Global Microbial Threats in the 1990s
Emerging Infectious Diseases
Thirty years ago, the threat of infectious diseases appeared to be receding. Modern scientific advances, including antibiotic drugs,vaccines against childhood diseases, and improved technology forsanitation, had facilitated the control or prevention of manyinfectious diseases, particularly in industrialized nations. Theincidence of childhood diseases such as polio, whooping cough,and diphtheria was declining due to the use of vaccines. Inaddition, American physicians had fast-acting, effectiveantibiotics to combat often fatal bacterial diseases such asmeningitis and pneumonia. Deaths from infection, commonplace atthe beginning of the twentieth century, were no longer a frequentoccurrence in the United States. Meanwhile, in other parts of theworld, chemical pesticides like DDT were lowering the incidenceof malaria, a major killer of children, by controllingpopulations of parasite-carrying mosquitoes.
As it turned out, our understandable euphoria was premature. Itdid not take into account the extraordinary resilience ofinfectious microbes, which have a remarkable ability to evolve,adapt, and develop resistance to drugs in an unpredictable anddynamic fashion. It also did not take into account theaccelerating spread of human populations into tropical forestsand overcrowded mega-cities where people are exposed to a varietyof emerging infectious agents.
Today, most health professionals agree that new microbial threatsare appearing in significant numbers, while well-known illnessesthought to be under control are re-emerging. Most Americans areaware of the epidemic of the acquired immunodeficiency syndrome(AIDS) and the related increase in tuberculosis (TB) cases in theUnited States. In fact, there has been a general resurgence ofinfectious diseases throughout the world, including significantoutbreaks of cholera, malaria, yellow fever, and diphtheria. Inaddition, bacterial resistance to antibiotic drugs is anincreasingly serious worldwide problem. Furthermore, the numberof people infected with the human immunodeficiency virus (HIV)that causes AIDS is increasing in many countries and may reach 40million by the year 2000. Most recently, Ebola virus, whichcauses an often fatal hemorrhagic illness, has appeared again inAfrica, and a formerly unknown virus of the measles family thatkilled several horses in Australia also infected two men, one ofwhom died.
New diseases have also appeared within the United States,including Lyme disease, Legionnaires' disease, and most recentlyhantavirus pulmonary syndrome (HPS). HPS was first recognized inthe southwestern United States in 1993 and has since beendetected in more than 20 states and in several other countries inthe Americas. Other new or re-emerging threats in the UnitedStates include multidrug-resistant TB; antibiotic-resistantbacteria causing ear infections; pneumonia; meningitis; rabies;and diarrheal diseases caused by the parasite Cryptosporidiumparvum and by certain toxigenic strains of Escherichia colibacteria.
Why are new infectious diseases emerging?
The reasons for the sharp increase in incidence of manyinfectious diseases - once thought to be under control - arecomplex and not fully understood. Population shifts andpopulation growth; changes in human behavior; urbanization,poverty, and crowding; changes in ecology and climate; theevolution of microbes; inadequacy of public healthinfrastructures; and modern travel and trade have allcontributed. For example, the ease of modern travel creates manyopportunities for a disease outbreak in remote areas to spread toa crowded urban area. Human behavioral factors, such as dietaryhabits and food handling, personal hygiene, risky sexualbehavior, and intravenous drug use can contribute to diseaseemergence. In several parts of the world, human encroachment ontropical forests has brought populations with little or nodisease resistance into close proximity with insects that carrymalaria and yellow fever and other, sometimes unknown, infectiousdiseases. In addition, local fluctuations in temperature andrainfall affect the number of microbe-carrying rodents in someareas. Finally, in many parts of the world there has been adeterioration in the local public health infrastructures thatmonitor and respond to disease outbreaks.
Are infectious disease surveillance and control cost-effective?
The costs of infectious diseases at home and abroad arestaggering, and the cost-effectiveness of disease prevention hasbeen demonstrated again and again. Every year, billions ofdollars are lost in the United States in direct medical costs andlost productivity, due to intestinal infections, sexuallytransmitted diseases, influenza, and other viral, bacterial, orparasitic diseases. When diseases are controlled or prevented,tremendous savings can be achieved. For instance, a timelyepidemiologic investigation in Washington State in 1993 led tothe prompt recall of 250,000 hamburgers contaminated with E. coliO157, saving millions of dollars as well as preventing humansuffering and death. Since smallpox was eradicated in 1977, thetotal investment of $32 million has been returned to the UnitedStates every 26 days. Based on the current rate of progresstowards eradication of poliomyelitis, the World HealthOrganization predicts "global savings of half a billion dollarsby the year 2000, increasing to $3 billion annually by the year2015." Furthermore, every dollar spent on the vaccine againstmeasles, mumps, and rubella, saves $21, while every dollar spenton the vaccine against diphtheria, tetanus, and pertussis saves$29. Clearly, public health measures that prevent or controlinfectious diseases are extremely cost-effective.
Today, two of the largest U.S. infectious disease health-careexpenses are for the treatment of TB and AIDS. When the firstcases of AIDS and drug-resistant TB were detected in the UnitedStates control measures were delayed, partly due to a lack ofsurveillance information. TB is an ancient disease, knownthroughout human history, that re-emerged in the United States inthe late 1980s, sometimes in a drug-resistant ormultidrug-resistant form. Government spending on infectiousdisease control had declined during the 1980s, and in 1986 thesurveillance system for drug-resistant TB was discontinued. By1993, multidrug-resistant TB had became a public health crisisand millions of federal dollars were necessary to control theemergency.
Unlike TB, AIDS is a newly emergent disease, unrecognized beforethe 1980s. AIDS might have been identified before it becameestablished in the United States if a global surveillance systemwith the capacity to identify new diseases had been in place inthe 1970s. As early as 1962, African doctors apparently witnessedcases of what was then known as "slim disease." Had theinternational community taken notice, epidemiologists might havegained a head start in learning how AIDS is transmitted andprevented, and many lives might have been saved.
Disease prevention is an investment in the young people of theworld and in our collective future. Every year, an estimated fourmillion infant and child deaths are prevented by vaccination andother preventive health measures, due to multilateral efforts. Atthe same time, many countries have dramatically strengthenedtheir health-care delivery systems, even in the face of economicstagnation. On the other hand, the AIDS pandemic and theresurgence of malaria and TB are impeding economic development inmany of the world's poorest countries.
Need for U.S. leadership
The modern world is a very small place; any city in the world isonly a plane ride away from any other. Infectious microbes caneasily travel across borders with their human or animal hosts. Infact, diseases that arise in other parts of the world arerepeatedly introduced into the United States, where they maythreaten our national health and security. Thus, controllingdisease outbreaks in other countries is important not only forhumanitarian reasons. It also prevents those diseases fromentering the United States, at great savings of U.S. lives anddollars. Moreover, U.S. support for disease investigations inother countries provides U.S. scientists with opportunities tobring U.S. capacity to focus on new pathogens like Ebola virusand consider how best to control, prevent, and treat theminternationally before they arrive on our shores. Thus, U.S.interests are served while providing support to other nations.
Actively promoting the effort to develop an internationalpartnership to address emerging infectious diseases is a naturalrole for the United States. American business leaders andscientists are in the forefront of the computer communicationsand biomedical research communities that must provide thetechnical and scientific underpinning for disease surveillance.The United States maintains more medical facilities and personnelabroad than any other country, in terms of both civilian andmilitary, and public and private sector institutions.Furthermore, American scientists and public health professionalshave been among the most important contributors to theinternational efforts to eradicate smallpox and polio. Thisposition of leadership should be fostered.
Our earlier successes in controlling infections have bredcomplacency. Consequently, the component of the public healthsystem that protects the public from infectious microbes has beenneglected, both here and abroad, and its focus has narrowed. Inthe United States, federal, state, and local efforts to controlcommunicable diseases are concentrated on a few targetedillnesses, with few resources allocated to address new orre-emerging diseases. This limits the ability of the U.S. medicalcommunity to detect and respond to outbreaks of newly emergingdiseases, whether here or in foreign countries.
International coordination of infectious disease preventionefforts
The challenge ahead outstrips the means available to any onecountry or to international organizations. The elimination ofsmallpox would not have been possible without a truly globaleffort. Similarly, multilateral leadership and resources propelthe international program to eradicate polio. Both examplesdemonstrate the value to American citizens of resources investedin global disease prevention.
In addition, an effective global disease surveillance andresponse network will enable the United States to respond quicklyand effectively in the event of terrorist incidents involvingbiological or chemical agents. The experience gained incontrolling naturally occurring microbes will enhance our abilityto cope with a biological warfare agent, should the need arise.The release of nerve gas in the Tokyo subway system in March 1995has underscored our need to be well prepared to counteractdeliberate attempts to undermine human health.
To address the growing threat of emerging infectious diseases theU.S. Government must not only improve its public healthinfrastructure, but also work in concert with other nations andinternational bodies, particularly WHO. The work and cost ofprotecting the world's people from infectious diseases must beshared by all nations. Some industrialized countries have alreadydecided to devote substantial resources to a surveillance effort,and some less developed nations may also be ready to engage in aninternational effort that is so clearly in their own interests.President Clinton and the other leaders of the G7 nationsrecently endorsed 11 pilot projects of the Global InformationInfrastructure at the Halifax Summit, including a projectentitled, "Toward a Global Health Network." This project isdesigned to help public health institutions in their fightagainst infectious diseases and major health hazards. Inaddition, the World Health Assembly recently passed a resolutionthat focuses on national capacity building related to detectingand controlling emerging infectious diseases. The U.S. Agency forInternational Development (USAID), other donors, and the WHO, arecontinuing to assist developing countries in establishing diseaseprevention and control programs and to encourage the developmentof disease reporting systems.
Although international efforts must be coordinated to preventglobal pandemics, disease surveillance is first of all theresponsibility of each sovereign nation. However, individualgovernments may not only lack the means to respond but may alsobe reluctant to share national disease surveillance information,fearing losses in trade, tourism, and national prestige.Nevertheless, because the United States is widely respected asthe world's foremost authority on infectious disease recognitionand control, we do learn about most major disease outbreaks inother countries, although not always in an official or timelyfashion. Individual doctors, laboratories, or ministries ofhealth often seek United States assistance when they areconfronted with a disease problem that they cannot solve. Toensure that we continue to be notified when an unusual outbreakoccurs, we must encourage and support other countries' efforts innational disease surveillance and respond when asked forassistance. We must strive to develop a sense of sharedresponsibility and mutual confidence in the global effort tocombat infectious diseases.
The effort to build a global surveillance and response systemsupports other foreign policy goals of the United States.Obviously, such a system will help protect the health of Americancitizens and of people throughout the world. In the post-Cold Warperiod, a major objective of U.S. foreign policy is the promotionof political stability through sustainable economic developmentaround the globe. Helping other countries to help themselves _ toimprove the lives of their citizens, develop their economies, andfind niches in the global economy _ is a major goal for U.S.foreign assistance. Healthy people are more productive and betterable to contribute to their country's welfare.
Building a global infectious diseases network
At the present time, a formal system for infectious diseasesurveillance does not exist on a global scale. When a cluster ofcases of a new disease occurs in a remote part of Africa, EasternEurope, Asia, or the Americas, the international community may ormay not learn about it. If a new disease of unknown cause occursin a part of the world that lacks modern communications, it mayspread far and wide before it is recognized and brought undercontrol. In most cases, however, news of a major outbreak spreadsinformally. When international resources are successfullymobilized, assistance in diagnosis, disease control andprevention can be made available to local health authorities.Clinical specimens can be sent to a diagnostic "reference"laboratory to rule out known disease agents. Epidemiologists canbe sent into the field to help investigate the source of the newinfection and determine how it is transmitted. Public healthofficials can use this information to implement appropriatecontrol measures. Once the infectious agent has been identified,which is often a difficult task, experimental scientists canstart to develop diagnostic tools and treatments if the diseaseis carried by a previously unknown agent.
The elements of a global network for disease surveillance alreadyexist but need to be strengthened, linked, and coordinated. Forinstance, many U.S. Government departments and agencies maintainor support field stations and laboratories in Africa, Asia, andthe Americas that may be electronically linked to provide aninitial framework for a network for global infectious diseasereporting. In partnership with other countries and with WHO, thisskeletal surveillance network could be expanded over time toinclude many international resources, including national healthministries, WHO Collaborating Centers, hospitals, andlaboratories operated by other nations, and American and foreignprivate voluntary organizations.
Information technology is revolutionizing communicationsworldwide; this technology needs to be applied to disease controlprograms, not only to effectively monitor program performance andprogress, but also to detect and report emerging problems.
The process of response encompasses a multitude of activities,including diagnosis of the disease; investigation to understandits source and modes of transmission; implementation of controlstrategies and programs; research to develop adequate means totreat it and prevent its spread; and production and disseminationof the necessary drugs and vaccines.
The international community does not always have adequateresources to respond to localized disease outbreaks and controlthem before they can spread across borders. If an "old" diseasere-emerges, there may be a need for epidemiologic investigationsand/or for emergency procurement or production of medicalsupplies. If the disease is new, efforts will be needed toidentify the causative microbe and determine how to stop itstransmission. To make the best possible use of U.S. expertise andresources, it is necessary to establish clear lines of authorityand communication among U.S. Government agencies.
Response to infectious disease outbreaks, whenever and whereverthey occur requires international preparation and planning. Agoal of the WHO is to assist each country to develop its abilityto provide laboratory diagnosis of diseases endemic to its areaand to refer specimens from suspected newly emergent orre-emergent diseases to an appropriate regional referencelaboratory. To reach this goal, each country must train medicalworkers and laboratory technicians and supply them withappropriate equipment and diagnostic resources.
In addition, several international elements must be in place toprovide the wherewithal for effective and timely disease controland prevention efforts. First, regional reference laboratoriesmust be maintained to provide diagnostic expertise and distributediagnostic tests. Second, an international communicationsmechanism must be made available to receive and analyze globaldisease surveillance information. Third, regional proceduresshould be instituted to facilitate the production, procurement,and distribution of medical supplies, including vaccines fordisease eradication programs. Fourth, enhanced public educationin simple health measures in both industrialized and developingcountries is very important.
Through programs administered by USAID and other agencies, theUnited States has invested in assisting developing countries toestablish disease prevention and control programs, trainedthousands of individuals, and strengthened scores ofinstitutions. As a consequence, developing country researchersare better prepared to solve their own disease problems andcontribute to solving global ones. Strengthening this foundationwill be critical to facilitating timely and effective responsesto disease outbreaks and minimizing the impact of emergingdisease threats.
An effective system for disease surveillance and control iscritically dependent on a strong and stable researchinfrastructure. Scientific studies of infectious agents and thediseases they cause provide the fundamental knowledge base usedto develop diagnostic tests to identify diseases, drugs to treatthem, and vaccines to prevent them. Traditionally, this has beenan area of U.S. strength and international leadership. To meetthe new challenges represented by emerging diseases, a strongresearch and training effort must be sustained and strengthened.The current level of support for research and training inlaboratory and field work on infectious diseases, other than AIDSand TB, is very limited. To combat new diseases for which notreatments are available, it is essential to maintain an activecommunity of well-trained epidemiologists, laboratory scientists,clinical investigators, behavioral scientists, entomologists, andpublic health experts ready and able to seek new solutions fordisease threats. At the present time, many of the brightest youngmicrobiologists in the United States are leaving the field,discouraged by the lack of jobs and research funds.
USAID, National Institutes of Health (NIH), and Centers forDisease Control and Prevention (CDC) support has fostered thecapacity of less developed countries to identify and solve theirinfectious disease problems. Applied research in these countriesis aimed at preventing disease transmission through control ofinsect and animal vectors, environmental factors, and behavior,and at evaluating new or improved therapeutic and preventivemeasures. In addition, the National Oceanic and AtmosphericAdministration is developing tools to predict local changes inweather that effect the incidence of vector-borne diseases.
Many research programs routinely incorporate trainingopportunities for graduate students and postdoctoral fellows. Inaddition, there is an urgent need to augment specialized trainingprograms in such areas as the handling of hazardous microbes,public health management, and field epidemiology.
Summary of Recommendations of the CISET Working Group
An interagency Government working group on emerging infectiousdiseases was formed in December 1994 under the auspices of theNational Science and Technology Council's Committee onInternational Science, Engineering, and Technology (CISET). Ledby CDC, the Department of State, USAID, Food and DrugAdministration, NIH, and the Department of Defense, the workinggroup makes the following recommendations for action by the U.S.Government.
Work in partnership with other countries, with WHO, and withother international organizations to improve worldwide diseasesurveillance, reporting, and response by
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