JPC Systemic Pathology

Respiratory System

August 2026 P-P01

HISTOPATHOLOGIC DESCRIPTION: Lung: Diffusely, alveolar septa and, to a lesser extent, peribronchial and peribronchiolar interstitium are expanded up to 30 μm by congestion, fibrin, edema, lymphocytes, macrophages, and fewer neutrophils. Multifocally, alveolar septa are discontinuous with replaced by eosinophilic and karyorrhectic debris, fibrin, hemorrhage, edema, and previously described inflammatory cells (alveolar septal necrosis). In approximately 70% of the section there is marked type II pneumocyte hyperplasia. Alveolar lumina, and to a lesser extent the bronchial and bronchiolar lumina, frequently contain macrophages, multinucleated giant cells, lymphocytes, hemorrhage, necrotic cellular debris, fibrin, and flocculent edema. Multifocally, alveolar macrophages and type II pneumocytes are distended by a intracytoplasmic parasitophorous vacuole that contains many 2-4 um, round to fusiform, basophilic tachyzoites. Tachyzoites are rarely free within alveolar lumina adjacent to ruptured alveolar macrophages. Multifocally, there are proliferative lymphoid nodules adjacent to blood vessels, bronchi, and bronchioles (mild BALT hyperplasia).

General Discussion

• Apicomplexan; ubiquitous, obligate intracellular, coccidian parasite; causes disseminated disease including enteritis (E-P01), myositis, pneumonia, hepatitis, encephalitis (N-P02), ophthalmitis, and abortions (R-P01) in a wide range of intermediate hosts
  • One of two common protozoa to affect the respiratory tract; the other is Neospora caninum
• Felids are the only definitive hosts (DH), but T. gondii can affect all warm-blooded animals; whereas many mammals and birds can serve as intermediate hosts (IH)
• Felids are unique in that they can serve as both definitive and intermediate host
• Severe disease most common in kittens and immunocompromised cats
• 3 infectious stages: Tachyzoites (IH/DH), tissue cysts (IH/DH), and oocysts (DH)

Life Cycle

• Definitive host (felids), intestinal “enteroepithelial” cycle:
  • Ingestion of infected prey tissue (tachyzoites or tissue cysts) or sporulated oocysts in contaminated food or water > sporozoites/ bradyzoites transition to tachyzoites and infiltrate intestinal epithelial cells > undergoing five asexual stages of reproduction (schizogony) and eventually form merozoites
  • In the sexual phase (gametogony), merozoites transform into a male microgamont or female macrogamont, microgamonts are released to fertilize a macrogamont and form an oocyst
  • Oocysts (unsporulated, noninfective) are shed in feces; sporulation (development of infective sporozoites inside the oocyst) takes 1 to 5 days
• Intermediate hosts, extraintestinal cycle (many mammals and birds, including felids):
  • Transmission: Ingestion (sporulated oocysts or tissue cysts), transplacental tachyzoites, or contaminated biological materials
  • Sporozoites or bradyzoites transition to tachyzoites and invade enterocytes > divide asexually (endodyogeny) within a parasitophorous vacuole to form duplicate tachyzoites > tachyzoites lyse the enterocyte and spread locally to adjacent enterocytes, the lamina propria, and tissue leukocytes > systemic spread via leukocyte trafficking (lymphocytes, macrophages, and granulocytes) or free in plasma via blood and lymphatics
  • With chronicity and the development of host antibody response, tachyzoites transform into slow-growing bradyzoites within tissue cysts (also in a parasitophorous vacuole)

Pathogenesis

• T. gondii has 3 infectious stages: tachyzoites, tissue cysts, and oocysts
• Can multiply and survive intracellularly in almost any tissue in the body (e.g. lungs, lymphoid system, liver, heart, skeletal muscle, pancreas, intestine, eyes, nervous system) within a parasitophorous vacuole, destroying the host cell > cell-to-cell transmission > focal necrosis
• Encystation allows immune evasion: Driven by increasing host antibody response, immune suppression can allow excystation/active infection
• Coinfection common: Immune suppressors: Canine Morbilivirus (CDV), Feline Leukemia Virus (FeLV), Cetacean Morbilivirus, Chlamydophila (small ruminant abortions), Ehrlichia (canine), Sarcocystis (seals)
• Virulence factors:
  • When in parasitophorous vacuoles T. gondii initiates the production of the anti-inflammatory cytokines IL-10 and transforming growth factor-β (TGF-β), which inhibit the production of proinflammatory cytokines IL-12 and TNF-α
  • Glycosylphosphatidylinositol-linked surface antigens (SAGs): Expressed by tachyzoites +/- sporozoites and serve as ligands and intestinal villous enterocytes receptors include laminin, lectin, and SAG receptor proteins
  • SAG1 and SAG3: Function in target cell attachment and immune modulation and may cause direct injury to intestinal epithelium; found abundantly on tachyzoites

Typical Clinical Findings

• Most common in animals with systemic disease: Fever, lethargy, anorexia, ocular and nasal discharges, and respiratory distress
• In adult, immune-competent cats: Self-limiting diarrhea or asymptomatic
• Extraintestinal cycle: Widespread seropositivity but disease is sporadic and rare unless immunocompromised; exception is abortion in sheep and goats
• CNS infection: Incoordination, circling, tremors, opisthotonos, convulsions, and paresis
• Radiculitis and myositis > paresis
• Rare cause of cutaneous nodules in cats, dogs, humans
• History of feeding raw meats or exposure to cats and/or cat feces
• Clin path: Selective granulocytic bone marrow hypoplasia, increased CK activity

Typical Gross Findings

• Systemic Toxoplasmosis Hallmarks: Interstitial pneumonia, multifocal necrotizing hepatic necrosis, lymphadenitis, myocarditis, and nonsuppurative meningoencephalitis
• Multiorgan multifocal necrosis from rapid tachyzoite replication
• Lung:
  • Pinpoint white foci scattered throughout the lung or diffuse interstitial; less common, hemorrhagic pneumonia with confluent involvement of ventral lung fields
  • Pneumonia (especially in kittens)
• Splenomegaly and lymphadenomegaly
• Eye: Granulomatous chorioretinitis
• Placenta: Multifocal necrosis and mineralization of cotyledonary villi; 1-2 mm yellow to white foci of necrosis throughout the villus; intercotyledonary chorioallantois edematous to unaffected
• Adrenal cortex: Focal cortical necrosis

Typical Light Microscopic Findings

• 3-6 μm crescentic zoites and/or cysts in areas of coagulative necrosis in one or more organs
• Tachyzoites rare in blood neutrophils and monocytes, common in macrophages of infected tissues (lung, intestine)
• Lung:
  • Severe, multifocal necrotizing interstitial pneumonia; type II pneumocyte hyperplasia; infiltration of macrophages and neutrophils
• Other tissues (liver, lymph nodes, spleen, pancreas, heart, skeletal muscle): Intracellular tachyzoites, random necrotic foci, with variable presence of inflammation (predominantly mononuclear); tissue cysts (bradyzoites)
• CNS (N-P02): Nonsuppurative meningoencephalitis of gray and white matter; necrotizing vasculitis, hemorrhage, tissue cysts, microglial nodules in chronic cases
• Radiculoneuritis and Myositis: Lymphoplasmacytic and histiocytic inflammation, myofiber necrosis and atrophy especially in puppies/kittens
• Eye: Chorioretinitis, lesion in retina, uvea, or extraocular muscles; in cats, lymphoplasmacytic anterior uveitis with positive T. gondii serology is more common
• Placenta (R-P01): Multifocal cotyledonary necrosis +/- mineralization with rare organisms within trophoblasts
• Aborted fetus: 95% of fetuses will have mild, nonsuppurative encephalitis or necrosis of cerebral white matter due to placentitis and hypoxemia

Ultrastructural Findings

• Tachyzoites present within a parasitophorous vacuole, 4-6 µm diameter, contain an anterior apical complex with conoid, micronemes, and rhoptries

Additional Diagnostic Tests

• Cytology (blood, CSF, body cavity aspirates, bronchoalveolar lavage): tachyzoites are small (1 × 3–7 μm) crescent-shaped bodies with a light–blue cytoplasm and a dark staining pericentral nucleus
• Definitive diagnosis is PCR; IHC in areas of lesions is highly supportive, but cross reactivity with N. caninum is possible
• Electron microscopy
• Serology not specific, but paired serology can aid in determining acute vs. chronic disease

Differential Diagnosis

• Neospora caninum: Requires immunohistochemical techniques or electron microscopy to differentiate from Toxoplasma organisms; may or may not have a parasitophorous vacuole; slightly thicker cyst wall than T. gondii or Sarcocystis; N. caninum cysts are found only in the CNS; N. caninum is commonly associated with bovine abortion
• Sarcocystis sp.: Requires Immunohistochemical techniques or electron microscopy to differentiate from Toxoplasma organisms; ultrastructurally, zoites of Sarcocystis are not within a parasitophorous vacuole, and merozoites lack rhoptries; associated with limited tissue necrosis
• Encephalitozoon cuniculi: Pseudocyst is larger (up to 120µm, Toxoplasma is 60µm), spores are acid fast (Toxoplasma is not), gram positive (Toxoplasma is gram negative), necrosis is not a common finding
• Hammondia hammondi: Has an entero-epithelial cycle in cats, but is not found in the lamina propria and does not cause extraepithelial infection in cats
• Leishmania and Trypanosoma: Tachyzoites with a kinetoplast and a distinct nucleus, often seen together as two basophilic dots
• Histoplasma sp.: Organisms are about the same size as Toxoplasma but have a PAS-positive and GMS-positive cell wall, and found only within macrophages/histiocytes; Toxoplasma is PAS-positive only
• Pneumocystis carinii: Much smaller and almost always found in pulmonary alveoli

Comparative Pathology

• Toxoplasma gondii can infect a wide variety of animals as intermediate hosts (extraintestinal life cycle) including birds, humans, and many other mammals
• Dogs: Most frequently seen in puppies; characterized by neurologic signs, gastrointestinal disease with diarrhea or pneumonia; disease is triggered by immunosuppression, such as with canine distemper virus infection
  • Current literature reports Hammondia heydorni as a differential for neutrophilic cholangitis, cholangiohepatitis, and cholecystitis in dogs with apicomplexan protozoal infections with features similar to T. gondii or N. caninum
• Sheep and Goats: Important cause of abortion
• Swine: Pneumonia, encephalitis, abortion (rare)
• Cattle: Not a significant abortifacient (unlike ddx Neospora caninum)
• Cetaceans: Nonsuppurative meningoencephalitis, necrotizing placentitis, and abortion in dolphins; possibly associated with morbillivirus coinfection; sporadic, but significant
• New World monkeys (especially captive squirrel monkeys, marmosets, and owl monkeys), meerkats, Pallas’ cats, sea otters, black-footed ferrets, free-ranging eastern barred Bandicoots are highly susceptible and acute disease can be fatal
• Avians: Significant cause of mortality in Hawaiian forest birds and canaries; causing conjunctivitis, blindness, and collapse of the globe +/- splenomegaly, hepatomegaly, and pericardial effusion
• Lab animal:
  • Mice: Wild mice are frequent intermediate hosts, but infections are nearly nonexistent in laboratory mice due to current housing practices
  • Rats: Occasional infection in laboratory rats; infection in rodents may cause loss of fear of cats and increased susceptibility to predation
  • Guinea pigs: Reported, but rare
  • Chinchilla: Reported outbreaks in farmed chinchillas; mucopurulent ocular and nasal discharge, diarrhea, and high mortality
  • Rabbits: Infection is common, but disease is rare
• Old World monkeys, rats, red-tailed hawks, cattle and horses seem highly resistant
• Wildlife: Infection has been described in many wildlife species including hyrax, raccoons with CDV, pinnipeds, bovids, dugong, flying foxes, and many more

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