Toxocariasis

Etiology & Epidemiology

• Visceral larva migrans (VLM): predominantly children aged 2–7 years
• Ocular larva migrans (OLM): older children/adolescents (5–10 years); more prevalent in southern US states

Pathobiology

Clinical Manifestations

Imaging

Diagnosis

• ELISA for anti-Toxocara antibodies (available via CDC) + confirmatory immunoblot — does not distinguish active from past infection
• Recombinant larval antigen ELISAs have improved sensitivity/specificity but are not yet widely available
• PCR not currently available
• Liver biopsy (demonstrates eosinophilic granulomas, larvae rarely seen) — low sensitivity, not routinely recommended
• Stool examination is not useful (humans are dead-end hosts; no adult worms form)

Treatment

Fascioliasis

Etiology & Epidemiology

Life Cycle

1. Eggs excreted in feces → deposited in water
2. Miracidia hatch (9–14 days) → infect freshwater snails (Lymnaea spp.) → sporocysts → rediae → cercariae (4–7 weeks)
3. Free-swimming cercariae encyst as metacercariae on aquatic vegetation (watercress, water lettuce, alfalfa, mint, parsley, khat)
4. Humans infected by ingestion of raw contaminated vegetation or water
5. Larvae excyst in duodenum → penetrate bowel wall → migrate through peritoneal cavity → reach liver within 4 weeks → penetrate Glisson's capsule
6. Migrate through liver parenchyma for 3–5 months → enter bile ducts → mature adults lay eggs (→ passed via sphincter of Oddi into stool)
7. Adults may survive in bile ducts for up to 13 years

Histopathology & Imaging

Clinical Phases

Acute (Invasive/Migratory) Phase

• Prolonged fever, hepatomegaly, right upper quadrant / epigastric pain, marked eosinophilia
• Anorexia, weight loss, nausea, vomiting, cough, diarrhea, urticaria, lymphadenopathy, arthralgias
• Acute diarrhea (2–5 days) may precede hepatic invasion
• Hyperbilirubinemia is notably absent in this phase
• CT shows multiple hypodense lesions that change in position, attenuation, and shape over time (migrating parasites) — can mimic metastases; also subcapsular hematoma, tracklike serpiginous lesions (2–10 mm)
• Ectopic/extrahepatic migration (rare): subcutaneous tissue, pancreas, eye, brain, stomach wall

Chronic (Biliary) Phase

• Colicky RUQ pain, biliary obstruction symptoms
• Eosinophilia may be absent in up to half of cases
• Bile ducts become dilated, thick-walled, fibrotic, and calcareous
• Complications: cholangitis, choledocholithiasis, hemobilia, liver abscess, liver fibrosis
• Elevated serum alkaline phosphatase (biliary obstruction)
• Adult flukes may be visible on ERCP
• Adults can survive in bile ducts up to 13 years

Diagnosis

Treatment

• Standard adult dose: 10 mg/kg once (or 10 mg/kg × 2 doses 12–24 hours apart for severe infection)
• Praziquantel is ineffective against Fasciola spp.
• Surgical/endoscopic intervention (ERCP) may be required for biliary obstruction

Key Comparison

TOXOCARIASIS

1. Etiology and Life Cycle

1. Infective eggs ingested by dog → larvae hatch, penetrate intestinal wall → migrate via portal blood to liver, then lungs → ascend bronchial tree → swallowed → develop to adult worms in small intestine → lay eggs excreted in feces.
2. In pregnant bitches, dormant somatic larvae reactivate → infect puppies transplacentally and via suckling (transmammary transmission) — making puppies the primary egg-shedding reservoir.
3. Eggs require 2–4 weeks of embryonation in the environment before becoming infectious. They do NOT hatch immediately upon shedding.

Humans ingest embryonated eggs → larvae hatch in the small intestine → penetrate the intestinal mucosa → enter the portal circulation → disseminate to liver, lungs, CNS, eyes, and other organs → cannot develop into adult worms → larvae remain in tissues, continue migrating, and eventually die, triggering eosinophilic granuloma formation.

2. Epidemiological Characteristics

3. Pathogenesis of Visceral and Ocular Involvement

• Liver — most common initial target: larvae lodge in sinusoids, triggering focal eosinophilic infiltration and granuloma formation. Granulomas consist of eosinophils, macrophages, epithelioid cells, and giant cells surrounding a central larva or necrotic track. Hepatomegaly results from cumulative granulomatous inflammation.
• Lungs — larvae traverse pulmonary capillaries, eliciting eosinophilic pneumonitis with wheezing and transient infiltrates.
• CNS — larvae cross the blood–brain barrier → eosinophilic meningoencephalitis, cerebral vasculitis, space-occupying granulomas, myelitis.
• Eyes — larvae that reach the retinal vasculature form a single eosinophilic granulomatous mass (usually in the posterior pole) around the entrapped larva, causing fibrous traction, retinal detachment, and loss of vision.
• Myocardium, kidney — less common sites.

• Immediate-type (Type I) hypersensitivity → IgE production, mast cell degranulation, eosinophil recruitment, urticaria, wheezing.
• Delayed-type (Type IV) hypersensitivity → macrophage/T-cell-mediated granuloma formation.

4. Clinical Manifestations

Covert Toxocariasis

• Most common form.
• Persistent peripheral eosinophilia, often without systemic symptoms.
• Represents the continuation of larval migration without heavy burden.

Visceral Larva Migrans (VLM)

• Fever (low-grade, prolonged), malaise, anorexia, weight loss.
• Pulmonary: cough, wheezing, dyspnea; transient pulmonary infiltrates on chest X-ray (~50% of symptomatic patients).
• Hepatosplenomegaly → right upper quadrant pain.
• Eosinophilia: can be extreme (up to 90% of leukocytes); leukocytosis, hypergammaglobulinemia.
• Urticaria or rash (IgE-mediated).
• Symptoms develop gradually and resolve over 4–8 weeks with or without treatment.
• Uncommon but serious: myocarditis, nephritis, eosinophilic meningoencephalitis.
• Rare deaths from severe neurologic, pneumonic, or myocardial involvement.

Neurotoxocariasis

• Eosinophilic meningoencephalitis, space-occupying brain lesions, myelitis, cerebral vasculitis.
• Seizures, encephalopathy, neuropsychiatric symptoms.

Ocular Larva Migrans (OLM)

• Affects older children and adolescents; usually no history of pica, no peripheral eosinophilia, no systemic features.
• Unilateral visual impairment, strabismus, eye pain.
• Fundoscopy: whitish eosinophilic granulomatous mass in the posterior pole of the retina, or endophthalmitis, uveitis, chorioretinitis.
• Can mimic retinoblastoma (leading to unnecessary enucleation if misdiagnosed).

5. Laboratory and Serological Diagnostics

6. Treatment Principles

7. Preventive and Hygienic Measures

• Regular deworming of dogs and cats, especially puppies and kittens (highest egg output) — reduces environmental contamination.
• Prevent children from eating soil (pica); supervise play in parks and sandboxes.
• Cover sandboxes when not in use to prevent animal defecation.
• Thorough handwashing after contact with soil, animals, or animal feces.
• Do not allow dogs to defecate in playgrounds or children's play areas.

• Proper disposal of dog and cat feces; municipal by-laws on leash and fecal disposal.
• Routine veterinary deworming programs reduce the community reservoir.
• Public health education about geophagia (pica) risk, especially in low-income communities.
• No vaccine is available.

FASCIOLIASIS

1. Etiology and Life Cycle

Adult flukes in host bile ducts
       ↓ (eggs pass via bile → feces)
Unembryonated eggs deposited in water
       ↓ (9–14 days)
Miracidia hatch → invade freshwater snails (Lymnaea spp.)
       ↓ (4–7 weeks in snail)
Sporocysts → Rediae → Cercariae
       ↓ (cercariae exit snail, swim freely)
Metacercariae encyst on aquatic vegetation
(watercress, water lettuce, alfalfa, mint, parsley, khat)
       ↓ HUMAN INFECTION (ingestion of contaminated plants/water)
Metacercariae excyst in duodenum
       ↓
Larvae penetrate intestinal wall → peritoneal cavity
       ↓ (~4 weeks)
Penetrate Glisson's capsule → migrate through liver parenchyma (3–5 months)
       ↓
Reach bile ducts → mature into adult flukes
       ↓ (~2 months after initial infection)
Adults lay eggs → eggs pass via sphincter of Oddi → stool
(Adults may survive in bile ducts for up to 13 years)

2. Epidemiological Characteristics

3. Pathogenesis of Hepatic Involvement

Acute (Invasive/Migratory) Phase — weeks to 3–5 months post-infection

1. Intestinal phase: Metacercariae excyst in the duodenum. Acute diarrhea may occur for 2–5 days before liver invasion.
2. Peritoneal phase: Larvae penetrate the bowel wall and traverse the peritoneal cavity.
3. Hepatic migration: Larvae penetrate the liver capsule and burrow through the hepatic parenchyma for 3–5 months, creating inflammatory tracks. The ongoing inflammatory process is accompanied by:
   • Eosinophilic infiltration at the migration front.
   • Focal hemorrhage, necrosis, and abscess formation along larval tracks.
   • Subcapsular liver hematoma in severe cases.
   • Enhancement of Glisson's capsule on imaging.
4. When larvae die during migration, they leave cavities filled with necrotic debris → replaced by scar tissue → eventually calcified granulomas.
5. On CT: multiple hypodense lesions that change in position and shape over time (actively migrating parasites) — characteristic of acute fascioliasis. May mimic hepatic metastases or abscesses.

Chronic (Biliary) Phase — after flukes establish in bile ducts

1. Mature adult flukes reside in hepatic and common bile ducts (and occasionally the gallbladder), consuming hepatocytes and duct epithelium.
2. Bile ducts develop: dilatation, thick walls, hyperplastic epithelium, marked periductal fibrosis, calcareous deposits, and yellowish-brown bile.
3. Biliary obstruction → elevated alkaline phosphatase, colicky pain.
4. Bacterial superinfection → ascending cholangitis.
5. Other complications: choledocholithiasis, hemobilia, liver abscess, liver fibrosis.
6. Adults may survive in the biliary tree for up to 13 years.
7. Ectopic migration (rare): subcutaneous tissue, pancreas, eye, brain, stomach wall — causing site-specific manifestations including ectopic pancreatitis (classic ERCP case: flukes extracted from the common bile duct causing acute pancreatitis).

4. Clinical Manifestations

Acute Phase

• Prolonged fever (weeks to months).
• Hepatomegaly with right upper quadrant / epigastric pain and tenderness.
• Marked eosinophilia (often the dominant laboratory finding).
• Anorexia, weight loss, nausea, vomiting.
• Cough (diaphragmatic irritation or pulmonary migration).
• Urticaria, arthralgia, lymphadenopathy.
• Mimics acute cholecystitis, but with significant eosinophilia and absent hyperbilirubinemia — a key distinguishing feature in the acute phase.

Chronic Phase

• Colicky RUQ pain (biliary colic pattern).
• Signs of biliary obstruction: jaundice, pale stools, dark urine.
• Elevated alkaline phosphatase; bilirubin rises (unlike acute phase).
• Eosinophilia may be absent in up to 50% of chronic cases.
• Recurrent bacterial cholangitis.
• Complications: choledocholithiasis, liver abscess, biliary cirrhosis, hemobilia.

Ectopic Fascioliasis

• Subcutaneous nodules (migratory), pancreatitis, ocular involvement, brain lesions.

5. Laboratory and Serological Diagnostics

6. Treatment Principles

• FDA approved triclabendazole for fascioliasis in patients aged ≥6 years.
• Serology is used to monitor treatment response (antibody titers should fall after successful treatment).
• Praziquantel is ineffective — must not be used for Fasciola.

7. Preventive and Hygienic Measures

• Do not eat raw watercress, water lettuce, or other aquatic plants from areas with grazing livestock.
• Wash and cook all aquatic vegetables thoroughly — metacercariae are killed by heat.
• Do not drink untreated water from streams or ponds in endemic areas; use filtered or boiled water.
• Avoid raw plant preparations (salads, juices) from endemic regions where contamination is plausible.

• Regular anthelmintic treatment of livestock (cattle, sheep, goats) reduces environmental egg contamination.
• Control of snail populations (Lymnaea spp.) in irrigation channels and water bodies (molluscicides, drainage management).
• Proper disposal of animal feces; prevent livestock from defecating near water sources or vegetable beds.
• Fencing of watercress cultivation sites to prevent livestock access.

• Health education in endemic communities about the risks of raw aquatic vegetable consumption.
• Surveillance and treatment programs in high-prevalence regions (Peru, Bolivia, Egypt).
• Travelers to endemic areas should be advised to avoid raw aquatic greens.
• WHO has included triclabendazole in its essential medicines list and preventive chemotherapy programs for fascioliasis.

Summary Comparison Table