JPC SYSTEMIC PATHOLOGY

RESPIRATORY SYSTEM

September 2023

P-P10 (NP)

 

Signalment (JPC #1042449): Wild rat, age and gender unspecified

 

HISTORY: Unknown

 

HISTOPATHOLOGIC DESCRIPTION: Lung: Affecting approximately 90% of the section, alveolar and bronchiolar lumina are markedly expanded up to 400µm in diameter (bronchiectasis) by aggregates of intraluminal embryonated and non-embryonated nematode eggs and larvae in various stages of development, which are surrounded by moderate numbers of epithelioid macrophages, lymphocytes, plasma cells, fewer eosinophils, and multinucleated giant cells. There is multifocal mild alveolar hemorrhage and few hemosiderin-laden macrophages. Eggs are round to oval, 40-50 µm x 150µm, and are either filled with eosinophilic granular material and contain a single basophilic, often eccentric, 10 µm diameter nucleus (non-embryonated) or are multinucleated with variable numbers of large foamy cuboidal cells (embryonated). Larvae are 150 x 50 µm and have a smooth, 1 µm wide, amphophilic cuticle surrounding numerous round, 4-6 µm diameter, basophilic nuclei with scant eosinophilic cytoplasm. Multifocally, alveolar septa are expanded up to 4 times normal by macrophages, lymphocytes, and plasma cells. Occasional nematode eggs and larvae are present within bronchiolar walls. Multifocally, the tunica media of pulmonary arterioles is expanded by increased smooth muscle that narrows the lumina (arteriolar medial hypertrophy). Bronchiolar epithelium is multifocally attenuated and/or sloughed. 

 

MORPHOLOGIC DIAGNOSIS: Lung: Pneumonia, granulomatous and eosinophilic, nodular, multifocally to coalescing, moderate, with arteriolar hypertrophy, bronchiectasis, and numerous intraalveolar nematode eggs and larvae, rat, rodent.

 

ETIOLOGICAL DIAGNOSIS: Pulmonary parastrongyliasis

 

ETIOLOGY: Parastrongylus (Angiostrongylus) cantonensis 

*Note:   This nematode was reassigned from the Angiostrongylus genus to the Parastrongylus genus in 1986, due to its morphology and the definitive host being the rat; however, the transfer/terminology has not been widely accepted and current literature predominantly uses Angiostrongylus cantonensis 

 

GENERAL DISCUSSION:

• A common, neurotropic, metastrongylid lungworm of rats found in Australia, the South Pacific, Southeast Asia, the Caribbean, and southern United States (Louisiana, Mississippi, Florida)
• Zoonotic; the most common cause of human eosinophilic meningoencephalitis
• Rats are the natural definitive host
• Adult nematodes reside in the pulmonary arteries and rarely the right heart
• Aberrant hosts include dogs, humans, and other species; aberrant infection results in vascular dissemination and aberrant migration of infected larvae to the brain, kidney, and muscle

 

PATHOGENESIS:

• Natural infections in rats usually cause little disease, but death can result from massive damage to the lungs or blockage of the pulmonary arteries
• In aberrant hosts, spectrum of disease varies with strain of parasite, severity of infection, and host response; typically minimal inflammation during prepatent development in the brain; clinical signs are due to inflammation associated with parasites, migration of larval nematodes in neural parenchyma, and thrombosis and occlusion of vessels leading to infarction
• In immunosuppressed individuals, parasites may migrate back to the lungs, causing fatal pulmonary edema and pneumonia; proliferative endarteritis may occur
• Egg emboli in pulmonary capillaries elicit granulomatous and eosinophilic inflammation

 

LIFE CYCLE:  

• Two-host life cycle involving a gastropod (intermediate host) and the rat (definitive host)
• Natural definitive host (rat): Adult parasite in pulmonary arteries lays eggs, which migrate and lodge in alveolar capillaries > larvae hatch in about 6 days and release L1 into alveoli > coughed up, swallowed, and released in feces (tracheal-intestinal route) to exterior > L1 larvae penetrate intermediate host (gastropod, e.g. slug, snail) or paratenic host (frog, crab, prawn) and develop to L3 > ingestion of infected intermediate or paratenic host by definitive host (rat) > migration to ileum > penetration of small intestine > mesenteric vessels > lodge within cerebral blood vessels (with little damage) > molt twice to L5 > reentry to circulation via meningeal veins > circulation to definitive site in the pulmonary arteries
• Aberrant host: Infected gastropod is ingested by an aberrant host (e.g. human, dog) > migration from gastrointestinal tract to the brain, kidney and muscle > additional molts in CNS to L5 and migration within neuroparenchyma results in inflammation, thrombosis, occlusion of vessels > infarction 

 

TYPICAL CLINICAL FINDINGS:

• Naturally occurring (light to moderate) infections are usually asymptomatic
• Experimental (heavy) infections can result in neurologic signs including ataxia, circling, or paraplegia
• Pulmonary signs include coughing, sneezing, and dyspnea

 

TYPICAL GROSS FINDINGS:  

• Heavy, swollen lungs with cobblestone appearance
• Pleural adhesions, emphysema, and consolidation of pulmonary parenchyma
• Adult nematodes within pulmonary arteries

 

TYPICAL LIGHT MICROSCOPIC FINDINGS:  

• Infection is typically subclinical
• Viable adult parasites usually cause little cellular response, but degenerate ones can cause endarteritis
• Larvae and eggs within alveoli may cause a granulomatous and eosinophilic pneumonia; adults in pulmonary arteries
• Splendore-Hoeppli material may be present around degenerating parasites
• Morphologic characteristics:
  • Females 280-560 µm in diameter; males 250 –420 µm in diameter
  • Barber-pole pattern (paired uterine and ovarian branches spiral around the blood filled intestine)
  • Cuticle is 3-6 µm, multilayered, and smooth
  • Coelomyarian-polymyarian musculature (characteristic of metastrongyles but not other strongyles [true strongyles, trichostrongyles])
  • Lateral and accessory hypodermal chords
  • Intestine is large with few multinucleated cells (characteristic of all strongyles)

 

ADDITIONAL DIAGNOSTIC TESTS:

 

DIFFERENTIAL DIAGNOSIS:

• Angiostrongylus costaricensis: Infects humans and wild rodents in South America; adults located in mesenteric arteries; thin-shelled eggs reside in the wall of the intestine (in humans, eggs are unembryonated; in rodents eggs are embryonated or unembryonated)
• Angiostrongylus vasorum (P-P02, French heartworm): Metastrongylid lungworm of dogs, foxes, and other wild canines; adult nematodes reside in pulmonary arteries and occasionally the right ventricle and cause granulomatous, interstitial pneumonia with arterial obstruction, thrombosis, and endarteritis; does not migrate to the CNS

 

COMPARATIVE PATHOLOGY: 

• Dogs: Granulomatous and eosinophilic meningoencephalitis and myelitis resulting in ascending paresis of the tail and urinary bladder and lumbar hyperalgesia
• Non-human primates: Granulomatous and eosinophilic meningoencephalitis; infections typically mild and self limiting; heavy infections occasionally fatal; reported in housed primates in Florida
• Frogs, toads, centipedes: Infection with P. cantonensis identified in several species in Hawaii, USA; possible paratenic hosts with a role in transmission and maintenance of the parasite in Hawaii; multiple human cases reported in the Hawaiian islands (Niebuhr, et al, J Wildl Dis. 2020)
• Kangaroo: Recent report of verminous meningoencephalomyelitis in a red kangaroo associated with Angiostrongylus cantonensis infection (Patial, JVDI 2022) 
• Other wildlife: Neurologic disease reported in brushtail possums and several bat species in Australia, 

 

REFERENCES:

1. Bowman DD. Helminths. In: Bowman DD, ed. Georgis’ Parasitology for Veterinarians. 11th ed. St. Louis, MO: Saunders Elsevier; 2021:204.
2. Cantile C, Youssef S. Nervous system. In: Maxie MG, ed. Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1. 6th ed. Philadelphia, PA: Elsevier; 2016:389.
3. Fahey MA, Westmoreland SV. Nervous system disorders of nonhuman primates and research models. In: Abee CR, Mansfield K, Tardif S, et al., eds. Nonhuman Primates in Biomedical Research: Diseases. Vol 2. 2nd ed. London, UK: Elsevier; 2012:748.
4. Farina LL, Lankton JS. Chiroptera. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:623-624. 
5. Gardiner CH, Poynton SL. Strongyles. In Gardiner CH, Poynton SL, eds. An Atlas of Metazoan Parasites in Animal Tissues. Washington, DC: Armed Forces Institute of Pathology; 1999:22-29.
6. Higgins D, Rose K, Spratt D. Monotremes and Marsupials. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. London, UK: Academic Press; 2018:472-473.
7. Niebuhr CN, Jarvi SI, Kaluna L, et al. Occurrence of Rat Lungworm (Angiostrongylus cantonensis) in Invasive Coqui Frogs (Eleutherodactylus coqui) and Other Hosts in Hawaii, USA. J Wildl Dis. 2020;56(1):203-207.
8. Patial S, Delcambre BA, DiGeronimo PM, Conboy G, Vatta AF, Bauer R. Verminous meningoencephalomyelitis in a red kangaroo associated with Angiostrongylus cantonensis infection. J Vet Diagn Invest. 2022;34(1):107-111.
9. Strait K, Else JG, Eberhard ML. Parasitic diseases of nonhuman primates. In: Abee CR, Mansfield K, Tardif S, et al., eds. Nonhuman Primates in Biomedical Research: Diseases. Vol 2. 2nd ed. London, UK: Elsevier; 2012:235-236.

 

 

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