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Ecology of Increasing Disease Population growth and environmental degradation Bioscience Vol. 48 No. 10 October, 1998 David Pimentel, Maria Tort, Linda D’Anna, Anne Krawic, Joshua Berger, Jessica Rossman, Fridah Mugo, Nancy Doon, Michael Shriberg, Erica Howard, Susan Lee, and Jonathan Talbot David Pimentel ( email: dpl8@cornell. edu ) is a professor in the College of Agriculture and Life Sciences, Cornell University, Ithaca, NY 14853-0901. Maria Tort, Linda D’Anna, Anne Krawic, Joshua Berger, Jessica Rossman, Fridah Mugo, Nancy Doon, Michael Shriberg, Erica Howard, Susan Lee, and Jonathan Talbot are graduate students in the College of Agriculture and Life Sciences, Cornell University, Ithaca. NY 14853-0901. All populations of organisms, including humans, are limited partially or completely by diseases in their ecosystems (Real 1996). Disease prevalence in populations and ecosystems is influenced by numerous environmental factors, including infectious organisms such as fungi and viruses, pollutants such as chemical and biological wastes, and shortages of food and nutrients (Dubos 1965). This complex of factors and their interactions makes tracking and assessing the causes and effects of individual diseases extremely difficult (McMichael 1993). For example, when a human is infected by a parasite that is drawing heavily on nutrients in the human, such as a blood parasite, it is difficult to determine whether the individual died from malnutrition or from the parasitic infection. It is more likely that death was due to a combination of factors. In addition, air, water, or soil pollutants or other stresses that affect humans and other species in the ecosystem add to the complexity of the situation. Disease dynamics are further complicated by the increased density of humans because high densities facilitate the increase and spread of infectious organisms among people (Lederberg et al. 1992, WHO 1992). Rapidly expanding human populations and widespread environmental degradation contribute to expanded world disease problems (WHO 1992, 1996c). Human plagues such as the Black Death, cholera, tuberculosis (TB), and HIV are essentially problems of dense urban populations. Crowded conditions in urban areas provide the ideal environment for the culture and spread of old diseases, such as cholera and TB, as well as for many newly emerging diseases, such as HIV (McMichael 1993). Today, infectious diseases cause approximately 37% of all deaths worldwide (Real 1996). Moreover, we have calculated that an estimated 40% of world deaths can be attributed to various environmental factors, especially organic and chemical pollutants. In addition, more than 3 billion humans suffer from malnutrition (WHO 1996e), and 4 million infants and children die each year from diarrhea, which is caused largely by contaminated water and food (WHO 1992, 1995). Newly developed chemicals also have increased the varieties, potencies, and quantities of chemicals that are available to humans and released into the air, soil, and water. These chemicals have increased ecosystem pollution and caused serious disease problems in humans. Worldwide, an estimated 100,000 different chemicals are used each year (Nash 1993). The United States uses over 2700 billion kg of chemicals each year, of which at least 20 billion kg are considered hazardous (WRI 1994). In this article, we assess the relationship between high population density and increasing environmental degradation. We also examine the effects of both factors (separately and in combination) on present and future disease incidence throughout the world. Population growth and disease transmission Based on current growth rates, the world’s population will double to 12 billion in the next 50 years, intensifying pollution and disease problems. The US population alone will double to 540 million during the next 70 years (PRB 1996, USBC 1996). Environmental problems are already particularly severe in urban areas of the world, in which the number of people continues to double especially quickly (i.e., every 20-25 years). By the turn of the century, according to projections, more than one-half of the world's population will live in cities that have more than 1 million people, and by 2025, two-thirds of the world's population will have settled in large urban areas (WRI 1994). Densely crowded urban environments, especially those without adequate sanitation, are of great public health concern because they are sources of disease epidemics (Iseki 1994). For example, dengue fever -- spread by the mosquito Aedes aegypti, which breeds in tin cans, old tires, and other water-holding containers -- is already expanding rapidly in crowded tropical cities (Lederberg et al. 1992). Dengue fever has increased dramatically since 1980, with 30-60 million dengue infections now occurring each year (Table 1; Monath 1994). Table 1. Human infections and deaths from water-related diseases each year worldwide. Disease Number of infected people Number of deaths Reference Diarrhea 2 billion 4 million WHO 1992 Ascariasis 0.8-1 billion 20,000 WHO 1992 Filariasis 900 million NA WHO 1992 Schistosomiasis 600 million 1 million Nash 1993 Malaria 300-500 million 2.7 million Travis 1997 Amoebiasis 500 million NA WHO 1992 Trichuriasis 500 million 100,000 WHO 1992 Dengue fever 30-60 million 21,000 WHO 1992 Onchocerciasis (river blindness) 18 million 20,000-50.000 WHO 1992 Leishmaniasis 12 million NA WHO 1992 Dracunculiasis 10 million NA WHO 1992 Trachoma (blindness) 6-9 million NA WHO 1992 Typhoid and Paratyphoid 1 million 25,000 WHO 1992 Cholera 210,000 10,000 WHO 1992 Yellow fever 10-25,000 NA WHO 1992 Total ~ 5 billion ~ 6 million Based on the increase in air, water, and soil pollutants worldwide, we estimate that 40% of human deaths each year result from exposure to environmental pollutants and malnutrition. These deaths are in addition to the toll taken by infectious diseases. Automobile use and energy consumption, which are steadily increasing in densely populated cities, are just two of the many sources of environmental pollution that contribute to the growing number of human illnesses and deaths (WHO 1992, 1995). The toxic chemicals to which humans are exposed include benzene, lead, pesticides, and cyanides. In addition, approximately 3.5 billion kg of toxic metals are released into the US environment annually (WRI 1994). Environmental factors, including various chemicals, ultraviolet and ionizing radiation, and tobacco smoke, are estimated to cause roughly 80% of all cancers (Murray and Lopez 1996). Of the approximately 80,000 chemicals in use today, including many pesticides used in the United States, nearly 10% are recognized as carcinogens (Darnay 1994, Newton and Dillingham 1994). Annually, approximately 5 million cancer deaths are reported worldwide (Murray and Lopez 1996). In the United States, cancer-related deaths from all causes increased from 331,000 in 1970 to approximately 521,000 in 1992 (USBC 1996). Of these, an estimated 30,000 can be attributed to chemical exposure (McGinnis and Forge 1993). Moreover, human exposure to chemicals may be increasing in the United States (Pimentel and Bashore 1998). The use of chemicals increased from approximately 3500 kg per person per year in 1941 to more than 10,000 kg per person per year in 1995 (FASE 1996). The prevalence of illnesses due to chemical exposure has also grown. Water pollution and diseases Waterborne infections account for 80% of all infectious diseases world wide and 90% of all infectious diseases in developing countries (Table 1; Epstein et al. 1994). Lack of sanitary conditions contributes to approximately 2 billion human infections of diarrhea, resulting in approximately 4 million deaths each year, mostly among infants and young children (WHO 1992). Even in developed countries, waterborne diseases are significant. In the United States, they account for 940,000 infections and approximately 900 deaths each year (Seager 1995). Approximately 1.2 billion people in developing nations lack clean, safe water because most household and industrial wastes are dumped directly into rivers and lakes without treatment, which contributes to the rapid increase in waterborne diseases in humans (Gleick 1993). Developing countries discharge approximately 95 % of their untreated urban sewage directly into surface waters (WHO 1993c). For example, of India's 3119 towns and cities, just 209 have partial treatment facilities, and only 8 have full wastewater treatment facilities (WHO 1992). Furthermore, 114 cities dump untreated sewage and partially cremated bodies directly into · the sacred Ganges River (NGS 1995). Then, downstream, the untreated water is used for drinking, bathing, and washing. This situation is typical of many rivers in developing countries. Similarly, in Alexandria, the production site for approximately 40 % of Egypt's total industrial output, untreated wastes are discharged into the Mediterranean Sea and Lake Maryut (WHO 1992). Over the past decade, pollution has resulted in an 80% decline in fish production in Lake Maryut and has contributed to the malnutrition problem (WHO 1992). Agricultural runoff threatens the world's drinking water because of the animal and chemical wastes present in field runoff entering rivers and other aquatic ecosystems. In the United States, nearly 50% of lake water is polluted by erosion runoff containing nitrates, phosphates, and other agricultural chemicals (Gleick 1993). Some disease outbreaks in the United States are due to microbial pollution and the spread of two protozoan pathogens, Cryptosporidium parum and Giardia lamblia. A water survey conducted in 1992 revealed that nearly 40% of treated drinking-water supplies in the United States are contaminated with these organisms (Platt 1996k During tile past 30-40 years, the number of infections in the United States caused by these waterborne organisms has increased (Guerrant 1997). For example, a serious outbreak of cryptosporidiosis that occurred in Milwaukee, Wisconsin, in the spring of 1993 was attributed to the contamination of the city's drinking water. As a result, 403,000 cases of diarrhea and 4400 hospitalizations occurred (CDC 1994). Cholera, a well-known waterborne disease, continues to be a serious global problem. Vibrio cbolerae outbreaks are closely associated with climatic cycles (e.g., El Niño Southern Oscillation) and ocean plankton blooms (Colwell 1996). These associations suggest the potential influence of global warming on the spread of certain diseases (Colwell 1996). In 1988, there were approximately 50,000 cases of cholera, but by 1991 that number rose to 600,000; deaths increased from 2000 to 18.000 over the same period (Gleick 1993). However, from 1991 to 1995 the number of cholera cases declined worldwide to approximately 210,000 per year because of effective public health efforts. Schistosomiasis, which is associated with contaminated fresh water, is expanding worldwide and currently causes an estimated 1 million deaths annually (Table 1). This expansion is due to an increase in suitable habitats for the snail intermediate-host population resulting from various human activities, including construction of dams and irrigation channels (Shiklomanov 1993). For example, construction of the Aswan High Dam in Egypt and related irrigation systems in 1968 led to an explosion in the prevalence of Schistosoma mansoni in the population; it increased from 5% in 1968 to 77% in 1993 (Shiklomanov 1993). Also associated with water is mosquito-borne malaria. This disease infects more than 500 million humans each year, killing approximately 2.7 million (Table 1; Marshall 1997, Travis 1997). Approximately 90% of all malaria cases occur in Africa, as do 90-95% of the world's malaria-related deaths. Between 1970 and 1990 in the African countries of Rwanda and Togo, the increase in malaria incidence ranged from fourfold to more than 150-fold, and it continues to rise (Figure 1). Figure 1. Trends of malaria incidence in Rawanda and Togo. Solid line Rawanda, dashed line Togo. After Brinkmann and Brinkmann 1991. In some regions of Asia and South America, malaria prevalence decreased from 1950 until 1980 and has since remained fairly stable, at approximately 5 million cases per year (Najera et al. 1992). But in other regions, the number of malaria cases is now increasing. For example, Peru recorded approximately 34,000 cases of malaria in 1991 but approximately 55,000 cases in 1992 (WHO 1996g). Similarly, in Bangladesh, malaria prevalence increased from approximately 33,000 cases in 1988, to 64,000 cases in 1991, to 125,000 cases in 1993 (WHO 1996h). Environmental changes, including more polluted water, have fostered the high incidence and increase of malaria. Deforestation in parts of Africa has exposed land to sunlight and promotes the development of temporary pools of water, thus favoring the breeding of human-biting, malariatransmitting mosquitoes, Anopheles gambiae (Coluzzi 1994). With some African populations doubling every 20 years, more people are living in close proximity to water ecosystems that are suitable for mosquito breeding. Concurrently, mosquito vectors are evolving resistance to insecticides that are polluting aquatic ecosystems, and protozoan pathogens are evolving resistance to antimalarial drugs, reducing the effectiveness of control efforts (Georghiou 1990, Olliaro et al. 1996). Atmospheric pollution and diseases Each year, air pollutants adversely affect the health of 4-5 billion people worldwide (World Bank 1992, Leslie and Haraprasad 1993, WHO/UNEP 1993). Air pollution is increasing because of the activities of the expanding world population: the burning of fossil fuels, the increased emissions of industrial chemicals, and the increased use of automobiles. In particular, automobile numbers are growing approximately three times faster than the world population (WHO/UNEP 1993). Although governmental efforts since the 1950s have led to significant improvements in urban air quality in many developed nations, overall emissions continue to rise with the expanding human population. Because developing and East European nations have negligible pollutant emission controls, living conditions are becoming especially hazardous in their growing urban areas. By 1993, air pollution levels in all 20 of the world's largest cities exceeded World Health Organization guidelines (WHO/UNEP 1993). For example, during the winter months, particulate concentrations in Santiago, Chile, were among the highest observed in world urban areas {300-400 ug/m3). Los Angeles has the highest density of automobiles per person in the world, so it is not surprising that EPA standards for ozone levels were exceeded at all city monitoring stations in 1990. Moreover, the average exposure to carcinogens from automobiles in Los Angeles is as much as 5000 times greater than the level considered acceptable by the EPA (Mann 1991, Wilken 1995). Air pollution is also rampant in China, where less than 1% of 500 Chinese cities surveyed have clean air (Zimmerman et al. 1996). From 1955 to 1984, the prevalence of respiratory diseases in China rose by 50%. Respiratory diseases occur at a rate five times higher in China than in the United States; indeed, they are the leading cause of death in China (Zimmerman et al. 1996). Compounding this public health problem is a nearly fivefold increase in cigarette use in China over the past few decades, from approximately 360 to nearly 1800 cigarettes per person each year (World Bank 1992). Although Chinese males smoke 98% of the cigarettes, mortality due to lung cancer is approximately equal in males and females (Leslie and Haraprasad 1993). The problem of respiratory diseases is not limited to China. Worldwide, the incidence of respiratory disease is increasing along with cigarette use. In fact, the two major underlying causes of premature death in the world are the significant increases in tobacco use and HIV. Exhaled tobacco smoke contains more than 3800 chemicals, including numerous carcinogens (Hulka 1990). Smoking causes approximately 3 million deaths annually, 2 million in developed countries and 1 million in developing countries (WHO 1995, Murray and Lopez 1996). In industrialized nations as a whole, the prevalence of lung cancer increased approximately threefold from 1950 to 1986. US death rates from lung cancer alone increased nearly fourfold between 1950 and 1990 (WHO 1994). In 1990, nearly 419,000 US deaths were attributed to smoking (WHO 1994). By 2020, predictions are that tobacco will cause 10 million deaths per year worldwide (Murray and Lopez 1996). Globally, but especially in developing nations where people cook with fuelwood and coal over open fires, approximately 4 billion humans suffer continuous exposure to smoke (WHO 1992, World Bank 1992, Leslie and Haraprasad 1993, WHO/UNEP 1993). This smoke, which contains large quantities of particulate matter (Leslie and Haraprasad 1993) and over 200 chemicals, including several carcinogens (Godish 1991), results in pollution levels that are considerably above those considered acceptable by the World Health Organization (WHO 1992, World Bank 1992, Leslie and Haraprasad 1993, WHO/UNEP 1993). Fuelwood cooking smoke is estimated to cause the death of 4 million children each year worldwide (World Bank 1992). In India, where people cook with fuelwood and dung, particulate concentrations in houses are reported to range from 8300 to 15,000 ug/m 3, greatly exceeding the 75 ug/m3 maximum standard for indoor particulate matter in the United States (Christiani 1993). Radon radiation from the earth, another indoor air pollution hazard, is a growing problem, in part because of the modern construction of airtight houses. During the past 30 years there has been a four- to five-fold increase in radon concentration in houses in Sweden (Lindvail 1992). In the United States, radon radiation is considered to be a significant cause of lung cancer, causing approximately 14,000 deaths per year (CEQ 1996). In general, air pollutants exacerbate asthma, which ultimately can become severe enough to cause death. Worldwide, the incidence of asthma has increased nearly 50%, from 1.3 cases per 100,000 people in 1980 to 1.9casesper 100,000in 1989 (WHO 1993a). Deaths of children younger than 5 years of age from acute respiratory infections more than doubled, from 2.2 million worldwide in 1985 (USBC 1996) to the current level of approximately 5 million per year (WHO 1995). In addition, 400 million cases of acute lower respiratory infections are reported each year, of which an estimated 4.4 million are fatal (WHO 1996f). Atmospheric pollution also adversely affects the stratospheric ozone layer, which protects organisms from heavy doses of ultraviolet radiation (McMichael 1993). Before October 1980 at the South Pole, which is the site of the greatest ozone depletion, the measures ranged between 250 and 325 DU (Dobson Units). These values have declined to dangerous levels -- between 125 and 175 DU. The acceptance of the 1987 Montreal Protocol has helped to reduce the worldwide production, use, and release of ozone-destroying chlorofluorocarbons (McMichael 1993). However, the ozone layer continues to be depleted, in part from the release of pollutants from increased burning of wood and from the worldwide use of the methyl-bromide fumigant (Coleman et al. 1993). Estimates are that every 1% decrease in the ozone layer increases cancer-inducing UV-B radiation by 1.4% (McMichael 1993). Exposure to sunlight, including UV-B radiation, accounts for 70% of skin cancers in the United States (McMichael 1993). At present, skin cancer prevalence is increasing between 30% and 50% every 5 years in many North American Caucasian populations (Coleman et al. 1993). For example, in the United States, the prevalence of new cases of skin cancer increased from approximately 10,000 cases in 1975 to 40,000 in 1996, while the number of deaths from skin cancer rose from approximately 4000 to 9490 (Schultz 1997). Although the use of lead in US gasoline has declined since 1985, yearly emissions of lead into the atmosphere from other sources remain near 2 billion kg and continue to threaten public health (O ECD 1985). Lead poisoning causes anemia, kidney problems, and brain damage. Children exposed to lead are particularly at risk of brain damage and reduced learning capabilities (Ittenbach et al. 1995, Renner 1995). Even now, an estimated 1.7 million children in the United States are exposed to hazardous levels of lead and have blood levels above the acceptable level of 10 ug/dL (CEQ 1996). Benzene, a carcinogen that causes leukemia even from exposure to low dosages (1-30 ppm), is a common component of gasoline and is therefore released into the atmosphere (Krstic 1994, UKDE 1996). From 1950 to 1980, US benzene production increased from 0.7 billion kg to 4.6 billion kg, and production is currently approximately 7.4 billion kg/yr (WR11994). Although the general use of benzene as a solvent has decreased as its negative effects have become better known (Krstic 1994, UKDE 1996), benzene use needs to be further reduced to lessen current public health problems. Pesticide pollution and disease Since the first use of DDT for crop protection in 1945, the global use of pesticides in agriculture continues to expand. From approximately 50 million kg of pesticides in 1945, global usage has since risen 50-fold, to approximately 2.5 billion kg/yr worldwide (Pimentel 1995). In the United States, the use of synthetic pesticides has grown 33-fold since 1945, to approximately 0.5 billion kg/yr (Pimentel 1995). The increase in related hazards is greater than the increase in applied amounts because most modern pesticides are more than 10 times as toxic to organisms than those used in the early 1950s (Pimentel 1995). In 1945, when synthetic pesticides were first used, few human pesticide poisonings were reported. But by the late 1960s, when pesticide use and toxicity had increased dramatically, the number of human pesticide poisonings also rose (Pimentel 1995). In California, the use of pesticides increased from 68 million kg in 1950 to 269 million kg in 1988, while the number of reported human poisonings rose from 115 to 903 cases per year (Maddy et al. 1990). The total number of pesticide poisonings in the United States increased from 67,000 in 1989 to the current level of 110,000 per year (Litovitz et al. 1990, Benbrook et al. 1996). This trend continues today. By 1973, when global pesticide use was approximately 1.3 billion kg/yr, the number of human pesticide poisonings reached an estimated 500,000, with approximately 6000 deaths (Labonte 1989). Two decades later, Pimentel (1995) reported that worldwide pesticide use had risen to approximately 2.5 billion kg. By 1992, approximately 3 million human pesticide poisonings were reported each year, with approximately 220,000 fatalities and 750,000 cases of chronic illnesses (WHO 1992). Available US data indicate that 18% of all pesticides and approximately 90% of all fungicides are carcinogenic and pose a hazard to human health (NAS 1987). Several other studies substantiate the adverse effects of pesticides on the human respiratory system. For example, among a group of professional pesticide applicators, 15% suffered asthma, chronic sinusitis, or chronic bronchitis, compared with only 2% for people who used pesticides infrequently (Weiner 1972). In addition, pesticides, especially the organophosphate and carbamate classes, adversely affect the nervous system by inhibiting cholinesterase. This problem is particularly critical for children because their brains are more than five times larger in proportion to body weight than the brains of adults. In California, 40% of the children working in agricultural fields have blood cholinesterase levels below normal, a strong indication of organophosphate and carbamate pesticide poisoning (Repetto and Baliga 1996). The effect of land degradation on disease incidence Soil is easily contaminated by a wide array of chemicals and pathogens. Humans may acquire chemical pollutants and pathogens directly from the soil (i.e., by contact with it) or indirectly, through food and water. At times, soil particles themselves may be pollutants, entering the eyes, nose, and mouth and acting as irritants or allergens. Cleared and exposed soil is highly susceptible to wind and water erosion. Wind erosion can cause serious health problems by blowing soil particles and microbes into the air. These windborne particles irritate the respiratory tract and eyes while aggravating allergies and asthma. Erosion also disperses toxic chemicals, such as heavy metals and pesticides, leading to contaminated food and water. Furthermore, erosion strips soil of its nutrients and thus lowers food crop productivity and ultimately reduces human nutrition. As people invade natural ecosystems and land is cleared of trees, soil is exposed and the chances increase of humans becoming infected by helminths, such as hookworms, and microbes, such as pathogenic Escherichia coli (WHO 1992). Such increases were observed in 1984 in Nepal, a mountainous country that is experiencing serious soil erosion and severe disease problems: 87% of the population was infected with helminths (Suguri et al. 1985, Metz 1991). Children suffer greater morbidity from helminthic infections than adults because children need more protein than adults per kilogram of body weight; under severe parasitic infections, they may be unable to utilize protein efficiently enough to remain healthy. In addition, many helminth species that infect humans are found in soil contaminated by human feces, thereby exacerbating the cycle of exposure. Worldwide, approximately 2 billion people are estimated to be infected with one or more helminth species, either by direct penetration or by consumption of contaminated food or water (Hotez et al. 1996). The most prevalent helminths are hookworms (Necator americanus and Ancylostoma duodenale), Strongyloides (Strongyloides stercoralis), and Ascarids (Ascaris lumbricoides). In locations in which sanitation is poor and people are overcrowded, as in parts of urban Africa, up to 90% of the population may be infected with one or more helminth species (Stephen-son 1994). Food contamination, disease, and malnutrition Worldwide, reported cases of food-borne diseases are as high as 240 million per year (WHO 1990). In the United States, approximately 6.5 million foodborne disease cases occur each year, causing approximately 9000 deaths (Todd 1996). Poultry, hogs, cattle, and other animals are easily contaminated with Salmonella enteritidis and various E. coli microbes, especially when they are crowded together in husbandry facilities with inadequate waste disposal systems (Lederberg et al. 1992). Further microbial contamination can be caused by unsanitary conditions during slaughtering, processing, and handling. In the United States, hen eggs have been identified as the main source of S. enteritidis, which can cause severe gastrointestinal illnesses and sometimes death in humans, especially among children and the infirm (Altekruse and Swerdlow 1996). Worldwide, between 1979 and 1987, S. enteritidis infections increased significantly in 24 of the 35 countries reporting to the World Health Organization (Altekruse and Swerdlow 1996). Malnutrition, which includes inadequate intake of calories, protein, and numerous essential vitamins and minerals, is a major disease related to environmental degradation. Malnutrition prevails in regions in which the overall food supply is inadequate, where populations lack economic resources to purchase food, and where political unrest and instability interrupt food supplies. In addition, rapidly expanding human populations intensify the food-supply problems by diminishing the per capita availability of cropland (Pimentel and Pimentel 1996). In 1950, 500 million people (20% of the world population) were considered malnourished (Grigg 1993). Today more than 3 billion people (one-half of the world population) suffer from malnutrition (WHO 1996e), the largest number and the highest rate in history. Each year, between 6 and 14 million people die from malnutrition (Murray and Lopez 1996). Malnutrition problems are also on the increase in the United States, especially among the poor. In many parts of the world, especially in developing countries, severe shortages of vitamin A cause blindness and death. For example, in the Sahelian region, as well as in west and east Africa, per capita consumption of vitamin A has been declining during the past 10-20 years, while associated serious eye problems have been increasing (ACC/SCN 1992). Worldwide, approximately 258 million children are vitamin A deficient (WHO 1996e). Each year, vitamin A deficiency causes approximately 2 million deaths and 3 million serious eye problems, including blindness (Murray and Lopez 1996). Similarly, iron intake per person has been declining during the past 10-30 years, especially in subSaharan Africa, south Asia, China, and South America, because of inadequate nutrition resulting from overall shortages of food (ACC/SCN 1992). Globally, more than 2 billion people are iron deficient, and the problem is severe enough that 2 billion people suffer from anemia (WHO 1996e). Worldwide, an estimated 20% of malnutrition deaths can be attributed to anemia (Murray and Lopez 1996). In addition, approximately 1.6 billion people live in iodine-deficient environments and suffer from iodine-deficiency disease (WHO 1996e). Malnutrition, complicated by parasitic infections, is frequently found in poverty-stricken areas with inadequate sanitation. Malnourished individuals, especially children, are seriously affected by parasitic infections because these infections can reduce nutrient availability. The presence of intestinal parasites frequently diminishes appetite and food intake. Their presence also increases the loss of nutrients by causing diarrhea and dysentery. Hookworms, for instance, can suck as much as 30 mL of blood from an infected person each day, gradually weakening individuals and lowering their resistance to other diseases (Hotez and Pritchard 1995). Because an estimated 5-20% of an individual's daily food intake is used to offset the effects of parasitic illnesses, the overall nutritional status of a parasite-infected person is greatly diminished over time (Pimentel and Pimentel 1996). Drug resistance in microbes Drug resistance and rapid changes in microbes contribute to global disease outbreaks, diminishing the ability to successfully control the illnesses they cause (Daily and Ehrlich 1996, Grady 1996). At least 11 major microbes, including Streptococcus spp., Staphylococcus spp., Shigella spp., enterobacteriaceae, and enterococci, have already become highly resistant to standard antibiotic treatment. The evolution of drug resistance in microbes can be surprisingly rapid. In 1979, only 6% of European pneumococcus strains were resistant to penicillin, but one decade later that percentage had grown to 44% (Platt 1996). Currently, in the United States, more than 90% of the strains of Staphylococcus aureus, one of the most common disease-producing microbes, are resistant to penicillin and similar previously effective antibiotics (ASM 1994). South African studies indicate that 40% of the invasive Streptococcus pneumoniae acquired in the community and 95% of the isolates acquired in hospitals are now resistant to penicillin (WHO 1996c). Rapid increase in drug resistance by disease organisms is caused by the widespread and overuse of more than 300 antibiotics by the medical profession (ASM 1994). In addition, one-half of the antibiotics used in the United States to treat humans are also used to treat disease-infected domestic animals (ASM 1994). The concurrent use of antibiotics for both humans and livestock enhances selection for drug-resistant microbes, further exacerbating the problem of antibiotic resistance. Re-emerging diseases The spread of new strains of E. coli is due in part to the rapidly expanding human population, especially in areas where humans are crowded and where water and food contamination are rampant (Table 2; Iseki 1994, Daily and Ehrlich 1996, Grady 1996). Table 2. New and re-emerging infectious diseases in humans since 1976.a Disease Year of emergence and reemergence Country AIDS 1975 Africa Legionnaires disease 1976 United States Cryptosporidiosis 1976 United States Ebola haemorrhagic fever 1976 Zaire Hantavirus 1977 Republic of Korea Creutzfeldt-Jakob disease (CJD) 1979 United Kingdom, Canada Human T-cell lymphotropic virus 1 1980 Japan Hepatitis D 1980 Italy Escherichia coli O157:H7 1982 United States New variant of CJD (related to mad cow disease) 1986 United Kingdom Salmonella enteritidis PT-4 1988 United Kingdom Hepatitis C 1989 United States Venezuelan haemorrhagic fever 1991 Venezuela Brazilian haemorrhagic fever 1994 Brazil Vibrio cholerae 1992 India Human and equine morbillivirus 1994 Australia a WHO 1996f, Stratton et al. 1997. The worldwide increase in TB also results from population crowding and drug resistance (WHO 1996f). Currently, an estimated 1.7 billion people worldwide are infected with TB, with approximately 95 % of TB deaths occurring in developing countries. In 1990, the number of new TB infections was 7.5 million; by 1995, new infections numbered 8.9 million; and by 2000, a total of 10.2 million new cases are expected (Lederberg et al. 1992, WHO 1996f). TB deaths per year have been estimated at 2.5 million in 1990 and 3.0 million in 1995 and are projected to rise to 3.5 million by 2000 (WHO 1996f). At present, TB kills more people each year than any other infectious disease in the world (WHO 1996f). Patterns of TB infection in the United States are similar to the world situation, in which TB cases increased by approximately 18% from 1985 to 1991 (USC 1993). Currently, approximately 37,000 new infections occur each year, up from approximately 23,000 in 1985 (USC 1993). Drug-resistant TB strains and reduced medical treatment account for this increase. TB treatment is further complicated by the use of illegal drugs and the rise in HIV infections, both of which help to spread the disease and lead to frequent reinfection (USC 1993). Filoviruses are another re-emerging pathogenic disease. These viruses -- of which there are two groups, Ebola and Marburg -- cause a severe, usually fatal hemorrhagic disease in humans. Outbreaks of Ebola hemorrhagic fever have resulted in over 1000 reported cases (Clegg and Lloyd 1995). In addition, over 40 cases of Marburg have been reported. Their rapid spread and the high mortality they cause make filoviruses a major public health concern. In reported outbreaks, 50-90% of the cases have been fatal (Clegg and Lloyd 1995). Increased international commerce and travel, limited experience in diagnosis and case management, importation of nonhuman primates, and the potential of filoviruses to evolve rapidly add to health threats and make curtailment difficult (McMichael 1993, Morse 1997). Brucellosis is another resurgent communicable disease. The causative bacteria, Brucella spp., infect cattle, sheep, goats, and some wild mammals worldwide and are harbored in the animal's udder. Humans usually contract the disease from infected animals or contaminated dairy products. The World Health Organization reports that the number of cases of brucellosis is increasing, especially in developing areas of the Mediterranean regions, the Middle East, western Asia, and parts of Africa and Latin America (WHO 1997b). Currently, in just six countries of the Middle East, the number of reported cases is 90,000 per year (WHO 1993b). Human plague is also on the rise. The plague parasite, Yersinia pestis, is transmitted by human contacts and interactions with rodents (WHO 1996b). In the 1980s, reported cases in the world numbered 1327; in 1993, they numbered 2194; and in 1994, they numbered 2935 (WHO 1996b). Most (nearly 60%) of the reported cases occurred in Africa. Diphtheria, which had been under control for many years, exploded in Russia after the breakup of the former Soviet Union. In 1975, only approximately 100 cases were recorded in Russia; by 1990, that number had increased to 1000, and in 1995, 51,000 new cases were reported (WHO 1996d). The explosion in diphtheria in Russia is attributed to a decline in the effectiveness of the public health program. Newly emerging diseases Changes in ecosystem biological diversity, evolution of parasites, and invasion by exotic species all frequently result in disease outbreaks. Several new and emerging diseases are listed in Table 2. For example, coccidioidomycosis fungal infections caused by Coccidioides immitis have exploded in California. The number of cases increased from approximately 500 in 1990 to nearly 5000 in 1992 (CDC 1994). With few known effective controls, this disease is expected to continue to spread in the future (CDC 1994). An emerging rodent-related disease that is related in part to increasing human numbers is the hantavirus pulmonary syndrome, which was first identified in 1993 in the United States and Canada (CDC 1994). By the end of 1995, 135 cases of hantavirus pulmonary syndrome were recognized in the United States and Canada, with a human mortality rate of 50% (CDC 1994). The disease, which has experienced a resurgence in the United States in 1998 due in part to increased rainfall associated with El Niño, has also been reported in several other countries, including Argentina. In the United States, Lyme disease is the most widespread vector-borne disease, with infections reported in 47 states. The bacterium that causes Lyme disease, Borrelia burgdorferi, is a spirochete similar to the one that causes syphilis in humans (WHO 1996f). It is thought to have existed naturally in the United States without incident until major ecological changes began occurring in the twentieth century, when suburban areas expanded along with white-tailed deer populations (e.g., from 2000 in s 1945 in Massachusetts to 9500 in e 1990; Spielman et al. 1993). Abundant rodent Peromyscus leucopus and deer tick Ixodes dammini (or a Ixodes capularius) populations enabled the Lyme disease organism to spread rapidly. Dramatically expanding since the initial description of the disease in 1976, Lyme disease now infects nearly 12,700 people in the United States each year and the incidence continues to grow (Table 3; CEQ 1997). Lyme disease is also an increasing problem in Europe and Asia, with more than 30,000 cases recently reported in Germany (Lederberg et al. 1992). Table 3. Disease fatalities in the United States. Disease 1970 1980 1992 AIDSa 0 199b 40,674c Aseptic meningitisa 6480 8028 12,223 Botulisma 12 89 91 Cancer 163,000 185,000 205,000 Hepatitis Bd 8310 19,015 26,000e Legioneosisa Not available 830e 1339 Lyme diseasea Not available 100f 12,669g Salmonellosisa 22,000 33,700 42,900 Shigellosisa 13,800 19,000 23,900 Syphilisa 91,000 69,000 113,000 a USBC 1996. USBC 1987. c CDC 1997. d CDC 1989. (For 1987, the number of cases was approximately 26,000.) e For 1985. f Estimated infections in 1976. g CEQ 1997. b Another rapidly increasing disease is AIDS, which is caused by HIV (Table 2). The growing human population, especially the increased number of people in urban areas, has fostered the spread of HIV and AIDS. It is estimated that in 1970, only 10,000 people were infected with HIV, but at present approximately 23 million are infected with HIV (WHO 1997a). The total number of AIDS cases is reported to be 6 million (WHO 1996a), with an estimated 1 million deaths per year (Murray and Lopez 1996). Approximately 30-50 million people are projected to become HIV positive by the year 2000 (McMichael 1993, WHO 1995). HIV infections are especially widespread in certain parts of the world (Mertens and Low-Beer 1996). For example, in Thailand the prevalence of HIV infections in males increased from 1% to 40% between 1988 and 1992 (Mueller 1993). In 1996, approximately 46,000 Indians out of 2.8 million (1.6 % of the population) tested were found to be infected with HIV (Burns 1996). By the year 2000, more than 10 million Indians, the largest number of any population in the world, will be infected (Burns 1996). In the United States, deaths from AIDS are increasing rapidly, from an estimated 199 deaths in 1980 to 40,674 in 1992 (Table 3; USBC 1987, CDC 1997). Although new HIV infections in homosexual men have started to decline, infections continue to rise in drug users. Conclusion The prevalence of human diseases is increasing rapidly worldwide, as is the number of deaths from diseases. The ecology of increased disease is exceedingly complex because of the diversity of infectious organisms and the effects of environmental degradation on the prevalence of disease. The rapid expansion of human populations is a major factor in the rise of human diseases: Humans living in crowded, urban areas are in an ecosystem that is ideal for the resurgence and rapid spread of old diseases as well as for the development and spread of new diseases. The unprecedented increase in air, water, and soil pollutants, including organic and chemical wastes, further stresses humans and increases disease prevalence. In particular, widespread malnutrition enhances the susceptibility of humans to infectious pathogens and other diseases. In addition, global climate changes are improving the environment for some diseases and disease vectors. Climate changes may also increase the susceptibility of food crops to some pests, which, in turn, could intensify food shortages and malnutrition. A concurrent problem is the rapid expansion in the number of "environmental refugees" (Myers 1993). These people, living in poverty and desperate for food, flee their home areas in a search for survival. Their malnutrition, stress, and dislocation foster the resurgence of old diseases and the development of new ones. This analysis confirms that many factors influence the increased prevalence of human diseases now occurring worldwide. Currently, 40% of deaths result from diverse environmental factors, including chemical pollutants, tobacco, and malnutrition. The growth in diseases is expected to continue, and according to Murray and Lopez (1996), disease prevalence is projected to increase 77% during the period from 1990 to 2020. Infectious diseases, which cause 37% of all deaths throughout the world, are also expected to rise. Deaths in the United States from infectious diseases increased 58% between 1980 and 1992, and this trend is projected to continue. To prevent diseases, poverty, and malnutrition from worsening, the growing imbalance between the escalating human population and the earth's environmental resources must be dealt with. The crowding of people into urban areas; the movement of populations into new environments; the increased use of chemicals that pollute soils, water, and air; the misuse of antibiotics, leading to resistance in disease microbes; and growing malnutrition all contribute to the worldwide increase of human diseases. Thus, comprehensive, fair population-control policies combined with effective environmental management programs are required. Without international cooperative efforts, disease prevalence will continue its rapid rise throughout the world and will diminish the quality of life for all humans. Acknowledgments We thank the following people for reading an earlier draft of this article and for their many helpful suggestions: M. Coluzzi, World Health Organization, Rome; D. W. T. Crompton, University. of Glasgow; P. Epstein, Harvard Medical School; A. R. B. Ferguson, Optimum Population Program, Oxon, UK: G. P. Georghiou, University of California-Riverside; D. Gubler, Centers for Disease Control, Fort Collins, Colorado; A. Haines, Royal Free Hospital School of Medicine, London: P. J. Hotez, Yale University School of Medicine: R. T. Johnson, Johns Hopkins .School of Medicine; V. W. Kimani, Pest Control Products Board, Nairobi. Kenya; J. Mackay, Asian Consultancy on Tobacco Control, Hong Kong: A. J. McMichael, London School of Hygiene and Tropical Medicine; N. Myers, Oxford University; D. M. 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