Signalment:  

11-year-old, male, entire, Cavalier King Charles Spaniel, Canis familaris, dogThis dog presented with a two month history of dyspnoea, lethargy, inappetance, and hemoptysis. Following hospitalization, anthelmintic treatment and concurrent supportive medical therapy (diuretics and corticosteroids), the dogs condition deteriorated acutely with marked respiratory distress. The dog died following respiratory and then cardiac arrest. The dog was submitted for a complete post mortem examination

Gross Description:  

On post mortem examination, the dog was in good body condition with adequate muscle mass and body fat stores. The lung parenchyma contained multifocal areas of dark red discoloration and consolidation (Fig. 4-1). The tracheo-bronchial lymph nodes were enlarged. The heart was markedly enlarged with a heart to body weight ratio of 1.48% (normal range 0.43-0.99%). The right atrium was dilated. The right ventricular wall was thickened (right atrial dilation and right ventricular hypertrophy). The right ventricle contained a thrombus, which was partially adhered to the endocardium, and numerous slender nematode worms measuring up to 15mm in length.

Histopathologic Description:

Lungs: The lung parenchyma was markedly effaced by multifocal to coalescing areas of granulomatous inflammation interspersed with areas of hemorrhage and edema.  The granulomatous inflammation was characterized by the presence of histiocytes, multinucleated giant cells of the foreign body type, fibroblasts, lymphocytes and plasma cells, which were arranged concentrically around myriad parasitic larvae and eggs. Very few eosinophils were noted. Larvae were elongate with a thin eosinophilic cuticle and a primitive enteron measuring 10-20 μm in diameter (Fig. 4-2). The thin-walled eggs were ovoid, measured 50-60 μm in diameter and contained either a morula or larva. Larvae and some histiocytes and multinucleated giant cells were also observed within bronchiolar and bronchial lumens surrounded by multinucleate giant cells. Lumens of numerous alveolar spaces and scattered bronchioli and bronchi contained proteinaceous material (edema) and red blood cells (acute hemorrhage). Lumens of some pulmonary arteries contained nematodes measuring about 300 x 150 μm (Fig. 4-3). The nematodes were characterized by an outer smooth cuticle, a hypodermis with accessory hypodermal cords, a coelomyarian musculature, and a body cavity with an oligocytous syncytous intestine and reproductive organs (consistent with adult Metastrongyles, Fig. 4-4). Intravascular nematodes were often surrounded by thrombi, which were partially adhered to the vessel wall. These thrombi were composed of fibrillary eosinophilic material (fibrin) or fibrous connective tissue containing multiple small blood filled channels (organized and recanalized thrombi). The tunica media of numerous pulmonary arteries was markedly thickened (smooth muscle hypertrophy). The pleura was segmentally thickened by fibrous connective tissue (pleural fibrosis) and contained scattered eggs and larvae, which were surrounded by some histiocytes. 

Microscopic examination of additional organs: The parenchyma of tracheo-bronchial lymph nodes, kidneys and brain contained scattered nematode larvae surrounded by granulomatous inflammation.

Morphologic Diagnosis:  

Lungs: Pneumonia, granulomatous with myriad intralesional nematode eggs and larvae and acute hemorrhage and edema
Lungs, pulmonary arteries: Intralesional adult metastrongyle nematodes, thrombosis and media hypertrophy

Lab Results:  

Microscopic examination of a direct faecal smear revealed the presence of nematode larvae consistent with Angiostrongylus vasorum larvae. On routine blood count, a moderately regenerative anemia with a hematocrit of 25.5% (reference value: 37-55%) was present. There was an inflammatory leukogram with leukocytosis (27.8 x109/L; reference value: 6.0 -17.1 x109/L), neutrophilia with mild toxic change (16.4 x109/L; reference value: 3.0 -11.5 x109/L) and monocytosis (3.06 x 109/L; reference value: 0.15 - 1.50 109/L). Biochemistry indicated increased total bilirubin (4.8μmol/L; reference value: 0.0-2.4μmol/L).

Condition:  

Angiostrongylus vasorum

Contributor Comment:  

Microscopic examination together with parasitology showed the presence of verminous pneumonia due to Angiostrongylus vasorum (A. vasorum) infestation. 

A. vasorum is a nematode parasite (superfamily Metastrongyloidae, family Angiostrongyloidae) of which domestic dogs and wild canids are the definitive hosts. Wild foxes serve as an important reservoir for infection in domestic dogs, and natural infection has also been reported in coyotes (Canis latrans), wolves (Canis lupus) and badgers (Meles meles).(3,9) Discrete endemic foci of A. vasorum infection in domestic and wild canids are recognized in Europe (France, Ireland, Denmark, Germany, Italy, Spain, Switzerland, Wales, England and Scandinavia), Africa (Uganda), South America (Columbia, Brazil), and more recently in Canada.(4,6)

A. vasorum has an indirect lifecycle. Adult worms live in the pulmonary arteries of the definitive host, and eggs are deposited in the lung parenchyma where they develop and hatch producing larvae (L1). L1 penetrate capillary and alveolar walls moving into alveoli, and the large airways are coughed up and secreted in saliva, or swallowed and then excreted in the feces. Aquatic and terrestrial gastropods ingest larvae and serve as the intermediate host in which larvae mature through L2 to L3 stages. Frogs may serve as paratenic and intermediate hosts.(2) When intermediate or paratenic hosts are ingested by the definitive host, A. vasorum larvae migrate via lymphatics or hepatic portal vessels to the right side of the heart where they develop to sexual maturity.

A. vasorum infection is a cause of chronic heart failure and pyogranulomatous interstitial pneumonia in dogs.(5) Aberrant migration of larvae, which was also observed in the present case, can be a cause of complications. Granulomatous foci, with or without association with larvae and eggs, have been reported in the brain, kidney, tracheo-bronchial lymph nodes, adrenal gland, skin, liver, pancreas, peripheral blood, cerebrospinal fluid, pericardial sac, urinary bladder, femoral artery, intestinal tract, thyroid gland, pituitary gland, skeletal muscle, heart, and eye.(4,7,10,11) Hemorrhage into tissues may also be observed. This is thought to occur secondarily to inappropriate activation of the clotting cascade by immune complex formation and compliment fixation directed against the parasites, leading to a consumptive coagulopathy.(12,13)

Interestingly, a low number of eosinophils were observed within the tissue of this case. This may have occurred secondarily to the use of glucocorticoids in the medical therapy for this case. Via their modulatory effects on cytokine production, glucocorticoids are thought to reduce numbers of eosinophils present in the airways by inducing apoptosis (via inhibition of granulocyte macrophage colony stimulating factor (GM-CSF) and IL-5) and perhaps through decreasing production in the bone marrow.(1)

Strongyle parasites of the respiratory tract in domestic and wild animals include Metastrongyloidean and Trichostrongyloidean parasites. Common Strongyle parasites of verminous pneumonia in domestic species are listed in Table 1. 

Nematode parasites can be identified by the presence of a cuticle, hypodermis and underlying musculature (platymyarian or coelomyarian) surrounding the pseudocoelom containing digestive and reproductive tracts.(8) The cuticle of the strongyle-type parasite is usually smooth and the intestine large and composed of a few multi-nucleated cells (syncytous, oligocytous intestine). Metastrongyloidean parasites are characterized by the presence of coelomyarian musculature, which is in contrast to the platymyarian musculature of the true strongyles and trichostrongyles. Adult females may produce either eggs or fully developed embryos. Metastrongyle L1 larvae are indentified by their distinctive kinked tail morphology and small dorsal spine.

Table 1 Strongyle parasites of the respiratory system of domestic animals ⁵

Superfamily	Definitive Host	Family	Species	Intermediate Host	Paratenic Host	Location of adult worms	Notes
Metastrongylidae	Domestic and wild canids	Filaroididae	Oslerus oslerii	Direct lifecycle, L1 infective		Tracheal nodules
			Filaroides (F.) hirthi	Direct lifecycle, L1 infective		Alveoli and respiratory bronchioles	Differentiate from A. milksi
		Crensomatidae	Crensoma vulpis	Gastropod		Bronchioles and small bronchii
		Angiostrongyloidae	Angiostrongylus vasorum	Gastropod, frog	Frog	Pulmonary arteries and right ventricle	Differentiate morphologically from Dirofilaria spp.
			Andersonstrongylus (A.) milksi (prev. Angiostrongylus milksi, Filaroides milksi)	Gastropod host proposed, lifecycle unknown		Alveoli and respiratory bronchioles	Differentiate from F. hirthi
	Domestic cats	Angiostrongyloidae	Aelurostrongylus abtrusus	Gastropod	Birds, rodents,frogs, lizards	Terminal and respiratory bronchioles
	Pig	Protostrongylidae	Metastrongylus apri M. pudendotectus M. salmi	Earthworm		Bronchi and bronchioles
	Sheep, goats	Protostrongylidae	Muellerius capillaris	Gastropod		Alveoli, rarely bronchioles
			Protostrongylus rufescens	Gastropod		Terminal bronchioles
			Neostrongylus linearis	Gastropod
Trichostrongyloidea	Cattle	Dictyocaulidae	Dictyocaulus viviparus	Direct lifecycle, L1 → L3 in environment		Large bronchii
	Sheep, goats	Dictyocaulidae	Dictyocaulus filaria	Direct lifecycle, L1 → L3 in environment		Small bronchii

JPC Diagnosis:  

1. Lung, arteries: Endarteritis, chronic, multifocal, severe with thrombi and intravascular adult nematodes consistent with Angiostrongylus vasorum
2. Lung: Pneumonia, granulomatous, multifocal to coalescing, severe with hemorrhage and nematode larvae and eggs

Conference Comment:  

The contributor did an outstanding job of not only describing this particular parasite but also giving an extensive list of other pulmonary parasites in domestic animals. 

References:

1. Barnes PJ, Pederson S, Busse WW: Efficacy and safety of inhaled corticosteroids. American Journal of Respiratory and Critical Care Medicine 157:S1-S53, 1998
2. Bolt G, Monrad J, Frandsen F, Henriksen P, Dietz HH: The common frog (Rana temporaria) as a potential paratenic and intermediate host for Angiostrongylus vasorum. Parasitology Research 79:428-430, 1993
3. Bolt G, Monrad J, Koch J, Jensen JL: Canine angiostrongylosis: a review. The Veterinary Record 135:447-452, 1994
4. Bourque AC, Conboy G, Miller LM, Whitney H: Pathological findings in dogs naturally infected with Angiostrongylus vasorum in Newfoundland and Labrador, Canada. Journal of Veterinary Diagnostic Investigation 20:11-20, 2008
5. Caswell JL, Williams KJ: Respiratory System. In: Jubb, Kennedy, and Palmer's Pathology of Domestic Animals, ed. Maxie MG, pp. 523 - 653. Elsevier Limited, Philadelphia, PA, 2007
6. Conboy GA: Canine angiostrongylosis (French heartworm). In: Companion and Exotic Animal Parasitology, ed. Bowman DD, www.ivis.org, accessed May 8 2008
7. Cury MC, Lima WS: Rupture of femoral artery in a dog infected with Angiostrongylus vasorum. Veterinary Parasitology 65:313-315, 1996
8. Gardiner CH, Poynton SL: An atlas of metazoan parasites in animal tissues. Armed Forces Institute of Pathology, Washington DC, 1999
9. Koch J, Willesen JL: Canine pulmonary angiostrongylosis: an update. The Veterinary Journal: doi:10.1016/j.tvjl.2007.11.014, 2007
10. Oliveira-J+�°nior SD, Bar+�-�ante JMP, Bar+�-�ante TA, Ribeiro VM, Lima WS: Ectopic location of adult worms and first-stage larvae of Angiostrongylus vasorum in an infected dog. Veterinary Parasitology 121:293-296, 2004
11. Perry AW, Hertling R, Kennedy MJ: Angiostrongylosis with disseminated larval infection associated with signs of ocular and nervous disease in an imported dog. The Canadian Veterinary Journal 32:430-431, 1991
12. Ramsey IK, Littlewood JD, Dunn JK, Herrtage ME: Role of chronic disseminated intravascular coagulation in a case of canine angiostrongylosis. The Veterinary Record 138:360-363, 1996
13. Schelling CG, Greene CE, Prestwood AK, Tsang VC: Coagulation abnormalities associated with acute Angiostrongylus vasorum infection in dogs. American Journal of Veterinary Research 47:2669-2673, 1986

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