NHP disease Flashcards
Most common disease in macaque colonies
Diarrhea (specifically chronic colitis)
Most common age group for diarrhea in macaques
<3 years but others affected
Clinical signs of chronic colitis in macaques
Persistent diarrhea (usually >6w duration), recurrent diarrhea episodes (>3 in 12mo period) Growth retardation, weight loss
Common causes of diarrhea in macaques
Campylobacter
Shigella
Giardia, trichomonads, Balantidium
Pathogenesis of chronic colitis in macaques
Multiple causes/predipsosing factors
(1) Repeated enteric infection
(2) malnutrition associated w chronic diarrhea
(3) compromised mucosal defenses
(4) dysregulation of mucosal immune response
(5) environmental stress
(6) hypersensitivity to dietary antigen and/or microbial flora
Location of lesions in chronic colitis of macaques
Cecum, cranial colon
Gross lesions present with chronic colitis of macaques
Thickened, flaccid/dilated colon
Mucosal erythema or erosion
Mucosal proliferation
Enlarged colonic LN
Histopath findings in chronic colitis of macaques
Mucosal hyperplasia Lymphoplasmacytic infiltrate Crypt abscesses Herniation of glands into lymphoid nodules Loss of goblet cells
Age group affected by cicatrizing ulcerative colitis?
Young adult - adult
Sequela associated with ulcerative colitis in macaques
secondary amyloidosis
cilnical signs of cicatrizing ulcerative colitis in macaques
weight loss
chronic diarrhea
rarely see stricture +/- obstruction (scant feces, vx, abdominal distension/bloat)
Gross findings in ulcerative colitis in macaques
annular colonic ulcers
stricture formation, partial obstruction
Histo findings in ulcerative colitis
Deep ulcers extending into mucosa
Fibroplasia/fibrosis
Lymphoid follicles prominant
Glandular dysplasia
Findings with gastric infarction in macaques
gastric infarction with ulceration
associated with conditiosn of massive tissue damage (rhabdomyolysis, pancreatitits, intussusception)
mucosal necrossis, hemorrhage, edema with thrombosis
Age group affected by gastric dilatation (acute bloat) in macaques?
Subadult to young adults in good nutritional condition
Predisposing factors for gastric dilatation (acute bloat) in macaques?
Hx of anesthesia, overfeeding, or feed restriction followed by food/water access
You see a young male macaque who was recently fasted and given access to a large amount of food presenting with acute collapse, a distended cranial abdomen and cutaneous ‘blisters.’ name one possiblediagnosis.
acute gastric dilatation
Most common tumor of aged macaques?
ileocecal adenocarcinoma
Clinical signs of ileocecal adenocarcinoma in macaques?
Weight loss, anorexia, scant feces or diarrhea, palpable mass in R cranial quadrant, fecal occult blood positive (if ulceration)
Most common location for metastasis of ileocecal adenocarcinoma in macaques?
1’: lymph nodes
2’: liver
3’: peritoneum leading to carcinomatosis
Common causes of rectal prolapse in macaques?
Stress
Diarrhea
Is amyloidosis in NHP primary or secondary?
secondary
Type of amyloid depositied in NHP?
AA
Precursor is serum Amyloid A
Predisposing conditions for amyloidosis in NHP?
chronic vascular catheterization
ulcerative colitis
chronic osteoarthritis
ASSOC WITH CHRONIC SYSTEMIC INFLAMMATION
clinical signs of amyloidosis in NHP?
weight loss, hepatic enlargement, protein-losing enteropathy, chronic renal disease, diarrhea
normochromic normocytic anemia, hypoalbuminemia
With islet amyloid, see diabetes mellitus
what organs does amyloid deposit into in NHP?
Liver, spleen, SI, renal medulla, adrenal glands, stomach, colon
Gross findings with amyloidosis?
Enlarged tan waxy liver, friable
Pale renal medulla with papillary necrosis, erosion, hemorrhage
Small intestinal mucosa thickened and corrugated
Enlarged pale waxy spleen
Stain to Id amyloid on slides?
Congo Red– birefringent, green
Most common signalment for fatal fasting in macaques?
obese adult females
Clinical signs associated with fatal fasting system?
History of anorexia
See weight loss, sudden death, azotemia, ketonuria, glucosuria
Gross findings of fatal fasting syndrome?
Enlarged pale friable liver (hepatic lipidosis vs amyloid)
Pale soft kidneys
Abdominal fat necrosis
Abundant fat stores +/- saponification of fat
Microscopic findings of fatal fasting syndrome?
Hepatocellular and renal tubular vacuolation with lipid
In what NHP species is amyloid deposition in the pancreas most likely to cause diabetes mellitus?
Macaca nigra (celebes crested macaque)
What NHP species has an absolute requirement for vitamin C in the diet?
all of them!
What are clinical signs with scurvy in NHP?
Rhesus–>lameness, periarticular hemorrhage, cutaneous bruising, gingival hemorrhage, loose teeth
Squirrel monkeys– subcutaneous, subperiosteal hemorrhage of head, cephalohematomas
Reactive arthritis is associated with what pathogen in NHP?
Enteric Shigella
Clinical signs of reactive arthritis in NHP?
Lameness, joint swelling 1-2 months after episode of clinical or subclinical enteric disease
Can see severe muscle atrophy, joint contracture
ASEPTIC–>due to ab: ag complex deposition in joint
Common cardiovascular lesions in aged NHP?
Valvular endocardiosis
Atherosclerosis
What is the etiology of rhabdomyolysis?
Conspecific crush trauma- usually multiple adult females, sometimes subadult males
Clinical signs of rhabdomyolysis
Soft tissue damage of face, elbows, thighs, ankles with necrosis, hemorrhage, and edema
Pigmentary nephrosis–> Tubular necrosis and renal failure can occur w anuria
What species is endometriosis found in?
Menstruating species
Location of endometriosis?
Caudal abdomen most common- assoc with repro organs but can be found anywhere
Gross findings of endometriosis?
Firm white stellate or gunpowder foci
Soft reddish brown cystic masses (‘chocolate cyst’)
Hemoperitoneum, stricture, hydronephrosis secondary to invasion or cyst rupture
Microscopic diagnostic criteria of endometriosis?
Presence of both stroma and glandular cells
Most common reproductive tract tumor in macaques?
Uterine leiomyoma
Also see endometrial polyps
Macaque placentation?
Bidiscoidal hemochorial placentation
Baboon placentation?
Monodiscoidal hemochorial placentation
Marmoset placentation?
Bidiscoidal hemochorial placentation with formation of vascular anastamoses between placentas of twins
Clinical signs of Tb in NHP?
rapid wasting, tachypnea, cough, enlarged LN, hepatosplenomegaly
Most commonly subclinical until severe
Describe the grading scale for intradermal Tb test of NHP.
Grade 0-5
0-negative, no change
1-negative, eyelid has mild bruising
2- negative, variable erythema with NO SWELLING
3- Indeterminate, varle degree of erythema, minimal swelling or slight swelling without erythema
4- positive; Obvious swelling with drooping of the lid, varying degrees of erythema
5- positive; see swelling of eyelid (almost closed), NECROSIS of eye
Tuberculosis testing methods?
Interferon gamma test (not commercially available now)
Intradermal Tb test
Culture
PCR
Antibody detection in lateral flow system (Stat-pak)
Radiographs, CT
Gross findings in tuberculosis
Necrotizing granulomas to pyogranulomas in lung, hilar LN, liver, spleen, adrenal, bone, really any organ
What is the classic lesion of tuberculosis?
Tubercle- Granuloma with central caseation, no mineralization, usually in TB lymph nodes. Prominant multinucleat giant cells with rare acid-fast organisms
Primary location of infection with Mycobacterium avium?
See more enteric involvement than with M. Tb
NHP species with natural disease caused by Mycobacterium leprae?
Grows on cooler parts of body of sooty mangabeys, chimps
Bonus: animal model is armadillos d/t low body temps
Clinical signs of leprosy in NHP?
Nodular thickening of skin, subcutis, nerves
Clinical signs of Rhodococcus equi in NHP?
Anorexia, weight loss, diarrhea
Pyogranulomatous colitis, pneumonia, lymphadenitis
When do monkeys show clinical signs of Rhodococcus infection?
Environmental contaminant, opportunistic infection associated with SRV immunosuppression
Most common cause of bacterial meningitis in NHP?
Streptococcus pneumoniae
Most common signalment for Strep pneumoniae infection in NHP?
Young, recently stressed animals
Gross findings of Strep pneumoniae in NHP
Fibrinosuppurative meningitis, arthritis, pneumonia
Where does Staph aureus come from in NHP infections?
Commensal skin bacteria, contaminant
Clinical signs of Staph aureus
Associated with chronic catheterization, Type D retrovirus immunosuppression.
See abscesses anywhere
NHP species most commonly affected by Dermatophilus congolensis?
Aotus
Histopathologic features of Dermatophilus congolensis
Filamentous branching to septate bacteria with beaded appearance (looks like a conga line of bacteria)
Acanthosis with keratin crust, neutrophils, proteinaceous material
Pathogenesis of listeriosis in NHP.
Ingestion–>penetration of GI mucosal barrier–>disseminated via macrophage–>tropism for CNS and gravid uterus
Lesions associated with Listeria in NHP
Placentitis, abortion, stillbirth, neonatal death associated with septicemia (pneumonia, meningoencephalitis)
Rare dz in adults, may bee meningoencephalitis
Clinical signs and etiologic agent of tetanus
Agent- Clostridium tetani
Clinical signs- stiff gait, extensor rigidity, grimace, opisthotonus
Most common Shigella species in NHP?
Shigella flexneri
Also S. dysenteriae, S. boydii, S. sonnei
Transmission for Shigella?
fecal-oral
Cause of lesions with Shigella infection?
Shiga-toxin damages epithelial cells, stimulates fluid secretion and hemorrhage
Clinical signs of Shigella in NHP?
Leukocytosis, neutrophila with left shift, azotemia, metabolic acidosis, hyponatremia, hypokalemia
Carriers common w dz in face of stress. Necrotizing ulcerative gingivitis, colitis
How to diagnose Shigella
Culture of feces, gingival mucosa
Most common species of Campylobacter in NHP?
Campy coli, Campy jejuni
Others- C. fetus, C. laridis, C. sputorum, C. hyointestinalis, C. troglodytis
Needs for culture of Campylobacter?
42C incubation temp, extra time, microaerophilic environment
Name the two species of Helicobacter in NHP
H. heilmannii
H. pylori
Clinical signs of Helicobacter in NHP
vomiting, subclinical
Gross lesions of Helicobacter in NHP
Gastritis
Clinical findings with Yersiniosis?
necrotizing enteritis, lymphadenitis, abortion/stillbirth, diarrhea, depression, vomiting, acute abdomen, hematochezia
Pathologic findings of Yersinia in NHP?
Enteric–>hemorrhagic ulcerative enterocolitis
Septicemic–>foci of necrosis/abscessation in liver, spleen, mesenteric lymphadenitis
Causative agent of Tularemia
Franciscella tularensis
Gross findings of tularemia?
White foci of caseous necrosis in spleen, liver
Pneumonitis, glomerulitis, enteritis, lymphadenitis
Clinical signs of Klebsiella pneumoniae in NWM?
suppurative lobar pneumonia, meningitis, peritonitis, peracute septicemia, air sacculitis in Aotus
Cause of bloody nose syndrome in cynos?
Moraxella catarrhalis
Clinical signs of Moraxella in NHP
Mucohemorrhagic rhinitis, epistaxis
Gross findings of Burkholderia pseudomallei in NHP?
paresis/paralysis associated with vertebral osteomyelitis
abscessation of lung, liver, spleen, soft tissue, skin
Etiologic agent of meliodosis?
Burkholderia pseudomallei
2 most common families of enveloped DNA viruses in monkeys?
Poxviridae
Herpesviridae
3 subfamilies of herpesviruses in NHP?
Alphaherpesvirus
Betaherpesvirus
Gammaherpesvirus
4 most common families of nonenveloped DNA viruses?
Adenoviridae
Polyomaviridae
Papillomaviridae
Parvoviridae
Name 4 orthopoxviruses of significance in NHP
Monkeypox
Cowpox
Variola (smallpox)
Ectromelia virus (mousepox)
Name the yatapoxviruses
Yaba monkey tumor virus
Yaba-like disease virus (benign epidermal monkey pox)
Transmission of monkeypox?
Aerosol, direct contact, biting insects
Gross findings of monkeypox in NHP?
Epidermal hyperplasia and necrosis with keratinocyte swelling
Papules, vesicles, central necrosis of skin
Intracytoplasmic inclusion bodies
Hemorrhagic necrosis of solid organs
Natural reservoir for cowpox virus?
rodents
Clinical signs of cowpox in NHP
Erythematous papules on face, scrotum, palmar/plantar surfaces
Cells infected by Yaba monkey tumor virus
Histiocytes (others infect epithelial cells)
Clinical signs of Yaba monkey tumor virus?
multiple rapidly growing SQ nodules on extremities that regress in 6-12w
Clinical signs of Yaba-like dz virus and alternate name?
Alternate name- benign epidermal monkey pox, Orteca dz (found in Oregon, Texas, California)
Clinical signs–>raised cutaneous nodules w ulceration/central umbilication of face, lips, nostrils, thorax, perineum, extremities. Self-limiting w resolution in 3-4 weeks
Inclusions found in poxviruses?
Intracytoplasmic
Alphaherpesviruses found in NHP?
simplexvirus
varicellovirus
Betaherpesviruses found in NHP?
Cytomegalovirus
Gammaherpesviruses found in NHP?
Lymphocryptovirus
Rhadinovirus
Clinical signs of simplexviruses in host species?
Oral or genital vesicles/ulcers
Clinical signs of simplexviruses in aberrant species?
Severe dz, often fatal
Natural host of B virus?
macacine herpesvirus 1
Only found in macaques
How long does infection with B virus last?
Persistent lifelong infection
Signs of B virus infection in humans?
Hx of exposure to macaque or fomite
Flu-like, fever, headache, vesicular rash at site of inoculation, neurologic disease leading to fatal encephalitis
Tx for humans with herpes B
acyclovir
Signs of B virus infection in macaques?
Only usually seen in acute phase. Vesicles progressing to ulcer on mucous membranes, skin; conjunctivitis with rare systemic disease
Intranuclear inclusions on histopath
Host of herpesvirus papio-2
baboons
Natural host of herpes T
aka herpesvirus tamarinus, now called Saimiriine herpesvirus 1 (SaHV-1)
natural host-squirrel monkey
Examples of aberrant hosts with disease caused by saimiriine herpesvirus 1
owl monkeys, marmosets, tamarins
See fatal disease w exposure to squirrel monkeys
Signs of human herpes simplexvirus 1 in NHP?
See dz in owl monkeys and callitrichids (marms and tamarins)
Clinically, grossly, microscopically indistinguishable from SaHV-1
Necrotizing vascular dermatitis, blepharitis, stomatitis, multiorgan necrosis w IN inclusions
Clinical signs of aberrant herpesviral infection in callitrichids and 2 causative agents?
Causes:
human herpes simplex 1
saimiriine herpesvirus 1
Signs:
Pruritis, anorexia, depression, fever, death; excessive salivation, conjunctivitis, vesicles; CNS involvement (ataxia, paralysis, blindness, seizures)
Cercopithecine herpesvirus-9 alternate name and clinical signs
aka simian varicella virus
see depression, dyspnea, vesicular or vesiculohemorrhagic dermatitis, hemorrhagic GI ulceration, pulmonary edema, systemic necrotizing lesions
Cytomegaloviruses? species specific or wide host range
species-specific viruses with ubiquitous distribution
Rhesus cytomegalovirus- etiologic agent, location of latent infection
Etiology: macacine herpesvirus 3
latency in renal epithelium (shed in urine)
Lesions of rhesus CMV
Only see with immunosuppression
necrotizing hepatitis, splenitis, enterocolitis, pancreatitis, interstitial pneumonia, orchitis
Segmental proliferative hemorrhagic enterocolitis in SIV, also hemorrhagic encephalitis, meningomyelitis
Type of herpesvirus that is a cause of lymphomas in NHP?
gammaherpesviruses
What does callitrichine herpesvirus 3 cause, and in which species?
B cell lymphoma in marmosets
Clinical signs of macacine herpesvirus 4 and in which species?
Non-Hodgkin lymphoma, B cell lymphoma in rhesus
Also hairy leukoplakia
Inclusion body fun! Negri bodies are diagnostic for what virus or type of virus? IC or IN?
Rabies!
intracytoplasmic
Inclusion body fun! Guarnieri bodies are diagnostic for what virus or type of virus? IC or IN?
Cowpox!
intracytoplasmic (it’s a pox)
Inclusion body fun! Bollinger bodies are diagnostic for what virus or type of virus? IN or IC?
fowlpox virus
intracytoplasmic (it’s a pox)
Inclusion body fun! Molluscum bodies are diagnostic for what virus or type of virus? IC or IN?
Molluscum contagiosum
intracytoplasmic
Inclusion body fun! Cowdry type A bodies are diagnostic for what virus or type of virus? IC or IN?
Herpesvirus, yellow fever
intranuclear
Inclusion body fun! Cowdry type B bodies are diagnostic for what virus or type of virus? IC or IN?
adenovirus, poliovirus
Intranuclear
Which virus in macaques is associated with retroperitoneal fibromatosis
rhesus rhadinovirus 1 (aka rhesus fibromatosis herpesvirus)
simian retrovirus
Rhesus rhadinovirus 2 has a tropism for what cell type?
CD20+ (B cells)
Causes B and T cell lymphoma in SIV or SRV infected macaques
What do herpesvirus ateles 2 and 3 and herpesvirus saimiri 2 cause in aberrant NWM?
T cell lymphoma or lymphocytic leukemia in owl monkeys, tamarins, marmosets, howler monkeys, spider monkeys
Lesions of adenoviral disease in NHP?
often no gross lesions; may see necrosis and hemorrhage in pancreas, lung, kidney, liver
Clinical signs of titi monkey adenovirus?
Hepatitis, pneumonia in titis
Self-limiting flu-like dz in humans and marmosets
Lesions associated with simian vacuolating virus-40?
Multifocal leukoencephalopathy
Interstitial pneumonia
Interstitial nephritis
Where is SV-40 latent in NHP?
renal epithelium, lymphocytes, oligodendrocytes
Family and type of inclusion bodies seen with SV-40?
polyomaviridae
intranuclear inclusions
Parvoviruses cause what type of inclusion bodies?
IN
The following viruses are examples of what?
Filoviridae Orthomyxoviridae Paramyxoviridae Arteriviridae Togaviridae Flaviviridae Arenaviridae Retroviridae
Enveloped RNA viral families
Reoviridae, picornaviridae, caliciviridae, and coronaviridae are examples of what?
Nonenveloped RNA viral families
What are the two most important filoviruses in NHP?
Marburg
Ebola
What are reservoirs for filoviruses?
fruit bats
Syndrome/signs associated with filoviruses?
viral hemorrhagic fevers, see DIC, lymphoid necrosis, fibrin deposition
Type of flu virus that naturally infects NHP?
influenza A
Influenza B experimental in cynos
Family for flu viruses?
Orthomyxoviridae
Measles reservoir host?
Humans
Transmission for measles?
aerosol, droplet
Family for measles? Genus?
Paramyxoviridae
Morbillivirus
Symptoms of measles in NHP?
Immunosuppression
OWM: bronchointerstitial pneumonia
NWM: necrotizing gastroenteritis
Type of sensitivity reaction that results in measles rash?
Arthus-type reaction (localized type III hypersensitivity Ag-Ab complex)
Species affected by paramyxovirus saguinus?
Saguineus sp- cotton top tamarins, moustached tamarins, white-lipped tamarins
Family of simian hemorrhagic fever?
Arteriviridae
Natural reservoir of simian hemorrhagic fever?
Patas monkeys (African NHP)
Key finding for simian hemorrhagic fever?
Hemorrhage in proximal duodenum
What members of togaviridae are emerging viruses in NHP?
Chikungunya
EEE, WEE, VEE
Common clinical signs of flaviviruses in NHP?
meningoencephalitis, hemorrhagic fever
Examples of flaviviruses?
Dengue Japanese encephalitis virus St. Louis encephalitis virus West Nile Yellow Fever Zika
2 transmission cycles for yellow fever?
Urban (human + Aedes aegypti)
Sylvatic (forest primates, canopy mosquitoes)
Main vector for urban yellow fever?
Aedes aegypti mosquito
Does yellow fever cause more severe signs in OWM or NWM?
NWM
Clinical signs of yellow fever?
fever, lethargy, jaundice, vomiting/hematemesis, hemorrhage
What virus has both Councilman’s bodies and Torres bodies?
Yellow fever
Councilman body–>eosinophilic intracytoplasmic inclusion, sign of hepatocellular apoptosis
Torres body– small, irregular IN body; intranuclear coagulum of host protein
How is zika transmitted?
Arthropods, STD
Family of lymphocytic choriomeningitis virus?
Arenaviridae
Causative agent of callitrichid hepatitis?
LCMV
Transmission of LCMV to NHP and species affected?
Marmosets, other callitrichids
D/t feeding pinkies or exposure to mouse excretion
Gross lesions of LCMV in marmosets?
icterus, enlarged yellow tan mottled liver, enlarged spleen, sq and muscle hemorrhage, pleural/peritoneal effusion
Histology findings in LCMV of marmosets?
hepatic necrosis, Councilman’s bodies, multi-organ necrosis, phlebitis, vasculitis
What type of virus is simian retrovirus (SRV)?
betaretrovirus
What type of virus is simian t-cell leukemia virus (STLV))?
deltaretrovirus
What type of virus is simian immunodeficiency virus (SIV)?
lentivirus
What type of virus is simian foamy virus (SFV)?
spumaretrovirus
How many serotypes of SRV are there?
5- only 1, 2, 5 of clinical significance
How is SRV transmitted?
saliva, biting, grooming, vertically
How long does it take for an NHP to clear SRV infection?
They don’t - persistent infection
Clinical signs associated with SRV in NHP?
Opportunistic infections with immunosuppression
Noma (cancrum otis)–>gingivitis with osteonecrosis
retroperitoneal fibromatosis
How is STLV transmitted?
Breeding, breast feeding, transfusion, contaminated blood products
Which species have worse disease with SIV: Asian or African?
Asian species (rhesus, cyno)
Model virus for HIV in humans?
SIV or SHIV recombinant (HIV genome into SIV backbone)
What are the three infection profiles for SIV?
normal (75%), disease course 18 months Rapid progressor (20%), death within 3-4 months Elite controller (5%); immune response limits viral replication
What is the major cause of death in SIV-infected monkeys?
opportunistic infections due to immunosuppression
Transmission for hepatitis A virus?
fecal-oral
Reservoir for encephalomyocarditis virus?
rodents
Clinical signs of encephalomyocarditis virus?
dyspnea, sudden death
clinical signs of hepatitis A in NHP?
uncommon, nonspecific with anorexia/diarrhea in some chimps