also will pose a threat.

• Although multidrug therapies have cut HIV/AIDS deaths by two-thirds to 17,000 annually since 1995, emerging microbial resistance to such drugs and continued new infections will sustain the threat.
• Some 4 million Americans are chronic carriers of the hepatitis C virus, a significant cause of liver cancer and cirrhosis. The US death toll from the virus may surpass that of HIV/AIDS in the next five years.
• TB, exacerbated by multidrug resistant strains and HIV/AIDS co-infection, has made a comeback. Although a massive and costly control effort is achieving considerable success, the threat will be sustained by the spread of HIV and the growing number of new, particularly illegal, immigrants infected with TB.
• Influenza now kills some 30,000 Americans annually, and epidemiologists generally agree that it is not a question of whether, but when, the next killer pandemic will occur.
• Highly virulent and increasingly antimicrobial resistant pathogens, such as Staphylococcus aureus, are major sources of hospital-acquired infections that kill some 14,000 patients annually.
• The doubling of US food imports over the last five years is one of the factors contributing to tens of millions of foodborne illnesses and 9,000 deaths that occur annually, and the trend is up.

Regional Trends

Developing and former communist countries will continue to experience the greatest impact from infectious diseases--because of malnutrition, poor sanitation, poor water quality, and inadequate health care--but developed countries also will be affected:

• Sub-Saharan Africa--accounting for nearly half of infectious disease deaths globally--will remain the most vulnerable region. The death rates for many diseases, including HIV/AIDS and malaria, exceed those in all other regions. Sub-Saharan Africa's health care capacity--the poorest in the world--will continue to lag.
• Asia and the Pacific, where multidrug resistant TB, malaria, and cholera are rampant, is likely to witness a dramatic increase in infectious disease deaths, largely driven by the spread of HIV/AIDS in South and Southeast Asia and its likely spread to East Asia. By 2010, the region could surpass Africa in the number of HIV infections.
• The former Soviet Union (FSU) and, to a lesser extent, Eastern Europe also are likely to see a substantial increase in infectious disease incidence and deaths. In the FSU especially, the steep deterioration in health care and other services owing to economic decline has led to a sharp rise in diphtheria, dysentery, cholera, and hepatitis B and C. TB has reached epidemic proportions throughout the FSU, while the HIV-infected population in Russia alone could exceed 1 million by the end of 2000 and double yet again by 2002.
• Latin American countries generally are making progress in infectious disease control, including the eradication of polio, but uneven economic development has contributed to widespread resurgence of cholera, malaria, TB, and dengue. These diseases will continue to take a heavy toll in tropical and poorer countries.
• The Middle East and North Africa region has substantial TB and hepatitis B and C prevalence, but conservative social mores, climatic factors, and the high level of health spending in the oil-producing states tend to limit some globally prevalent diseases, such as HIV/AIDS and malaria. The region has the lowest HIV infection rate among all regions, although this is probably due in part to above-average underreporting because of the stigma associated with the disease in Muslim societies.
• Western Europe faces threats from several infectious diseases, such as HIV/AIDS, TB, and hepatitis B and C, as well as from several economically costly zoonotic diseases (that is, those transmitted from animals to humans). The region's large volume of travel, trade, and immigration increases the risks of importing diseases from other regions, but its highly developed health care system will limit their impact.

Response Capacity

Development of an effective global surveillance and response system probably is at least a decade or more away, owing to inadequate coordination and funding at the international level and lack of capacity, funds, and commitment in many developing and former communist states. Although overall global health care capacity has improved substantially in recent decades, the gap between rich and poorer countries in the availability and quality of health care, as illustrated by a typology developed by the Defense Intelligence Agency's Armed Forces Medical Intelligence Center (AFMIC), is widening.

Alternative Scenarios

We have examined three plausible scenarios for the course of the infectious disease threat over the next 20 years:

Steady Progress
The least likely scenario projects steady progress whereby the aging of global populations and declining fertility rates, socioeconomic advances, and improvements in health care and medical breakthroughs hasten movement toward a "health transition" in which such noninfectious diseases as heart disease and cancer would replace infectious diseases as the overarching global health challenge. We believe this scenario is unlikely primarily because it gives inadequate emphasis to persistent demographic and socioeconomic challenges in the developing countries, to increasing microbial resistance to existing antibiotics, and because related models have already underestimated the force of major killers such as HIV/AIDS, TB, and malaria.

Progress Stymied
A more pessimistic--and more plausible--scenario projects little or no progress in countering infectious diseases over the duration of this Estimate. Under this scenario, HIV/AIDS reaches catastrophic proportions as the virus spreads throughout the vast populations of India, China, the former Soviet Union, and Latin America, while multidrug treatments encounter microbial resistance and remain prohibitively expensive for developing countries. Multidrug resistant strains of TB, malaria, and other infectious diseases appear at a faster pace than new drugs and vaccines, wreaking havoc on world health. Although more likely than the "steady progress" scenario, we judge that this scenario also is unlikely to prevail because it underestimates the prospects for socioeconomic development, international collaboration, and medical and health care advances to constrain the spread of at least some widespread infectious diseases.

Deterioration, Then Limited Improvement
The most likely scenario, in our view, is one in which the infectious disease threat--particularly from HIV/AIDS--worsens during the first half of our time frame, but decreases fitfully after that, owing to better prevention and control efforts, new drugs and vaccines, and socioeconomic improvements. In the next decade, under this scenario, negative demographic and social conditions in developing countries, such as continued urbanization and poor health care capacity, remain conducive to the spread of infectious diseases; persistent poverty sustains the least developed countries as reservoirs of infection; and microbial resistance continues to increase faster than the pace of new drug and vaccine development. During the subsequent decade, more positive demographic changes such as reduced fertility and aging populations; gradual socioeconomic improvement in most countries; medical advances against childhood and vaccine-preventable killers such as diarrheal diseases, neonatal tetanus, and measles; expanded international surveillance and response systems; and improvements in national health care capacities take hold in all but the least developed countries. Barring the appearance of a deadly and highly infectious new disease, a catastrophic upward lurch by HIV/AIDS, or the release of a highly contagious biological agent capable of rapid and widescale secondary spread, these developments produce at least limited gains against the overall infectious disease threat. However, the remaining group of virulent diseases, led by HIV/AIDS and TB, continue to take a significant toll.

Economic, Social, and Political Impact

The persistent infectious disease burden is likely to aggravate and, in some cases, may even provoke economic decay, social fragmentation, and political destabilization in the hardest hit countries in the developing and former communist worlds, especially in the worst case scenario outlined above:

• The economic costs of infectious diseases--especially HIV/AIDS and malaria--are already significant, and their increasingly heavy toll on productivity, profitability, and foreign investment will be reflected in growing GDP losses, as well, that could reduce GDP by as much as 20 percent or more by 2010 in some Sub-Saharan African countries, according to recent studies.
• Some of the hardest hit countries in Sub-Saharan Africa--and possibly later in South and Southeast Asia--will face a demographic upheaval as HIV/AIDS and associated diseases reduce human life expectancy by as much as 30 years and kill as many as a quarter of their populations over a decade or less, producing a huge orphan cohort. Nearly 42 million children in 27 countries will lose one or both parents to AIDS by 2010; 19 of the hardest hit countries will be in Sub-Saharan Africa.

The relationship between disease and political instability is indirect but real. A wide-ranging study on the causes of state instability suggests that infant mortality--a good indicator of the overall quality of life--correlates strongly with political instability, particularly in countries that already have achieved a measure of democracy. The severe social and economic impact of infectious diseases is likely to intensify the struggle for political power to control scarce state resources.

Implications for US National Security

As a major hub of global travel, immigration, and commerce with wide-ranging interests and a large civilian and military presence overseas, the United States and its equities abroad will remain at risk from infectious diseases.

• Emerging and reemerging infectious diseases, many of which are likely to continue to originate overseas, will continue to kill at least 170,000 Americans annually. Many more could perish in an epidemic of influenza or yet-unknown disease or if there is a substantial decline in the effectiveness of available HIV/AIDS drugs.
• Infectious diseases are likely to continue to account for more military hospital admissions than battlefield injuries. US military personnel deployed at NATO and US bases overseas, will be at low-to-moderate risk. At highest risk will be US military forces deployed in support of humanitarian and peacekeeping operations in developing countries.
• The infectious disease burden will weaken the military capabilities of some countries--as well as international peacekeeping efforts--as their armies and recruitment pools experience HIV infection rates ranging from 10 to 60 percent. The cost will be highest among officers and the more modernized militaries in Sub-Saharan Africa and increasingly among FSU states and possibly some rogue states.
• Infectious diseases are likely to slow socioeconomic development in the hardest-hit developing and former communist countries and regions. This will challenge democratic development and transitions and possibly contribute to humanitarian emergencies and civil conflicts.
• Infectious disease-related embargoes and restrictions on travel and immigration will cause frictions among and between developed and developing countries.
• The probability of a bioterrorist attack against US civilian and military personnel overseas or in the United States also is likely to grow as more states and groups develop a biological warfare capability. Although there is no evidence that the recent West Nile virus outbreak in New York City was caused by foreign state or nonstate actors, the scare and several earlier instances of suspected bioterrorism showed the confusion and fear they can sow regardless of whether or not they are validated.

Discussion

Patterns of Infectious Diseases

Broad advances in controlling or eradicating a growing number of infectious diseases--such as tuberculosis (TB), malaria, and smallpox--in the decades after the Second World War fueled hopes that the global infectious disease threat would be increasingly manageable. Optimism regarding the battle against infectious diseases peaked in 1978 when the United Nations (UN) member states signed the "Health for All 2000" accord, which predicted that even the poorest nations would undergo a health transition before the millennium, whereby infectious diseases no longer would pose a major danger to human health. As recently as 1996, a World Bank/World Health Organization (WHO)-sponsored study by Christopher J.L. Murray and Alan D. Lopez projected a dramatic reduction in the infectious disease threat. This optimism, however, led to complacency and overlooked the role of such factors as expanded trade and travel and growing microbial resistance to existing antibiotics in the spread of infectious diseases. Today:

• Infectious diseases remain a leading cause of death (see figure 1). Of the estimated 54 million deaths worldwide in 1998, about one-fourth to one-third were due to infectious diseases, most of them in developing countries and among children globally.
• Infectious diseases accounted for 41 percent of the global disease burden measured in terms of Disability-Adjusted Life Years (DALYS) that gauge the impact of both deaths and disabilities, as compared to 43 percent for noninfectious diseases and 16 percent for injuries.
• Although there has been continuing progress in controlling some vaccine-preventable childhood diseases such as polio, neonatal tetanus, and measles, a White House-appointed interagency working group identified at least 29 previously unknown diseases that have appeared globally since 1973, many of them incurable, including HIV/AIDS, Ebola hemorrhagic fever, and hepatitis C. Most recently, Nipah encephalitis was identified. Twenty well-known diseases such as malaria, TB, cholera, and dengue have rebounded after a period of decline or spread to new regions, often in deadlier forms (see table 1).
• These trends are reflected in the United States as well, where annual infectious disease deaths have nearly doubled to some 170,000 since 1980 after reaching historic lows that year, while new and existing pathogens, such as HIV and West Nile virus, respectively, continue to enter US borders.

Source: US Institute of Medicine, 1997; WHO, 1999.

The Deadly Seven
The seven infectious diseases that caused the highest number of deaths in 1998, according to WHO and DIA's Armed Forces Medical Intelligence Center (AFMIC), will remain threats well into the next century. HIV/AIDS, TB, malaria, and hepatitis B and C--are either spreading or becoming more drug-resistant, while lower respiratory infections, diarrheal diseases, and measles, appear to have at least temporarily peaked (see figure 2).

HIV/AIDS. Following its identification in 1983, the spread of HIV intensified quickly. Despite progress in some regions, HIV/AIDS shows no signs of abating globally (see figure 3). Approximately 2.3 million people died from AIDS worldwide in 1998, up dramatically from 0.7 million in 1993, and there were 5.8 million new infections. According to WHO, some 33.4 million people were living with HIV by 1998, up from 10 million in 1990, and the number could approach 40 million by the end of 2000. Although infection and death rates have slowed considerably in developed countries owing to the growing use of preventive measures and costly new multidrug treatment therapies, the pandemic continues to spread in much of the developing world, where 95 percent of global infections and deaths have occurred. Sub-Saharan Africa currently has the biggest regional burden, but the disease is spreading quickly in India, Russia, China, and much of the rest of Asia. HIV/AIDS probably will cause more deaths than any other single infectious disease worldwide by 2020 and may account for up to one-half or more of infectious disease deaths in the developing world alone.

A Word About Data

All data concerning global disease incidence, including WHO data, should be treated as broadly indicative of trends rather than accurate measures of disease prevalence. Much disease incidence in developing countries, in particular, is either unreported or under-reported due to a lack of adequate medical and administrative personnel, the stigma associated with many diseases, or the reluctance of countries to incur the trade, tourism, and other losses that such revelations might produce. Since much morbidity and mortality are multicausal, moreover, diagnosis and reporting of diseases can vary and further distort comparisons. WHO and other international entities are dependent on such data despite its weaknesses and are often forced to extrapolate or build models based on relatively small samples, as in the case of HIV/AIDS. Changes in methodologies, moreover, can produce differing results. The ranking of AIDS mortality ahead of TB mortality in figure 2, for example, partly owes to the fact that HIV-positive individuals dying of TB were included in the AIDS mortality category in the most recent WHO survey.

TB. WHO declared TB a global emergency in 1993 and the threat continues to grow, especially from multidrug resistant TB (see figure 4). The disease is especially prevalent in Russia, India, Southeast Asia, Sub-Saharan Africa, and parts of Latin America. More than 1.5 million people died of TB in 1998, excluding those infected with HIV/AIDS, and there were up to 7.4 million new cases. Although the vast majority of TB infections and deaths occur in developing regions, the disease also is encroaching into developed regions due to increased immigration and travel and less emphasis on prevention. Drug resistance is a growing problem; the WHO has reported that up to 50 percent of people with multidrug resistant TB may die of their infection despite treatment, which can be 10 to 50 times more expensive than that used for drug-sensitive TB. HIV/AIDS also has contributed to the resurgence of TB. One-quarter of the increase in TB incidence involves co-infection with HIV. TB probably will rank second only to HIV/AIDS as a cause of infectious disease deaths by 2020.

Glossary

Infectious Disease
An illness due to a specific infectious agent that is spread from an infected person, animal, or inanimate reservoir to a susceptible host, either directly or indirectly, through an intermediate plant or animal host, vector, or the inanimate environment.

Endemic
The constant presence of a disease or infectious agent within a given geographic area.

Epidemic
The occurrence in an area of a disease or illness in excess of what may be expected on the basis of past experience for a given population (in the case of a new disease, such as AIDS, any occurrence may be considered "epidemic").

Pandemic
A worldwide epidemic affecting an exceptionally high proportion of the global population.

Prevalence
The number of existing cases of a disease among a total or specified population in a given period of time; usually expressed as a percent or as the number of cases per thousand, 10,000, and so forth.

Malaria, a mainly tropical disease that seemed to be coming under control in the 1960s and 1970s, is making a deadly comeback--especially in Sub-Saharan Africa where infection rates increased by 40 percent from 1970 to 1997 (see figure 5). Drug resistance, historically a problem only with the most severe form of the disease, is now increasingly reported in the milder variety, while the prospects for an effective vaccine are poor. In 1998, an estimated 300 million people were infected with malaria, and more than 1.1 million died from the disease that year. Most of the deaths occurred in Sub-Saharan Africa. According to the US Agency for International Development (USAID), Sub-Saharan Africa alone is likely to experience a 7- to 20-percent annual increase in malaria-related deaths and severe illnesses over the next several years.

Hepatitis B and C. Hepatitis B, which caused at least 0.6 million deaths in 1997, is highly endemic in the developing world, and some 350 million people worldwide are chronic carriers (see figure 6). The less prevalent but far more lethal hepatitis C identified in 1989 has grown dramatically and is a significant contributor to cirrhosis and liver cancer. WHO estimated that 3 percent of the global population was infected with the hepatitis C virus by 1997 (see figure 7), which means that more than 170 million people were at risk of developing the diseases associated with this virus. Various studies project that up to 25 percent of people with chronic hepatitis B and C will die of cirrhosis of the liver and liver cancer over the next 20 to 30 years.

Lower respiratory infections, especially influenza and pneumonia, killed 3.5 million people in 1998, most of them children in developing countries, down from 4.1 million in 1993. Owing to immunosuppression from malnutrition and growing microbial resistance to commonly used drugs such as penicillin, these children are especially vulnerable to such diseases and will continue to experience high death rates.

Diarrheal diseases--mainly spread by contaminated water or food--accounted for 2.2 million deaths in 1998, as compared to 3 million in 1993, of which about 60 percent occurred among children under five years of age in developing countries. The most common cause of death related to diarrheal diseases is infection with Escherichia coli. Other diarrheal diseases include cholera, dysentery, and rotaviral diarrhea, prevalent throughout the developing world and, more recently, in many former communist states. Such waterborne and foodborne diseases will remain highly prevalent in these regions in the absence of improvements in water quality and sanitation.

Measles. Despite substantial progress against measles in recent years, the disease still infects some 42 million children annually and killed about 0.9 million in 1998, down from 1.2 million in 1993. It is a leading cause of death among refugees and internally displaced persons during complex humanitarian emergencies. Measles will continue to pose a major threat in developing countries (see figure 8), particularly Sub-Saharan Africa, until the still relatively low vaccination rates are substantially increased. It also will continue to cause periodic epidemics in areas such as South America with higher, but still inadequate, vaccination rates.

Factors Affecting Growth and Spread

With few exceptions, the resurgence of the infectious disease threat is due as much to dramatic changes in human behavior and broader social, economic, and technological developments as to mutations in pathogens (see table 2). Changes in human behavior include population dislocations, living styles, and sexual practices; technology-driven medical procedures entailing some risks of infection; and land use patterns. They also include rising international travel and commerce that hasten the spread of infectious diseases; inappropriate use of antibiotics that leads to the development of microbial resistance; and the breakdown of public health systems in some countries owing to war or economic decline. In addition, climate changes enable diseases and vectors to expand their range. Several of these factors interact, exacerbating the spread of infectious diseases.

Source: Adapted from US Institute of Medicine, 1997.

Human Demographics and Behavior
Population growth and urbanization, particularly in the developing world, will continue to facilitate the transfer of pathogens among people and regions. Frequent and often sudden population movements within and across borders caused by ethnic conflict, civil war, and famine will continue to spread diseases rapidly in affected areas, particularly among refugees. As of 1999, there were some 24 major humanitarian emergencies worldwide involving at least 35 million refugees and internally displaced people. Refugee camps, found mainly in Sub-Saharan Africa and the Middle East, facilitate the spread of TB, HIV, cholera, dysentery, and malaria. Well over 120 million people lived outside the country of their birth in 1998, and millions more will emigrate annually, increasing the spread of diseases globally. Behavioral patterns, such as unprotected sex with multiple partners and intravenous drug use, will remain key factors in the spread of HIV/AIDS.

Technology, Medicine, and Industry
Although technological breakthroughs will greatly facilitate the detection, diagnosis, and control of certain infectious and noninfectious illnesses, they also will introduce new dangers, especially in the developed world where they are used extensively. Invasive medical procedures will result in a variety of hospital-acquired infections, such as Staphylococcus aureus. The globalization of the food supply means that nonhygienic food production, preparation, and handling practices in originating countries can introduce pathogens endangering foreign as well as local populations. Disease outbreaks due to Cyclospora spp, Escherichia coli, and Salmonella spp. in several countries, along with the emergence, primarily in Britain, of Bovine Spongiform Encephalopathy, or "mad cow" disease, and the related new variant Creutzfeldt-Jakob disease (nvCJD) affecting humans, result from such food practices.

Economic Development and Land Use
Changes in land and water use patterns will remain major factors in the spread of infectious diseases. The emergence of Lyme disease in the United States and Europe has been linked to reforestation and increases in the deer tick population, which acts as a vector, while conversion of grasslands to farming in Asia encourages the growth of rodent populations carrying hemorrhagic fever and other viral diseases. Human encroachment on tropical forests will bring populations into closer proximity with insects and animals carrying diseases such as leishmaniasis, malaria, and yellow fever, as well as heretofore unknown and potentially dangerous diseases, as was the case with HIV/AIDS. Close contact between humans and animals in the context of farming will increase the incidence of zoonotic diseases--those transmitted from animals to humans. Water management efforts, such as dambuilding, will encourage the spread of water-breeding vectors such as mosquitoes and snails that have contributed to outbreaks of Rift Valley fever and schistosomiasis in Africa.

International Travel and Commerce
The increase in international air travel, trade, and tourism will dramatically increase the prospects that infectious disease pathogens such as influenza--and vectors such as mosquitoes and rodents--will spread quickly around the globe, often in less time than the incubation period of most diseases. Earlier in the decade, for example, a multidrug resistant strain of Streptococcus pneumoniae originating in Spain spread throughout the world in a matter of weeks, according to the director of WHO's infectious disease division. The cross-border movement of some 2 million people each day, including 1 million between developed and developing countries each week, and surging global trade ensure that travel and commerce will remain key factors in the spread of infectious diseases.

Note: Antimicrobial resistance occurs when a disease-carrying microbe (bacteria, virus, parasite, or fungus) is no longer affected by a drug that previously was able to kill the microbe or prevent it from growing. Even among populations of microorganisms that are susceptible to a particular antimicrobial agent, at least a small percentage of those organisms are naturally resistant, and their proportion will grow as the others succumb to the antimicrobial agent. Eventually this process renders the agent ineffective against the microorganism.

Source: US Institute of Medicine, 1997; WHO, 1999.

Microbial Adaptation and Resistance
Infectious disease microbes are constantly evolving, oftentimes into new strains that are increasingly resistant to available antibiotics. As a result, an expanding number of strains of diseases--such as TB, malaria, and pneumonia--will remain difficult or virtually impossible to treat. At the same time, large-scale use of antibiotics in both humans and livestock will continue to encourage development of microbial resistance. The firstline drug treatment for malaria is no longer effective in over 80 of the 92 countries where the disease is a major health problem. Penicillin has substantially lost its effectiveness against several diseases, such as pneumonia, meningitis, and gonorrhea, in many countries. Eighty percent of Staphylococcus aureus isolates in the United States, for example, are penicillin-resistant and 32 percent are methicillin-resistant. A US Centers for Disease Control and Prevention (USCDC) study found a 60-fold increase in high-level resistance to penicillin among one group of Streptococcus pneumoniae cases in the United States and significant resistance to multidrug therapy as well. Influenza viruses, in particular, are particularly efficient in their ability to survive and genetically change, sometimes into deadly strains. HIV also displays a high rate of genetic mutation that will present significant problems in the development of an effective vaccine or new, affordable therapies.

Breakdown in Public Health Care
Alone or in combination, war and natural disasters, economic collapse, and human complacency are causing a breakdown in health care delivery and facilitating the emergence or reemergence of infectious diseases. While Sub-Saharan Africa is the area currently most affected by these factors, economic problems in Russia and other former communist states are creating the context for a large increase in infectious diseases. The deterioration of basic health care services largely accounts for the reemergence of diphtheria and other vaccine-preventable diseases, as well as TB, as funds for vaccination, sanitation, and water purification have dried up. In developed countries, past inroads against infectious diseases led to a relaxation of preventive measures such as surveillance and vaccination. Inadequate infection control practices in hospitals will remain a major source of disease transmission in developing and developed countries alike.

Climate Change
Climatic shifts are likely to enable some diseases and associated vectors--particularly mosquito-borne diseases such as malaria, yellow fever, and dengue--to spread to new areas. Warmer temperatures and increased rainfall already have expanded the geographic range of malaria to some highland areas in Sub-Saharan Africa and Latin America and could add several million more cases in developing country regions over the next two decades. The occurrence of waterborne diseases associated with temperature-sensitive environments, such as cholera, also is likely to increase.

Regional Trends and Response Capacity

The overall level of global health care capacity has improved substantially in recent decades, but in most poorer countries the availability of various types of health care--ranging from basic pharmaceuticals and postnatal care to costly multidrug therapies--remains very limited. Almost all research and development funds allocated by developed country governments and pharmaceutical companies, moreover, are focused on advancing therapies and drugs relevant to developed country maladies, and those that are relevant to developing country needs usually are beyond their financial reach. This is generating a growing controversy between rich and poorer nations over such issues as intellectual property rights, as some developing countries seek to meet their pharmaceutical needs with locally produced generic products. Malnutrition, poor sanitation, and poor water quality in developing countries also will continue to add to the disease burden that is overwhelming health care infrastructures in many countries. So too, will political instability and conflict and the reluctance of many governments to confront issues such as the spread of HIV/AIDS. A global composite measure of health care infrastructure devised by DIA's Armed Forces Medical Intelligence Center (AFMIC) assesses factors such as the priority attributed to health care, health expenditures, the quality of health care delivery and access to drugs, and the extent of surveillance and response systems. The AFMIC typology highlights the disparities in health care capacity (see figure 9), as do various WHO, UNAIDS, and World Bank studies.

Sub-Saharan Africa
Sub-Saharan Africa will remain the region most affected by the global infectious disease phenomenon--accounting for nearly half of infectious disease-caused deaths worldwide. Deaths from HIV/AIDS, malaria, cholera, and several lesser known diseases exceed those in all other regions. Sixty-five percent of all deaths in Sub-Saharan Africa are caused by infectious diseases. Rudimentary health care delivery and response systems, the unavailability or misuse of drugs, the lack of funds, and the multiplicity of conflicts are exacerbating the crisis. According to the AFMIC typology, with the exception of southern Africa, most of Sub-Saharan Africa falls in the lowest category. Investment in health care in the region is minimal, less than 40 percent of the people in countries such as Nigeria and the Democratic Republic of the Congo (DROC) have access to basic medical care, and even in relatively well off South Africa, only 50 to 70 percent have such access, with black populations at the low end of the spectrum.

Four-fifths of all HIV-related deaths and 70 percent of new infections worldwide in 1998 occurred in the region, totaling 1.8-2 million and 4 million, respectively. Although only a tenth of the world's population lives in the region, 11.5 million of 13.9 million cumulative AIDS deaths have occurred there. Eastern and southern African countries, including South Africa, are the worst affected, with 10 to 26 percent of adults infected with the disease. Sub-Saharan Africa has high TB prevalence, as well as the highest HIV/TB co-infection rate, with TB deaths totaling 0.55 million in 1998. The hardest hit countries are in equatorial and especially southern Africa. South Africa, in particular, is facing the biggest increase in the region.

Sub-Saharan Africa accounts for an estimated 90 percent of the global malaria burden (see figure 10). Ten percent of the regional disease burden is attributed to malaria, with roughly 1 million deaths in 1998. Cholera, dysentery, and other diarrheal diseases also are major killers in the region, particularly among children, refugees, and internally displaced populations. Forty percent of all childhood deaths from diarrheal diseases occur in Sub-Saharan Africa. The region also has a high rate of hepatitis B and C infections and is the only region with a perennial meningococcal meningitis problem in a "meningitis belt" stretching from west to east. Sub-Saharan Africa also suffers from yellow fever, while trypanasomiasis or "sleeping sickness" is making a comeback in the DROC and Sudan, and the Marburg virus also appeared in DROC for the first time in 1998. Ebola hemorrhagic fever strikes sporadically in countries such as the DROC, Gabon, Cote d'Ivoire, and Sudan (see figure 11).

Asia and the Pacific
Although the more developed countries of Asia and the Pacific, such as Japan, South Korea, Australia, and New Zealand, have strong records in combating infectious diseases, infectious disease prevalence in South and Southeast Asia is almost as high as in Sub-Saharan Africa. The health care delivery system of the Asia and Pacific region--the majority of which is privately financed--is particularly vulnerable to economic downturns even though this is offset to some degree by much of the region's reliance on traditional medicine from local practitioners. According to the AFMIC typology, 90 to 100 percent of the populations in the most developed countries, such as Japan and Australia, have access to high-quality health care. Forty to 50 percent have such access among the large populations of China and South Asia, while southeast Asian health care is more varied, with less than 40 percent enjoying such access in Burma and Cambodia, and 50 to 70 percent in Thailand, Malaysia, and the Philippines. In South and Southeast Asia, reemergent diseases such as TB, malaria, cholera, and dengue fever are rampant, while HIV/AIDS, after a late start, is growing faster than in any other region.

TB caused 1 million deaths in the Asia and Pacific region in 1998, more than any other single disease, with India and China accounting for two-thirds of the total. Several million new cases occur annually--most in India, China and Indonesia--representing as much as 40 percent of the global TB burden. HIV/AIDS is increasing dramatically, especially in India, which leads the world in absolute numbers of HIV/AIDS infections, estimated at 3-5 million. China is better off than most of the countries to its south, but it too has a growing AIDS problem, with HIV infections variously estimated at 0.1-0.4 million and spreading rapidly. Regionwide, the number of people infected with HIV could overtake Sub-Saharan Africa in absolute numbers before 2010.

There were 19.5 million new malaria infections estimated in the Asia and Pacific region in 1998, many of them drug resistant, and 100,000 deaths due to malaria. Acute respiratory infections, such as pneumonia, cause about 1.8 million childhood deaths annually--over half of them in India--while dengue (including dengue hemorrhagic fever/dengue shock syndrome) outbreaks have spread throughout the region in the last five years. Waterborne illnesses such as dysentery and cholera also take a heavy toll in poor and crowded areas. Asian, particularly Chinese, agricultural practices place farm animals, fowl, and humans in close proximity and have long facilitated the emergence of new strains of influenza that cause global pandemics. Hepatitis B is widely prevalent in the region, while hepatitis C is prevalent in China and in parts of southeast Asia. In 1999 the newly recognized Nipah virus spread throughout pig populations in Malaysia, causing more than 100 human deaths there and a smaller number in nearby Singapore.

Latin America
Latin American countries are making considerable progress in infectious disease control, including the eradication of polio and major reductions in the incidence and death rates of measles, neonatal tetanus, some diarrheal diseases, and acute respiratory infections. Nonetheless, infectious diseases are still a major cause of illness and death in the region, and the risk of new and reemerging diseases remains substantial. Widening income disparities, periodic economic shocks, and rampant urbanization have disrupted disease control efforts and contributed to widespread reemergence of cholera, malaria, TB, and dengue, especially in the poorer Central American and Caribbean countries and in the Amazon basin of South America. According to the AFMIC typology, Latin America's health care capacity is substantially more advanced than that of Sub-Saharan Africa and somewhat better than mainland Asia's, with 70 to 90 percent of populations having access to basic health care in Chile, Costa Rica, and Cuba on the upper end of the scale. Less than 50 percent have such access in Haiti, most of Central America, and the Amazon basin countries, including the rural populations in Brazil.

Cholera reemerged with a vengeance in the region in 1991 for the first time in a century with 400,000 new cases, and while dropping to 100,000 cases in 1997, it still comprises two-thirds of the global cholera burden. TB is a growing problem regionwide, especially in Brazil, Peru, Argentina, and the Dominican Republic where drug-resistant cases also are on the rise. Haiti does not provide data but probably also has a high infection rate. HIV/AIDS also is spreading rapidly, placing Latin America third behind Sub-Saharan Africa and Asia in HIV prevalence. Prevalence is high in Brazil and especially in the Caribbean countries (except Cuba), where 2 percent of the population is infected. Malaria is prevalent in the Amazon basin. Dengue reemerged in the region in 1976, and outbreaks have taken place in the last few years in most Caribbean countries and parts of South America. Hepatitis B and C prevalence is greatest in the Amazon basin, Bolivia, and Central America, while dengue hemorhagic fever is particularly prevalent in Brazil, Colombia, and Venezuela. Yellow fever has made a comeback over the last decade throughout the Amazon basin, and there have been several recent outbreaks of gastrointestinal disease attributed to E. coli infection in Chile and Argentina. Hemorrhagic fevers are present in almost all South American countries, and most hantavirus pulmonary syndrome occurs in the southern cone.

Middle East and North Africa
The region's conservative social mores, climatic factors, and high levels of health spending in oil-producing states tend to limit some globally prevalent diseases, such as HIV/AIDS and malaria, but others, such as TB and hepatitis B and C, are more prevalent. The region's advantages are partially offset by the impact of war-related uprooting of populations, overcrowded cities with poor refrigeration and sanitation systems, and a dearth of water, especially clean drinking water. Health care capacity varies considerably within the region, according to the AFMIC typology. Israel and the Arabian Peninsula states minus Yemen are in far better shape than Iraq, Iran, Syria, and most of North Africa. Ninety to 100 percent of the Israeli population and 70 to 90 percent of the Saudi population have good access to health care. Elsewhere, access ranges from less than 40 percent in Yemen to 50 to 70 percent in the smaller Gulf states, Jordan and Tunisia, while most North African states fall into the 40- to 50-percent category.

The HIV/AIDS impact is far lower than in other regions, with 210,000 cases, or 0.13 percent of the population, including 19,000 new cases, in 1998. This owes in part to above-average underreporting because of the stigma associated with the disease in Muslim societies and the authoritarian nature of most governments in the region. TB, including multidrug resistant varieties, is more problematic, especially in Iran, Iraq, Yemen, Libya, and Morocco, with an estimated 140,000 deaths in 1998. Malaria is significant only in Iran, Iraq, and Yemen, but diarrheal and childhood diseases caused 0.3 million deaths each in 1998. Other prominent or reemerging diseases in the region include all types of hepatitis, with Egypt reporting the highest prevalence worldwide of the C variety. Brucellosis now infects some 90,000 people; leishmaniasis and sandfly fever also are endemic in the region; and various hemorrhagic fevers occur, as well.

The Former Soviet Union and Eastern Europe
The sharp decline in health care infrastructure in Russia and elsewhere in the former Soviet Union (FSU) and, to a lesser extent, in Eastern Europe--owing to economic difficulties--are causing a dramatic rise in infectious disease incidence. Death rates attributed to infectious diseases in the FSU increased 50 percent from 1990 to 1996, with TB accounting for a substantial number of such deaths. According to the AFMIC typology, access to health care ranges from 50 to 70 percent in most European FSU states, including Russia and Ukraine, and from 40 to 50 percent in FSU states located in Central Asia. This is generally supported by WHO estimates indicating that only 50 to 80 percent of FSU citizens had regular access to essential drugs in 1997, as compared to more than 95 percent a decade earlier as health care budgets and government-provided health services were slashed. Access to health care is generally better in Eastern Europe, particularly in more developed states such as Poland, the Czech Republic, and Hungary, where it ranges from 70 to 90 percent, while only 50 to 70 percent have access in countries such as Bulgaria and Romania. More than 95 percent of the population throughout the East European region had such access in 1987, according to WHO.

Crowded living conditions are among the causes fueling a TB epidemic in the FSU, especially among prison populations--while surging intravenous drug use and rampant prostitution are substantially responsible for a marked increase in HIV/AIDS incidence. There were 111,000 new TB infections in Russia alone in 1996, a growing number of them multidrug resistant, and nearly 25,000 deaths due to TB--numbers that could increase significantly following periodic releases of prisoners to relieve overcrowding. The number of new infections for the entire FSU in 1996 was 188,000, while East European cases totaled 54,000. More recent data indicate that the TB infection rate in Russia more than tripled from 1990 to 1998, with 122,000 new cases reported in 1998 and the total number of cases expected to reach 1 million by 2002. After a slow and late start, HIV/AIDS is spreading rapidly throughout the European part of the FSU beyond the original cohort of intravenous drug users, though it is not yet reflected in official government reporting. An estimated 270,000 people were HIV-positive in 1998, up more than five-fold from 1997. Although Ukraine has been hardest hit, Russia, Belarus, and Moldova have registered major increases. Various senior Russian Health Ministry officials predict that the HIV-positive population in Russia alone could reach 1 million by the end of 2000 and could reach 2 million by 2002. East European countries will fare better as renewed economic growth facilitates recovery of their health care systems and better enables them to expand preventive and treatment programs.

Diphtheria reached epidemic proportions in the FSU in the first half of the decade, owing to lapses in vaccination. Reported annual case totals grew from 600 cases in 1989 to more than 40,000 in 1994 in Russia, with another 50,000 to 60,000 in the rest of the FSU. Cholera and dysentery outbreaks are occurring with increasing frequency in Russian cities, such as St. Petersburg and Moscow, and elsewhere in the FSU, such as in T'bilisi, owing to deteriorating water treatment and sewerage systems. Hepatitis B and C, spread primarily by intravenous drug use and blood transfusions, are on the rise, especially in the non-European part of the FSU. Polio also has reappeared owing to interruptions in vaccination, with 140 new cases in Russia in 1995.

Western Europe
Western Europe faces threats from a number of emerging and reemerging infectious diseases such as HIV/AIDS, TB, and hepatitis B and C, as well as several zoonotic diseases. Its status as a hub of international travel, commerce, and immigration, moreover, dramatically increases the risks of importing new diseases from other regions. Tens of millions of West Europeans travel to developing countries annually, increasing the prospects for the importation of dangerous diseases, as demonstrated by the importation of typhoid in 1999. Some 88 percent of regional population growth in the first half of the decade was due to immigration; legal immigrants now comprise about 6 percent of the population, and illegal newcomers number an estimated 6 million. Nonetheless, the region's highly developed health care infrastructure and delivery system tend to limit the incidence and especially the death rates of most infectious diseases, though not the economic costs. Access to high-quality care is available throughout most of the region, although governments are beginning to limit some heretofore generous health benefits, and a growing antivaccination movement in parts of Western Europe, such as Germany, is causing a rise in measles and other vaccine-preventable diseases. The AFMIC typology gives somewhat higher marks to northern over some southern European countries, but the region as a whole is ranked in the highest category, along with North America.

After increasing sharply for most of the 1980s and 1990s, HIV infections, and particularly HIV/AIDS deaths, have slowed considerably owing to behavioral changes among high-risk populations and the availability and funding for multidrug treatment. Some 0.5 million people were living with HIV/AIDS in 1998, down slightly from 510,000 the preceding year, and there were 30,000 new cases and 12,000 deaths, with prevalence somewhat higher in much of southern Europe than in the north. TB, especially its multidrug resistant strains, is on the upswing, as is co-infection with HIV, particularly in the larger countries, with some 50,000 TB cases reported in 1996. Hepatitis C prevalence is growing, especially in southern Europe. Western Europe also continues to suffer from several zoonotic diseases, among which is the deadly new variant Creutzfeldt-Jakob disease (nvCJD), linked to the bovine spongiform encephalopathy or "mad cow disease" outbreak in the United Kingdom in 1995 that has since ebbed following implementation of strict control measures. Other recent disease concerns include meningococcal meningitis outbreaks in the Benelux countries and leishmaniasis-HIV co-infection, especially in southern Europe.

International Response Capacity

International organizations such as WHO and the World Bank, institutions in several developed countries such as the US CDC, and Nongovernmental Organizations (NGOs) will continue to play an important role in strengthening both international and national surveillance and response systems for infectious diseases. Nonetheless, progress is likely to be slow, and development of an integrated global surveillance and response system probably is at least a decade or more away. This owes to the magnitude of the challenge; inadequate coordination at the international level; and lack of funds, capacity, and, in some cases, cooperation and commitment at the national level. Some countries hide or understate their infectious disease problems for reasons of international prestige and fear of economic losses. Total international health-related aid to low- and middle-income countries--some $2-3 billion annually--remains a fraction of the $250 billion health bill of these countries.

WHO
WHO has the broadest health mandate under the UN system, including establishing health priorities, coordinating global health surveillance, and emergency assistance in the event of disease outbreaks. Health experts give WHO credit for major successes, such as the eradication of smallpox, near eradication of polio, and substantial progress in controlling childhood diseases, and in facilitating the expansion of primary health care in developing countries. It also has come under criticism for becoming top heavy, unfocused in its mission, and overly optimistic in its health projections. WHO defenders blame continued member state parsimony that has kept WHO's regular biennial budget to roughly $850 million for several years and forced it to rely more on voluntary contributions that often come with strings attached as the cause of its shortcomings.

The election last year of Gro Harlem Bruntland as Secretary General, along with a series of reforms, including expansion of the Emerging and other Communicable Diseases Surveillance and Control (EMC) Division, has placed WHO in a better position to revitalize itself. Internal oversight and transparency have been expanded, programs and budgets are undergoing closer scrutiny, and management accountability is looming larger. Bruntland has moved quickly to streamline upper-level management and has installed new top managers, mostly from outside the organization, including from the private sector. She also is working to strengthen country offices and to make the regional offices more responsive to central direction. WHO is increasing its focus on the fight against resurgent malaria, while a better-funded EMC is expanding efforts to establish a global surveillance and response system in cooperation with UNAIDS, UNICEF, and national entities such as the US CDC, the US DoD, and France's Pasteur Institute.

Other UN Agencies Involved in Health Care

WHO competes for resources with the many other UN agencies that are increasingly involved in health care. The United Nations Children's Fund (UNICEF) focuses on children's health. The United Nations AIDS Program (UNAIDS) focuses on improving the response capacity toward HIV/AIDS at the country, regional, and global levels in cooperation with WHO and other UN agencies. Other UN agencies involved in health care issues include the UN Development Program (UNDP); the UN Family Planning Agency (UNFPA); the UN High Commissioner for Refugees (UNHCR); the UN Educational, Scientific and Cultural Organization (UNESCO); the International Labor Organization (ILO); the Food and Agricultural Organization (FAO); and the World Food Program (WFP).

The World Bank
The growing sense that health is linked inexorably to socioeconomic development, has prompted the World Bank to expand its health activities. According to a 1997 study by the US Institute of Medicine, the most significant change in the global health arena over the past decade has been the growth in both financial and intellectual influence of the World Bank, whose health loans have grown to $2.5 billion annually, including $800 million for infectious diseases. Health experts generally welcome the Bank's greater involvement in the health sector, viewing it as efficient and responsive in areas such as health sector financial reform. Some remain concerned that the Bank's emphasis on fiscal balance can sometimes have a negative health and social impact in developing countries. Some developing countries resent what they perceive as the domination of Bank decisionmaking and priority setting by the richer countries.

Nongovernmental Organizations
Another major change in the global health arena over the last decade is the increasingly important role of NGOs, which provide direct assistance, including emergency shelter and aid, as well as long-term domestic health care delivery. NGOs also build community awareness and support for WHO and other international and bilateral surveillance and response efforts. At the same time, health experts note that NGOs, like their governmental counterparts, are driven in part by their own self interests, which sometimes conflict with those of host and donor governments.

Bilateral Assistance
The United States, through USAID, the CDC, the National Institutes for Health (NIH), and the Defense Department's overseas laboratories, is a major contributor to international efforts to combat infectious diseases. It is joined increasingly by other developed nations and regional groupings, such as the European Union (EU), that provide assistance bilaterally, as well as through international organizations and NGOs. The Field Epidemiology Training Programs--run jointly by the CDC and WHO--as well as the EU-US Task Force on Emerging Diseases and the US-Japan Common Scientific Agenda, are key examples of developed-country programs focusing on infectious diseases.

National Limitations
A major obstacle to effective global surveillance and control of infectious diseases will continue to be poor or inaccurate national health statistical reporting by many developing countries and lack of both capacity and will to properly direct aid (see figure 12) and to follow WHO and other recommended health care practices. Those areas of the world most susceptible to infectious disease problems are least able to develop and maintain the sophisticated and costly communications equipment needed for effective disease surveillance and reporting. In addition to the barriers dictated by low levels of development, revealing an outbreak of a dreaded disease may harm national prestige, commerce, and tourism. For example, nearly every country initially denied or minimized the extent of the HIV/AIDS virus within its borders, and even today, some countries known to have significant rates of HIV infection refuse to cooperate with WHO, which can only publish the information submitted by surveying nations. Only a few, such as Uganda, Senegal, and Thailand, have launched major preventative efforts, while many WHO members do not even endorse AIDS education in schools. Similarly, some countries routinely and falsely deny the existence of cholera within their borders.

Aid programs to prevent and treat infectious diseases in developing countries depend largely on indigenous health workers for their success and cannot be fielded effectively in their absence. Educational programs aimed at preventing disease exposure frequently depend on higher literacy levels and assume cultural and social factors that often are absent.

Alternative Scenarios and Outlook for Infectious Diseases

The impact of infectious diseases over the next 20 years will be heavily influenced by three sets of variables. The first is the relationship between increasing microbial resistance and scientific efforts to develop new antibiotics and vaccines. The second is the trajectory of developing and transitional economies, especially concerning the basic quality of life of the poorest groups in these countries. The third is the degree of success of global and national efforts to create effective systems of surveillance and response. The interplay of these drivers will determine the overall outlook.

On the positive side, reduced fertility and the aging of the population, continued economic development, and improved health care capacity in many countries, especially the more developed, will increase the progress toward a health transition by 2020 whereby the impact of infectious diseases ebbs, as compared to noninfectious diseases. On the negative side, continued rapid population growth, urbanization, and persistent poverty in much of the developing world, and the paradox in which some aspects of socioeconomic development--such as increased trade and travel--actually foster the spread of infectious diseases, could slow or derail that transition. So, too, will growing microbial resistance among resurgent diseases, such as malaria and TB, and the proliferation or intensification of new ones, such as HIV/AIDS.

Two scenarios--one optimistic and one pessimistic--reflect differences in the international health community concerning the global outlook for infectious diseases. We present and critically assess these scenarios, elaborate on the pessimistic scenario, and develop a third, combining some elements of each, that we judge as more likely to prevail over the period of this Estimate.

The Optimistic Scenario: Steady Progress
According to a key 1996 World Bank/WHO study cited earlier that articulated the optimistic scenario, a health transition--resulting from key drivers, such as aging populations, socio-economic development, and medical advances--already is under way in developed countries and also in much of Asia and Latin America that is likely to produce a dramatic reduction in the infectious disease threat. The study projects that deaths caused primarily by infectious diseases will fall steadily from 34 percent of the total disease burden in 1990 to 15 percent in 2020. Those from noninfectious diseases are likely to climb from 55 percent of the total disease burden to 73 percent, with the remainder of deaths due