Conditions in Common Avian and Aquatic Species

ILAR Journal, 2021, Vol. 62, No.
1–2, 169–202
https://doi.org/10.1093/ilar/ilab008
Review
Research-Relevant Background Lesions and
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Conditions in Common Avian and Aquatic Species
Lisa M. Mangus 1, Monique S. França2 , H. L. Shivaprasad3 and
Jeffrey C. Wolf4
1 Department of Molecular and Comparative Pathobiology, Department of Pathology, Johns Hopkins School of
Medicine, Baltimore, Maryland, USA, 2 Poultry Diagnostic and Research Center, The University of Georgia,
Athens, Georgia, USA, 3 California Animal Health and Food Safety Laboratory System, University of California,
Davis, Tulare, California, USA and and 4 Experimental Pathology Laboratories, Inc., Sterling, Virginia, USA
*Corresponding Author: Lisa M. Mangus, DVM, PhD, DACVP, Department of Molecular and Comparative Pathobiology, Department of Pathology, Johns
Hopkins School of Medicine, Baltimore, MD 21205, USA. E-mail: lmangus1@jhu.edu.
Abstract
Non-mammalian vertebrates including birds, fish, and amphibians have a long history of contributing to ground-breaking
scientific discoveries. Because these species offer several experimental advantages over higher vertebrates and share
extensive anatomic and genetic homology with their mammalian counterparts, they remain popular animal models in a
variety of fields such as developmental biology, physiology, toxicology, drug discovery, immunology, toxicology, and
infectious disease. As with all animal models, familiarity with the anatomy, physiology, and spontaneous diseases of these
species is necessary for ensuring animal welfare, as well as accurate interpretation and reporting of study findings. Working
with avian and aquatic species can be especially challenging in this respect due to their rich diversity and array of unique
adaptations. Here, we provide an overview of the research-relevant anatomic features, non-infectious conditions, and
infectious diseases that impact research colonies of birds and aquatic animals, including fish and Xenopus species.
Key words: Anatomy; animal model; bacteria; infectious disease; neoplasia; physiology; pathology; virus
INTRODUCTION diseases. Due to their relatively low cost and ease of manipu-
From Glick and Chang’s landmark studies of the avian Bursa lation, nonmammals often serve as intermediate, or surrogate,
of Fabricius, which led to the concept of a 2-armed immune animal models that ultimately reduce the number of higher
response involving B and T cells,1 to Loewi’s Nobel prize-winning vertebrates (eg, rodents, nonhuman primates) required by pre-
work demonstration chemically mediated nerve impulses in clinical studies. These species are also critical for research inves-
frog hearts,2 research using nonmammalian vertebrates has tigating infectious diseases of major economic, zoonotic, and
spurred numerous discoveries that are fundamental to modern ecological importance such as avian influenza, mycobacteriosis,
biomedical science. Birds, fish, and amphibians offer several and chytridiomycosis.
experimental advantages over their mammalian counterparts, As with all animal models, the generation of rigorous, repro-
including external embryonic development, rapid maturation, ducible data from nonmammalian studies relies on a thorough
and the ability to produce large numbers of offspring. Many understanding of the species’ unique husbandry requirements,
anatomic, genetic, and physiologic features of these species are anatomical structures, and spontaneous diseases.3,4 Because
highly conserved, making them appropriate models for inves- of the incredible diversity among avian and aquatic species,
tigating basic biological processes as well as complex human as well as major differences between nonmammals and
Received: September 24, 2020. Revised: November 18, 2020. Accepted: December 20, 2020
© The Author(s) 2021. Published by Oxford University Press on behalf of the National Academies of Sciences, Engineering, and Medicine.
All rights reserved. For permissions, please email: journals.permissions@oup.com
169
170 Lisa M. et al.
more conventional models, working with these species can the birds may be exposed to in research facilities. General hous-
be especially challenging for researchers, clinicians, and ing and management conditions greatly affect the behavior of
pathologists alike. For instance, familiarity with the various the birds. Gallinaceous poultry are highly social and, as long as
immune cell types and inflammatory responses seen in these space requirements for each bird are met, display their natural
species is essential for correctly interpreting gross and histologic behaviors when housed in groups.15 Additionally, beak trim-
lesions and, in some cases, for distinguishing inflammation ming and toe trimming are standard practices done by skilled
from neoplastic processes. Furthermore, retrospective reviews personnel to prevent cannibalism and cutaneous trauma in
of published fish toxicology studies have shown that normal poultry flocks.
microanatomy and common postmortem artifacts have been Infectious diseases affecting the respiratory and gastroin-
frequently misconstrued as true, test article-related lesions.5–8 testinal tracts are some of the most common conditions
It is likely that similar confounding factors affect studies of diagnosed in gallinaceous birds raised indoors and intensively.16
birds and amphibians as well. The aim of this paper is to provide Stressors such as overcrowding, extreme ambient temperature
a broad-ranging but accessible reference describing the unique (too hot or cold), poor air quality, improper nutrition, and/or

anatomic and physiologic features of commonly used birds, fish, suboptimal cleaning and disinfection commonly predispose
and Xenopus species. The subsequent tables outline important the birds to infectious diseases. Very rarely are domestic
metabolic, environmental, neoplastic, and infectious diseases poultry confronted with 1 single etiology such as a single virus,
that can be encountered in these animals. Resources providing bacterium, or parasite. Rather, it is common to find a combi-
more detailed information are cited within the corresponding nation of etiologies and disease processes when performing
sections and tables. postmortem examinations in sick birds. Neoplasia is common
and often associated with a viral etiology. Lymphosarcoma due
to Marek’s disease is a useful model to study herpesvirus-
AVIAN SPECIES
induced oncogenesis, and the disease in chickens is readily
Birds are commonly used in scientific research due to their prevented by vaccination.17 Spontaneous tumors also occur and
short generation time, large numbers of progeny, low cost, and most commonly involve the reproductive tract (eg, leiomyoma
ease of handling. There are, however, important variations in of mesosalpinx and ovarian/oviductal carcinoma in hens). Spon-
anatomy, physiology, and behavior between avian species used taneous ovarian carcinoma in chickens has been a viable model
in research.9 Hence, it is important to refer to relevant species- to study the early events and progression of ovarian cancer
specific literature when developing animal use protocols and in women.18,19
to design a research setting that complies with the biological Psittacines belong to the order Psittaciformes, a large group
needs of the species used. Cages and aviaries should be suf- of land birds comprising over 350 species in about 84 genera.
ficiently large and properly designed with perches, nests, and They are mainly found in the tropical and subtropical regions
dust boxes for the display of typical behaviors. Birds housed of the Southern Hemisphere: South and Central America, Aus-
in free-range systems should have access to a shelter during tralia, South Asia, Africa, New Zealand, Indonesian Islands, etc.
inclement weather,10 and all birds in the enclosure should have They are commonly called parrots and are the third-most pop-
easy access to high-quality feed and clean drinking water. It is ular companion animal in the United States. Amazon parrots,
important to provide a well-formulated diet that provides the budgerigars, and cockatiels have been used in research inves-
nutritional requirements for each species, taking into consid- tigating cognition, behavior, pharmacology, and infectious dis-
eration the age of the birds and their physiological state. Envi- eases. Because parrots have strong and powerful beaks and
ronmental conditions such as ambient temperature, humidity, propensity to chew, larger parrots are best housed individually
ventilation, and air quality should be properly maintained to in metal enclosures or large flight cages. Small parrots such
optimize the comfort of the birds. Lighting cycles vary for each as budgerigars and cockatiels can be housed in multiples in
species based on age and physiological requirements. Research galvanized (free of zinc) box wire mesh of 1 × 1 inch. Psittacines
facilities and enclosures should be properly cleaned and disin- are highly intelligent birds and require a lot of environmental
fected and must have adequate operational and structural biose- enrichment. Strong sturdy round bars for the birds to roost,
curity measures in place to prevent disease outbreaks. Neverthe- feeders, waterers, and safe toys inside the cages should be pro-
less, personnel working with birds should wear adequate per- vided. Formulated processed complete and balanced diets avail-
sonal protective equipment to minimize exposure to zoonotic able from manufacturers provide the best option for complete
pathogens such as Chlamydia psittaci, the cause of psittacosis or nutrition. Fruits and vegetables should also be provided.
“parrot fever.” Passerines such as finches, sparrows, starlings, and canaries
Gallinaceous poultry such as chickens, quail, and turkeys are rarely used in experimental pathology in comparison with
have been used as animal models in various research fields, other animal models; however, passerines are an attractive
including vaccine development, infectious diseases, toxicology, model to study neurobiology, behavior, cognition, memory,
immunology, cancer biology, ocular diseases, and avian trans- song learning, hearing, and ecotoxicology. Domesticated zebra
genesis/genome editing research.10–12 Chicken embryos have finches (Taeniopygia guttata) are the most commonly used
been frequently used in developmental biology research inves- species among all passerines. Finches have an average weight
tigating cell migration, tissue patterning and symmetry, organo- of 10–16 g and reach sexual maturity at 4 months. Because
genesis, and cardiac development as well as in cancer biology passerines are used in neurobiology research, it is important
research.13,14 Poultry species are susceptible to a variety of dis- to optimize husbandry conditions, and researchers need to
eases as these birds are often exposed to natural elements, may account for potential variations in bird behavior and physiology
lack proper nutrition, and be raised under suboptimal husbandry caused by the experimental design and research setting. It
conditions in poultry farms. Genetics, nutrition, housing, and is important to minimize stressful conditions when handling
management conditions play a significant role in the initia- small passerines and psittacines in research facilities to avoid
tion and outcome of diseases affecting these birds. Vaccination undesirable maladaptive or abnormal behaviors.20 High levels
programs should be focused on preventing infectious diseases of stress can also cause sudden death in these birds. The diet
ILAR Journal, 2021, Vol. 62, No. 1–2 171
Table 1 Anatomy and Physiologic Features of Galliformes, Psittaciformes, and Passeriformes16 ,47–51
System Organ/Tissue Comments
Alimentary
Beak Contains a thick stratum corneum in the epidermis, a thin dermis with prominent Herbst corpuscles, and
bone in the inner core. Stout, curved beak topped by a cere in Psittaciformes.
Crop Diverticulum of the esophagus. Lacks mucous glands.
Esophagus Lined by thick stratified and nonkeratinized squamous epithelium with mucous glands in the lamina propria.
Gizzard Gizzard is the muscular stomach and has a thick tunica muscularis. The mucosa is lined by a thick layer of
keratinoid (koilin) produced by tubular glands in the mucosa.
Intestines Duodenum forms a loop enclosing the pancreas. Absence of duodenal glands. Long jejunum and small ileum.
Ileum with long villi and numerous goblet cells. Ceca are paired, blind, and well developed in Galliformes.
Vestigial ceca in Passeriformes. Absent in Psittaciformes. The colon is small. Cloaca subdivided into

coprodeum, urodeum, and proctodeum.
Oral cavity Lack teeth. Salivary glands are mucous glands located in the roof and floor of the oral cavity, pharynx, and
tongue. Sparse taste buds at the base of the tongue and in the pharynx. Hyaline cartilage in the tongue.
Finches have long, slender, flat, and cornified tongue.
Pancreas, exocrine Composed of tubuloacinar glands. Lack of interlobular connective tissue.
Proventriculus Proventriculus is the primary glandular stomach and contains tubular glands lined by oxynticopeptic cells,
arranged around a central duct. Oxynticopeptic cells secrete both pepsinogen and HCl. Mucosa arranged into
folds (plicae).
Cardiovascular
Great vessels Aorta develops from the right arterial arch and bends to the right. Three vena cava open in the right atrium.
Heart Four-chambered heart (2 atria and 2 ventricles). The right atrioventricular valve is a muscular flap. The wall of
the left ventricle is 3–4 times thicker than the right ventricular wall. Normal EMH in the myocardium of young
birds. Variable amounts of fat in the coronary groove.
Portal system Renal portal circulation. Venous blood from the legs, pelvic region, and hindgut is carried to the kidneys. Renal
venous portal valves when opened allow direct passage of blood to the vena cava. Medication administered in
the leg may be delivered directly to the kidney before entering the systemic circulation.
Endocrine
Adrenals Located at the anterior poles of the kidneys. Lack distinct cortex and medullary regions. Groups of cortical and
medullary cells intermingle.
Pancreas, endocrine Most pancreatic islets located in the splenic lobe of the pancreas. Alpha and beta islets.
Pituitary Within sella turcica posterior to optic chiasm. Adenohypophysis and neurohypophysis. Absence of
intermediate lobe.
Thyroid and parathyroid Associated with common carotid artery and located in the thoracic inlet. Parathyroid located posterior to the
thyroid.
Ultimobranchial body Located posterior to the thyroid. Contains C cells that secrete calcitonin.
Hematopoietic-
immunologic52
Blood Large, elongated, and flat erythrocytes with oval nucleus. Absence of platelets; have nucleated thrombocytes
instead, which are phagocytic. Lymphocytes are the predominant leukocytes. Absence of neutrophils.
Heterophils have lance-shaped granules, lack myeloperoxidase and alkaline phosphatase. Liquefaction or pus
formation is rarely seen in birds. Heterophilic inflammation undergoes caseation with granulomatous
inflammation developing within 12–24 h. Eosinophils are rarely found in tissues of birds, and the role of these
cells in hypersensitivity reactions is not well known; ascarids can cause a prominent eosinophilic enteritis in
turkeys.
Bone marrow Erythropoiesis in vascular sinusoids. Granulocytic series develop in extravascular spaces of the marrow.
Bursa Dorsal diverticulum of the proctodeum composed of tall plicae filled with lymphoid follicles. Site of
B-lymphocyte development. Undergoes involution at sexual maturity.
Cecal tonsils Large collection of diffuse lymphoid tissue and germinal centers.
Gland of Harder (Harderian Situated medially and dorsally on the posterior surface of the eye and contains numerous plasma cells
gland) surrounding tubular secretory units.
Lymphatics and lymphoid Nonencapsulated lymphoid nodules in virtually all avian tissues. Lymphatics are small and less numerous in
nodules avian species. Mural lymphoid nodules within the wall of lymphatic vessels. Accumulations of lymphoid
tissue in the head (HALT), respiratory tract (MALT, BALT) and gastrointestinal tract (GALT).
Lymph node Absent.
Peyer’s Patches Collections of lymphoid tissue and germinal centers in the small intestine. Well-developed in duodenum.
Spleen (PALS) contains a dense population of T-lymphocytes. Germinal centers contain B-lymphocytes. Ellipsoids
contain mononuclear phagocytic system cells. PALS, germinal centers, and ellipsoids form the white pulp. Red
pulp composed of venous sinuses and a network of lymphoid and nonlymphoid cells among red blood cells.
Round to oval spleen in Galliformes and Psittaciformes. Elongated spleen in Passeriformes.
Thymus In pairs (7 paired lobes in chickens), located along jugular veins embedded in the subcutaneous tissue. Site of
T-lymphocyte maturation. Undergoes involution at sexual maturity, vestiges persist throughout the life.
(Continued)
172 Lisa M. et al.
Table 1 Continued
Hepatobiliary
Liver Composed of right and left lobes, which join cranially. Numerous lobules indistinctly separated by one
another. Hepatic plates are 2 cells wide.
Gallbladder Present in Galliformes and Passerifomes. Elongate gall bladder in Passeriformes. Absent in most
Psittaciformes.
Integumentary
Appendages Presence of comb, wattles, ear lobes, snood (turkey), caruncles (turkeys), spurs, claws, scales.
Dermis Absence of sebaceous and sweat glands. Uropygeal gland (preen gland) and ceruminous glands in the external
ear are the only cutaneous glands present. Herbst corpuscles (mechanoreceptors) adjacent to feather follicles
and in the beak.

Epidermis 3–4 layers thick in feathered skin; unfeathered skin has a thickened epidermis.
Uropygial gland Bilobed and holocrine gland near the base of the tail. The gland has sebaceous (outer) and glycogen (inner)
zones.
Musculoskeletal
Bone Pneumonic bones with air sacs extending into the proximal humerus, clavicle, sternum, skull, vertebrae, and
pelvic girdle. Thoracic to sacral vertebrae are fused except for T-4. Fused tibiotarsus, tarsometatarsus, and
carpometacarpus. Ulna is larger than the radius. Secondary center of ossification only present in the
tibiotarsus. Laying hens form medullary bone is response to estrogen (source of calcium during egg
production). Anisodactyly (3 toes forward and 1 back) in Galliformes and Passeriformes. Zygodactyly (2 toes
facing forward and 2 back) in Psittaciformes.
Cartilage Embryonic cartilage persists in the metaphysis of long bones until 7–10 d old. Epiphysis is the cartilage that
caps the ends of long bones. Physis or growth plate composed of zone of resting chondrocytes, zone of
proliferation, zone of pre-hypertrophy, zone of hypertrophy, and zone of ossification.
Skeletal muscle Slow-contracting red fibers (type 1) contain high levels of myoglobin, numerous mitochondria, and less
glycogen. Fast-twitching white fibers (type 2) have less myoglobin and fewer mitochondria. Intermediate
(Type 3 fibers) present.
Nervous
Brain Cerebrum lacks sulci and gyri. Cerebral hemispheres divided into a thin dorsolateral true cortex (general
cortex) and large ventromedial multi-layered cortex (neocortex). Very large optic lobes. Large medulla
oblongata and minimal pons.
Spinal cord Absence of cauda equina. Glycogen body present in the rhomboid sinus of lumbar segment of the spinal cord.
Reproductive
Accessory glands Absence of seminal vesicle, bulbourethral glands, and prostate.
Ovary Only the left ovary develops.
Oviduct Only the left oviduct develops. The oviduct has 5 parts: infundibulum, magnum (albumen secretion), isthmus
(formation of eggshell membranes), uterus (formation of eggshells), and vagina.
Testis Paired and located at the cranial poles of the kidneys.
Respiratory
Air sacs Thin-walled extensions from lungs. 9 air sacs in Galliformes and Psittaciformes - cervical (2), interclavicular
(1), paired cranial thoracic, caudal thoracic and abdominal air sacs. Air sacs allow unidirectional flow of air
through the lungs.53 7 air sacs in Passeriformes: cranial thoracic air sacs fused to the single median clavicular
air sac.
Diaphragm Absent.
Lungs Rigid thoracic cage. Lungs are rigid and attached to the body wall. Secondary bronchi give rise to
parabronchioles, which contain atria that give rise to infundibula and air capillaries for gas exchange. Absence
of alveoli. Lungs are of “paleopulmo” (unidirectional movement of air) and “neopulmo” (bi-directional) types
Nasal passages/sinuses Extra orbital nasal or salt glands are present in the nasal septum. Communicating right and left sinuses in
Psittaciformes.
Trachea Has complete and overlapping rings. Syrinx is the vocal organ located at the base of the trachea.
Special senses
Eyes Salient features include the presence of pecten, overlapping scleral ossicles, scleral cartilage, an avascular
retina with 10 layers, well-developed nictitating membrane, thin and less distinct Descemet’s membrane in
the cornea and striated muscles in iris and ciliary body, an annular pad, and fluid-filled cleft in the lens.
Tapetum lucidum is absent. Lacrimal apparatus or gland located in the ventrotemporal part of the orbit.
Ear Have external, middle, and internal ears. Lack external pinna. Ceruminous glands in external ears. Convex
tympanic membrane. Lack maleus, stapes, and incus in the middle ear. Presence of a rod-like ossicle called
columella in the middle ear, which carries sound waves from the tympanic membrane to the inner ear. Inner
ear composed of bony and membranous labyrinth.54
Urinary
Kidney Lobulated with 3 lobes (cranial, middle, and caudal lobes). Absence of renal capsule and renal pelvis.
Mammalian and reptilian (without loop of Henle) nephrons. Most nephrons are reptilian type. Uric acid is the
end product and is precipitated in the ureters.
Urinary bladder Absent.
EMH, extramedullary hematopoiesis; HALT, head associated lymphoid tissue; MALT, mucosa associated lymphoid tissue; BALT, bronchial associated lymphoid tissue;
GALT, gastrointestinal associated lymphoid tissue; PALS, periarteriolar lymphoid sheaths.
Table 2 Metabolic, Spontaneous (and Neoplastic) Conditions in Chickens, Turkeys, and Quail16,47,55
System Condition Comments
Alimentary
Beak deformities Improper beak trimming cause inflammation and necrosis and can result in neuroma formation. Beak overgrowth
associated with chronic liver disease. Beak deformities caused by nutritional deficiencies (eg, selenium toxicosis).
Gizzard erosions Characterized by fragmentation, detachment, and inflammation of the koilin layer, sometimes with ulceration of
the mucosa. Caused by toxicities, nutritional deficiencies, ingestion of caustic substances, adenovirus infection in
chickens, among others.
Meckel’s diverticulitis Bacterial infection of the yolk stalk. Dilated Meckel’s diverticulum containing caseous exudate.
Pendulous crop Distended crop full of feed, bedding material, and/or fluid. Associated with hot weather and excessive water
intake.
Cardiovascular

Aortic rupture (turkeys) Dissecting aneurysm, most common in male turkeys 7–24 wk old. Most common in the abdominal aorta at the
origin of the celiac artery. Characterized by sudden death and internal hemorrhage. Associated with genetics,
hypertension, copper deficiency, absence of vasa vasorum in the abdominal aorta, and lower levels of lysyloxidase
activity.
Ascites syndrome Common in broiler chickens. Associated with rapid growth and insufficient pulmonary capacity, which result in
(chickens) pulmonary hypertension and right-sided heart failure. Predisposed by high altitude, cold temperature, and
respiratory hypoxia. Characterized by right heart hypertrophy followed by dilation, pulmonary congestion and
edema, chronic passive congestion of liver, and ascites.
Coronary artery Condition seen in 15- to 16-wk-old male turkeys. Characterized by subintimal thickening, medial degeneration,
aneurysm (turkeys) and rupture of coronary artery, resulting in hemorrhage at the base of the heart and hemopericardium. Associated
with genetics, hypertension, copper deficiency, increased body weight.
Medial hyperplasia Thickened tunica media due to hyperplasia of smooth muscle cells. Incidental finding, more commonly seen in
turkeys. May be associated with pulmonary hypertension.
Round heart disease Also known as dilated cardiomyopathy. Common in young commercial turkeys, peaks at 2–3 wk old, occasionally
(turkeys) in turkeys up to 10–12 wk old. Characterized by dilated ventricles, chronic passive congestion of liver. Abnormal
troponin T in turkeys may predispose turkeys to this condition.56 Also predisposed by high altitude, cold
temperature, and hypoxic conditions during incubation. Used as a model to study cardiomyopathy.
Sudden death syndrome Common in male broiler chickens, between 2–4 wk old. Sudden death associated with enlarged heart and
in broiler chickens pulmonary congestion due to cardiac arrythmia, ventricular tachycardia, and fibrillations. Associated with
(flip-over) mutations and dysregulation in intracellular (CASQ2) and (RYR2).57 ,58
Sudden death syndrome Sporadic condition of rapidly growing male turkeys, between 8–14 wk old. Characterized by hypertrophy of the left
of turkeys (turkeys) ventricle and interventricular septum, pulmonary congestion and edema, congested viscera, and perirenal
hemorrhage. Etiology remains unclear.
Endocrine
Autoimmune thyroiditis Spontaneous condition in obese strain of chickens. Affected birds have long and silky feathers. Thyroids are
(chicken) atrophied and have lymphocytic thyroiditis with lymphoid nodules. Hyperlipidemia, low T3 and T4, and IgA
deficiency. Model for Hashimoto’s thyroiditis. Also described in Fayoumi breed of chickens with feather
amelanosis.
Goiter Seen in male mature buff Cochin chickens. Characterized by enlarged cystic thyroid glands with follicles lined by
flattened epithelial cells. Possibly caused by genetics.
Hematopoietic-
immunologic
Extramedullary Common in healthy young birds. Increased extramedullary granulopoiesis common in sick birds.
granulopoiesis
Extramedullary Red foci of EMH can be seen in the small intestine of healthy chickens and can be prominent in birds with
hematopoiesis bacterial septicemia.
Lymphoid hyperplasia Reactive lymphoid follicles (germinal centers) with connective tissue capsule develop in secondary lymphoid
tissues after antigenic stimulation.
Hepatobiliary
Bile duct hyperplasia Nonspecific lesion associated with chronic hepatic injury. Commonly seen in birds exposed to certain mycotoxins,
such as aflatoxin.
Fatty liver hemorrhagic Condition of obese layer-type chickens. Characterized by marked hepatic lipidosis and hemorrhagic and/or
syndrome (chickens) ruptured liver. Associated with high-energy diets, restricted exercise, and hot weather.
Hepatic lipidosis Physiologic hepatic lipidosis is a normal finding in newly hatched birds due to yolk sac resorption and in laying
hens in active egg production. Also caused by high-energy diets and hepatocellular injury. Turkeys with hepatic
lipidosis may have severe hepatic necrosis and hemorrhage.
Integumentary
Albinism Complete albinism caused by a recessive autosomal gene. Imperfect albinism caused by a single sex-linked
recessive gene. Lack of pigment in skin and retinal epithelium.
Autoimmune vitiligo In Smyth line of chickens. Model for studying vitiligo in humans. Spontaneous postnatal cutaneous amelanosis
and blindness.
Breast blister Condition seen in heavy chickens and male turkeys. Characterized by swollen sternal bursa with fluid
accumulation. Caused by pressure or trauma to the sternal bursa and keel.
(Continued)
174 Lisa M. et al.
Table 2 Continued
Epidermal inclusion Dilated, filled with keratin. Seen in neck, breast, and back of older laying hens.
cysts
Feather cysts Caused by dysplastic feather and feather follicle growth. Characterized by hard yellow lumps within and projecting
from skin. Cysts are lined by stratified squamous epithelium and filled with lamellar keratin, may also see barbs
and barbules. Ruptured cysts cause dermal granuloma.
Frostbite Dry gangrene of comb, wattles, toes, and feet caused by freezing of the skin and underlying tissues.
Keratoacanthoma Dermal squamous cell carcinoma. Crateriform cutaneous ulcers common in feather tracts of the back and sides.
(chickens)
Pododermatitis, breast Characterized by ulcerative cutaneous lesions in footpad, posterior surface of the hock, or breast. Caused by
burn (chickens), and prolonged contact with wet litter and high stocking density.

breast button (turkeys)
Segmental feather “Stress marks” in feathers. Indicative of episodes of acute stress. Experimentally induced by single injections of
dysplasia glucocorticoids.
Vent pecking, feather Vent pecking can occur in laying hens raised in floor systems and at the beginning of egg production. Vent pecking
picking can cause cloacal and intestinal prolapse and may predispose to infections. Feather picking has been attributed to
genetics. Also predisposed by nutritional deficiencies, stress, ectoparasites, and management factors such as
overcrowding conditions, bright light, lack of foraging materials, and improper beak trimming.
Multisystemic
Amyloidosis Associated with chronic infections and chronic antigenic stimulation. Amyloid arthropathy is common in Brown
Leghorn chickens with bacterial synovitis. Hepatic amyloidosis and hemorrhages following vaccination with
certain bacterins (bacterin-associated hepatopathy). Hepatic and splenic amyloidosis in mature chickens with
Hepatitis-Splenomegaly syndrome.
Early chick mortality Can be caused by bacterial or fungal infections, dehydration, starvation, and suboptimal brooding conditions.
Prevented by optimal management of temperature, light intensity, access to good-quality feed and water, cleaning,
and disinfection.
Heat stress Caused by high temperature and humidity. Cause reduction in feed intake, thin-shelled eggs, decreased egg
production, immunosuppression, and increased incidence of infections. Hyperthermia (heat stroke) can cause
rhabdomyolysis.
Incubation-related May be associated with embryonic mortality, unhealed navels, bacterial or fungal infections, leg problems, growth
problems depression, and unevenness in the flock. Adequate monitoring of temperature, humidity, ventilation, and egg
turning are critical for good-quality chicks.
Visceral gout Caused by dehydration or renal disease. Characterized by urate deposits in kidneys and on serous membranes.
Musculoskeletal
Angular bone Valgus (outward) and varus (inward) deviation. Associated with increase in growth rate. Often unilateral, with the
deformities right leg more commonly affected. Valgus deformation of the tibiotarsal-tarsometatarsal joint more common in
broiler chickens. The gastrocnemius tendon may be displaced. Varus deformation of the femoro-tibiotarsal joint is
more common in turkeys.59
Articular gout Urate deposits in joints, mostly in males. Normal kidneys. Soft tissues other than synovium are rarely involved.
Associated with genetic and high-protein diets.
Deep pectoral myopathy Condition seen in well-muscled chickens and turkeys. Green discoloration of primarily supracoracoideus muscle
(green muscle disease) due to ischemic necrosis secondary to excessive muscle activity (exertional myopathy and compartment
syndrome).
Dyschondroplasia Common in broiler chickens and turkeys. Abnormal mass of avascular and necrotic cartilage in the growth plate
and metaphysis. Multifactorial etiology, associated with genetics, nutritional deficiencies, and mycotoxicosis,
among others. Primarily affects the proximal tibiotarsus (tibial dyschondroplasia), also in tarsometatarsus, femur,
humerus, vertebrae.
Inherited muscular Seen in New Hampshire and Cornish chicken breeds. Unable to elevate wings beyond horizontal plane and unable
dystrophy (chickens) to right themselves when placed on their backs. Grossly enlargement of pectoral muscles initially and later
atrophy, microscopically variation in fiber size, increased nuclei, vacuoles, necrosis, fragmentation, and
replacement by adipose tissue.
Myopathy of the Conditions seen in meat-type chickens. Wooden breast is a degenerative myopathy characterized by hardening of
pectoralis major the breast muscle due to degeneration, necrosis, inflammatory cell infiltration, and fibrous tissue proliferation.
“wooden breast” and White striping is characterized by white stripes on breast and thigh muscles due to myofiber degeneration, fibrosis,
“white striping” and fat infiltration.
(chickens)
Oil-emulsion vaccine Vaccine reaction characterized by granulomas with lipid vacuoles (oil adjuvant). Misdirected vaccination can cause
reaction more severe inflammatory reaction.
Osteochondrosis Degeneration and fractures (clefts) in the epiphysis and physis caused by weight-bearing mechanical forces that
result in ischemic injury. Most common in proximal femur and T-4 vertebra. Can predispose to secondary bacterial
infection.
Osteoporosis (chickens) Also known as cage layer fatigue. Age-related disease of egg-laying chickens caused by decrease in bone
mineralization. Characterized by bone fractures, deformed sternum, enlarged parathyroid glands. Predisposed by
lack of exercise and inadequate intake or lack of absorption of calcium, vitamin D3, or phosphorus.
(Continued)
Table 2 Continued
Rupture of the Common in meat-type chickens and rare in turkeys. Acute lameness and hock sitting posture with bilateral
gastrocnemius tendon rupture. Hemorrhage or green discoloration seen through the skin. Caused by infectious tenosynovitis or trauma.
Spondylolisthesis Rotation of T-4 vertebra causing spinal cord compression and posterior paralysis in broiler chickens. Associated
(chickens) with genetics and rapid growth.
Spraddle legs One or both legs splayed laterally from coxofemoral joint. Associated with high humidity during incubation or
placement of chicks in slippery floors.
Nervous
Encephalocele Normal anatomic finding in certain chicken breeds such as Silkie, Polish, and Araucana breeds. Extension of brain
tissue through a defect in the skull (cranioschisis).
Peripheral neuropathy Autoimmune disease of pullets 6–9 wk old. Affects White Leghorns and Rhode Island Red chickens. Associated
with certain B haplotypes, with the B∗19 haplotype being the most susceptible. Characterized by swollen peripheral

(chickens)
nerves with edema and lymphoplasmacytic inflammation. Predisposed by vaccinations and infection with
Campylobacter jejuni.60
Reproductive
Cystic right oviduct Caused by incomplete regression of the right Müellerian duct. The immature right oviduct becomes dilated and
(chickens) fluid-filled.
Egg-bound Characterized by the presence of a retained egg in the vagina. Predisposed by obesity, calcium deficiency, stress,
improper husbandry, and vent pecking. Prolapse, internal laying, bacterial salpingitis, and peritonitis are common
sequelae.
Egg-yolk peritonitis Presence of yolk material in the coelomic cavity. Yolk material induces a mild inflammatory response in serous
membranes of abdominal viscera. Secondary bacterial infections result in morbidity and mortality.
Leiomyoma of Common in adult chickens. Pale nodule in the mesosalpinx and oviduct wall. Occasional small nodules in coelomic
mesosalpinx (chickens) cavity and abdominal viscera.
Ovarian/oviductal Common in adult chickens. Multiple, miliary implant tumors on the mesentery and other visceral surfaces. Ascites
adenocarcinoma common. Ovarian carcinoma in hens used as model to study ovarian cancer in women.
(chickens)
Prolapse Common in obese chickens. Cloacal and oviduct prolapse predisposed by oviposition of a large egg and vent
pecking. Can result in cannibalism and death.
Testicular and Due to normal seasonal involution or caused by infectious or noninfectious conditions such as nutritional
epididymal atrophy deficiencies and toxicosis.
Respiratory
High environmental Impairs the mucociliary apparatus. Causes epithelial deciliation, inflammation, goblet cell hyperplasia, mucus
ammonia secretion, and erosions in the mucosa of the upper respiratory tract. Prevented by cleaning and disinfection, proper
litter management, and adequate ventilation.
Carbon monoxide Characterized by congestion, edema and hemorrhage in the lungs, and bright red colored blood.
poisoning
Pneumoconiosis Histiocytic infiltrates in the wall of the parabronchi containing intracytoplasmic dust or carbon particles.
Polytetrafluoroethylene Polytetrafluoroethylene-coated light bulbs release toxic gases that cause acute pulmonary congestion and edema.
toxicosis
Special senses
Ammonia toxicity Caused by high environmental ammonia. Characterized by corneal ulceration and conjunctivitis.
Blepharoconjunctivitis Characterized by ocular discharge, swelling and ulceration of the eyelid, caseous exudate in the conjunctiva,
(turkeys) corneal necrosis, and lens opacity. Seen in turkey breeders during cold season. Unknown cause.
Cataracts Caused by ocular inflammation due to viral (avian encephalomyelitis), bacterial or fungal infections, nutritional
deficiencies (eg, vitamin E), old age, suboptimal incubation conditions, and heredity. May be associated with retinal
dysplasia.
Eye-notch syndrome Condition seen in caged layers. Blepharoconjunctivitis characterized by small scar in the lower eyelid that develops
(chickens) into a fissure with a tag of flesh attached to 1 side.
Glaucoma Can be induced by rearing birds under continuous light. Light-induced avian glaucoma animal model. Condition
seen in various breeds of chickens and turkeys.
Keratoconus (Pop-eye) Condition of White Leghorn chickens, noticeable in chickens older than 5–6 wk old. Bilateral protrusion of the
(chickens) cornea. Inherited as a sex-linked recessive trait.60
Microphthalmia Hereditary condition, usually bilateral. Autosomal recessive in Barred Plymouth Rocks, New Hampshire chickens.
(chickens) Dominant with incomplete penetrance in Brown Leghorns. Sex-influenced heritance in color-mutant chickens.
Characterized by eyeball with a diameter approximately one-half that of normal birds.
Retinal degeneration Hereditary retinal degeneration in several chicken lines, such as the Smyth chicken and Rhode Island reds
(autosomal recessive rdd gene) among others.60
Urinary
Proliferative Mesangioproliferative glomerulonephritis can be a normal finding in broiler chickens. Membranoproliferative
glomerulopathy glomerulonephritis seen with immune-mediated injury associated with certain viral infections (such as infection
with Aviadenovirus and infectious bursal disease virus).
Renal hypoplasia and Congenital anomalies. Rarer than in mammals. Agenesis primarily unilateral. Hypoplasia most commonly
agenesis affecting anterior lobes.61
Urolithiasis Characterized by ureters distended with uroliths (composed of mineralized urates) and renal atrophy. Often
associated with renal and visceral gout. Also caused by high-calcium diet.
CASQ2, Ca2+ cycling components calsequestrin-2; RYR2, ryanodine receptor 2.
176 Lisa M. et al.
Table 3 Common Infectious Diseases of Chickens, Turkeys, and Quail16,62–64
Class Agent Comments
Virus
Adenoviruses Inclusion body hepatitis: caused by Aviadenovirus. Primarily a disease of chickens, rare in turkeys. Liver
enlarged, pale with foci of necrosis, hemorrhage, and basophilic intranuclear inclusion bodies. Also see
pancreatitis, hydropericardium, swollen and pale kidneys with glomerulonephritis. Gizzard erosions
with basophilic intranuclear inclusions in the epithelium. Quail bronchitis: caused by Aviadenovirus.
High mortality in young bobwhite quail associated with bronchopneumonia, tracheitis, hepatitis,
pancreatitis, bursal necrosis, intranuclear inclusions. Hemorrhagic enteritis: caused by Siadenovirus.
Disease of young turkeys (4–12 wk old). Characterized by small intestinal hemorrhage and enlarged
mottled white spleen. Amphophilic intranuclear inclusions in mononuclear cells in intestine, spleen
and renal epithelial cells. Egg drop syndrome: caused by Atadenovirus. Drop in egg production and poor

eggshell quality in chickens with no apparent lesions.
Avian encephalomyelitis Cause an egg-transmitted viral disease of young (1–3 wk old) gallinaceous birds. Neurological signs
virus (epidemic tremor) in young birds and drop in egg-production in layers. Gross lesions usually absent.
Occasionally see pale foci of inflammation in the tunica muscularis of the gizzard or proventriculus of
young birds and cataracts in survivors. Encephalitis with central chromatolysis of neuronal cell bodies,
and lymphocytic infiltrates primarily in heart, pancreas, and tunica muscularis of the gastrointestinal
tract commonly seen.
Avian hepatitis E virus Orthohepevirus B. Causes hepatitis-splenomegaly syndrome in mature chickens. Drop in egg production
(chickens) and increased mortality. Hemorrhagic hepatitis, amyloidosis in liver and spleen.
Avian Influenza virus Influenza A virus. Low Pathogenic Avian Influenza viruses: subclinical infection or disease affecting the
respiratory, gastrointestinal, urinary, and reproductive tracts. Lesions include catarrhal sinusitis,
tracheitis, airsacculitis, conjunctivitis, pneumonia, yolk peritonitis, oophoritis, salpingitis, pancreatic
necrosis (turkeys), thymic and bursal atrophy, nephritis/nephrosis. Secondary bacterial infections
enhance disease severity. Highly Pathogenic Avian Influenza viruses of H5 and H7 subtypes: systemic
disease with high mortality in chickens and turkeys. Lesions include hemorrhage in skin of face, comb,
shanks, and gastrointestinal tract, lymphocytic encephalitis, disseminated vasculitis and thrombosis, as
well as multi-organ necrosis, hemorrhage, and inflammation.65 ,66
Avian leukosis virus (chickens) Primarily vertically transmitted. Leukosis/sarcoma viruses cause: Lymphoid Leukosis: neoplastic
disease of chickens older than 16 wk caused by retrovirus subgroups A, B, C, and D. B-cell lymphoma
with large lymphocytes (lymphoblasts) in various organs such as bursa of Fabricius (intrafollicular),
liver, spleen, kidney, gonads, etc. Absence of lesions in central and peripheral nervous system.
Myelocytomatosis: neoplastic disease of broilers and broiler breeders caused by retrovirus, subgroup J.
Myeloid cell neoplasia in various organs such as liver, kidney, spleen, skull, sternum, etc. Other
neoplasia: soft tissue sarcomas, epithelial cell tumors (mainly renal tumors), and endothelial cell
tumors (hemangioma/hemangiosarcoma). Osteopetrosis in long bones.
Avian metapneumovirus Cause of Turkey Rhinotracheitis of turkeys and Swollen Head Syndrome of chickens. Characterized by
swollen sinuses, sinusitis, tracheitis, rhinitis, conjunctivitis.
Avian Paramyxovirus −1 Avian orthoavulavirus 1. Isolates vary greatly in pathogenicity. Lentogenic viruses: subclinical infection or
(APMV-1)/Newcastle disease mild respiratory disease. Mesogenic viruses: egg production/eggshell quality problems and respiratory
viruses (NDV) disease with low mortality. Lesions caused by low virulence NDV include tracheitis, conjunctivitis,
pneumonia, and airsacculitis. Velogenic viruses (neurotropic and viscerotropic): Newcastle disease with
high mortality (up to 100%) in chickens. Lesions include lymphocytic encephalitis, disseminated
vasculitis, as well as necrosis and hemorrhage in lymphoid organs, trachea, conjunctiva, and
gastrointestinal mucosa.
Avian poxvirus Avipoxviruses; numerous species including Fowlpox virus, Turkeypox virus, Pigeonpox virus. See
proliferative lesions primarily on unfeathered skin of the head, legs, and feet (cutaneous form) and
yellow raised plaques in the mucosa of the upper gastrointestinal tract, respiratory tract, and
conjunctiva (wet or diphtheritic form). Microscopically, see epidermal or epithelial hyperplasia,
ballooning degeneration and eosinophilic, intracytoplasmic inclusion bodies (Bollinger bodies).
Avian orthoreovirus Causes disease in chickens and turkeys. Arthritis, tenosynovitis, with rupture of the gastrocnemius
tendon in heavy birds. Also, myocarditis, enteritis, and lymphoid atrophy in thymus and bursa of
Fabricius.
Chicken anemia virus Causes vertically transmitted disease in young chickens characterized by aplastic anemia and
(chickens) immunosuppression. See low hematocrit, pale bone marrow, severe thymic and bursal atrophy,
hemorrhages in skeletal muscles. Predisposes to viral, bacterial, and fungal infections such as inclusion
body hepatitis, gangrenous dermatitis, aspergillosis, etc.
Chicken proventricular A novel birnavirus that causes transmissible viral proventriculitis in chickens. Necrosis of glandular
necrosis virus (chickens) epithelium, lymphocytic inflammation in the glands and mucosa, ductular hyperplasia, and lymphoid
nodule formation.
Enteric viruses Different viruses including astroviruses, reoviruses, coronaviruses, and rotaviruses. Common in young
chickens and turkeys. Characterized by diarrhea, loss of weight, pale intestine filled with watery and
frothy contents. Cystic enteritis with crypt necrosis and dilation in chickens with Runting-Stunting
Syndrome.
(Continued)
Table 3 Continued
Infectious bronchitis virus Avian coronavirus. Highly contagious viral respiratory disease of chickens. Characterized by tracheitis,
(chickens) conjunctivitis, bronchitis, sinusitis, and airsacculitis. Secondary bacterial infections such as
colibacillosis enhance the severity of respiratory disease. Drop in egg production, poor egg quality (poor
shell and thin albumen), and left cystic oviduct in layers. Nephritis and nephrosis with
nephropathogenic strains.
Infectious bursal disease virus Variant, classical, and very virulent strains. Immunosuppressive disease of young chickens (1–6 wk).
(chickens) Enlarged, edematous, and hemorrhagic bursa of Fabricius during acute infection followed by atrophy in
later stages of the disease. Lymphoid necrosis and depletion. Virulent viruses cause hemorrhages in
proventriculus and skeletal muscles.
Infectious Laryngotracheitis Gallid alphaherpesvirus 1. Primarily in chickens, turkeys are susceptible.67 Oculonasal discharge,

virus catarrhal, hemorrhagic, and/or fibrinonecrotic tracheitis. Also see conjunctivitis, bronchitis, sinusitis,
airsacculitis. Pathognomonic syncytial cells containing eosinophilic intranuclear inclusion bodies.
Marek’s Disease virus Gallid alphaherpesvirus 2. Common in unvaccinated and sexually immature chickens from 2 to 7 mo old
but can occur at any age. Rare in turkeys.68 Lesions include pleomorphic T cell lymphoma in various
organs such as liver, spleen, kidney, skin, eyes, gastrointestinal tract etc. Neoplastic or inflammatory
lesions in nerves, brain, and spinal cord. Lymphoid necrosis and depletion in bursa and thymus.
Intranuclear inclusion bodies may be seen in feather follicle epithelium.
Reticuloendotheliosis virus Avian retrovirus that causes lymphoma in various organs in chickens and turkeys, acute reticular cell
sarcoma, and nonneoplastic conditions such as thymic/bursal atrophy, neuritis, and enteritis.
Turkey viral hepatitis virus Disease of young turkey caused by a novel Picornavirus. Characterized by foci of necrosis and
(turkeys) inflammation in liver and pancreas, and syncytial cells in liver.
Bacteria
Avibacterium paragallinarum Infectious coryza in chickens. Rare in turkeys. Upper respiratory tract infection; swollen sinus
(sinusitis/rhinitis), facial edema, conjunctivitis. Occasionally tracheitis, bronchitis and airsacculitis,
cellulitis in the head and neck.
Bordetella avium Primarily affect turkey poults (turkey coryza). Young chickens susceptible. Upper respiratory tract
infection characterized by swollen sinus, collapsed trachea, watery eyes. Tracheitis with cilia-associated
bacteria, deciliation, and squamous metaplasia (chronic lesion).
Campylobacter spp. Campylobacter jejuni: generally nonpathogenic for poultry. Associated with vibrionic hepatitis
Campylobacter hepaticus: causes spotty liver disease in egg layers. Drop in egg production and increased
mortality. See necrosis and inflammation in the liver.
Chlamydia psittaci Rare in galliforms, turkey most commonly affected. Characterized by nasal discharge, respiratory
distress, and yellowish-green diarrhea. See polyserositis, pneumonia, enlarged and congested spleen,
hepatitis, conjunctivitis, nasal (salt) gland adenitis (turkeys).
Clostridium spp. Necrotic enteritis: acute disease in chickens and turkeys caused by Clostridium perfringens. Characterized
by fibrinonecrotic enteritis and high mortality in the flock. Focal duodenal necrosis: subclinical disease
of egg-laying chickens associated with Clostridium perfringens and Clostridium colinum. Characterized by
multifocal reddened to gray erosions in the mucosa of duodenum and jejunum.69 Ulcerative enteritis:
acute disease in Bobwhite quail, chickens and turkeys caused by Clostridium colinum. Characterized by
multifocal intestinal ulcers and foci of hepatic necrosis in liver. Gangrenous dermatitis: acute disease in
chickens and turkeys caused by Clostridium septicum or Clostridium perfringens. Dark and gangrenous skin
with edema, hemorrhage, and emphysema. Botulism: caused by exotoxin of Clostridium botulinum (type
C most common). Flaccid paralysis. No characteristic lesions.
Erysipelothrix rhusiopathiae Acute septicemic disease of chickens and turkeys. Characterized by hemorrhages over epicardium,
abdominal fat, skin, muscle, congested and enlarged spleen, foci of hepatic necrosis. Chronic disease
characterized by vegetative endocarditis and arthritis.
Escherichia coli Colibacillosis cause localized or systemic infections. Colisepticemia with polyserositis, coligranulomas
(Hjarre’s disease), salpingitis, yolk sac infection, cellulitis, osteomyelitis/synovitis, swollen head
syndrome, and panophthalmitis.
Gallibacterium anatis biovar Causes salpingitis, peritonitis, and septicemia in chickens. Associated with respiratory disease in
hemolytica turkeys.
Ornithobacterium Causes respiratory disease in chickens and turkeys. See sinusitis, tracheitis, fibrinous
rhinotracheale bronchopneumonia with consolidated lungs, airsacculitis.
Mycobacterium avium Avian mycobacteriosis. Caseous granulomas in many tissues including liver, spleen, intestine, bone
marrow, lung.
Mycoplasma spp. Mycoplasma gallisepticum: chronic respiratory disease in chickens and infectious sinusitis in turkeys. See
sinusitis, tracheitis, bronchopneumonia, airsacculitis. Coinfections enhance disease severity. Drop in
egg production in layers. Mycoplasma synoviae: infectious synovitis and subclinical respiratory disease in
chickens and turkeys. See swollen joints and breast blisters. Mycoplasma meleagridis and Mycoplasma
iowae: affect mainly turkeys. See drop in egg production, decreased hatchability, and chondrodystrophy,
with mild or no respiratory signs.
(Continued)
178 Lisa M. et al.
Table 3 Continued
Pasteurella multocida Cause fowl cholera. Acute septicemic disease with high mortality and morbidity in chickens and
turkeys. Petechiae on viscera, fibrinous bronchopneumonia with consolidated lungs, enlarged liver with
foci of necrosis, polyserositis. Chronic and localized infections including facial cellulitis, synovitis, otitis
media, sinusitis, etc.
Riemerella anatipestifer Respiratory disease in turkeys. Ocular discharge, neurological signs, as much as 10% mortality. Usually
(turkeys) see fibrinous polyserositis, meningitis, and uveitis.
Salmonella spp. Cause acute or chronic septicemic disease in chickens and turkeys. Caseous granulomas or fibrinous
inflammation in affected organs. Pullorum disease and Fowl Typhoid - caused by Salmonella enterica

subsp. enterica serotypes Pullorum and Gallinarum, respectively. Paratyphoid salmonellosis: caused by
various serotypes. Asymptomatic infections or disease in young and immunosuppressed birds.
Arizonosis: septicemic disease in chicks and turkey poults.
Staphylococcus aureus Causes systemic disease characterized by pododermatitis, tenosynovitis, osteomyelitis, endocarditis,
and yolk sac infection.
Streptococcus/Enterococcus Septicemia characterized by valvular endocarditis with secondary infarcts in heart, liver, spleen. Also,
osteomyelitis, arthritis, tenosynovitis, salpingitis, meningoencephalitis. Enterococcus cecorum cause
vertebral spondylitis in chickens.
Protists
Cochlosoma anatis (turkeys) Flagellate enteric protozoon. Causes catarrhal enteritis in turkeys.
Cryptosporidium spp. Cryptosporidium baileyi infects the respiratory tract, bursa, and cloaca. See naso-ocular discharge, swollen
sinuses, respiratory signs. C. meleagridis infects the small intestine and can cause severe diarrhea in
turkey poults. See basophilic, intracellular, and extracytoplasmic 2–4 μm organisms in mucosal
epithelium.
Eimeria spp. Pathogenic coccidiosis: Coccidiosis in chickens: Eimeria tenella (ceca), E acervulina (upper small intestine),
E maxima, and E necatrix (mid small intestine). Coccidiosis in turkeys: Eimeria melagrimitis (small
intestine), E gallopavonis, and E adenoeides (ileum and ceca). Catarrhal to necrohemorrhagic enteritis.
Coccidiosis in quail: Eimeria lettyae, E dispersa, and E coloni.
Histomonas meleagridis Cause histomoniasis/blackhead. Saucer-shaped depressions or pale white foci in liver and
fibrinonecrotic typhlitis. Lymphoplasmacytic to granulomatous inflammation with round, 10- to 20-μm,
PAS-positive trophozoites.
Hexamita meleagridis Flagellate enteric protozoon. Cause catarrhal enteritis and foamy or watery diarrhea in turkeys.
(turkeys)
Fungi
Aspergillus spp. Aspergillus fumigatus and A flavus most common. Acute or chronic respiratory disease. Caseous nodules
or plaques in the lungs, air sacs, bronchi, trachea, brain, eyes, visceral organs, etc. Greenish mold growth
in air sacs. Microscopically see granulomas with fungal hyphae.
Candida albicans Candidiasis is a common mycosis of the upper gastrointestinal tract. See white proliferative plaques
primarily in oral cavity, esophagus, and crop with yeasts, hyphae, and pseudohyphae.
Ochroconis gallopava Ochroconiasis is a mycotic disease of young chickens and turkey poults. Respiratory and neurological
signs. Granulomas with pigmented fungal hyphae in lungs, brain, and eyes.
Nematodes
Ascaridia spp. Ascaridia galli in chickens; Ascaridia dissimilis in turkeys. Eosinophilic enteritis, loss of weight, and
intussusception. Granulomas and or necrosis in livers due to larval migration in turkeys.
Capillaria spp. Capillaria contorta and C annulata affect the upper digestive tract. Hyperplastic mucosa with nematodes
within mucosa, fibrinonecrotic esophagitis, and ingluvitis. C obsignata, C caudinflata cause catarrhal
enteritis.
Heterakis gallinarum Asymptomatic infection. Nematodes in the cecal lumen. Carrier of H meleagridis.
Syngamus trachea Y-shaped bright red nematodes in tracheal lumen. Cause granulomatous tracheitis and occasionally
bronchitis.
Tetrameres americana Bright red female worms embedded in proventricular glands.
Cestodes Raillietina cesticillus and Choanotenia infundibulum most common. Pathogenic in large numbers, can cause
enteritis and intestinal blockage.
Ectoparasites
Lice Chicken body louse (Menacanthus stramineus) and shaft louse (Menopon gallinae). Female lice glue their
eggs (nits) to host feathers. Minimal lesions.
Mites Can cause anemia, feather alopecia, drop in egg production, low fertility in males and weight loss.
Dermanyssus gallinae (Red mite): feed mostly at night. Mortality in heavy infestations. Ornithonyssus
sylviarum (Northern fowl mite): blackened feathers surrounding the vent with scabbed skin.
Knemidocoptes mutans (scaly leg mite): proliferative and hyperkeratotic dermatitis in legs and feet.
PAS, periodic acid-Schiff.

Table 4 Common Metabolic, Spontaneous (and Neoplastic) Conditions in Parrots and Budgerigars51 ,70,71
Beak overgrowth Caused by malnutrition or hepatopathy.

Gastric carcinoma and Most common in budgerigars, gray-cheeked parakeets, cockatiels, and Amazon parrots. Common in
adenocarcinoma proventricular-ventricular junction. Tumors are usually flat rather than nodular and may extend to the
serosal surface, causing peritonitis. Metastasis to lungs and liver are uncommon.
Hemorrhagic diathesis In budgerigars and nestlings with low fat stores. Affected birds are anorexic, have an empty crop, and reflux
of black blood from intestines into the stomach.
Pancreatic necrosis Characterized by necrosis and hemorrhage in pancreas, and mesenteric fat necrosis. Associated with
high-fat diet.
Papillomatosis Common neoplasm of the oral cavity and cloaca of New World psittacines. White to pink raised nodules,
often with a cauliflower-like appearance. Associated with psittacid herpesvirus (PsHV)-1. Bile duct and

occasionally pancreatic duct tumors may occur in birds with cloacal papillomas. Oral papillomas are rare in
Amazon parrots.
Cardiovascular
Atherosclerosis Very common in psittacines, especially in Amazon and African gray parrots. Higher prevalence in older
birds. Also predisposed by fat-rich diets and reproductive disease. Atheromatous yellow plaques often seen
in aorta, brachiocephalic trunks, pectoral and carotid arteries; other arteries rarely involved. Coronary
arteries rarely involved; associated with myocardial degeneration and necrosis.72 Affected arteries have
thickening of tunica intima and media with vacuolated, lipid-laden smooth muscle cells and macrophages,
chondroid metaplasia, and fibrosis. Enlargement of the heart and right-sided heart failure in severe cases.
Endocrine
Diabetes mellitus Affected birds have polyuria/polydipsia and loss of weight. Hypoplasia, atrophy, and/or vacuolation of islet
cells.
Goiter Hyperplastic goiter: caused by feeding iodine-deficient diets. Budgerigars are particularly susceptible.
Bilateral hyperplasia; thyroid size can exceed 10 mm. Enlarged thyroid put pressure on trachea, crop and
may cause collapse of interclavicular air sac. Thyroids have small follicles, with little to no colloid. Colloid
goiter: involution phase of thyroid hyperplasia. Thyroids have large follicles with abundant colloid.
Hematopoietic-
immunologic
Hemopoietic tumors Multicentric lymphosarcoma is most common involving liver, spleen, kidneys, bone marrow, skin, thymus,
pancreas, etc. The tumors can be diffuse or nodular.
Hepatobiliary
Extramedullary Caused by chronic blood loss.
erythropoiesis
Extramedullary Associated with chronic inflammatory diseases.
granulopoiesis
Hepatic lipidosis Obesity, enlarged, pale yellow and friable liver. Associated with high-fat diets. Environment, toxicities,
hormones, genetics (shell parakeets) influence lipidosis.
Neoplasia Bile duct proliferation and tumors (adenomas and carcinomas) common and often associated with
papillomatosis.
Integumentary
Amazon foot skin necrosis In Amazons, common in yellow-naped Amazon. Erythema and necrosis on the unfeathered skin of the legs
and feet. Unknown cause, possibly due to delayed hypersensitivity. Associated with staphylococcal
dermatitis and exposure to tobacco smoke. Predispose to self-mutilation and secondary bacterial infection.
Feather cysts Caused by dysplastic feather and feather follicle growth. Characterized by hard yellow lumps within and
projecting from skin. Cysts are lined by stratified squamous epithelium and filled with lamellar keratin,
may also see barbs and barbules. Ruptured cysts cause dermal granuloma.
Feather-duster disease Congenital condition characterized by excessive and continued growth of contour, tail and flight feathers in
budgerigars. Affected birds are unable to fly.
Feather picking Characterized by missing and frayed feathers, reddened cutaneous lesions and ulcers. Microscopically, see
dermal scarring, perivascular dermatitis, edema, epidermal and follicular hyperkeratosis. Many
predisposing factors including underlying disease conditions, hormonal derangements, and psychogenic
disorders.73
Malcolored feathers Associated with hepatopathy and malnutrition in Amazon parrots.
Nail overgrowth Caused by malnutrition or hepatopathy.
Neoplasia Lipoma is common. Subcutaneous mass containing well-differentiated adipocytes. Other tumors include
liposarcoma, myelolipoma, hemagioma/sarcoma, squamous cell carcinoma, fibroma/sarcoma, lymphoma,
melanoma, uropygial gland tumors, etc.
Alimentary
Beak anomalies Congenital or acquired. Genetically induced anomalies reported in budgerigars. Also associated with
vitamin deficiency, toxicity, and improper incubation temperatures.
Pododermatitis (bumblefoot) Ulcerative dermatitis and cellulitis of toes and footpad usually caused by cutaneous trauma followed by
bacterial infection (usually Staphylococcus sp. and Escherichia coli). Often associated with husbandry
conditions (improper perches, lack of sunlight exposure) and malnutrition.
(Continued)
180 Lisa M. et al.
Table 4 Continued
Xanthoma Common in older budgerigars and cockatiels. Yellow subcutaneous swellings usually present in the skin
over the ventral abdomen, wings, thighs, eyelids, and face. Rarely present in internal organs and bone
marrow. Microscopically see foamy macrophages, multinucleated giant cells, and cholesterol clefts.
Predisposed by high fat or cholesterol diets, genetics, and trauma.
Wing web dermatitis Common in African gray parrots. Exudative and ulcerative dermatitis in propatagium and axillary areas
with loss of feathers. One or both wings affected. Poorly understood condition. May be self-induced or
initiated by hypersensitivity, excessive moisture in wing web, and hormonal feather loss.
Self-mutilation and secondary infections can occur in chronic cases.
Multisystemic
Hypovitaminosis A Squamous metaplasia of glandular epithelium with hyperkeratosis in respiratory tract, conjunctiva,

mouth, esophagus, ureters, kidneys, uropygial gland, nasal lacrimal duct, salivary glands, etc.
Lead poisoning From exposure to galvanized wire. Clinical signs include weakness, vomiting, polyuria/polydypsia,
neurological signs, anemia, hemoglobinuria, and diarrhea.74 Lesions include hepatocyte necrosis,
hemosiderosis, erythrophagocytosis, and nephrosis.
Vitamin D3 toxicity Due to excess vitamin D3 supplementation. See mineralization in kidneys and soft tissues such as
proventriculus, heart, air sacs, etc. Also see renal tubular necrosis, secondary renal gout, and
mineralization of hepatic sinusoids and blood vessels.
Visceral gout Caused by dehydration, renal disease, and obstruction of urine flow. Precipitation of uric acid crystals in
kidneys and on serous membranes.
Zinc poisoning From exposure to galvanized wire and containers. Affected birds may have erosive ventriculitis,
pancreatic acinar degeneration and necrosis, enteritis, renal tubular necrosis, nephrosis, hemosiderosis,
and erythrophagocytosis.
Musculoskeletal
Rickets/osteomalacia Rickets in younger birds and osteomalacia/osteoporosis in older birds. Deficiency of calcium,
phosphorus, or vitamin D3 or an imbalance in calcium to phosphorus ration. Soft and pliable beak,
claws and keel, beading of ribs (“rickety rosary”), enlarged metaphysis, fractures of long bones, enlarged
parathyroid glands.
Split sternum Open wound of the skin and muscle over the cranial portion of the sternum. May result in secondary
(automutilation of the bacterial infections and osteomyelitis. Caused by self-mutilation or improper wing trimming in parrots.
sternum)
Spraddle leg One or both legs splayed laterally from the hip or stifle. Associated with nutritional deficiencies,
trauma, poor footing, improper incubation, and genetic defects.
Nervous
Neuronal lipofuscinosis Common in neuronal cell bodies of older parrots.
Traumatic brain damage Usually caused by aggression from cage mates. See bruises and hemorrhage on the skin overlying the
skull, hemorrhages in meninges and within brain parenchyma.
Reproductive
Egg-binding Characterized by the presence of a retained egg in the vagina. Predisposed by calcium deficiency,
obesity, environmental stressors, and deficiency of vitamin E and selenium. Oviduct prolapse is a
common sequela.
Egg-yolk coelomitis Egg yolk material deposited on serosal surfaces and that induce histiocytic inflammation. Associated
with chronic reproductive tract disease, such as salpingitis, neoplasia, as well as ectopic ovulation and
oviduct rupture. Can be associated with bacterial infection. Respiratory distress may occur due to
retrograde yolk inhalation and embolic pneumonia.
Ovarian cysts Congenital condition most common in budgerigars. Cysts are fluid-filled and thin-walled.
Testicular tumors Commonly described in budgerigars. Include seminoma, Sertoli cell tumor, interstitial cell tumor, and
others such as lymphoma, sarcomas, and teratoma. Change in cere color from blue to brown in
budgerigars with Sertoli cell tumor.
Respiratory
Choanal atresia Closed choanal slit in young African Grey parrots. Affected birds have chronic nasal or ocular discharge,
and distended sinuses with clear exudate.
Chronic pulmonary In older Amazon parrots. Pulmonary interstitial fibrosis and right-sided cardiomyopathy.
interstitial fibrosis
Oxygen toxicosis Edema and interstitial pneumonia in budgerigars.
Pneumoconiosis Histiocytic infiltrates in the wall of the parabronchi containing intracytoplasmic dust or carbon
particles.
Polytetrafluoroethylene Polytetrafluoroethylene-coated heat lamps and lightbulbs release toxic gases that cause acute
toxicosis pulmonary congestion, hemorrhage, and edema.
Urinary
Renal neoplasia Common in young to middle-aged male budgerigars. Most tumors affect the cranial lobes.
Nephroblastomas, renal adenocarcinomas, and carcinomas. Size can vary but some impinge on sciatic
nerve causing paresis.
Urolithiasis Characterized by ureters distended with uroliths (composed of mineralized urates) and renal atrophy.55
Often associated with renal and visceral gout. Also caused by high-calcium diet.
Table 5 Common infectious diseases in parrots and budgerigars16 ,51,70,71
Virus
Adenoviruses Characterized by necrotizing hepatitis associated with intranuclear inclusion bodies. May also see enteritis,
bronchitis, pancreatitis, nephritis, encephalitis, etc, associated with intranuclear inclusions. Intranuclear
inclusions may be darkly basophilic or clear.
Avian Bornavirus Psittaciform 1 orthobornavirus (Parrot Bornavirus genotypes 1, 2, 3, 4, and 7), Psittaciform 2 orthobornavirus
(Parrot Bornavirus genotype 5). Cause proventricular dilatation disease. Common and chronic disease of
psittacines. Characterized by dilation of the proventriculus, anorexia, regurgitation, passing of undigested
seeds in feces, diarrhea, neurological signs, and loss of weight. Common microscopic lesions include
lymphoplasmacytic ganglioneuritis of splanchnic nerves of the gastrointestinal tract, encephalomyelitis,
myocarditis, and adrenalitis. Budgerigars may be resistant.

Avian Papillomavirus Proliferative cutaneous lesions characterized by fronds of epidermal hyperplasia supported by a connective
tissue stroma.
Avian Paramyxovirus type 3 Characterized by encephalitis with or without intranuclear and intracytoplasmic inclusion bodies in
neurons and glial cells.
Avian Polyomavirus Cause budgerigar fledgling disease. Young psittacines are highly susceptible with very high mortality; adult
birds also susceptible. Characterized by feather dystrophy, hemorrhages in skin, skeletal muscle, heart, and
intestine, necrotizing and hemorrhagic hepatitis, necrosis, inflammation and hemorrhage in various
organs. See basophilic and karyomegalic intranuclear inclusion bodies in various tissues.
Avian poxvirus Psittacinepox virus. Characterized by proliferative lesions primarily on unfeathered skin of the head, legs, and
feet (cutaneous form), and yellow raised plaques in the mucosa of the upper gastrointestinal tract,
respiratory tract, and conjunctiva (wet or diphtheritic form). Microscopically, see epidermal or epithelial
hyperplasia, ballooning degeneration and eosinophilic, intracytoplasmic inclusion bodies (Bollinger bodies).
Beak and feather disease virus Psittacine Beak and Feather Disease. Characterized by chronic feather and beak dystrophy,
immunosuppression, and sudden death in young birds due to secondary bacterial septicemia and fungal
infections. Usually see basophilic and botryoid intracytoplasmic inclusions in feather follicular epithelium,
feather pulp, and dermis.
Psittacid alphaherpesvirus 1 Causes Pacheco’s disease. Characterized by fatal, peracute to acute viral hepatitis. Common disease in
Amazon parrots. Characterized by enlarged and mottled liver, occasionally with petechiae. Microscopically,
see multifocal to massive hepatic necrosis with eosinophilic intranuclear inclusion bodies and minimal
inflammation. Necrotizing splenitis and pancreatitis also commonly seen.
Bacteria
Chlamydia psittaci Affected birds may have sinusitis, dyspnea and yellowish-green diarrhea, weight loss, and neurological
signs. Gross lesions include enlarged and congested liver and spleen, airsacculitis, and pericarditis.
Microscopically, see inflammation, necrosis, and intracellular bacteria in hepatocytes and macrophages.
Clostridium sp. Clostridium perfringens cause necrotizing enteritis. Clostridium colinum cause ulcerative enteritis.
Coxiella sp. Characterized by severe hepatitis, splenitis, pneumonia, nephritis, encephalitis, etc. Microscopically, see
small basophilic coccoid organisms in the cytoplasm of macrophages.
Escherichia coli Localized or systemic infection. Colisepticemia with polyserositis, hepatitis, and meningoencephalitis. May
also see enteritis with attaching and effacing E coli.
Klebsiella sp. Localized or systemic infection involving respiratory tract, liver, and brain.
Mycobacterium sp. Chronic progressive disease of semimature to mature birds, most commonly causes by infection with
Mycobacterium avium and M genavense. Also caused by M tuberculosis and M bovis. Characterized by enlarged
liver and spleen, thickened intestinal wall, and tan to white nodules in affected tissues. Microscopically, see
diffuse or focal infiltration of foamy macrophages with myriads of acid-fast staining bacilli in the
cytoplasm. Necrosis is not common.
Salmonella sp. Salmonella enterica serotype typhimurium most frequently isolated. Cause enteric and systemic disease with
high mortality in young birds. Characterized by hepatomegaly, splenomegaly, pneumonia, and catarrhal to
hemorrhagic enteritis. Microscopically, there is necrosis and inflammation in intestines, liver, spleen, and
other visceral organs.
Yersinia pseudotuberculosis Chronic contagious disease of psittacines. Birds often found dead, loss of weight, digestive and respiratory
signs can be seen. Characterized by miliary, pale yellow nodules of caseous granulomas resembling
mycobacteriosis in various organs including liver, spleen, intestine, lung, air sacs. Microscopically, see
necrosis and inflammation associated with large numbers of Gram-negative bacteria.
Protists
Giardia psittaci Cause enteric disease in budgerigars. Asymptomatic infections are common in these birds. Microscopically,
see flattened and pyriform protozoa in crypts and along intestinal villi, often without inflammatory
reaction in the lamina propria.
Sarcocystis falcatula Causes systemic disease characterized by pulmonary congestion, edema and hemorrhage, hepatomegaly
and splenomegaly. Microscopically, see lymphoplasmacytic interstitial pneumonia with edema and
schizonts in capillaries. May also see myocarditis, hepatitis, splenitis, nephritis, encephalomyelitis, neuritis,
myositis, uveitis, etc, associated with schizonts, as well as mature cysts in the heart and skeletal muscle.
Opossum is the definitive host, cowbirds and grackles are intermediate hosts. Old World psittacines are
highly susceptible.
(Continued)
182 Lisa M. et al.
Table 5 Continued
Spironucleus meleagridis Flagellated enteric protozoan that cause weight loss, diarrhea, poor feathering, and mortality. See
distended, hyperemic, fluid-filled intestine, or catarrhal enteritis. Microscopically, there is mixed
inflammatory infiltrate and pyriform protozoa measuring 5–12 μm long along the mucosal epithelium
and in crypts.
Trichomonas gallinae Proliferative and diphtheritic plaques in crop and esophagus associated with flagellated protozoa.
Common in budgerigars.
Fungi
Aspergillus sp. Usually cause mycotic pneumonia and airsacculitis. Characterized by caseous nodules or plaques in the
lungs, air sacs, bronchi, trachea, syrinx, and occasionally systemic infection with lesions in visceral

organs and brain. May also see greenish mold growth in air sacs. Microscopically, see granulomatous
inflammation associated with fungal hyphae. Predisposed by immunosuppression, coinfections, poor
husbandry, and malnutrition (especially hypovitaminosis A).
Candida albicans Characterized by white proliferative plaques of hyperkeratosis primarily in oral cavity, esophagus and
crop with yeasts, hyphae, and pseudohyphae. Predisposed by immunosuppression, antibiotic therapy,
coinfections, environmental stressors, and malnutrition (especially hypovitaminosis A). Fatal systemic
disease may occur in young birds.
Encephalitozoon hellem Primarily seen in young birds. Often associated with immunosuppression such as caused by psittacine
beak and feather disease and other coinfections. Lesions include necrosis and inflammation in kidney,
liver, spleen, intestine, conjunctiva, and cornea associated with Gram-positive organisms.
Macrorhabdus ornithogaster Often asymptomatic infections. Also associated with chronic wasting disease. Proventriculitis
characterized by inflammation in lamina propria, goblet cell hyperplasia, and excessive mucus
secretion. Large (2 × 20–40 μm) Gram-positive, PAS positive organisms commonly found on the mucosal
surface of the gastric isthmus.
Nematodes
Ascaridia sp. Intestinal nematodiasis associated with loss of weight, diarrhea, intussusception, and partial or total
intestinal obstruction in heavy infections.
Cestodes Cestodiasis such as caused by Raillietina, Hymenolepis, Amoebotaenia, etc are common in psittacines.
Pathogenic in large numbers, associated with enteritis and intestinal obstruction.
Ectoparasites
Mites Knemidocoptes pilae in budgerigars cause proliferative lesions in the skin of the leg, beak, and cere.
Microscopically, see epidermal acanthosis, hyperkeratosis, and pleocellular inflammation associated
with mites within tunnels in the epidermis.
Table 6 Common Metabolic, Spontaneous (and Neoplastic) Conditions in Finches51,70,75–77
Hematopoietic- immunologic
Neoplasia Lymphoma is common in finches.
Hepatobiliary
Extramedullary granulopoiesis Associated with chronic inflammatory diseases.
Hepatic lipidosis Obesity, swollen, yellow or tan and friable liver. Associated with high-energy diets and inadequate
exercise.
Integumentary
Dry gangrene of extremities Induced by trichothecene T-2 toxin. Affected toes require amputation.75
Feather picking and cannibalism Aggressiveness ranging from loss of feathers on the back of the head to cannibalism. Usually
associated with 1 or more dominant males. Also predisposed by overcrowding.
Pododermatitis (bumblefoot) Ulcerative dermatitis and cellulitis of toes and footpad usually caused by cutaneous trauma followed
by bacterial infection (usually Staphylococcus sp. and Escherichia coli).
Multisystemic
Amyloidosis Common in Gouldian finches. Associated with chronic diseases. Amyloid deposits commonly seen in
the liver, spleen, kidneys, and blood vessel walls.
Visceral gout Caused by dehydration, renal disease, and obstruction of urine flow. Precipitation of uric acid crystals
in kidneys and on serous membranes.
Musculoskeletal
Foreign body constrictive toe necrosis Strangulated digit caused by synthetic nest material such as nylon. Necrotic toe requires amputation.
Prevention by using natural fibers or nest pads.78
Reproductive
Egg-binding Usually associated with malnutrition caused by lack of dietary calcium, protein, vitamin E, and
selenium. May cause oviduct prolapse and sudden death.
Respiratory
Pneumoconiosis Histiocytic infiltrates in the wall of the parabronchi containing intracytoplasmic dust or carbon
particles.
Table 7 Common Infectious Diseases of Finches51,70,76–79
Virus
Avian Papillomavirus Proliferative lesions in the skin of the legs and feet. Microscopically, see fronds of epidermal hyperplasia
supported by a vascular stroma. Enlarged nuclei in epidermal cells.
Avian Paramyxovirus Serotypes 1, 2, and 3. Associated with conjunctivitis, respiratory signs, diarrhea, and neurological signs.
Lesions include pulmonary edema, pancreatic atrophy, and pale myocardium. Inclusion bodies may be
seen in heart, brain, and pancreas.
Avian Polyomavirus Liver enlarged and mottled white, splenomegaly, serosal or subserosal hemorrhage of intestine, pale
myocardium, hemorrhage, and muscle pallor. Tubular elongation of the lower mandible in Gouldian

finch. Hemorrhages, necrosis, and lymphoplasmacytic inflammation in various organs such as liver,
spleen, bursa, thymus, etc. Karyomegalic intranuclear inclusions in various tissues.
Finch Circovirus Characterized by feather dystrophy and characteristic circovirus inclusions in bursa of Fabricius.
Finch Herpesvirus Passerid Herpesvirus: 1. Disease primarily seen in Gouldian finches characterized by high mortality,
conjunctivitis, tracheitis, bronchitis, associated with epithelial hyperplasia, cytomegaly, karyomegaly,
and intranuclear inclusion bodies. May also see hepatic necrosis with typical viral inclusions.
Bacteria
Mycoplasma gallisepticum Conjunctivitis and sinusitis in captured wild house finches. Microscopically, see lymphoplasmacytic
inflammation and epithelial hyperplasia in conjunctiva and upper respiratory tract.
Mycobacterium sp. Mycobacterium genavense, Mycobacterium avium-intracellulare complex, and M peregrinum in finches.
Granulomatous inflammation with acid-fast bacteria in affected tissues.
Salmonella sp. Salmonella typhimurium var. copenhagen. Cause granulomas in liver, spleen, rudimentary ceca, ocular
lesions, and osteomyelitis.
Staphylococcus sp. and Common bacterial infections in finches. Associated with hepatitis and nephritis. Systemic infections
Streptococcus sp. may originate from chronic cutaneous lesions or an infected air sac.
Yersinia pseudotuberculosis Associated with diarrhea and death. Usually see granulomas in liver, spleen, and intestine.
Prototists
Atoxoplasma sp. Liver enlarged with white foci, splenomegaly. Enteritis, hepatitis, myocarditis with arteritis, splenitis,
myositis, dermatitis, pneumonia, etc. Schizonts in cytoplasm of macrophages.
Cochlosoma sp. Flagellate enteric protozoan of small intestine associated with diarrhea, undigested seeds in the
intestine, as well as dehydration and death in young birds.
Cryptosporidium sp. Associated with loss of weight and yellowish droppings with undigested seeds. See inflammation,
necrosis, and hyperplasia of glandular epithelial cells of the proventriculus. May be associated with
environmental stressors and immunosuppressive diseases.
Giardia sp. Infection may be asymptomatic or associated with weight loss and diarrhea.
Trichomonas gallinae Common in Australian finches. Usually see proliferative and yellow diphtheritic plaques in the mouth,
crop, esophagus, and occasionally in proventriculus associated with flagellated protozoa.
Fungi
Aspergillus sp. Usually causes mycotic pneumonia and airsacculitis. Characterized by caseous nodules or plaques in
the lungs, air sacs, bronchi, trachea, syrinx, and greenish mold growth in air sacs. Microscopically, see
granulomatous inflammation associated with fungal hyphae.
Candida albicans Characterized by white proliferative plaques of hyperkeratosis primarily in oral cavity, esophagus and
crop with yeasts, hyphae, and pseudohyphae. Ventricular mycosis is common in finches. Usually see
fungal organisms within the koilin layer. Predisposed by nutritional deficiencies, antibiotic therapy and
poor hygiene.
Dermatophytosis Microsporum gallinae and Trichophyton sp. cause feather loss and hyperkeratosis in the skin of the head
and neck.
Macrorhabdus ornithogaster Proventriculitis characterized by inflammation in lamina propria, goblet cell hyperplasia, and excessive
mucus secretion. Large (2 × 20–40 μm) Gram-positive, PAS positive organisms commonly found on the
mucosal surface of the gastric isthmus.
Nematodes
Ascaridia sp. Intestinal nematodiasis associated with loss of weight, diarrhea, intussusception, and partial or total
intestinal obstruction in heavy infections.
Cestodes Tapeworm infestation is common in finches. Low infectivity levels do not cause clinical disease.
Pathogenic in large numbers, associated with enteritis and intestinal obstruction.
Ectoparasites
Mites Knemidocoptes pilae: scaly face and scaly leg. Sternostoma tracheacolum: respiratory tract mite (trachea,
syrinx, lung, air sac), common in Gouldian finches. Small black masses in the lumen of the trachea.
Mites attach to the mucosal epithelium. Microscopically, see epithelial necrosis, hyperplasia, and
inflammation in the lamina propria.

184 Lisa M. et al.
Table 8 Commonly Used Fish Species in Research80–84
Name (Species) Comments/Common Research Areas
Atlantic salmon (Salmo salar) Economically valuable, multi-continent, net-farmed, and aquacultured
anadromous food fish, research emphasis on parasitic and viral
diseases that affect production and meat quality.85
Channel catfish (Ictalurus punctatus) Important freshwater aquacultured food fish and most abundant wild
catfish in North America.86 ,87
Fathead minnow (Pimephales promelas) North American freshwater cyprinid used as a bait or feeder fish; it is
a common subject for endocrine disruption research.88
Flounders (Pleuronectes, Platichthys, and Paralichthys spp.) Commercially valuable food fishes with worldwide distribution, they
can develop primary liver neoplasms that have been associated with
environmental contamination in some studies.89 –91

Goldfish (Carassius auratus) This domesticated freshwater ornamental and feeder fish of the
family Cyprinidae is studied for neuroendocrinology, developmental
biology, and the pathogenesis of infectious diseases.92 –95
Guppy (Poecilia reticulata) This domesticated freshwater ornamental fish bears live young and is
studied for evolutionary biology, genetics, and aging.96
Japanese medaka (Oryzias latipes) First vertebrate in which Mendelian inheritance was demonstrated
and first transgenic fish. Hardy and prolific, studied for developmental
genetics, carcinogenesis, and endocrine disruption research.
Transparent varieties allow in vivo observation of green fluorescent
protein-labeled internal structures and reactions.97 –100
Mummichog (Fundulus heteroclitus) Estuarine killifish baitfish along the North American Atlantic coast
known to survive in extreme environmental conditions. Demonstrated
link between hepatic and pancreatic neoplasia and creosote
contamination. Also used in endocrine disruption research.101,102
Platyfish and swordtails (Xiphophorus spp.) Freshwater species naturally found in rivers and ponds in central
America. Certain hybrids, particularly crosses of X maculatus and X
helleri, are frequently used in genetic studies of melanoma.103
Rainbow trout (Oncorhynchus mykiss) Widely distributed freshwater and anadromous salmonid fish, it is a
traditional subject in environmental carcinogenesis studies.104
Roach (Rutilus rutilus) Freshwater and brackish water cyprinid native to Europe and western
Asia, it studied for endocrine disruption research in which male
feminization was linked with wastewater treatment facility
effluents.105
Gilthead seabream (Sparus aurata) Aquacultured marine food fish found naturally in the Mediterranean
Sea and eastern North Atlantic, often used in immunologic studies.106
Stickleback (Gasterosteus spp.) Freshwater and marine species distributed naturally across the
Northern Hemisphere, they have been important models in
evolutionary biology and endocrine disruption research.107,108
Tilapia (Oreochromis spp.) Predominantly freshwater and less commonly brackish water fish
originating from Africa, most commonly raised food fish across the
globe and can be invasive. Research efforts focused on maximizing
aquaculture production.109
Japanese yellowtail (Seriola quinqueradiata) These and other marine amberjacks (Seriola spp.) are important
aquacultured food fish, and research is typically centered on various
aspects of production.110
Zebrafish (Danio rerio) This aquarium-sized freshwater cyprinid is important as medical
research model for developmental biology, toxicological studies
(including endocrine disruption), carcinogenesis, genomics, and
transgenesis.111 –114
of captive finches should contain commercial pelleted feed, Fish

seed mixes, and vegetables. Grit should be added to the diet
as a source of calcium and to assist with mechanical digestion The practice of fish pathology is literally centuries old.21 Cur-
of feed. rently, tissues and other bodily samples are examined macro-
In summary, birds are ideal subjects for use in research due scopically and microscopically to determine the presence and
to their short generation time, small size, low cost, and ease extent of infectious or noninfectious disease in fish reared for
of animal handling and care. We have indicated in Table 1 the food, sport, or the pet trade, and in captive or wild animals
anatomy and physiologic features of Galliformes, Psittaciformes, used as research subjects. Various examples (in no specific order)
and Passeriformes. Tables 2–7 list noninfectious and infectious include the assessment of wild-caught fishes to identify and/or
diseases that most frequently affect birds in these taxonomic monitor problems of environmental contamination; the utiliza-
orders. tion of captive fishes as research subjects in bioassays involving
Table 9 Anatomic and Physiologic Features of Fish Models115,116
Alimentary
Gizzard Certain species (eg, shad, menhaden) possess an avian-like gizzard.
Intestines Salmonids and a few other species have multiple finger-like pyloric ceca that project from the proximal
intestine.
Oral cavity Certain species do not have oral teeth but instead have teeth located in the pharynx, which grind food against a
keratinized pharyngeal pad.
Pancreas, exocrine The exocrine pancreas is not a single discrete organ but is distributed as islands throughout the intestinal
mesentery, while some species have additional intra-hepatic pancreas in the portal regions.
Stomach Certain species (eg, some herbivorous fishes) lack a glandular stomach or any type of discernable pouch.
Swim bladder Essentially a large diverticulum off the esophagus, it is used for buoyancy, sound production, sound

amplification, and/or respiration, depending on the species.
Swim bladder, gas gland More modern fishes (physoclists) have a gas gland and vascular rete complex that secretes gas into the swim
bladder.
Swim bladder, pneumatic More ancient fishes such as cyprinids and salmonids (physostomes) retain a convoluted duct connection to the
duct esophagus that allows them to gulp air to fill the swim bladder.
Cardiovascular
Great vessels Fish have a ventral and dorsal aorta (pre- and post-gills, respectively), and blood from the respiratory system is
pumped directly into the systemic circulation without return to the heart (ie, no pulmonary artery and vein
equivalents).
Heart The fish heart has 4 compartments but only 2 chambers: sinus venosus, atrium, ventricle, and bulbus
arteriosus. Piscine cardiac muscle has profound regenerative abilities.
Portal system In addition to a hepatic portal system as in mammals, the fish kidney receives blood directly from the caudal
musculature via renal portal vessels.
Endocrine
Chromaffin and interrenal Respectively analogous to the mammalian adrenal medulla and cortex, these tissues, which produce adrenergic
tissue and corticosteroid hormones, are typically located in the anterior kidney where they often surround the
cardinal veins.
Corpuscle of Stannius Paired organ embedded in posterior kidney, it secretes stanniocalcin, which reduces plasma calcium by
decreasing absorption via gills and intestine.
Pancreas, endocrine Many teleosts have a large primary islet (Brockman body) and relatively few small secondary islets associated
with the mesenteric exocrine pancreas.
Thyroid Rather than discrete glands, in most teleosts the thyroid follicles are scattered along the ventral aorta in the
lower jaw/ventral oropharynx region. It is not unusual to observe occasional follicles in ectopic sites such as the
kidney. Fish thyroid lacks c-cells; this function is assumed by the ultimobranchial body.
Ultimobranchial body This is a single midline organ located within the transverse membrane that separates the pericardial cavity
from the abdominal cavity. It secretes calcitonin, which reduces plasma calcium via increased renal excretion
and sequestration into bone.
Hematopoietic-
immunologic
Anterior kidney The renal interstitium, and to a lesser extent the spleen, generally replaces the mammalian bone marrow as the
primary source of hematopoiesis.
Bone marrow, lymph nodes Fish lack bone marrow and lymph nodes.
Pigmented macrophage Pigmented macrophage aggregates, which can be in a variety of tissues depending on species, are thought to
aggregates serve as antigen-presenting centers in addition to iron storage depots and sites for the sequestration of cell
(melanomacrophage breakdown products. Increases in the size and numbers of these constituent structures, which should be
centers) distinguished from inflammatory granulomas, may occur with age/size and toxicant exposure.
Spleen White pulp tends to be comparatively sparse in fish spleens, and germinal centers are rare.
Thymus T-cell maturation occurs in the thymi, which are located bilaterally beneath the dorsal opercula, and lack
well-defined cortical and medullary regions.
Hepatobiliary
Liver The classic hexagonal lobular architecture is not readily apparent in fish livers, and hepatic arteries are sparse.
The livers of cyprinid fishes have 3 lobes, which often have sinuous caudal extensions. In some species, the liver
contains pancreatic tissue in the portal regions.
Gallbladder A few species (eg, cod) do not have gallbladders.
Integumentary
Alarm substance cells Located periodically within the epidermis, dermal injury causes these cells to release the Schreckstoff
pheromone, which serves as a danger warning for other fish.
Epidermis In most teleosts the epidermis is non-keratinized.
Mucous cells Goblet cells located within the epidermis.
Pigment cells Termed chromatophores, these include iridophores (silver), melanophores (brown), and xanthophores (yellow).
Scales Scales are actually plates of membranous bone embedded within the dermis.
Taste buds Taste buds may be embedded in the epidermis, especially around the head.
(Continued)
186 Lisa M. et al.
Table 9 Continued
Musculoskeletal
Bone Fish have both endochondral and membranous bones (skull, scale), and fish bone varies from poorly cellular to
essentially acellular.
Cartilage Relative to mammals, fish skeletons have a greater proportion of non-arthrodial cartilage, most of which is
hyaline cartilage, but fibrocartilage and elastic cartilage (eg, barbels) are also present.
Skeletal muscle The functional unit of trunk musculature is the myomere, and these are attached to the axial skeletal at angles
and distances that allow for synchronous contraction.
Nervous
Brain Relative to mammals, the telencephalon is much reduced, but the mesencephalon is proportionally enlarged.
Brain and spinal cord Compared with mammals, gray and white matter tracts are less easily distinguished, and spinal cord white

matter generally appears looser and more vacuolated.
Reproductive
Ovary The functional unit of the ovary is the follicle (oocyte surrounded by granulosa and theca cells). There are 3
major ovary configurations: gymnovarian (oocytes released directly into coelomic cavity, then pass through
ostium before entering oviduct), secondary gymnovarian (oocytes released directly into coelomic cavity, then
enter oviduct), and cystovarian (lumen of ovary contiguous with oviduct).
Oviduct The ovarian wall is contiguous with the oviduct in most teleosts, and there is no true uterus.
Testis The functional unit of the testis is the spermatocyst. There are 3 major testis configurations: restricted lobular
(spermatocysts form only at the terminal end of the lobule, and migrate toward a central efferent duct),
unrestricted lobular (spermatocysts form along the length of the lobule, and sperm discharged into a lumen
channel into a central efferent duct), and tubular (spermatocysts form along the length of tubules, and sperm
discharged into a lumen channel through a series of anastomosing ducts).117
Ductus deferens Transports sperm to the vent, although not thought to be developmentally homologous to the mammalian vas
deferens.
Respiratory
Chloride cells Mitochondria-rich cells found primarily in the gill interlamellar sulci, they are involved in osmoregulation.
Gills The bilaterally paired gills of teleosts consist of 4 cartilaginous arches, from which paired filaments branch off
at right angles, which in turn sprout lamellae at right angles. In addition to serving as the major respiratory
organ, they are also the primary sites of nitrogenous waste excretion.
Mucous cells Goblet mucous cells are typically sparse in healthy gills but proliferate in response to gill irritation.
Pillar cells Specialized endothelial cells that provide structural support to gill capillaries.
Pseudobranch Bilateral gill arch remnant that theoretically supplies increased oxygenated blood to the eyes.
Urinary
Kidney The fish mesonephric kidney lacks defined cortical and medullary regions. In some species (eg, salmonids,
centrarchids) the anterior kidney is wholly hematopoietic, whereas in others (eg, medaka, guppy, zebrafish) the
anterior kidney additionally contains urinary elements. Certain marine species (eg, seahorses, toadfish) have
aglomerular kidneys. New nephrons (nephron neogenesis) can form throughout life, and thus the kidneys of
adult fish may contain low numbers of developing embryonic nephrons.
Mesonephric Essentially the piscine ureters.
(opisthonephric ducts)
Urinary bladder Some fish species have a terminal expansion of the distal mesonephric duct (lined by columnar epithelium)
that is called a bladder, but it is neither embryologically nor structurally analogous to the mammalian bladder.
toxicologic substances, infectious diseases, or carcinogens; the raceways, cages placed in natural waterways, or outdoor meso-
pharmacologic screening of potential therapeutic compounds cosms. Studies may be performed using static, static renewal,
for toxic effects or efficacy in fish embryos; the use of fish filtered recirculating, or flow-through water systems. Compared
to investigate basic biological processes or as surrogate mod- with mammals, fish are much more acutely dependent on pre-
els of human disease; and the diagnostic examination of fish cise conditions of their immediate surroundings, and study suc-
kept as household pets or in public aquaria. Advantages of fish cess often depends on the stable maintenance of various envi-
as research models include small size, rapid generation time, ronmental parameters such as water quality (eg, nitrogenous
fecundity, a wide variety of species, and the ability to expose wastes, pH, sediment, O2 ), temperature, and lighting at opti-
animals to toxicants via dermal, respiratory, and gastrointestinal mal levels. Well-conceived and executed biosecurity measures,
routes simultaneously. The major disadvantage of fish studies including periodic health checks, help to minimize the intro-
is that they tend to be highly labor intensive, and the technical duction and spread of infectious disease or toxic contamination.
support of long-term experiments can be especially challenging. Fish may be dosed by immersion, feed, oral gavage, or injection
Fish used in research may be wild caught or obtained from (most commonly intramuscular or intraperitoneal). Following
commercial suppliers, in-house cultures, collaborating facilities, humane euthanasia often via overdose of the anesthetic tricaine
private hatcheries, or pet shops. Typically, fish brought in from methanesulfonate, tissues intended for histopathology may be
outside sources can acclimate for 1 to several weeks in a captive excised from larger fishes or small aquarium-sized species may
environment that simulates the upcoming experimental condi- be processed and sectioned as whole-body specimens. Whole-
tions. Experiments may be conducted in tanks of various sizes, body sectioning allows multiple organ systems to be viewed in
Table 10 Spontaneous Conditions of Fish Used in Research5 ,118
Endocrine
Thyroid follicular cell hyperplasia Dietary iodine imbalance or presence of goitrogens in feed. Diffuse or nodular enlargement (potentially massive) of
(goiter) ventral pharyngeal thyroid tissue; however, follicles are lined by single layer of flattened to low columnar cells.
Proliferations in nonpharyngeal locations may represent ectopic thyroid hyperplasia rather than neoplasia.
Hepatobiliary
Altered hepatic foci Can occur as an aging change but may also increase in response to toxic exposures. Localized change in hepatocyte
coloration and size, but with little or no compression of adjacent liver, and lacking cytologic atypia. Fish foci strongly
resemble comparable foci in mammals.
Cystic degeneration Considered an aging change of uncertain cause. Variably sized unilocular or multilocular spaces, sometimes associated
with blood vessels, but not lined by endothelium. May contain small amounts of pale fluid, but usually not erythrocytes.

Also called spongiosis hepatis, or hepatic cysts, common finding in medaka, especially older females.
Hepatocyte vacuolation The degree and character of hepatocyte vacuolation are dependent on the diet, energy expenditure, and overall health.
Altered vacuolization can also be a response to toxic exposure. Lipid-type vacuoles are spherical with sharply-defined
edges, and large lipid vacuoles may displace the nucleus. Glycogen-type vacuoles tend to be more angular and flocculent,
with indistinct margins. Captive-reared fish often store relatively large amounts of glycogen and/or lipid in their livers.
Therefore, moderate vacuolation should not necessarily be deemed abnormal (ie, lipidosis) in captive fish.5,8
Integumentary
Pseudo-ulceration Mechanical trauma post mortem. Focal or regional loss of epidermis unaccompanied by inflammation. Caused by rough
handling during capture or necropsy.
Musculoskeletal
Electrocution Electroshock used for wild fish collection or from lightning strike. Skeletal muscle necrosis/degeneration, often along
broad linear pattern, with or without spinal fractures. Fibrosis and body curvature may occur over time. Fish may survive
long term if kept adequately nourished.
Idiopathic myodegeneration Possible exercise-related myopathy induced during netting/capture. Peracute segmental myocyte degeneration affecting
occasional myofibers of the trunk. Distinguished from treatment effect by peracute nature of lesions.
Skeletal malformations Idiopathic, genetic predisposition, or malnutrition. Can see a multitude of anomalies involving the skull, operculum,
and/or axial skeleton. Seen more commonly in certain species and facilities.
Nervous
Focal gliosis Myxozoan infection may be responsible for at least some of these in Atlantic salmon. Small glial nodules distributed
throughout the CNS, especially the brainstem. Observed periodically in Atlantic salmon.
Multisystemic
Gas bubble disease Due to supersaturation of water with nitrogen or oxygen in natural waters or manmade containment systems. Gas
emboli may be visible macroscopically, in gill or fin clips, or less commonly, in histologic sections. Exophthalmia and or
dermal emphysema may be present. Thought to cause distress and death via obstruction of gill capillaries by gas emboli.
Reproductive
Egg-bound Seen spontaneously in aged captive brood stock, potentially associated with lack of behavioral cues for spawning and
other husbandry factors. Abdomen of female massively enlarged with mature follicles, some or all of which may be
atretic (degenerating). Emaciation in chronically affected females. In addition to energy devoted to egg production, fish
may not be able to ingest sufficient quantities of food due to compression of viscera by egg mass.
Gonadal intersex Idiopathic, or caused by perturbation of the hypothalamic-pituitary-gonadal axis by exogenous factors, eg, chemical
hormone mimics. In the testis, intersex most often presents as scattered perinucleolar phase oocytes. Less commonly,
spermatogenic tissue may be observed in the ovary. Certain fishes such as centrarchids (black basses and sunfishes)
seem particularly predisposed to testicular oocyte development, whereas this tends to occur more sporadically in other
species.24
Testicular mineralization Idiopathic in cultured and wild-caught fishes; may be related to diet or husbandry practices in some captive fish.
Mineralized concretions may be found in intratubular and/or interstitial locations. Common in fathead minnows, for
example.
Respiratory
Lamellar epithelial hyperplasia A low level of LEH is common in captive fishes, especially in crowded systems, those with sub-ideal water quality, or in
(LEH) association with gill ectoparasitism. See partial filling of interlamellar sulci by epithelial cells, with or without increased
chloride cells, mucous cells, and/or inflammatory cells. Moderate to severe LEH can be associated with partial to
complete lamellar fusion. LEH can also be caused or exacerbated by physical or chemical irritants or cytotoxic agents.5
Lamellar epithelial lifting Poor water quality, formalin fixation artifact, or gill edema. Focal separation of the lamellar epithelium from lamellar
capillaries. Because this is a frequent artifact, diagnosis of edema should be made cautiously. Edema may be indicated by
the presence of proteinaceous or flocculent material within the subepithelium.5
Lamellar telangiectasis Peracute lesion may be induced during capture or sacrifice. Aneurysmal dilation of 1 or more lamellar capillaries. Most
instances occur during the perimortem period and are thus not relevant in-life findings. Look for thrombosis as evidence
of pathologically relevant telangiectasis.5
Special senses
Cataracts Cited causes include exposure to UV light, ocular fluke infection, and rapid variation in salinity. Lenticular opacities that
may be minor and focal at the anterior pole or diffuse throughout the lens. Occur with some regularity in farmed Atlantic
salmon, in which the cause is probably multifactorial.119
Urinary
Renal mineralization Idiopathic in cultured and wild-caught fishes, and possibly related to diet or husbandry practices in some captive fish.
Mineralized concretions may be found in intratubular and/or interstitial locations. Associated with a granulomatous
response in severe cases. Extensive renal mineralization (nephrocalcinosis) has occurred in captive-reared salmonids.120
CNS, central nervous system; LEH, lamellar epithelial hypertrophy.

188 Lisa M. et al.
Table 11 Common Infectious Diseases of Captive Research Fish118
System Condition Description/Comments
Alimentary
Cestodiasis Cestode infections in which the fish species of interest is the definitive host. Bothriocephalus acheilognathi (Asian
tapeworm) is found in cyprinid fishes. Causes enteritis at attachment sites and beyond. Intestinal cestodiasis is
an uncommon finding in most research fish.121,122
Nematodiasis Nematode infections in which the fish species of interest is the definitive host. Pseudocapillaria tomentosa is a
common pathogen of laboratory zebrafish. P tomentosa can be observed tunneling through the mucosa, where it
is associated with mucosal epithelial hyperplasia and inflammation. Nematode parasitism must be
distinguished from ingested free-living nematodes, which are unattached in the intestinal lumen. P tomentosa
infection has also been associated with intestinal carcinogenesis in zebrafish.123,124
Flagellates Cryptobia iubilans, Spironucleus vortens (‘Hexamita’). Cryptobia causes granulomatous gastritis and transmural
stomach ulcers. Spironucleus is associated with enteritis and wasting. Infections intensify in debilitated

fish.125,126
Hematopoietic- Immunologic
Megalocytivirus infection Several closely related iridoviruses have been identified. See enlarged cells (probably leukocytes) with
basophilic inclusions in various organs, eg, spleen. Morbidity and mortality have been attributed to vascular
damage caused by enlarged infected cells. Includes infectious spleen and kidney necrosis virus, red sea bream
iridovirus, and turbot reddish body iridovirus. Affects wild and captive fresh and saltwater fishes.127,128
Integumentary
Columnaris infection Flavobacterium columnare, the most common of several related motile filamentous bacterial pathogens in fish.
Common cause of trunk and tail ulcers (“saddleback disease”). Wet mount preparations of skin scrapings can be
diagnostic. One of the most important pathogens of cultured fish, and typically stress-induced.129
Costiasis Ichthyobodo necator and other Ichthyobodo spp. flagellates. Excess mucus production in early stages, followed by
ulceration and secondary infection in later stages. Tiny parasites are teardrop-shaped and adhere to the
epidermal surface via fine stalks. Light infections are usually well-tolerated, while heavy infections occur in
weakened fish. I. necator is a freshwater parasite, and other Ichythyobodo spp. are marine fish pathogens.130,131
Ich Ichthyophthirius multifiliis is an obligate parasite of freshwater fish that has a remarkably broad host range.
Holotrich ciliate, and largest fish protist, with characteristic horseshoe-shaped nucleus. Increased mucus and
white spot appearance caused by epithelial proliferation around parasites. Marine counterpart (although not
closely related) is Cryptocaryon irritans.132–135
Lymphocystis Iridovirus (genus Lymphocystivirus). Massively enlarged dermal fibroblasts result in white nodules or
cauliflower-like growths on fins and skin, (and occasionally internally). Lesions are stress-induced and often
regress once stressors are removed.136
Monogeneans Gyrodactylus, Dactylogyrus, and Neobenedenia spp. Flatworm that attaches to gill and skin surfaces via posterior
haptor structures (hooks, clamps, anchors). Once thought to be trematodes, more likely related to turbellarians
and cestodes. Fairly well tolerated unless numbers are large.137
Scuticociliatosis Miamiensis (= Philasterides), Uronema, and Pseudocohnilembus spp. (Freshwater: Tetrahymena spp.). Widely
distributed marine ciliates that can penetrate skin, muscle, and invade the peritoneum and vascular system.
Can cause tissue necrosis via vascular thrombosis. A broad range of teleosts are susceptible.138
Trichodinosis Trichodina spp. Peritrichial ciliate characterized by the presence of a denticular ring, they are commonly found in
low numbers on the gills, skin and fins. They feed on bacteria and actually only use fish as attachment sites,
which causes irritation. Trichodinids proliferate in poor quality water.139
Velvet disease Amyloodinium ocellatum (marine fish), Oodinium spp. (freshwater fish). Parasitic dinoflagellates, which causes
focal proliferative dermal lesions smaller than those of Ich.140
Water mold infection Saprolegnia spp.; Aphanomyces spp.; Achyla spp. Oomycete fungi cause dermal erosions and ulcers that
preferentially affect the fin epidermis and trunk areas around the fins. Saprolegnia is typically a secondary
pathogen following initial injury or other infection, and often invades post mortem. Aphanomyces seems more
likely to invade skin and muscle without prior insult.141,142
Musculoskeletal
Microsporidiosis Many microsporidia affect fish, and most are host specific. Pleistophora hyphessobryconis and Glugea stephani are
common pathogens that have unusually broad host ranges. Obligate Gram-positive intracellular organisms that
can cause muscle degeneration and necrosis. Spores may also be observed within other internal organs.
Microsporidia are currently classified with fungi rather than with the protists. P hyphessobryconis is the cause of
“neon tetra disease;” however, infections have also been observed in captive zebrafish and other fish
species.143,144
Myxozoan infection Hundreds of species, many of which are host specific. Many infections are well tolerated, whereas others can
cause extensive disease. Some myxozoans demonstrate a predilection for cartilage, eg, Myxobolus cerebralis, the
cause of “whirling disease” in salmonids. Obligate cnidarian parasites with a 2 host life-cycle involving an
aquatic annelid and a fish.145
Scuticociliatosis Pseudocohnilembus spp., Uronema spp. Widely distributed marine ciliates that can penetrate skin and muscle and
invade the peritoneum. A broad range of teleosts are susceptible.138
Water mold infection Saprolegnia spp.; Aphanomyces spp.; Achyla spp. Dermal erosions and ulcers that preferentially affect the fin
epidermis and trunk areas around the fins. Saprolengia is typically a secondary pathogen following initial
injury or other infection, and often invades post mortem. Aphanomyces seems more likely to invade skin and
muscle without prior insult.141,142
Nervous
Edwardsiellosis Edwardsiella ictlaluri. Chronic infections associated with meningoencephalitis and draining tract through skull
(“hole-in-the-head disease”). Also called enteric septicemia of catfish. A similar syndrome has also been
reported in laboratory zebrafish.146–148
(Continued)
Table 11 Continued
System Condition Description/Comments
Microsporidiosis Pseudoloma neurophilia. Cysts primarily in spinal cord, spinal nerves, ganglia, epaxial musculature. Often, little
associated inflammation in nervous tissue. Causes impaired swimming and debilitating disease. A major problem in
many zebrafish facilities. As a result, zebrafish specifically free of this pathogen are commercially available.123
Streptococcosis Streptococcus iniae and other species. Meningoencephalitis seen in chronic infections. Infections seen in tilapia,
channel catfish, and hybrid striped bass.149,150
Multisystemic
Acid-fast bacterial infection Various mycobacteria, eg, M marinum, M fortuitum, and M chelonei. and also Nocardia spp. Chronic disease manifesting
as diffuse granulomatous inflammation and/or discrete granulomas, often with necrotic centers. Organisms are
ubiquitous and thrive in biofilms, especially in recirculating systems. Potential zoonotic disease.151
Gram-positive and Aeromonas, Edwardsiella, Streptococcus, and Vibrio spp., among many others. Common pathologic findings include

Gram-negative bacterial multifocal hemorrhages, exophthalmos, multifocal inflammation with necrosis, dermal ulcers. Some organisms
infections have species predilections, eg, Edwarsiella spp. for large catfishes and zebrafish, Streptococcus spp. for tilapia.152,153
Migrating or encysted Cestodes, digenetic trematodes, nematodes. Trematode metacercarial cysts often lack inflammatory response in
helminth larvae contrast to migrating cestode and nematode larvae. Trematode metacercariae require intermediate hosts and are
therefore pathogens of fish raised or acquired outdoors.154
Systemic mycosis Saprolegnia, Branchiomyces, Cladosporium, Ichthyophonus, Pythium, or Exophalia spp. Oomycetes, and true unpigmented
and pigmented fungi, some are vasculotropic, and severe infections may be associated with infarcts.155,156
Reproductive
Microsporidiosis Many genera and species of microsporidia affect fish, and most are host specific. Obligate Gram-positive
intracellular organisms that can cause muscle degeneration and necrosis. Spores may also be observed within other
internal organs. Microsporidia are currently classified with fungi. Pleistophora spp. have been detected in the ovaries
and testes of fathead minnows where they may interfere with the evaluation of gonads for endocrine disruption
studies.143,144,157
Respiratory
Amebiasis Neoparamoeba pemaquidensis is the cause of amoebic gill disease in Atlantic salmon and other marine species or
freshwater fishes, eg, rainbow trout. Amoeba typically found palisading along the surface of markedly to severely
hyperplastic and fused lamellae, the distribution of which may be segmental. Organisms may be overlooked because
they resemble exfoliated lamellar pavement cells. Highlighted by Giemsa staining. Fish gill amoebae are free-living
opportunistic, and sometimes secondary, pathogens.158–160
Columnaris infection Flavobacterium columnare, the most common of several related motile filamentous bacterial pathogens in fish. Causes
necrotizing branchitis. One of the most important pathogens of cultured fish, and typically stress-induced.129
Costiasis Ichthyobodo necator and other Ichthyobodo spp. flagellates. Excess mucous production in early stages, followed by
ulceration and secondary infection in later stages. Tiny parasites are teardrop-shaped in histologic sections and
adhere to the epidermal surface via fine stalks. Light infections are usually well tolerated, while heavy infections
occur in weakened fish. I. necator is a freshwater parasite, and other Ichythyobodo spp. are marine fish
pathogens.130,131
Epitheliocystis Chlamydial disease in which different genera and species affect myriad freshwater and marine species, with a
surprising degree of host specificity. Macroscopically see white nodular lesions on gills and skin (heavy infections).
Host cells of are massively distended by large spherical granular inclusions that are generally blue-gray in H&E
sections. Light infections are extremely common in wild and cultured fish and are usually well tolerated. The reason
why heavy infections occur in some populations is not well understood, but those can be associated with high
mortality.161,162
Ich Ichthyophthirius multifiliis is an obligate parasite of freshwater fish that has a remarkably broad host range. Holotrich
ciliate, and largest fish protist, with characteristic horseshoe-shaped nucleus. Increased mucus and white spot
appearance caused by epithelial proliferation around parasites. Marine counterpart (although not closely related) is
Cryptocaryon irritans.132 –135
Monogeneans Gyrodactylus, Dactylogyrus, and Neobenedenia spp. Flatworm that attaches to gill and skin surfaces via posterior haptor
structures (hooks, clamps, anchors). Once thought to be trematodes, more likely related to turbellarians and
cestodes. Fairly well tolerated unless numbers are large.137
Myxozoan infection Hundreds of species, many of which are host specific. Many infections are well tolerated, whereas others can cause
extensive disease. Some myxozoans demonstrate a predilection for cartilage, eg, Henneguya ictaluri, the cause of
“hamburger gill disease” in channel catfish. Obligate cnidarian parasites with a 2 host life-cycle involving an aquatic
annelid and a fish.145,163
Trichodinosis Trichodina spp. Peritrichial ciliate characterized by the presence of a denticular ring, they are commonly found in low
numbers on the gills, skin and fins. They feed on bacteria and actually only use fish as attachment sites, which
causes irritation. Trichodinids proliferate in poor-quality water.139
Special senses
Eye fluke Diplostomum spathaceum. Presence of metacercaria within ocular lens and associated inflammation. A high parasite
burden is associated with death of the host. Requires intermediate bird and snail hosts, therefore a pathogen of fish
reared or collected outdoors.164
Urinary
Trichodinosis Trichodina spp. Peritrichial ciliate characterized by the presence of a denticular ring, they are commonly found in low
numbers on the gills, skin, and fins. In certain species such as Japanese medaka, they can be found in the urinary
bladder and collecting ducts where they cause mild epithelial hyperplasia. Trichodinids proliferate in poor-quality
water.139
Myxozoans Myxidium streisingeri occurs in the renal collecting ducts of zebrafish. Acauda hoffmani occurs in the kidneys of
bluegill sunfish. These infections tend to be well tolerated by the host.165,166
190 Lisa M. et al.
Table 12 Neoplastic Conditions of Captive Research Fish118,167,168

Alimentary
Oral cavity Ameloblastoma. Invasive and exophytic irregular masses primarily located along the dental arcade. Palisading
ameloblastic cells arranged in lobules with acantholytic clefts. Ameloblastomas of undetermined cause are observed
occasionally in wild Pacific salmon.169
Squamous papilloma/carcinoma. Usual squamous cell appearance comprised of polygonal cells in sheets with
intercellular bridges (desmosomal attachments). Fish squamous cell tumors typically do not contain keratinized material
(ie,
“keratin pearls”). Epizootics of oral and dermal papillomas have occurred in bullhead catfish.170
Intestine Intestinal carcinomas. A rare spontaneous primary tumor in most fish species. Has been associated with Pseudocapillaria
tomentosa infection in zebrafish.123,171
Cardiovascular
Gill Hemangioma or hemangiosarcoma. Various forms, including cavernous hemangioma. Extremely rare unless carcinogen

induced.172,173
Endocrine
Thyroid Follicular cell adenoma/carcinoma. Benign thyroid tumors are expansile nodular structures that often exhibit abnormal
growth patterns, while malignant tumors are irregularly outlined and generally feature increased cytologic atypia with
less follicle formation. Because thyroid tissue can be found in ectopic sites, proliferations in nonpharyngeal locations are
usually not metastases.174
Hematopoietic- immunologic
Multisystemic Lymphoma/leukemia. Monomorphic population of medium to large (lymphoblastic) lymphocytes that distend sinusoidal
spaces of various tissues and are observed within blood vessels. Occasional apparently spontaneous finding in medaka
and other fishes.175,176
Integumentary
Skin Chromatophoroma. Locally invasive dermal spindle cell tumors that may resemble nerve sheath or collagen-forming
tumors. Includes melanomas, erythrophoromas, and iridophoromas.168
Lepidocytoma. Sarcomatous tumor with linear osteoid formation and osteoblast-like cells. Seen rarely in a variety of
species, but maybe slightly more common in goldfish and koi. Possibly underdiagnosed due to resemblance to other
tumor types.177 ,178 Essentially, a dermal osteosarcoma of scale-forming cells.172
Squamous cell papilloma/carcinoma. Usual squamous cell appearance comprised of polygonal cells in sheets with
(ie, “keratin pearls”). Epizootics of oral and dermal papillomas have occurred in bullhead catfish. Dermal papillomas (and
sarcomas) in some species may be retroviral induced.170 ,179
Musculoskeletal
Skeletal muscle Rhabdomyoma or rhabdomyosarcoma. Similar to mammalian tumors, these tumors may feature strap-like cells,
racquet-shaped cells, myoblastic and multinucleate cells. Striations may or may not be apparent. Rare tumors.180 –182
Nervous
Peripheral nerves of integument Nerve sheath tumor. Typical pattern of fine fibers that form storiform bundles with palisading nuclei. Occasional whorls
and abdominal mesentery resembling hemangiopericytoma may also be present. Certain species, eg, gray snapper, bicolor damselfish, appear
predisposed. A retroviral etiology is suspected in some cases.179
Reproductive
Gonads Dysgerminoma. Mass consisting of oogonia-like cells, with or without oocyte formation. Chemically induced and
spontaneous in medaka.183 ,184
Granulosa or theca cell tumor. Mass may consist of cords of palisading spindle cells, although malignant version may be
disorganized and exhibit a high degree of atypia. Malignant granulosa cell tumor possibly induced by microsporidian
infection in wild-caught, adult longjaw mudsucker (Gillichthys mirabilis).185
Seminoma. Enlarged and disorganized male germinal epithelium, may additionally contain low numbers of perinucleolar
oocytes. Many fish seminomas are of the “spermatocytic” type, ie, spermatogenic progression to spermatozoa is evident.
Can be malignant and spread via seeding or vascular metastasis, although most are probably benign. Common tumor in
older male zebrafish of certain strains; less frequent in most other fish species.171
Sertoli cell tumor. Aggregated round to oval cells with abundant clear cytoplasm assembled into tubule-like structures.
Well known to occur in wild carp and koi-carp hybrids.186
Teratoma. Mass consisting of tissues representing multiple mesenchymal and epithelial cell lines, often dominated by
cartilage and nervous tissue. Benign vs malignant classification usually depends on degree of differentiation. Although
most often observed in the ovary, fish teratomas can rarely be found in extragonadal (ectopic) locations.187
Respiratory
Gill, pseudobranch Branchioblastoma. Disorganized tumor that usually contains structures resembling lamellar capillaries and/or filament
cartilage, along with cords of dark primitive blastema cells. Can be spontaneous but more likely to be chemically
induced.188
Squamous cell papilloma/carcinoma. Typical squamous cell appearance comprised of polygonal cells in sheets with
(ie, “keratin pearls”). Gill tumors of squamous cell origin extremely rare unless chemically induced.189
Special senses
Olfactory organ Esthesioneuroblastoma. Irregular sheets or ribbons of primitive neuroblast-like cells, often with rosette/pseudorosette
formation. Rare spontaneous neoplasm observed in medaka.190
Eye Retinoblastoma/medulloepithelioma. Streams or ribbons of spindle-shaped or palisading carrot-like cells that may form
rosettes and/or pseudorosettes. Medulloepitheliomas exhibit additional neuronal differentiation. Primitive
neuroepithelial tumors of the eye have been observed in a number of captive fish species.191
Urinary
Kidney Nephroblastoma. Most common renal tumor type. Poorly circumscribed masses consisting of primitive blastemal,
epithelial, and mesenchymal components, often with abortive glomerular-like structures. Nephroblastomas in Japanese
eels may contain abundant myoblastic tissue and resemble rhabdomyosarcoma. Spontaneous or induced
nephroblastomas have been observed in a wide variety of fish species.192,193
Renal adenoma or adenocarcinoma. Primarily expansile mass comprised of variably well-differentiated anastomosing
tubular structures. Spontaneous adenomas and cystadenomas have been observed in oscar cichlids (Astronatus ocellatus)
and chemically induced in rainbow trout. Papillary adenocarcinomas chemically induced in medaka and guppy.192
Table 13 Comparison of Xenopus Species Biology and Use in Research36,38
Species Commentsa
X laevis Adult body size: females 9–14 SVL, 20–150 g; males 10–30% smaller; brood size: 2000–3000+; egg size: 1–1.3 mm;
generation time: 1–2 years; optimal temperature range: 16–22◦ C; genome: allotetraploid, 3.1 × 109 base pairs;194 primary
uses in research: developmental, cell, and molecular biology, physiology, pharmacology, toxicology
X tropicalis Adult body size: females 4–5 cm SVL, 10–50 g; males 10–30% smaller; brood size: 500–2000; egg size: 0.7–0.8 mm;
generation time: <5 mo; optimal temperature range: 25–30◦ C; genome: diploid, 1.7 × 109 base pairs;195 primary uses in
research: similar to X laevis; greater utility for genetics and genomic studies due to smaller, simpler genome and shorter
generation time33,34
a SVL = snout-to-vent length.

a relatively small number of histologic slides. Not only does this outbreak status in some facilities. Many noninfectious back-
approach enhance efficiency, it allows background diseases to ground disorders (eg, gas bubble disease) may also be related
be more readily observed and diagnosed because a wide variety to inadequate system design or poorly conceived or executed
of tissues can be examined in situ. husbandry procedures.
According to the FishBase web site, there are presently 33 900 Fish can develop many of the same kinds of tumors seen in
known freshwater, marine, and estuarine fish species,22 only a mammals as either spontaneous findings or as lesions induced
minute fraction of which undergo pathologic evaluation with by exposure to carcinogenic chemicals, oncogenic viruses, radi-
any regularity. Species are frequently selected as test subjects ation, or heightened cell proliferation that occurs in response to
according to the global geographic location in which they are chronic inflammation. An increased prevalence of neoplasms
found naturally, and in other cases, species choice may be influ- may also occur in certain transgenic lines, for example those
enced by the research goals or traditions of a particular insti- with tumor suppressor gene knockouts (eg, p53 deficient). As
tution. A given species may also have attributes that make it in mammals, the onset of fish neoplasia tends to be age asso-
especially suitable for a certain line of research (eg, the use ciated, but it is important to remember that for some small
of zebrafish Danio rerio for embryological studies), or research aquarium species (eg, zebrafish), a 2- to 3-year-old fish may be
may be focused on a particular organism because it is the considered elderly. Certain tumor types are never observed in
primary target of investigation (eg, endangered species). Some fish for obvious reasons (eg, pulmonary, mammary gland, or
of the more common candidates are listed in Table 8. Many of hair follicle tumors), whereas others (eg, osteosarcomas) tend
these fishes have been domesticated, and for certain species to be comparatively rare, and still other types (eg, swim bladder
(eg, zebrafish, medaka) transparent varieties and/or transgenic gas gland tumors) are entirely unique to fish. Most benign and
models are commercially available. malignant fish tumors closely resemble their mammalian coun-
Compared with captive-reared fish, wild-caught specimens terparts and are diagnosed using similar morphologic criteria.
typically present with a greater number and variety of back- Because distant intravascular metastasis occurs comparatively
ground findings, particularly in terms of infectious diseases. rarely in fish, determinations of malignancy are often based
Because of the wide range of wild fish species that could poten- on the degree of cellular atypia, abnormality of growth pattern,
tially be examined and the even greater diversity of wildlife fish and/or evidence of local invasion.23
diseases, the fish section will focus primarily on background Another important confounding factor that can impact the
diseases, disorders, and histologic lesions of captive-reared fish, results of fish research is the misdiagnosis of tissue handling
with emphasis on species that are most commonly used for and processing artifacts, or even normal microanatomical struc-
research in North America. Most captively reared fishes used in tures, as pathologic findings. Recent reviews of fish toxicological
research are teleosts, which have moveable jaw bones in contrast studies suggest that the overall credibility of histopathology data
to other more primitive bony fishes (eg, bowfins, gars, stur- in many published reports is less than desirable and that the
geons) or the cartilaginous elasmobranchs (eg, sharks and rays). misinterpretation of postmortem artifacts as in-life lesions is too
Notably, some of the background lesions listed in Tables 9–12 are frequent a problem.5–8,24 Further histopathological training and
fairly species specific (eg, Pseudoloma neurophilia microsporidian more diligent journal peer review will be required to combat this
infections in zebrafish), whereas others are more promiscuous issue, which is apparently not limited to fish research.
(eg, mycobacteriosis).
Among wild-caught or captively reared fish used in research,
the predominant infectious agents are typically various forms of
Xenopus species
ecto- and endoparasites, including protists (eg, amoeba, apicom-
plexans, ciliates, dinoflagellates, flagellates, and myxozoans) The African clawed frog (Xenopus laevis) became a promi-
and helminths (eg, cestodes, digenetic trematodes, monogenes, nent laboratory species in the mid-20th century when the
and nematodes). Microsporidia are also observed periodically in ability of females to produce large numbers of eggs on
some species, but those organisms are more recently classified induction with gonadotropic hormones, combined with exter-
as fungi. Most often, healthy fish present with only low numbers nal embryogenesis, led to major advances in the fields
of parasites (or none at all), and such light infections are usu- of developmental and cell biology as well as one of the
ally well tolerated. Stressors can precipitate rapid increases in first early pregnancy tests for humans.25 Since the 1980s,
parasite burdens, which are then often associated with clinical the Frog Embryo Teratogenesis Assay–Xenopus has been a
disease and debilitation. Although a less common occurrence mainstay in toxicological studies, providing a standardized
in well-managed research fish, stressors may also trigger the method for evaluating developmental toxicity of industrial
onset of bacterial, viral, or fungal infections, which may attain and pharmacologic compounds.26,27 In the molecular era, X
192 Lisa M. et al.
Table 14 Anatomic and Physiologic Features of Xenopus Species38 ,43,197–199
System Organ/Process Comments
Alimentary
Oral cavity Xenopus lack the sticky, mobile tongue found in other types of amphibians. Food enters the mouth via a
combination of sweeping motions of the front feet and negative pressure produced by hyobranchial
movements (ie, suction feeding).200 Tooth structures composed of dentin are present beneath the oral
epithelium along the rostral and lateral maxilla.199
Esophagus Lined by ciliated pseudostratified columnar epithelium196
Stomach Xenopus can regurgitate their stomach to expel toxic substances. Stressing or handling animals shortly after
eating may cause them to regurgitate the stomach, along with the contents.
Intestines Relatively short and simple. The sections are grossly and histologically more difficult to distinguish than in
birds and mammals; small intestine lacks distinct crypts; colonic mucosa is smooth (rather than glandular)

and arranged in small folds.196 ,199
Cloaca As in reptiles and birds, the amphibian cloaca serves as a common collecting chamber for the
gastrointestinal, reproductive, and urinary tracts.
Cardiovascular
Heart Adult Xenopus have a 3-chambered heart (2 atria, 1 ventricle) with the right atrium being larger than the left.
The ventricle is composed of thick myocardial trabeculae. Larvae have a 2-chambered heart, similar to fish.
Because Xenopus do not have a tongue or prominent midventral abdominal vein, anesthetized
cardiocentesis is the primary method of terminal blood collection.38 Can continue to beat for many hours
after death, both in vivo and in vitro.38
Plasma osmolality Lower in Xenopus than in mammals, ranging from 200 to 233 mOsm/kg.38 Must be considered treating
dehydrated frogs with replacement fluids and when preparing media for in vitro work using frog tissues.43
Subcutaneous lymph hearts Pairs of contractile, subcutaneous lymphatic hearts are found anteriorly and posteriorly just beneath the
dorsal skin. Drain fluid from the subcutaneous lymph sacs into venous system.38
Endocrine
Adrenal tissue Steroid-producing adrenocortical cells and catecholamine-producing chromaffin cells are located within
the renal parenchyma, along the medial aspects of the kidneys. Sometimes referred to as the interrenal
gland.199
Thyroid glands Small paired structures located on either side of the pharynx. Rarely identified grossly. Histologically similar
to those of other vertebrates. The process of amphibian metamorphosis is primarily controlled by effects of
thyroid hormone.201
Hematopoietic-
immunologic
Bone marrow Present in adults, but absent in tadpoles. Primarily contains cells of myeloid lineage (developing granulocyte
and monocytes). Not a major site of lymphopoiesis or erythropoiesis.202
Blood cells Nucleated red blood cells and thrombocytes. Innate and adaptive immune cells are also fundamentally
similar to humans, making Xenopus amenable for immunological studies.203
Extramedullary Prominent in the liver, spleen, and kidneys of tadpoles, which lack bone marrow. Can also be found in
hematopoiesis (EMH) adults, wherein the subcapsular liver is thought to remain a primary site of erythropoiesis.202 Increased
extramedullary granulopoiesis can also be seen with chronic inflammation/antigenic stimulation.196
Lymph nodes True lymph nodes are absent. Although there are histologic descriptions of lymph node-like structures in X
laevis,199 these are likely more accurately characterized as part of the diffuse lymphoid tissue or tertiary
lymphoid organs.204
Spleen Small, round, and located on the right side of the coelomic cavity within a loop formed by the large
intestine. Red pulp composed of sinusoids containing circulating blood cells. White pulp surrounds central
arteries, contains lymphocytes and macrophages. Main site of B-cell differentiation in adult Xenopus.
Thymus Small and bilateral, located near the temporomandibular joints. Major site of T-cell differentiation.
Hepatobiliary
Liver Large and bilobed. As in other amphibians, contains variable numbers of darkly pigmented
melanomacrophage centers. Vacuolization of hepatocytes due to glycogen storage is also considered a
normal, physiologic finding.196
Gall bladder Located between the liver lobes and lined by simple columnar epithelium.
Integumentary
Epidermis Composed of thin, stratified squamous epithelium with only 1–2 layers of keratinized epithelial cells. The
permeable nature of Xenopus skin renders them highly sensitive to dissolved gases, solutes, and
contaminants (see toxicosis in Tab. 3).
Dermal glands Mucous glands produce the protective slime layer that covers the epidermis. Animals should be handled
with rinsed latex gloves and soft nets to avoid disrupting the slime layer and damaging the skin. Harsh
soaps and scrubs should not be used for surgical prep.43 Granular glands produce antimicrobial peptides
that protect against a range of bacterial and fungal pathogens.205
Cutaneous homeostatic As in other amphibians, the skin of Xenopus plays a central role in electrolyte and osmoregulatory
functions homeostasis.206 ,207 The vast majority of water uptake occurs through the skin; oral drinking is minimal.
(Continued)
Table 14 Continued
System Organ/Process Comments
Continuous shedding Due to continuous shedding and ingestion of the outer layers of the skin, tattooing is not a permanent
means of individual identification in Xenopus. Alternative methods include using photographs or drawings
of natural marking, suturing colored beads into toe webs using nonabsorbable suture material, and
integrated transponder tags.41
Musculoskeletal
Pelvic girdle and limbs Highly adapted for jumping in most anurans. In X laevis, the ileosacral joint can slide cranially and caudally
along the vertebral column, increasing hindlimb propulsion.200 Xenopus will readily jump out of containers
when their escape response is evoked (ie, due to low water levels, external stimuli). Secure, perforated
plastic lids or screens should be provided.
Nervous

Brain Overall structure is typical of the amphibian brain with the telencephalon, diencephalon, and
mesencephalon being of roughly similar size. The tectum, located in the roof of the mesencephalon, is a
prominent structure with a distinctive layered cortical architecture, receives visual and
auditory/mechanosensory input.
Regenerative potential208 Larval X laevis have high capacity for brain and spinal cord regeneration, which is lost during
metamorphosis. Regeneration of the optic nerve is retained throughout adult life.
Reproductive
Cloacal papilla Readily visible in sexually mature females, absent in males. Also referred to as the cloacal flap.
Nuptial pads Darkly pigmented areas on the inner forelimbs and digits of males. Help the male hold onto the female’s
back during amplexus.
Ovaries Mature, vitellogenic follicles contain large numbers of brightly eosinophilic, ovoid yolk platelets, and a
prominent nucleus with multiple, peripheral nucleoli. A large mass of mitochondria, known as a Balbani
body, may be seen adjacent to the nucleus.199
Oviducts Highly coiled and lined by glandular mucosa that produces the “jelly coat” covering oocytes.
Testes In adult make X laevis, the testes are approximately 1 cm long and whitish. Sperm can be isolated from
extracted Xenopus testes for in vitro fertilization. Histologically similar to other vertebrates. Male Xenopus do
not possess the ovarian remnant (Bidder’s organ) found in bufonid toads.
Respiratory
General Cutaneous respiration is less well developed in Xenopus than some other amphibian species. Air is gulped
into the lungs at the water surface, meaning animals may drown if trapped underwater for extended
periods.41 No ribs or diaphragm. During inhalation, air is forced into lungs by contraction of the floor of the
buccopharyngeal cavity. Exhalation occurs via a combination of flank muscle contraction, elastic recoil, and
smooth muscle of the lungs.38
Large airways and lungs Trachea is extremely short. Bronchi are supported by rings of hyaline cartilage. Bronchioles lack cartilage
and have a thin layer of subepithelial smooth muscle; lead to blind-ended alveolar sacs lined by
pneumocytes.199
Special senses
Lateral line system Similar to that of fish. Runs down either side of the body and used to detect changes in water movement via
rows of mechanoreceptive hair cells.209 Innervated by branches of the cranial nerves.
Eyes Eyes are located on the dorsal aspect of the head and adapted for detecting food and predators at the water
surface rather than underwater.38 The hiding response is often evoked by objects moving above the water.41
Vomeronasal organ Involved in olfaction and located just dorsal to the oral cavity. Lined by sensory epithelium that is
continuous with that of the nasal cavity. Also called the Jacobson’s organ.
Urinary
Kidneys Elongate and located in the caudal dorsal coelom. Amphibian kidneys lack a Loop of Henle and cannot
concentrate urine above the osmolality of plasma. Corticomedullary organization also absent. Primarily
excrete nitrogenous waste in the form of ammonia, which is strongly alkaline but quickly diluted by water
in the environment. Frequent or continuous water changes are necessary to prevent ammonia toxicity. In
low water conditions, Xenopus are able to convert ammonia into less-toxic urea.210,211
Urinary bladder Small, lined by transitional epithelium. Located ventral to the large intestine. Opens into the cloaca.
Urine first enters the cloaca via the ureters, then is forced into the bladder by smooth muscle
contractions.211
laevis oocytes and embryos are often used as heterologous same advantages as X laevis but has a faster generation time
expression platforms to study ion channel physiology and and smaller genome, making it a more tractable option for
elucidate protein function and signaling pathways.28–31 Recent some genetic and genomic studies.33 Advanced genome-editing
years have also seen the rise of another Xenopus species, X techniques, such as the CRISPR/Cas9 system, are regularly
tropicalis (sometimes referred to using the subgenus Silurana),32 used to efficiently create transgenic and knock-out Xenopus
as a popular nonmammalian animal model. Differing biological for use in a diverse range of applications, including human
features and research uses of X laevis and X tropicalis are disease modeling.34,35 Currently, a network of specialized online
outlined in Table 13. Briefly, X tropicalis offers many of the resources exists to support Xenopus research, facilitate sharing of
194 Lisa M. et al.
Table 15 Metabolic, Spontaneous (and Neoplastic) in Xenopus Species38 ,43,44,212
Alimentary
Cloacal prolapse Cloacal or rectal prolapse may occur secondary to intestinal parasites, inflammation, fecal impaction,
or space-occupying lesions within the coelom (eg, gastric overload, neoplasia, fluid accumulation,
ovarian enlargement).
Gastric prolapse Although eversion of the stomach can be a normal physiologic response, animals can suffocate if the
prolapse is prolonged due to anatomic obstruction or stimuli, including environmental noise and
vibration.213
Hematopoietic-
immunologic
Lymphoma Lymphoma is the most commonly reported neoplasm in Xenopus and can affect multiple organs.38,45

Differentiation from granulomatous inflammation by routine histology can be challenging; previous
reports of “transmissible Xenopus lymphoma” were later found to be granulomatous disease caused by
Mycobacterium marinum.214 ,215 Acid-fast staining is recommended in any case of putative lymphoma in
Xenopus.
Integumentary
Melanophoroma The second-most commonly reported neoplasm in Xenopus, arises from black-pigmented
chromatophores in the skin. Can be benign or malignant.45 Herpesvirus particles were identified in
nuclei of melanophorma cells in a Japanese colony of X laevis, suggestive of possible viral etiology in
these cases.216
Multisystemic
Dehydration Laboratory Xenopus are highly susceptible to dehydration/desiccation and must not be kept out of water
for more than 15–20 min.38 Dehydrated frogs are often in hypovolemic shock and present with dull,
wrinkled skin, sunken eyes, and a sticky, opaque slime coat.
Gas bubble disease Also called gas supersaturation, this disease occurs when environmental conditions cause aqueous gas
concentrations to rise above the saturation point (eg, air leakage in water pipes, delivery of deep well
water).217 Affected animals may show abnormal buoyancy, visible cutaneous gas bubbles (particularly in
the interdigital webbing), hemorrhage, and erosions.44 ,218 Death can occur due to secondary infections
and formation of gas emboli, but many animals recover with rapid identification and correction of the
underlying problem.
Injury Bite wounds resulting from normal predatory and social behaviors may lead to secondary infections,
debilitation, and death. Frequency of bite wounds is reduced by decreasing stocking density and
providing adequate amounts of food and enrichment items, such as pipes or other structures where
subordinate animals can seek refuge.219
Nutritional disorders Amphibians are susceptible to a wide range of conditions related to insufficiency or excess of dietary
elements (eg, metabolic bone disease, muscular underdevelopment AKA spindly leg, short tongue
syndrome, weight loss, obesity).198 However, these diseases can be prevented in laboratory Xenopus by
feeding appropriate amounts of pelleted food specifically formulated for these species.
Thermal shock Although gradual temperature changes are generally tolerated, Xenopus may die acutely when exposed
to sudden small increases or decreases in temperature (2–5◦ C different than primary enclosure).38
Toxicosis Xenopus are sensitive to a number of chemicals routinely used as disinfecting agents in laboratories and
animal facilities. All recently cleaned equipment and enclosures must be thoroughly rinsed before
returning to use.44 Chlorine and chloramines are oxidizing agents commonly found in cleaning
products and municipal water supplies. Exposure to high levels of these chemicals can result in skin
sloughing, eye irritation, and acute death.38 ,217 Water quality issues such as elevated ammonia,
nitrate/nitrite, and extreme pH can also result in nonspecific clinical signs that mimic and predispose
animals to infectious disease.44 ,218
Reproductive
Ovarian hyper-stimulation A rare condition of female X leavis receiving exogenous gonadotropin hormones to induce ovulation
syndrome and egg laying. Affected animals develop severe, full-body edema and have large numbers of
free-floating eggs in the coelom. Prognosis is poor.220
datasets and genetically modified strains, and promote optimal best suited for facilities with low numbers of animals. More
husbandry practices.36,37 sophisticated (and expensive) flow-through and recirculating
All Xenopus species are fully aquatic and require water systems are available commercially and offer several advantages
throughout their larval and adult life stages. In their native sub- in regards to space usage, stocking density, and ease of
Saharan Africa, these highly adaptable frogs are found in a wide maintenance. Regardless of the type of housing, water source
range of aquatic habitats, both natural and man-made. In the and quality are of upmost importance in maintaining Xenopus
laboratory, different types of housing systems may be employed health, welfare, and optimal utility for research.41 Although
depending on colony size and available resources.38–41 Static some key water quality factors are discussed in Tables 14 and 15,
systems consisting of individual, closed tanks are inexpensive readers should refer to previous publications for more specific
but require frequent, manual water changes and are therefore detailed information on this topic.38–43 As ectotherms, Xenopus
Table 16 Infectious Diseases Affecting Xenopus Species38 ,43,44
Viruses221
Ranaviruses Multiple viruses in the genus Ranavirus (family Iridoviridae) are pathogens of ectothermic vertebrates and cause large mortality
events in free-ranging amphibians.222 Presentation varies widely and may include lethargy, hemorrhage and necrosis of the skin
and internal organs, or sudden death without clinical signs.44,221 Skin lesions may mimic “red leg syndrome” caused by
Gram-negative bacteria.218 X leavis tadpoles are highly susceptible, whereas immune-competent adults are relatively resistant to
disease and may serve as asymptomatic carriers.223,224 Interspecies transmission among amphibians, fish, and reptiles has been
proposed;225 no known zoonotic risk.
Bacteria226 ,227
Chlamydiosis Multisystemic disease caused by intracellular Gram-negative pathogens in the family Chlamydiaceae. Original reports of outbreaks
in laboratory Xenopus implicated Chlamydophila psittaci based on histologic findings,228 whereas more recent reports that utilized
molecular methods have primarily identified C. pneumoniae.229,230 Clinical signs are indistinguishable from other causes of sepsis.
At necropsy the liver and spleen may be enlarged and contain foci of lymphohistiocytic and/or granulomatous inflammation.44

Potential for zoonotic transmission.
Chryseobacterium sp. Formerly known as Flavobacterium, these ubiquitous, Gram-negative bacilli have been shown to cause significant mortality in
laboratory Xenopus colonies.231 Clinical signs are nonspecific and similar to those seen with other Gram-negative septicemias.
Chryseobacterium are highly resistant to many antibiotics as well as disinfection by chlorine/chloramines.43 Potential for zoonotic
transmission.
Dermatosepticemia Generalized bacterial infection in Xenopus is often referred to as “red leg syndrome” due to associated hyperemic or ulcerative skin
lesions on the hindlimbs. Other clinical signs may include lethargy, anorexia, subcutaneous and coelomic edema, and neurologic
deficits.43 This condition can be caused by numerous Gram-negative organisms that thrive in aquatic environments (Aeromonas,
Pseudomonas, Proteus, and E coli) and is often precipitated by stress and/or suboptimal husbandry practices.38,226,227 Antibiotic
therapy may be effective in some circumstances38 but should be guided by culture and sensitivity testing as well as exclusion of
concurrent fungal or viral infection.
Mycobacteriosis232 Xenopus are susceptible to natural and experimental infection by a number of acid-fast bacilli in the genus Mycobacterium including
M marinum, M liflandii, M xenopus, and M avium intacellulare complex.227,232 Mycobacteriosis usually occurs in adult animals and may
be subclinical or present as chronic nodular to ulcerative skin lesions and generalized wasting and debilitation (similar to fungal
disease).43,218 Disease may be rapidly progressive and fatal disease in immune-compromised animals.233 Typical necropsy
findings include granulomas and/or necrotizing inflammation in the skin and internal organs, acid-fast stains on cytology or
histology. Potential for zoonotic transmission.
Protists226,234
Cryptosporidia spp. Single case report of cryptosporidiosis causing emaciation and proliferative gastritis in a laboratory X laevis.235 Although rare in
Xenopus, these organisms are of concern due to their zoonotic potential and transmission via contaminated water.
Fungi and fungal-like
organisms236,237
Chytridiomycosis Batrachochytrium dendrobaditidis is an emerging pathogen that has contributed to severe declines in free-ranging amphibian
populations.222,238 Spread of the fungus to vulnerable species has linked to global trade and accidental release of X laevis, which
can act as asymptomatic carriers.239,240 Although infections in X laevis are typically subclinical, severe disease and high mortality
have been reported in a laboratory colony of X tropicalis.241 Clinical findings included hyperkeratosis, abnormal pigmentation, skin
shedding, and weight loss. Diagnosis is made by identification of characteristic, round to flask-shaped thalli in wet mounts of shed
skin or on histology; PCR testing is also available.242
Saprolegniasis Infection by water molds, such as Saprolegnia sp. and other similar organisms, is often associated with poor water quality and
(water molds) hygiene.243 As opportunists, these organisms frequently colonize preexisting skin lesions and appear as cottony, white to gray
material that is easiest to appreciate when submerged in water. Infection of harvested oocytes and eggs may decrease their utility
for research.38 Diagnosis is confirmed by culture and/or observation of broad, aseptate filaments on wet mounts or histology.237
Other fungal infections Amphibians are susceptible to infection by a broad range of saprophytic fungi that thrive in damp environments (eg, Mucor,
Rhizopus, and Basidiobolus sp.). These infections often occur secondarily to skin injury, underlying disease, or suboptimal husbandry
practices. Clinical signs may be limited to nodular or ulcerative skin lesions, or with visceral dissemination, progress to generalized
signs and death.44 Lesions caused by pigmented fungal infection (chromomycoses) may appear gray or black grossly.218 Diagnosis
of fungal infection can be made by observation of hyphae or spores on wet mounts or histology. Specific identification requires
culture and/or sequencing.
Metazoans226,234
Acariasis (mites) Xenopacarus africanus is a mite found in the nasal cavity and Eustachian tubes of X laevis. They are commensal organisms that do
not cause clinical signs.38
Pseudocapillaroides A nematode that infects the dorsal skin of Xenopus leading to increased shedding, depigmentation, rough pitted skin, and
xenopi ulcers.218 Generalized debilitation and fatal secondary infections may also occur.244 Because of the direct life cycle and
transmission, heavy infestations can develop in research colonies.38 Adult worms and characteristic bipolar eggs can be observed
in skin scrapings and wet mounts of shed skin. Anthelminthic compounds may be effective but may cause death due to massive
immune response in heavily infested animals.38,245
Rhabdias spp. Adult nematodes in the genus Rhabdias inhabit the lungs of frogs, where they can cause pneumonia and failure to thrive.38 The life
(lungworms) cycle is direct: eggs are coughed up, swallowed, and shed in feces along with larvae, which go on to penetrate the skin of the
subsequent host.44,226 Repeated reinfection may lead to heavy infestation and progressive debilitation.234 Thin-shelled, larvated
eggs can be observed in tracheal washes and fecal preparations.234
PCR, polymerase chain reaction.
rely almost entirely on environment for thermoregulation and corresponding husbandry considerations, are summarized in
are sensitive to abrupt changes; therefore, ambient temperatures Table 14.
in rooms holding Xenopus should be fairly constant.38 Additional Xenopus are susceptible to a number of spontaneous dis-
biological and physiologic features of Xenopus, along with eases that can impact research by causing either a sudden loss
196 Lisa M. et al.
of animals (acute toxicosis, viral, and bacterial infections) or 6. Wolf JC, Maack G. Evaluating the credibility of histopathol-
progressive debilitation (nutritional disorders, chronic bacterial, ogy data in environmental endocrine toxicity studies. Env-
and fungal infections). The vast majority of noninfectious and iron Toxicol Chem 2017; 36(3):601–611.
infectious diseases in Xenopus are generalized, simultaneously 7. Wolf JC, Ruehl-Fehlert C, Segner HE et al. Pathology work-
affecting multiple organ systems, and related to underlying hus- ing group review of histopathologic specimens from three
bandry issues and environmental stressors (Tables 15 and 16). laboratory studies of diclofenac in trout. Aquat Toxicol 2014;
As such, a careful assessment of husbandry practices and water 146:127–136.
quality should be part of any clinical work-up.38,43,44 Transmis- 8. Wolf JC, Wheeler JR. A critical review of histopatho-
sion of infectious agents typically occurs through direct contact logical findings associated with endocrine and non-
with affected animals, fomites such as handling and laboratory endocrine hepatic toxicity in fish models. Aquat Toxicol
equipment, and contaminated water. Because several pathogens 2018; 197:60–78.
that affect Xenopus are highly infectious to other animals in 9. King AS, McLelland J. Birds: Their Structure and Function. 2nd
the system or pose zoonotic risks, euthanasia is often elected, ed. London, UK: Bailliere Tindall; 1984.

rather than antimicrobial therapy, for frogs with infectious dis- 10. O’Rourke DP, Cox JD, Baumann DP. Nontraditional species.
ease.38 Spontaneous neoplasia is relatively rare in laboratory and In: Weichbrod RH, Thompson GAH, Norton JN, eds. Manage-
free-ranging amphibians. Lymphoma and melanophoromas are ment of Animal Care and Use Programs in Research, Education,
the most commonly reported and best-characterized tumors in and Testing. Boca Raton (FL): CRC Press/Taylor & Francis;
Xenopus. Reports of other neoplasms are primarily limited to 2018. p. 579–596.
single case reports.45,46 11. Sid H, Schusser B. Applications of gene editing in chickens:
a new era is on the horizon. Front Genet 2018; 9:456.
12. Wisely CE, Sayed JA, Tamez H et al. The chick eye in vision
research: an excellent model for the study of ocular disease.
Prog Retin Eye Res 2017; 61:72–97.
Summary 13. Vilches-Moure JG. Embryonic chicken (Gallus gallus domes-
Familiarity with the spectrum of spontaneous conditions that ticus) as a model of cardiac biology and development. Comp
affect avian and aquatic species enhances our ability to optimize Med. 2019; 69(3):184–203.
their health and welfare in the laboratory setting. Importantly, 14. Kain KH, Miller JW, Jones-Paris CR et al. The chick embryo
many of the diseases presented in this paper can be prevented as an expanding experimental model for cancer and car-
in research colonies by employing housing and husbandry prac- diovascular research. Dev Dyn 2014; 243(2):216–228.
tices that minimize social and physiologic stress and by enforc- 15. Guide for the Care and Use of Agricultural Animals in
ing stringent biosecurity protocols. Moreover, pathologists and Research and Teaching (Ag Guide). 3rd ed: American Dairy
peer-reviewers can take an active role in ensuring that gross Association, American Society of Animal Science, and Poultry
and histologic findings in nonmammalian species are accurately Science Association; 2010. Available at: https://www.aaalac.
interpreted, so that the data generated from these models, and org/pub/?id=E900BDB6-CCCF-AB13-89B6-DA98A4B52218.
disseminated to the scientific community at large, are valid and 16. Shivaprasad HL. Pathology of Birds – An Overview. 2017.
reproducible. Available at: https://www.asav.es/wp-content/uploads/
2016/06/5a_Overview-of-Poultry-Pathology-in-Poultry_Bird
Path_2015_Shivaprasad-1.pdf.
17. Boodhoo N, Gurung A, Sharif S et al. Marek’s disease in
chickens: a review with focus on immunology. Vet Res 2016;
Acknowledgments 47(1):119.
The authors thank Dr Cory Brayton for her role in the conception 18. Lee HJ, Bahr JM, Bitterman P et al. Polycystic ovarian con-
and coordination of this manuscript. dition may be a risk factor for ovarian tumor development
Potential conflicts of interest. All authors: No reported conflicts. in the laying hen model of spontaneous ovarian cancer. J
Immunol Res 2018; 2018:2590910.
19. Hawkridge AM. The chicken model of spontaneous ovarian
cancer. Proteomics Clin Appl 2014; 8(9–10):689–699.
References
20. Bateson M, Feenders G. The use of passerine bird species
1. Glick B, Chang TS, Jaap GR. The bursa of Fabricius in laboratory research: implications of basic biology for
and antibody production. Poultry Sci 1956; 35(1): husbandry and welfare. ILAR J 2010; 51(4):394–408.
224–225. 21. Sneiszko SF. History and present status of fish diseases. J
2. Loewi O. Über humorale übertragbarkeit der Herznerven- Wildl Dis 1975; 11(4):446–459.
wirkung. Pflügers Arch 1921; 189:239–242. 22. Froese RP. Fishbase. 2018; www.fishbase.org. Accessed
3. Casadevall A, Fang FC. Rigorous science: a how-to guide. March 23, 2018.
MBio 2016; 7(6):16. 23. Martineau D, Ferguson HW. Neoplasia. In: Ferguson HW, ed.
4. Zeiss CJ, Johnson LK. Bridging the gap between repro- Systemic Pathology of Fish. London, UK: Scotian Press; 2006. p.
ducibility and translation: data resources and approaches. 321–335.
ILAR J 2017; 58(1):1–3. 24. Wolf JC. The case for intersex intervention. Environ Toxicol
5. Wolf JC, Baumgartner WA, Blazer VS et al. Nonlesions, Chem 2011; 30(6):1233–1235.
misdiagnoses, missed diagnoses, and other interpretive 25. Hogben L. Xenopus test for pregnancy. BMJ 1939; 2(4095):38.
challenges in fish histopathology studies: a guide for inves- 26. Bantle JA, Rayburn JR, Burton DT et al. Initial interlaboratory
tigators, authors, reviewers, and readers. Toxicol Pathol 2014; validation study of FETAX: phase I testing. J Appl Toxicol
43(3):297–325. 1994; 14(3):213–223.
27. Dumont JN, Schultz TW, Buchanan M et al. Frog Embryo 48. Riddell C. Avian Histopathology. 2nd ed. Tallahassee, FL: The
Teratogenesis Assay: Xenopux: (FETAX) - a short term assay American Association of Avian Pathologists; 1996.
applicable to complex environmetnal mixtures. In: Waters 49. Bacha Jr WJ, Bacha LM. Color Atlas of Veterinary Histology. 3rd
MD, Shahbeg SS, Lewtas J, Claxton L, Chernoff N, Nesnow ed. Ames, IA: Wiley-Blackwell; 2012.
S, eds. Bioassays in the Analysis of Complex Environmental 50. Brugere-Picoux J, Vaillancourt J, Shivaprasad HL, Venne D,
Mixtures III. New York: Plenum Press; 1983:393–405. Bouzouaia M. Manual of Poultry Diseases. 1st ed. Paris, France:
28. Marchant JS. Heterologous protein expression in the AFAS; 2015.
Xenopus oocyte. Cold Spring Harb Protoc 2018; 2018(4): 51. Schmidt RE, Reavill DR, Phalen DN. Pathology of Pet and Aviary
pdb.prot096990. Birds. 1st ed. Ames, IA: Blackwell Publishing; 2003.
29. Mowry KL. Using the Xenopus oocyte toolbox. Cold Spring 52. Barnes HJ, Fletcher O. Hemic system. In: Abdul-Aziz T,
Harb Protoc 2020; 2020(4):pdb.top095844. Fletcher O, Barnes HJ, eds. Avian Histopathology. Madison,
30. Chernet BT, Levin MA. Versatile protocol for mRNA electro- WI: The American Association of Avian Pathologists; 2016.
poration of Xenopus laevis embryos. Cold Spring Harb Protoc 53. Ritchison G. Avian respiration. http://people.eku.edu/ritchiso

2012; 2012(4):pdb.prot067694. ng/birdrespiration.html. Accessed October 6, 2020.
31. Delpire E, Gagnon KB, Ledford JJ et al. Housing and hus- 54. Shivaprasad HL. Eye and ear. In: Abdul-Aziz T, Fletcher O,
bandry of Xenopus laevis affect the quality of oocytes for Barnes HJ, eds. Avian Histopathology. 4th ed. Madison, WI:
heterologous expression studies. JAALAS. 2011; 50(1):46–53. The American Association of Avian Pathologists; 2016.
32. Evans BJ, Carter TF, Greenbaum E et al. Genetics, morphol- 55. Crespo R. Developmental, metabolic, and other noninfec-
ogy, advertisement calls, and historical records distinguish tious disorders. In: Swayne DE, Boulianne M, Logue CM
six new Polyploid species of African clawed frog (Xeno- et al., eds. Diseases of Poultry. Hoboken, NJ: Wiley Blackwell;
pus, Pipidae) from west and Central Africa. PLoS One 2015; 2020. p. 1286–1329.
10(12):e0142823. 56. Biesiadecki BJ, Jin JP. Exon skipping in cardiac troponin T of
33. Grainger RM. Xenopus tropicalis as a model organism for turkeys with inherited dilated cardiomyopathy. J Biol Chem
genetics and genomics: past, present, and future. Methods 2002; 277(21):18459–18468.
Mol Biol 2012; 917:3–15. 57. Basaki M, Asasi K, Tabandeh MR et al. Polymorphism iden-
34. Kakebeen A, Wills A. Advancing genetic and genomic tech- tification and cardiac gene expression analysis of the calse-
nologies deepen the pool for discovery in Xenopus tropi- questrin 2 gene in broiler chickens with sudden death
calis. Dev Dyn 2019; 248(8):620–625. syndrome. Br Poult Sci 2016; 57(2):151–160.
35. Guo X, Zhang T, Hu Z et al. Efficient RNA/Cas9-mediated 58. Basaki M, Tabandeh MR, Aminlari M et al. Sequence and
genome editing in Xenopus tropicalis. Development 2014; expression analysis of cardiac ryanodine receptor 2 in broil-
141(3):707–714. ers that died from sudden death syndrome. Avian Pathol
36. Horb M, Wlizla M, Abu-Daya A et al. Xenopus resources: 2019; 48(5):444–453.
transgenic, inbred and mutant animals, training opportu- 59. Riddell C. A survey of skeletal disorders in five turkey flocks
nities, and web-based support. Front Physiol 2019; 10:387. in Saskatchewan. Can J Comp Med 1980; 44(3):275–279.
37. Karimi K, Fortriede JD, Lotay VS et al. Xenbase: a genomic, 60. Shivaprasad HL. Poultry ophthalmology. In: Gelatt KN, ed.
epigenomic and transcriptomic model organism database. Veterinary Ophthalmology. 3rd ed. Philadelphia, PA: Lippin-
Nucleic Acids Res 2018; 46(D1):D861–D868. cott, Williams and Wilkins; 1999:1177–1207.
38. Green SL. The Laboratory Xenopus sp. Boca Raton, FL: CRC 61. Siller WG. Renal pathology of the fowl–a review. Avian Pathol
Press; 2010. 1981; 10(3):187–262.
39. McNamara S, Wlizla M, Horb ME. Methods in molecular 62. Crespo R, Franca MS, Fenton H et al. Galliformes and
biology. Methods Mol Biol 2018; 1865:1–17. Columbiformes. In: Terio KA, McAloose D, Leger JS, eds.
40. Browne RK, Odum RA, Herman T et al. Facility design and Pathology of Wildlife and Zoo Animals. San Diego, CA: Aca-
associated services for the study of amphibians. ILAR J 2007; demic Press; 2018. p. 741–767.
48(3):188–202. 63. Boulianne M, Logue CM, McDougald LR, Nair V, Suarez DL.
41. Schultz TW, Dawson DA. Housing and husbandry of Xeno- Diseases of Poultry. Vol 1 and 2. 14th ed. Hoboken, NJ: Wiley
pus for oocyte production. Lab Anim 2003; 32(2):34–39. Blackwell; 2020.
42. Whitaker B. Water quality. In: Wright KM, Whitaker B, 64. Boulianne M, Barger K, Dorko N, et al. Avian Disease Manual.
eds. Amphibian Medicine and Captive Husbandry. Malabar, FL: 8th ed. Jacksonville, FL: The American Association of Avian
Krieger; 2001:147–158. Pathologists; 2019.
43. O’Rourke DP, Rosenbaum MD. Biology and diseases of 65. Pantin-Jackwood MJ, Swayne DE. Pathogenesis and patho-
amphibians. In: Fox J, Anderson L, Otto G, Pritchett-Corning biology of avian influenza virus infection in birds. Rev Sci
K, Whary M, eds. Laboratory Animal Medicine. 3rd ed. Cam- Tech 2009; 28(1):113–136.
bridge, MA: Academic Press; 2015:931–965. 66. Franca MS, Brown JD. Influenza pathobiology and patho-
44. Densmore CL, Green DE. Diseases of amphibians. ILAR J genesis in avian species. Curr Top Microbiol Immunol 2014;
2007; 48(3):235–254. 385:221–242.
45. Green DE, Harshbarger JC. Spontaneous neoplasia in 67. Portz C, Beltrao N, Furian TQ et al. Natural infection of
amphibia. In: Wright KM, Whitaker BK, eds. Amphib- turkeys by infectious laryngotracheitis virus. Vet Microbiol
ian Medicine and Captive Husbandry. Malabar, FL: Krieger; 2008; 131(1–2):57–64.
2001:335–400. 68. Hauck R, Mays J, Dunn J et al. Two cases of Marek’s disease
46. Stacy BA, PJ M. Amphibian oncology. Vet Clin Exot Anim Pract. in backyard turkeys. Avian Dis 2020; 64(3):347–351.
2004; 7:673–695. 69. Franca M, Barrios MA, Stabler L et al. Association of Beta2-
47. Abdul-Aziz T, Fletcher O, Barnes HJ. Avian Histopathology. positive Clostridium perfringens type a with focal duodenal
4th ed. Madison, WI: The American Association of Avian necrosis in egg-laying chickens in the United States. Avian
Pathologists; 2016. Dis 2016; 60(1):43–49.
198 Lisa M. et al.
70. Ritchie BW, Harrison GJ, Harrison LR. Avian Medicine: Prin- Americanus, from Boston Harbor, Massachusetts. Environ
ciples and Application. Lake Worth, FA: Wingers Publishing, Health Perspect 1991; 90:17–26.
Inc.; 1994. 91. Stentiford GD, Viant MR, Ward DG et al. Liver tumors in wild
71. Reavill DR, Dorrestein G. Psittacines, Coliiformes, flatfish: a histopathological, proteomic and metabolomic
Musophagiformes, Cuculiformes. In: Terio K, McAloose study. Omics 2005; 9(3):281–299.
D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. 1st 92. Blanco AM, Sundarrajan L, Bertucci JI et al. Why goldfish?
ed. San Diego, CA: Academic Press; 2018:775–796. Merits and challenges in employing goldfish as a model
72. Walsh AL, Shivaprasad HL. Unusual lesions of organism in comparative endocrinology research. Gen Comp
atherosclerosis in Psittacines. J Exot Pet Med 2013; 22(4): Endocrinol 2018; 257:13–28.
366–374. 93. Choe Y, Yu JE, Park J et al. Goldfish, Carassius auratus,
73. Garner MM, Clubb SL, Mitchell MA et al. Feather-picking as an infection model for studying the pathogenesis of
psittacines: histopathology and species trends. Vet Pathol Edwardsiella piscicida. Vet Res Comm 2017; 41(4):289–297.
2008; 45(3):401–408. 94. Ota KG, Abe G. Goldfish morphology as a model for evolu-

74. Lightfoot TL, Yeager JM. Pet bird toxicity and related tionary developmental biology. Wiley Interdiscip Rev Dev Biol
environmental concerns. Vet Clin Exot Anim Pract 2008; 2016; 5(3):272–295.
11(2):229–259 vi. 95. Talaat AM, Reimschuessel R, Wasserman SS et al. Goldfish,
75. Rosskopf WJ Jr. Common conditions and syndromes Carassius auratus, a novel animal model for the study of
of canaries, finches, lories and lorikeets, lovebirds, and Mycobacterium marinum pathogenesis. Infect Immun 1998;
macaws. Sem Avian Exotic Pet Med 2003; 12(3). 66(6):2938–2942.
76. Harrison GJ, Lightfoot TL. Clinical Avian Medicine. Palm 96. Gerhard GS. Small laboratory fish as models for aging
Beach, FL: Spix Publishing, Inc.; 2005. research. Ageing Res Rev 2007; 6(1):64–72.
77. Trupkiewicz J, Garner M, Juan-Salles C. Passeriformes, 97. Ishikawa Y. Medakafish as a model system for ver-
Caprimulgiformes, Coraciiformes, Piciformes, Buceroti- tebrate developmental genetics. Bioassays 2000; 22(5):
formes, and Apodiformes. In: Terio KA, Mcaloose D, St. 487–495.
Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, 98. Shima A, Mitani H. Medaka as a research organism: past,
CA: Academic Press; 2018:799–823. present and future. Mech Dev 2004; 121(7–8):599–604.
78. Doneley B, Harrison GJ, Lightfoot TL. Maximizing Information 99. Wakamatsu Y, Pristyazhnyuk S, Kinoshita M et al. The
From the Physical Examination. Vol 1 and 2. Palm Beach, FL: see-through medaka: a fish model that is transparent
Spix Publishing, Inc.; 2005. throughout life. Proc Natl Acad Sci U S A 2001; 98(18):
79. Joseph V. Infectious and parasitic diseases of captive 10046–10050.
passerines. Sem Avian Exotic Pet Med. 2003; 12(1):21–28. 100. Wittbrodt J, Shima A, Schartl M. Medaka - a model organism
80. Bailey GS, Williams DE, Hendricks JD. Fish models for envi- from the Far East. Nat Rev Genet 2002; 3(1):53–64.
ronmental carcinogenesis: the rainbow trout. Environ Health 101. Lister AL, Van der Kraak GJ, Rutherford R et al. Fundulus het-
Perspect 1996; 104(Suppl 1):5–21. eroclitus: ovarian reproductive physiology and the impact
81. Bolis CL, Piccolella M, Valle AZD et al. Fish as model in phar- of environmental contaminants. Comp Biochem Physiol CTox-
macological and biological research. Pharmacol Res 2001; icol Pharmacol 2011; 154(4):278–287.
44(4):265–280. 102. Vogelbein WK, Fournie JW, Vanveld PA et al. Hep-
82. Carvan MJ 3rd, Gallagher EP, Goksoyr A et al. Fish models in atic neoplasms in the Mummichog Fundulus-Heteroclitus
toxicology. Zebrafish 2007; 4(1):9–20. from a creosote-contaminated site. Cancer Res 1990;
83. Planchart A, Mattingly CJ, Allen D et al. Advancing toxicol- 50(18):5978–5986.
ogy research using in vivo high throughput toxicology with 103. Meierjohann S, Schartl M. From Mendelian to molecular
small fish models. ALTEX 2016; 33(4):435–452. genetics: the Xiphophorus melanoma model. Trends Genet
84. Ankley GT, Johnson RD. Small fish models for identifying 2006; 22(12):654–661.
and assessing the effects of endocrine-disrupting chemi- 104. Sinnhuber RO, Hendricks JD, Wales JH et al. Neoplasms in
cals. ILAR J 2004; 45(4):469–483. rainbow trout, a sensitive animal model for environmental
85. McVicar AH. Disease and parasite implications of the coex- carcinogenesis. Ann N Y Acad Sci 1978; 298:389–408.
istence of wild and cultured Atlantic salmon populations. 105. Tyler CR, Lange A, Paull GC et al. The roach (Rutilus rutilus)
ICES J Mar Sci 1997; 54(6):1093–1103. as a sentinel for assessing endocrine disruption. Environ Sci
86. Bader JA, Nusbaum KE, Shoemaker CA. Comparative 2007; 14(5):235–253.
challenge model of Flavobacterium columnare using 106. Ortuno J, Esteban MA, Meseguer J. Effects of short-term
abraded and unabraded channel catfish, Ictalurus puncta- crowding stress on the gilthead seabream (Sparus aurata
tus (Rafinesque). J Fish Dis 2003; 26(8):461–467. L) innate immune response. Fish Shellfish Immunol 2001;
87. Tidwell JH, Allan GL. Fish as food: aquaculture’s contri- 11(2):187–197.
bution - ecological and economic impacts and contribu- 107. Katsiadaki I, Sanders M, Sebire M et al. Three-spined stick-
tions of fish farming and capture fisheries. EMBO Rep 2001; leback: an emerging model in environmental endocrine
2(11):958–963. disruption. Environ Sci 2007; 14(5):263–283.
88. Ankley GT, Villeneuve DL. The fathead minnow in aquatic 108. McKinnon JS, Rundle HD. Speciation in nature: the three-
toxicology: past, present and future. Aquat Toxicol 2006; spine stickleback model systems. Trends Ecol Evol 2002;
78(1):91–102. 17(10):480–488.
89. McArn GE, Chuinard RG, Miller BS et al. Pathology of skin 109. Rezk MA, Ponzoni RW, Khaw HL et al. Selective breeding
tumors found on English sole and starry flounder from for increased body weight in a synthetic breed of Egyp-
Puget Sound, Washington. JNCI 1968; 41(1):229. tian Nile tilapia, Oreochromis niloticus: response to selec-
90. Murchelano RA, Wolke RE. Neoplasms and nonneoplas- tion and genetic parameters. Aquaculture 2009; 293(3–4):
tic liver-lesions in winter flounder, pseudo-Pleuronectes- 187–194.
110. Matsunari H, Hamada K, Mushiake K et al. Effects of 130. Robertson DA. A Review of Ichthyobodo Necator (Henneguy,
taurine levels in broodstock diet on reproductive perfor- 1883) an important and damaging fish parasite. In: Muir JF,
mance of yellowtail Seriola quinqueradiata. Fish Sci 2006; Roberts RJ, eds. Recent Advances in Aquaculture: Vol. 2. Boston,
72(5):955–960. MA: Springer US; 1985:1–30.
111. Feitsma H, Cuppen E. Zebrafish as a cancer model. Mol 131. Urawa S, Ueki N, Karlsbakk E. A review of Ichthyobodo
Cancer Res 2008; 6(5):685–694. infection in marine fishes. Fish Pathol 1998; 33(4):311–320.
112. Hill AJ, Teraoka H, Heideman W et al. Zebrafish as a model 132. Colorni A, Burgess P. Cryptocaryon irritans Brown 1951, the
vertebrate for investigating chemical toxicity. Toxicol Sci cause of ’white spot disease’ in marine fish: an update.
2005; 86(1):6–19. Aquarium Sci Conserv 1997; 1(4):217–238.
113. Lele Z, Krone PH. The zebrafish as a model system in devel- 133. Dickerson H, Clark T. Ichthyophthirius multifiliis: a model
opmental, toxicological and transgenic research. Biotechnol of cutaneous infection and immunity in fishes. Immunol Rev
Adv 1996; 14(1):57–72. 1998; 166:377–384.
114. Spitsbergen JM, Kent ML. The state of the art of the 134. Jorgensen LVG. The fish parasite Ichthyophthirius multifil-

zebrafish model for toxicology and toxicologic pathology iis - host immunology, vaccines and novel treatments. Fish
research–advantages and current limitations. Toxicol Pathol Shellfish Immunol 2017; 67:586–595.
2003; 31(Suppl):62–87. 135. Matthews RA. Ichthyophthirius multifiliis Fouquet and
115. Menke AL, Spitsbergen JM, Wolterbeek AP et al. Normal Ichthyophthiriosis in freshwater teleosts. Adv Parasitol 2005;
anatomy and histology of the adult zebrafish. Toxicol Pathol 59:159–241.
2011; 39(5):759–775. 136. Borrego JJ, Valverde EJ, Labella AM et al. Lymphocystis dis-
116. Wedemeyer G. Physiology of Fish in Intensive Culture Systems. ease virus: its importance in aquaculture. Rev Aquac 2017;
Boston, MA: Springer; 1996. 9(2):179–193.
117. Uribe MC, Grier HJ, Mejia-Roa V. Comparative testicular 137. Whittington ID. The Capsalidae (Monogenea: Monopistho-
structure and spermatogenesis in bony fishes. Spermatoge- cotylea): a review of diversity, classification and phylogeny
nesis 2014; 4(3):e983400. with a note about species complexes. Folia Parasitol (Praha)
118. Smith SA. Fish Diseases and Medicine. 1 ed. Boca Raton, FL.: 2004; 51(2–3):109–122.
CRC Press; 2019. 138. Moustafa EMM, Naota M, Morita T et al. Pathological study
119. Bjerkas E, Sveier H. The influence of nutritional and on the Scuticociliatosis affecting farmed Japanese floun-
environmental factors on osmoregulation and cataracts der (Paralichthys olivaceus) in Japan. J Vet Med Sci 2010;
in Atlantic salmon (Salmo salar L). Aquaculture 2004; 72(10):1359–1362.
235(1–4):101–122. 139. Vanas JG, Basson LA. Further contribution to the taxon-
120. Harrison JG, Richards RH. Pathology and histo-pathology omy of the Trichodinidae (Ciliophora, Peritrichia) and a
of nephrocalcinosis in rainbow-trout Salmo-Gairdneri review of the taxonomic status of some fish ectoparasitic
Richardson in fresh-water. J Fish Dis 1979; 2(1):1–12. trichodinids. Syst Parasitol 1989; 14(3):157–179.
121. Hoole D, Nisan H. Ultrastructural studies on intestinal 140. Cobb CS, Levy MG, Noga EJ. Acquired immunity to amyloo-
response of carp, Cyprinus-Carpio L, to the pseudophyl- diniosis is associated with an antibody response. Dis Aquat
lidean tapeworm, Bothriocephalus-Acheilognathi Yam- Org 1998; 34(2):125–133.
aguti, 1934. J Fish Dis 1994; 17(6):623–629. 141. Grandes JMF, Diez MF, Gancedo JMA. Experimental
122. Morand S, Robert F, Connors VA. Complexity in parasite life- pathogenicity in rainbow trout, Oncorhynchus mykiss
cycles - population biology of Cestodes in fish. J Anim Ecol (Walbaum), of two distinct morphotypes of long-spined
1995; 64(2):256–264. Saprolegnia isolates obtained from wild brown trout,
123. Kent ML, Bishop-Stewart JK, Matthews JL et al. Pseudocapil- Salmo trutta L., and river water. J Fish Dis 2001; 24(6):
laria tomentosa, a nematode pathogen, and associated neo- 351–359.
plasms of zebrafish (Danio rerio) kept in research colonies. 142. Noga EJ. Water mold infections of freshwater fish: recent
Comp Med 2002; 52(4):354–358. advances. Annu Rev Fish Dis 1993; 3:291–304.
124. Kent ML, Harper C, Wolf JC. Documented and potential 143. Kent ML, Shaw RW, Sanders JL. Microsporidia in fish. In:
research impacts of subclinical diseases in zebrafish. ILAR Weiess JJ, ed. Microsporidia: Pathogens of Opportunity. Chich-
J 2012; 53(2):126–134. ester, UK: John Wiley and Sons; 2014. p. 493–520.
125. Sangmaneedet S, Smith SA. Efficacy of various chemother- 144. Lom J, Nilsen F. Fish microsporidia: fine structural diversity
apeutic agents on the growth of Spironucleus vortens, an and phylogeny. Int J Parasitol 2003; 33(2):107–127.
intestinal parasite of the freshwater angelfish. Dis Aquat 145. Sitja-Bobadilla A. Fish immune response to Myxozoan par-
Org 1999; 38(1):47–52. asites. Parasite 2008; 15(3):420–425.
126. Yanong RP, Curtis E, Russo R et al. Cryptobia iubilans 146. Baldwin TJ, Newton JC. Pathogenesis of enteric septicemia
infection in juvenile discus. J Am Vet Med Assoc 2004; of channel catfish, caused by Edwardsiella ictaluri: bacteri-
224(10):1644–1650 1606. ologic and light and electron microscopic findings. J Aquat
127. Gibson-Kueh S, Netto P, Ngoh-Lim GH et al. The pathology Anim Health 1993; 5(3):189–198.
of systemic iridoviral disease in fish. J Comp Pathol 2003; 147. Hawke JP, Kent M, Rogge M et al. Edwardsiellosis caused by
129(2–3):111–119. Edwardsiella ictaluri in laboratory populations of zebrafish
128. Whittington RJ, Becker JA, Dennis MM. Iridovirus infections Danio rerio. J Aquat Anim Health 2013; 25(3):171–183.
in finfish - critical review with emphasis on ranaviruses. J 148. Shotts EB, Blazer VS, Waltman WD. Pathogenesis of
Fish Dis 2010; 33(2):95–122. experimental Edwardsiella-Ictaluri infections in channel
129. Declercq AM, Haesebrouck F, Van den Broeck W catfish (Ictalurus-Punctatus). Can J Fish Aquat Sci 1986;
et al. Columnaris disease in fish: a review with 43(1):36–42.
emphasis on bacterium-host interactions. Vet Res 2013; 149. Baums CG, Hermeyer K, Leimbach S et al. Establishment
44:27. of a model of streptococcus iniae meningoencephalitis in
200 Lisa M. et al.
Nile tilapia (Oreochromis niloticus). J Comp Pathol 2013; 170. Harshbarger JC, Clark JB. Epizootiology of neoplasms in
149(1):94–102. bony fish of North America. Sci Total Environ 1990; 94(1–
150. Shoemaker CA, Klesius PH, Evans JJ. Prevalence of strep- 2):1–32.
tococcus iniae in tilapia, hybrid striped bass, and channel 171. Spitsbergen JM, Buhler DR, Peterson TS. Neoplasia and
catfish on commercial fish farms in the United States. Am neoplasm-associated lesions in laboratory colonies of
J Vet Res 2001; 62(2):174–177. zebrafish emphasizing key influences of diet and aquacul-
151. Decostere A, Hermans K, Haesebrouck F. Piscine mycobac- ture system design. ILAR J 2012; 53(2):114–125.
teriosis: a literature review covering the agent and the 172. Bunton TE, Wolfe MJ. N-methyl-N’-nitro-N-
disease it causes in fish and humans. Vet Microbiol 2004; nitrosoguanidine-induced neoplasms in medaka (Oryzias
99(3–4):159–166. latipes). Toxicol Pathol 1996; 24(3):323–330.
152. Thune RL, Stanley LA, Cooper RK. Pathogenesisof gram- 173. Sahoo PK, Mohanty BR, Das A et al. Cavernous haeman-
negative bacterial infections in warmwater fish. Annu Rev gioma in cultured olive barb, Puntius sarana (Hamilton). J
Fish Dis 1993; 3:37–68. Fish Dis 2012; 35(9):695–697.

153. Toranzo AE, Magarinos B, Romalde JL. A review of the main 174. Fournie JW, Wolfe MJ, Wolf JC et al. Diagnostic criteria for
bacterial fish diseases in mariculture systems. Aquaculture proliferative thyroid lesions in bony fishes. Toxicol Pathol
2005; 246(1–4):37–61. 2005; 33(5):540–551.
154. Secombes CJ, Chappell LH. Fish immune responses to 175. Battalora MS, Hawkins WE, Walker WW et al. Occurrence of
experimental and natural infection with helminth para- Thymic lymphoma in carcinogenesis bioassay specimens
sites. Annu Rev Fish Dis 1996; 6:167–177. of the Japanese Medaka (Oryzias-Latipes). Cancer Res 1990;
155. Bocklisch H, Otto B. Mycoses in fish. Mycoses 2000; 43(Suppl 50(17):S5675–S5678.
1):76–78. 176. Harada T, Hatanaka J, Kubota SS et al. Lymphoblastic lym-
156. Yanong RP. Fungal diseases of fish. Vet Clin Exot Anim Pract. phoma in Medaka, Oryzias-Latipes (Temminck et Schlegel).
2003; 6(2):377–400. J Fish Dis 1990; 13(2):169–173.
157. Ruehl-Fehlert C, Bomke C, Dorgerloh M et al. Pleistophora 177. Ishikawa T, Masahito P, Matsumoto J et al. Morpho-
infestation in fathead minnows, Pimephales promelas logic and biochemical characterization of erythrophoro-
(Rafinesque). J Fish Dis 2005; 28(11):629–637. mas in goldfish (Carassius auratus). J Natl Cancer Inst 1978;
158. Dykova I, Lom J. Advances in the knowledge of amphizoic 61(6):1461–1470.
amoebae infecting fish. Folia Parasitol (Praha) 2004; 51(2– 178. Okihiro MS. Chromatophoromas in two species of Hawaiian
3):81–97. butterflyfish, Chaetodon multicinctus and C. miliaris. Vet
159. Munday BL, Zilberg D, Findlay V. Gill disease of marine fish Pathol 1988; 25(6):422–431.
caused by infection with Neoparamoeba pemaquidensis. J 179. Coffee LL, Casey JW, Bowser PR. Pathology of tumors in
Fish Dis 2001; 24(9):497–507. fish associated with retroviruses: a review. Vet Pathol 2013;
160. Noble AC, Herman RL, Noga EJ et al. Recurrent amoebic gill 50(3):390–403.
infestation in rainbow trout cultured in a semiclosed water 180. Hawkins WE, Fournie JW, Overstreet RM et al. Rhab-
recirculation system. J Aquat Anim Health 1997; 9(1):64–69. domyosarcoma in the Japanese Medaka, Oryzias-Latipes
161. Nowalk BF, Harrison LR, Styer EL. Epitheliocystis in fish. J (Temminck and Schlegel) and guppy, Poecilia-Reticulata
Fish Dis 2006; 29(10):573–588. Peters. J Fish Dis 1988; 11(3):259–266.
162. Stride MC, Polkinghorne A, Nowak BF. Chlamydial infec- 181. Kimura I, Morikawa S, Kiriyama T et al. An epizootic occur-
tions of fish: diverse pathogens and emerging causes of rence of Rhabdomyoma and a case of Ganglioneuroma in
disease in aquaculture species. Vet Microbiol 2014; 170(1– hatchery-reared Ayu, Plecoglossus-Altivelis Temminck and
2):19–27. Schlegel. J Fish Dis 1983; 6(2):195–200.
163. Burtle GJ, Harrison LR, Styer EL. Detection of a triactino- 182. Rezaie A, Mousavi SM, Ansari MB. Rhabdomyosarcoma
myxid myxozoan in an oligochaete from ponds with pro- in a silver carp. J Aquat Anim Health 2016; 28(2):
liferative gill disease in channel catfish. J Aquat Anim Health 118–121.
1991; 3(4):281–287. 183. Harada T, Okazaki N, Kubota SS et al. Spontaneous ovarian
164. Brassard P, Rau ME, Curtis MA. Infection dynamics of tumor in a Medaka (Oryzias-Latipes). J Comp Pathol 1991;
Diplostomum-Spathaceum Cercariae and parasite-induced 104(2):187–193.
mortality of fish hosts. Parasitology 1982; 85(Dec):489–493. 184. Hawkins WE, Fournie JW, Ishikawa T et al. Germ cell neo-
165. Whipps CM. Interrenal disease in bluegills (Lepomis plasms in Japanese Medaka. J Aquat Anim Health 1996;
macrochirus) caused by a new genus and species of Myx- 8(2):120–129.
ozoan. J Parasitol 2011; 97(6):1159–1165. 185. Boorman G, Crabbs TA, Kolenda-Roberts H et al. Proceedings
166. Whipps CM, Murray KN, Kent ML. Occurrence of a Myx- of the 2011 National Toxicology Program Satellite Sympo-
ozoan parasite Myxidium streisingeri N. Sp in laboratory sium. Toxicol Pathol 2012; 40(2):321–344.
zebrafish danio Rerio. J Parasitol 2015; 101(1):86–90. 186. Romano LA, Klosterhoff M, Fuhr F et al. Neoplasia of the
167. Masahito P, Aoki K, Egami N et al. Life-span studies on Sertoli cells in wild carp, Cyprinus carpio: optical, immuno-
spontaneous tumor development in the medaka (Oryzias histochemical and ultrastructural study. Bull Eur Assoc Fish
latipes). Jpn J Cancer Res 1989; 80(11):1058–1065. Pathol 2013; 33(3):84–90.
168. Vergneau-Grosset C, Nadeau ME, Groff JM. Fish oncology: 187. Romanucci M, Arbuatti A, Massimini M et al. Ovarian
diseases, diagnostics, and therapeutics. Vet Clin Exot Anim teratoma in an adult female Zoogoneticus tequila (Webb
Pract. 2017; 20(1):21–56. and Miller 1998): histological and immunohistochemical
169. Grim KC, Wolfe MJ, Edwards M et al. Epizootic ameloblas- features. J Fish Dis 2017; 40(6):859–862.
tomas in Chinook salmon (Oncorhynchus tshawytscha) 188. Chen HC, Pan IJ, Tu WJ et al. Neoplastic response in Japanese
of the Northwestern United States. Vet Pathol 2009; medaka and channel catfish exposed to N-methyl-N’-nitro-
46(4):622–635. N-nitrosoguanidine. Toxicol Pathol 1996; 24(6):696–706.
189. Fournie JW, Vogelbein WK, Overstreet RM. Squamous Cell 211. Parker-Graham C, Clayton LA, Mangus LM. Amphibian renal
Carcinoma in the Gulf Menhaden, Brevoortia Patronus disease. Vet Clin Exot Anim Pract. 2020; 23(1):215–230.
Goode. Washington, DC; US Environmental Protection 212. Stetter MD. Noninfectious medical disorders of amphib-
Agency, 1987;EPA/600/J-87/308(NTIS PB88196274). ians. Sem Avian Exotic Pet Med 1995; 4(1):49–55.
190. Torikata C, Mukai M, Kageyama K. Spontaneous olfactory 213. Felt SA, Cowan AM, Luong R et al. Mortality and mor-
neuroepithelioma in a domestic Medaka (Oryzias-Latipes). bidity in African clawed frogs (Xenopus laevis) associated
Cancer Res 1989; 49(11):2994–2998. with construction noise and vibrations. JAALAS. 2012; 51(2):
191. Kagan RA, Pinkerton ME, Kinsel MJ. Neuronal embryonal 253–256.
tumors in fish. Vet Pathol 2010; 47(3):553–559. 214. Asfari M. Mycobacterium-induced infectious granuloma in
192. Lombardini ED, Hard GC, Harshbarger JC. Neoplasms of the Xenopus: histopathology and transmissibility. Cancer Res
urinary tract in fish. Vet Pathol 2014; 51(5):1000–1012. 1988; 48(4):958–963.
193. Masahito P, Ishikawa T, Okamoto N et al. Nephroblas- 215. Balls M, Ruben LN. The transmission of Lymphosarcoma in
tomas in the Japanese eel, Anguilla japonica Temminck and Xenopus laevis, the South African clawed toad. Cancer Res

Schlegel. Cancer Res 1992; 52(9):2575–2579. 1967; 27(4):654–659.
194. Session AM, Uno Y, Kwon T et al. Genome evolution 216. Oinuma T, Seki M, Asashima M. Histological and electron
in the allotetraploid frog Xenopus laevis. Nature 2016; microscopical studies on neoplasia subcutaneously occur-
538(7625):336–343. ing in Xenopus laevis. Proc Jpn Acad Ser B 1984; 60(B):265–268.
195. Hellsten U, Harland RM, Gilchrist MJ et al. The genome of 217. Diana SG, Beasely VB, Wright KM. Clinical toxicology. In:
the western clawed frog Xenopus tropicalis. Science 2010; Wright KM, Whitaker B, eds. Amphibian Medicine and Captive
328(5978):633–636. Husbandry. Malabar, FL: Krieger; 2001:223–232.
196. Pessier AP. Amphibia. In: Terio KA, Mcaloose D, St. Leger 218. Pessier AP. An overview of amphibian skin disease. Sem
J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA: Avian Exotic Pet Med 2002; 11(3):162–174.
Academic Press; 2018. p. 915–944. 219. Torreilles SL, Green SL. Refuge cover decreases the inci-
197. Wright KM. Applied physiology. In: Wright KM, Whitaker B, dence of bite wounds in laboratory South African clawed
eds. Amphibian Medicine and Captive Husbandry. Malabar, FL: frogs ( Xenopus laevis ). JAALAS 2007; 46(5):33–36.
Krieger; 2001. p. 31–34. 220. Green SL, Parker J, Davis C et al. Ovarian hyperstimula-
198. Wright KM. Nutritional disorders. In: Wright KM, Whitaker tion syndrome in gonadotropin-treated laboratory South
BK, eds. Amphibian Medicine and Captive Husbandry. Malabar, African clawed frogs (Xenopus laevis). JAALAS. 2007;
FL: Krieger; 2001. p. 73–88. 46(3):64–67.
199. Wiechmann A, Wirsig-Wiechmann C. Color Atlas of Xenopus 221. Johnson AJ, Wellehan JFX. Amphibian virology. Vet Clin Exot
laevis Histology. New York: Springer Science + Business Anim Pract. 2005; 8(1):53–65.
Media, LLC; 2003. 222. Latney LTV, Klaphake E. Selected emerging infectious
200. Measy J. Terrestrial prey capture in Xenopus laevis. Copeia diseases of amphibians. Vet Clin Exot Anim Pract. 2020;
1998; 3:787–791. 23(2):397–412.
201. Brown DD, Cai L. Amphibian metamorphosis. Dev Biol 2007; 223. Andino F, Chen G, Li Z et al. Susceptibility of Xenopus laevis
306(1):20–33. tadpoles to infection by the ranavirus frog-virus 3 correlates
202. Yaparla A, Reeves P, Grayfer L. Myelopoiesis of the amphib- with a reduced and delayed innate immune response in
ian Xenopus laevis is segregated to the bone marrow, away comparison with adult frogs. Virology 2012; 432(2):435–443.
from their hematopoietic peripheral liver. Front Immunol 224. Robert J, Abramowitz L, Gantress J et al. Xenopus laevis:
2020; 10:3015. a possible vector of ranavirus infection? J Wildl Dis 2007;
203. Robert J, Cohen N. The genus Xenopus as a multispecies 43(4):645–652.
model for evolutionary and comparative immunobiology of 225. Brenes R, Gray MJ, Waltzek TB et al. Transmission of
the 21st century. Dev Comp Immunol 2011; 35(9):916–923. ranavirus between ectothermic vertebrate hosts. PLoS One
204. Colombo BM, Scalvenzi T, Benlamara S et al. Microbiota 2014; 9(3):e92476.
and mucosal immunity in amphibians. Front Immunol 2015; 226. Klaphake E. Bacterial and parasitic diseases of amphibians.
6:111. Vet Clin Exot Anim Pract 2009; 12(3):597–608.
205. Robert J, Ohta Y. Comparative and developmental study 227. Taylor SK, Green DE, Wright KM et al. Bacterial diseases. In:
of the immune system in Xenopus. Dev Dyn 2009; Wright KM, Whitaker B, eds. Amphibian Medicine and Captive
238(6):1249–1270. Husbandry. Malabar, FL: Krieger; 2001. p. 159–180.
206. Pessier AP. Edematous frogs, urinary tract disease, and 228. Wilcke BW, Newcomer CE, Anver MR et al. Isolation of
disorders of fluid balance in amphibians. J Exot Pet Med 2009; chlamydia psittaci from naturally infected African clawed
18(1):4–13. frogs (Xenopus laevis). Infect Immun 1983; 41(2):789–794.
207. Hillyard SD. Behavioral, molecular and integrative mech- 229. Blumer C, Zimmermann DR, Weilenmann R et al. Chlamy-
anisms of amphibian osmoregulation. J Exp Zool 1999; diae in free-ranging and captive frogs in Switzerland. Vet
283:662–674. Pathol 2007; 44(2):144–150.
208. Lee-Liu D, Mendez-Olivos EE, Munoz R et al. The African 230. Reed KD, Ruth GR, MJ A et al. Chlamydia pneumoniae infec-
clawed frog Xenopus laevis: a model organism to study tion in a breeding colony of African clawed frogs (Xenopus
regeneration of the central nervous system. Neurosci Lett tropicalis). Emer Infect Dis 2000; 6(2):196–199.
2017; 652:82–93. 231. Green SL, Bouley DM, Tolwani RJ et al. Identification
209. Winklbauer R. Development of the lateral line system in and management of an outbreak of Flavobacterium
Xenopus. Prog Neurobiol 1989; 32(3):181–206. meningosepticum infection in a colony of South African
210. Balinsky JB, Cragg MM, Baldwin E. The adaptation of clawed frogs (Xenopus laevis). JAVMA 1999; 214(12):1833.
amphibian waste nitrogen excretion to dehydration. Comp 232. Martinho F, Heatley JJ. Amphibian mycobacteriosis. Vet Clin
Biochem Physiol 1961; 3(4):236–244. Exot Anim Pract. 2012; 15(1):113–119.
202 Lisa M. et al.
233. Ramakrishan L, Valdivia RH, McKerrow JH et al. Mycobac- Africa (1871–2000) and in California (2001–2010). PLoS One
terium marinum causes both long-term subclinical infec- 2013; 8(5):e63791.
tion and acute disease in the leopard frog (Rana pipiens). 240. Weldon C, du Preez LH, Hyatt AD et al. Origin of the amphib-
Infect Immun 1997; 65(2):767–773. ian Chytrid fungus. Emer Infect Dis 2004; 10(12):2100–2105.
234. Poynton SL, Protozoa WB. Metazoa infecting amphibians. 241. Parker JM, Mikaelian I, Hahn N et al. Clinical diag-
In: Wright KM, Whitaker B, eds. Amphibian Medicine and nosis and treatment of epidermal chytridiomycosis in
Captive Husbandry. Malabar, FL: Krieger; 2001. p. 193–222. African clawed frogs (Xenopus tropicalis). Comp Med 2002;
235. Green SL, Bouley DM, Josling CA et al. Cryptosporidiosis 52(3):265–268.
associated with emaciation and proliferative gastritis in 242. Tinsley RC, Coxhead PG, Stott LC et al. Chytrid fungus
a laboratory-reared South African clawed frog (Xenopus infections in laboratory and introduced Xenopus laevis
laevis). Comp Med. 2003; 53(1):81–84. populations: assessing the risks for U.K. native amphibians.
236. Parè JA. Fungal diseases of amphibians: an overview. Vet Clin Biol Conserv 2015; 184:380–388.
Exot Anim Pract 2003; 6(2):315–326. 243. Pritchett KR, Sanders GE. Epistylididae ectoparasites in a

237. Taylor SK. Mycoses. In: Wright KM, Whitaker B, eds. Amphib- colony of African clawed frogs (Xenopus laevis). JAALAS
ian Medicine and Captive Husbandry. Malabar, FL: Krieger; 2007; 46(2):86–91.
2001. p. 181–192. 244. Brayton C. Wasting disease associated with cutaneous and
238. Lips KR. Overview of chytrid emergence and impacts on renal nematodes, in commercially obtained Xenopus laevis.
amphibians. Philos Trans R Soc London B Biol Sci 2016; Ann N Y Acad Sci 1992; 653(1):197–201.
371(1709):20150465. 245. Wright KM, Whitaker B. Pharmacotherapeutics. In: Wright
239. Vredenburg VT, Felt SA, Morgan EC et al. Prevalence of KM, Whitaker B, eds. Amphibian Medicine and Captive Hus-
Batrachochytrium dendrobatidis in Xenopus collected in bandry. Malabar, FL: Krieger; 2001. p. 309–330.

Conditions in Common Avian and Aquatic Species

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ILAR Journal, 2021, Vol. 62, No.

Research-Relevant Background Lesions and

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System Organ/Tissue Comments

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System Organ/Tissue Comments

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System Condition Comments

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System Condition Comments

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System Condition Comments

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Table 3 Common Infectious Diseases of Chickens, Turkeys, and Quail16,62–64

Class Agent Comments

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Class Agent Comments

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Class Agent Comments

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PAS, periodic acid-Schiff.

System Condition Comments

Beak overgrowth Caused by malnutrition or hepatopathy.

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System Condition Comments

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Table 5 Common infectious diseases in parrots and budgerigars16 ,51,70,71

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Class Agent Comments

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PAS, periodic acid-Schiff.

Table 6 Common Metabolic, Spontaneous (and Neoplastic) Conditions in Finches51,70,75–77

System Condition Comments

Table 7 Common Infectious Diseases of Finches51,70,76–79

Class Agent Comments

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PAS, periodic acid-Schiff.

Table 8 Commonly Used Fish Species in Research80–84

Name (Species) Comments/Common Research Areas

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of captive finches should contain commercial pelleted feed, Fish

Table 9 Anatomic and Physiologic Features of Fish Models115,116

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Table 10 Spontaneous Conditions of Fish Used in Research5 ,118

System Condition Comments

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CNS, central nervous system; LEH, lamellar epithelial hypertrophy.

Table 11 Common Infectious Diseases of Captive Research Fish118

System Condition Description/Comments

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System Condition Description/Comments

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Table 12 Neoplastic Conditions of Captive Research Fish118,167,168

System Organ/Tissue Comments

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