A framework for the integration of ecosystem and human health
in public policy: two case studies with infectious agents $ Hillel S. Koren ,1 and Douglas Crawford-Brown Carolina Environmental Program, University of North Carolina at Chapel Hill, CB# 1105, 208 Miller Hall, Chapel Hill, NC 2759-1105, USA Received 5 March 2003; received in revised form 4 June 2003; accepted 24 June 2003 Abstract Despite that a signicant body of published literature exists in the complex area of interconnection among the environment, ecosystems, and human activity, relatively little attention has been paid to the integration and analysis of ecological and human health data in the form of a conceptual model. Human and ecological health protection generally have been treated as separate domains of policy, with signicant differences in both the analytic methods used to characterize risks and the policies developed for risk reduction. Understanding the relationships among population growth, development, natural resource use, the environment, human health, and ecosystems is an important area of both scientic inquiry and environmental policy. The present paper focuses on the development of a conceptual model for understanding disease causation, particularly infectious disease, and the implications of such a model for public policy. The conceptual model incorporates ecological and human health risk assessment information applied to case studies of two infectious diseases. This article takes an initial step toward formalizing the conceptual model so that research and assessment procedures can be developed. Published by Elsevier Inc. Keywords: Interconnections; Ecology; Human health; Public policy; Risk assessment 1. Introduction The interconnection among the environment, ecosys- tems, and human activity is a complex and poorly understood phenomenon and has been the subject of numerous publications and meetings (Aron and Patz, 2001; DiGulio and Benson, 2002; DiGulio and Monosson, 1996; Fisher, 2001). Local, regional, and global environmental changes, traceable to popula- tion growth and development patterns, as well as human activities that move populations within geographic re- gions, have led to increasing use of natural resources and degradation of ecosystems. This is particularly proble- matic when those ecosystems perform natural services (Daily, 1997), such as purication of environmental media and control of the spread of infectious disease. It is becoming increasingly obvious that numerous issues that were previously thought of as independent of the environment are intimately connected to it. Human health, the economy, social justice, ecological processes, and national security all have important environmental aspects the magnitude and interconnections of which are not generally reected in public policy. A system of public policy with two dening char- acteristics has evolved. First, human and ecological health protection generally have been treated as separate domains of policy, with signicant differences in both the analytic methods used to characterize risks and the policies developed for risk reduction. Second, individual human health risks (e.g., of malaria, schistosomiasis, or cholera) have been analyzed in isolation. The objective of risk assessment is to support decision making by assessing risks of adverse effects on human health and the environment from chemicals, physical factors, and other environmental stresses. For practical reasons, the ARTICLE IN PRESS $ The research described in this article has been reviewed by the National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, and approved for publication. Approval does not signify that the contents necessarily reect the views and policies of the Agency, nor does mention of trade or commercial products constitute endorsement or recommendation for use.
Corresponding author. Fax: +919-843-3113.
E-mail address: koren@unc.edu (H.S. Koren). 1 HSK is on an IPA assignment from the US EPA/ORD/NHEERL to the Carolina Environmental Program at the University of North Carolina at Chapel Hill, NC. 0013-9351/$ - see front matter Published by Elsevier Inc. doi:10.1016/S0013-9351(03)00137-3 methodologies for human health and ecological risk assessment developed independently. However, with increased recognition of the need to more effectively protect both humans and the environment, it is time to consider a move to a more integrated, holistic approach to risk assessment. The recent WHO report on Integrated Risk Assessment (WHO, 2001b) lists ve major advantages to the integration of health and ecological assessments: 1.1. Coherent expression of assessment results Integrated health and ecological risk assessments provide a strong basis for action to support decision making. 1.2. Interdependence Ecological and human health risks are interdependent (Lubchenco, 1998; Wilson, 1998). Assessments that do not integrate health and ecological risks are likely to miss important modes of action that involve interactions between effects on the environment and effects on humans. 1.3. Sentinel organisms Nonhuman organisms can serve as sentinels, suggest- ing potential sources of human hazards (Burkhart and Gardner, 1997; NRC, 1991; Shefeld et al., 1998). 1.4. Quality The scientic quality of assessments is improved through the sharing of information and techniques between assessment scientists in different elds. 1.5. Efciency Integration of human health and ecological risk assessments offers signicant increases in efciency. In fact, isolated assessments are inherently incomplete when both humans and ecological systems are poten- tially at risk. Antagonistic or synergistic interactions between effects generally also have not been considered, as well as the separate risks to health and economic well-being. This is despite appreciable evidence that economic well- being is related to health (Graham and Wiener, 1995). Faced with a large number of such effects, however, the most effective public policies might be those that focus on common, or root, causes rather than on proximate causes. These policies would also treat the process of diseases as a problem of systems analysis, more common perspective in ecological analysis than in human health risk analysis. By focusing on common causes and systems behavior, risk reduction across a large class of human health, ecological, economic, and other effects can be produced. It is useful to consider here what we mean by root cause. Risks (both human and ecological) arise from the conuence of the four causal factors shown in Table 1 [see e.g., Tesh (1988)]. The present paper focuses on the development of a conceptual model for understanding disease causation, ARTICLE IN PRESS Table 1 Four causal factors of human and ecological risk Risk agent or stressor This might be a particular chemical, microbe, or other form of stress such as temperature. The cause of the disease is explained in terms of the properties of the stressor. For example, the cause of malaria is the plasmodium protozoan. Organism This includes the biological properties of the organism exposed to the risk agent or stressor. The cause of the disease is explained in terms of these properties, each of which is crucial in determining both the kind of health effects and their magnitudes from a given stressor. For example, the cause of malaria is the inability of the organisms biological defenses to combat the parasite and its waste products, which induce fever episodes in the organism. Environmental or ecological structure This reects the structure of the ecosystem, including the system of compartments for environmental media, which allows the stressor to come into contact with the organism. The cause of the disease is explained in terms of the interconnections and spatial and temporal relationships that exist in organized environmental and ecological systems due in part to patterns of human development and consumption. For example, the cause of malaria is the existence of stagnant water, allowing the expansion of a population of mosquitoes, the location of human settlements within the range of these mosquitoes, and the eld of exposure produced by the movement of those mosquitoes through the air. In most diseases poverty and poor sanitation and living conditions (lifestyle/activity patterns) are part of the cause. Lifestyle or activity patterns This reects the ways in which human populations and other species move throughout a eld of exposure. The cause of the disease then lays in this pattern of movement, which in turn inuences the temporal pattern of exposure to the risk agent through the environmental media and other species. For the case of malaria, the lifestyle aspect of causation includes the activities that bring people close to the edge of water supplies containing infected mosquitoes and their sanitary practices. Based on Tesh (1988). H.S. Koren, D. Crawford-Brown / Environmental Research 95 (2004) 92105 93 particularly infectious disease, and the implications of such a model for public policy. The conceptual model incorporates ecological and human health risk assess- ment information by all four causes of disease. The importance of studying the ecology of infectious disease was recently underscored by National Research Council (NRC) Committee on Grand Challenges in Environ- mental Sciences. The committee recommended four high-priority research areas with implications for the next generation and that need immediate attention (NRC, 2001): (1) biological diversity and ecosystem functioning; (2) hydrologic forecasting; (3) infectious disease and the environment; and (4) land-use dynamics. Our paper addresses solely the infectious disease topic mentioned above. The NRC committee recommended developing a comprehensive ecological and evolution- ary understanding of infectious diseases affecting human, plant, and animal health. The conceptual model developed in the present paper seeks to integrate at least the rst, third, and fourth areas above. This model is then applied to case studies of two infectious diseases. The paper takes an initial step toward formalizing the conceptual model so that research and assessment procedures can be developed. The rationale for developing the conceptual model is shown in Table 2. 2. What will the conceptual model not address? We have chosen to focus specically on issues related to the spread of infectious disease, particularly on those aspects that integrate human and ecosystem risk assessment. We will not focus, therefore, on other factors, listed below in Table 3, that have been addressed extensively elsewhere. This is not to say that the conceptual framework cannot incorporate these factors, only that their inuence within the framework is not formally reected in the following discussion. 3. The case for using infectious disease as a health endpoint for studying the consequences of ecosystem perturbation Ecosystem services include such vital functions as regulating the concentration of oxygen and carbon dioxide, ltering pollutants from drinking water, and reducing the virulence of microbes (Daily, 1997). In a recent review on the environment and health Chivian (2001) commented on ecosystem services: One critically important service is the role ecosystems play in controlling the emergence and spread of infectious disease by maintaining equilibria between predators and prey, and among hosts, vectors and parasites in plants, animals, and humans, as well as by controlling the virulence of microbes. The protective function of biodiversity has only begun to be appreciated (McMichael, 2001; Morse, 1995; Anderson et al., 2000). A large number of new or newly discovered infectious diseases has been recorded in the past 25 years, including rotavirus, cryptosporidiosis, legio- nellosis, the Ebola virus, hepatitis C, HIV/AIDS, hantavirus pulmonary syndrome, and others (Morse, 1995). Rapid urbanization is expanding the traditional roles of cities as gateways to infections. Population movement from rural areas into cities, and the resulting amplied urbanrural and interurban contacts, is open- ing new vistas of possibility to otherwise marginal microbes. Infectious disease patterns are also increas- ingly being affected by the intensication of food production and processing methods. It is becoming clear that large-scale human interventions in the natural environment often, and usually adversely, affect natural services performed by ecosystems, leading to changes in infectious disease patterns. 4. Elements of human health risk and ecological assessments The challenge facing the development of a common modeling and policy framework for infectious disease is the challenge of integrating what are often two different perspectives on scientic study of disease processes. The traditional conceptual model of human health risk ARTICLE IN PRESS Table 2 Rationale for developing a conceptual model Illustrate basic concepts for a general audience. Give the broad context within which an assessment is conducted. Provide a basis for discussion and debate regarding assessment scope. Serve as a means to track data collection and analysis efforts. Provide a powerful communication tool. Based on WHO (2001a). Table 3 Factors not to be included in the conceptual model Natural stressors (e.g., lighting and res, volcanic eruptions, droughts, earthquakes, etc.) and their consequences. Economic or social science issues, despite the fact that these are clearly critical factors in any public policy. Direct effects of pollutants or chemicals on human health without the need to rst perturb an ecosystem (e.g., national ambient air quality standards). Stressors that affect only ecosystem health but not human health (e.g., turbidity in water affects systems by limiting light requirements for survival). Cases where a stressor will pass unaffected through an ecosystem even though it may eventually cause health effects in humans (e.g., when shellsh that have various levels of fecal coliform are healthy but toxic to humans). H.S. Koren, D. Crawford-Brown / Environmental Research 95 (2004) 92105 94 assessment, which has traditionally focused on chemical risk, is shown in Fig. 1 (NRC, 1994). In that model, a source of a risk agent is characterized by a source term and location in space. This source term is into one or more specic environmental media, followed by disper- sion and transformation of the risk agent through the system of compartments. This produces a four-dimen- sional (three dimensions of space and one of time) eld of concentration in each environmental medium, char- acterized by some functions C i x; y; z; t: Here, C i refers to the concentration of the risk agent in environmental medium i; (x; y; z) are the three spatial coordinates, and t is time. A human population conducts activities that bring the population in contact with the environmental media and, hence, the risk agent; these activities may be formalized as a function F A x; y; z; which is the fraction of time an individual spends at spatial location (x; y; z) conducting some activity A: The result is an exposure, Et; which varies between individuals due to their different spatial locations and activity patterns. This exposure results in intake, uptake, retention, etc., in the human body, producing a dose, Dt: Finally, this dose is related to the probability and/or severity of effect through a specic doseresponse function, PDt; where P is the probability (or severity) of the effect given that the individual has a temporal pattern of dose, Dt; over a lifetime. To the extent that there is consideration of nonlinear aspects in such models, they are embedded in possible feedback loops such as the excretion of the risk agent back into the environment as humans develop disease, as shown in the dashed line of Fig. 1. The nonlinear aspects of the model appear as a result of the feedback loops. For the most part, however, human health risk assessment proceeds in the linear fashion shown as the solid lines in Fig. 1 (NRC, 1994). This linearity limits the applicability of such models for the cases explored in the present paper. This limitation, however, is accom- panied by a strength of human health risk assessment: the ability to perform detailed quantitative calculations of the relationship between the source term and the probability and/or severity of disease. Human health risk assessments, therefore, while limited in scope, nonetheless provide a quantitative modeling framework for predicting the effect of policies on the incidence and/or severity of disease. Therefore, these models are simple and cost effective. By contrast, ecological risk assessment has proceeded by rst dening the ecosystem to be considered and then dening functional endpoints for the ecosystem (e.g., primary productivity, or ecosystem diversity). Eco- logical risk assessment has traditionally been less reliant on quantitative models of the spread of risk agents through organized systems of compartments (US EPA, 1994, 1998; WHO, 2001a, b). The next step has been to dene stressors (e.g., temperature or habitat fragmenta- tion) that may play a causal role in affecting those endpoints. Finally, the magnitude of the resulting change in the functional endpoint has been estimated through empirical relationships between the stressor and the endpoint. This is shown in Fig. 2. There are several important distinctions in the conceptual models developed for risk assessment in human health (Fig. 1) and ecosystems (Fig. 2). First, the ARTICLE IN PRESS Source Term Dispersion and Transformation Concentration Field Dose Exposure Effect Fig. 1. The conceptual model typically employed in human health risk assessment (NRC, 1994; WHO, 2001b). Human Material and Energy Use Production of Stressors on Ecosystems Perturbation and Degradation of Natural Services Change in Fitness of Populations and Ecosystems Alteration of Earth System Processes Fig. 2. The conceptual model typically employed in ecological risk assessment (US EPA, 1994). H.S. Koren, D. Crawford-Brown / Environmental Research 95 (2004) 92105 95 models of human health tend to be more linear, in the sense that feedback loops are less likely to be considered. Second, the models in human health tend to be signicantly more rooted in principles of molecular processes and focused on individuals, while those for ecosystems tend to focus on populations and communities. Finally, the connections between boxes (shown as arrows) tend to be much more formal for human health. The arrows in Fig. 1 are specic mathematical opera- tions, such as dispersion models, pharmacokinetic models, and doseresponse models. By contrast, the arrows in Fig. 2 are more conceptual, denoting that there is a causal relationship between the boxes, but with little specicity regarding the mathematical form of that relationship. Therefore, our approach in this paper has been to integrate analysis frameworks that create a conceptual model for better understanding causation, particularly of infectious disease, and the implications of such a model for public policy (Fig. 3). The key to Fig. 3 is as follows: (A) Human activity. The model employed here begins with the four categories of human activity, each of which involves material and energy use and, therefore, inuences both source terms into environmental media and the spatial relationship between components of the ecosystems and human populations. These four Source Terms are ST ind ; ST comm ; ST tran ; and ST res for indus- trial/agricultural, commercial, transportation, and resi- dential activities, respectively. In each case, the units are those of loading (e.g., coliform fecal units per day, grams per day, etc.). (B) Stressors. The human activities produce anthro- pogenic stressors capable of perturbing the environ- mental system; the box simply indicates that the stressors may be in the form of either source terms (C) or changes in spatial relationships (D). (C) Source terms. One aspect of stressors is the production of pollutants, represented here by the total source term released into the environmental media. It is the sum of the source terms from the four categories of human activity (in A), with separate source terms for air (ST A ), water (ST W ), soil (ST S ), and ecosystem (ST E ). The source terms for air, water, soil and ecosystem are divided into the compartments of atmosphere, hydro- sphere, lithosphere, and ecosystem, respectively, in E; the arrow in this case connecting DE represents the rate of ow of the risk agent (e.g., the loading) into the environmental system (E). For example, ST A may be calculated from (ST ind F ind,A +ST comm F comm,A + ST tran F tran,A +ST res F res,A ), where ST j is the source term from activity category j and F j;i is the fraction of the source term from activity j released into compart- ment i (here, i is air). (D) Spatial changes. Another aspect of stressors is the change in spatial relationships between components of the ecosystems, including humans, due to land-use aspects of the four activities, such as urban sprawl. An example is shown in Fig. 4. The relevant mathematical formulations here are the areal densities, D k x; y; t for all species k in the study region. For example, the species might be deer ticks, and the metric for D ticks x; y; t might be ticks per hectare. The arrow in this case connecting DE represents the alteration of the spatial relationships in the environmental system (E). (E) The environmental system. The source term interacts with the environmental system to produce the movement and dispersion of the risk agent through environmental media, consisting of the hydrosphere, atmosphere, lithosphere, and biosphere; it also repre- sents the interactions of organisms in the ecosystem (producers, consumers, and decomposers) that result in the tness of that ecosystem. (E.1) Air, water, and soil. One aspect of dispersion in the system is through the nonbiological components, in which humans are exposed through direct contact with those media. Arrows between the media indicate transfer of the risk agent from one medium to another. The movement is described through dispersion models summarized here by a dispersion coefcient DC ij x; y; z; t; where i represents the medium or compartment into which the dispersion occurs when the source term is in medium or compartment j: For example, DC AW x; y; z; t is the dispersion coefcient into the air when the source term is into the water. (E.2) Biota. The biological components of the ecosystem are divided here into the functional categories of producers, consumers, and decomposers. Interest is in the transfer of the risk agent between biota, rather than a process of dispersion. Arrows between these functional categories indicate transfer of the risk agent (e.g., infectious agent) between organisms at each of these levels, or predatorprey relationships that affect the population dynamics. (F) Concentration. The processes of dispersion in the environmental media and the presence of biota carrying the risk agent produce a four-dimensional eld of concentration of the risk in the environmental system; this includes the concentration in water, C W x; y; z; t; air, C A x; y; z; t; soil, C S x; y; z; t; and ecosystem species serving as food, C F x; y; z; t; as well as the density of vectors for the risk agent, such as mosquitoes or deer, D V x; y; t: The concentration in a given environmental medium is calculated in the form C i x; y; z; t ST A DC iA x; y; z; t ST W DC iW x; y; z; t ST S DC iS x; y; z; t ST E DC iE x; y; z; t: (G) Exposure. The concentration eld then interacts with the eld of movement of people through space to ARTICLE IN PRESS H.S. Koren, D. Crawford-Brown / Environmental Research 95 (2004) 92105 96 produce the exposure, Et; of the human population to the risk agent, which is a function of both the concentration eld C i x; y; z; t and the activities that bring the human population into contact with the concentration eld, such as urban sprawl, reforestation, or suburbanization. The arrow from A to G represents the inuence of the four categories of activities on the movement of people spatially through the exposure eld. The exposure in this case is summarized by the average daily rate of intake and is calculated for an individual from Et SC i x; y; z; t FT i x; y; z; t IR i x; y; z; t=BWt; ARTICLE IN PRESS Atmosphere Producers Consumers Lithosphere Decomposers Hydrosphere Transportation Activities Industrial and Agricultural Activities Commercial Activities Residential Activities Spatial Development Source Term into media Illness Asymptomatic Excretion Source Term A C D Biosphere Environmental System E E1 E2 Concentration Field Exposure Field Infection F G H I J K L Recovery B Fig. 3. The conceptual model proposed here for integrating human health with ecosystem assessment for infectious disease. H.S. Koren, D. Crawford-Brown / Environmental Research 95 (2004) 92105 97 where FT i x; y; z; t is the fraction of time an individual is connected to environmental medium i at spatial location (x; y; z) (e.g., through ingesting water at that location); IR i x; y; z; t is the intake rate of that medium (or the dermal permeability coefcient in the case of dermal absorption); and BWt is the body weight. The summation is over all environmental media (air, water, soil, and food). In addition, there is spread of the risk agent through direct contact with species in the ecosystem. For this component, Et is calculated as Et SD V x; y; t FTx; y; z; t CRx; y; z; t TCt; where D V x; y; t is as dened in item F above; FTx; y; z; t is the fraction of time an individual spends at spatial location (x; y; z); CRx; y; z; t is a contact rate coefcient between an individual and the vector (units of contacts per unit time per unit areal density of the vector); and TCt is a transmission coefcient (units of amount of risk agent per contact). The summation is over all vectors for the risk agent. (H) Infection. Exposure can in turn result in infection of the human population by the microbe (WHO, 2001a, b). In this model, it is assumed that the probability of infection per unit time is a function of (i) the exposure rate (from item G), (ii) the virulence of the microbe, and (iii) the susceptibility or sensitivity of the body to infection by this agent. These factors are summarized here as P inf;exp ; which is the probability of infection per unit exposure to the microbe. The probability of infection per unit time, PR inf t; then equals: PR inf t Et P inf;exp : (I) Illness. Infection is followed by illness in suscep- tible individuals in the population. In this model, it is assumed that the probability of illness is given by a conditional probability of illness given infection, P ill;inf ; which in turn is a function of the sensitivity or immune status of the person. The probability of new illness per unit time, PR ill t; then equals PR ill t PR inf t P ill;inf : The arrow from I to A indicates that illness may in turn inuence human activities (e.g., causing greater time spent indoors). (J) Asymptomatic infection. Some individuals in the population will be infected but asymptomatic, reducing the probability of treatment. In this model, it is assumed that the probability of being infected but asymptomatic is given by a conditional probability of no illness with given infection, P notill;inf ; which in turn is a function of the sensitivity or immune status of the person. In terms of calculation, the probability of asymptomatic infection at any moment in time equals the difference between the number of infected individuals (calculated in item H) minus the number of infected and symptomatic indivi- duals (calculated in item I). (K) Excretion. Both infected/symptomatic and in- fected/asymptomatic individuals may excrete the risk agent back into the environmental system, producing an additional source term indicated by the arrow from K to E. The excretion source term, ESTt ; with units of microbes per day, is calculated from ESTt N P ill t PCEST ill t P asy t PCEST asy t; where N is the total population size; P ill t is the probability of illness from item I; PCEST ill t is the per capita excretion rate (microbes per unit time) for people with symptoms; P asy t is the probability of being asymptomatic but infected from item J; and PCEST asy t is the per capita excretion rate (microbes per unit time) for people who are infected but asymptomatic. Note that ESTt then is added to the ARTICLE IN PRESS Fig. 4. The change in land use in a 100-km 2 area of the Research Triangle Metropolitan Area (NC, USA). The pattern on the left is in 1988; the pattern on the right is in 2000. Black grids are forested, containing a habitat for deer. Grey grids are residential. White grids are agricultural. The two habitat areas in 1988 had been fragmented into ve habitat areas as of 2000. The total habitat area in 2000 had been reduced by approximately 65% from the 1988 value. H.S. Koren, D. Crawford-Brown / Environmental Research 95 (2004) 92105 98 source term from item B, allocated between the compartments as described in that item. (L) Recovery. In this model, it is assumed that the probability of recovery is given by a conditional probability of recovery from the given illness, P rec;ill ; which in turn is a function of the sensitivity or immune status of the person. The probability of recovery per unit time, PR rec t; then equals PR rec t PR ill t P rec;ill : 5. Case studies We turn now to two case studies to examine how the conceptual model might be applied both in improved quantitative assessment of the spread of infectious disease and in the design of policies to reduce that spread. 5.1. Case study no. 1: Lyme disease in areas of reforestation and suburbanization 5.1.1. The problem: denition and background Lyme disease provides an example of a disease that is dependent on vector and host populations as well as having certain ecological conditions that may be used to predict habitats at risk for disease outbreak. Therefore, this is a very complex disease that will be discussed here only briey in a simplied manner. Lyme disease was named in 1977 when arthritis was observed in a cluster of children in and around Lyme, Connecticut. Other clinical symptoms and environmental conditions sug- gested that this was an infectious disease probably transmitted by an arthropod. Further investigation revealed that Lyme disease is caused by the bacterium (spirochete) Borrelia burgdorferi. These bacteria are transmitted to humans by the bite of infected ticks (using deer and mice and other animals as hosts or as a feeding ground) and cause more than 16,000 infec- tions in the United States each year. White-legged ticks (Ixodes scapularis) are the vectors responsible for transmitting Lyme disease bacteria to humans in the northeastern and north-central United States. On the Pacic Coast, the bacteria are transmitted to humans by the western black-legged tick. Ixodes ticks are much smaller than common dog and cattle ticks (CDC Lyme disease homepage, URL http://www.cdc.gov/ncidod/ dvbid/lyme/index.htm). Ticks have three postegg life stages, larva, nymph, and adult, which are very small and nearly undetectable. Each of these stages takes a single blood meal from the host, which can last anywhere from several days to a week. After feeding, the tick drops off the host and either molts into the next stage or, in the case of the adult, reproduces and dies. Typically, various small mammals are fed upon by larvae and nymphs, while white-tailed deer and other large mammals serve as hosts to adult ticks. White- footed mice serve as the main reservoir for B. burgdorferi. Larvae or nymphs may acquire infection with the bacterial agent of Lyme disease, which then can be transmitted during subsequent blood feeding by nymphs or adults. Nymphs are considered the main agent for human disease transmission because of their small size. Ostfeld (1997) identied that the number of acorns serves as an important indicator of the number of potentially infected nymphs for a given area. He found an association between the number of acorns in bumper years inuencing the distribution and infection rates of ticks and ultimately Lyme disease. The relationship between bumper acorn crops and Lyme disease operates on a 2-year delay. The deer are attracted to the acorn- rich oak woodlands, and adult female ticks that are feeding on them drop their eggs there. These eggs hatch the following spring and molt into larvae that summer. The larvae molt into nymphs in late summer, but usually go dormant until the following spring, when they feed for the rst time. Since humans are most likely to be infected by a nymph, increased Lyme disease transmis- sion in oak woodlands takes 2 years after the bumper crop. Ostfeld was able to show that deer prefer oak habitats during a bumper crop year for foraging during the autumn. In non-bumper crop years, the deer would forage in other habitats such as maple-dominated forests (Ostfeld et al., 1996). Lyme disease most often presents with a characteristic bulls-eye erythema, accompanied by nonspecic symptoms such as fever, malaise, fatigue, headache, muscle aches, and joint ache. The incubation period from infection to onset of erythema is typically 714 days. Some infected individuals have no recognized illness (asymptomatic infection determined by serologi- cal testing) or manifest only nonspecic symptoms such as fever, headache, fatigue, and aches (myalgia). The manufacturer of the LYMErix Lyme disease vaccine no longer recommends vaccination and thus the vaccine is not commercially available as of February 25, 2002. According to treatment experts, antibiotic treatment for 34 weeks with doxycycline or amoxicillin is generally effective in early disease. Cefuroxime axetil or erythro- mycin can be used for persons allergic to penicillin or who cannot take tetracyclines. Later disease, particu- larly with objective neurologic manifestations, may require treatment with intravenous ceftriaxone or penicillin for 4 weeks or more, depending on disease severity. In later disease, treatment failures may occur and retreatment may be necessary (CDC Lyme disease homepage). The relative cost effectiveness of postexpo- sure treatment of tick bites to avoid Lyme disease in endemic areas (areas where the disease is known to occur regularly) is dependent on the probability of B. ARTICLE IN PRESS H.S. Koren, D. Crawford-Brown / Environmental Research 95 (2004) 92105 99 burgdorferi infection after a tick bite. In most circum- stances, treating persons who only have a tick bite is not recommended. Individuals who are bitten by a deer tick should remove the tick promptly and may wish to consult their health care provider. 5.1.2. Human activity/stressor Rapid urbanization and suburbanization, which are sometimes accompanied by reforestation, are expanding the traditional role of cities as gateways for infections. The GIS data in Fig. 4 illustrate the change in land use in the Research Triangle Metropolitan Area, NC, USA, comparing the changes between 1988 and 2000. Ana- lyses of the data indicate that the circumference/edge of residential area adjacent to forested areas (serving as habitat for deers and ticks) has increased approximately 600%. This illustration is provided only as an example of the actual change of the circumference/edge of the habitat between during this time. This type of calcula- tion may be done more accurately only when a ner resolution of the GIS data is available. Ecological factors that affect the vectors abundance, longevity, activity, or feeding behaviors may inuence enzootic transmission. These factors include weather, natural or agricultural vegetation, housing construction, land-use patterns (e.g., fragmentation), surface water, and other variables. Still other circumstances affect the risk of transmission to humans by altering the proximity of people to vectors or reservoirs or by inuencing the extent and timing of outdoor activities that expose people. People whose lifestyles involve intimate interac- tion with nature through housing in proximity to woodland environments or outdoor occupational and recreational activities will experience increased contact with vector ticks and greater risk of acquiring Lyme disease. 5.1.3. The ecosystem response to the stressor The fragmentation of forests in the eastern US seems to play a major role in the prevalence of Lyme disease. The New Jersey landscape in the 1980s demonstrates a mix of forest patches of different sizes in agricultural and suburban landscapes. These are the landscapes in which Lyme disease is the biggest problem. One of the most common phenomena described in forest fragments is the species area curve, which describes a log-linear relationship between the area and number of species in fragments. Species disappear at certain levels of fragmentation because they need larger habitats to exist. Schmidt and Ostfeld (2001) coined the term dilution effect to explain the phenomenon where vertebrate hosts with a low capacity to infect feeding vectors dilute the effect of highly competent reservoirs. Also missing from the small forest fragments are more disturbance- sensitive host species that are not as competent for B. burgdorferi infection as white-footed mice. This may be the reason why Schmidt and Ostfelds dilution effect theory does not operate in small fragments. Other species that tend to be missing in these fragments are carnivores that prey on mice. The population density of the white-footed mouse skyrockets in small forest fragments below 12 ha in size (but remains much lower in larger, continuously forested areas), and there is a tendency toward a rapid increase of the white-footed mouse population and Lyme disease risk under habitat fragmentation. The role of fragmentation as a stressor is likely to be more complicated in this situation than is implied by simply noting that there is a relationship between patch size and Lyme disease. In the northeast the emergence of Lyme disease is taking place in the context of a complicated mix of reforestation, an increase in forest patch sizes, some limited deforestation, and increases in edge habitat associated with people moving into the suburban/rural interface. Fragmenta- tion by itself is also not sufcient for explaining Lyme disease without the rapid increase in deer populations in proximity to people. Similarly, in the absence of predators of deer their numbers tend to increase. Lyme disease risk is about 10 times higher in small forest fragments than in much larger fragments (Ostfeld and Keesing, 2000a). Recent data suggest that the presence of alternative (non-mouse) hosts can inuence both the population density of mice and the average larval burdens on white-footed mice. One can conclude tentatively that as species richness increases there is a decrease in the number of infected nymphs. Biodiversity, in the case of Lyme disease, does have a strong and protective impact on human health (Ostfeld and Keesing, 2000b; Schmidt and Ostfeld, 2001). It is therefore evident that the ecology of Lyme disease is complex and occurring against a backdrop of reforesta- tion at large regional scales, which has brought the white-tailed deer back to precolonial levels. At the same time, humans are moving into exurban settings at an unprecedented speed, perturbing this new forest land. While the reforested habitat is more healthy than the denuded landscape, heavily fragmented forest is not suitable for many wildlife species and may not be considered healthy from a native biodiversity stand- point. 5.1.4. The consequence of ecosystem perturbation on human health Surveillance of reported cases demonstrates that Lyme disease is a rapidly emerging vector-borne infectious disease in the United States. More than 145,000 cases have been reported to health authorities in the USA since 1982, when systematic national surveil- lance was initiated. Lyme disease now accounts for more than 95% of all reported vector-borne illness in the USA. The overall incidence rate of reported cases in the USA is about 5 per 100,000 populations, but there is ARTICLE IN PRESS H.S. Koren, D. Crawford-Brown / Environmental Research 95 (2004) 92105 100 considerable underreporting. The disease occurs in distinct and geographically limited areas. The incidence in a few of the most highly endemic communities may reach 13% per year. Persons of all ages and both genders are equally susceptible, although the highest attack rates are in children aged 014 years and in persons 30 years of age and older. Although cases of Lyme disease have been reported in 49 states and the District of Columbia, signicant risk of infection with the agent of Lyme disease, B. burgdorferi, is found in only about 100 counties in 10 states located along the northeastern and mid-Atlantic seaboard, in the upper north-central region, and in a few counties in northern California (CDC Lyme disease epidemiology web page, URL http://www.cdc.gov/ncidod/dvbid/lyne/epi.htm). 5.1.5. Application of the conceptual model The causes of Lyme Disease arise in large measure from the alterations in Spatial Development (D in Fig. 3) that conne the deer and other possible hosts to smaller habitat areas; the resultant change in the Concentration Field (F in Fig. 3; given here by the density of the vector, deer ticks); and the human activities (A in Fig. 3) that bring humans into contact with these vectors. These human activities, associated with outdoor lifestyles in suburban areas where spatial range overlaps the limited habitat of the deer, result in higher exposure. This is because the exposure rate is a function of the product of the human density, D H x; y; t; and the density of infected deer, D D x; y; t; integrated over the spatial range of a geographic area in which humans carry out their activities. As deer or other host animals are conned to progressively smaller geographic areas due to habitat fragmentation, D D x; y; t increases in the remaining habitats. As humans move onto the edges of, or into, those habitats, D H x; y; t also increases in those habitats. As a result, the product of D D x; y; t and D H x; y; t increases. In addition, the decreased habitat causes the total biomass of producers (E1 in Fig. 3) available to the deer to decrease, and the deer must roam outside their normal habitat to nd sufcient biomass. This brings them into spatial regions normally conned to humans (e.g., suburbs), again increasing exposure by increasing the product of D D x; y; t and D H x; y; t in the suburbs. The policies available in this case are those associated with treatment of illness and changes in Spatial Development. One possibility is the application of cures for infection and illness in humans. A second possibility is the increase of habitat for the deer and mice, which will result in a lower density, D D x; y; t: This involves a reduction in urban sprawl, at least in those areas serving as habitats for deer. A third possibility is an increase in the productivity of producers in that habitat, reducing the need for the deer to expand their ranging areas to nd sufcient nutrition and, therefore, reducing the overlap between D D x; y; t and D H x; y; t: Fourth, the possibility of reducing the deer population by modifying hunting laws has also been entertained as a measure for reducing the number of deer. Finally, outdoor activities that increase the overlap between D D x; y; t and D H x; y; t could be reduced, again decreasing the exposure of humans to the deer and the vector. 5.2. Case study no. 2: intensication of feed production for cattle and bovine spongiform encephalopathy 5.2.1. The problem: denition and background Bovine spongiform encephalopathy (BSE) (sometimes referred to as mad cow disease) and its variants belong to the unusual group of progressive, degenerative neurological diseases known as transmissible spongi- form encephalopathies (TSEs). These diseases are characterized by a long incubation period of up to several years, during which there is no visible indication of the disease. The incubation period for BSE among cattle ranges from 3 to 8 years; in humans, where the disease is termed CreutzfeldJakob disease (CJD), the incubation period is at least 5 years and could extend up to 20 years or longer. The diseases are invariably fatal; there is no known treatment or cure. Several US government agencies have informative websites on this topic [CDC Emerging infectious disease web page on BSE (http://www.cdc.gov/ncidod/cid/vol7no1/brownG. htm); CDC web page on BSE (http://www.cdc.gov/ ncidod/diseases/cjd/cjd.htm); FSIS (http://www.fsis.us- da.gov/OA/topics/bse.htm); FDA and page on BSE (http://www.cfsan.fda.gov/B/rd/hhsbse2.html)]. The nature of the transmissible agent is unknown. Currently, the most accepted theory is that the agent is a modied form of a normal cell surface component known as prion protein, a pathogenic form of the protein that is both less soluble and more resistant to enzyme degradation than the normal form. Using extracts of scrapie-infected (sheep) brains, the infectious agent was determined to be a single protein (Hadlow et al., 1982). Research in the 1990s linked two outbreaks of CJD in Europe and Israel to a genetic mutation in the victims. It is now known that about 10% of CJD can be inherited, although it is not known if the genetic defect causes the disease or if another agent, such as a prion, is required. In contrast to the classic form of CJD, the new variant form in the United Kingdom (vCJD) predomi- nantly affects younger persons (median age at death: 27.5 years as of October 2000) and has atypical clinical features, with prominent psychiatric or sensory symp- toms at the time of clinical presentation and a delayed onset of neurological abnormalities, including ataxia within weeks or months, dementia late in the illness, a duration of illness of at least 6 months, and a diffusely abnormal nondiagnostic electroencephalogram. ARTICLE IN PRESS H.S. Koren, D. Crawford-Brown / Environmental Research 95 (2004) 92105 101 Recently published data show an increasing trend for the epidemic of new variant CJD in the United Kingdom [DEFRA home page; see BSE (http:// www.defra.gov.uk/)]. 5.2.2. Human activity/stressor BSE among cattle was rst described in the UK in November 1986 (DEFRA home page). Epidemiological evidence established that the outbreak of BSE was related to the production and use over many years of contaminated meat-and-bone meal. The source of the BSE outbreak is uncertain. There is strong evidence and general agreement that the outbreak was amplied by the feeding of rendered bovine meat-and-bone meal to young calves. The outbreaks were widespread and almost simultaneous, and hence there seemed to be only one common probable cause: food contamination. Protein of animal origin, including discarded brain and spinal tissue from previously rendered cattle and sheep, had increased from 1% to 12% of British cattle feed in the 1980s in response to the increasing price of imported soy and sh meal. Simultaneous changes in the permitted manufacturing methods of cattle feed contain- ing animal protein (among others, permission to use lower processing temperatures) meant that greater numbers of cattle were consuming feed that may have contained the infectious agent. Underlying all this is the consumer demand for cheap food. This cheap food policy is in part driven by an ideological framework, which dictates that lower food prices, rather than greater equality of income, is the correct way to solve the very real problem of malnour- ishment among the poor. Therefore, in the context of this example, the ecosystem affected by the human activities (methods of cattle feed) is the cattle, which can be referred to as an agro-ecosystem. Economic and policy issues clearly play a major role in this case study. 5.2.3. The agro-ecosystem response to the stressor The mechanisms by which infection occurs for most naturally occurring TSEs (BSE being one of them) are uncertain. Different animal TSEs appear to be passed in part by lateral transmission and perhaps by maternal transmission to offspring in natural settings. The human spongiform encephalopathies are considered to be sporadic, inherited, or acquired by an infectious mechanism (Brown et al., 1994; Hsiao and Prusiner, 1990; Masters et al., 1978). Transmission of TSE diseases from one animal to another of the same species in the absence of experi- mental intervention has been extensively documented in the case of sheep-borne scrapie (Hadlow et al., 1982). The mechanism by which other sheep in the same ock become infected appears to be associated with exposure to infected placenta (Race and Chesebro, 1998). Presumably, some long-lived agent in the environment can pass the disease between individuals in the herd. Transmission of a TSE disease from one human to another appears to be associated with surgery, use of cadaveric hormones, and ritualistic cannibalism (Gajdusek et al., 1966; Zigas and Gajdusek, 1957). Kuru has been transmitted from person to person as the result of ritualistic cannibalism in the people of Papua New Guinea. In this case, the most likely route of exposure was via ingestion, although transdermal or mucous membrane exposure cannot be ruled out. 5.2.4. The consequence of the agro-ecosystem perturbation on human health As of November 2000, more than 177,500 cases of BSE were conrmed in the United Kingdom alone in more than 35,000 herds. The BSE epidemic in the United Kingdom peaked in January 1993 at almost 1000 new cases per week. Regularly updated numbers of reported BSE cases, by country, are available on the website of the Ofce International Des Epizooties (http://www.oie.int/eng/info/en esb.htm). Neither BSE among cattle nor the new human variant of CJD has been found in the United States. In 1996, following outbreaks of BSE among British cattle, scientists found for the rst time a possible link between BSE and a new vCJD. While it is not certain how BSE may be spread to humans, evidence indicates that humans may acquire vCJD after consuming BSE-contaminated cattle pro- ducts. The number of human vCJD victims remains small, approximately 100 cases between 1996 and 2000 (Lyal, 2000), compared to the over 160,000 cattle. 5.2.5. Application of the conceptual model The causes of BSE arise in large measure from the introduction of a feedback loop in the ecosystem shown as E2 in Fig. 3. Consider the model of infection and illness shown in boxes H through L in Fig. 3, which may be applied here to the case of the cattle. In Fig. 3, the Excretion Source Term (K) arises from the excretion of the microbe back into the environmental system, with releases to the air, water, soil, and/or producers and consumers. A given consumer (such as cattle) is then infected through the infection of feed materials, which normally would be the producers (e.g., hay). In the alteration shown in Fig. 5, a feedback loop (dashed line from Source Term to Exposure) is introduced due to Agricultural Activities (A in Fig. 3) and Spatial Development (C in Fig. 3). Specically, the agricultural productivity and spatial extent of land containing the cattle is insufcient for relying solely on producers in the ecosystem for support of the nutritional needs of the cattle. Additional nutrition is provided to the cattle by introducing tissue back into their feed. If this tissue is infected, this increases the Source Term through food, which in turn increases Exposure of the cattle to the agent. The result is a positive feedback loop that permits ARTICLE IN PRESS H.S. Koren, D. Crawford-Brown / Environmental Research 95 (2004) 92105 102 the BSE to spread more rapidly than would be the case without the feedback loop. The policies available in this case are those associated with economic activity, allocation of land, and their relationships to the nutritional needs of the cattle. New approaches for formulating public policy with links between agricul- ture, food, health, and the environment have been described in detail recently (Waltner-Toews and Lang, 2000). One possibility is to develop cures for the infection, shunting cattle from Infection directly to Recovery in Fig. 5, and thus reducing the Source Term. A second possibility is to break the feedback loop by no longer introducing infected tissue back into the feedstock (which is the policy currently adopted). A third possibility is to expand the spatial region of the cattles ecosystem, allowing larger ranges for the cattle and smaller density of cattle. This would increase the biomass of producers available to the cattle, reducing the need for the feedback loop. 6. More complex cases Fig. 3 may also be applied to more complex cases such as illness from exposure to Cryptosporidium. In such cases, the roles of the environmental media and of feedback loops between species are more pronounced. In the case of cryptosporidiosis, for example, human exposures (G in Fig. 3) result from Concentration Fields (F in Fig. 3) present in air, water, soil, and food (E in Fig. 3). Humans also provide an effective Excretion Source Term (K in Fig. 3) back into the environmental media, particularly into water and food if sanitation practices are insufcient. Spatial Development (D in Fig. 3) is an important component of these feedback loops from people to the environment, since overlapping water supplies and sewage (resulting in cross-contam- ination from the later to the former) in crowded areas increases the magnitude of the source term into the food and water (WHO, 2001a). 7. Discussion and conclusions Understanding the relationships among population growth, development, natural resource use, the environ- ment, human health, and ecosystems is an important area of both scientic inquiry and environmental policy. The potential applicability of understanding biocom- plexity and incorporating it into integrated human and ecological risk assessments makes this issue both important and timely. The differences between ecological assessment and human health risk assessment suggest an approach for integrating the two perspectives (WHO, 2001b). Our approach in this paper was to take from human health the tendency to create chains of quantitative causal models and from ecosystem studies the tendency to incorporate complex interaction components with orga- nized ecosystems. Following Ravetz (1996), we take from human health risk assessment a concern for rigor of execution, and we take from ecological assessment a concern for completeness of conception (Fig. 3). Therefore, there are clear advantages to an integrated conceptual model such as the one proposed in this paper. Despite that a signicant body of published literature exists in the area of interconnection, relatively little attention has been paid to its integration with the analysis of ecological human health data in the form of a conceptual model. The health effects considered here have been examples of infectious disease, but one can envisage how this model could accommodate other types of diseases. In both cases, the incidence of disease in the human population was related both causally and mathemati- cally to changes in human activities (residential in the case of Lyme disease and agricultural in the case of BSE) that in turn altered the ow of the risk agent through the environmental and ecological system. This ow in turn altered the exposure of both humans and other species to the agent. In both cases, all four causes of disease were evident (see Table 1): a risk agent (the microbe or prion) and stressor (habitat fragmentation); the biolo- gical properties of the infected organism (humans); the ARTICLE IN PRESS Exposure Infection Illness Asymptomatic Sequellae Recovery Source Term Fig. 5. The alteration of the model of infectious disease (WHO, 2001b) in the case of BSE. The arrow from the source term now represents the fact that the risk agent from the cattle is reintroduced into the feed of those cattle through use of infected tissue as a nutritional supplement to counteract the decreased habitat available for grazing. H.S. Koren, D. Crawford-Brown / Environmental Research 95 (2004) 92105 103 environmental situation (media and food chains through which the risk agent may move); and human activities or lifestyle (outdoor activities in suburban areas and a quest for cheap food). Finally, we note how the conceptual model proposed here relates to other models found in the literature. We identify three functional stages of models: 7.1. Analysis framework models Which show steps of analysis that must be performed. These often show, for example, problem formulation followed by risk assessment. These are not models of physical or biological processes, but rather models of steps in analysis or decisions. 7.2. Conceptual models Which show the entities and/or activities that play a causal role in producing risk. Fig. 3 is an example of such a conceptual model. The boxes and arrows in such models refer not only to administrative steps but also to specic classes of mathematical and empirical models that must be used to make predictions of the effect of policies on risk endpoints. 7.3. Predictive models Which allow calculation of the probability and/or severity of effect. Such models are rooted in a conceptual model but formalize each of the boxes and arrows in those models with specic mathematical operations (i.e., mathematical models). Our contention here is that the analysis framework class of models has been well developed for many years (US EPA, 1994, 1998; WHO, 2001a, b), that the second class is now recognized as important to the extent that one can integrate conceptual models used in human and ecological risk assessment, and that the third is emerging. Integration of human and ecological risk assessments offers signicant increases in the relevance of this process. Isolated assessments are by their nature incomplete when both humans and ecological systems are at risk. The most important reason for integrated assessment is the need for a coherent expression of results to support public policy and decision making. The conceptual model has immediate and practical utilities. For instance, it can be used to anticipate impacts of environmental change and explore their impacts on human health. The model could also aid in better understanding the impacts of environmental variability on disease etiology, vectors, and toxic organisms. It can also improve theoretical models of hostpathogen ecology capable of predicting infectious disease, transmission, and disease incidence. 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ARTICLE IN PRESS H.S. Koren, D. Crawford-Brown / Environmental Research 95 (2004) 92105 105