Environmental Health Perspectives Volume
103, Supplement 4, May 1995
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Green Turtle Fibropapillomatosis: Challenges to Assessing the Role of
Environmental Cofactors
Lawrence H. Herbst1 and Paul A. Klein1,2,3
1Department of Comparative and Experimental Pathology;
2Department of Pathology and Laboratory Medicine; 3Program
in Biotechnologies for the Ecological, Evolutionary, and Conservation Sciences
(BEECS), University of Florida, Gainesville, Florida
Abstract
Green turtle fibropapillomatosis (GTFP) is a growing threat to the survival
of green turtle (Chelonia mydas) populations worldwide. Recent transmission
studies point to an infectious etiology. Several field studies suggest that
high GTFP prevalence is associated with marine habitats that have been impacted
by agricultural, industrial, or urban development. Environmental contaminants
could be involved in GTFP through several plausible mechanisms including
cocarcinogenesis and contaminant-induced immune suppression. However, an
association of contaminants with GTFP has not been established. A broader
perspective is needed when studying infectious diseases such as GTFP in
complex ecosystems. Alternative explanations for high GTFP prevalence in
some near-shore habitats include the following: a) these habitats
provide an optimum physical environment for survival and transmission of
the infectious agent; b) these habitats attract a high density of
susceptible turtles or harbor a higher density of potential vectors, facilitating
transmission of the pathogen in a density-dependent fashion; and c)
these habitats may contain other stressors that render turtles more susceptible
to GTFP. Application of scientifically rigorous criteria in the epizootiology
of GTFP in free-ranging populations remains a formidable challenge. --
Environ Health Perspect 103(Suppl 4):00-00 (1995)
Key words: marine turtles, contaminants, pollution, infectious
disease, fibropapillomatosis, epizootiology
This paper was presented at the Conference on Environmentally
Induced Alterations in Development: A Focus on Wildlife held 10-12 December
1993 in Racine, Wisconsin.
This study was supported by grants from SAVE-A-TURTLE,
Islamorada, Florida, a joint contract from the U.S. Fish and Wildlife Service,
Department of the Interior, and National Marine Fisheries Service, Southwest
Fisheries Science Center, NOAA, Department of Commerce (RWO No. 96), and
a training fellowship from the National Institutes of Health (National
Center for Research Resources RR07001).
Address correspondence to Dr. Lawrence H. Herbst, D.V.M.,
M.S. c/o Hybridoma Laboratory, Box 100275 HSC, University of Florida, Gainesville,
FL 32611-0275. Telephone (904) 392-1634. Fax (904) 392-1619.
Emergence and Impact of Green Turtle Fibropapillomatosis
All seven existing species of marine turtles have suffered various severe
population declines from overharvesting for their eggs, meat, leather, and
shells, from entrapment by fishing lines and nets, from collisions with
boats, from dredging operations, and from destruction of nesting beaches
and foraging habitat; these species are currently either threatened or endangered
(1). A serious new threat to the survival of endangered green turtles
(Chelonia mydas) has emerged in the form of an epizootic disease,
green turtle fibropapillomatosis (GTFP) (2-4).
Fibropapillomatosis is characterized by single to multiple histologically
benign fibroepithelial tumors (ranging from 0.1 cm to greater than 30 cm
in diameter) that are found commonly on areas of soft skin (flippers, neck,
chin, inguinal and axillary regions, and tail base) and conjunctivae (Figure
1). Green turtles with multiple cutaneous and ocular fibropapillomas may
become severely debilitated. Visceral tumors may also be present, and their
expansive growth disrupts normal organ functions which leads to death. GTFP
primarily affects age groups of high reproductive value, large juveniles
and, to a lesser extent, adult green turtles (1,4). As a result,
GTFP poses a significant threat to the long-term survival of this endangered
species. Exact mortality is unknown but is probably high based on disease
severity (4).
Figure 1. Green
turtle (Chelonia mydas) with cutaneous fibropapillomatosis.
Fibropapillomatosis was first reported over 50 years ago in green turtles
from Florida (5). A survey of the Key West turtle fishery at that
time revealed a prevalence of 1.5%, indicating that the disease was sporadic.
Additional early reports showed that the prevalence of GTFP in several populations
around the world was probably very low (6,7).
In the last decade, GTFP has emerged as a significant worldwide epizootic
in green turtle populations, with documentation of the disease at new localities
and prevalences as high as 92% in some population samples (2,4).
In addition, lesions similar to GTFP have been observed in other marine
turtle species, including olive ridleys (Lepidochelys olivacea),
flatbacks (Natator depressus), and loggerheads (Caretta caretta)
(4), raising concerns about disease impacts on these species as well.
Etiology and Prevalence of GTFP
Evidence from controlled transmission experiments now implicates a filterable
infectious agent, most probably a virus, as the primary cause of GTFP (8).
Similar epithelial and fibro-epithelial tumors in other vertebrate species
have also been shown to have viral etiologies (4,9).
GTFP prevalence varies considerably among geographic locations, ranging
from 0 to 92%, and substantial differences that are stable through time
may be found over relatively short distances (4,10). Data from several
field studies indicate that GTFP is more prevalent in near-shore ecosystems
such as lagoons and bays (4). For example, the prevalence of fibropapillomatosis
among juvenile green turtles in the Indian River lagoon has averaged about
50% since 1982, whereas a nearby (<1 km away) demographically matched
population from the ocean side of the barrier island system has had 0% disease
prevalence (10). The maintenance of large differences in GTFP prevalence
through time over relatively small geographic distances suggests that environmental
cofactors may be important for the full expression of this disease. Alternatively,
the availability of susceptible (naive) hosts and the presence or absence
of the infectious agent in various locations may be sufficient to explain
the variation in prevalence among sites. Anecdotal reports suggest that
GTFP is most prevalent in those near-shore habitats that have been impacted
by human activities, including agricultural, urban, and industrial development
within the catchment areas (reviewed in 4,7,10,11).
Do Environmental Contaminants Play a Role in GTFP?
Identification of putative environmental cofactors and analysis of their
specific roles in GTFP development is a major challenge. Development of
hypotheses for specific cofactors in GTFP pathogenesis must be met with
suitable criteria for accepting or rejecting them. Koch's postulates are
one set of criteria that are appropriate for primary infectious disease,
but they are probably inappropriate for complex, multifactorial diseases
(12). Hill's criteria (12) are more appropriate for epidemiologic
analysis and conclusions based on statistical inference and should be used
when deciding between alternate explanations for the observed GTFP prevalence
patterns .
The perceived association of high GTFP prevalence with near-shore habitats
in proximity to human activities has led to speculation that environmental
contaminants may play a role in GTFP pathogenesis. Associations between
contaminant levels and neoplastic diseases have been made in several aquatic
species (13-18). Biologically plausible mechanisms (hypotheses) for
environmental chemical contaminant effects in GTFP currently include cocarcinogenesis,
including induction of latent virus infections, and contaminant-induced
immune suppression, with subsequent failure of turtles to recognize or eliminate
the relevant pathogen or fibropapilloma tumor cells that facilitate development
or persistence of this disease. Contaminants could also suppress the immune
system of turtles or act as cocarcinogens indirectly by disrupting neuroendocrine
functions (19). Cocarcinogenic effects have been documented for a
wide range of xenobiotics (20,21). Similarly, a wide variety of chemical
contaminants are known to disrupt immune system functions (22-24).
Criteria relating to the strength of the association between GTFP and
environmental contaminants, as well as the consistency and specificity of
this association, are certainly not met by the available data. The perceived
association between GTFP and pollution is based upon subjective assessment
of human impacts in certain catchment areas (reviewed in 4). Objective
documentation of contaminant exposure in high and low GTFP prevalence sites
is needed.
Problems arise in how to document the contaminant exposure of marine
turtles. Few data are available for comparing contaminant residue levels
in water, sediment, or benthic organisms from high GTFP prevalence areas
with those from areas where GTFP is rare. Similarly, data on contaminant
levels in green turtle tissues are scant and difficult to obtain because
of the endangered status of this species. The few studies that have been
published are difficult to interpret in the context of GTFP. For example,
whereas one study in 1983 found significant amounts of hydrocarbons in two
green turtles that stranded after a major oil spill (25), most surveys
of organochlorine and polychlorinated biphenyl residues in green turtle
tissues including eggs have yielded relatively low levels, often below the
limits of detection of the methods (26-29).
Where data exist, there are problems with relating contaminant levels
to the prevalence of this infectious disease. First, the biologic effect
(toxicity) of any particular residue level in green turtles is unknown.
Second, surveys of residue levels are usually limited to those chemicals
that persist in the environment or bioaccumulate, although important toxic
effects such as genetic damage (in a multistage carcinogenesis model) can
result from transient exposures to compounds that do not bioaccumulate.
In addition, exposure to a potent chemical carcinogen or immunotoxin may
occur transiently in a completely different habitat from that being monitored.
For example, before entering near-shore feeding habitats, marine turtles
spend several years in the open ocean where they become associated with
convergence zones in which the potential for exposure to concentrated marine
debris and pollutants is high. Third, toxic effects may not be direct as
in some experimental models but may involve complex interactions with other
abiotic and biotic factors. Thus, fulfilling the criteria for implicating
specific chemical contaminants as important cofactors for GTFP expression
could be extremely difficult (12,30). Finally, the same biological
effects may be caused by any of a number of different classes of compounds
acting through several different mechanisms. Decisions about which contaminant
residues to measure should be made with specific a priori mechanistic
hypotheses in mind and in light of a documented history of exposure to specific
compounds.
The Broader Perspective
Although the hypothesis that contaminants may be involved in GTFP epidemiology
should be considered, a broader perspective is needed when studying disease
in complex ecosystems. A comprehensive analysis must begin by outlining
all of the abiotic and biotic factors that may explain differences in GTFP
susceptibility, transmissibility, and severity between different habitats.
The strongest association of GTFP prevalence is with habitat type (near-shore
embayments). These marine environments may provide favorable physical conditions
for either infectious or noninfectious disease agents. For example, certain
sediment types may accumulate chemical contaminants and, combined with low
flushing rates, could increase the level of exposure to chemical carcinogens
or immunotoxins. However, these same sediment properties and hydrodynamic
conditions may also favor the accumulation and maintenance of high concentrations
of infectious agents. More variable water temperatures in shallow embayments
could affect the rate of xenobiotic metabolism, tumor cell proliferation,
immune system function, and pathogen replication. For example, thermal stress
has been shown to exacerbate virus infection in hatchling green turtles
(31). Variable salinity in near-shore habitats may have similar stress
effects.
Certain marine habitat types may also provide an optimum biotic environment
for survival and transmission of an infectious etiologic agent. Disease
transmission could be enhanced by high population densities of vectors or
intermediate host species. Feeding grounds may attract a high density of
susceptible turtles that would facilitate the transmission of pathogens
in a density- dependent fashion, as has been shown for horizontally transmitted
damselfish neurofibromatosis (32) and the herpesvirus of Lucké's
renal adenocarcinoma (33). Recruitment of susceptible turtles from
many different breeding stocks into common foraging grounds may allow the
exchange of many diseases, including GTFP, from exposed to naive individuals.
Habitat differences in levels of other stressors such as concurrent infectious
disease (parasites) and disturbance by human activity (fishing, boating,
dredging) may render turtles more susceptible to or less able to recover
from GTFP.
The Challenges
It is clear that the primary etiologic factor in GTFP is an infectious
agent (8), and the major goal at present is to identify this agent
and fulfill Koch's postulates. Successful isolation and characterization
of the infectious GTFP agent must be followed by the development of appropriate
diagnostic tools to enable us to study the epidemiology of this disease.
Individuals and populations could then be monitored for exposure to the
GTFP agent allowing the natural routes of transmission, potential vectors
and reservoirs, and the effects of environmental cofactors on susceptibility
to be identified.
Assessment of the role of environmental cofactors in GTFP will require
objective documentation of all potential interacting factors and human impacts
in selected study areas, including monitoring of contaminant levels and
monitoring of turtles for evidence of sublethal biologic damage (biomarkers).
Testing hypotheses concerning a role for environmental contamination will
first require objective documentation of the association of GTFP-affected
turtles with sources of contaminants. This could be done by screening for
residue levels but will require a priori selection of residues to
monitor based on a known history of exposure to specific contaminants. Alternatively,
hypotheses linking specific contaminants with GTFP could be developed using
data from biomarker studies that point to the disruption of key physiological
systems in turtles residing in contaminated habitats. For example, hypotheses
that contaminants influence GTFP prevalence or pathogenicity through endocrine
disruptive effects or immune suppression will require demonstration of these
perturbations in turtles from near-shore areas. Controlled laboratory and
field experiments, as have been carried out in some other aquatic species
(34,35), would provide the best data linking contaminants and susceptibility
to GTFP. All of these studies will be difficult to conduct in free-ranging
populations of this endangered species.
In conclusion, although there may be an association of high GTFP prevalence
with certain habitat types and with human impacts including contaminants,
it is premature to conclude that environmental contaminants are involved
in the etiology of this infectious disease. Whereas plausible hypotheses
about contaminant effects on GTFP susceptibility or GTFP expression can
be developed, it is important to rule out alternative hypotheses and to
remember that virulent pathogenic agents (in contrast to opportunistic pathogens)
need not depend on prior host debilitation (e.g., immune suppression) to
cause disease. Diseases caused by virulent pathogens are an ever present
risk to animals in both captive and wild populations and are capable of
causing significant population declines (36,37). It is clear that
further understanding of any interactions between the infectious agent and
environmental contaminants in producing GTFP epizootics will require thorough
sampling in many different populations and locations, consideration of alternative
hypotheses, and controlled experimentation.
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