Summary and Assessment

Joshua Lederberg, Ph.D.

Nobel Laureate and Sackler Foundation Scholar, The Rockefeller University

In October 1999, the Forum on Emerging Infections of the Institute of Medicine convened a 2-day workshop titled “International Aspects of Emerging Infections.” Key representatives from the international community explored the forces that drive emerging infectious diseases to prominence. Representatives from the Americas, Africa, Asia and the Pacific, and Europe made formal presentations and engaged in panel discussions. Summaries of the formal presentations can be found in Chapter 1, Chapter 2, Chapter 3, Chapter 4 through Chapter 5 of this report. The topics addressed during this conference cover a wide range of issues, including trends in the incidence of infectious diseases around the world, descriptions of the wide variety of factors that contribute to the emergence and reemergence of these diseases, efforts to coordinate surveillance activities and responses within and across borders, and the resource, research, and international needs that remain to be addressed. This section of the report summarizes the issues raised during the 2-day meeting and suggests an agenda for future action.

EMERGING INFECTIONS: THE GLOBAL PICTURE

In his keynote address, David Heymann, Executive Director of Communicable Diseases for the World Health Organization (WHO), described the global proportions of infectious diseases. Infectious diseases are undergoing a global resurgence and threaten the health of everyone. They remain the world's greatest killer of children and young adults, accounting for more than 13 million deaths a



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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections Summary and Assessment Joshua Lederberg, Ph.D. Nobel Laureate and Sackler Foundation Scholar, The Rockefeller University In October 1999, the Forum on Emerging Infections of the Institute of Medicine convened a 2-day workshop titled “International Aspects of Emerging Infections.” Key representatives from the international community explored the forces that drive emerging infectious diseases to prominence. Representatives from the Americas, Africa, Asia and the Pacific, and Europe made formal presentations and engaged in panel discussions. Summaries of the formal presentations can be found in Chapter 1, Chapter 2, Chapter 3, Chapter 4 through Chapter 5 of this report. The topics addressed during this conference cover a wide range of issues, including trends in the incidence of infectious diseases around the world, descriptions of the wide variety of factors that contribute to the emergence and reemergence of these diseases, efforts to coordinate surveillance activities and responses within and across borders, and the resource, research, and international needs that remain to be addressed. This section of the report summarizes the issues raised during the 2-day meeting and suggests an agenda for future action. EMERGING INFECTIONS: THE GLOBAL PICTURE In his keynote address, David Heymann, Executive Director of Communicable Diseases for the World Health Organization (WHO), described the global proportions of infectious diseases. Infectious diseases are undergoing a global resurgence and threaten the health of everyone. They remain the world's greatest killer of children and young adults, accounting for more than 13 million deaths a

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections FIGURE 1 Leading infectious killers; millions of deaths worldwide, all ages, 1998. *HIV-positive people who died with TB have been included among AIDS deaths. SOURCE: WHO, 1999. year and half of all deaths in developing countries, with six diseases causing 90 percent of deaths from infectious diseases: pneumonia, tuberculosis (TB), diarrheal diseases, malaria, measles, and human immunodeficiency virus infection (HIV)/AIDS (Figure 1). Even though most deaths from infectious diseases occur in developing countries, no region of the world is free from concern. In 1996 and 1997 alone, every continent experienced a large outbreak of some type of infectious disease, from Lyme disease in North America to Ross River virus in Australia (Figure 2). Therefore, it is in the best interest of all countries to support global initiatives to control infectious diseases. In addition, the growing rise and spread of antimicrobial resistance is of increasing concern in developed countries as the inappropriate use of antibiotics goes unchecked. Moreover, increasing numbers of international travelers provide a vehicle for the rapid spread of microbes resistant to antimicrobial agents. For example, in 1995 two different clones of multidrug-resistant Streptococcus pneumoniae were first identified in Spain, and within 2 months the strains had

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections been found in Croatia, France, Mexico, Portugal, Korea, South Africa, and the United States (Figure 3). The reemergence of infectious diseases once thought to be under control or eliminated is also a growing concern. For example, dengue fever is a disease of humans in tropical and subtropical regions caused by the dengue virus, which is transmitted from human to human by the bite of an infected Aedes mosquito. In the past decade, countries in the Americas, Southeast Asia, and Western Pacific have witnessed a resurgence of dengue fever and its most serious manifestation, dengue hemorrhagic fever (Figure 4). Yet, the rise of dengue is not the only concern of the global population public health community. In 1996, outbreaks of polio in Albania, Greece, and Yugoslavia, and more recently in Haiti and the Dominican Republic, demonstrated that when immunization practices and disease surveillance are neglected, diseases can easily be reintroduced into countries once free of a malady. Financial Costs of Infectious Diseases Beyond the human suffering, the financial costs of infectious diseases are great, especially for developing countries (Table 1). The economic burden of malaria alone has cost Africa billions of dollars over the past decade. When infectious diseases are not controlled, they take a tremendous toll on the econo port of goods. Although they are not always high on the list of causes of mortality, infectious diseases may be high on the list of causes of economic morbidity: In 1994, the panic over plague in India cost the country an estimated $1.8 billion in lost tourist income and trade. FIGURE 2 Emerging/reemerging infectious diseases, 1996 and 1997. SOURCE: WHO/ CDS, 1999.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections TABLE 1 Infectious Diseases and Their Costs to Economies Year(s) Country Disease Cost (millions of US$) 1990 to 1998 United Kingdom Bovine Spongiform Encephalopathy >5,740 1991 Peru Cholera 770 1991 India Plague 1,800 1994 India Tuberculosis >1,000 1997 Tanzania Cholera 36 1997 to 1998 Thailand HIV/AIDS 2,500 SOURCE: Workshop presentation by David Heymann, World Health Organization,1999. In 1996 the European Union banned the worldwide export of British beef in response to fears about bovine spongiform encephalopathy (so-called mad cow disease). In 1998 the European Union erected trade barriers because of a cholera outbreak in East Africa, where the disease is endemic. FIGURE 3 Streptococcus pneumoniae: probable spread of two multi-resistant clones in a two-month period. First clone in Spain, subsequently in Croatia, France, Mexico, Portugal, Republic of Korea, South Africa, and the United States. Different clone, first seen in Spain, and subsequently in Iceland. SOURCE: WHO Report WHO/CDS/ BVI/95.7.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections Figure 4 Resurgence of dengue fever and dengue hemorrhagic fever; number of cases. SOURCE: WHO/CDS, 1999.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections Additionally, the economic and societal costs of controlling infectious diseases are directly proportional to the response time to control the disease. For example, the emergence of HIV/AIDS has prompted a global resurgence of tuberculosis (TB), especially multidrug-resistant TB (MDR-TB). Treatment costs for TB can vary between $15 and $40 per person to achieve a complete cure, whereas treatment costs for MDR-TB are $3,000 per person. Considering that total spending for health care in some of the poorest countries in the world is less than $7 per person per year, the increased costs associated with a delayed response to disease control are beyond the reach of the poorest countries. Not only does treatment become impossible as economic and societal costs increase, but infectious disease control is often neglected, as are disease prevention efforts. Infectious Diseases and Human Rights In some countries the issues of the spread and control of infectious diseases are interwoven with concerns about human rights. In some Asian countries large populations migrate to neighboring countries. However, if an immigrant contracts HIV or even viral hepatitis, the person is frequently sent back to the country of origin, a place from which he or she might have fled. Thus, some are hesitant to seek medical care and often go “underground,” spreading the disease even further. The Hong Kong Special Administration Region counters this possibility by ensuring that individuals who are positive for HIV are offered a full range of services, with the assurance that they will not be deported or detained if they seek medical care. Infectious diseases among incarcerated individuals are also on the rise worldwide. In Russia, 42 percent of all TB cases are detected in the prison population. Every year the system incarcerates 300,000 otherwise healthy Russians and releases another 300,000, most of whom will have been exposed to TB during their incarcerations. Among these individuals, approximately 10 percent develop active disease and 80 percent carry the TB bacterium in a latent state. Approximately 40 percent of those patients are exposed to MDR strains. Among the amplifiers of drug resistance is the delay of implementation of directly observed treatment (short course) and poor health care services in Russian prisons. Tragically, the MDR-TB crisis is almost at the point at which the disease may never be controlled there unless second line drugs are introduced into the prison system (see Chapter 5). Thus, efforts to control the spread of infectious diseases often encounter national and regional issues to which the international community is sometimes hesitant or unable to respond. Better surveillance for diseases in refugee and prison populations is needed to detect infectious agents, institute therapy or control strategies, and prevent or mitigate the impact and further spread of contagion.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections FACTORS IN EMERGENCE OF INFECTIOUS DISEASES Specific factors are responsible for the emergence of infectious diseases. With proper epidemiological investigations and laboratory surveillance, the determinants of disease outbreaks can be identified, as most emerging infections (even those resistant to antimicrobial agents) usually originate in one location and then disseminate to new areas. Complacency about vaccination and antibiotic use, however, and the lack of investment in surveillance and control programs have exacerbated the spread of many diseases. Climate variability and natural disasters also play a role in the emergence of many infectious diseases. For example, the traditional meningitis A belt was limited to Saharan Africa. Recently, however, there have been epidemics occurring farther south, in Uganda, Kenya, and Tanzania, and these are likely related to droughts in those areas. In some countries, devastating earthquakes and floods have contributed to outbreaks of cholera, malaria, TB, and diarrheal diseases. In the past 20 years a number of global activities have resulted in an increase in the level of spread of infectious microbes and have promoted the emergence of diseases and epidemics (Table 2). Many of these factors lie outside the purview of the health sector, making it difficult to mitigate their impact on the transmission of infectious diseases and requiring coordinated approaches among various sectors of society for successful control. For example, economic and environmental policies can have direct and negative effects on the emergence and spread of infectious diseases. Deforestation and changes in land and water use can also affect disease patterns, triggering outbreaks of parasitic or other infectious diseases. TABLE 2 Factors in Infectious Disease Emergence and Reemergence Increased human intrusion into tropical forests Lack of access to health care Population growth and changes in demographics Changes in human behaviors Inadequate and deteriorating public health infrastructure Misuse of antibiotics and other antimicrobial drugs Microbial adaptation Urbanization and crowding Modern travel Increased trade and expanded markets for imported foods SOURCE: IOM, 1992.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections Global Trade and Travel Global trade has increased 1,000 percent since World War II. Sixty percent of global trade occurs in the Asia-Pacific region alone, resulting in an incredible movement of merchandise and people. Moreover, 20 percent of global agricultural trade occurs in Asia, which is the major destination market for U.S. trade goods, with the rate of agricultural product sales increasing 7 percent each year. As a large fraction of the economies of most developed nations are invested in trade, the level of exchange of goods will continue to increase. One of the drawbacks to this movement of goods is that antimicrobial agents and other drug classes used to treat products may result in alterations in the ways in which people react to infections. Therefore, trade can introduce new pathogens or their vectors into a region through the shipping of contaminated products. In addition, increased world trade—combined with greater world travel—is precipitating some infectious disease events. Mitigation of these events requires greater investment in the public health infrastructure, disease investigation, sanitary infrastructure, strengthening of health ministries and other health agencies within governments, and coordinated action among the various sectors of society that deal with these issues. Global travel also affects the transmission of infectious diseases. Nearly 1.5 billion travelers board airplanes every year, and the proportion of international arrivals among continents is increasing (Figure 5). The resulting effects include the importation of infectious diseases and infectious disease agents; for example, importation of influenza, pneumonic plague, TB, malaria, and even poliovirus by air travelers has been reported. In 1996, sporadic cases of yellow fever were diagnosed among travelers returning to the United States and Switzerland. Beyond tourism, as mentioned previously, migration also contributes to the spread of disease, which can be exacerbated when immigrants and refugees live in overcrowded and unsanitary conditions. Seasonality and Climate Variation The rise and fall in the rates of infectious diseases, particularly influenza, have long been associated with changes of seasons. In the tropical areas of the world there is a greater occurrence of influenza during the rainy season, and some believe that closer human contact during the rainy season in the tropics, when people tend to congregate indoors, might be responsible for more cases of influenza. This is in contrast to the epidemic situation in temperate regions, where there is a winter seasonality for influenza. In the winter, cooler, drier air favors the survival of influenza viruses, and just as in the tropics during the rainy season, people tend to congregate inside. Other diseases show seasonal trends as well. Outbreaks of Venezuelan equine encephalitis in Colombia are associated with the rainy season. Respiratory syncytial virus (RSV) causes disease in the Northern Hemisphere in the

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections FIGURE 5 Frequent flyers: the most popular routes between continents, 1997. Percentage increase in international arrivals, 1993–1997. SOURCE: World Tourism Organization and Civil Aviation Organization.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections winter and in the tropics during the rainy season. In England, for example, RSV is as important as influenza virus in causing morbidity and excess mortality among elderly people (Fleming and Cross, 1993). The use of climate information for public health purposes deserves additional attention. Incorporation of climate and environmental variables into predictors of disease outbreaks could be an important tool for infectious disease prevention and control. For example, climate data have been used in retrospective analyses and modeling of Rift Valley fever outbreaks in East Africa. Refinement of such models could contribute to the planning for animal immunization programs. Knowledge and understanding of seasonal climate and meteorological conditions in West Africa have also been important for the elimination of onchocerciasis from that region. Historically, modeling has been used to predict malaria transmission on the basis of climate data, but the challenge to using these models is obtaining and validating quality data on the ground. Zoonoses In both developing and developed countries a number of new zoonoses (diseases transmitted from animals to humans) have emerged. These have been caused by either newly discovered pathogens or agents that are already known, often appearing in animal species in which the disease had not previously been detected. Zoonotic disease agents have also reemerged in some areas after being absent for many years, sometimes decades. Examples of emerging and reemerging zoonotic disease agents include equine morbillivirus, Japanese encephalitis virus, and Australian bat lyssavirus in Australia, equine encephalitis virus in Colombia and Venezuela, enterohemorrhagic Escherichia coli in Japan, the bovine spongiform encephalopathy agent in the United Kingdom, and dengue virus in South America. A dramatic example of a recent zoonotic disease outbreak was the occurrence of H5N1 influenza A virus—the so-called avian or bird flu—in Hong Kong in 1997 (Figure 6), which resulted in the slaughter of millions of chickens. Hong Kong is particularly vulnerable to infectious diseases because it is densely populated (6.68 million population in 1998), is in the crossroads between the East and the West, encounters a heavy volume of international travel, and has live poultry markets in close proximity to residential areas, which facilitate the spread of the virus from infected chickens to humans (see Chapters 4). Intense media attention to the outbreak highlighted the power of telecommunications to transmit images and mobilize and accelerate the response to an outbreak. The juxtaposition of human and animal populations increases the likelihood of such outbreaks. Another example is Argentine hemorrhagic fever (AHF), which has been a major public health concern since 1955. The Argentine government is effectively using the AHF vaccine to reduce the incidence of disease. The incidence of AHF, however, has gradually increased among adult agricul-

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections tural workers in rural areas, indicating an occupational exposure to the virus, and the focal incidence of AHF correlates well with the distribution of rodent infestation. The affected area in Argentina has gradually been extending and now covers approximately 150,000 square kilometers (58,000 square miles) including densely populated areas in parts of Argentina where the population at risk is approximately 5 million (see Chapter 2). Of the novel zoonotic diseases, Hendra virus was first recognized as an outbreak of an unknown illness among horses in Brisbane, Australia. The virus was shown to occur naturally in fruit bats and to be widely distributed in northern and eastern Australia, as well as in Papua New Guinea. Hendra virus has been classified as the first member of a new genus in the family Paramyxoviridae. Studies of Hendra virus led to the discovery of Australian bat lyssavirus, a rabies-like virus, in both fruit and insectivorous bats. Australian bat lyssavirus is in the same group to which classical rabies belongs, antigenic group 1 of the lyssaviruses, but Australian bat lyssavirus can be differentiated from rabies virus on genetic grounds (see Chapter 4). The emergence of zoonoses is likely to persist owing to increased human-to animal interactions, increased production and manufacture of animal-derived food products, changes in food-processing practices, and encroachment of human populations into feral animal habitats, as well as increased global trade and FIGURE 6 Geographic distribution of H5N1 cases in Hong Kong.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections end of the pandemic. Currently, the effort is to bring the plan into concordance with that of WHO (see Chapter 5). Other efforts have been explicitly transnational. For example, a project developed jointly by the African Regional Office of WHO, the CDC, and the U.S. Agency for International Development (USAID) aims to improve the well-being of the approximately 600 million people currently residing in the 47 member states of the African Regional Office of WHO. The project implements integrated infectious disease surveillance and improved epidemic preparedness and response (see Chapter 3). Correspondingly, in June 1995 the Pan American Health Organization (PAHO) convened a meeting of international experts to discuss strategies for the prevention and control of emerging infectious diseases. As a result of that meeting, a regional plan of action was prepared to develop regional and subregional approaches and to guide member states in addressing specific problems (Figure 9). The regional plan has four goals: (1) strengthening regional surveillance networks for infectious diseases in the Americas; (2) establishing national and regional infrastructures for early warning about and rapid response to infectious disease threats through multidisciplinary training programs and enhancement of laboratory capabilities; (3) promoting the further development of applied research in the areas of diagnosis, epidemiology, prevention, and clinical studies; and (4) strengthening the regional capacity for effective implementation of prevention and control strategies (see Chapter 2). The European Union (EU) has changed the environment for public health issues in Europe by providing funds and the opportunity to share information. FIGURE 8 Suveillance in response to natural disaster. “Operativo Frontero Sur” XII/ 98–III/99: Campeche, Chiapas, Quintana Roo, Tabasco and Veracruz. SOURCE: INDRE.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections Although that part of the world does not face the same types of infectious disease problems found in Asia and Latin America, it has a unique set of infectious disease issues with which it must contend. For example, in Sarajevo, Bosnia-Herzegovina, and other parts of Eastern Europe in 1993–1994, WHO had to establish new communicable disease surveillance because of anxieties about the re-emergence of some diseases, in particular, typhus, diphtheria, and TB (see Chapter 5). The capacity to enhance communicable disease control efforts in Europe was further advanced by the Delphi technique for consensus building. Data information and exchange that provide an earlier warning and detect infectious disease threats that require international coordinated action were identified and evaluated at the national levels. Questionnaires and feedback rounds circulated among a group of experts from individual European countries were among the data collection methods used. The results of the Delphi exercise were submitted to the European Commission (EC) as part of its expert advice to EC members on the development of communicable disease surveillance at the European level. Influenza was ranked among the high-priority diseases requiring international surveillance. DOD is establishing a syndromic surveillance system called the Early Warning Outbreak Recognition System, in Indonesia. Once every 24 hours several sites around the Indonesian archipelago report data on clinical syndromes to a central point in Jakarta, where a DOD laboratory is collocated with the Indonesian Ministry of Health. The system is conducted out of hospitals located around Indonesia, where nurses collect syndromic data from patients. These data are entered into a database into which one can enter not only the signs and symptoms but also the specific working diagnosis. In close to real time the frequencies of various syndromes can be tracked across the Indonesian archipelago. Emerging infections require substantial multisectoral and multinational approaches, as well as sufficient funds. Additional examples of collaborative efforts and the various mechanisms by which they can be achieved are described below. Cooperation Across Borders Nations that share borders are sometimes the most logical place to initiate efforts. For example, the CDC Division of Quarantine is collaborating with Mexico on a pilot sentinel surveillance project along the U.S.-Mexico border for febrile exanthemas and hepatitis. This effort aims to strengthen the sensitivity of infectious disease surveillance through the observation of clinical syndromes and to enhance the public health capacity along the border through surveillance efforts at the provider level. A binational notification process informs the appropriate officials in each country of any reported infections. The protocol calls for rapid local, regional, and national sharing of information about sentinel cases of

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections FIGURE 9 Regional CD surveillance. Countries participating in drug resistance surveillance. SOURCE: PAHO/WHO.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections illness or disease that meet either country's notification requirements. Similarly, Brazil and Argentina are investing in strengthening a network of laboratories. The trend toward globalization of public health is not without its problems. Some countries believe that these efforts undermine their ability to protect the health of their citizens or to retain state sovereignty. Some countries are concerned about the diminishment of their authority within their own territories. This can be especially contentious among bordering countries. Thus, international and national laws, regulations, and practices must be understood and discussed in the context of establishing cooperative efforts. Local needs must be recognized and addressed. Bilateral Agreements In recent years the U.S. and South African governments have discussed the issues of AIDS and TB at key bilateral and multilateral meetings. Similarly, in bilateral meetings with Russia, the United States has raised awareness of TB and promoted the use of directly observed treatment (short course), an inexpensive strategy for the detection and treatment of TB. Emerging infectious diseases have also been discussed under the Asian-Pacific Economic Cooperation (APEC), as well through the U.S.-European Union New Transatlantic Agenda. Discussions surrounding debt relief at trade summits have identified the health care system as a priority for infrastructure development in the poorest countries. Bilateral and multilateral trade agreements signed between Argentina and its neighboring countries (Bolivia, Brazil, Chile, Paraguay, and Uruguay) have included health protection components. Since the 1970s, emphasis has been given to health of the populations within the borders of each country, and internationally agreed upon health care and safety standards (see Chapter 2). International Health Regulations In 1969, the International Health Regulations aimed to ensure maximum security against the international spread of diseases with minimum interference with world trade, tourism, and business. The regulations set out a series of guidelines for monitoring and surveying the normal ports of a vector's entry into countries (airports, seaports) so that agents that might arrive on conveyances do not spread from the port area. The regulations require reporting of a relatively small number of infectious diseases: yellow fever, cholera, and plague. There are disincentives to reporting, which diminish the value of the program. For example, when cholera has been reported, some countries have erected economically damaging trade barriers around the country that reported cholera. Furthermore, reporting does not always result in a response. New regulations are being drafted that will cover more infectious diseases and that will require electronic communication among quarantine officers. Ef-

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections FIGURE 10 Global surveillance of communicable diseases: a network of networks. SOURCE: WHO/CDS. forts are being made to increase the response capabilities of all countries and to decrease the stigma of reporting. Critical aspects of international collaboration are establishing trust and harmonizing epidemiological and laboratory practices. Conflicts can arise around jurisdictions, costs, and international politics. Furthermore, countries have different traditions in terms of accountability and data dissemination that must be acknowledged. In addition, conflicts among international agencies and with nongovernmental organizations (NGOs) will inevitably occur. The potential for disagreement must be recognized and dealt with early in the course of an infectious disease outbreak. NETWORKS OF GLOBAL SURVEILLANCE Current global surveillance comprises a network of networks (Figure 10), as well as electronic discussion sites and the media. Some of these are laboratory networks, others are epidemiology training networks, and still others are reporting networks. Between November 1996 and June 1998, 260 outbreaks were reported through these networks. Once they are validated, reports of the outbreaks are distributed to a limited number of health professionals to improve the level of awareness of reported outbreaks that might have international implications. The new international health regulations may require that some actions be taken against countries that are not reporting. Global Epidemic Intelligence, established by WHO in 1996, was created to improve international preparedness for epidemics by sharing the same information in a timely fashion, thereby countering confusing information that may be

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections disseminated. Confusion can have a major impact on the international prevalence of a disease. Through active collection of information about ongoing outbreaks worldwide, including validation of the sources of information and the rapid verification of the outbreak, WHO is able to share this information with those who need to know. The Internet provides an unprecedented opportunity for information sharing. Efforts are under way to establish networks for the surveillance of emerging infectious diseases in nine countries of the Amazon Region and the Southern Cone Region. A plan of action was developed for each region in collaboration with international reference centers, including CDC, the University of Texas Medical Branch at Galveston, and the U.S. Army Medical Research Institute of Infectious Diseases. The network should be able to perform active surveillance on the basis of a syndromic approach. Five disease syndromes were selected for both regions, and two additional ones were recommended for the Southern Cone Region. The five syndromes are undifferentiated febrile syndrome, hemorrhagic fever, febrile icteric syndrome, acute respiratory distress syndrome, and sudden unexplained death. The WHO Global Influenza Surveillance Program, now 50 years old, was responsible for the early identification of the H5N1 influenza A virus, as well as the H9N2 virus that occurred later. The program has served as a model for many surveillance programs established in subsequent years. It is an action-oriented program. Because WHO must issue recommendations for the composition of influenza vaccines twice a year—once for the Northern Hemisphere in February and once for the Southern Hemisphere in September—data must be gathered throughout the year. The infrastructure in place allows the identification of new variants, whether they are new epidemic variants or new variants with pandemic potential. The infrastructure rests on a number of national influenza centers that serve as the key laboratories for the isolation and identification of influenza viruses, using a kit of reagents produced by CDC and distributed globally. The laboratories also collect epidemiological information for transmittal to WHO headquarters in Geneva. International collaborating centers conduct comparative analyses of influenza viruses from all over the world. Collaboration with industry is essential because the strains that are identified as vaccine candidates are provided free of charge to the pharmaceutical industry for vaccine production. In September 1998, the European Parliament and the Council of Europe agreed to establish a network for the epidemiological surveillance and control of communicable diseases in the community. This effort, which became active in July 1999, builds on an established set of networks for individual diseases such as travel-related Legionnaire 's disease, HIV/AIDS, and TB, networks for drug resistance surveillance and the EntreNet for enteric organisms. National surveillance institutes have collaborated in looking at standards for surveillance. A field epidemiology training program, European Programme for Intervention Epidemiology Training, trains people in the science of epidemiology and estab-

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections lishes communication among public health authorities from different countries. Regular surveillance bulletins in both paper and electronic form have been produced. In addition, inventories of capacity and capabilities across Europe have been generated, including a directory of vaccination policies. Despite these multiple national and international efforts, existing and planned networks focus on known infectious diseases, which means that new agents may go undetected. A future challenge will be to transform established methods and infrastructures to detect and respond to known diseases and novel infectious agents. DNA sequence-based analysis, polymerase chain reaction-based analysis, and multicomponent-array chips will increasingly allow rapid identification of stray nonhuman DNA that is present in internal organs or blood. Deployment of these technologies will require money and awareness. Continuing Need for Local Surveillance Even with extensive intranational and cross-national cooperation, local surveillance remains the most important function in the early warning of and response to infectious diseases. At the local level, disease intelligence functions enhance the ability to assess indicator events. Individuals in charge of surveillance systems at the local level must work closely with their colleagues in the agricultural and veterinary sciences and those who are conducting disease surveillance in related fields. These systems must also adapt to changing patterns of health care, for example, the trend toward patients calling nurses for assistance rather than visiting a general practitioner's office, where surveillance data might be collected. Local efforts need to be integrated so that local, national, and international efforts are not competing or being duplicated. Databases must be interrelated and designed so that they can be linked while protecting confidentiality and privacy. Local efforts also reveal much about behavioral change measures that might be required. For example, revised guidelines for dengue control elevate behavioral change indicators to the same level as entomological or epidemiological indicators, using as a model behavioral surveillance for HIV/AIDS. This requires more bottom-up surveillance programs, modeled after many nutrition and child health programs, in which indicators can be used at the household level; for example, households can determine whether removing domestic containers that may be sources of mosquito breeding is either improving the dengue situation or making the dengue situation worse. This is an important approach, as it paves the way for consumer-based control measures for other diseases, such as the use of insecticide-treated mosquito nets or the use of domestic aerosols for the control of malaria in Africa. NGOs can play a progressive role in this area by being proximate to the problem and, through advocacy, ensure that infectious disease control issues are placed on local, national, and international agendas. NGOs can develop pilot

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections programs, conduct assessments, provide training, and contribute to the wider implementation of surveillance and control efforts. Accordingly, NGOs must have access to affordable and essential drugs and must have sustained financing to support long-term intervention activities and programs. Preservation of Samples The availability of archived biological samples can facilitate understanding of new pathogens and can speed the response to outbreaks. Therefore, more countries must be encouraged to preserve blood and tissue specimens, whether from zoonotic or human events, to make it feasible to search for specific susceptibility factors. For example, an outbreak of viral encephalitis caused by the previously unrecognized Nipah virus occurred in Malaysia in 1998. The ability to analyze archival collections of serum samples from pigs collected in Malaysia in 1995 showed that some porcine samples had antibodies to Nipah virus. This allowed investigators to conclude that the virus had been circulating in the population for some time. A large and invaluable resource of archived samples is DOD's triservice serum repository, begun in 1985, which contains 25 million specimens collected from military personnel. This resource serves many research needs; it most recently provided important information on hantavirus from samples obtained from military recruits from the southwest United States. Using the Internet for Reporting and Communication The Internet is providing a whole new means for the posting of disease alerts and information about new therapies and technologies, informing public health officials about relevant meetings, and providing new opportunities for collaboration. The Internet is increasingly being used as a source of outbreak-related information through media newswires, electronic discussion groups, and websites. Quality assurance, however, is an important requirement for officials using worldwide web-based information as a source of infectious disease information. To explore the extent to which this form of nontraditional reporting can be channeled for good use, WHO developed with the Canadian Ministry of Health a computer application that scans thousands of websites 10 times a day, including media newswires, for information that could lead to a report or reports of communicable diseases or disasters. This information is then transmitted to WHO. The Global Public Health Intelligence Network serves as an example of an innovative new approach to surveillance. Of about 450 outbreaks verified in the past 2.5 years, more than 50 percent of the reports came from the media. “Hits” gathered from websites are then monitored to obtain more detailed in

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections formation. This information is entered into a database that also contains data from more traditional reporting mechanisms. TAKING ADVANTAGE OF WINDOWS OF OPPORTUNITY Too often, delayed responses to outbreaks and the spread of infectious diseases result in missed opportunities for treatment and control. Lessons from the past should teach people today about the dangers of missing important openings for intervention. For example, in Africa the rates of resistance patterns to penicillin and tetracycline by the organism that causes gonorrhea are on the rise. In the 1950s and 1960s, when the prevalence of gonorrhea throughout African countries was extremely high governments did not attempt to change behavior or offer treatment. Had public health education been offered back in the 1960s and had antibiotics been used effectively, gonorrhea would not be present to the same extent throughout Africa today and would not be causing needless suffering and infertility in women. Today, HIV poses a similar new challenge, as several African countries have infection rates of greater than 25 percent. Many believe that the opportunity to halt the spread of this deadly virus has already been missed. Fighting the global spread of infectious disease takes political resolve and sufficient financial resources, just as eradication of smallpox did. In many cases, the tools required to detect, isolate, and control microbial agents are available but are underused or inaccessible. For example, measles vaccination rates in Africa range from 19 to 90 percent. A vaccine exists for hepatitis B and Haemophilus influenzae type B infection, yet the perception of the burdens of these diseases relative to those of other diseases and the costs of vaccines against both pathogens has led to their low level of use. The health system required to deliver these vaccines needs to be strengthened. In addition, government policies that can lead to the censuring of information about the extent to which a disease such as HIV/AIDS is present in the population undermine disease surveillance and control activities. Some parts of the world are ripe for intervention. For example, there is an enormous need and opportunity to introduce new infectious disease control infrastructures into the Central Asia republics and Russia because their relatively new state of independence has left them with no experience in international procurement and self-governance. For example, they lack the logistical wherewithal to purchase reagents or vaccines or implement directly observed therapy. USAID, CDC, the Soros Foundation, and WHO have been collaborating to bring the necessary resources to these evolving health care systems. The eradication of smallpox, which was declared in 1980, serves as an example of an effective worldwide effort to engender political will and muster resources. The disease, which was causing as many as 1.9 million deaths a year

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections by the late 1960s, was eradicated because of concerted efforts to further develop an effective vaccine and to create a global infrastructure for its distribution and for smallpox surveillance. Today, the use of linkages through the Internet offers several possibilities for faster reporting and faster responses to disease threats. It must be recognized, however, that even the fundamental tools needed to capitalize on new information technologies may not be available in some of the developing countries, and training workshops are needed when new tools are introduced. Although many developing countries are aiming for self-sufficiency in developing, storing, and maintaining necessary supplies of reagents and in-country expertise, organizations such as CDC, WHO (including PAHO and other regional offices), USAID, and NGOs will be needed to supply routine diagnostic reagents, provide training, enhance communication, and exert quality control. More structured agreements are needed to ensure that the requisite laboratories are adequately equipped and that channels of communication are left open. A structured agreement that could bring technology transfers, communication, and reporting into a coordinated program to strengthen public health laboratories and surveillance is the Biological Weapons Convention. Article X of the Convention requires that the signatories exchange technologies. This would improve the diagnostic capabilities of laboratories and improve information sharing. These enhanced capabilities could also add to those resources used to support the public health capabilities of laboratories in other countries. Similarly, the medical research laboratories of overseas military assets can help local civilian medical communities find ways to adapt the many new and emerging detection technologies to infectious disease surveillance. Training and education activities sponsored by the military could also be coordinated with those programs administered by the public health infrastructures of governments and NGOs. To achieve an integrated system of surveillance and monitoring with an appropriate and timely response, the world community must work toward the following common goals: Strengthening disease surveillance of humans and domestic animals. Priority areas include improving communication and information sharing between the medical and veterinary communities and designing integrated medical and veterinary disease surveillance systems at the regional level. Building on existing disease-specific reporting systems. Consider the use of novel technology, such as remotely sensed data, in existing disease surveillance systems and expand disease-specific surveillance systems to monitor other closely related diseases. Enhancing and improving the use of communication and information Technologies. Promoting the International Health Regulations. Developing improved, low-cost laboratory infrastructure for surveillance.

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EMERGING INFECTIOUS DISEASES FROM THE GLOBAL TO THE LOCAL PERSPECTIVE: A Summary of a Workshop of the Forum on Emerging Infections Fostering good public health practices. Training personnel. Educating the public and professionals to slow the rate of increase of antimicrobial resistance. Conducting collaborative research. Priority areas for investigation include preventing the development of drug-resistant microbes by promoting the appropriate use of antibiotics; understanding the transmission patterns of food-, water-, vector-, and air-borne pathogens; and improving diagnostic tests and prevention and control strategies for infectious diseases. Accelerating vaccine development and distribution. Fostering credible coordinating international groups. Encouraging overseas institutions, such as military medical research units, to be more involved in helping the host country develop an infectious disease surveillance infrastructure. All nations should promote the participation of the health sector in international trade agreements that may affect human, animal, or plant health. This requires a commitment at the highest levels of government to improve the components of the global surveillance system, upgrading the infrastructure and the qualifications of the human resources needed to control emerging infections, and supporting and encouraging rapid intra- and intercountry communications on health issues, including infectious disease outbreaks. This kind of high-level dialogue must be intentional and ongoing. Outreach to countries not involved in international discussions on disease surveillance is especially important, as they are most likely at high risk for infectious disease outbreaks. Within and across borders there must be integration of the public health system, epidemiologically, building on the laboratory and the clinical health care base. This requires efforts at the local level. Economic globalization, demographic changes, and the increased costs of infectious disease control and prevention for human health and welfare emphasize the interdependence of all nations. As efforts are made to improve trade and bring democratic governance to countries in the developing world, the crucial needs of public health cannot be forgotten. Strengthened national and regional public health systems not only will reduce the level of human suffering from infectious diseases but also can promote economic growth and political stability among those countries most affected.