Environmental epidemiology is the branch of epidemiology concerned with discovery of the environmental exposures that

contribute to or protect against injuries, illnesses, developmental conditions, disabilities, and deaths; and identification of public
health and health care actions to avoid, prepare for, and effectively manage the risks associated with harmful exposures.
Environmental epidemiology studies external factors that affect the incidence, prevalence, and geographic range of health
conditions. These factors may be naturally occurring or may be introduced into environments where people live, work, and play.
Environmental exposures are involuntary and thus generally exclude occupational exposures and voluntary exposures such as
active smoking, medications, and diet. Environmental exposures can be broadly categorized into those that are proximate (e.g.
directly leading to a health condition), including chemicals, physical agents, and microbiological pathogens, and those that are more
distal, such as social conditions, climate change, and other broad scale environmental changes. Proximate exposures occur through
air, food, water, and dermal contact. Distal exposures cause adverse health conditions directly by altering proximate exposures, and
indirectly through changes in ecosystems and other support systems for human health.
Environmental epidemiology seeks to:
1. understand who is most vulnerable and sensitive to an exposure,
2. evaluate mechanisms of action of environmental exposures,
3. identify public health and health care policies and measures to manage risks, and
4. evaluate effectiveness, costs, and benefits of these policies and measures, as well as provide evidence for accountability.
Environmental epidemiology research can inform risk assessments; development of standards and other risk management
activities; and estimates of the co-benefits and co-harms of policies designed to reduce global environment change, including
policies implemented in other sectors (e.g. food and water) that can affect human health.
Vulnerability is the summation of all risk and protective factors that ultimately determine whether an individual or subpopulation
experiences adverse health outcomes when an exposure to an environmental agent occurs. Sensitivity is an individuals or
subpopulations increased responsiveness, primarily for biological reasons, to that exposure
[1]
. Biological sensitivity may be related
to developmental stage, pre-existing medical conditions, acquired factors, and genetic factors. Socioeconomic factors also play a
critical role in altering vulnerability and sensitivity to environmentally mediated factors by increasing the likelihood of exposure to
harmful agents, interacting with biological factors that mediate risk, and/or leading to differences in the ability to prepare for or cope
with exposures or early phases of illness. Populations living in certain regions may be at increased risk because of the physical
location and/or environmental characteristics of a region.
Epidemiology is the study of health-events, health-characteristics or health-determinant patterns in a population. It is the
cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk
factors for disease and targets for preventive medicine. Epidemiologists are involved in the design of studies, collection
and statistical analysis of data, and interpretation and dissemination of results (including peer review and occasional systematic
review). Major areas of epidemiological study includeoutbreak investigation, disease surveillance and screening
(medicine), biomonitoring, and comparisons of treatment effects such as in clinical trials. Epidemiologists rely on a number of other
scientific disciplines such as biology (to better understand disease processes), biostatistics (to make efficient use of the data and
draw appropriate conclusions), and exposure assessment and social science disciplines (to better understand proximate and distal
risk factors, and their measurement).
Epidemiology, literally meaning "the study of what is upon the people", is derived from Greek epi, meaning "upon, among", demos,
meaning "people, district", and logos, meaning "study, word, discourse", suggesting that it applies only to human populations.
However, the term is widely used in studies of zoological populations (veterinary epidemiology), although the term 'epizoology' is
available, and it has also been applied to studies of plant populations (botanical or plant disease epidemiology).
[1]

The distinction between 'epidemic' and 'endemic' was first drawn by Hippocrates,
[2]
to distinguish between diseases that are 'visited
upon' a population (epidemic) from those that 'reside within' a population (endemic).
[3]
The term 'epidemiology' appears to have first
been used to describe the study of epidemics in 1802 by the Spanish physician Villalba in Epidemiologa
Espaola.
[3]
Epidemiologists also study the interaction of diseases in a population, a condition known as a syndemic.
The term epidemiology is now widely applied to cover the description and causation of not only epidemic disease, but of disease in
general, and even many non-disease health-related conditions, such as high blood pressure and obesity.


Introduction
Infectious diseases, once expected to be eliminated as a significant public health
problem, remain the leading cause of death in the world [1]. Many factors have
contributed to the persistence and increase in the occurrence of infectious diseases,
such as societal changes, health care, food production, human behaviour,
environmental change, public health infrastructure and microbial adaptation [2]. Many
diseases related to environmental factors have recently emerged worldwide and are of
a degree to raise serious concerns.
The focus of this paper is on the environmental factors associated with emergence of
disease. Pathogens, such as bacteria, viruses and parasites, that cause disease in
humans and animals may depend partially or entirely for their existence on other
physical, chemical, or biological factors. Many are strictly vector-dependent while others
are not. For both types, environmental factors can affect directly, or indirectly, survival,
persistence and ability to produce disease. Temperature is a key factor (Figure 1).
Sunlight can affect the persistence and spread of a pathogen if it is associated with
phytoplankton and/or algae. For example, when algae and phytoplankton increase in
bio-mass, zooplankton blooms rapidly follow. Bacteria associated with zooplankton also
increase. Also, humidity resulting from evaporation due to elevation of temperature may
play an important role in the occurrence of many diseases. With appropriate humidity
and moisture, most bacteria survive longer than they would in less humid or dry areas.
There are many diseases common to tropical climates that are linked to water
transmission. If transmission between hosts does not involve vectors, then water, or at
least humid conditions, can be involved in transmission [3]. For example, in warm and
humid regions, where water is available as a transmitting medium, Vibrio cholerae may
proliferate rapidly to the level of an infective dose. In general, it is impossible to
separate environmental factors from biological factors, as can be seen from
interrelationships in nature that play a significant role in the emergence of infectious
diseases.
Effect of bacterial attachments on their growth
Bacteria often require a substrate to attach themselves to before they can multiply, and
the attachment can be host specific or site specific. Davis et al. [4] emphasized the
importance of attachment or colonization in defining the pathogenicity of bacteria: "the
term virulence ... is the degree of pathogenicity used to encompass two features of a
pathogenic organism, a) its infectivity, the ability to colonize a host, and b) the severity
of the disease produced". The surface characteristics of various materials, as well as
their chemical and organic origin, when suspended in water, can influence colonization
by bacteria [5]. More than half a century ago, Heukelekian and Heller [6] showed that at
low nutrient concentrations substrate plays an important role in bacterial multiplication.
Suspended particle-associated microorganisms are abundant in the aquatic
environment. The range of these surfaces is diverse and multiple in origin. Some are
man-made (for example, created by ocean dumping), the surfaces of which may differ
from one location to another. However, substrates in the vast natural environment,
controlled by climate, may be even more diversified. Climate change in the environment
is usually not rapid, allowing cells to acclimatize. Zobell [7] reported that bacteria
attached themselves to inert particles and hypothesized that adsorption was beneficial
for the growth of bacteria. The factors that influence attachment include temperature,
pH and nutrient concentration [8].
Phytoplankton, zooplankton and the eggs of several invertebrate species, when
suspended in the water column for several months, afford an excellent surface rich with
nutrients to attract bacteria [9,10]. These biological components themselves are directly
affected by the physical and chemical parameters of the environment.
Southward et al. [11] published a report of changes in the distribution and abundance of
zooplankton and intertidal organisms in the western English Channel as sea
temperature rose. The authors observed extensive changes in marine communities off
the coast of south-west Britain and the western English Channel during the past
70 years, a period of time during which there was climate warming from the early 1920s,
then cooling to the early 1980s, with recent resumption of warming. The change in
annual mean temperature was approximately 0.5 C. The authors observed marked
changes in the plankton community structure as well as the distribution of plankton and
intertidal organisms, an increase or decrease of two or three orders of magnitude. It was
interesting to note that there was an increase in the abundance and range of warm-
water species during periods of warming, with a decrease for cold water species. The
reverse occurred during the period of cooling. From climate models, it is predicted that a
rise of 2 C mean temperature in the next 50 years will result in 200-400 latitudinal shifts
in the distribution of fish and benthos, including extensive restructuring for planktonic,
pelagic and benthic communities.
The role of temperature and humidity on disease occurrence
Higher animals are very sensitive to climate change. Terrestrial vertebrate hosts are
more likely to be affected by changes in environmental temperature (and humidity)
compared to those animals living in an aquatic environment [12].
In aquatic environments, higher temperature means more evaporation, causing
increased humidity, an increased concentration of nutrients and a general change in
ecology. The physics and chemistry of the ocean change with climate, altering
functional relationships in the marine food web [13]. The initial effects are observed in
the lower trophic levels, with significant changes in phytoplankton biomass and shifts in
species dominance. For example, phytoplankton blooms and red tides have been
known since ancient times, causing disease among fish and shellfish [13].
Diseases such as malaria and eastern encephalitis are transmitted via the mosquito, the
life cycle of which is dependent on temperature and precipitation. Similarly, rodent-
associated diseases are also correlated with climate. A good example is the emergence
of hantavirus in the United States. In 1993, hantavirus pulmonary infection was
confirmed among 94 persons, involving 20 states, with 48% mortality. In the southern
United States, after six years of drought, heavy rains in 1992-93 caused grasshoppers
to thrive and pine nuts to increase in abundance, resulting in a ten-fold increase in deer
mice [14], which are the vectors of hantavirus. Komar and Spielman [15] concluded that
recent landscape and faunal changes had caused zoonotic eastern encephalitis to re-
emerge in Massachusetts after having been dormant for 100 years.
The aquatic environment and Vibrio cholerae
One emerging health problem is the spread of a newly recognized serotype
of Vibrio cholerae, O139, which has caused epidemic cholera in Bangladesh and India.
Serotype O139 of V. cholerae was first identified in India and a few months later in part
of coastal Bangladesh, gradually moving inland.
The association of V. cholerae, the causative agent of cholera, and its host, the
copepod, has been under study for more than 25 years. It is now well established
that V. cholerae is autochthonous to the aquatic environment and closely associated
with crustacea. Cockburn and Cassanos in 1960 first addressed the association
of V. cholerae with plankton, observing a correlation between the incidence of cholera
and presence of increased numbers of blue-green algae in the water [16]. This
correlation was explained as resulting from photosynthesis of the algae, resulting in
increased dissolved oxygen in the water and an elevated pH, supporting growth
of V. cholerae. In addition, V. cholerae releases an enzyme, mucinase, which actively
degrades mucin and mucin-like substances present in plant cells. Several investigators
have tested the hypothesis of Cockburn and Cassanos, and suggested a possible
relationship between V. cholerae and phytoplankton [17].
Silvery and Roach [18] found that when blue-green algae begin to disintegrate after the
peak bloom, the Gram-negative heterotrophic bacterial population immediately begins
to increase. The authors further noted the presence of high concentrations of Gram-
negative bacilli in the gelatinous cover of the blue-green filaments. By using a direct
detection method, V. cholerae was observed to be associated with the
cyanobacteriumAnabaena variabilis, persisting in the mucilaginous sheath for around
15 months [19]. However, the specificity of the association of V. cholerae with
phytoplankton was not clear, only inferential, especially since several peaks of algae
bloom are observed in a given season. In addition, amplification of V. cholerae O1 has
not been correlated with algae. Silvery and Roach [18] observed only one big peak of
an algae bloom occurring during an annual cycle, suggesting that once an algae bloom
has disintegrated, the bacterial cells require another mechanism of survival and
multiplication to cause an epidemic.
Association of V. cholerae with aquatic plants in laboratory microcosm experiments has
been demonstrated by Spira et al. [20]. In this study, V. cholerae was found to
concentrate on the surface of the water hyacinth, Eichhornia crassipes, the most
abundant aquatic plant in Bangladesh. They postulated this mechanism accounted for
enhanced survival and offered a potential reservoir for V. cholerae. Other floating
plants, such as Lemna minor, a common duckweed found in freshwater environments,
have also been reported to harbour V. cholerae [21]. However, these plants were also
found to be colonized by Aeromonas spp. [22], indicating nonspecific bacterial
attachment to aquatic vegetation. The specificity of the association of V. cholerae with
phytoplankton has not been demonstrated, and the role of aquatic vegetation, other
than as a passive carrier, in the epidemiology of V. cholerae is doubtful.
In laboratory microcosm experiments, V. cholerae O1 and the newly recognized
serogroup O139 of V. cholerae were also observed to attach to chitin particles [23]. This
has led Nalin et al. [24] to hypothesize thatV. cholerae O1 attached to chitin particles
would be protected from the acid environment of the stomach. In a recent field
investigation in Bangladesh, one of twelve plankton samples was positive
for V. cholerae by culture, whereas four were positive by direct fluorescent antibody
(DFA) staining [25]. When examined for V. cholerae O139 Bengal, two out of 12
plankton samples were positive by DFA and none by culture. One of the plankton
samples carried both V. ch.olerae O1 and O139, determined by DFA staining [25].
Enhanced survival of V. cholerae O1 could be demonstrated in laboratory
experiments [10] when live copepods were present. V. cholerae O1 associated with
planktonic living copepods survived significantly longer in laboratory microcosms
than V. cholerae O1 attached to dead copepods, with or without Pseudoisochrysis spp.,
a blue-green upon which the copepods feed. Copepod egg cases were found to have
significant attachment by V. cholerae when examined by scanning electron
microscopy [10]. Other organisms, such as Pseudomonas spp. and Escherichia coli,
showed nonspecific attachment [10].
There are two distinct seasons (one major and the other minor) for cholera epidemics in
Bangladesh, spring and autumn [26]. During the years 1964-80, the major cholera peak
was during September and November [26]. The minor peak, however, was longer,
between January and April. According to Oppenheimer et al. [27], zooplankton
populations decrease during the monsoon season, because of less nutrient availability,
then increase significantly during August and September, once the post monsoon
phytoplankton blooms occur. An important report by Kiorboe and Neilsen [28] indicates
that there are two distinct seasons for several species of copepod egg production. One
is between February and April and the other is during August and September. This fits
very well into our hypothesis of copepods' role in the survival, multiplication and
transmission of V. cholerae in the natural aquatic environment [10]. The findings of
Kiorboe and Neilsen [28] on the production of copepod eggs fit well because production
occurs just before the cholera season in Bangladesh; this is particularly important
because free-swimming cells of V. cholerae, even in the nonculturable state, can attach
to copepod eggs and multiply rapidly [10].
The number of V. cholerae O1 cells ingested must be high enough to constitute an
infective dose10
4
to 10
6
cells, depending on the state of health of the victim [29].
There are enough V. cholerae O1 occurring on copepods to cause cholera if ingested
while bathing or swimming or by drinking untreated water from ponds, rivers and lakes
of cholera-endemic countries, notably Bangladesh. The number in a glass of water of
150-200 millilitres would be enough to cause cholera, i.e., trigger an infection or even an
epidemic.
Viable but nonculturable V. cholerae
Isolating V. cholerae from environment samples throughout the year, especially
between epidemics, has not been consistently achievable until recently [30]. In fact, an
explanation was sought for the "mysterious" disappearance of V. cholerae O1 from the
environment during interepidemic periods, notably in cholera-endemic countries like
Bangladesh. Furthermore, cholera was not recognized in Latin America before the
current pandemic for at least two reasons: lack of recognition of the existence of an
aquatic reservoir of V. cholerae in Latin America and lack of routine investigation of O1
and non-O1 cholera vibrios [31]. However, the discoveries of the past decade have
revealed the existence of a dormant, i.e., viable but nonculturable state,
which V. cholerae O1 enters in response to nutrient deprivation and other environmental
conditions [32] as well as the persistence of V. cholerae in estuarine, riverine and
coastal environments as a natural habitat.
The use of the term "viable but nonculturable" has increased steadily during the past
15 years. Counts of bacteria obtained by direct microscopy were often 200 to 5000
times more than the number of colonies on plates. Zobel in 1946 reconfirmed earlier
findings that only a small percentage of bacterial cells actually present in a given water
sample are enumerated by plate count [7]. Furthermore, it was assumed until recently
that when bacterial cells were unable to grow on culture plates they were dead [33].
However, these so called "dead cells" can be shown to be viable, but nonculturable,
using direct viable count methods [34]. Very recently, reactivation of viable but
nonculturable V. cholerae O1 has been reported [35]. Significant changes in cell
morphology have been observed by electron microscopy during the process of
conversion of culturable cells to the nonculturable state [36]. Adverse nutritional
conditions and fluctuation of environmental parameters, such as temperature, can
cause bacteria to become nonculturable. The time required for different species of
bacterial cell may vary from several hours to months. It is speculated that there may be
one or more factors in the environment responsible for converting a normal culturable
cell to the viable but nonculturable state [23]. The viable but nonculturable state
reported for V. cholerae is now recognized to be a common phenomenon in many
species of bacteria [37].
Serotype conversion of V. cholerae
Another important and well studied phenomenon is serotype or biotype conversion,
which has been reported by many investigators. For cholera, V. cholerae serotype O1 is
considered to be the most virulent and the epidemic serotype. All other serotypes,
known as non-O1, are usually but not always nontoxigenic and are not considered to be
of major epidemic relevance. Recent outbreaks of cholera in India, Bangladesh and
several other countries have been found to be caused by a non-O1 V. cholerae,
assigned to serotype O139 [38]. This serotype is now considered to have been derived
from the environment. For the first time, serious concerns have been raised about other
potentially pathogenic serotypes that may be present in the environment. In laboratory
microcosm experiments, seroconversion of V. cholerae non-O1 to O1 and vice versa
have been demonstrated [39]. Seroconversion and/or changes in cell surface properties
may occur naturally in the environment [40]. Seroconversion has been observed
in V. cholerae under different temperature and salinity conditions, suggesting that the
phenomenon may occur more commonly than known before, in brackish, estuarine or
sea water throughout the year. Clearly, environmental factors have a direct influence on
the pathogenicity of V. cholerae.
In conclusion, V. cholerae, an environmental (authochthonous) inhabitant of brackish,
estuarine, and marine ecosystems represents an important agent of disease that can be
dramatically influenced by environmental changes, including global environmental
change.