Spirocerca lupi: Carcinogenic Esophageal Nematode of Canids – Life Cycle, Pathogenesis, Diagnostic Approaches, and Molecular Epidemiology

Introduction

Spirocerca lupi is a spirurid nematode parasite that primarily infects domestic dogs and wild canids, causing a potentially fatal disease known as spirocercosis [1]. This helminth is distributed across tropical and subtropical regions worldwide [2, 3]. The infection is characteristically associated with the formation of granulomatous nodules in the esophagus that can undergo malignant transformation into sarcomas, including fibrosarcomas and osteosarcomas [4, 5]. Additionally, aberrant larval migration can lead to severe pathology in the aorta, spinal cord, mesentery, and other ectopic sites [6, 7, 8]. The parasite has a complex indirect life cycle involving coprophagous beetle intermediate hosts and a range of paratenic hosts [6, 9].

Life Cycle and Transmission

Spirocerca lupi requires an obligate indirect life cycle. Adult worms reside within esophageal nodules of the definitive canid host, where they produce embryonated eggs that are shed in feces [6]. Eggs are ingested by coprophagous beetles (Coleoptera: Scarabaeidae), which serve as intermediate hosts [9, 10]. Within the beetle, first-stage larvae (L1) develop through two molts to infective third-stage larvae (L3) [9]. L3 larvae are approximately 1880–2662 μm in length and can be morphologically differentiated from other spirurid larvae by buccal cavity length and tail characteristics [9]. A recent study identified Catharsius molossus and Copris szechouanicus as new intermediate hosts in Vietnam [9], while Scarabaeus armeniacus has been reported in Iran [10]. Canids become infected by ingesting beetles harboring L3 larvae, or by ingesting paratenic hosts such as birds, reptiles, or small mammals that have accumulated L3 larvae in their tissues [6]. The practice of feeding uncooked chicken viscera to dogs has been identified as a risk factor in endemic areas [6].

After ingestion, L3 larvae penetrate the gastric or intestinal wall and migrate via the coelomic cavity to the thoracic aorta, where they undergo further development [3]. From the aorta, larvae migrate to the esophagus, where they induce the formation of granulomatous nodules and mature to adults [3]. The prepatent period is approximately 5–6 months [1].

Clinical Forms of Spirocercosis

Esophageal Spirocercosis

The classic presentation of spirocercosis involves esophageal nodules, which are granulomatous lesions containing adult worms [11]. Clinical signs include regurgitation, vomiting, dysphagia, and weight loss [11, 12]. In a case series from Vietnam, 10.5% of domestic dogs were found positive by copromicroscopy and PCR [13]. Outdoor access, season, and age were significant risk factors, with outdoor dogs having a 5.48-fold higher odds of infection [13].

Aortic Spirocercosis

During migration through the aortic wall, larvae can cause severe damage, leading to aneurysm formation, thrombosis, and even fatal aortic rupture [14, 3]. In a retrospective study of coyotes in Costa Rica, a significant association was found between S. lupi infection and the presence of esophageal granulomas and aortic aneurysms [14].

Aberrant Migrations

Aberrant migration of S. lupi L3 larvae can occur to a variety of ectopic sites, leading to diverse clinical syndromes.

Spinal Cord Migration. Aberrant intraspinal migration causes progressive neurological deficits, including pelvic limb paresis or paralysis, spinal pain, and urinary incontinence [7, 15]. In a large cohort of 284 dogs with spinal S. lupi (SSL), 46% had complete recovery at 1 month and 75% at 3 months [7]. Dogs with urinary incontinence and higher neurological grade had poorer prognosis [7]. Prophylactic treatment was associated with a lower risk of SSL (OR 0.43) [7]. CSF analysis typically reveals eosinophilic pleocytosis and elevated protein concentration [7]. PCR detection of 18S rDNA in CSF has a sensitivity of 86% for diagnosing SSL [29].

Mesenteric Aberrant Migration. Larvae can migrate through mesenteric arteries rather than gastric arteries, causing necrotizing eosinophilic arteritis, thrombosis, and intestinal infarction [8, 31]. This syndrome presents acutely with anorexia, weakness, vomiting, diarrhea, and collapse, often requiring surgical resection and anastomosis [8, 31].

Subcutaneous and Other Ectopic Sites. Nodular cyst-like masses containing adult worms have been reported over the thoracic wall [6] and in subcutaneous cervical tissues [16]. Aberrant migration to the ovary has also been documented [17]. The first molecular confirmation of S. lupi from a subcutaneous nodule in Central America was reported in Costa Rica [16].

Pathology and Neoplastic Transformation

Esophageal nodules induced by S. lupi are classified as inflammatory, preneoplastic, or neoplastic [3]. Chronic inflammation is thought to drive malignant transformation. Sarcomas occur in approximately 25% of infected dogs [5]. Histologically, esophageal fibrosarcomas consist of spindle cells arranged in intertwining whorls [4].

Immunohistochemical studies on non-neoplastic nodules demonstrated significantly increased expression of GDNF (glial cell-derived neurotrophic factor), Ki67 (proliferation marker), CD3 (T lymphocytes), CD20 (B lymphocytes), and CD68 (macrophages) compared to normal esophageal tissue [18]. The proliferation rate (Ki67) was 6–8 times higher and apoptosis rate (TUNEL assay) 2–3 times higher in nodules [18]. p53 expression was not significantly elevated [18]. These findings suggest GDNF involvement in nodule pathogenesis and that high proliferation/apoptosis ratios may predispose to neoplastic transformation [18].

The excretory-secretory products (ESP) of S. lupi are thought to drive sustained inflammation and carcinogenesis [5, 19]. Proteomic analysis identified 211 proteins, including annexin 6, which in humans is associated with cancer [19]. Stage-specific proteins were identified, with L4 females expressing unique proteins enriched in collagen trimers and macromolecular complexes [19].

Diagnosis

Fecal Examination

Routine copromicroscopy (flotation) can detect embryonated eggs of S. lupi, but sensitivity is limited. In a comparative study, fecal flotation detected only 27.8% of confirmed cases [30]. The eggs are thick-shelled, barrel-shaped, and contain a larva when freshly passed [11].

Molecular Diagnostics

High-resolution melt quantitative PCR (HRM qPCR) targeting the ITS1 locus demonstrated superior sensitivity, detecting as few as 0.2 eggs per gram, and did not cross-amplify with other canine gastrointestinal parasites [30]. The 18S HRM qPCR had equal sensitivity but cross-reacted with Toxocara canis and Toxascaris leonina [30]. The previously described semi-nested PCR targeting cox1 had a limit of detection of 526 epg [30].

PCR targeting the 18S rDNA in CSF is highly sensitive (86%) for ante-mortem diagnosis of spinal spirocercosis [29]. PCR confirmation from tissue samples and molecular characterization of ITS1 and cox1 genes are used for genotype assignment [20, 13].

Imaging

Esophagoscopy remains the gold standard for visualizing esophageal nodules [12, 21]. Nodules appear as glistening, pale pink protrusions in the proximal thoracic esophagus [12]. Thoracic radiography may reveal elevated trachea and enlarged mediastinal lymph nodes [12]. Ultrasonography of the abdominal aorta and celiac artery has low sensitivity but high specificity for detecting vascular wall irregularity associated with S. lupi migration [21].

Serology

Immunoreactivity of naturally infected dog sera against S. lupi somatic antigens reveals prominent bands at 199, 148, 100, 87, 49, 16, and 12 kDa [33]. Common antigenic bands between naturally infected dog sera and hyperimmune rabbit sera were observed at 100, 49, 16, and 12 kDa [33]. These antigens merit further investigation for diagnostic test development [33].

flowchart TD
    A[Clinical suspicion of spirocercosis], > B{Esophageal signs?}
    B, >|Yes| C[Esophagoscopy + biopsy]
    B, >|No| D{Neurologic signs?}
    D, >|Yes| E[CSF analysis + 18S PCR]
    D, >|No| F{Acute abdominal signs?}
    F, >|Yes| G[Exploratory laparotomy + histopathology]
    F, >|No| H[Fecal flotation + HRM qPCR]
    C, > I[Confirm nodule + histopathology]
    E, > J[Positive CSF PCR = SSL]
    G, > K[Larvae in mesenteric arteries]
    H, > L[ITS1 HRM qPCR most sensitive]
    I, > M[Grade nodule: inflammatory/preneoplastic/neoplastic]

Molecular Epidemiology and Genetics

Genotypes and Species Delineation

Two genotypes of S. lupi have been defined based on phylogenetic analyses of ITS1 and cox1 loci [3, 20]. Genotype 1 occurs in Africa, Asia, and Australia, while genotype 2 is found in Europe (Hungary, Italy) [20, 13]. Pairwise nucleotide distances between genotypes are 8.06% for ITS1 and 6.48% for cox1 [20]. A new species, Spirocerca vulpis, was described from red foxes in Europe based on morphological and molecular differences [3, 20].

Phylogeographic analysis using cox1 sequences suggests that S. vulpis originated in Europe and later diverged into S. lupi, which spread first to Africa, then to Asia, and finally to the Americas [2]. American S. lupi isolates cluster with genotype 1 (Israeli specimens) and show higher nucleotide similarity to Asian than to European strains [2]. In the Americas, S. lupi has been confirmed in dogs, coyotes (Canis latrans), and Andean foxes (Lycalopex culpaeus) [14, 22, 16].

The cox1 gene sequences from Andean foxes in Chile showed 93.1–95.8% similarity to S. lupi genotypes 1 and 2, and Poisson Tree Processes did not support a new species, suggesting these may represent a new variant or cryptic species [22].

Mitochondrial Genomics

The complete mitochondrial genome of S. lupi from South Africa is approximately 13.9 kb and contains 12 protein-coding genes and 2 rRNA genes [23]. Comparison with S. lupi from China revealed 6.1% mean genetic diversity [23]. Single-nucleotide polymorphisms in the nad2 gene, with ten sequence variants detected from a single nematode, suggest possible heteroplasmy [23].

Nuclear Genome and Population Genetics

The draft nuclear genome is approximately 150 Mb with 13,627 predicted protein-coding genes [24]. Known anthelmintic targets (β-tubulin, glutamate and GABA receptors) and vaccine candidates (cysteine protease inhibitor, cytokines) were identified [24]. Novel predicted targets include DNA-directed RNA polymerases and chitin synthase [24].

Population genetic analysis in South Africa using nine microsatellite loci revealed high polymorphism and two genetically distinct populations, with worms within a single dog being more closely related than worms from different dogs, indicating non-random transmission [34]. Long-distance dispersal appears frequent [34].

Prophylaxis and Treatment

Preventive treatment against S. lupi is recommended in endemic regions, as it may reduce the risk of spinal aberrant migration (OR 0.43, 95% CI 0.30–0.62) [7]. However, prophylactic therapy does not completely prevent infection, as half of dogs with mesenteric spirocercosis were receiving prophylaxis [8].

Treatment of esophageal spirocercosis includes anthelmintics (doramectin, avermectins) along with supportive care (rabeprazole, ondansetron) [12]. Surgical resection of esophageal nodules is indicated for neoplastic transformation; predictors of surgical outcome include nodule size and location [25]. Prognosis for spinal spirocercosis is favorable with appropriate supportive care, though recovery may take months [7].

Role of Paratenic and Wildlife Hosts

Coyotes in Costa Rica show high prevalence (84.6%) of S. lupi-associated lesions and likely play a significant role in transmission dynamics [14]. Raccoons (Procyon lotor) in Germany have been found infected with S. lupi larvae, representing the first autochthonous infection in that country and indicating the invasive species may serve as an additional host [26]. S. lupi in the Andean fox has been molecularly characterized, with cox1 sequences showing 99.95–99.98% similarity between individuals from Chile [22, 32].

FAQ

What is the primary definitive host of Spirocerca lupi?

The primary definitive hosts are domestic dogs and wild canids, with coyotes, foxes, and jackals also serving as competent hosts [14, 22, 3, 35].

How does Spirocerca lupi cause cancer in dogs?

Through sustained chronic inflammation driven by excretory-secretory products (ESP) that contain proteins homologous to those of other carcinogenic helminths, leading to high cellular proliferation (6–8 fold increase in Ki67) and dysregulated apoptosis, which can predispose to sarcomatous transformation [18, 5].

What diagnostic method is most sensitive for detecting Spirocerca lupi in feces?

High-resolution melt quantitative PCR targeting the ITS1 locus, with a limit of detection of 0.2 eggs per gram and no cross-reactivity with other common canine gastrointestinal parasites [30].

What is the prognosis for dogs with spinal aberrant migration of Spirocerca lupi?

Overall prognosis is favorable; 46% recover completely within 1 month and 75% within 3 months, though urinary incontinence and higher neurological severity grades are negative prognostic indicators [7].

Are there different genotypes of Spirocerca lupi?

Yes, two main genotypes have been identified: genotype 1 (Africa, Asia, Australia, Americas) and genotype 2 (Europe) based on ITS1 and cox1 sequences [2, 20]. A closely related species, Spirocerca vulpis, infects red foxes in Europe [3, 20].

References

[1] Alfaro-Segura, P., Baneth, G., & Rojas, A. (2024). Spirocerca lupi. Trends in Parasitology. https://www.semanticscholar.org/paper/c04a46a40f3f22ad10b3d4a3fb3e8b4a563bdeb9

[2] Alfaro-Segura, P., Robleto-Quesada, J., Montenegro-Hidalgo, V., et al. (2023). Elucidating Spirocerca lupi spread in the Americas by using phylogenetic and phylogeographic analyses. Frontiers in Parasitology. https://www.semanticscholar.org/paper/867db990d12ee57fb09da9fcd30c6993390f5c6a

[3] Rojas, A., Dvir, E., & Baneth, G. (2019). Insights on Spirocerca lupi, the Carcinogenic Dog Nematode. Trends in Parasitology. https://www.semanticscholar.org/paper/694862c7ea1d2af31865f1ceb10f696fac224526

[4] Gopal, K. (2025). Pathology of Spirocerca lupi associated oesophageal fibrosarcoma in a dog: A case report. Indian Journal of Veterinary Pathology. https://www.semanticscholar.org/paper/93b44a53211d79374665df854d1961211a74c36f

[5] Porras-Silesky, C., Mejías-Alpízar, M. J., Mora, J., et al. (2021). Spirocerca lupi Proteomics and Its Role in Cancer Development: An Overview of Spirocercosis-Induced Sarcomas and Revision of Helminth-Induced Carcinomas. Pathogens. https://www.semanticscholar.org/paper/293c9d092088785f4bb2f969dffa8916acb3df10

[6] Mayer, D., Deleza, M., & Sargison, N. (2025). Aberrant migration of Spirocerca lupi resulting in a nodular cyst‐like mass over the thoracic wall of an 18‐month‐old dog in Malawi. Veterinary Record Case Reports. https://www.semanticscholar.org/paper/896a63f1e17d26c7dc1711f408c598e2bbc096a7

[7] Lamy Casoy, Y., Srugo, I., Barnoon, I., et al. (2024). Aberrant Migration of Spirocerca Lupi to the Spinal Cord in Dogs: Association of Clinical Signs, CSF Analysis, Preventive Treatment, and Outcome. The Veterinary Journal. https://www.semanticscholar.org/paper/e1aade0797aea70b5451e2dd4d1da837455b7e7f

[8] Brenner, O., Botero-Anug, A.-M., Rojas, A., et al. (2019). Aberrant Mesenteric Migration of Spirocerca lupi Larvae Causing Necrotizing Eosinophilic Arteritis, Thrombosis, and Intestinal Infarction in Dogs. Veterinary Pathology. https://www.semanticscholar.org/paper/4dfe6424e0e5ea7f96626274d158a02fe4f5897d

[9] Doanh, P., Hoa, L., Hien, H., et al. (2023). Larvae of Spirocerca lupi and another spirurid species in the same dung beetles: notes on species identification. Journal of Helminthology. https://www.semanticscholar.org/paper/18deb0aabbb8565d2c7f9cbe80150a6ed7f01f5b

[10] Mohtasebi, S., Teimouri, A., Abbaszadeh Afshar, M. J., et al. (2021). First report of Spirocerca lupi larva in dung beetles (Scarabaeus armeniacus) in the central region of Iran: A morphological and molecular identification. Comparative Immunology, Microbiology & Infectious Diseases. https://www.semanticscholar.org/paper/9302e8b8f8d6ee8dff549cfb6f6d178cd4649d33

[11] Bora, S. (2026). Unraveling the enigma of Spirocerca lupi infection in dogs: A hidden menace. Indian Journal of Veterinary Pathology. https://www.semanticscholar.org/paper/26023eeb519a8e500cc949fc0ab529cbdfe91d92

[12] Jayakrishnan, J., Venugopal, S., Philip, L., et al. (2022). Endoscopic evaluation of Spirocerca lupi infection in a non-descript dog: A case report. Journal of Veterinary and Animal Sciences. https://www.semanticscholar.org/paper/4f5d06cd076c216083f202f46f8d1938e0823666

[13] Tran, N. H., Chuc, T., Bang, P. N., et al. (2022). The prevalence and risk factors of Spirocerca lupi in domestic dogs in the Mekong Delta of Vietnam. Veterinary Integrative Sciences. https://www.semanticscholar.org/paper/b1936da5e810df7855560cde79815361a19704c0

[14] Romero-Vega, L., Rojas, A., Santoro, M., et al. (2025). Retrospective study of spirocercosis in coyotes (Canis latrans) in Costa Rica: epidemiology, pathological findings, and molecular characterization of Spirocerca lupi. Parasites & Vectors. https://www.semanticscholar.org/paper/4aa76940c73faac7b6def666e25619817a2464c3

[15] Chai, O., Yas, E., Brenner, O., et al. (2018). Clinical characteristics of Spirocerca lupi migration in the spinal cord. Veterinary Parasitology. https://www.semanticscholar.org/paper/326c563c47e7b7f30a6587504707e4891a09aa8d

[16] Porras-Silesky, C., Fernández-Trejos, L., Villalobos, R., et al. (2022). Subcutaneous spirocercosis in a dog from Costa Rica and first molecular confirmation of Spirocerca lupi in Central America. Veterinary Parasitology: Regional Studies and Reports. https://www.semanticscholar.org/paper/b31b595fe055412136ecd994754e536c39099b91

[17] Sreeranjani, R., Anbarasi, P., Senthilvel, K., et al. (2024). Spirocerca lupi in the ovary of a dog. Journal of Veterinary Parasitology. https://www.semanticscholar.org/paper/259c262cf5dc09d9d2204203fedf2aa8c8ad500c

[18] Amoorahim, S., & Amniattalab, A. (2025). Immunohistochemical Expression of GDNF, P53 and Ki67 with Tunel Assay in Canine Non-Neoplastic Esophageal Nodules Induced by Spirocerca lupi. Macedonian Veterinary Review. https://www.semanticscholar.org/paper/d95353b7b1e30d0d8fd8fe96f1137446aab7103b

[19] Rojas, A., & Baneth, G. (2019). Secretome of the carcinogenic helminth Spirocerca lupi reveals specific parasite proteins associated with its different life stages. Veterinary Parasitology. https://www.semanticscholar.org/paper/9637657e0a748497a54ca52917489809c547c

[20] Rojas, A., Dvir, E., Farkas, R., et al. (2018). Phylogenetic analysis of Spirocerca lupi and Spirocerca vulpis reveal high genetic diversity and intra-individual variation. Parasites & Vectors. https://www.semanticscholar.org/paper/7270c61ae02e91d22dd675d84e34453e8be46545

[21] Merhavi, N., Segev, G., Dvir, E., et al. (2020). Ultrasonography is insensitive but specific for detecting aortic wall abnormalities in dogs infected with Spirocerca lupi. The Veterinary Record. https://www.semanticscholar.org/paper/0581e3600a5716f7e26130f2b59c18b425413950

[22] Di Cataldo, S., Cevidanes, A., Sepúlveda-García, P., et al. (2023). Spirocerca lupi in the stomach of two Andean foxes (Lycalopex culpaeus) from Chile. Parasitology Research. https://www.semanticscholar.org/paper/0ae524fdef94cb7e41aeb9a61e99bea17376d5f4

[23] Rothmann-Meyer, W., Naidoo, K., & de Waal, P. J. (2021). Comparative mitogenomics of Spirocerca lupi from South Africa and China: Variation and possible heteroplasmy. Veterinary Parasitology. https://www.semanticscholar.org/paper/a289c54008a237f983f2d65ae26f6bd68d20d1d1

[24] Rothmann-Meyer, W., Naidoo, K., & de Waal, P. J. (2024). Spirocerca lupi Draft Genome, Vaccine and Anthelmintic Targets. Molecular and Biochemical Parasitology. https://www.semanticscholar.org/paper/d163b640f7e893abf9accb1485446f030de48c0a

[25] Pazzi, P., Kavkovsky, A., Shipov, A., et al. (2018). Spirocerca lupi induced oesophageal neoplasia: Predictors of surgical outcome. Veterinary Parasitology. https://www.semanticscholar.org/paper/51943b33ab5ecc21628d3b7f06d17c1c6ee987ed

[26] Langner, T., Otranto, D., Santos, M. A. B., et al. (2024). Detection of Spirocerca lupi and an unknown Trichinella-like nematode in raccoon (Procyon lotor). International Journal for Parasitology: Parasites and Wildlife. https://www.semanticscholar.org/paper/b897aa29027045ac42e70887959bd1b196e43b40

[27] Caldas, D. E. P. (2024). SARCOMA ESOFÁGICO INDUZIDO POR SPIROCERCA LUPI. Anais do III Congresso Brasileiro de Clínica Médica Veterinária. https://www.semanticscholar.org/paper/6452a67dcb692b0a4dac5e8e471d087c2ecb8a35

[28] Hoa, L., Van Hien, H., Phúc, P., et al. (2021). Morphological and molecular characterization of Spirocerca lupi (Nematoda: Spirocercidae) from domestic dogs in Vietnam with reference to Spirocerca vulpis. Parasitology International. https://www.semanticscholar.org/paper/857e5514d077b21e717b1ab3ee4d1d78a10fcbc2