AFIP Wednesday Slide Conference - No. 10
- 10 November 1999
- Conference Moderator:
LTC David G. Young
US Army Center for Health Promotion and Preventive Medicine
Directorate of Toxicology
Aberdeen Proving Ground, MD 21010-5422
- NOTE: Click on images for larger views. Use
browser's "Back" button to return to this page.
Return to WSC Case Menu
- Case I - ND1 (AFIP 2676132)
- Signalment: Four adult mink (Mustela vison) carcasses
were submitted to North Dakota State University Veterinary Diagnostic
- History: Clinical signs included: anorexia, dyspnea,
tremors, seizures, and ataxia. Ten percent of affected animals
died, primarily dark and mahogany color varieties. Death occurred
in some animals as long as three weeks after the onset of symptoms.
Mink on the ranch were vaccinated for canine distemper virus,
mink enteritis virus and botulism.
- Gross Pathology: Diffuse congestion of lungs and livers
in all animals.
- Laboratory Results: Bacterial culture of brain tissue
from all animals yielded low numbers of mixed contaminants. Fluorescent
antibody and virus isolation tests performed on brain tissue
were negative for pseudorabies virus, canine distemper virus
and rabies virus. Immunohistochemical stains for Newcastle's
disease virus, Listeria monocytogenes, Toxoplasma gondii and
Neospora caninum were negative.
- Aleutian disease parvovirus (ADV) was identified through
PCR examination of mesenteric lymph node, spleen, brain, and
liver. DNA sequencing of the isolate showed the capsid sequence
of the virus had several amino acid differences from other characterized
pathogenic ADV isolates suggesting a tropism for the central
Contributor's Diagnosis and Comments: Meningoencephalitis,
nonsuppurative, diffuse, subacute, severe with gliosis, astrocytosis
and satellitosis due to Aleutian Disease parvovirus.
Causes of non-suppurative meningoencephalitis in mink include
Encephalitozoon spp., Toxoplasma gondii, a Sarcocystis neurona-like
protozoan, Newcastle disease virus (NDV), pseudorabies virus
(PRV), canine distemper virus (CDV), and although not reported
but still a consideration, rabies virus (RV). Aleutian mink disease
parvovirus (ADV) infection in adult animals is associated with
glomerulonephritis, interstitial nephritis, disseminated plasmacytosis
and polyarteritis, plasma cell hepatitis with bile duct proliferation,
uveitis, and hyperplastic intrapulmonary lymphoid tissue. Infection
of newborn mink kits results in acute interstitial pneumonia.
Nonsuppurative encephalomyelitis is reported in ferrets seropositive
for ADV. Idiopathic nonsuppurative meningoencephalitis in ranch
mink, and lymphoplasmacytic meningitis, arteritis and periarteritis
have been described in mink seropositive for ADV; however, severe
meningoencephalitis associated with tissues from which ADV DNA
has been identified has not been reported.
- Variability in lesion location and intensity associated with
ADV infections appears to be at least in part dependent upon
factors such as age, color variety, immune status of the host,
and strain of the virus. The aforementioned interstitial pneumonia
in kits may show wide variability in mortality and lesion development
dependent upon the strain of ADV encountered. Nervous system
disease associated with ADV also may be the result of similar
or as yet undefined host factors.
- Pathogenicity of ADV has been suggested to be determined
by the capsid proteins. The capsid sequence of the virus identified
in this outbreak, showed several amino acid differences from
other characterized pathogenic ADV isolates. Perhaps, these few
differences endow the isolate with the ability to produce more
severe disease in the central nervous system.
- AFIP Diagnosis: Brain: Meningoencephalitis, nonsuppurative,
multifocal, moderate, with necrosis, mink (Mustela vison), mustelid.
- Conference Note: Aleutian mink disease (AMD) is caused
by Aleutian Disease Virus (ADV) (Genus Parvovirus, Family Parvoviridae),
a small (28nm), enveloped, single-stranded DNA virus. ADV was
originally characterized as affecting only mink with the Aleutian
phenotype, but it is now known to affect all colors of mink to
varying degrees, as well as ferrets. Forty-two percent of adult
female mink were positive for ADV antibody in one study, and
skunks, raccoons, and foxes have been reported to have titers
to ADV. Transmission can be horizontal or vertical, and the incubation
period is generally 5-6 months. The two classic features of AMD
are multisystemic plasmacytic inflammation and hypergammaglobulinemia.
ADM is used as an animal model for immune-mediated glomerulonephritis.
- Contributor: North Dakota State University, Fargo,
1. Aasted B, Alexandersen S, Christensen J: Vaccination with
Aleutian mink disease parvovirus (AMDV) capsid proteins enhances
disease, while vaccination with the major non-structural AMDV
protein causes partial protection from disease. Vaccine 16:1158-1165,
- 2. Alexandersen S: Acute interstitial pneumonia in mink kits:
experimental reproduction of the disease. Vet Pathol 23:579-588,
- 3. Alexandersen S, Larsen S, Aasted B, Uttenthal A, Bloom
ME, Hansen M: Acute interstitial pneumonia in mink kits inoculated
with defined isolates of Aleutian mink disease parvovirus. Vet
Pathol 31:216-228, 1994
- 4. Bjerkas I: Brain and spinal cord lesions in encephalitozoonosis
in mink. Acta Vet Scand 31:423-432, 1990
- 5. Bloom ME, Fox JM, Berry BD, Wolfinbarger JB: Construction
of pathogenic molecular clones of Aleutian mink disease parvovirus
that replicate both in vivo and in vitro. Virol 251:288-296,
- 6. Dietz HH, Henriksen P, Lebach M, Henricksen SA: Experimental
infection with Toxoplasma gondii in farmed mink (Mustela vison
S.). Vet Parasitol 47:1-7, 1993
- 7. Drommer W, Trautwein G: Pathogenesis of Aleutian mink
disease. VII. Chronic hepatitis with bile duct proliferation.
Vet Pathol 12:77-93, 1975
- 8. Dubey JP, Hedstrom OR: Meningoencephalitis in mink associated
with a Sarcocystis neurona-like organism. J Vet Diagn Invest
- 9. Haagsma J, Rondhuis PR, Lensing HH: Meningo-encephalitis
in mink caused by NCD virus. Tijdschr Diergeneeskd 100:633-640,
- 10. Hadlow WJ: Ocular lesions in mink affected with Aleutian
disease: Vet Pathol 19:5-15, 1982
- 11. Hadlow WJ, Race RE, Kennedy RC: Comparative pathogenicity
of four strains of Aleutian disease virus for pastel and sapphire
mink. Infect Immun 41:1016-23, 1983
- 12. Jericho KW: Intrapulmonary lymphoid tissue in mink infected
with Aleutian disease virus. Res Vet Sci 32:206-212, 1982
- 13. Kanno H, Wolfinbarger JB, Bloom ME: Identification of
Aleutian mink disease parvovirus transcripts in macrophages of
infected adult mink: J Virol 66:5305-5312, 1992
- 14. Kimman TG, van Oirschot JT: Pathology of Aujeszky's disease
in mink. Vet Pathol 23:303-309, 1986
- 15. Mori S, Nose M, Miyazawa M, Kyogoku M, Wolfinbarger JB,
Bloom ME: Interstitial nephritis in Aleutian mink disease. Possible
role of cell-mediated immunity against virus-infected tubular
epithelial cells. Am J Pathol 144:1326-1333, 1994
- 16. Nieto JM, Alvarez C, Flores JM, Romano J: Glomerular
lesions in Aleutian disease of mink (Mustela vison): a morphological
and differential morphometrical study. Histol Histopathol 6:141-148,
- 17. Oie KL, Durrant G, Wolfinbarger JB. Martin D, Costello
F, Perryman S, Hogan D, Hadlow WJ, Bloom ME: The relationship
between capsid protein (VP2) sequence and pathogenicity of Aleutian
mink disease parvovirus (ADV): a possible role for raccoons in
the transmission of ADV infections. J Virol 70:852-61, 1996
- 18. Schmitz JA, Wustenberg W, Gorham JR: Nonsuppurative meningoencephalitis
of unknown etiology in mink. Vet Pathol 22:112-116 1985
- 19. Sutherland-Smith MR, Rideout BA, Mikolon AB, et al: Vaccine-induced
canine distemper in Europeon mink, Mustela lutreola. J Zoo Wildl
Med 28:312-318, 1997
- 20. Welchman D de B, Oxenham M, Done SH: Aleutian disease
in domestic ferrets: diagnostic findings and survey results.
Vet Rec 132:479-84,1993
- Case II - C99094102 (AFIP 2689020)
- Signalment: A 4-week-old, female, dachshund puppy
- History: This puppy had been sick for one day. A littermate
had died the previous day and two others were weak. The puppy
presented for necropsy had an increased respiratory rate and
labored breathing for 6 hours prior to death. The owner had vaccinated
against DHLP/CPV/CCV and dewormed with Strongid two days prior
- Gross Pathology: The lungs were mildly congested.
Epicardial blood vessels were injected and pronounced. No other
significant gross findings were noted.
- Contributor's Diagnosis and Comments: Heart, myocardium:
Myocarditis, interstitial, nonsuppurative, mild to moderate,
subacute, with intranuclear inclusion bodies, dachshund, canine.
There was mild to moderate interstitial inflammation in the myocardium
composed of macrophages and occasional lymphocytes. There was
degeneration of occasional myocardial fibers characterized by
cytoplasmic eosinophilia and loss of striations. Some myocardial
fibers had enlarged nuclei with amphophilic to basophilic intranuclear
inclusion bodies. Microscopic lesions in other tissues included
severe chronic pulmonary edema, hepatic centrilobular congestion
and multifocal lymphoid necrosis in the spleen. The lesions and
myocardial intranuclear inclusions were considered compatible
with canine parvovirus infection. Direct fluorescent antibody
staining of fixed and frozen sections of myocardium were positive
for canine parvovirus-2.
- During the original epizootic in the 1970's, canine parvovirus
produced 2 main forms of the disease: vomiting and diarrhea in
dogs of approximately 8-12 weeks of age with histologic findings
of necrotizing enteritis, and sudden death in puppies 3-8 weeks
of age with histologic findings of nonsuppurative myocarditis
with intranuclear inclusions. The myocardial form was presumed
to be due to infection while replication of myocardial cells
was occurring. In recent years, the myocardial form of the disease
has become very uncommon, and disease associated with CPV-2 is
attributed primarily to the enteric form. In recent weeks, we
have seen several cases of the myocardial form, and at this time
the significance is unknown.
- AFIP Diagnosis: Heart: Myocarditis, lymphohistiocytic,
necrotizing, diffuse, moderate, with intranuclear inclusion bodies,
- Conference Note: Canine parvovirus type 2 (CPV2) is
a small (28nm), enveloped, single-stranded DNA virus. Another
parvovirus, feline panleukopenia virus, is thought to have mutated
to form the original CPV2. CPV2 can naturally infect most wild
canids including coyotes, bush dogs, wolves, crab eating foxes,
and has experimentally infected raccoons, cats, ferrets, and
- The myocardial form of CPV2 results from infection of neonatal
(<2 weeks) puppies that are deprived of colostrum or are born
to bitches that have no previous exposure to CPV2 antigen. CPV2
infection occurs oronasally; the virus enters epithelial and
lymphoid cells and is disseminated throughout the body. The virus
is dependent on DNA polymerase, and therefore, replicates in
rapidly dividing cells. Cardiomyocytes actively divide for approximately
two weeks after birth, thus explaining the limited window of
cardiac infection (<2 weeks cardiomyocyte susceptibility +
1-2 weeks incubation = first 1-4 weeks of life).
Clinically, animals can have a spectrum of cardiac lesions depending
on the severity of infection and the duration of infection. The
cases that are generally attributed to CPV2 present with dyspnea
or sudden death, but animals that survive the initial infection
may develop heart failure as adults as a result of myocardial
Other causes of nonsupurative myocarditis in dogs include: canine
distemper virus, canine parvovirus type 1 (minute virus of canines),
infectious canine hepatitis, vitamin E/selenium toxicity, and
- Contributor: Texas Veterinary Medical Diagnostic Lab,
Texas A&M University System, P.O. Box 3040, College Station,
- 1. Agungpriyono DR, Uchida K, Tabaru H, Yamaguchi R, Tateyama
S: Subacute massive necrotizing myocarditis by canine parvovirus
type 2 infection with diffuse leukoencephalomalacia in a puppy.
Vet Pathol 36:77-80, 1999
- 2. Hoskins JD: Canine Viral Enteritis. In: Greene's Infectious
Diseases of the Dog and Cat, ed. Greene CE, 2nd ed, pp. 40-48.
W.B. Saunders, Philadelphia PA, 1998
- 3. Robinson WF, Humtable CR, Pass DA: Canine parvoviral myocarditis:
A morphologic description of the natural disease. Vet Pathol.
- 4. Lenghaus C, Studdert MJ: Acute and chronic viral myocarditis.
Acute diffuse nonsuppurative myocarditis and residual myocardial
scarring following infection with canine parvovirus. Amer Journ
of Pathol 115(2):316-319, 1984
- Case III - MK96-944 (AFIP 2674593 )
- Signalment: 18-month-old male common marmoset, Callithrix
- History: This young adult marmoset was found dead
in his cage; clinical signs were limited to a 6 gram weight loss
over a 2 week period.
- Gross Pathology: Left lung lobes were consolidated
and diffusely reddened. 1 to 2ml of thick blood tinged fluid
was present in the left pleural cavity. Left parietal pleura
was thickened and rough.
- Laboratory Results: Bacterial cultures from thoracic
cavity and lung yielded Klebsiella pneumoniae. Enterococcus faecalis
and alpha hemolytic Streptococcus was also isolated from the
lung, but in fewer numbers.
Contributor's Diagnoses and Comments:
- 1. Lung, left: Bronchopneumonia, fibrinosuppurative, diffuse,
severe; etiology: Klebsiella pneumoniae.
- 2. Liver: Bacteremia (liver sections are not present on all
- Klebsiella pneumoniae is a gram-negative, aerobic,
encapsulated bacillus that may be cultured from soil, air, water,
and fresh vegetables; it may also occur as normal flora in the
gastrointestinal and respiratory tracts in some animals. K.
pneumoniae is an important pathogen in New World monkeys,
where it can cause lymph node abscessation, meningitis, air sacculitis,
pneumonia and peritonitis. The organism is generally considered
an opportunistic pathogen, causing disease in debilitated or
immunocompromised individuals. It can invade the body through
inhalation, aspiration, ingestion or through an open wound. It
disseminates hematogenously and can infect multiple organs. Clinical
signs include listlessness, anorexia, nasal discharge, swelling
or abscessation of lymph nodes, and/or depression. Klebsiella
pneumoniae is generally susceptible to a variety of antibiotics,
but may develop multi-drug resistance through plasmid-transfer.
Some strains may resist phagocytosis and complement-mediated
- This marmoset was part of a colony maintained in an AAALAC
accredited biomedical research facility, which were used in minimally
invasive behavioral studies. Over a 28-month period, between
December 1995 and February 1998, 49 clinical cases (out of approximately
70 marmosets) occurred, with a case fatality rate of 84%. In
this outbreak, the animals were generally young adults, with
no evidence of debilitation or pre-existing disease (which is
in marked contrast to the usual view of K. pneumoniae as an opportunistic
invader). Weight loss over one to several weeks period, was the
most consistent clinical sign. Affected animals were generally
depressed, with variable pyrexia and lymphadenopathy. Common
necropsy findings included peritonitis, pneumonia, pleuritis,
lymph node abscessation and tonsillitis. Survivors generally
manifest cervical swelling and abscessation which generally responded
to antibiotic therapy and lancing.
- A small colony of squirrel monkeys housed in different rooms
in the same building were less severely affected, with the majority
of affected animals recovering with appropriate therapy.
- Klebsiella pneumoniae was cultured from the feces
of rhesus and capuchin monkeys, which were also housed in the
building, although none of these species manifested clinical
disease. It appears likely that the infection was introduced
to the marmoset and squirrel monkey colonies by fecal contamination
of a cart that was used throughout the building. Subclinically
infected carriers, which shed pathogenic bacteria in their feces,
apparently perpetuated the infection within the colony.
- Frequent occurrence of mesenteric lymph node abscessation
and peritonitis suggest that the organism invaded through the
intestinal wall. Nodal parenchyma was frequently totally necrotic
and effaced by myriad neutrophils and bacteria. As occurred in
this case, most animals also had a terminal bacteremia, with
bacilli easily visible on H&E stained sections within large
and small vessels throughout the body. K. pneumoniae's capsule
gives the bacilli a very characteristic appearance both in sections,
smears and touch preparations. Preparation of Wright-Giemsa stained
smears or touch impressions from affected organs at necropsy
allows for a presumptive same-day diagnosis.
- The reason for the increased virulence of K. pneumoniae in
this outbreak is not apparent. Endotoxins released from the cell
wall may vary in potency from strain to strain, and a few strains
have been shown to produce enterotoxins of questionable potency.
- Changes in husbandry practices that help to eliminate the
infection from the colony included: elimination of the use of
any equipment between species; repeat fecal, nasal, and oral
cultures on all colony animals to identify carriers; separation
of carriers and their cagemates from uninfected animals; treatment
of the entire colony with neomycin and repeated treatment and
culture of identified carriers; washing of all fruit with 10%
- AFIP Diagnoses:
- 1. Lung: Pneumonia, fibrinosuppurative and hemorrhagic, acute,
diffuse, severe, with myriad bacilli, common marmoset (Callithrix
jacchus), non-human primate.
2. Liver: Bacteremia.
- Conference Note: Among laboratory animals, infection
with K. pneumoniae (Friedlander's bacillus) is
most common in non-human primates, especially those subjected
to some "stress", such as splenectomy or infection
with malaria or yellow fever. It is an important cause of pneumonia,
middle ear infections, meningitis, peritonitis, cystitis and
septic abortion. The most common bacterial isolate from non-human
primates with pneumonia is Klebsiella pneumoniae, followed by
Escherichia coli, Streptococcus pneumonia, Bordetella bronchiseptica,
Corynebacterium pseudotuberculosis, and Mycobacterium tuberculosis.
Other bacteria that may be responsible for pneumonia in non-human
primates include Diplococcus pneumoniae, Pasteurella multocida,
Haemophilus influenza and ß-hemolytic Streptococci.
- Contributor: Veterinary Resources Program, National
Institutes of Health, Bethesda, MD 20892.
- 1. Berendt RF, Knutsen GL, Powanda MC: Nonhuman primate model
for the study of respiratory Klebsiella pneumoniae infection.
Inf and Immun 22:276-281, 1978
- 2. Hunt DE, Pittillo RF, Deneau GA: Control of an acute Klebsiella
pneumoniae infection in a rhesus monkey colony. Lab Ani Care
- 3. Giles RC, Hildebrandt PK, Tate C: Klebsiella air sacculitis
in the owl monkey (Aotus trivirgatus). Lab Ani Sci 24:610-616,
- 4. Good RC, May BD: Respiratory pathogens in monkeys. Inf
and Immun 3:87-93, 1971
- 5. Obaldia N: Detection of Klebsiella pneumoniae antibodies
in Aotus l. lemurinus (Panamanian owl monkey) using an enzyme
linked immunosorbent assay (ELISA) test. Lab Anim 25:133-141,
- 6. Synder SB, Lund JE, Bone J: A study of Klebsiella infections
in owl monkeys (Aotus trivirgatus). JAVMA 157:1935-1939, 1970
- Case IV - 99-1215 (AFIP 2685269)
- Signalment: Eight-week-old, male domestic feline kitten.
- History: 4 day history of lethargy and pulmonary congestion.
The kitten was euthanized.
- Gross Pathology: The left lung lobes and right cranial
and middle lung lobes were pink/brown with indistinct, white
miliary foci intermingled. Foamy red fluid was present in the
trachea and bronchi.
- Laboratory Results: Chlamydia and bacterial cultures
were negative. Feline calicivirus was isolated from lung tissue.
Fluorescent antibody stain for feline herpesvirus was negative.
Contributor's Diagnosis and Comments:
Bronchointerstitial pneumonia, necrotizing, subacute, moderate
to severe lung. (Etiology: calcivirus).
Feline calicivirus causes infections, which generally fall into
one of several types: 1.) upper respiratory track and oral epithelium.
2.) pneumonia. 3.) ulcerative stomatitis. 4.) enteritis. 5.)
acute arthritis. 6.) chronic stomatitis.
- The type of lesions seen tends to depend on the virulence
and tropism of the strain. More than one type of lesion may occur
in a given outbreak. Some strains have a strong tropism for alveolar
type I cells resulting in severe pneumonia and up to 30% mortality.
The lesions are an acute to subacute interstitial pneumonia with
necrosis of pneumocytes and alveolar influx of neutrophils and
serum protein. Hyalin membranes may form. As the disease progresses,
type II pneumocytes proliferate along alveolar walls. Concurrent
infection with other respiratory pathogens such as feline herpesvirus-1
may be present and complicate the picture.
- AFIP Diagnosis: Lung: Bronchopneumonia, fibrinous,
necrotizing, subacute, diffuse, moderate, domestic cat, feline.
- Conference Note: Feline calicivirus (FCV) is a member
of the family Picornaviridae. It is a non-enveloped single stranded
RNA virus that replicates within the cytoplasm. Ultrastructurally,
the 35-40nm virions have a dense 20nm core and often align into
laminated arrangements. FCV is closely related genetically to
swine vesicular exanthema virus and San Miguel sea lion virus.
- FCV is a common upper respiratory infection of young cats,
but rarely produces significant clinical disease, unless animals
are immuno-compromised. As noted by the contributor, different
strains produce different lesions; pneumonic infection is generally
produced by strains that have a strong trophism for type I pneumocytes.
Damage to type I pneumocytes leads to attraction of alveolar
macrophages and replacement of type I pneumocytes with type II
pneumocytes. In the absence of significant secondary infections,
most animals recover with eventual maturation of type II pneumocytes
to type I pneumocytes, resulting in normal pulmonary architecture.
- Contributor: Arizona Veterinary Diagnostic Lab, 2831
N. Freeway, Tucson, AZ 85705-5021
1. Barr ME, Olsen CW, Scott FW: Feline Viral Diseases. In: Textbook
of Veterinary Internal Medicine. eds. Ettinger BJ and Feldmen
EC, 4th ed. Vol 1, pp409-439. W.B. Saunders, Philadelphia, PA,
- 2. Dungworth DL: The Respiratory System. In: Pathology of
the Domestic Animals, Vol 2, eds. Jubb KVF, Kennedy PC, and Palmer
N, 4th ed., pp. 539-699. Academic Press Inc. San Diego, CA,1993
- 3. Hoover EZ, Kohn DE: Experimentally Induced feline calicivirus
infection: Clinical signs and lesions. JAVMA, 166:436-468, 1975
- J Scot Estep, DVM
Captain, VC, USA
Registry of Veterinary Pathology*
Department of Veterinary Pathology
Armed Forces Institute of Pathology
(202)782-2615; DSN: 662-2615
- * The American Veterinary Medical Association and the American
College of Veterinary Pathologists are co-sponsors of the Registry
of Veterinary Pathology. The C.L. Davis Foundation also provides
substantial support for the Registry.
- Return to WSC Case Menu