When “Fungal” Isn’t Fungal: Recognizing Pythium insidiosum in Veterinary Patients

By Dr. Aiswarya Prasad

At MiDOG Animal Diagnostics, we often encounter pathogens that highlight the diagnostic complexity of infectious disease in veterinary medicine. One such organism is Pythium insidiosum, which causes pythiosis, a severe and often life-threatening disease most commonly affecting dogs and horses, with less frequent reports in cats and cattle.

Diagnosis of pythiosis is particularly challenging because the organism responsible can closely resemble fungal pathogens both clinically and histologically. However, Pythium insidiosum is not a true fungus. Instead, it belongs to Oomycetes, a group of eukaryotic organisms more closely related to algae than fungi. This biological distinction has important implications for both diagnosis and treatment, especially in cases where infections fail to respond to standard antifungal therapy.

In this post, we review the clinical significance of Pythium insidiosum, recommended diagnostic samples, and how molecular diagnostics can improve detection of this unusual pathogen.

What is Pythium insidiosum?

Pythium insidiosum is unique among members of the genus Pythium in that it can cause disease in animals. It is commonly found in standing or slow-moving freshwater environments, particularly in warm or subtropical climates, but has recently also been reported in California and Arizona.

Infection occurs when motile zoospores present in contaminated water contact damaged skin or mucosal surfaces or are ingested during drinking or grooming. Infection is typically locally invasive, with dissemination occurring less commonly.

One key reason the distinction of this pathogen from fungi is clinically relevant is that its cell wall and membrane structure differ from true fungi. Oomycetes lack the ergosterol-containing membranes targeted by many antifungal drugs, which contributes to the limited effectiveness of conventional antifungal therapy in pythiosis.

Clinical Presentation in Veterinary Patients

The clinical presentation of pythiosis varies depending on the species affected and the site of infection.

A quiet change in posture, energy, or comfort can be easy to overlook. In the context of pythiosis, subtle or nonspecific signs may delay recognition and make earlier diagnostic clarity even more important.

A brown and white dog lies quietly on a bed with its head resting low, illustrating a subdued posture that can reflect nonspecific signs of illness in canine patients.

Dogs

Dogs most commonly develop gastrointestinal or cutaneous disease.

  • Gastrointestinal pythiosis in dogs typically affects the stomach, small intestine, or colon.
    • Clinical signs may include chronic vomiting, diarrhea (sometimes hemorrhagic), weight loss, abdominal pain, and palpable abdominal masses. Imaging often reveals marked intestinal wall thickening, which can mimic neoplastic disease. Regional lymphadenopathy is commonly present.
  • Cutaneous pythiosis typically presents as ulcerated nodules, nonhealing wounds, draining tracts or fistulas or rapidly progressive granulomatous lesions.
    • Lesions often occur on the extremities, tail base, ventral neck, or perineal region, areas frequently exposed to contaminated water.
Horses

In horses, pythiosis most commonly presents as ulcerative granulomatous skin lesions, sometimes referred to historically as “swamp cancer.”

  • Typical features include large ulcerative masses, copious serosanguinous discharge, firm necrotic concretions called kunkers.
  • Lesions typically develop on the lip, genital regions, lower limbs, abdomen, or chest, reflecting environmental exposure to contaminated water sources.

A close-up of a tabby cat lying down with one paw covering its face, illustrating how discomfort or illness in veterinary patients can be subtle and easy to miss.

Cats

Pythiosis in cats is less common but has been reported in several forms, including:

  • Cutaneous lesions
  • Subcutaneous masses
  • Nasal or gastrointestinal infections

Because feline cases are relatively rare, diagnosis is often delayed or overlooked in early stages.

Diagnostic Challenges

Diagnosing Pythium insidiosum infection can be challenging for several reasons.

  • Clinical signs often overlap with fungal infections, bacterial granulomas, or neoplastic disease, making initial clinical suspicion difficult.
  • Histopathologic identification requires tissue sampling and is often inconsistent. Organisms may be sparse or entirely absent on cytology or histopathology, and when present cannot be reliably distinguished from other fungal or oomycete pathogens based on morphology alone.
  • Traditional culture methods may be slow and require specialized laboratory conditions, and organism recovery can be inconsistent.
  • Serologic testing (e.g., ELISA for anti-Pythium antibodies) is available and can be helpful, but results must be interpreted in the context of clinical findings and may not always distinguish active infection from exposure.
  • PCR-based assays can detect Pythium insidiosum DNA from tissue samples. However, these tests are targeted, meaning they require prior suspicion of Pythium and will not detect organisms outside of the assay design.

Because of these limitations, pythiosis is believed to be underrecognized in veterinary medicine, particularly when it is not initially included in the differential diagnosis or when targeted testing does not include the causative organism.

Best Sample Types for Detecting Pythium insidiosum

Selecting appropriate specimens is critical for improving diagnostic success and should be guided by the site of infection and expected organism distribution.

Pythium insidiosum is typically localized within actively inflamed and infiltrated tissues, where it forms granulomatous and eosinophilic lesions. As a result, diagnostic yield is highest when sampling areas of active disease rather than superficial or necrotic material.

Affected tissue from primary lesions, as the organism is most consistently recovered from deep tissue at the site of infection, including

  • Cutaneous and subcutaneous lesions
  • Gastrointestinal lesions (e.g., thickened stomach, small intestine, or ileocolic region)
  • Nasal or paranasal tissue when upper respiratory involvement is present

Sampling should preferentially target viable, advancing margins of lesions, as central necrotic areas may contain fewer intact organisms.

Surgically resected tissue – When lesions are excised, surgical specimens often provide the most representative material, including both organism-rich and actively inflamed regions.

Lesion-associated exudate or aspirates – Fluid or aspirates from affected sites may contain inflammatory cells and occasional hyphal elements, although organism burden can be variable, and these samples are generally less reliable than tissue.

A laboratory image showing test tubes and a stylized DNA strand, representing molecular diagnostics and genomic testing used to detect infectious agents with greater specificity.

The Role of Next-generation sequencing (NGS)

NGS-based diagnostics provide a powerful approach to overcome challenges in diagnosing oomycete infections such as pythiosis.

In contrast to targeted PCR assays, NGS does not rely on predefined targets and does not require prior suspicion of specific pathogens. Instead, it analyzes all nucleic acid present in a sample, allowing for unbiased detection of all types of organisms simultaneously.

NGS-based diagnostics is especially valuable in situations such as these where other tests may be off-target, or histopathology and culture results are inconclusive, allowing more rapid and comprehensive pathogen identification.

In a recent MiDOG case, genomic analysis detected Pythium insidiosum in a cat presenting with chronic nonhealing skin lesions. Based on the clinical history provided, the symptoms were present for over 5 months and had been treated with antibiotics and corticosteroids without resolution prior to submission. This type of presentation is consistent with the chronic, treatment-resistant cutaneous lesions described in pythiosis, where the underlying etiology may not be initially suspected.

When pythiosis is mistaken for fungal disease, earlier recognition often depends on looking beyond conventional assumptions. Molecular diagnostics can help clarify the true cause of infection and support more informed next steps

Integrating Molecular Diagnostics into Clinical Practice

For veterinarians managing animals with chronic gastrointestinal disease or nonhealing skin lesions, early recognition of pythiosis is critical.

Prognosis is often guarded to poor when lesions cannot be completely surgically removed, and medical therapy alone has limited success in many cases.

Situations where advanced diagnostics may be particularly helpful include:

  • Chronic gastrointestinal disease with unexplained intestinal thickening
  • Nonhealing cutaneous lesions following water exposure
  • Suspected fungal infections that do not respond to antifungal therapy
  • Cases with negative or conflicting PCR and serology results

Accurate pathogen identification allows clinicians to reach a diagnosis sooner and pursue appropriate treatment strategies earlier in the disease course.

Learn More

You can view the full MiDOG Animal Diagnostics report for a case here:

A MiDOG Animal Diagnostics All-in-One Microbial Test report for a cat skin and tissue sample showing no bacteria or fungi detected and Pythium insidiosum identified under parasites, with 100% of the microbial composition listed as other eukaryota.

VIEW REPORT HERE

If you have questions about submitting samples or using genomic diagnostics in veterinary infectious disease cases, the MiDOG team is always happy to help.

References
  1. Merck Veterinary Manual. Oomycosis in Animals (Pythiosis and Lagenidiosis).
  2. Gaastra W, Lipman LJA, De Cock AWAM, et al. Pythium insidiosum: An overview. Veterinary Microbiology. 2010;146:1–16.
  3. Krajaejun T, et al. Global distribution and clinical features of pythiosis. Journal of Fungi. 2022;8:182.
  4. Mendoza L, Hernandez F, Ajello L. Life cycle of the human and animal oomycete pathogen Pythium insidiosum. Journal of Clinical Microbiology. 1993;31:2967–2973.
  5. Berryessa NA, Marks SL, Pesavento PA, et al. Gastrointestinal pythiosis in dogs. Journal of Veterinary Internal Medicine. 2008;22:142–148.
  6. Chaffin MK, Schumacher J, McMullan WC. Cutaneous pythiosis in the horse. Veterinary Clinics of North America: Equine Practice. 1995;11:91–103.
  7. Brown CC, Roberts ED. Intestinal pythiosis in animals: pathologic findings. Veterinary Pathology. 1988;25:131–143.
  8. Barua S, Tarannum A, Newton J, et al. Improving noninvasive diagnosis of Pythium insidiosum infections in dogs: complementary roles of ELISA and PCR. American Journal of Veterinary Research. 2026.
  9. Carnaúba RTM, do Prado AC, Camargo GG, et al. Pythium insidiosum and pythiosis: a review of the literature. Revista de Veterinária e Zootecnia. 2023.