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3. Factors of Emergence
Pages 53-148

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From page 53...
... Future scientific discoveries and an increased understanding of the complexity of the emergence of infectious diseases will no doubt add to the list of factors identified in this report. In this light, the committee developed a model for conceptualizing how the factors in emergence converge to impact on the human-microbe interaction and result in infectious disease (see Figure 3-1~.
From page 54...
... Microbial adaptation and change continually challenge our responses to disease control and prevention. For example, the influenza virus is renowned for its ability to continually evolve so that new strains emerge each year, giving rise to
From page 55...
... At the center of the model is a box representing the convergence of factors leading to the emergence of an infectious disease. The interior of the box is a gradient flowing from white to black; the white outer edges represent what is known about the factors in emergence, and the black center represents the unknown (similar to the theoretical construct of the "black box" with its unknown constituents and means of operation)
From page 56...
... Now, of course, the inherently variable nature of these early microbial species is well known. Microbes have enormous evolutionary potential and are continually undergoing genetic changes that allow them to bypass the human immune system, infect human cells, and spread disease.
From page 57...
... Some microbes coat their surfaces with mimics of human tissue to prevent recognition by their human host as "nonself." As a result, the human immune response is not activated, and the microbe is ignored and left to survive and reproduce at will. Some microbes have evolved mechanisms to downregulate the human innate immune system, which would otherwise serve as the human body's first line of defense.
From page 60...
... Susceptibility to infection can result when these normal defense mechanisms are altered or when host immunity is otherwise compromised as a result of impaired immune function; genetic polymorphisms; and other factors, such as aging and poor nutrition. Impaired Host Immunity The innate or nonspecific immune response is the body's initial inflammatory reaction to any kind of injury or microbial invasion.
From page 61...
... New knowledge about the innate and specific immune responses is being used to develop potential therapies for infectious disease control. For example, the key to a good innate immune system defense is a balanced, regulated production of inflammatory cytokines.
From page 62...
... The presence of malaria in a population does more than modify hemoglobin. Several other malaria-related balanced polymorphisms, many of which involve the red blood cell structure and metabolism, have likewise evolved in response to the tremendous selective force exerted by the disease.
From page 63...
... A strong and consistent relationship has been found between childhood malnutrition and increased risk of death from diarrhea, acute respiratory infection, and possibly malaria (Rice et al., 2000~. Conversely, infectious processes, especially those associated with diarrhea, drive malnutrition in young children (Mata, 1992; Mata et al., 1977)
From page 64...
... Likewise, these same factors can affect human behavior or exposure to infection by impacting outdoor activities, housing, the quality and quantity of food, and agricultural or other uses of the environment. Among the numerous elements of the physical environment that influence the emergence of infectious diseases, climate and weathers have received a great deal of attention in recent years.
From page 65...
... Many argue that at present, other factors including human population density and the capacity of the public health system to prevent and control infectious disease outbreaks affect disease risk more than does global climatic change. Indirectly, if global climatic change were to result in reduced food availability, thereby producing undernourished human populations more vulnerable to disease, its impact on infectious disease could be dramatic (Intergovernmental Panel on Climate Change, 2001b)
From page 67...
... report, Under The Weather: Climate, Ecosystems, and Infectious Disease, addresses the impact of climate and weather change in further detail (NRC, 2001~. CHANGING ECOSYSTEMS The abundance and distribution of plants and animals can, conversely, impact on components of the physical environment.
From page 68...
... To the pressing issues of environmental conservation, natural resource utilization, population growth, and economic development can be added the need to understand the interplay of these processes with the emergence of infectious diseases. Such environmental and ecological factors are playing an increasingly important role in disease emergence.
From page 70...
... In Latin America, an estimated 20 million people have Chagas disease. In Africa, approximately 45 million people are at risk for African trypanosomiasis, which has virtually precluded domestic livestock production in a geographic region of Africa larger than the United States and now is tragically resurgent in humans in areas in East Africa.
From page 71...
... These same areas are also at risk for introduction of yellow fever virus, which is likewise transmitted by Ae. aegypti.
From page 72...
... Many newly emerged viruses (e.g., Sin Nombre virus and other hantaviruses, and Guanarito and other arenaviruses) have rodents as primary hosts.
From page 73...
... The case fatality rate was approximately 60 percent, causing widespread anxiety and enormous media interest in this newly emerged disease. Sin Nombre virus (genus Hantavirus, family Bunyaviridae)
From page 74...
... Hence, Sin Nombre virus shares a similar widespread distribution, but prevalence rates of the virus in this rodent reservoir can differ temporally and spatially (Mills et al., 1999~. Identification of a hantavirus as the etiologic agent of the hantavirus pulmonary syndrome epidemic prompted increased surveillance for these agents in the Western Hemisphere that has revealed an array of heretofore unrecognized hantaviruses.
From page 75...
... Most economic development activities, including the consumption of natural resources, deforestation, and dam building, have some intended or unintended impact on the environment, or both. In the present context, it is important to note that a growing number of emerging infectious diseases arise from increased human contact with animal reservoirs as a result
From page 76...
... . Other examples include increases in malaria following the clearing of land for rubber plantations in Malaysia; increases in schistosomiasis, malaria, and other infectious diseases following the Volta River project in Africa; increases in vector-borne diseases after the construction of new transportation routes in Brazil; and the emergence of Lyme disease in the United States after the reforestation of abandoned farmlands in the northeast (Mayer, 2000~.
From page 77...
... Human disease is a consequence of reaction to the eggs deposited in tissues by adult worms that live for years inside chronically infected people. The eggs are released when people urinate or defecate, and if they do so into snail-infested waters, more snails become infected, hence perpetuating the cycle.
From page 78...
... Increases in life expectancy have also increased the proportion of elderly among the population, who are at greater risk of infection by virtue of the natural decrease in immune function with age. At the opposite end of the age spectrum, the epidemiology of childhood infections has been altered by the numbers of children in day care centers, often the result of maternal employment (see Box 3-7~.
From page 80...
... The efficacy of immunizations also decreases with advancing age (Bernstein et al., 19991. Some elderly are more vulnerable to infectious disease because of a breakdown in host defenses due to chronic disease, use of medications, and malnutrition.
From page 81...
... In developed countries, the average national gain in life expectancy at birth was 66 percent for males and 71 percent for females between 1900 and 1990 (Kinsella and Velkoff, 2001~. Increases were more rapid in the first half than in the second half of the century because of the expansion of public health services and infectious disease control programs that greatly reduced death rates, particularly among infants and children in developed countries.
From page 82...
... 82 ~0~ ~~ ~ ~~ So+ 70-74 80-84 ! so-s4 < 40-44 an10-14 80+ I 70-74 80-84 50-54 40-44 30-34 20-24 10-14 0-4 80+ 70-74 80-84 40~4 50-54 30-34 20-24 10-14 0-4 2030 male Female 400 300 200 1 00 0 1 00 200 300 400 1 990 Wale Female 400 300 200 1 00 0 1 00 200 300 400 1950 male 400 300 200 ~pula110n (mllllons)
From page 83...
... Rural-to-urban migration in cities without adequate infrastructure has serious health consequences, not the least of which is the spread of infectious diseases. Many recent arrivals live in dire circumstances and suffer serious environmental health problems due to inadequate infrastructure and poor access to health services (WHO, 2001c)
From page 84...
... In recent decades, the incidence of several vector-borne diseases has increased dramatically, partly as a result of changing patterns of settlement (Gratz, 19991. Increased transport to centralized markets has helped spread emerging infections between rural and urban areas; an example is the movement of leishmaniasis to urban 3In the 1970s, the United Nations coined the term ``megacities to describe cities with lo million or more residents.
From page 85...
... The highly infectious diseasesusceptible population of transplant patients has also been increasing. Likewise, the widespread use of potent antiretroviral combination therapy has led to a growing population of people living with HIV, who retain a potentially lifelong risk of spreading this infection to others.
From page 86...
... Illicit Drug Use Infectious diseases have a long history of being associated with illicit drug use. In the 1920s, drug users were often infected with malaria and syphilis as a result of sharing unsterilized syringes while injecting heroin or opium.
From page 87...
... HIV has arguably had the greatest impact on awareness of the dangers of illicit drug use with regard to infectious diseases. People who share drug injection equipment, those who have unprotected sex with injection drug users, and children born to mothers who contracted HIV by sharing needles or having unprotected sex with an illicit drug user are at increased risk for HIV infection.
From page 88...
... New infectious diseases have emerged as a direct result of changes in technology and industry; these include Legionnaires' disease (air-conditioning cooling towers)
From page 91...
... (see Box 3-101. Even the manner in which animals are raised before entering the meat processing industry, such as the use of antimicrobials for growth production, can impact on microbial threats to health.
From page 92...
... coli, Salmonelia, Campylobacter, and Listeria have all been linked to human disease from fecal contamination of food and water, some of which has involved antimicrobial-resistant strains. Antimicrobials are used in food animals for the treatment and prevention of infections, as well as for growth promotion and enhanced feed efficiency (Gorbach, 2001; McEwen and Fedorka-Cray, 2002~.
From page 93...
... It is estimated that 25 to 75 percent of the antibiotics administered to feediot animals may be excreted unaltered in feces. Given that the annual production of livestock and poultry waste in the United States is nearly 180 million tons, this waste is a potentially large source of antibiotics released into the environment.
From page 94...
... The number of people who are willing to donate blood is increasing; in 2001, nearly 7.5 million potential donors participated in Red Cross blood drives across the nation, a 6.1 percent increase over the previous year. During the past decade, however, numerous infectious agents worldwide have been identified as potential threats to the blood supply (Chamberiand et al., 2001~.
From page 95...
... The total number of single- and multi-organ transplants increased by 45 percent between 1991 and 2000. The immunosuppressive drugs used to prevent rejection of the transplanted organs weaken the body's immune system and leave the host susceptible to infectious diseases.
From page 96...
... While xenotransplantation offers potential benefit for both individual recipients and society, it also represents a public health concern. Such procedures have the potential to
From page 97...
... In the United States, regulation of xenotransplantation procedures is within the purview of FDA, which has ruled that nonhuman primates should not be used as source animals for transplants until scientists have sufficient information to address the associated infectious disease risks (DHHS, 2000a)
From page 98...
... Fortunately, in most cases the factors necessary to establish a transmission cycle are not present, and few human cases typically occur subsequent to introduction. On the other hand, all of the necessary ingredients for the establishment of West Nile virus were present in New York City in 1999, and the virus is now established across the United States (see Box 3-12)
From page 99...
... Air Travel The interactions that occur during travel are another important component of the travel process, with implications for the emergence and spread of infectious disease. In particular, many documented transmission incidents or outbreaks of both airborne and foodborne infections including influenza, smallpox, tuberculosis, measles, cholera, shigellosis, salmonello
From page 100...
... 100 MICROBIAL THREATS TO HEALTH sis, and staphylococcal food poisoning have occurred inside airplanes, (Ritzinger, 1965; CDC, 1983; Kenyon et al., 1996~. Influenza outbreaks have been known to affect more than 70 percent of the passengers on a single aircraft (Moser et al., 1979~.
From page 101...
... Cruise Ships Cruise ship travel has increased dramatically. Nearly 7 million people took North American cruise vacations in 2001.
From page 102...
... . Cruise ships also have a history of infectious respiratory illnesses, including both influenza A and B (CDC, 2001i; Miller et al., 2000)
From page 103...
... Unfortunately, this wider array of product options brings with it the risk of cross-border transmission of infectious agents. Many species enter the United States each year as contaminants of commodities.
From page 104...
... For this reason, pet dogs and cats are subject to inspection at ports of entry for evidence of infectious diseases that can be transmitted to humans (CDC, 2001j)
From page 105...
... ~- ~ -~~ ~ rid ~~ ·~ ~~~ ~·I`74~ arm ulna- I: Just to meet today's year-round demand for fresh produce, the volume of produce imported from developing countries has increased dramatically. For example, 95 percent of green onions sold in the United States during 2000 were imported from Mexico.
From page 106...
... More than 200 food-transmitted diseases are known (Bryan, 1982~; in 82 percent of foodborne ilinesss, however, the identity of the pathogen is unknown (IOM, 2002a)
From page 107...
... BREAKDOWN OF PUBLIC HEALTH MEASURES A breakdown or lack of public health measures, such as adequate sanitation, immunizations, and tuberculosis control, has had a dramatic effect on the emergence and persistence of infectious diseases throughout the world. For example, infectious diseases have resurged in the former Soviet Union over the past decade because of the country's enormous socioeconomic upheavals and the fracturing of its health services that has resulted from poor funding for treatment, vaccine prophylaxis, and health education (Netesov and Conrad, 2001; Coker, 2001~.
From page 108...
... The infection often results in mild symptoms but can sometimes cause severe, lifethreatening diarrhea. The bacterium survives and multiplies outside the human body; it can then spread rapidly in human populations where living conditions are crowded and unprotected water sources are in close proximity to fecal repositories.
From page 109...
... Between 1965 and 1991, just 136 cases were reported to CDC. From 1992 through 1994, the number jumped to 160; half of these were among airline passengers traveling from Latin America (75j and cruise ship passengers from Southeast Asia (5)
From page 110...
... In 1970, cholera was found in West Africa, where it eventually proliferated and became endemic throughout most of the continent. It then spread to Latin America in 1991, and within the year had reached 11 countries in this region.
From page 111...
... .. Nosocomial Infections Nosocomial (hospital-acquired)
From page 112...
... Overuse of parenteral treatments, inadequate surgical facilities, and poorly trained personnel also fueled the spread of the virus among patients and health care providers (Fisher-Hoch et al., 1995~. Similarly, in the absence of appropriate precautions to prevent exposure to blood and other body fluids, hospital outbreaks of Ebola viral hemorrhagic fever in Zaire in 1995 Passed from patients to health care workers and to family 1 1 1 )
From page 113...
... FACTORS IN EMERGENCE 113 cures performed on them, and their typically older ages. According to the National Nosocomial Infections Surveillance (NNIS)
From page 114...
... agrees increased 29 percent in 2000 as compared with the mean of the previous 5 years (1995-1999~. Resistance of Pseudomonas aeruginosa to quinolones increased 53 percent during the same period in the same population; vancomycin-resistant enterococci increased 31 percent (National Nosocomial Infections Surveillance System, 2001~.
From page 115...
... The epidemic of diphtheria in the Newly Independent States of the former Soviet Union in the early 1990s marked the first large-scale diphtheria epidemic in industrialized countries in three decades (Vitek and Wharton, 1998~. In 1993, the number of reported diphtheria cases surged to nearly 20,000, occurring primarily throughout urban Russia, the Ukraine, Belarus, and the Baltics.
From page 116...
... . 1 1 man 1 960 Bear lg8O 1996 FIGURE 3-9 Reported diphtheria cases in the Soviet Union and the Newly Independent States, 1965-1996.
From page 117...
... Control of Vector-borne and Zoonotic Diseases One major factor in the resurgence of vector-borne and zoonotic diseases is the decreased support for and deterioration of public health infrastructure. Continued surveillance and control programs for these diseases are expensive.
From page 118...
... With the emergence of West Nile virus, CDC's Division of Vector-borne Infectious Diseases had to institute capacity-building programs for the states and emergency training programs in arbovirus surveillance and medical entomology (CDC, 2001m)
From page 119...
... Many public health laws, however, have not been regularly reviewed or revised since the middle of the twentieth century (Gostin et al., 1999~. State laws regarding infectious diseases are often fragmented and inconsistent (embodying differing approaches among the states)
From page 120...
... Antiquated laws are increasingly being reviewed and updated to eliminate inconsistencies and reflect current medical knowledge and legal and ethical norms. By 2002, thirty-six states had introduced bills and twenty states had enacted legislation based on the Mode!
From page 121...
... POVERTY AND SOCIAL INEQUALITY As we enter the twenty-first century, mortality from infectious diseases is correlated more closely than ever before with transnational inequalities in income (Houweling et al., 2001~. Countries throughout the developing world and the former communist bloc have been embracing the marketbased policies advocated by Europe and North America.
From page 122...
... It is not coincidental that many of the latter countries have been hardest hit by microbial threats to health such as HIV, dengue, drug-resistant TB, and malaria (Murray and Lopez, 1997~. The relationship between infectious diseases and economic development has been of increasing interest to scholars and practitioners in a variety of fields (See, 1999; Gwatkin et al., 1999; Whitehead Institute, 2002~.
From page 124...
... Without proper planning, health-sector privatization can interfere directly with government efforts to combat emerging infectious diseases (Kim et al., 1999~. Meanwhile, high levels of indebtedness in many countries with high disease prevalence can divert desperately needed funds from the health sector (Plot and Coll Seck, 2001)
From page 125...
... in sub-Saharan Africa; 9 of these emergencies were directly related to civil strife (FAO, 2001~. So-called "complex humanitarian emergencies" provoked by the combined conditions of famine and war contribute directly to the spread of infectious diseases and have fairly consistent sequelae, including mainutrition, measles, diarrhea!
From page 126...
... Refugee camps are usually crowded and dirty, with little or no access to medical care or protection from vectors, and full of people from many different geographic areas (and thus probably carrying a broad range of infectious agents)
From page 127...
... To proceed with any hope of success in the struggle against emerging infectious diseases, our model of political will must commit four key groups of stakeholders donors, health professionals, country authorities, and pa
From page 128...
... 28 MICROBIAL THREATS TO HEALTH tients and civil society to the necessity of collective action. These groups are quite interdependent in their commitments.
From page 129...
... FACTORS IN EMERGENCE 129 oriented program activity. To achieve high-level cooperation in establishing those programs, it is necessary to convince country authorities that adequate and consistent funding will be available.
From page 130...
... Given sufficient attention and resources, they have the capacity not only to turn the tide against these emerging infectious diseases, but also to build infrastructure and perhaps more important, global consensus sufficient to combat infections that have not yet emerged. INTENT TO HARM The threat of intentional attacks using biological agents on the United States and other countries has never been as serious as it is today.
From page 131...
... Nations suspected of having offensive biological warfare programs have been named by the Office of Technology Assessment (U.S. Congress, 1993a)
From page 132...
... Food items, however, are usually not consumed synchronously except at special events; although the extensive network of global commerce can assist in distributing an initial source over wide geographic areas. Improved surveillance of foodborne diseases and newer methods of molecular typing of offending organisms should provide a countermeasure to the possible wide dissemination of contaminated food.
From page 133...
... FACTORS IN EMERGENCE 133 allies. The deficiencies of aerosols, such as dependence on meteorological conditions, the unsuitability of most organisms for airborne spread, and the technical demands involved, may be counterbalanced in the hands of skillful perpetrators by the advantages of standoff attack, the silent spread of incapacitating or lethal disease, and wide-area coverage.
From page 134...
... In the laboratory, aerosol promulgation of tularemia, rickettsiae, viral hemorrhagic fevers, and many other agents is a threat to the microbiologist (DHHS, 1999~. Artificially generated aerosols of anthrax and other agents are high on the list of terrorist attack options.
From page 135...
... Toxins are inherently less efficient because they cannot match the killing or incapacitating power of these highly infectious organisms; the toxins must produce their effects as delivered, but the infectious agents grow and produce toxins or other effects in the recipient's body. According to a WHO scenario, several infectious agents could be expected to produce 35,000 to more than 100,000 casualties if 50 kg were delivered in a line source and carried downwind over a populated area.
From page 136...
... Humanity's struggle with influenza is illustrative of such a convergence of factors, which has resulted in maintaining the presence of this virus and periodically led to epidemics of the disease. Social, political, and economic factors interact with ecological factors to drive influenza viruses to respond through biological and genetic factors, thus circumventing human defense mechanisms and, in today's increasingly global society, exerting effects on economic, social, and political life worldwide (see Figure 3-1 for a visual mode!
From page 138...
... This event raises the specter of the reappearance of H2N2 influenza viruses that have been stored since the pandemic of 1957. No one born after 1957 has high-level immunity to these viruses, and the biosecurity of such agents is a matter of increasing concern.
From page 139...
... indicates that aquatic avian influenza viruses have adapted to these species, overcoming differences between avian and mammalian hosts in body temperature, cell surface receptors, and mode of transmission (see Figure 3-11~. In aquatic birds, influenza virus is an enteric parasite that is transmitted by ingestion of focally contaminated water.
From page 140...
... each encode two proteins in different reading frames. The NS gene is important in regulating the host cell response to influenza virus infection.
From page 141...
... (oc2-6 terminal sialic acid) influenza viruses and thus can act as intermediate hosts.
From page 142...
... adapt to humans, however, was sufficiently disquieting to prompt the wholesale slaughter of poultry in Hong Kong on two occasions. During and after adaptation of influenza viruses to a new host, a continuing battle for supremacy occurs between microbe and host.
From page 143...
... Two classes of antivirals are used against influenza viruses: the adamantines, which block the ion channel formed by the influenza matrix (M2) protein, and the neuraminidase inhibitors, which prevent virus release by blocking NA enzyme activity (Hayden, 2001~.
From page 144...
... However, the direct transmission of avian HSN1 and H9N2 influenza viruses to humans in Hong Kong in 1997 and 1999 suggests the possibility that all subtypes can infect humans. The adaptation of influenza viruses to wild aquatic birds that migrate over vast distances (e.g., from southern South America to the North Slopes of Alaska)
From page 145...
... Poultry, pigs, and people are the known hosts of influenza viruses, and most of the influenza pandemics of the twentieth century have originated in China. Substantial influenza activity has been noted in Hong Kong, which is hypothesized to be a documentable epicenter for the emergence of influenza pandemics.
From page 146...
... The tourist and poultry industries collapsed because of the HSN1 "bird flu" incident, and Hong Kong suffered a severe economic downturn. Intent to Harm Recent advances in reverse genetics of influenza viruses now make it possible to generate influenza viruses to order (Neumann and Kawaoka, 2001~.
From page 147...
... Modeling studies are needed to plan the most effective use of such a stockpile of drugs. The steps needed to deal effectively with interpandemic influenza can also help in preparing for an influenza pandemic.
From page 148...
... The cause of great concern was the possibiTity that this virus could have come from a frozen source, released accidentally from a laboratory. This event raises the specter of the reappearance of H2N2 influenza viruses that have been stored since the pandemic of 1957.


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