THE SPECTER OF EMERGING AND RE-EMERGING INFECTION EPIDEMICS

by Donald B. Louria, MD

In the field of infectious diseases, one of the topics creating the greatest current interest is the potential for future epidemics due to emerging and re-emerging infections. Emerging infections are those that are completely new (such as HIV-AIDS or Ebola virus) or infections that are not new, but occur in new geographic areas, or infections that suddenly increase in frequency. For example, dengue, a mosquito-borne viral disease that causes an influenza-like illness (but can be fatal) is both increasing in frequency and appearing in new geographic areas. Re-emerging infections are those that reappear after a variable period of dormancy when they were absent or at very low frequency; thus, in the last seven years, there have been more than 100,000 cases of diphtheria in the ex-Soviet Union.

Epidemics of infectious diseases have always played a major role in the course of human history, altering economic and community stability, determining where people will live, and human migration patterns. In 1918, influenza savaged the planet, killing an estimated 20 million persons, 1 of every 100 persons in the world population. In previous centuries, epidemics of plague and cholera shattered and, not infrequently, decimated communities.

Now we have HIV-AIDS which is in its own way every bit as venomous as the influenza, plague, and cholera epidemics of past decades and centuries. Since it first appeared in the 1980s, the virus has infected more than 60 million people and killed at least 20 million; in some countries in Africa, 20 to 25 percent of the adult population are HIV-positive, a terrifying figure. And, it is far from done.

HIV is just one example. The next century will bring with it a variety of other severe infections with the ability to affect large numbers of people, potentially with very high death rates. Additionally, emerging infections can be deliberately introduced (bioterrorism). Almost certainly in the coming decades, emerging infections due to bioterrorism will be inflicted on our global society. Faced with the threat of these very dangerous emerging and re-emerging infections, our goals are to detect them early, precisely define the microorganism, intervene promptly, control them, and, above all, prevent them. I have summarized the approaches to prevention and control in Table 1.

The current emphasis is on worldwide surveillance to allow very early detection. That certainly is necessary. Recently, there was a substantial delay in establishing that the Ebola virus infection in Africa and plague in India were causing epidemics. The Centers for Disease Control in Atlanta and the World Health Organization are leading the effort to improve surveillance in every country so emerging and re-emerging infections will be suspected early, proper specimens collected and rapidly transported to sophisticated diagnostic laboratories. A marked improvement in surveillance capabilities requires money, trained personnel, and organization. Fortunately, the amount of money needed to establish a more effective (but not a perfect) surveillance system is modest. Unfortunately, a major problem in creating effective worldwide surveillance for emerging infections is dependence on organizational capabilities in less affluent countries and on the strength of a their public health infrastructure. In most developing countries, the public health infrastructure ranges from inadequate to horrendous. That is why 1.5 billion people do not have safe water to drink and explains, in large part, the billions of episodes of diarrhea that account for millions of deaths each year. Surely the most basic functions of a country’s public health infrastructure are to provide safe water and uncontaminated food. Only after these basic functions are in place and operating reasonably effectively can a country allocate the resources needed to include proper infection surveillance as part of its program.

Most developing countries spend less than 30 dollars (often a lot less) per person per year on their populations for health. If that is all the money that is available, most of it will be spent on administration and on treatment of established illness, not on the public health infrastructure or surveillance. In the United States, annual spending on health by the government far exceeds 1,000 dollars per person, and we spend large amounts on public health infrastructure.

We can, and will, have better surveillance, but such surveillance cannot be optimal until each country has a very good public health infrastructure - and that is unlikely to happen in the absence of major economic gains among the less affluent countries of the world in Africa, Asia, and Latin America.

Another mechanism for coping with emerging and re-emerging infections is immunization. Millions of children die every year of vaccine preventable diseases, mostly in developing countries, just because they have not been given available safe and effective vaccines. In contrast to established infections, such as influenza, epidemics of new emerging infections often present a daunting challenge, and it may take a long time before an effective vaccine is developed. HIV/AIDS is a good example; it has been with us for more than twenty years, and we still do not have a vaccine. Similarly, we do not have vaccines for Ebola or Hanta viruses. The bottom line is that immunization is important, but we cannot depend on it to prevent epidemics of emerging and re-emerging infections.

In actuality, I believe that potentially the most effective approach we could take to ameliorate the problem of emerging and re-emerging infections is modification of the societal variables that provide the mileau in which these infections arise and thrive. Because modifying societal determinants can avoid some emerging infections entirely, it is true prevention, unlike global surveillance which focuses on early detection, after the epidemic has started.

In Table 2, I have listed some of these societal variables whose modification or amelioration I believe to be crucial to prevention and control of these infections. The two overarching determinants are population pressures and global warming.

POPULATION GROWTH AND ITS CONSEQUENCES

Modern civilization dates from approximately 10,000 BC. It took almost that entire span for the planetary population to reach one billion persons. Once that milestone was achieved (in 1830), the population express gathered steam. It required only 100 years for world population to double to two billion, and 70 more years to reach six billion. Fertility rates are falling so that some developed countries are at zero population growth, but overall world population is growing at average of 1.3 percent per annum, with a projected population doubling time of 54 years. It seems almost certain there will be eight billion people on the planet by the year 2030.

A huge problem in moving towards population stability is the geographic disparities. In North America, the population is projected to double in about 120 years. That is quite reasonable. Europe is even closer to zero population growth. In contrast, in Asia (excluding China) and in Latin America, the population will double in 39 years. In Latin America, the doubling time is 40 years, and in Africa, it is an almost unbelievable 29 years.

Estimates of the ultimate population of the planet depend on assumptions about changing fertility rates (the average number of children a woman will bear). Very optimistic projections for eventual final population of planet Earth are six to eight billion; in contrast, very pessimistic estimates are 18 to more than 20 billion. Medium estimates are in the 10 to 11 billion range.

Whatever projection is used, it seems clear that the crowding that characterizes much of the current human condition will increase — and crowding promotes the spread of newly emerging and re-emerging infectious diseases. Some of the adverse effects that may occur consequent to a doubling or tripling of world population are summarized in Table 3.

I have included rainforest and wetland destruction. These do not usually directly impact on emerging infections, but they may. As flies, mosquitoes, and rodents are deprived of their usual ecological niche in forests or wetlands, they may migrate to population centers, become established, and spread a variety of infections. I have put an asterisk by hunger and inadequate potable water. Hunger is associated with malnutrition, and malnutrition predisposes individuals to all sorts of infections, but it may be that, with newer technologies, we can feed a population of 10 or 15, or even 20 billion persons. Similarly, technologies may be developed to inexpensively desalinate water and, thus, avoid the impending catastrophic shortage of water for daily use.

One of the most important consequences of the massive increase in population numbers has been the progressive urbanization of the planet. The latter half of the 20th century has been characterized by creation of large cities with ever greater population densities that draw inhabitants from rural areas and often act as sinkholes for hordes of newly landless people displaced by economic hardships or the ravages of war. Lured to the cities by hopes of a better life, large numbers of migrants experience underemployment or no employment and become inhabitants of teeming slums. The crowed slums, often with inadequate sanitation and stagnant water, are not only ideal settings for the initiation of epidemics and then rapid person-to-person spread, but are also virtual breeding grounds for rodents and for fly and mosquito vectors. At the beginning of the 20th century, about 15 percent of the world population of less than two billion people lived in cities; at the beginning of the 21st century, approximately half of the world’s six billion persons are urban dwellers; that figure is expected to grow to 60 to 65 percent by the year 2030; 80 percent of this massive urbanization will take place in the so-called developing countries. By the end of the first decade of the 21st century, there will be at least 26 megacities, each with more than ten million inhabitants.

Doubling of our present population absolutely guarantees a planet with a very large number of crowded cities, each with populations of one to thirty million persons, most with areas of teeming slums. And, that, in turn, translates into a profound increase in the risk of contagious diseases, some of which will be emerging and re-emerging infections, and some of which will turn into rapidly spreading, severe epidemics. The only way to avoid this is to limit population growth. Ten or 11 billion people on the planet will be bad enough; 14 to 18 billion would be an infectious diseases catastrophe.

Perhaps no human activity is so conductive to emergence or re-emergence of infectious diseases as warfare, a human activity that, measured by the number of people involved, becomes more extensive every century (in part because of population growth). The 20th century was the bloodiest in history. There were 150 wars in the last half of that century, resulting in more than 23 million deaths, two-thirds of them civilians.

Wars create the milieu for infection in many ways: massive injuries that invite microbial infection; forced migration of non-immunized persons into areas inhabited by disease-carrying mosquitoes and flies; crowding in refugee camps with inadequate sanitation facilities; exposure to disease-carrying rodents; malnutrition, even starvation; and destruction of public health infrastructures and safe water supplies. Additionally, mass rape as an accepted or deliberately overlooked behavior of conquerors, or sometimes as an intentional military and governmental technique of intimidation and cruelty, can become a vehicle for spread of sexually-transmitted diseases.

The prospects for less warfare are not good. The ethnic, religious, racial, and tribal strife that currently savages planet Earth will be worsened by population growth, crowding, and competition for increasingly depleted natural resources. In future decades, competition for a decreasing supply of fresh water will be an ever more important motivation for combat. Water shortages will result from a combination of population growth, increased irrigation requirements to feed that growing population, and the effects of urbanization and industrialization.

As the planetary population increases, the need to produce more food and find more sources of energy will result in massive irrigation projects and dam building. In 1950, there were 5,000 dams designated as large (defined as more than 15 meters in height). Now, there are 38,000 of these dams, and 1,200 more are under construction; two-thirds of these will be more than 30 meters in height. So, we are building more and larger dams primarily to create electricity. Additionally, increase in the land under irrigation is cutting into the remaining forests and damaging our crucial wetlands.

In developing countries, new infectious disease patterns have often been an untoward consequence of dam construction. Habitat advantages have been created particularly for mosquitoes and snails. The Aswan Dam resulted in 200,000 new cases of a serious mosquito-borne virus infection ‘Rift Valley’ Fever, as well as a marked increase in the parasitic disease schistosomiasis (from snails) and malaria (from mosquitoes) among populations adjacent to the dam. Additionally, large dams, such as the gargantuan one being constructed on the Yangtze River in China, require relocation of tens of thousands, even millions, of people; this forced displacement is often associated with worse living conditions and increased poverty, both risk factors for increased infection rates. In some cases, the enormity of the construction project requires the recruiting of large numbers of workers from distant parts of the country or from other countries. These new "temporary" immigrants bring their own infections with them, creating the potential for emerging or re-emerging infections in local populations. Furthermore, the newly-created large bodies of water are subject to massive fecal contamination, increasing the likelihood of re-emerging pathogen epidemics (for example, cholera).

As the world population increases and travel becomes easier and more affordable, it is inevitable that the number of international travelers will increase. In 1990, there were 280 million persons traveling outside their own nations’ borders. By the year 2000, that figure increased to more than 400 million people. Some of these travelers will carry organisms with them and start epidemics in countries to which they travel. Others will become infected during their travels and bring the organism back with them to their own countries. And, of course, infected mosquitoes, flies, and rodents love to hitch rides on airplanes or sea-going vessels.

GLOBAL CLIMATE CHANGE

The climatological event most likely to affect infectious diseases is global warming. The evidence for global warming gets progressively more convincing. It is likely that, in the 21st century, the planet will become 1.5ºC to 4ºC warmer. The warming will result in winners and losers; some geographic areas, now quite cold, will be more productive; others will suffer from severe floods or drought, and the entire world will experience more severe and turbulent weather events, in particular ferocious storms. At least half the greenhouse (heat trapping) gas burden responsible, in considerable part, for the warming is due to carbon dioxide. Methane (10 to 20 percent), chlorofluorocarbons (10 to 20 percent), and nitrogen oxides (4 to 7 percent) are the other principal greenhouse gases. More than 25 billion tons of CO₂ are released yearly into the environment. Of that amount, about 60 percent results from industrial and home fossil fuel use, and 10 to 20 percent from emissions from the more than 500 million cars and trucks used around the globe. An additional 20 percent comes from felling and burning trees in the world’s ever-diminishing forests. Atmospheric carbon dioxide concentrations have risen 30 percent in the last two centuries; the current concentration of 360 parts per million could increase by an additional 60 percent by the end of the 21st century.

Changes in temperature will alter the distribution and behavior of mosquitoes and flies. At higher temperatures, some mosquitoes tend to be more active, eat more voraciously, and bite more frequently. Additionally, they have more rapid reproductive cycles and the time required for development of infectious agents, such as malaria, in the mosquito is lessened. Mosquitoes that have found higher elevations cold and inhospitable will be able to thrive in previously mosquito-free areas that become warmer; this, in turn, will introduce certain mosquito-borne diseases, such as malaria and dengue, to unexposed areas and, therefore, to nonimmune populations. This introduction of infectious agents as a result of vector (mosquitoes, flies) redistribution into non-immune populations is likely to be one of the major worldwide consequences of global warming.

Malaria, dengue, and schistosomiasis lead the list of infections likely to increase as a consequence of global warming. Malaria is perhaps the most feared disease on the planet. There are an estimated 300 to 500 million people affected each year and one to three million deaths. Only tuberculosis rivals malaria in the number of deaths. Global warming could markedly increase the number of cases. Dengue is a viral disease transmitted by mosquitoes that affects 100 million persons yearly. In most persons, it causes fever, chills, and severe muscle aches, with recovery in a period of several days to several weeks. However, in those who have had previous infections, a second attack can produce severe bleeding and even death.

The future appears bleak in regard to global warming. Although the United States is the world’s leader in production of greenhouse gases, contributing more than 20 percent of total annual carbon dioxide burden, China, now in second place, is increasing its CO₂ release at a stunning rate (up 27 percent in less than ten years). With understandable determination to become more affluent, China will require a profound increase in energy, almost certainly by use of its abundant supply of coal. That presents a gargantuan problem.

But, it is not only the progressive increase in carbon dioxide levels that is of concern. Methane could be an equally important greenhouse gas in the next century. Methane traps heat far more effectively than CO₂. Its sources are much harder to control. They include: swamps, marshes, wetlands, fens, and bogs; coal, oil, and gas extraction; rice paddies; termites; and the intestinal tracts of ruminants. The rule of thumb is for every one billion new people on planet Earth, there will be 500 million more cattle; the more cattle, the more methane.

Because there will be difficulties in controlling methane emissions, the only solution will be to control population increase and to compensate for the likely methane increase by a marked reduction in the main greenhouse gas, CO₂.

One important reason population growth and global warming are such critical variables is that, once the global population has grown excessively and the planet is warmer, there is no logically thought out behaviors of man that will quickly remedy the situation in regard to these two superordinating determinants. To achieve cooling of a planet heated by human actions would take at least several decades, plenty of time for the planet to be savaged by multiple severe emerging infections. If excessive population growth creates immense problems, it would take centuries to effect significant reductions in that population size.

POVERTY, MALNUTRITION, AND EXPOSURE TO UNSAFE WATER

A reasonable estimate is that between one-quarter and one-third of the population of planet Earth live in poverty. Some two billion persons suffer from under nutrition or malnutrition; one billion experience hunger on a daily basis, and at least 400 million suffer from dire poverty and major nutritional deprivation. In the range of 1.5 billion people lack access to basic health care. A similar number do not have access to safe water. With a substantial increase in population size expected in the 21st century, these disturbing figures could get substantially worse.

The link between poverty and under nutrition or malnutrition is clear; so is the connection between under nutrition and infectious diseases. Malnutrition increases the frequency and severity of many infections. Those living in poverty around the planet usually are also the ones particularly exposed to unsafe water. The adverse consequences of that exposure are fully established; diarrheal disease from water contaminated by bacteria, viruses, and parasites accounts for billions of episodes each year and, as a consequence, billions of dollars in lost productivity, millions of deaths, and an extraordinary toll in hardship and misery.

DISPLACED PERSONS

In a hotter world with a larger population, huge numbers of people will be displaced by floods, drought, and reduced ability to produce enough food. At present, there are approximately 40 million persons who are either refugees outside their own borders or internally displaced. In the year 2050, with 9 to 10 billion persons on the planet and the uprooting effects of global climate change, there could be hundreds of millions of refugees and internally displaced persons. That is likely to be beyond the coping capacity of man. That huge number of refugees, often living in squalor, crowded together in unhygienic circumstances, creates an ideal situation for development of emerging and re-emerging infections with rapid person-to-person spread, and then spread outside the refugee camps to local populations.

Once established, given the ease of travel, the infections can reach virtually any part of our planet.

The determinants I have discussed are, for the most part, intensely interrelated. Thus, as the number of people on planet Earth increases by billions, the likelihood of global warming increases. These two variables together influence other variables, such as warfare and forced migration, that establish the setting in which emerging and re-emerging infections arise and thrive. A modicum of control can be the difference between manageable problems and uncontrollable problems. That, in turn, can be the difference between a relatively small number of emerging and re-emerging infections of limited severity and more frequent epidemics of far greater severity.

Recognition of the interrelatedness of the determinants is important because it leads to a systems (holistic) approach rather than a more simplistic, but more comfortable, focus on single determinants with the implicit (but erroneous) assumption that modification of single variables can have a major impact without a simultaneous change in the entire system, particularly in the two superordinating factors - global warming and population growth.

If these variables, these determinants, can decide the frequency and severity of infection epidemics in future decades and centuries, then, if we can modify them, we can, to some extent, be the masters of our fate. There is no way to prevent all major epidemics. No matter what we do, some major epidemics of emerging and re-emerging infections will occur and some will kill tens of thousands or hundreds of thousands or even millions of people. But, we have the capacity to determine whether there will be many or only a few major epidemics severe enough to kill or damage large numbers of people.

There may be no way to avoid an eventual planetary population of 10 billion, but prudent actions could make sure we do not have a world population of 14 or 18 billion. That would be a huge difference. Similarly, we may be committed to a 1ºC to 2ºC increase in global temperature, but we should be able to avoid a 4ºC or greater rise.

How can we best approach these issues? The answer is there is plenty we can do. There are three domains - individual actions, changes in our educational system, and political actions.

INDIVIDUAL ACTIONS

One of the rationales used for continuing non-involvement is the perception that individuals are feckless and are unable to exert any major influence on events. That is a mistake. As Sidney Smith, a 19th century English clergyman, noted (slightly modified), "No man or woman makes a greater mistake than he or she who does nothing because he or she can only do a little".

An example of the potential for individual actions is global climate change. The public views global warming as a distant phenomenon unrelated to their daily lives, but, in point of fact, individuals can have an impact on two-thirds of carbon dioxide emissions (see Table 4).

EDUCATIONAL MODIFICATION

Much of the vision about educational change in future decades focuses on technological advances that permit ready access to information, distance learning, and sharing information and projects through sophisticated communication technologies. But, in one critical area, our educational system is failing young people, and that is in instilling long-term commitment to participating in attempts to solve or ameliorate major societal problems.

I would suggest we need a small, but critical, change in our educational system that could have far-reaching and beneficial effects.

I would propose that, at every educational level, students have, on a mandatory basis, interdisciplinary courses with the following goals:.

1.To provide them with a reasonably comprehensive view of the major issues facing the society at all levels.

2. To have them understand that many of the major issues are interrelated.

3. To teach the importance of systems (holistic) thinking about critical problems.

4. To have them think like futurists, drawing up alternative scenarios for future years or decades, and then suggesting ways of moving towards the most attractive of the scenarios.

5. Above all, to consciously instill in them long-term, part-time, or even full-time, commitment to solving or ameliorating one or more of the important problems at local, state, national, or international levels.

These courses should probably start at the junior high school level, certainly in high schools, and should be a part of college and graduate school (law, medicine, business) curricula.

If we do not modify our educational offerings to achieve the goals I have enumerated, our education system will continue to fail our young people, and they will not be committed to societal problem solving.

(In September 2002, a special feature article on educational change will appear on this site)

POLITICAL ACTIONS

Emerging infections may be dangerous, but they also offer an extraordinary opportunity to use their threat to compel politicians to face and take action against the major problems facing our society - problems that also happen to be the major determinants of emerging and re-emerging infections. Politicians around the world show a remarkable ability to avoid doing anything aside from rhetorical hand wringing about the issues I have discussed - population explosion, global warming, wars, growing numbers of refugees, massive urbanization with equally massive slums, dwindling supply of fresh water, etc.

Part of the reason for this insouciance is that the problems, important as they are, do not strike a responsive chord among the constituents of those politicians. The problems seem remote and not applicable to the daily lives of most people, in particular people in the more affluent developed countries. After all, who cares if another billion people are added to the world’s population so long as that billion is in the developing world and out of sight, and who cares if hundreds of millions of children in those same developing countries suffer from horrendous poverty and hunger, or if another ten million people are added to the growing rolls of refugees.

It has been said that politicians think of the next election, statesmen of the next generation. We have a lot of politicians, but very few statesmen in the so-called developed world. In the United States, the public has been interested primarily in the present or in the next few years, and in issues such as taxes and crime - not in world population, the greenhouse effect, or refugees in far off countries. Indeed, the public apathy in the United States is so pervasive that the majority of adults do not even care enough about their democracy to vote. If people do not know about or care about the critical issues facing the global society, it is hardly surprising the politicians do not feel any pressure to focus on these issues. But, the concerns about emerging and re-emerging infections could change all that, as could the concerns about international terrorism.

Politicians and their constituents may have a lot of trouble in relating to, or doing anything about, expanding world populations or the threat of global warming, but those same politicians and their constituents can understand, and be concerned about lethal, rapidly-spreading epidemics.

Hopefully, we can use the specter of, indeed the virtual certainty of, severe epidemics of emerging and re-emerging infections to persuade politicians that insouciance is no longer acceptable, and that they must focus upon and take steps to mitigate these major societal determinants.

Unfortunately, at present, the United States has a distressingly poor record in regard to these critical issues:

• Inadequate funds are provided for family planning (population control) and attempts are being made to restrict the population control efforts of governmental and non-governmental organizations around the world.

• The United States is perceived as undercutting the implementation of bioterrorism and biological warfare prevention treaties.

• The United States has made grossly inadequate efforts in regard to fuel efficiency and alternatives to fossil fuels.
  
  

We need a combination of individual activism, educational modification, and public pressure that modifies the behavior of politicians and societal leaders. One thing is clear. We must have activists who work to change our political behavior so that we tackle the major societal determinants of emerging and re-emerging infections. If we do not succeed as a global society in achieving that objective, the future of our global society will be bleak in regard to savage emerging infection epidemics.

A version of this essay appeared in Scheld WM, Armstrong D, and Hughes JM (editors). Emerging Infections. American Society for Microbiology. Washington DC. 1998.