Gnathostomiasis

Gnathostomiasis is a food-borne zoonotic disease caused by the third-stage larvae of Gnathostoma nematodes. It is endemic to regions such as Asia and Central and South America and is transmitted primarily through ingestion of raw or undercooked intermediate hosts (e.g., frogs, birds, freshwater fish). The clinical presentation is classified as either cutaneous or visceral. Cutaneous gnathostomiasis, the most common form, is characterized by intermittent, migratory subcutaneous swelling. Visceral gnathostomiasis involves larval migration to internal organs, which can lead to severe complications (e.g., vision loss). Central nervous system (CNS) involvement is known as neurognathostomiasis and is a life-threatening form of the disease. Diagnosis is based on clinical features, peripheral eosinophilia, and a relevant exposure history, with confirmation via biopsy or serology. Management includes surgical removal of larvae and/or pharmacological treatment (e.g., albendazole). Relapse is common and may require further treatment courses. Prevention focuses on avoiding consumption of raw or undercooked intermediate hosts.

• Approximately 5,000 cases have been reported worldwide. ^[1]
• Endemic in: ^{[2] [1]}
  • Asia (i.e., Southeast Asia, China, Japan, Korea)
  • South America (particularly Ecuador and Peru)
  • Central America (i.e., Mexico)
• Considered an emerging disease in exposed travelers returning to nonendemic areas ^[1][2]

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen: third-stage larvae (L3) of Gnathostoma spp. nematodes ^[1]
  • At least five species are known to infect humans. ^[1]
  • G. spinigerum: most common species (particularly in Asia) ^[2]
  • G. binucleatum: typically in Mexico, Peru, and Ecuador ^[2]
• Mode of transmission ^[1]
  • Oral (primary route)
    • Ingestion of undercooked or raw meat of intermediate hosts (e.g., frogs, snakes, birds, freshwater fish)
    • Drinking water containing infected copepods
  • Other routes (rare)
    • Skin penetration, especially through wounds
    • Transplacental transmission in pregnant individuals with a high burden of infection
• Life cycle ^[1]
  • Adult Gnathostoma nematodes live and replicate in the stomach of the definitive host (e.g., dog, cat, large felines) → Eggs are excreted in feces → First-stage larvae (L1) hatch in freshwater→ L1 are ingested by first intermediate host (i.e., freshwater copepods) → L1 develop into second-stage larvae (L2) → First intermediate host is ingested by second intermediate host (e.g., fish or tadpoles) → L2 larvae develop into L3 larvae in muscle tissue → Intermediate host is ingested by definitive host.

Symptoms are caused by larvae migrating through subcutaneous tissue and penetrating other tissue and organs.

Systemic symptoms

• Onset: may occur within 1–2 days of ingestion ^[1]
• Duration > 2 weeks
• Symptoms include: ^[1]
  • Fever
  • Anorexia, nausea, vomiting
  • Abdominal pain
  • Joint pain

Cutaneous manifestations ^[1][2]

• Most common presentation
• Intermittent, migratory subcutaneous swelling, plaques, nodules (panniculitis), and/or serpiginous lesions (i.e., cutaneous larva migrans) that are often pruritic and painful
  • Commonly on the chest, abdomen, and/or extremities
  • Episodes may recur intermittently for over 10 years if untreated.
• Furuncle-like lesions (small papules or pustules)

Visceral manifestations ^[1]

• Ocular, e.g.:
  • Eyelid edema
  • Conjunctival pain and erythema
  • Vision loss
• Auricular, e.g.:
  • Tinnitus
  • Dizziness
  • Hearing loss
• Pulmonary, e.g.:
  • Cough
  • Chest pain
  • Pneumothorax
• Gastrointestinal, e.g.:
  • Abdominal pain
  • Anorexia
  • Vomiting
  • Indigestion
  • Gastric ulcer or perforation
• Genitourinary, e.g.:
  • Hematuria
  • Foreign body sensation with urination
• CNS (neurognathostomiasis), e.g.:
  • Acute onset of severe radicular pain with headache
  • Loss of cranial nerve function
  • Weakness and/or paralysis
  • Quadriparesis
  • Bladder dysfunction
  • Cerebral edema
  • Intracerebral and/or subarachnoid hemorrhage

Approach

• Diagnosis is based on the following: ^[1]
  • Suggestive clinical features (e.g., intermittent, migratory subcutaneous or cutaneous swelling)
  • Relevant exposure history (e.g., consumption of raw fish)
  • Peripheral eosinophilia
• Perform biopsy to confirm presence of Gnathostoma larva and tissue eosinophilia.
• Consider alternative diagnostic methods to confirm diagnosis when biopsy is not possible (e.g., serology).

Laboratory studies

• CBC: eosinophilia
• Serology ^[3]
  • Considered when biopsy or removal of larvae is not possible (e.g., in visceral gnathostomiasis)
  • Method: serum or CSF antigen-specific IgG (e.g., 24 kDa or 33 kDa antigens)

Biopsy ^[1]

• Method: biopsy of lesion (most commonly cutaneous) with or without surgical removal of larvae ^[1]
• Histopathology
  • Varying degrees of eosinophil infiltration (most commonly lobular infiltration of numerous eosinophils) ^[2]
  • Identification of L3 larva in tissue (rare)
• Molecular testing (e.g., PCR of tissue or nematode): Consider as an alternative confirmatory test and/or to identify Gnathostoma spp.

Imaging ^[1]

• Considered in visceral disease in combination with serology
  • Modalities: MRI (preferred in neuroimaging), CT, and/or ultrasound of affected viscera ^[1]
  • Findings: may show larval migration tracks (particularly in the CNS) ^[1]

• Sparganosis ^[1]
• Cysticercosis ^[1]
• Other causes of cutaneous larva migrans (e.g., Ancylostoma spp., Strongyloides stercoralis) ^[3]
• Angiostrongyliasis ^[3]
• Wells cellulitis ^[2]

The differential diagnoses listed here are not exhaustive.

Surgical removal of larvae is the most effective treatment. Pharmacological treatment is used when surgical management is not possible. ^[1]

Pharmacological treatment ^[1][3]

• Antihelminthics
  • First-line: albendazole ^[1]
  • Alternative: ivermectin ^[1][3]
• Glucocorticoids ^[3]
  • Agents: prednisolone, dexamethosone
  • Considered in neurognathostomiasis to relieve cerebral and spinal edema
  • May cause further larval migration ^[1]

Management of relapse ^[1][3]

• Relapses are common after initial pharmacological treatment; patients may require multiple courses of therapy.
• Strategies for recurrence include: ^[3]
  • Switching to the alternative drug
  • Administering a second course of the initial drug
  • Extending the duration of therapy

Complications are caused by larval migration into vital organs and can be severe. ^[1]

• Ocular: permanent vision loss or blindness ^[1]
• Neurological ^[1]
  • Paralysis
  • Coma
  • Death (if larvae invade the brainstem)

We list the most important complications. The selection is not exhaustive.

• Adequately cooking food to effectively kill larvae ^[1]
• Freezing infected food for 3–5 days at -20°C (-4°F) ^[1]