Perspectives in Health Magazine
The Magazine of the Pan American Health Organization
Special Centennial Edition
Volume 7, Number 1, 2002
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Perspectives in Health Magazine |
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As human impact on the earth increases exponentially, the chances for unpleasant surprises from the microbial world will also grow.
A young man--a trained athlete in the prime of life--lies on his sofa with aches that penetrate to his bones. He turns up the air conditioner as his fever drenches him in sweat. He drinks a little water but has no appetite after vomiting throughout the night. He feels as bad as he has ever felt in his life. The weight of his lethargy presses him down into the couch. Soon, he begins to feel short of breath. In a few hours, he will go to the hospital, but it won t matter. Even state-of- the-art intensive care cannot revive his failing heart, suction his edematous lungs fast enough or replace the fluid with sufficient oxygen for him to breathe. Within 48 hours, the young man will have drowned in his own blood plasma.
It may sound like a fiction writer's overheated imagination, but this is what really happened in the southwestern United States in 1993. Cases of the "mystery disease" piled up. Newspapers alarmingly reported the "experts stumped." Local physicians quickly realized they were up against something beyond their knowledge, and even the accumulated scientific wisdom at the nearby university proved little help. State public health authorities were unable to solve the problem, and when officials of the U.S. national Centers for Disease Control and Prevention were called in, they had nothing to offer but an investigation. Finally, after a concerted effort, authorities discovered the root of the malady was a virus carried by a local rodent, which showed no signs of illness itself. This new hantavirus caused a new disease, hantavirus pulmonary syndrome, or HPS, which to this day we do not know how to prevent or treat.
The story of HPS exemplifies our increasing awareness of threats from the microbial world and our halting efforts to confront them. The dangers are not just a media invention; they are real and significant. The main components of the problem are the emergence of "new" organisms, shifting tactics of known infectious agents and the growing resistance of pathogens to existing antimicrobial drugs.
Although the threat of emerging and reemerging infectious diseases is greatest in the developing countries of the tropics, countries with higher incomes face the danger as well. Two other "new" hantaviruses were discovered after people died in small, poor Amerindian communities in Paraguay and in one of the most expensive neighborhoods on Long Island, New York, in the United States.
While the industrialized world has more resources to prepare for these threats, its impressive health progress over the last century has led to widespread complacency about diseases that seem to affect primarily the world's poor. Yet with the growth of global travel, changes in the earth's ecology and natural viral mutation, one country's emerging disease is potentially another's next epidemic. What's more, the factors that favor emerging diseases are also present--in some cases even accentuated--in the developed world.
"New," but not so new
The evolution of pathogens is measured in centuries or millennia, so truly new organisms do not simply burst upon the scene from nothing. Usually, they have undergone quiet periods of development in nonhuman hosts, then changes in ecology or human society lead to their emergence as killers and their recognition by medical science.
Such was the story of the rodent-borne hantaviruses: they have been parasites of native rodents in the Americas for at least 30 million years, but in 1993, climate changes caused by the El Niņo southern oscillation led to increased breeding and rapid growth of rodent populations in the southwestern United States and a subsequent spillover of the virus into human populations.
Cases of the disease had occurred but gone unrecognized for many years until more accurate tests for viruses allowed us to define a "new" disease that had not been diagnosed previously. More important, scientists found that in the Americas, more than 20 different viruses could cause this new clinical disease. Each virus is carried by a different rodent species, with distinct epidemiological patterns dependent on the host species and its interaction with people. HPS has now been recognized in most of the countries of the Americas and is considered a significant threat to the Region's public health.
Another "recently emerged" virus, HIV (human immunodeficiency virus), illustrates a different process. The simian version was a chronic infector of chimpanzees in Africa before crossing species and infecting humans, causing acquired immune deficiency syndrome, or AIDS. Transmitted primarily by sexual intercourse, unsterilized needles and blood transfusions, AIDS has spread rapidly worldwide by capitalizing on its chronic nature and the long period during which carriers show no symptoms but can transmit the virus. In spite of its stealth strategy, AIDS claims the lives of virtually everyone it infects within a decade or so. Some will be able to stave off its lethal effects by taking expensive and toxic medications, but the majority of the 40 million people infected today will die without even this benefit. In all likelihood, HIV will be the most significant infectious agent of the 21st century barring the emergence of something even worse.
A more agile offender is the influenza A virus. We tend to think of influenza as a minor illness that comes to torment us every winter. But this is only partially true. The virus circulates in humans and gradually changes its covering proteins to escape protective responses from our immune system. We monitor those changes through a global surveillance system coordinated by the World Health Organization (WHO), and in an annual WHO meeting, a new vaccine formula is devised to fight the emerging strains. We are fairly successful in coping with the evolutionary changes of the virus, yet every year some 20,000 people die of the flu in the United States alone.
Independent of this slow strain drift is another process that occurs outside humans, in which many different influenza strains randomly exchange their genes. When a highly virulent and transmissible combination occurs and makes its way into the human population, a worldwide epidemic, or pandemic, results. The virus spreads quickly because no one has any significant immunity to the novel strain, and the illness it causes can be unusually severe. The worst pandemic was in 1918, when more than 20 million people died worldwide from a particularly virulent influenza strain. The last was the 1968-69 "Hong Kong flu," which killed 700,000. Since flu pandemics tend to occur every 10 to 40 years, we are statistically overdue for a new one. In 1997 we had a very close call: a virus appeared in domestic fowl in Hong Kong and killed nearly one-third of the people subsequently infected. Fortunately, it proved to be of limited transmissibility between humans, and prompt surveillance and disposal of infected birds eliminated the threat.
What would happen in a new pandemic? It is questionable whether we could detect a new virus in time to prepare a new vaccine in quantity. We might turn to antiviral drugs, but stocks are low, and expanding them rapidly would not be feasible. The death toll from a new pandemic might be only a million or so or it could rival or exceed the 20 million deaths in 1918.
Ecological change
The driving forces behind these problems are in great part related to population growth and human behavior. Satellite images show that people have modified more than half the world's surface, leading to profound changes in land use, water availability and even climate. As agriculture occupies progressively larger zones, flora, fauna and associated infectious disease agents are shifting rapidly. The movement of species from one ecosystem to another in these disrupted ecological zones can result in an overrun by a new invader.
In North America, we think of this most frequently with plants such as kudzu and dandelions, but many animals were also introduced. The most dangerous of these are the ubiquitous Rattus norvegicus (the urban gray rat) and Mus musculus (the domestic house mouse), which were introduced into the Americas from the Old World, bringing with them plague, rickettsialpox, Seoul virus and lymphocytic choriomeningitis virus. Aedes aegypti, the mosquito vector of dengue and yellow fever, was also introduced into the Americas, carrying those viruses and making possible their spread across the entire Region. More recently, in 1999, West Nile virus was introduced, probably via a stowaway mosquito on an airplane, into New York from the Middle East. Dr. Robert Tesh, at the University of Texas Medical Branch in Galveston, recently isolated the virus from a Houston blue jay, confirming its spread as far west as Texas. Nationwide, the virus has caused 149 human cases, including 18 deaths, and will probably reach Central and South America in the near future.
By far the most common underlying causes of emergence can be found in changes in the ecology of the infectious disease or its hosts. A classic example is Bolivian hemorrhagic fever, which emerged in the 1960s. Machupo virus, which causes this dangerous disease, is carried by rodents, and settlements in new areas of Bolivia's department of Beni led to its emergence as a concentrated human health problem. The cause of the disease was unknown, but it invaded small towns, causing high death rates and often prompting the abandonment of entire settlements. When authorities discovered that the disease was caused by a rodent-borne virus, the animals were eliminated and the towns were safe again. However, rodents continue to live in clearings where isolated houses are built and in fields where crops are planted to sustain nearby towns. The well-fed animals in the fields remain a constant threat to the rural people who work there.
By far the most common underlying causes of emergence can be found in changes in the ecology of the infectious disease or its hosts. A classic example is Bolivian hemorrhagic fever, which emerged in the 1960s. Machupo virus, which causes this dangerous disease, is carried by rodents, and settlements in new areas of Bolivia's department of Beni led to its emergence as a concentrated human health problem. The cause of the disease was unknown, but it invaded small towns, causing high death rates and often prompting the abandonment of entire settlements. When authorities discovered that the disease was caused by a rodent-borne virus, the animals were eliminated and the towns were safe again. However, rodents continue to live in clearings where isolated houses are built and in fields where crops are planted to sustain nearby towns. The well-fed animals in the fields remain a constant threat to the rural people who work there.
The need to provide increasing amounts of food and water for the world's burgeoning population also contributes to the emergence of new diseases. Intensive agricultural methods often mean that a single, genetically homogeneous species is raised in a limited area, creating a perfect target for emerging diseases, which proliferate happily among a large number of like animals in close proximity. The growing impoundment of water and expanding irrigation are important elements in the emergence of mosquito-borne diseases, and the lack of potable water for consumption and washing in poorer populations leads to increasing transmission of intestinal diseases such as cholera and typhoid. The problem is not only that these ecological changes are occurring, but that they are occurring at an accelerated rate. Indeed, the rate of increase is itself increasing. In this sense, it is very possible that we are hurrying toward an appointment with disaster.
Drug resistance Up to now, we have successfully battled many of the classic bacterial infectious diseases through the use of antibiotics such as penicillin to treat them. Yet many pathogens are now coming back to haunt us. Plague, pneumococcal meningitis and pneumonia, tuberculosis and typhoid are only a few of the once-subjugated bacteria now reemerging as significant pathogens that we can no longer successfully deal with. Future generations may be impressed with our discoveries of powerful drugs to fight lethal bacteria, but they are likely to be less impressed with the way we squandered these drugs life-saving qualities by using them in ways that predictably lead to resistance.
The problem is clear in evolutionary terms: using antibacterial drugs selectively and with proper controls minimizes the emergence of resistant organisms. But their widespread use for trivial infections or against viruses that are not inhibited by the drugs destroys the sensitive bacteria in hosts and assures that the next infections will be with bacteria that have evolved ways to escape the drugs' action. Some very important infections fall into this category, among them typhoid fever. Thanks in large part to the widespread use of inexpensive antibiotics for uncertain indications, the typhoid bacterium has developed resistance to all three drugs that have been used successfully to treat the disease in the past. Typhoid is also rapidly developing resistance to a newer, expensive class of drugs that is currently the last bastion of defense. In poorer countries, the effect on people who lack access to clean water will be devastating; but the impact will also flow over to the more affluent in our global society who travel or otherwise come in contact with carriers of resistant typhoid bacteria. A similar situation is evolving with tuberculosis and many other bacteria.
Meanwhile, the pharmaceutical industry faces declining profits from the production of antimicrobials, and both science and industry are lagging in the development of new drugs to replace those that have been lost. We can save the remaining ones only by improving doctors prescribing practices and patients attitudes, by controlling over-the-counter sales and by eliminating the most important drugs from use in livestock production.
If the antibacterial drug situation is bleak, antiparasitic drugs present an even more distressing problem. Profit margins for critical compounds used to treat parasitic diseases in tropical countries are even lower than for antibacterial drugs. Malaria--which kills 1 million people annually--economically justifies a small continuing effort by the pharmaceutical industry, but lesser killers, such as trypanosomiasis and schistosomiasis, do not provide sufficient incentive.
As for antivirals, few drugs are available other than for HIV because market forces are too weak to spur development and production. This is also true for new pesticides that could curb disease vectors in the world's poorest countries.
As the world's population continues to grow, as people continue to alter earth's ecological systems, and as globalization spurs increasing travel and transport, the problem of emerging diseases is likely to become more acute. So far, most recently emerging diseases do not pass readily from human to human. But infectious diseases of the future are a big unknown, and pathogens--emerging or reemerging--are likely to bring new surprises. The specter of the return of smallpox through a deliberate act of bioterrorism is a particularly sobering example raised by the Sept. 11, 2001, attacks and their aftermath.
How can we prepare for diseases of the future?
First, we must jump-start the process of developing new anti-infective drugs, vaccines and pesticides. If development is not economically feasible for the private sector, we must involve the public sector in their development. This does not represent a socialization of private enterprise, but rather a recognition that there is insufficient motivation for the private sector and that there is a pressing need to accomplish a common good. Second, we must employ new science more effectively. The huge advances in molecular and structural biology and genomic science have given us tools that have already enlarged our understanding of emerging diseases and the recurring problems of the tropics. Yet we have seen few direct benefits for drug development or vaccines. These will be available only when we address a complex nexus of social, economic and regulatory barriers.
Third, we must devise new strategies to fight and prevent the spread of infectious diseases. We have already seen impressive results from some simple but innovative approaches targeted at critical weaknesses in the propagation of infectious diseases. For example, in tuberculosis treatment, the use of directly observed therapy (DOTS) has been highly effective in increasing cures and limiting the emergence of further antibacterial drug resistance. Insecticide-treated bed nets represent a radical change in the traditional approach to malaria amelioration. While questions remain about sustainability and the development of resistance to insecticides, this approach exemplifies the kind of solutions we need to develop and implement.
We must also find ways of strength- ening public health infrastructure, which is critical to surveillance what s happening with old diseases as well as new ones and to prevention and con-trol. While public health is invisible to most of us, and so gets little attention and inadequate funding, it is critically important to keeping us safe from infectious diseases, including the threat of bioterrorism. Public health infra-structure is weak in almost all countries but is particularly at risk in the devel-oping world. We must find new ways to augment our greatest protection against infectious disease worldwide and particularly in those countries with greatest need.
Other factors loom even larger and will be even more difficult to address. The earth's growing population continually challenges our ability to deal effectively with emerging infectious diseases. Land use, water availability and likely even climate change are driven by population expansion. Moreover, the increasing use of resources leaves us with fewer alternatives to address problems when they inevitably arise. At the least, we must make intelligent choices so that we have the least possible impact on our natural environment.
What to do, in fact, may be less of an unknown than how to accomplish it. The work of physicians, public health officials, government agencies and the private sector must be coordinated. Both professionals and the public must be better educated to attack these difficult problems. Only a coordinated effort sufficiently funded by governments, foundations, scientific establishments and international organizations will allow us to keep infectious diseases of the future in check.
