History
A 450-kg (990-lb) 16-year-old American Saddlebred gelding was evaluated at the University of Georgia Large Animal Teaching Hospital because of progressing neurologic disease. The horse lived in a pasture until 1 week prior to initial evaluation, at which time it was noted that the horse had lost a large amount of weight and was moved indoors. In the week prior to initial evaluation, signs of depressed mentation developed and progressed to ataxia and head pressing. Except for evidence of mild dehydration, results of routine hematologic and serum biochemical analysis performed by the referring veterinarian were within reference ranges. No other horses on the premises appeared ill. The horse was vaccinated earlier that year against rabies and West Nile virus encephalitis; it had not been dewormed recently because a routine fecal floatation had revealed a low parasite burden.
Clinical and Gross Findings
On initial evaluation, the horse was obtunded and minimally responsive to stimuli. Head tilt and neck flexion to the right were observed as well as decreased sensation over the cutaneous trunci muscle and along the cervical region on the right side. The horse was markedly ataxic (grade 4/5) on all 4 limbs when forced to move and had periods of stupor, during which it would nearly fall but would subsequently arouse and compensate. Upon intense stimulation, alertness increased and the ataxia improved (grade 3/5). A CBC, serum biochemical analysis, and blood gas analysis revealed high creatinine concentration (2.5 mg/dL; reference range, 0.7 to 2.2 mg/dL), hyperproteinemia (10.5 g/dL; reference range, 5.4 to 7.5 g/dL) with marked hyperglobulinemia (7.5 g/dL; reference range, 3 to 5 g/dL), and hypercalcemia (total calcium concentration, 14.7 mg/dL; reference range, 10.8 to 12.8 mg/dL). Analysis of a sample of CSF revealed no abnormalities. Before the results of CSF analysis became available, treatment involving IV administration of polyionic fluids, flunixin meglumine, dimethyl sulfoxide, and dexamethasone and oral administration of potentiated sulfonamides and rifampin, ponazuril, and fenbendazole was initiated, but the horse's signs progressed, and the owners elected euthanasia 3 days after admission to the hospital.
Necropsy revealed a severely enlarged right kidney that was mostly effaced by 2 large, firm, yellow nodules measuring approximately 11 × 8 cm and 13 × 12 cm (Figure 1). At the margo plicatus, a circumferential area (approx 3 cm in width) of nonglandular gastric mucosa was hyperkeratotic and yellow-orange. The lateral ventricles of the brain were mildly dilated. No other important gross lesions were noted.
Photograph of the cut surface of the right kidney of a 16-year-old American Saddlebred gelding with progressive neurologic disease. Prior to euthanasia, the horse was obtunded with periods of somnolence and markedly ataxic. At necropsy, the right kidney was greatly enlarged and contained 2 large, firm, yellow nodules, one of which is visible adjacent to an area of kidney with normal appearance (K). The lateral ventricles in the brain were mildly dilated, but no other gross changes were observed in the brain or spinal cord.
Citation: Journal of the American Veterinary Medical Association 241, 6; 10.2460/javma.241.6.703
Photograph of the cut surface of the right kidney of a 16-year-old American Saddlebred gelding with progressive neurologic disease. Prior to euthanasia, the horse was obtunded with periods of somnolence and markedly ataxic. At necropsy, the right kidney was greatly enlarged and contained 2 large, firm, yellow nodules, one of which is visible adjacent to an area of kidney with normal appearance (K). The lateral ventricles in the brain were mildly dilated, but no other gross changes were observed in the brain or spinal cord.
Citation: Journal of the American Veterinary Medical Association 241, 6; 10.2460/javma.241.6.703
Photograph of the cut surface of the right kidney of a 16-year-old American Saddlebred gelding with progressive neurologic disease. Prior to euthanasia, the horse was obtunded with periods of somnolence and markedly ataxic. At necropsy, the right kidney was greatly enlarged and contained 2 large, firm, yellow nodules, one of which is visible adjacent to an area of kidney with normal appearance (K). The lateral ventricles in the brain were mildly dilated, but no other gross changes were observed in the brain or spinal cord.
Citation: Journal of the American Veterinary Medical Association 241, 6; 10.2460/javma.241.6.703
Formulate differential diagnoses from the history, clinical findings, and Figure 1—then turn the page →
Histopathologic Findings
Sections of various tissues (including brain, pituitary gland, spinal cord, lungs, heart, lymph node, liver, pancreas, spleen, kidneys, adrenal glands, and gastrointestinal tract) were prepared for histologic examination. Sections of the right kidney revealed coalescing granulomatous inflammation composed of numerous epithelioid macrophages, multinucleated giant cells, plasma cells, and lymphocytes along with mild fibrosis (Figure 2). Numerous sections of larvae and small adult female nematodes as well as occasional ovoid embryonated eggs were present throughout the area of inflammation. The adult nematodes had a smooth, thin cuticle; characteristic rhabditiform esophagus (3 portions: corpus, isthmus, and bulb); deeply basophilic internal structures; and uterus with 1 mature egg (Figure 3). Larvae also had a characteristic rhabditiform esophagus. These findings were consistent with Halicephalobus gingivalis.1 The left kidney had mild fibrosis but no evidence of inflammation or nematodes.
Photomicrograph of a section of a large, yellow renal nodule in the right kidney of the horse in Figure 1. The nodule is characterized by coalescing granulomatous inflammation composed of epithelioid macrophages, multinucleated giant cells (G), and lymphocytes and plasma cells (L). Renal parenchyma is visible (K). Numerous sections of adult and larval nematodes are present in the area of granulomatous inflammation but are not obvious at this magnification. H&E stain; bar = 200 μm.
Citation: Journal of the American Veterinary Medical Association 241, 6; 10.2460/javma.241.6.703
Photomicrograph of a section of a large, yellow renal nodule in the right kidney of the horse in Figure 1. The nodule is characterized by coalescing granulomatous inflammation composed of epithelioid macrophages, multinucleated giant cells (G), and lymphocytes and plasma cells (L). Renal parenchyma is visible (K). Numerous sections of adult and larval nematodes are present in the area of granulomatous inflammation but are not obvious at this magnification. H&E stain; bar = 200 μm.
Citation: Journal of the American Veterinary Medical Association 241, 6; 10.2460/javma.241.6.703
Photomicrograph of a section of a large, yellow renal nodule in the right kidney of the horse in Figure 1. The nodule is characterized by coalescing granulomatous inflammation composed of epithelioid macrophages, multinucleated giant cells (G), and lymphocytes and plasma cells (L). Renal parenchyma is visible (K). Numerous sections of adult and larval nematodes are present in the area of granulomatous inflammation but are not obvious at this magnification. H&E stain; bar = 200 μm.
Citation: Journal of the American Veterinary Medical Association 241, 6; 10.2460/javma.241.6.703
Photomicrograph of a section of a large, yellow renal nodule in the right kidney of the horse in Figure 1. An adult Halicephalobus gingivalis female is visible with adjacent epithelioid macrophages (G) in the kidney lesion. The nematode has a long rhabditiform esophagus with 3 portions: corpus (C), isthmus (I), and bulb (B). A single ovoid uninucleate egg (long arrow) is present in the uterus. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 241, 6; 10.2460/javma.241.6.703
Photomicrograph of a section of a large, yellow renal nodule in the right kidney of the horse in Figure 1. An adult Halicephalobus gingivalis female is visible with adjacent epithelioid macrophages (G) in the kidney lesion. The nematode has a long rhabditiform esophagus with 3 portions: corpus (C), isthmus (I), and bulb (B). A single ovoid uninucleate egg (long arrow) is present in the uterus. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 241, 6; 10.2460/javma.241.6.703
Photomicrograph of a section of a large, yellow renal nodule in the right kidney of the horse in Figure 1. An adult Halicephalobus gingivalis female is visible with adjacent epithelioid macrophages (G) in the kidney lesion. The nematode has a long rhabditiform esophagus with 3 portions: corpus (C), isthmus (I), and bulb (B). A single ovoid uninucleate egg (long arrow) is present in the uterus. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 241, 6; 10.2460/javma.241.6.703
The brain had few changes. However, multiple areas of perivascular infiltration of epithelioid macrophages, plasma cells, and lymphocytes were observed in the brainstem at the level of the internal capsule. Some sections of nematodes were noted in these areas of inflammation in close proximity to the affected vessels. Sections of spinal cord revealed few acute hemorrhages in the gray matter from the thoracic to sacral areas and acute hemorrhages in the cauda equina along with multifocal small areas of lymphoplasmacytic infiltration in the perineurium and epineurium.
A lymph node from an unknown region of the body (most likely perirenal) had histologic changes similar to those in the right kidney, including epithelioid macrophages, multinucleated giant cells, and adult female nematodes and rhabditiform larvae. No remarkable microscopic changes were observed in sections of the pituitary gland, lungs, heart, liver, pancreas, spleen, adrenal glands, or gastrointestinal tract.
Diagnosis
Locally extensive granulomatous nephritis (right kidney), lymphadenitis, and encephalitis with intralesional adult and larval H gingivalis.
Comments
Halicephalobus gingivalis (previously called Halicephalobus deletrix or Micronema deletrix) is an opportunistic parasite that is most commonly associated with equid species (mainly horses)2,3 and humans4 but has also been reported in the scrotal skin of a bull.5 Cases of infection have been reported in North America, Egypt, Europe, and Japan, suggesting a worldwide distribution of the nematode.6,7
The life cycle and habitat of H gingivalis outside of a vertebrate host is unclear but is thought to be associated with manure, soil, and decaying humus.5 No male forms have been identified for this species, and reproduction by females in host tissues appears to be parthenogenic.1
Route of exposure to H gingivalis is also unclear, with theories including inhalational exposure,8 opportunistic infection of wounds in the skin or mucosal surfaces,9 and at least 1 case of apparent horizontal transfer from a mare with verminous mastitis to its suckling foal.10 In humans, exposure has most often been associated with inoculation of a wound with soil or manure.4 In the case described in the present report, no evidence of mucosal or dermal abrasions was detected. However, due to the chronicity of the disease, it is unlikely that any wound present at the time of infection would still be apparent.
Hematogenous spread is thought to be the method of transfer of parasites from the original inoculated site to various other organs and tissues.1 Such transfer is supported by the findings in the horse of this report, given the intimate association of nematode adults and larvae with the perivascular inflammation in the horse's brain. In equids, these organisms appear to have a tropism for the CNS and kidneys but have also been detected in the nasal cavity, bones, heart, lungs, liver, eyes, mammary glands, subcutaneous tissues, uterus, and testes. Organisms have been observed in samples of urine and semen in some cases.3,10–13
Neurologic signs are the most commonly reported clinical signs in affected horses.8,12 Changes in function12 and ultrasonographic appearance13 of the kidneys have been observed in cases with renal involvement. Serum biochemical changes reported for horses with H gingivalis infection have included hyperproteinemia and hyperglobulinemia.8 However, there may be no antemortem evidence to suggest nematode infection, particularly if only the CNS is involved. For the horse of the present report, the antemortem differential diagnoses included neoplasia, brain abscess, equine protozoal encephalomyelitis, aberrant parasitic migration, viral encephalitis, and trauma.
Microscopic lesions are usually granulomatous with areas of necrosis and vasculitis, in which large numbers of adult and larval nematodes as well as eggs can be seen.2,6,7,10,12 Halicephalobus gingivalis can be identified on the basis of morphological characteristics, including a rhabditiform esophagus featuring a corpus, isthmus, and bulb; a uterus with only 1 egg; and size (250 to 450 × 15 to 20 μm).1 Inflammatory cells including plasma cells, lymphocytes, and neutrophils may be present in the lesion. The few serum biochemical abnormalities in the case described in the present report were difficult to interpret because the analyses were not repeated. Differential diagnoses for high creatinine concentration included dehydration and renal compromise. It was possible that the detected hypercalcemia may have been induced by the granulomatous disease. Hypercalcemia has been associated with a number of granulomatous disorders in various species and is thought to develop as a result of extrarenal synthesis of 1,25-dihydroxyvitamin D by activated macrophages.14,15 However, to our knowledge, hypercalcemia has not been associated with granulomatous disease in horses.
Reports of successful treatment of horses infected with H gingivalis are limited, and there are no such reports for affected horses that had neurologic signs.2,11,13,16 Treatment of horses with ivermectin at doses near the maximum safe dose has been successful.16 Fenbendazole has been reported to be inefficacious; however, in horses with no overt neurologic signs, concurrent treatment with ivermectin and thiabendazole may increase chances for success because thiabendazole may be able to penetrate the blood-brain barrier and contact parasites in the CNS.2 Because humans may be susceptible to H gingivalis, it is recommended that precautions such as double-gloving and use of face shields and eye protection be used when dealing with an animal that is infected. Preventative treatment protocols for people who may have been exposed to H gingivalis are based on the treatment protocols for infection with Strongyloides stercoralis, a related nematode.2
Halicephalobus gingivalis is an uncommon facultative pathogen of horses. However, it is an important differential diagnosis for horses with neurologic signs, especially in conjunction with cutaneous, osteolytic, or renal signs.
References
- 1.↑
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Dunn DG, Gardiner CH, Dralle KR, et al. Nodular granulomatous posthitis caused by Halicephalobus (syn. Micronema) sp. in a horse. Vet Pathol 1993; 30:207–208.
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Kinde H, Mathews M, Ash L, et al. Halicephalobus gingivalis (H. deletrix) infection in two horses in southern California. J Vet Diagn Invest 2000; 12:162–165.
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Mealey KL, Willard MD, Nagode LA, et al. Hypercalcemia associated with granulomatous disease in a cat. J Am Vet Med Assoc 1999; 215:959–962.
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LeBlanc CJ, Echandi RL, Moore RR, et al. Hypercalcemia associated with gastric pythiosis in a dog. Vet Clin Pathol 2008; 37:115–120.
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Pearce SG, Bouré LP, Taylor JA, et al. Treatment of a granuloma caused by Halicephalobus gingivalis in a horse. J Am Vet Med Assoc 2001; 219:1735–1738.
