non-huma primate pathology
TRANSCRIPT
Gross Morbid Anatomy of Pathology of Nonhuman Primates
Anne D. Lewis, DVM, PhD, Diplomate, ACVPOregon National Primate Research Center
505 NW 185th AvenueBeaverton, OR 97008
Please Note: The species, organ and morphologic descriptions contained in the boxes will match the images presented. The emphasis of the presentation will be on the gross images. The more extensive notes included here are provided primarily for reference.
Viral Diseases
Alpha herpesvirusesIn general, alphaherpesviruses cause mild infection in their natural hosts characterized by oral and/or genital vesicles and clinical latency with virus persisting in neural tissues. They may cause severe necrotizing systemic disease in aberrant hosts or in immunosuppressed individuals of normal host. Alphaherpesviruses include simplexviruses (HSV-1, HSV-2, CHV-1, SA 8, Herpesvirus papio 2, and Ateline herpesvirus 1 ) and varicelloviruses (Cercopithecine herpesvirus 9 which includes all the simian varicella viruses)
Cercopithecine herpesvirus-1 Etiology: CHV-1 (syn. B virus, monkey B virus, Herpesvirus simiae) (Alphaherpesvirus)General Nonpathogenic in host species (macaques), causes oral and genital ulcers, rarely causes
disseminated necrotizing lesions in immunosuppressed host animals. (Interestingly, B virus reactivation with clinical disease is not a feature of SIV-induced immunosuppression.) High rate of seropositivity in most non-SPF populations. Seropositive rate in macaque populations is approximately 70-100% by adulthood. Important zoonosis. Causes severe, often fatal, debilitating neurologic disease in man. Modes of transmission to humans (when known) include ocular and mucous membrane splashes, needlestick, bites and scratches. Macaques are persistently infected for life. Virus is latent in sensory ganglia. Intermittent reactivation and shedding occurs sporadically throughout life. All macaques should be considered potential carriers of CHV-1 regardless of serologic status (rare cases of seronegative carriers.) CHV-1 may infect and cause fatal disease in several NHP including epizootics in DeBrazza’s monkeys, bonnet macaques.
Pathology: Vesicles progressing to ulcers on lips, tongue, buccal mucosa, genital epithelium, conjunctivitis. Disseminated disease: ulcers extending to esophagus and stomach, foci of necrosis in liver, lung, pancreas, adrenal, spleen, lymph nodes, other organs. Necroulcerative stomatitis, esophagitis, gastritis. Multifocal necrosis with syncytia, eosinophilic INIB in epithelial cells and syncytia. May see meningoencephalomyelitis in some cases.
Pigtail macaque Oral cavity Labial vesicles: Vesicular cheilitis
Rhesus macaque Face Vesicular and ulcerative facial dermatitis
Macaque Oral cavity Necroulcerative glossitis
Macaque Penis Vesicular and ulcerative balanitis
Macaque Esophagus Multifocal necroulcerative esophagitis
Macaque Liver Multifocal to coalescing necrotizing hepatitis
Herpesvirus tamarinus Etiology: Saimiriine herpesvirus 1, Herpesvirus tamarinus, Herpes TGeneral: Natural host is squirrel monkey in which it rarely causes disease: oral vesicles and ulcers
similar to CHV-1 in macaques and HSV-1 in humans. Causes severe fatal disease in owl monkeys, marmosets and tamarins.
Pathology: In owl monkeys and callitrichids: vesicles, erosions and ulcers in oral cavity, skin, variably sized areas of necrosis in any organ. Areas of necrosis with multinucleated syncytial cells and INIB.
Owl monkey Face Necrotizing ulcerative dermatitis, conjunctivitis
Owl monkey Tongue Vesicular glossitis, multifocal to coalescing
Owl monkey Liver Multifocal to coalescing hepatic necrosis
Owl monkey Liver Multifocal hepatic necrosis
Herpes simplexEtiology: Human herpesvirus 1, Herpes simplex virus 1General: Causes severe fatal disease in owl monkey and callitrichids. Resembles herpesvirus tamarinus
infection in same species. Pathology: Necrotizing vesicular dermatitis, blepharitis, stomatitis, multiorgan necrosis
Owl monkey Lung Embolic pneumonia
Common marmoset Liver and spleen Multifocal hepatic and splenic necrosis
Herpesvirus papio-2Etiology: Cercopithecine herpesvirus 16, HVP-2, (previously SA8)General: HVP-2 is endemic in baboons. (SA8 is an endemic herpesvirus of African green monkeys.)
Neurotropic. Latency occurs in ganglia. Resembles HSV-2 in humans. Pathology: HVP-2 causes oral, genital and cutaneous lesions in baboons. Lesions range from vesicles to
ulcers, secondary bacterial infection common. Epidermal necrosis with central erosions and peripheral parakeratosis. INIB in epithelial cells.
Baboon Oral cavity Necroulcerative glossitis
Baboon Penis Ulcerative posthitis
Baboon Bladder Diffuse hemorrhagic cystitis (secondary bacterial infection)
Baboon Kidney Suppurative pyelonephritis (ascending secondary bacterial infection)
Simian Varicella VirusEtiology: Cercopithecine herpesvirus 9. Group of related alpha herpesviruses: Delta herpesvirus,
Medical Lake macaque virus, Liverpool vervet monkey virus. Antigenically related to human varicella-zoster virus (chicken pox)
Clinical: Vesicular rash, depression, dyspnea. May be clinically inapparent in certain species and within individuals.
Pathology: Vesicular to vesiculohemorrhagic rash, hemorrhagic ulcers in GI tract, pulmonary edemaMultifocal necrosis with hemorrhage in liver, spleen, lymph nodes, GI tract. Skin, tongue, esophagus develop vesicles with epithelial hyperplasia, ballooning degeneration, and subsequent ulceration. Multifocal necrosis with hemorrhage in liver, spleen, lymph nodes, GI tract. Eosinophilic intranuclear inclusions. Vascular involvement with INIB in endothelial cells and smooth muscle. Latency in ganglia.
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Macaque Skin Hemorrhagic vesicular dermatitis, multifocal to coalescing
Pigtail macaque Skin, face Vesicular and vesiculohemorrhagic dermatitis
Pigtail macaque Liver, spleen Multifocal necrotizing hepatitis, splenitis
Betaherpesviruses More host specific group of herpesviruses. Are slowly cytolytic and induce cytomegaly. Latent infection of lymphoreticular cells and renal epithelium.
CytomegalovirusEtiology: Cytomegalovirus (many, species-specific) Cercopithecine herpesvirus 8 is the cytomegalovirus
of the rhesus monkey.General: Endemic in host populations, latency in renal epithelium, causes disease in
immunosuppressed individuals (SIV, chemical/iatrogenic and highly stressed juveniles) Pathology: Hemorrhagic meningoencephalitis/meningomyelitis, m-f necrotizing hepatitis and splenitis,
orchitis, interstitial pneumonia, segmental hemorrhagic enterocolitis. Multifocal to focally extensive areas of necrosis with intense neutrophilic infiltration. Cytomegalic cells with large discrete eosinophilic intranuclear inclusions. Often affects mesenchymal (vs epithelial cells). Vasculitis with inclusions in endothelial cell nuclei. May rarely see rare cytomegalic cells in renal collecting duct epithelium of normal animals.
Rhesus macaque Spinal cord Acute segmental hemorrhagic meningomyelitis
Rhesus macaque Brain Acute hemorrhagic meningoencephalitis
Rhesus macaque Intestine Segmental hemorrhagic enteritis
Gamma herpesviruses Tand B lymphocyte tropic viruses. Two families: lymphocryptoviruses related to Epstein-Barr virus in humans and rhadinoviruses related to Kaposi’s Sarcoma associated virus (Human herpesvirus 8)..
Herpesvirus saimiri Etiology: Saimiriine herpesvirus 2, Squirrel monkey herpesvirus.General: Produces latent nonpathogenic infection in host species (spider monkeys). Causes T cell
lymphoma, lymphocytic leukemia in aberrant hosts: maromosets, tamarins, owl monkeys. Findings identical to that of Herpesvirus ateles infection.
Pathology: Uniformly enlarged pale to mottled liver and spleen, enlarged gray lymph nodes. Kidneys are enlarged, soft, mottled. Less commonly may see solitary masses in the kidney, orbit, peritoneum. Microscopically, sheets of immature neoplastic lymphocytes infiltrating between preexisting structures in any organ. Hepatic infiltration is primarily portal with extension into adjacent lobule.
Marmoset Spleen Splenic lymphoma
Owl monkey Kidneys Bilateral renal lymphoma
Common marmoset Lung Pulmonary lymphoma
Common marmoset Small Intestine and lymph nodes
Lymphoma, intestine, lymph nodes
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Owl monkey Lung Retrobulbar lymphoma
Retroviruses
SIVEtiology: Simian Immunodeficiency Virus, Lentivirus, Retroviridae. Many related viruses, generally
named by species within which the virus was first discovered (e.g. SIVagm,) many laboratory propagated strains (e.g. SIVmac251.)
General: SIV is closely related to HIV-1, the causative agent of AIDS in humans. Some important differences in regulatory genes (SIV has vpx, vpr and lacks vpu; HIV-1 has vpu, vpr and lacks vpx) and envelope structure (V3 loop is highly variable in HIV-1 and is an important neutralizing domain; SIV lacks variability in the V3 loop region). SIV strains are generally nonpathogenic in endemic host species of African monkeys but cause progressive immunosuppression and primary retroviral induced disease in aberrant hosts (macaques). SIV is currently an experimental/iatrogenic disease. SIV infects CD4+ lymphocytes, macrophages and causes progressive CD4 T cell decline.
Clinical: In macaques, maculopapular rash, mild febrile illness, lymphadenomegaly within first few weeks of infection in some individuals; may be clinically inapparent initially. Progressive disease results in weight loss, persistent diarrhea, opportunistic infections. Rapid progressors, in particular, may develop neurologic signs, tremors and ataxia. Some laboratory strains (eg SIVmac E660 and others) have a predisposition to cause pulmonary arterial and right atrial thromboses with acute onset of dyspnea or death.
Pathology: Lesions associated with primary retroviral infection include marked lymphoid hyperplasia in lymph nodes and spleen progressing to lymphoid depletion; right atrial and pulmonary thrombosis; arteriopathy; maculopapular rash, giant cell pneumonia, giant cell encephalitisCommon secondary opportunistic infections include: candidiasis, biliary and respiratory cryptosporidiosis, disseminated CMV, Pneumocystis carinii pneumonia, M avium complex granulomatous enteritis, others. Lymphoma is highly associated with SIV infection in macaques.
Rhesus macaque Skin, axilla Maculopapular dermatitis
Rhesus macaque Spleen Marked follicular lymphoid hyperplasia, splenic white pulp
Rhesus macaque Peripheral lymph nodes
Marked follicular lymphoid hyperplasia, lymph node
Rhesus macaque Heart Right atrial thrombosis, right ventricular hypertrophy
Rhesus macaque Lung Pulmonary arterial embolus with pulmonary infarction
Rhesus macaque Lung Pulmonary proliferative arteriopathy and infarction
Rhesus macaque Lung Granulomatous pneumonia (SIV giant cell pneumonia) DDX: Pneumocystis pneumonia
Rhesus macaque Stomach Gastric lymphoma
Rhesus macaque Small intestine Enteric lymphoma
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Type D retrovirusEtiology: Simian Retrovirus Type D, Oncovirus Type D, Five major serotypes recognized.General: SRV-1, SRV-2 and SRV-5 are the serotypes of clinical significance. Virus infects both B and T
(CD4 and CD8) lymphocytes as well as macrophages, epithelial cells. Infected animals may be persistently viremic without developing measurable antibodies. Diagnosis must be based on both viral detection (by PCR or isolation) and antibody detection.
Clinical: Highly variable dependent on host and viral stain factors. May be clinically inapparent or may result in anemia and immunosuppressive disease. SRV-2 infection is endemic in many cynomolgus macaque laboratory populations.
Pathology: None or marked lymphadenopathy. Anemia, neutropenia. Retroperitoneal fibromatosis and subcutaneous fibromatosis are likely secondary to coinfection with rhesus rhadinovirus (RRV, a gammaherpesvirus) and immunosuppression. Retroperitoneal fibromatosis results in multiple firm pale masses in the peritoneum which may progress to complete encasing of the abdominal viscera with dense fibrous tissue and marked ascites. Subcutanous fibromatosis is characterized by multiple firm white raised subcutaneous nodules. Opportunistic infections which occur more commonly in Type D retroviral infection (vs SIV) include bacterial diseases (likely due to neutropenia) such as staphlyococcal abscesses, Rhodocccus equi enteritis, and noma. Noma is a rapidly progressive destructive ulcerative gingivitis with bony necrosis and facial deformity. Noma is microscopically characterized by mucosal ulcer covered by necrotic debris and mixed bacteria. Underlying zone of necrosis and intense neutrophilic infiltration and mixed bacteria and spirochetes and vascular thrombi in areas of necrosis. Osteonecrosis.
Celebes macaque Intestines Retroperitoneal fibromatosis, multifocal to coalescing
Celebes macaque Peritoneal cavity Retroperitoneal fibromatosis with ascites
Rhesus macaque Skin Subcutaneous fibromatosis
Macaque Oral cavity Noma: Necrotizing gingivitis and osteomyelitis
Rhesus macaque Skull Noma: Necrotizing osteomyelitis
Simian Hemorrhagic Fever VirusEtiology: Simian Hemorrhagic Fever Virus, ArterivirusGeneral: Rare epizootic disease with high mortality in macaques (Patas monkeys, other African NHP
act as reservoir host.) Clinical: Fever, depression, anorexia, ataxia, diarrhea, abortion, DICPathology: Gross changes appear at terminal stages (within 24 hours of death). Findings consistent with
DIC: epistaxis, ecchymoses, hemorrhage of the proximal duodenal mucosa (not pathognomic but suggestive), enlarged uniformly dark spleen. Perifollicular hemorrhage visible more clearly after fixation. Petecchial and ecchymotic hemorrhages anywhere. Microscopically, splenic lymphoid necrosis rimmed with hemorrhage in sinuses surrounding white pulp. Necrosis of follicular lymphocytes in other lymphoid tissues. Hemorrhages, infarcts, vascular thromboses. Fibrin in capillaries. May see lymphohistiocytic meningoencephalitis.
Macaque Spleen (fixed) Perifollicular hemorrhage and lymphoid necrosis
MeaslesEtiology: Human measles virus. Morbillivirus, ParamyxoviridaeGeneral: Humans are reservoir hostClinical: Rash, fever, depression, diarrhea.
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Pathology: Erythematous maculopapular rash of abdomen and inner thighs. Silvery scale is it fades. Raised white foci (“Koplick spots”) on oral mucosa (cheek, tongue). Patchy to lobular consolidation of lungs. Necrotizing bronchiolitis, bronchointerstial pneumonia. Syncytial giant cells with or without intracytoplasmic and/or intranuclear inclusion bodies in lungs and GI tract. Lymphocyte necrosis in GALT and lymph nodes. In New World species see hemorrhagic gastroenteritis.
Rhesus macaque Oral cavity, tongue Multifocal lingual necrosis: central necrosis with peripheral hyperemia (Koplick’s spots)
Rhesus macaque Skin Erythematous maculopapular dermatitis
Macaque Lungs Diffuse acute bronchointerstitial pneumonia
Callitrichid hepatitisEtiology: Lymphocytic choriomeningitis virus, Arenavirus, Arenaviridae General: Acute epizootic disease of callitrichids. LCM is endemic in mice. Callitrichids may acquire
through feeding of “pinkies” or contact with secretions of wild mice. Clinical: Weakness, anorexia, may see respiratory distress, icterus.Pathology: Icterus, subcutaneous and muscular hemorrhages, enlarged spleen, enlarged yellow-tan
mottled liver. Pleuropericardial effusion. Hepatocellular swelling, patchy hepatic necrosis with lymphocytic and neutrophilic infiltrates, Randomly scattered apoptotic hepatocytes. Formation of acidophilic bodies in degenerating hepatocytes and within hepatic sinusoids.
Marmoset Whole body Diffuse hepatic necrosis, icterus
SV40Etiology: Simian Virus 40, Polyomavirus, PolyomaviridaeGeneral: Endemic virus in macaques, Similar to human polyoma viruses, JCV and BKV. Generally no
signs in immunocompetent hosts. Primary infection in immunocompromised hosts may result in interstitial nephritis and pneumonitis. Also a meningoencephalitis affecting grey matter has been described. Reactivation of latent infection results in progressive multifocal leukoencephalopathy (PML). Latency in renal tubular epithelium, possibly oligodendrocytes and lymphocytes.A distinct polyoma virus has also been described in cynomolgus macaques causing interstitial nephritis and ureteritis in immunosuppressed monkeys.
Pathology: Small firm tan kidneys. PML: small gray pink foci to areas of malacia scattered within the cerebral white matter Chronic tubulointerstial nephritis, interstitial pneumonia. Histologically: PML: Gliosis and demyelination. Large basophilic intranuclear inclusions in renal tubular epithelium and oligodendrocytes.
Rhesus macaque Cerebrum (cut section)
Leukoencephalomalacia
Poxviruses
MonkeypoxEtiology- Orthopoxvirus, antigenically related to smallpox and vaccinia
Natural disease in African spp. NHP are not natural host. Probably arboreal squirrelsClinical: Highly variable, dependent on viral strain and host species, may be mild cutaneous infection to
fatal systemic disease. Pathology: Multiple raised umbilicated cutaneous pox lesions. Epidermal hyperplasia and necrosis with
keratinocyte swelling and large eosinophilic cytoplasmic inclusions.
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African monkey Skin Multifocal proliferative dermatitis with central necrosis
YabapoxEtiology: Yaba monkey tumor virus (Yabapoxvirus), Yatapoxvirus (genus). Virus is related to tanapox
virusGeneral: Infects rhesus and baboons, also man. Yabapoxvirus infects histiocytes (vs epithelial cells.)Pathology: Rapidly growing subcutaneous nodules on head and extremities. Spontaneously regress in 6
to 12 weeks. Micro:subcutaneous masses composed of large pleomorphic histiocytes with large eosinophilic ICIB. Resemble histiocytomas histologically.
Baboon Skin Subcutaneous proliferative nodule
Baboon Subcutis, elbow Subcutaneous proliferative nodule
Benign epidermal monkey pox group Etiology: Tanapox virus, OrTeCa poxvirus, benign epidermal monkey pox virus, Yatapoxvirus (genus),
related to yabapox, unrelated to smallpoxGeneral: Affects macaques, zoonotic, outbreaks of OrTeCa in several primate centers during 1960’s.
Self-limiting disease. Lesions resolve in 3-4 weeks. Pathology: Multiple raised cutaneous nodules which become ulcerated with central umbilication.
Epidermal proliferation, ballooning degeneration, eosinophilic ICIB.
Rhesus macaque Face Multifocal proliferative dermatitis with necrosis and ulceration
Rhesus macaque Face Multifocal proliferative dermatitis, stomatitis, conjunctivitis with ulceration
Rhesus macaque Skin/tattoo Multifocal proliferative dermatitis with central necrosis
Encephalomyocarditis virus Etiology: Encephalomyocarditis virus, Cardiovirus, PicornaviridaeGeneral: Epizootic infections reported in several species; owl monkeys, callitrichids, baboons highly
susceptible. Rodent reservoirClinical: Dyspnea, sudden death. Pathology: Abundant clear to fibrinous pericardial fluid, pale, streaked, friable myocardium, pulmonary
edema. Microscopically, myocardial degeneration and necrosis, neutrophilic, lymphocytic, histiocytic infiltration. May see pancreatic acinar necrosis +/- suppurative or lymphocytic infiltrate in pancreas.
Baboon Thoracic cavity Myocardial necrosis, pericardial effusion, pulmonary edema, hepatic congestion
PapillomavirusGeneral: Numerous papilloma viruses identified. Generally cause papillomas on skin, oral mucosa,
genital mucosa.
Rhesus macaque Face Conjunctival and facial papillomatosis
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Baboon Thoracic skin Papillomatosis
Chimpanzee Oral mucosa Oral papillomatosis
Bacterial Diseases
TuberculosisEtiology: Mycobacterium tuberculosis, M. bovisGeneral: More prevalent in Old World than New World spp, attributed to differences in susceptibility.
Significant concern in primate facilities. Most facilities test animals regularly by intradermal tuberculin test administered in upper eyelid. Zoonosis. Transmission in primate facilities is typically from man to monkey. Reportable disease. Ancillary testing such as the IFN-based Primagam assay available.
Clinical: M. tuberculosis generally causes rapidly progressive disease in macaques. Latency not considered a common feature in monkeys although more recent publications suggest cynos may develop a more clinically silent disease. Weight loss, tachypnea, coughing, enlarged peripheral lymph nodes, hepatosplenomegaly.
Pathology: Yellow white nodules in lung, hilar/tracheobronchial lymph nodes, liver, spleen, adrenal, any organ. Central liquefactive necrosis. Granulomas to pyogranulomas with prominent multinucleated giant cells. Central caseation. Mineralization is rare. Small numbers of acid fast organisms in lesions.
Rhesus macaque Whole body Unilateral necrotizing blepharitis
Rhesus macaque Thoracic cavity, hilar lnn
Necrotizing pyogranulomatous lymphadenitis
Rhesus macaque Lung (fixed) Multifocal to coalescing granulomatous bronchopneumonia
Cynomolgus macaque
Lungs and hilar lymph node
Granulomatous lymphadenitis
Cynomolgus macaque
Liver Multifocal granulomatous hepatitis
Cynomolgus macaque
Adrenal gland Granulomatous adrenalitis
Rhesus macaque Vertebrae Granulomatous vertebral osteomyelitis with pathologic fracture and spinal cord compression(Pott’s disease)
Mycobacterium avium complexEtiology: Mycobacterium avium-intracellure complex, MACGeneral: Disease occurs primarily in immunosuppressed individuals (often SIV infected.) Starts as a
primary enteric infection, may become disseminated. Unusual manifestation in immunocompetent hosts of solitary pulmonary granulomas with rare AFB.
Clinical: Weight loss, diarrheaPathology: Both small and large intestine are affected. Thickened intestinal wall, mucosa may have
coarse folds. Small nodules on serosa and mesentery. Diffusely enlarged yellow-white mesenteric lymph nodes. May see enlarged liver with scattered yellow-white foci. Most cases lack discrete caseated granulomas/tubercles. Diffuse histiocytic infiltrate in the lamina propria of the small intestine and colon. Large epithelioid histiocytes with foamy cytoplasm. Rare multinucleate giant cells, few lymphocytes. Villi are thickened and blunted. Large numbers of intracellular acid fast bacteria.
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Macaque Intestine, mesenteric lymph nodes
Diffuse histiocytic enteritis and lymphadenitis
Macaque Lungs Diffuse granulomatous pneumonia
Leprosy Etiology: Mycobacterium lepraeGeneral: Natural infection reported in chimpanzees and sooty mangabeysPathology: Variably sized yellow white cutaneous and subcutaneous nodules. Nerve involvement is
pathognomic. Lesions occur on extremities, cooler areas of skin. Dermal thickening, depigmentation and ulceration of larger lesions. Lepromatous form of inflammation is most common, large numbers of histiocytes, fewer lymphocytes within dermis and subcutis and around neurovascular bundles. Acid fast bacilli in histiocytes, nerves, smooth muscle cells.
Chimpanzee Hands Granulomatous dermatitis with depigmentation and ulceration
ShigellosisEtiology: Shigella flexneri, (S, dysenteriae, S. sonnei, S. boydii) gram negative bacillusGeneral: Gastrointestinal disease resulting in clinical diarrhea is one of the most common problems in
laboratory housed nonhuman primates. Shigella is an important cause of diarrhea. Carrier state occurs. Disease often exacerbated by stress. Shigellosis tends to cause more severe disease than other common pathogens (Campylobacter). Zoonosis. Shigellosis is a disease of primates only. Shigella invades, replicates within and ultimately destroys the colonic epithelial cells.
Clinical: Loose soft stool to fluid watery diarrhea to severe bloody diarrhea (dysentery), dehydration, rectal prolapse; if untreated, renal failure secondary to dehydration and hypovolemic shock. Often accompanied by marked leukocytosis, neutrophilia.
Pathology: Catarrhal to mucopurulent to necroulcerative typhlocolitis, scant colonic contents. Colonic mucosa is thickened and edematous with erosions to ulcers. Enlarged edematous colonic lymph nodes. Affects cecum and ascending (proximal) colon preferentially. Diphtheritic membrane in severe cases. SI is spared. May see acute gastritis. Although Shigella doesn’t spread hematogenously, severely ill animals may have systemic changes including severe adrenal congestion and edema. Infiltration of neutrophils in lamina propria, mucosal necrosis, hemorrhage and edema, erosions and ulcerations of superficial mucosa, crypt abscesses. Lumen contains desquamated epithelium and exuded neutrophils. Shigella sp also causes a separate syndrome of ulcerative gingivitis in macaques.
Rhesus macaque Colon Diffuse mucohemorrhagic colitis
Macaque Colon Fibrinohemorrhagic and ulcerative colitis
Rhesus macaque Cecum Suppurative and exudative typhlitis
Rhesus macaque Mouth Necroulcerative gingivitis with gingival recession and dental plaque
Rhesus macaque Kidneys Acute tubular necrosis (nonspecific associated lesion)
Rhesus macaque Adrenals Bilateral adrenal congestion, hemorrhage and necrosis (nonspecific associated lesion)
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CampylobacteriosisEtiology: Campylobacter jejuni, (Campylobacter coli)General: Carrier state is common. Zoonosis. Small curved gram negative bacillus. Requires special
culture media and conditions for isolation: 42C and microaerophyllic.Clinical: Soft mucoid to fluid and yellow diarrhea. Pathology: Colonic mucosa is edematous, thickened, and reddened. Chronic infection may lead to
proliferative typhlocolitis. Proximal colon and cecum generally more severely affected. Chronic: proliferative chronic active typhlocoltis with numerous crypt abscesses. Part of the multifactorial chronic active colitis of macaques.
Macaque Colon Ulcerative and proliferative colitis
Rhesus Macaque Colon Chronic proliferative colitis
HelicobacterEtiology: Helicobacter pylori, gram negative spiral bacteriumGeneral: Highly prevalent in the stomachs of rhesus macaques. Can use rapid urease test on mucosal
biopsies to diagnose.Clinical: Generally inapparent, may cause vomitingPathology: May see reddening, mild erosions, ulcers of gastric fundic/antral mucosa. In
immunosuppressed macaques may cause proliferative gastritisMild chronic gastritis with epithelial hyperplasia. In immunosuppressed individuals may see more severe disease. Can see the organisms on H&E but are best demonstrated with silver stains.
Macaque Stomach Chronic proliferative gastritis with focal ulcer
Rhesus macaque Stomach Proliferative gastritis
StreptococcosisEtiology: Streptococcus pneumoniaeClinical: Causes acute septicemic disease. May see as meningitis, arthritis, or pneumonia, depression,
sudden death.Pathology: Distended joints with thick yellow white exudate in joint space. Yellow white exudates beneath
the leptomeninges with marked vascular congestion, fibrinosuppurative pneumonia and/or pleuritis. Joint involvement may occur in clusters of animals.
Spider monkey Brain Hemorrhagic and suppurative meningitis
Rhesus Brain Suppurative meningitis
Rhesus Stifle joint Suppurative arthritis
ListeriosisEtiology: Listeria monocytogenes, gram-positive, intracellular bacillus, facultative anaerobe, common
soil contaminantGeneral: In NHP, most commonly see a syndrome of abortion and/or perinatal septicemia. Generally no
signs of illness in the dams. Late gestation abortion/stillbirth. Often advanced autolysis in the fetus due to in utero death. Placentitis.
Pathology: Still birth often in advanced autolysis. May see small white-gray foci to abscesses in liver, placenta, other organs.
Cynomolgus Lungs (fetal) Suppurative bronchopneumonia
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macaque
Macaque Placenta Suppurative placentitis
YersiniosisEtiology: Yersinia pseudotuberculosis, Y. enterocolitica, gram negative bacillusGeneral: Both species cause similar diseases. Two patterns: enteric and septicemic. Clinical: Diarrhea, dehydration, anorexia, and weight loss. Septicemia may result. Illness may also be
peracute. Abortion and stillbirth have been reported.Pathology: Multifocal necrosis or abscessation in the spleen and liver, mesenteric lymphadenopathy and
ulcerative enterocolitis. Histologically, ulcerative enterocolitis with necrosis, an inflammatory infiltrate composed primarily of neutrophils with fewer mononuclear cells, and colonies of gram-negative coccobacilli. Other lesions include multifocal acute and necrotizing hepatitis, splenitis, and lymphadenitis.
Rhesus macaque Small intestine and colon
Necrohemorrhagic enterocolitis
Rhesus macaque Colon Necroulcerative colitis
Squirrel monkey Spleens Necrosuppurative splenitis
TularemiaEtiology: Francisella tularensis, gram negative bacillus.General: Disease of outdoor housed animals. Suspect rodent reservoir. Difficult to culture. Clinical: May see enlarged and draining abscessed lymph nodes. May present as acute septicemia and
death. Pathology: Multiple coalescing pale dull white areas of necrosis in the spleen, necrotizing, hemorrhagic
pneumonia, pale off white areas of necrosis within mesenteric lymph nodes, pinpoint pale areas of necrosis within the liver. Highly lymphotropic. Severe lymphoid necrosis in lymphoid follicles of lymphoid tissues. Necrotizing pneumonia and hepatitis, minimal neutrophilic infiltration. Generally cannot see bacteria within lesions.
Japanese macaque Spleen, cut section Necrotizing splenitis
Rhesus macaque Liver Multifocal necrotizing hepatitis
Rhesus macaque Lumbosacral lymph nodes
Necrotizing lymphadenitis
KlebsiellaEtiology: Klebsiella pneumoniae, gram negative bacillus. Capsule is a virulence factor. General: More commonly reported in New World species. May cause severe/lobar pneumonia,
meningitis in all NHP. Epizootics of septicemia and/or pneumonia have been reported in callitrichids, owl monkeys and squirrel monkeys (NWM).
Pathology: Air sacculitis in owl monkeys. Lobar pneumonia, suppurative peritonitis with enlarged mesenteric lymph nodes, suppurative leptomeningitis, mesenteric vascular congestion and hemorrhages. Fibrinopurulent pneumonia and pleuritis, suppurative meningitis, suppurative peritonitis with acute lymphadenitis.
Rhesus macaque Lung Acute lobar pneumonia, unilateral
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Rhesus macaque Lung Acute fibrinosuppurative pleuropneumonia
Owl monkey Lung Acute lobar pneumonia
Squirrel monkey Adrenal and kidney Acute adrenal hemorrhage and necrosis (septicemia)
Squirrel monkey Female reproductive tract
Acute ovarian hemorrhage (septicemia)
StaphylococcusEtiology: Staphylococcus aureus, gram positive cocciGeneral: Generally systemic disease is associated with complications of chronic catheterization in the
laboratory setting. Also immunosuppression due to SRV type D infection. Pathology: Abscesses with abundant off white purulent material anywhere in body.
Suppurative inflammation with prominent colonies of coccoid bacteria.Hematogenous spread from infected skin wounds, catheter sites.
Rhesus macaque Heart Suppurative epicarditis, and myocarditis (or cardiac abscesses)
Cynomolgus macaque
Thorax Fibrinosuppurative pericarditis and epicarditis
Macaque Lung cross section Pulmonary abscesses with cavitation
Macaque Liver Hepatic abscess (secondary to SRV-D immunosuppression)
DermatophilosisEtiology: Dermatophilus congolensis, gram positive bacterium, dormant stage is zoospore. Requires
chronic wetting of skin and abrasion/damage to skin for infection. Generally self limiting infection
General: Reported as natural disease predominately in owl monkeysPathology: Variable sized, well circumscribed raised, crusted circular skin lesions. Face, distal extremities
and tail more commonly affected. Acanthosis and superficial crust
Owl monkey Skin Orthokeratotic and parakeratotic hyperkeratosis and suppurative epidermitis
TetanusEtiology: Clostridium tetani gram positive obligate anaerobe, found in soilGeneral: Disease caused by neurotoxin produced during vegetative growth of bacteria. Associated with
contaminated wounds, recent parturition Clinical: Torpor, difficulty swallowing, change in gait, leading to trismus, opisthotonus and seizuresPathology: Clinical diagnosis. May see external wound or evidence of recent parturition.
Rhesus macaque Whole body Opisthotonus, extensor rigidity of hind limbs
Rhodococcus equiEtiology: Rhodococcus equiGeneral: Infection associated with immunosuppression due to type D retrovirus infection
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Pathology: Pyogranulomatous enteritis and lymphadenitis, characteristic hemorrhagic centers in areas of granulomatous inflammation.
Macaque Intestine Pyogranulomatous enteritis (associated with SRV-D)
Macaque Intestine Pyogranulomatous enteritis with central hemorrhage (associated with SRV-D)
Nonspecific bacterial diseases
Baboon Throat Suppurative airsacculitis
Baboon Air sac Necrosuppurative airsacculitis
Macaque Kidney Chronic active pyelonephritis with hemorrhage, necrosis and effacement of the renal papilla
Macaque Heart Valvular endocarditis, mitral valve (Often associated with long term vascular catheterization)
Bacterial Diseases not pictured to be aware of:
BranhamellosisEtiology: Moraxella (Branhamella) catarrhalis, gram negative cocciClinical: Epistaxis, “bloody nose” syndrome of cynomolgus macaques, also reported in rhesusGross: Epistaxis. mucohemorrhagic rhinitisMelioidosis Etiology: Burkholderi (Pseudomonas) pseudomalleiGeneral: Reported sporadically in wild caught macaques with clusters of cases in groups of imported
cynomolgus macaques. The organism is a ubiquitous saprophyte in soil and water in tropics and causes endemic disease in southeast Asia. There may be an extended period of clinical latency.
Pathology: Multiple abscesses in lung, liver, spleen, soft tissue, skin and bone.
Fungal Diseases
CandidiasisEtiology: Candida albicansGeneral: Associated with immunosuppression, stressed infants/juveniles or retroviral infectionPathology: White linear to round slightly raised plaques in the oral, esophageal mucosa. Hyperkeratosis
with yeast and pseudohyphae throughout the hyperkeratotic keratin
Rhesus macaque Palate Oral hyperkeratosis (pseudomembrane formation)
Rhesus macaque Esophagus Esophageal hyperkeratosis
PneumocystosisEtiology: Pneumocystis carinii (P. jaroveci in humans) Nomenclature in flux. Pneumocystis spp.
considered to be generally host specific. General: Disease of immunosuppression. Common OI of retrovirus-infected macaques. Clinical: May see dyspnea, tachypnea, fever, coughPathology: Noncollapsing grayish pulmonary parenchyma. Patchy to diffuse distribution. Nodular pattern
also described. Multifocal to diffuse histiocytic pneumonia. Alveolar spaces filled with foamy
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amphophilic to eosinophilic fluid with alveolar macrophages. Interstitial thickening with lymphocytic infiltrate, variable type II pneumocyte hyperplasia. Organisms visible with GMS.
Rhesus macaque Lung Diffuse histiocytic pneumonia with alveolar proteinosis
Rhesus macaque Lung Multifocal (nodular) histiocytic pneumonia with alveolar proteinosis
Histoplasma capsulatum var. duboisiiGeneral: Reported only in African origin baboons and humans. Generally restricted to skin,
subcutis, may cause osteolytic lesions in underlying bone, not systemic. Etiology: Histoplasma capsulatum var. duboisii Pathology: Raised 1 to 5 mm or larger lesions on skin. Reddish brown exudates if ulcerated. Generally on
exposed areas of skin: hands, face, buttocks, tail, feet. H. capsulatum var.duboisii are round to ovoid yeast (8-15 microns) with narrow based buds. May create short chains.
Baboon Face Pyogranulomatous dermatitis
Baboon Hands Pyogranulomatous dermatitis with ulceration
Miscellaneous Fungal infections in NHP
Macaque Spleen Diffuse granulomatous splenitis (Histoplasma capsulatum capsulatum)
Macaque Skin Pyogranulomatous panniculitis (Coccidioides immitis)
Metazoan Parasites
Lung mitesEtiology: Pneumonyssoides spp. and Pneumonyssus spp. Pneumonyssus simicola is the lung mite of
rhesus. General: Historically common parasite of Old World monkeys. Up to 100% infection rate before the
routine use of Ivermectin.Clinical: Clinically inapparentPathology: Tan to greenish tan raised plaques elevate the pleural surface. On cut section, there is marked
dilatation and thickening of bronchiolar walls. Lesions scattered throughout the lungs. Fine fibrous adhesions of visceral to costal pleura. After treatment with ivermectin, small thin walled translucent subpleural bullae remain. Chronic eosinophilic granulomatous bronchiolitis with bronchiolar dilatation and smooth muscle hyperplasia and intrahistiocytic pigment (mite pigment.)
Macaque Lung Eosinophilic granulomatous pneumonia with bronchiectasis
Macaque Lung Eosinophilic granulomatous pneumonia with bronchiectasis
Macaque Lung (fixed section) Granulomatous pneumonia with bronchiolar dilatation and smooth muscle hyperplasia
Gelada baboon Lung Multiple subpleural emphysematous bullae
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Lice: Several species of sucking and biting lice have been described. Generally occurs on debilitated singly housed animals. Normal grooming behavior precludes infection in most cases.
Rhesus macaque Face Pediculosis; cutaneous excoriations
Pentastomes: Etiology: Armillifer and Porocephalus in Old World; Porocephalus in New World. “Degenerate” arthropod
parasites, share some characteristics of annelids. General: NHP are intermediate hosts of nymph stage. Adult parasites are found in the respiratory tract
of monkey eating snakes. Clinical: NonePathology: C shaped nymphs with annular bands encysted in the peritoneal or pleural cavity.
Cynomolgus macaque Omentum Omental pentastomiasis
Cestodes:General: Adult cestodes in GI tract include Bertiella, Hymenolepsis, Raillietina). Nonhuman primates
may serve as intermediate hosts for a number of larval cestodes.
Rhesus macaque Small intestine Enteric cestodiasisBertiella sp
Cysticercosis: Adult: Taeniid. Larvae are oval translucent cysts with invaginated scolex. Found in retroperitoneum, abdominal or pleural cavity, subcutis, muscle and CNS.
Rhesus macaque Omentum Omental cysticercosis(Note unusually large size.)
Rhesus macaque Scolex of cysticercus
Rhesus macaque Brain Cerebral cysticercosis
Hydatidosis:Also known as echinococcosis. Adult Echinococcus spp. Hydatid cysts of E. granulosis are large, unilocular and contain numerous brood capsules. Multiple scolices are found within brood capsules. Found in peritoneal, pleural cavity, lungs, retrobulbar area, subcutis. Alveolar hydatids are the larvae of E. multilocularis which create multiloculated cysts with laminated outer layer, inner germinal layer and multiple protoscolices. Recent reports of Echinococcus multilocularis infection (alveolar echinococcosis) in cynos in European zoos, Japanese macaques in Japan.
Greater galago Abdominal cavity Peritoneal hydatidosis (Peritoneal alveolar echinococcosis)
Tetrathyridiosis: Adult Mesocestoides sp.. Larvae are flat with a contractile body, resemble spargana. Found in peritoneal, pleural cavity or encysted in other tissues.
Baboon Intestinal serosa Peritoneal tetrathyridiosis
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Trematodes
Schistosomiasis
Chimpanzee Liver Hepatic fibrosis and macronodular regeneration (cirrhosis)
Natural infection with Schistosoma mansoni
Hepatic trematodiasis. Liver flukes: Athesmia (New World spp,) Dicrocoelium, Eurytrema,Clonorchis others.
Rhesus macaque Liver Chronic suppurative cholangitis with intraductal trematode
Rhesus macaque Liver Liver fluke/hepatic trematode
Nematodes
FilaridsEtiology: Dipetalonema sp, Tetrapetalonema sp, Wuchereria sp, Edsonfilaria sp, othersClinical: NonePathology: Slender filarid nematodes in the peritoneum and subcutis, more common in New World spp.
May see mild serous peritonitis.
Squirrel monkey Peritoneal cavity Abdominal filariasis
Squirrel monkey Small intestine Serosal filariasis
NochtiasisEtiology: Nochtia nochti (trichostrongyle)Clinical: NonePathology: Raised sessile to pedunculated polypoid mass in the gastric mucosa adjacent to the pylorus.
Red, threadlike adult nematode within the nodule.Polyps composed of mucus secreting columnar cells, marked mucus neck cell hyperplasia. Nematodes and embryonated ova.
Rhesus macaque Stomach Nodular gastric hyperplasia
PhysalopteraEtiology: Physaloptera tumefaciens, Physaloptera dilatata (spirurids)Pathology: Raised polypoid mass in stomach. Adults attached to gastric mucosa. May see nematode
protruding from mass. Nematode is 5 x larger than NochtiaCockroach is intermediate host.
Baboon Stomach Focal nodular gastric hyperplasia with intralesional nematodes
Baboon Stomach Proliferative and erosive gastritis with intralesional nematodes
Gastric physalopteriasis
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OesophagostomiasisEtiology: Oesophagostomum spClinical: May be inapparent or may result in diarrheaPathology: Raised reddish brown nodules in the colonic submucosa visible from the serosal surface
Fourth stage larvae produce submucosal abscesses containing central necrotic core with mixed inflammatory cells and fibrotic wall. Adults are free living within colonic lumen.
Pigtail macaque Colon Multifocal subserosal granulomatous colitis with hemorrhage
Colonic oesophagostomiasis
Rhesus macaque Ileocecal junction Multifocal subserosal granulomatous colitis with hemorrhage
Colonic oesophagostomiasis
ProsthenorchiasisEtiology: Prosthenorchis elegans, Prosthenorchis spirula, Acanthocephalans, thorny headed wormsGeneral: Predominately disease of NW species. Can detect characteristic brown, double-walled
embryonated ova on direct fecal smears and sedimentation (won’t float.)Pathology: Adult acanthocephalans embed in terminal ileum, cecum and colon. Create ulcer extending in
to submucosa and muscularis and surrounded by fibrous tissue. Occasionally rupture through wall of intestine resulting in peritonitis.Deep ulcers extending into muscularis containing the embedded hook-laden head of the parasite surrounded by necrotic debris, eosinophils, neutrophils, macrophages and lymphocytes and fibrous connective tissueTransmission occurs through ingestion of cockroach, intermediate host.
Squirrel monkey Ileocecal junction Enteric prosthenorchiasis
New World Monkey Intestine Enteric prosthenorchiasis
Trichuriasis Etiology: Trichuris spGeneral: Common nematodiasis of ground raised macaques. Find in cecum and ascending colon.
Minimally pathogenic. Often increased numbers with concurrent typhlocolitis (Campylobacteriosis, chronic colitis.)
Rhesus macaque Ileocecal junction Chronic active proliferative typhlocolitis and trichuriasis Lymph node edema
Rhesus macaque Colon Chronic proliferative typhlocolitis and trichuriasis
Protozoa
HepatocystisEtiology: Hepatocystis spp. Hepatocystis kochi (H. simiae) is the species commonly found in African
baboons, H. bouillezi, H. cercopitheci, H. semnopitheci, and H. taiwanensis. General: Hepatocystis is a protozoan parasite classified in the family Plasmodiidae In endemic areas,
the incidence can range from 24 to 75% in nonhuman primates. Animals exhibit a parasitemia as well as characteristic hepatic cysts that correspond to mature merocysts. Diagnosis is based on identification of the erythrocytic stage (trophozoite or gametocyte) in thick or thin blood smears and/or the histologic identification of merocysts in liver sections
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Clinical: Hepatocystis rarely causes clinical disease. Schizogony takes place in the liver rather than the erythrocyte; therefore, cyclical fevers or parasitemic waves that may characterize malarial infections do not occur. A mild, microcytic anemia may be noted
Pathology: The grossly visible mature merocysts on the hepatic surface are characteristic findings. They appear as raised, grayish-white to translucent foci with a central accumulation of fluid. Multiple, depressed areas of fibrosis with calcification representing healed lesions may also be present. Protozoal cyst in the liver characterized by an irregular central space filled with faintly eosinophilic, acellular, flocculent material with a peripheral rim of myriad, round, lightly basophilic merozoites that measure approximately 1.0–2.0 mm in diameter. Cyst is delineated by a thin, convoluted, eosinophilic, hyaline capsule There may or may not be a significant inflammatory response to the merocysts. If present, the response is typically granulomatous with an admixture of eosinophils and lymphocytes. Transmission: Hepatocystis is transmitted to the vertebrate host by a Culicoides species. Sporozoites, inoculated during feeding, enter hepatocytes and develop into meronts termed merocysts. When mature, they rupture and release merozoites which invade erythrocytes and develop into gametocytes. The ring form, an intra-erythrocytic trophozoite may be confused with malarial parasites. Some of the merozoites may reinvade hepatocytes. The gametocytes are picked up by Culicoides during a meal and sporogony occurs in the invertebrate host.
Macaque Liver Multifocal eosinophilic granulomatous hepatitis with protozoal merocysts
Vervet Liver Eosinophilic granulomatous hepatitis with protozoal merocysts
CryptosporidiosisEtiology: Cryptosporidium spGeneral: May cause disease in young or immunosuppressed animals. Common OI of SIV infected
macaques. Clinical: Weight loss, diarrhea, Pathology: In SIV infected macaques infection commonly involves the biliary tree, pancreatic ducts,
respiratory tract as well as the intestine. Numerous superficial organisms. In SIV infected macaques see marked mucosal proliferation and periductal fibrosis.
Macaque Liver and gall bladder Chronic biliary hyperplasia
Macaque Liver Chronic biliary hyperplasia
Noninfectious Diseases
Systemic amyloidosisGeneral : Secondary or reactive amyloidosis. Reported in macaques, baboons, marmosets, most other
common NHP species. Deposition of AA amyloid in numerous tissues. Precursor protein is SAA , an acute phase reactant protein produced by the liver. High correlation with chronic colitis and diarrhea in macaques. Also associated with chronic vascular catheterization, chronic ulcerative (cicatrizing) colitis, chronic osteoarthritis
Clinical: Weight loss, hepatic enlargement with abdominal distension, protein losing enteropathy with diarrhea. Clinical pathology may reveal lowered albumen and A:G ratio of less than 1.0.
Pathology: Most commonly affected organs are SI, liver, spleen. See massively enlarged liver up to 14% of body weight. Liver is pale tan to pale red and waxy. Hepatic margins often affected more severely. Spleen is light red and waxy. SI mucosa may appear normal or thickened with loss of villous appearance. Deposition of homogenous to fibrillar, acellular eosinophilic material in tissues. In the liver, deposition begins in the space of Disse, eventually causes almost complete atrophy of hepatic cords. Deposition in lamina propria of the intestine SI>colon.
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Deposition in the renal medullary interstitium, the corticomedullary junction of the adrenal and the colonic lamina propria are common. May see deposition in almost any organ: lymph node, thyroid.
Rhesus macaque Liver Hepatic amyloidosis
Rhesus macaque Liver cut section Hepatic amyloidosis
Rhesus macaque Spleen cut section Splenic amyloidosis
Rhesus macaque Small and large intestine
Enteric amyloidosis
Fatal Fasting Syndrome of macaquesGeneral: Also known as fatal fatty liver syndrome, occurs primarily obese female macaques Clinical: Brief period of anorexia, precipitous weight loss of up to 30% and sudden death are seen.
Clinicopathologic change: azotemiaPathology: Animals frequently still have abundant fat. Abdominal fat necrosis, pale soft kidneys, enlarged
pale friable liver Microscopically, vacuolar change in hepatocytes and proximal renal tubular epithelium. Renal tubular necrosis may also be present. May see lesions in pancreas: acinar ectasia, decreased zymogen granule content, small foci of necrosis.
Rhesus macaque Liver Hepatic lipidosis
Rhesus macaque Liver (cut section) Hepatic lipidosis
Rhesus macaque Kidney Renal tubular lipidosis and acute renal tubular necrosis
Rhesus macaque Subcutaneous fat Fat necrosis, multifocal
Islet amyloidosisGeneral: Reported in macaques, baboons, other Old World spp. Strongly associated with the
development of diabetes mellitus (DM). Islet amyloid is deposited in the pancreatic islets of Langerhans from the precursor protein, islet associated polypeptide (IAPP), a 37 amino acid polypeptide co-secreted with insulin by beta cells of the endocrine pancreas.
Clinical: DM: polyphagia, polydypsia, polyuria, weight loss. In most species DM is frequently associated with obesity.
Pathology: Generally none, may see numerous off white, tan foci in pancreasHomogeneous extracellular eosinophilic material in islets. Congophilic.
Rhesus macaque Pancreas Islet amyloidosis
Chronic colitis of macaquesGeneral: By far the most common disease causing morbidity and mortality in many facilities. Occurs
both in nursery raised and group-housed, maternally reared animals. Primarily seen in young animals between 1 and 3 years of age. Initial episodes of diarrhea may be associated with positive fecal cultures for Campylobacter or Shigella and the presence of pathogenic protozoa.
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Subsequent episodes are characterized by normal enteric flora and the variable presence of protozoa. The pathogenesis is thought to be complex involving repeated enteric infections, malnutrition associated with enteric disease, compromised mucosal defenses, environmental stresses and possible hypersensitivity to dietary antigens
Clinical: Persistent or recurrent liquid diarrhea, dehydration, weight loss and poor growth.Pathology: Colons may be thickened or flaccid and dilated. There are often copious amounts of liquid
colonic content. The mucosa may be multifocally eroded or ulcerated. In other animals, the predominant change is thickened and rugose mucosal surfaces. Typically, the cecum and proximal colon are most severely affected. Colonic lymph nodes are enlarged. Histologic change is chronic active proliferative typhlocolitis with crypt abscessation.
Rhesus macaque Abdominal cavity Diffuse colitis with marked distension
Rhesus macaque Colon Diffuse proliferative colitis
Rhesus macaque Cecum and colon Diffuse proliferative typhlocolitis
Rhesus macaque Colon Chronic proliferative and erosive colitis
Cicatrizing ulcerative colitisGeneral: A syndrome of ulcerative colitis with marked fibroplasia is seen occasionally in macaques.
Frequently associated with the secondary development of generalized amyloidosisClinical: Weight loss and chronic diarrhea. Signs of colonic obstruction, such as scant feces, vomiting,
and abdominal distention, may develop in some animals. Pathology: Linear to focally extensive regions of deep mucosal ulceration in the cecum and proximal
colon. Chronic ulcers are surrounded by marked deposition of fibrous connective tissue resulting in stricture formation. Strictures can result in partial to complete obstruction and resulting distention of the anterior intestinal tract occurs. The lesion must be distinguished microscopically from intestinal adenocarcinomas that frequently arise in similar anatomic locations. Deep ulceration of the mucosa and underlying submucosa. Lymphoid aggregates are prominent in the adjacent mucosa, submucosa, and subserosal tissues.
Rhesus macaque Colon Multifocal colonic annular ulcers
Rhesus macaque Ileocecal junction Chronic multifocal cecocolonic ulcers with stricture formation
Japanese macaque Colon Chronic multifocal colonic ulcers with fibrosis and stricture formation
Intestinal adenocarcinoma of aged macaquesGeneral: Most common malignant neoplasm of aged rhesus. locally aggressive but slow to metastasize.
Local lymph node most common site of metastasis occurs in 10% cases. Clinical: Weight loss, partial to complete anorexia, scant or no feces, diarrhea and vomiting, palpable
abdominal mass in upper right abdominal quadrant. Clinicopathologic findings are nonspecific and include hypoproteinemia, hypoalbuminemia, and anemia. Evaluations for fecal occult blood are frequently positive.
Pathology: Circumferential or nodular thickenings in the cecum or proximal colon (less commonly in the small intestine), sessile to polypoid mass with variable degrees of ulceration and constriction of the lumen (“napkin-ring” lesion). Subset of cases reported arising in the ampullary region of the duodenum in aged macaques with more aggressive biological behavior and higher incidence of metastasis.
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Neoplastic cuboidal to columnar cells forming poorly organized tubules and acini (arise from the mucosa and generally extend into the muscularis and often to the subserosa. Subset are mucinous adenocarcinomas with lakes of mucin in cystic spaces lined by neoplastic epithelial cells.
Rhesus macaque Colon Stricture with proximal megacolon (secondary to adenocarcinoma)
Rhesus macaque Colon Colonic adenocarcinoma with stricture and proximal megacolon
Rhesus macaque Colon Colonic adenocarcinoma
Rhesus macaque Omentum Omental carcinomatosis
Rhesus macaque Duodenum Ampullary carcinoma
Gastric infarctionGeneral: Uncommon but remarkable gross appearance. Reported in cynos, also seen in rhesus.
Unexpected finding. Cases had massive tissue damage (intraspecific trauma with myonecrosis/rhabomyolysis, pancreatitis and intestinal intussusception)
Pathology: Focally extensive ulceration of the gastric mucosa involving the fundus and pylorus. Microscopically, see mucosal necrosis, hemorrhage and edema with prominent thrombosis of submucosal venous vasculature.
Rhesus macaque Stomach Focally extensive gastric necrosis and ulceration with infarction
Acute gastric dilatationGeneral: Occurs with relative frequency as a sporadic disease in macaques and other NHP in captivity.
Generally occurs in subadult to adult monkeys in good condition. Historical include overfeeding and/or feed restriction, and prior anesthesia.
Clinical: Clinical course is frequently peracute. Clinical signs, when observed, include hunched posture, facial grimacing indicative of abdominal pain, and abdominal distension. Untreated, the disease is invariably fatal.
Pathology: Marked abdominal distension and gastric dilatation without volvulus, terminal hemorrhages. Occasionally, post mortem gastric rupture. Death is attributed to impaired venous return and cardiopulmonary compromise.
Macaques Abdominal cavity Gastric dilatation and enteric vascular congestion
Chronic colitis of tamarinsGeneral: Colitis occurs commonly in several species of callitrichids including the cotton top tamarin
(Saguinis oedipus), saddle back tamarin (Saguinus fuscicollis), and common marmoset (Callithrix jacchus) It has been most extensively studied in cotton top tamarins in which it is associated with intestinal adenocarcinoma and is proposed as a model of colitis and adenocarcinoma in humans. Affects both sexes equally etiology of colitis in callitrichids is unknown disease of captivity Possible factors include unidentified transmissable agents, social stress, caging, ambient temperature and humidity. Diet does not appear to play a primary role in the development of colitis but may influence chronic changes. Stress is thought to play an important role in the pathogenesis.
Clinical: Diarrhea and weight loss acute exacerbations followed by periods of remission
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Pathology: Variable appearance ranging from no grossly visible changes to multiple areas of hemorrhage and ulceration of the mucosa. The entire large intestine from the cecum to rectum is affected.
Tamarin Colon Diffuse colitis with hemorrhage and ulceration
Colon carcinoma of CTTGeneral: Relatively high incidence of colonic adenocarcinoma in CTT in captivity. Associated with
chronic colitis. Age range 3-8 years. Metastasis relatively common. Clinical: Weight loss, poor body condition, and nonresponsive chronic diarrhea. palpable discrete
abdominal masses and thickened bowels. Intestinal obstruction may occur.Pathology: Masses occur anywhere in colon from ileocecal junction to the rectum. Range from inapparent
mucosal plaques to thickened fibrotic masses. Metastases to local lymph nodes, lung and pancreas.Neoplastic epithelial cells forming sheets and nests, poorly organized glands. Cells are often mucin producing and PAS positive.
Cotton top tamarin Colon Colonic adenocarcinoma
Cotton top tamarin Colon Colonic adenocarcinoma
EndometriosisGeneral: Disease of menstruating (Old World) primates. Characterized by the presence of ectopic
endometrial tissue which undergoes regular cyclical changes under the influence of estrogen and progesterone similar to normal endometrium
Clinical: Often vague and not specific but may see cyclic depression and anorexia, weight loss, menorrhagia, irregular menstrual cycles, abdominal distension, constipation, absence of feces, decreased fertility, and/or anemia. Palpable masses, uterine distortion or other pelvic abnormalities
Pathology: Most frequently found over the visceral and peritoneal surfaces of the pelvis. The serosa of the uterus, urinary bladder, omentum, distal colon and the uterine ligaments are often affected. Ovarian involvement in macaques is common May see throughout the abdominal cavity, the thoracic and abdominal surfaces of the diaphragm and the intercostal musculatureAppears as firm white to tan punctate, puckered foci or soft red-brown raised masses adhered to serosal surfaces. Variably sized cysts containing brown fluid (“chocolate cysts”). The cysts have a thick wall with a shaggy, irregular brown to yellow-brown lining. Fibrous adhesions are common and may cause obstruction of the colon or uretersEctopic endometrial glands (columnar cells with apical blebs or cilia) and underlying densely cellular spindle cell stroma. Glandular lumina often contain blood and cellular debris. Accompanied by fibrosis, variable numbers of lymphocytes and plasma cells, and accumulations of hemosiderin-laden macrophages
Rhesus macaque Female reproductive tract
Normal
Rhesus macaque Female reproductive tract and bladder
Endometriosis, involving uterus, ovary and urinary bladder
Rhesus macaque Female reproductive tract
Endometriosis
Rhesus macaque Diaphragm Endometriosis, peritoneal diaphragm
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Vitamin C deficiencyGeneral: NHP have absolute dietary requirement for Vitamin C. Basis of lesions is defects in collagen
and intercellular cement formation resulting in increased vascular fragility and defects in bone formation. Outbreaks of scurvy have occurred due to defects in manufacture or handling of commercial diets. Species dependent differences in disease manifestation.
Clinical: Squirrel monkeys: Subcutaneous swelling of head, weakness and gingival hemorrhagesRhesus macaques: lameness, reluctance to move and weakness
Pathology: Squirrel monkeys , particularly juvenile and subadults, develop subcutaneous and subperiosteal hemorrhages of the head, leading to ossification and exostoses. Cephalhematomas result in enlargement of the head (described as “turban head”) and deformation of facial features Rhesus macaques develop changes in the long bones, teeth and ribs. Animals may exhibit swelling of the wrists, periosteal hemorrhage, cutaneous bruising, anemia and loose teeth. Metaphyseal fractures, periosteal hemorrhages and gingival hemorrhage.
Macaque Forelimb Periosteal hemorrhage
Macaque Oral cavity Gingival hemorrhage
Squirrel monkey Head Facial deformities, cutaneous necrosis, cephalhematoma
Squirrel monkey Head Periosteal proliferation and ossification and subcutaneous hemorrhage (cephalhematoma)
Hemolytic anemia of owl monkeys and callitrichids General: Disease of callitrichids and owl monkeys associated with low serum levels of vitamin E.
(Dietary levels of Vitamin E are adequate.) In owl monkeys disease occurs only in certain karyotypes
Clinical: Weakness, collapse, icterus in somePathology: Pale mucous membranes and viscera due to anemia, Skeletal muscle pallor due to anemia,
atrophy and necrosis. Enlargement and bronzing of liver and spleen due to hemosiderosis. May see centrilobular pallor (“nutmeg”) due to CL necrosis during hemolytic crises. Heinz body hemolytic anemia, skeletal muscle necrosis, and generalized steatites. Hemosiderin laden macrophages in liver, spleen and bone marrow and lymph nodes. Lesions attributed to anemia are centrilobular hepatic necrosis and cerebral ring hemorrhages
Owl monkey Whole body Anemia/visceral pallor; hepatomegaly/hemosiderosis
Owl monkey Whole body Splenohepatomegaly/hemosiderosis
Reactive ArthritisGeneral: Reactive arthritis is an inflammatory non infectious arthritis which occurs in humans and NHP
following enteric and urogenital infections. It is most commonly associated with Shigella infection in NHP
Clinical: Acute onset of lameness and joint swelling 1 to 2 months following an episode of enteric disease May progress to severe muscle atrophy with joint contracture.
Pathology: Stifle, elbow, coxofemoral and interphalangeal joints most commonly affected . Mild to moderate joint effusion.Mature neutrophils in joint effusions, aseptic.
Rhesus macaque Stifle Severe erosive and suppurative osteoarthritis
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Rickets/OsteomalaciaGeneral: NWM have a dietary requirement for Vitamin D3.Pathology: Rickets: bowing of long bones, enlargement of growth plates, rachitic rosary, soft bones.
FOD in adultsIrregular growth plate, retention of cartilage cores.
Cotton top tamarin Lower extremity Bowing of long bones with pathologic fractures (rickets)
Langur Tibia Rickets: Retention of cartilage cores, pathologic fracture, irregular growth plate
Langur Ribs Rachitic rosary
Squirrel monkey Ribs Fibrous osteodystrophy
Cardiomyopathy of owl monkeysGeneral: Spontaneous cardiomyopathy has been described with relatively high frequency in owl
monkeys. Hypertrophic cardiomyopathy> dilated cardiomyopathy. Associated with systemic hypertension in affected monkeys
Clinical: Dyspnea, ascites, and subcutaneous edema. In many, premonitory signs are lacking and “sudden death” is the presenting complaint.
Pathology: Hypertrophic hearts have severe concentric thickening of the left ventricular free wall and interventricular septumMyocyte hypertrophy, necrosis, and fibrosis
Owl monkey Thoracic cavity Cardiomegaly
Owl monkey Heart Left ventricular hypertrophyHypertrophic cardiomyopathy
Owl monkey Heart Dilatative cardiomyopathy
Owl monkey Heart Left ventricular hypertrophy with fibrosisHypertrophic cardiomyopathy
Owl monkey Liver Chronic passive congestion: centrilobular (periacinar) fibrosis, hepatocellular loss and chronic congestion
Aortic aneurysms General: Aneurysms of the aorta and carotid arteries have been reported in a number of species; the
majority of cases have been in New World species, particularly owl and squirrel monkeysPathology: Majority of aneurysms are dissecting; fusiform and saccular types are less common.
Owl monkey Heart Aortic aneurysm
Cerebral Venous ThrombosisGeneral: Rare sporadic disease of rhesus macaques. Etiology unknown, may be associated with factors
leading to hypercoagulability such as dehydration
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Clinical: Clinical signs are variable and may be inapparent. Animals may present with mild to moderate neurologic and cognitive deficits. Signs referable to an acute onset cerebral vascular accident may be seen. Abnormal gait and seizures.
Pathology: Numerous variably sized thrombi and hemorrhages in the white matter particularly at the junction with gray matter within all levels of the cerebrumNumerous thrombosed veins of varying chronicity with recanalization, multifocal hemorrhage, leukoencephalomalacia,
Rhesus macaque Brain Multifocal venous thrombosis with hemorrhage and necrosis
RhabdomyolysisGeneral: Intraspecific trauma (seen frequently in group housed macaques) results in extensive soft
tissue/muscle damage, particularly crushing injuries. Sites most affected are caudal aspect of arms, face, anterior aspect of thighs, inguinal/genital region resulting in myonecrosis/rhabdomyolysis. Subsequent hypovolemic shock and myoglobinemia result in renal failure due to acute tubular necrosis.
Pathology: Pale enlarged kidneys. Massive soft tissue/muscle necrosis, hemorrhage and edema. Anuria.Renal tubular necrosis and degeneration with marked intratubular cast formation: hyaline, granular and cellular.
Macaque Kidney Acute tubular necrosis with myoglobin casts
Sprue-like enteropathyGeneral: Has similarities to celiac sprue in humans. Associated with protein losing
enteropathy/malabsorption syndrome in macaques.Pathology: Loss of villous appearance in small intestine. Microscopically characterized by
lymphoplasmacytic enteritis, villous blunting and fusion and increased goblet cells.
Rhesus macaque Small intestine Enteric villous atrophy. Villous blunting and fusion.DDX: enteric amyloidosis
Rhesus macaque Small intestine Enteric lymphangiectasia (non specific finding) Compare to previous image
Miscellaneous
Gastrointestinal I
Rhesus macaque Esophagus Squamous cell carcinoma
Rhesus macaque Colon Diverticulitis (Diverticulosis is a common finding in aged rhesus
colon. Diverticulitis is uncommon.)
Reproductive tract
Rhesus macaque Uterus Uterine leiomyoma Common benign neoplasm in aged female macaques
Rhesus macaque Uterus Endometrial polyps Increased incidence associated with unopposed
estrogenRhesus macaque Ovary Ovarian teratoma
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Cardiovascular
Rhesus macaque Aorta and iliac arteries Aortic and iliac atherosclerosis with iliac atheromas (Atherosclerosis is generally a dietary induced disease,
cynos and vervets preferred models.)Rhesus macaque Aorta Aortic intimal atheromatous plaque
Rhesus macaque Heart, mitral valve Mitral valve endocardiosisCommon change in aged rhesus
Rhesus macaque Heart Dilatative cardiomyopathy with marked right ventricular dilatation
Rhesus macaque Lower extremities Subcutaneous edema.Common manifestation of decompensated CHF in
macaques is peripheral edema of dependent portions of body (lower limbs, prepuce)
Rhesus macaque Abdomen Subcutaneous edema
Rhesus macaque Heart Myocardial degeneration, necrosis and mineralization.Uremic myocarditis
Rhesus macaque Stomach Multifocal gastric mucosal congestion, edema and necrosis
Uremic gastritis
Respiratory
Rhesus macaque Lungs (neonatal) Diffuse granulomatous pneumonia with pigmentationMeconium aspirationAssociated with in utero fetal distress, evacuation of
meconium and aspiration
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Recommended References
Monographs on Pathology of Laboratory Animals: Nonhuman Primates I and II. T. C. Jones, U. Mohr, and R. D. Hunt (eds.), Springer-Verlag, Berlin and New York, 1993.
Nonhuman Primates in Biomedical Research, Diseases, eds. Bennett BT, Abee CR, and Henrickson R. Academic Press, San Diego, CA, 1995
*Lowenstine, L. J. 2003. A primer of primate pathology: lesions and nonlesions. Toxicol. Pathol. 31 Suppl:92-102.
Ludlage, E. and K. Mansfield. 2003. Clinical care and diseases of the common marmoset (Callithrix jacchus). Comp Med. 53:369-382.
Baskin, G.B. 2002. Pathology of Nonhuman Primates 2002. Notes with extensive bibliography. C.L. Davis Foundation.
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