JPC SYSTEMIC PATHOLOGY
HEMOLYMPHATIC SYSTEM
April 2018
H-P03

SIGNALMENT: Juvenile male cynomolgus macaque

HISTORY:  Found comatose and hypothermic.  Necropsy findings included cachexia, severe congestion and edema of the lungs, and mild discoloration of the liver.

HISTOPATHOLOGICAL DESCRIPTION: 

SLIDE A: Peripheral blood smear:  Few erythrocytes (up to five per 40X high power field) contain intracellular parasites that vary in size from 1-2 um ring forms to larger trophozoites that occupy up to 50% of the erythrocyte.  The cytoplasm of the parasites stains light blue and often contains small, 1 um or less, black-brown, anisotropic pigment granules (hemozoin or malaria pigment).  There is mild anisocytosis and polychromasia of erythrocytes.

MORPHOLOGIC DIAGNOSIS:  Cytologic specimen, peripheral blood smear:  Trophozoites, intraerythrocytic, few, with hemozoin pigment, etiology consistent with Plasmodium sp., cynomolgus macaque (Macaca fascicularis), nonhuman primate.

SLIDE B: Spleen: Multifocally, primarily within the red pulp, there are increased numbers of macrophages that often contain abundant intracytoplasmic, faintly birefringent, golden-brown, globular pigment (hemozoin).  Diffusely, periarteriolar lymphoid sheaths are moderately expanded by increased numbers of lymphocytes (lymphoid hyperplasia).

Liver: Kupffer cells are mildly increased in number and often contain abundant intracytoplasmic hemozoin as previously described.  Multifocally, there are moderate numbers of lymphocytes and plasma cells surrounding portal areas and to a lesser extent surrounding centrilobular veins.

MORPHOLOGIC DIAGNOSIS:

  1. Spleen, white pulp: Lymphoid hyperplasia, diffuse, moderate.
  2. Spleen, red pulp: Histiocytosis, multifocal, moderate, with abundant intrahistiocytic hemazoin pigment.
  3. Liver: Kupffer cell hyperplasia, multifocal, moderate with abundant intrahistiocytic hemazoin pigment, and mild, multifocal, periportal lymphoplasmacytic hepatitis.

CAUSE:  Plasmodium sp. (P. knowlesi)

ETIOLOGIC DIAGNOSIS:  Plasmodial erythroparasitemia

CONDITION:  Malaria

GENERAL DISCUSSION: 

LIFE CYCLE:

  1. Vertebrate host: (asexual reproduction): Female mosquito penetrates skin of vertebrate host (in research settings, rodents are inoculated intraperitoneally and NHPs are inoculated intravenously) à introduces sporozoites into peripheral circulation à exoerythrocytic/hepatic stage with intrahepatocyte development from sporozoite to schizont that develop thousands of merozoites à merozoites released from schizonts à merozoites enter erythrocytes (erythrocytic stage) and reside in parasitophorous vacuoles (some species appear as ring forms; the variability of location within erythrocytes and different morphologies assist in speciation) à enlarge into trophozoites à transform into schizonts that undergo asexual division to form merozoites à relatively synchronous RBC lysis that releases merozoites to infect other RBCs
  2. Invertebrate host (sexual reproduction), commonly Anopheles mosquitoes: Within the vertebrate host, some merozoites develop into gametocytes and remain in the blood as micro- and macrogametocytes à ingested by a female mosquito à in the mosquito’s stomach, male and female gametocytes develop into gametes, which fuse to form a motile zygote (ookinete), which enters the gastric mucosa and further develops to the oocyst stage in the gastric stroma à repeated nuclear division à rupture of oocyst à sporozoites released into hemolymph à migration to salivary gland à transferred to vertebrate host during blood meal

PATHOGENESIS: 

TYPICAL CLINICAL FINDINGS:

TYPICAL GROSS FINDINGS:

TYPICAL LIGHT MICROSCOPIC FINDINGS:

ULTRASTRUCTURAL FINDINGS:

ADDITIONAL DIAGNOSTIC TESTS: 

DIFFERENTIAL DIAGNOSIS:

Blood Parasites in NHPs:

COMPARATIVE PATHOLOGY:

FAMILY PLASMODIIDAE

OTHER INTRAERYTHROCYTIC PARASITES:

REFERENCES:

  1. Brockus CW.   In:  Lattimer, KS.  Duncan and Prasse’s Veterinary Laboratory Medicine Clinical Pathology.  5th Ed. Ames, IA: Wiley-Blackwell; 2011:21.
  2. Calle PP, Ott Joslin J. New world and old world monkeys.  In: Miller RE, Fowler ME.  Fowler’s zoo and wild animal medicine. Vol. 8.  Louis, MO: Elsevier; 2015: 314.
  3. Fitz-Choy SH. Parasitic diseases.  In: Boulianne M., ed. Avian Disease Manual. 7th Jacksonville, FL: American Association of Avian Pathologists; 2013:159-163.
  4. Galinski MR, Barnwell JW. Nonhuman primate models for human malaria research.  In: Abee CR, Mansfield K, Tardiff S, Morris T, eds.  Nonhuman Primates in Biomedical Research: Diseases, Vol. 2.  2nd ed.  Waltham, MA: Academic Press; 2012:299-323.
  5. Lombardini ED, Gettayacamin M, Turner GDH, Brown AE. A review of Plasmodium coatneyi – macaque models of severe malaria.  Vet Pathol. 2015;52(6):998-1011.
  6. Smith JA. Passeriformes (songbirds, perching birds).  In: Miller RE, Fowler ME.  Fowler’s zoo and wild animal medicine. Vol. 8.  Louis, MO: Elsevier; 2015: 243-244.
  7. Strait K, Else JG, Eberhard ML. Parasitic diseases of nonhuman primates.  In: Abee CR, Mansfield K, Tardiff S, Morris T, eds.  Nonhuman Primates in Biomedical Research: Diseases, Vol. 2.  2nd ed.  Waltham, MA: Academic Press; 2012:213-218.
  8. Wallace RS. Sphenisciformes (penguins).  In: Miller RE, Fowler ME.  Fowler’s zoo and wild animal medicine. Vol. 8.  Louis, MO: Elsevier; 2015: 86.


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