4 -+ year old male rhesus macaque (Macaca mulatta)This rhesus macaque was inoculated with SIVmac251as part of an experimental single-cycle SIV vaccination trial and had undergone routine phlebotomies. Twenty months post inoculation, the animal developed chronic weight loss (25% weight loss over four months.) The animal was also reported to have anorexia and chronic diarrhea. On clinical examination, the animal was in poor body condition and was observed to have pale mucous membranes as well as a large palpable abdominal mass. Due to suspicion of progression to simian acquired immune deficiency syndrome, the animal was humanely euthanized.
A large, roughly oval, firm, encapsulated mass was adhered to the serosal surface of the mid-distal colon.Â On cut surface, the mass was friable, with interlacing patterns of pale tan to white.Â The mucosa of the colon was thickened and pale with an irregular cobblestone appearance.Â The mucosa of the duodenum and most of the jejunum was also thickened with prominent lacteals.Â The right lung lobes were atelectatic with multifocal to coalescing white fibrotic areas and firm white raised nodules on the tissue margins.Â A large thrombus partially obstructed a pulmonary artery.Â The left lung lobes were red and diffusely edematous.Â There were no gross lesions noted on examination of the central nervous system.
Colon: Replacing and disrupting the muscular layers and submucosa of the colon is a large region of liquefactive necrosis that is characterized by innumerable degenerative neutrophils, large numbers of macrophages, fewer plasma cells, and lymphocytes admixed with fibrin, cellular and karyorhectic debris (necrosis).Â Interspersed with the inflammation and necrosis are marked numbers of 2-3 um, pale basophilic, round to oval, protozoal organisms that have apically oriented nuclei.Â Large numbers of viable and non-viable organisms are also noted within macrophages.Â Numerous colonic crypts also contain protozoal organisms similar to those described above.Â Inflammatory cells breach the colonic basement membrane in multiple places and to varying degrees separate and surround colonic crypts.Â Endothelial cells of the vasculature within the abscesses are plump, branched, and reactive.Â The serosa is proliferative and thickened with abundant fibroplasia, edema, and scattered numbers of inflammatory cells in similar proportions to those noted above.Â Submucosal lymphoid aggregates are often disrupted by the inflammation and there are several ectopic lymphoid follicles close to the serosa.Â There are small numbers of epithelial associated bacteria noted along the lumen surface of the colonic epithelium (Brachyspira sp.).
Colon: Locally extensive, severe, chronic, necrosuppurative, and histiocytic abscessation with intralesional protozoal organisms consistent with Spironucleus spp.
The genus Spironucleus is composed of flagellated protists of the phylum Sarcomstigophora and is closely related to other flagellates of the genera Giardia and Hexamita.(1,7) Being of the order Diplomonadida, this organism is bilaterally symmetrical with two karyomastigonts and flagella that are typically not appreciated using light microscopy.(1,7,8) It lacks an undulating membrane(7).Â This genus inhabits the gastrointestinal tract of a variety of animal hosts including birds, fish, mice, and non-human primates(1,5,10,12,13,14).Â Spironucleus can remain as a normal commensal in the intestine but also possesses the capacity to invade the intestinal epithelium and localize to other organ systems(5,8).Â Following ingestion, Spironucleus transforms from a resistant non-motile cyst into a motile trophozoite (flagellated form)(1,7,14).Â Currently, the taxonomy of the closely related genera of flagellates is being elucidated through the use of small subunit ribosomal DNA (SSU rDNA) sequencing and Spironucleus can be broken out into three separate clades.Â The first and most primitive clade likely originated in marine environments.Â The second clade was isolated from freshwater Ide and Angelfish while the third clade was isolated from terrestrial animals(1,8).Â The three clades are likely only distantly related to one another.
In fish, Spironucleus salmonicida causes significant mortality in farmed salmon(10).Â Spironucleus vortexes is a fresh water species that causes disease in the ornamental fish industry and is highly suspected to be one of the potential causative agents of hole-in-the-head disease in cichlids(5,11).Â In birds, Spironucleus meleagridis was first isolated from turkeys and described and named by McNeil, Hinsha and Kofoid in 1941 but was later found to infect many species of birds(5,9,14).Â Infection with Spironucleus meleagridis is reported to cause infectious catarrhal enteritis in turkeys and other fowl including Chukar partridges and ring-necked pheasants and is also associated with significant morbidity and mortality(5).Â Cysts of S.Â meleagridis are found most frequently in thick mucus and are less frequently found in feces.Â This mechanism may enhance transmission and survival of the organism in the environment(14).Â
In laboratory rodents, Spironucleus muris (and potentially other Spironucleus species) is a commensal organism of the small intestine of rats, mice, and hamsters but can cause significant disease in immunocompromised animals (i.e.Â disease, environmental stress, very young animals).Â In severe outbreaks, there can be up to 50% mortality particularly in young mice that clinically have depression, diarrhea, and weight loss.Â The organism primarily colonizes the duodenal crypts and may cause an acute or chronic form of disease(12).
In non-human primates, a flagellated organism (Octomitus pithily) was described in the feces of nonhuman primates as early as 1929 by DaCunha and Muniz(6).Â More recently, phylogenetic analysis was performed on an unknown diplomonad isolated from two rhesus macaques immunocompromised from simian acquired immune deficiency syndrome (SAIDS).Â The organism was most closely related to Spironucleus meleagridis.Â Further investigation and screening of both SIV infected and uninfected rhesus macaques revealed that the organism was prevalent in the colony and most likely a commensal organism in normal macaques.Â It is suspected that the organism invades the colonic mucosa in immunocompromised animals, striking the gastrointestinal associated lymphatic tissue and disseminating either to regional lymph nodes or systemically via the lymphatics or vasculature(1).Â We suspect that in the present case, the abscess originated in a colonic lymph node following invasion from the colon.Â Lesions associated with Spironucleus were not seen in other tissues.
The bacteria noted along the epithelial border are consistent with Brachyspira sp.Â (B.Â pilsicoli is the most common).Â This is a common, often incidental finding in the large intestine of macaque species.Â The role that this bacterium plays in colonic inflammation is currently unknown; however, since it can be found in the colon of almost all macaque species, its role in causing disease is likely negligible.
Colon: Colitis, necrosuppurative, transmural, diffuse, severe, with innumerable protozoan trophozoites.
Pathologic infection with commensal organisms or parasites that would otherwise be cleared by an immunocompetent animal is common in non-human primates with SIV, and often results in death.Â Because the lentivirus depletes CD4+ T cells, infected non-human primates commonly develop opportunistic infections with Pneumocystis carinii, Mycobacterium avium-intracellulare and M.Â tuberculosis, Cryptosporidium spp., cytomegalovirus (CMV), adenovirus, papovavirus (SV40), Cryptococcus neoformans, Toxoplasma gondii, Candida albicans and Plasmodium(2,3).Â
In SIV-infected monkeys, lymphadenopathy and splenomegaly due to lymphoid hyperplasia is present in early stages of disease with lymphoid atrophy (depletion) in later stages, and thymic atrophy occurs in young animals.Â Histologically, there is giant cell (syncitial) interstitial pneumonia, granulomatous and giant cell lymphadenitis and splenitis, giant cell meningoencephalomyelitis, non-septic vegetative valvular endocarditis, glomerulosclerosis, and syncitial giant cells may also be present in lymph nodes, kidney, and the gastrointestinal tract(2,3).
Other lentiviruses of veterinary importance include equine infectious anemia virus in horses, Maedi-visna virus which produces ovine progressive pneumonia in sheep, caprine arthritis-encephalitis virus in goats, feline immunodeficiency virus in wild and domestic felids, and bovine immunodeficiency-like virus in cattle(4).
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