Environmental Research 95 (2004) 92105

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,
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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
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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
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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
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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;
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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
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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.
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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
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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.
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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
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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.
It is a daunting challenge to bring the conceptual
models in human and ecological risk assessment
together and to formalize them in predictive models,
but it is a challenge that is both scientically interesting
and a necessary step in the development of effective
policies to control the spread of infectious disease.
Acknowledgments
The authors thank Drs. John Paul (EPA), Jennifer
Orme-Zavaleta (EPA), Laura Jackson (EPA), and Fred
Pfaender (UNC) for their thoughtful and critical review.
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