Gross Morbid Anatomy of Pathology of Nonhuman Primates

Anne D. Lewis, DVM, PhD, Diplomate, ACVP

Oregon National Primate Research Center
505 NW 185th Avenue
Beaverton, OR 97008
503-690-5356
lewisann@ohsu.edu

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 herpesviruses
In 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

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Herpesvirus tamarinus
Etiology: Saimiriine herpesvirus 1, Herpesvirus tamarinus, Herpes T
General: 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 simplex
Etiology: Human herpesvirus 1, Herpes simplex virus 1
General: 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-2
Etiology: 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 Virus

Etiology: 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 edema
Multifocal 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.

Cytomegalovirus
Etiology: 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 Lymphoma, intestine, lymph nodes

lymph nodes
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Owl monkey Lung Retrobulbar lymphoma

Retroviruses

SIV
Etiology: 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 encephalitis
Common 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 Marked follicular lymphoid hyperplasia, lymph
nodes 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 retrovirus
Etiology: 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 Virus

Etiology: Simian Hemorrhagic Fever Virus, Arterivirus
General: Rare epizootic disease with high mortality in macaques (Patas monkeys, other African NHP
act as reservoir host.)
Clinical: Fever, depression, anorexia, ataxia, diarrhea, abortion, DIC
Pathology: 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

Measles
Etiology: Human measles virus. Morbillivirus, Paramyxoviridae
General: Humans are reservoir host
Clinical: 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 hepatitis
Etiology: 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

SV40
Etiology: Simian Virus 40, Polyomavirus, Polyomaviridae
General: 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 Leukoencephalomalacia

section)

Poxviruses

Monkeypox
Etiology- Orthopoxvirus, antigenically related to smallpox and vaccinia
Natural disease in African spp. NHP are not natural host. Probably arboreal squirrels
Clinical: 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

Yabapox
Etiology: Yaba monkey tumor virus (Yabapoxvirus), Yatapoxvirus (genus). Virus is related to tanapox
virus
General: 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 smallpox
General: 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, Picornaviridae
General: Epizootic infections reported in several species; owl monkeys, callitrichids, baboons highly
susceptible. Rodent reservoir
Clinical: 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

Papillomavirus
General: 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

Tuberculosis
Etiology: Mycobacterium tuberculosis, M. bovis
General: 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-γ 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 Necrotizing pyogranulomatous lymphadenitis

lnn

Rhesus macaque Lung (fixed) Multifocal to coalescing granulomatous

bronchopneumonia

Cynomolgus Lungs and hilar Granulomatous lymphadenitis

macaque lymph node

Cynomolgus Liver Multifocal granulomatous hepatitis

macaque

Cynomolgus Adrenal gland Granulomatous adrenalitis

macaque

Rhesus macaque Vertebrae Granulomatous vertebral osteomyelitis with

pathologic fracture and spinal cord compression
(Pott’s disease)

Mycobacterium avium complex

Etiology: Mycobacterium avium-intracellure complex, MAC
General: 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, diarrhea
Pathology: 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 Diffuse histiocytic enteritis and lymphadenitis

lymph nodes

Macaque Lungs Diffuse granulomatous pneumonia

Leprosy
Etiology: Mycobacterium leprae
General: Natural infection reported in chimpanzees and sooty mangabeys
Pathology: 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

Shigellosis
Etiology: Shigella flexneri, (S, dysenteriae, S. sonnei, S. boydii) gram negative bacillus
General: 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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Campylobacteriosis
Etiology: 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

Helicobacter
Etiology: Helicobacter pylori, gram negative spiral bacterium
General: Highly prevalent in the stomachs of rhesus macaques. Can use rapid urease test on mucosal
biopsies to diagnose.
Clinical: Generally inapparent, may cause vomiting
Pathology: May see reddening, mild erosions, ulcers of gastric fundic/antral mucosa. In
immunosuppressed macaques may cause proliferative gastritis
Mild 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

Streptococcosis
Etiology: Streptococcus pneumoniae
Clinical: 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

Listeriosis
Etiology: Listeria monocytogenes, gram-positive, intracellular bacillus, facultative anaerobe, common
soil contaminant
General: 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.
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Cynomolgus Lungs (fetal) Suppurative bronchopneumonia

macaque

Macaque Placenta Suppurative placentitis

Yersiniosis
Etiology: Yersinia pseudotuberculosis, Y. enterocolitica, gram negative bacillus
General: 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 Necrohemorrhagic enterocolitis

colon

Rhesus macaque Colon Necroulcerative colitis

Squirrel monkey Spleens Necrosuppurative splenitis

Tularemia
Etiology: 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 Necrotizing lymphadenitis

nodes

Klebsiella
Etiology: 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 Acute ovarian hemorrhage (septicemia)

tract

Staphylococcus
Etiology: Staphylococcus aureus, gram positive cocci
General: 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 Thorax Fibrinosuppurative pericarditis and epicarditis

macaque

Macaque Lung cross section Pulmonary abscesses with cavitation

Macaque Liver Hepatic abscess (secondary to SRV-D

immunosuppression)

Dermatophilosis
Etiology: 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 monkeys
Pathology: 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

Tetanus
Etiology: Clostridium tetani gram positive obligate anaerobe, found in soil
General: 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 seizures
Pathology: Clinical diagnosis. May see external wound or evidence of recent parturition.

Rhesus macaque Whole body Opisthotonus, extensor rigidity of hind limbs

Rhodococcus equi
Etiology: Rhodococcus equi
General: Infection associated with immunosuppression due to type D retrovirus infection
 13

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:

Branhamellosis
Etiology: Moraxella (Branhamella) catarrhalis, gram negative cocci
Clinical: Epistaxis, “bloody nose” syndrome of cynomolgus macaques, also reported in rhesus
Gross: Epistaxis. mucohemorrhagic rhinitis
Melioidosis
Etiology: Burkholderi (Pseudomonas) pseudomallei
General: 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

Candidiasis
Etiology: Candida albicans
General: Associated with immunosuppression, stressed infants/juveniles or retroviral infection
Pathology: 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

Pneumocystosis
Etiology: 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, cough
Pathology: Noncollapsing grayish pulmonary parenchyma. Patchy to diffuse distribution. Nodular pattern
also described. Multifocal to diffuse histiocytic pneumonia. Alveolar spaces filled with foamy
 14

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. duboisii

General: 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 mites
Etiology: 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 inapparent
Pathology: 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

 15

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: None
Pathology: 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 cestodiasis

Bertiella 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

 16

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

Filarids
Etiology: Dipetalonema sp, Tetrapetalonema sp, Wuchereria sp, Edsonfilaria sp, others
Clinical: None
Pathology: 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

Nochtiasis
Etiology: Nochtia nochti (trichostrongyle)
Clinical: None
Pathology: 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

Physaloptera
Etiology: 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 Nochtia
Cockroach is intermediate host.

Baboon Stomach Focal nodular gastric hyperplasia with intralesional

nematodes

Baboon Stomach Proliferative and erosive gastritis with intralesional

nematodes
Gastric physalopteriasis
 17

Oesophagostomiasis
Etiology: Oesophagostomum sp
Clinical: May be inapparent or may result in diarrhea
Pathology: 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

Prosthenorchiasis
Etiology: Prosthenorchis elegans, Prosthenorchis spirula, Acanthocephalans, thorny headed worms
General: 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 tissue
Transmission occurs through ingestion of cockroach, intermediate host.

Squirrel monkey Ileocecal junction Enteric prosthenorchiasis

New World Monkey Intestine Enteric prosthenorchiasis

Trichuriasis
Etiology: Trichuris sp
General: 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

Hepatocystis
Etiology: 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
 18

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 µ m 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

Cryptosporidiosis
Etiology: Cryptosporidium sp
General: 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 amyloidosis
General : 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.
 19

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 Enteric amyloidosis

intestine

Fatal Fasting Syndrome of macaques

General: 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: azotemia
Pathology: 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 amyloidosis
General: 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 pancreas
Homogeneous extracellular eosinophilic material in islets. Congophilic.

Rhesus macaque Pancreas Islet amyloidosis

Chronic colitis of macaques

General: 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.
 20

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 colitis

General: A syndrome of ulcerative colitis with marked fibroplasia is seen occasionally in macaques.
Frequently associated with the secondary development of generalized amyloidosis
Clinical: 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 macaques

General: 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.
 21

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 infarction
General: 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 dilatation

General: 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 tamarins

General: 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
 22

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 CTT

General: 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

Endometriosis
General: 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 musculature
Appears 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 ureters
Ectopic 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 Normal

tract

Rhesus macaque Female reproductive Endometriosis, involving uterus, ovary and urinary
tract and bladder
bladder
Rhesus macaque Female reproductive Endometriosis
tract

Rhesus macaque Diaphragm Endometriosis, peritoneal diaphragm

 23

Vitamin C deficiency
General: 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 hemorrhages
Rhesus 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 some
Pathology: 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 Arthritis
General: 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

 24

Rickets/Osteomalacia
General: NWM have a dietary requirement for Vitamin D3.
Pathology: Rickets: bowing of long bones, enlargement of growth plates, rachitic rosary, soft bones.
FOD in adults
Irregular 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 monkeys

General: 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 septum
Myocyte hypertrophy, necrosis, and fibrosis

Owl monkey Thoracic cavity Cardiomegaly

Owl monkey Heart Left ventricular hypertrophy

Hypertrophic cardiomyopathy

Owl monkey Heart Dilatative cardiomyopathy

Owl monkey Heart Left ventricular hypertrophy with fibrosis

Hypertrophic 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 monkeys
Pathology: Majority of aneurysms are dissecting; fusiform and saccular types are less common.

Owl monkey Heart Aortic aneurysm

Cerebral Venous Thrombosis

General: 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 cerebrum
Numerous thrombosed veins of varying chronicity with recanalization, multifocal hemorrhage,
leukoencephalomalacia,

Rhesus macaque Brain Multifocal venous thrombosis with hemorrhage and

necrosis

Rhabdomyolysis
General: 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 enteropathy
General: 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
estrogen
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Rhesus macaque Ovary Ovarian teratoma

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 endocardiosis

Common 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 pigmentation

Meconium aspiration
Associated 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.