How should I evaluate a patient with eosinophilia, fever, and splenomegaly to rule out parasitic infection, given recent travel to tropical or subtropical regions and possible exposure to raw or undercooked meat, freshwater, or animals?

Ruling Out Parasitic Infection in Eosinophilia with Fever and Splenomegaly

Obtain three separate concentrated stool specimens for ova and parasites on consecutive days, perform Strongyloides serology immediately, and request schistosomiasis serology if the patient had any freshwater exposure in Africa—these three tests are mandatory before any other workup or discharge. 1, 2

Critical First Steps

The diagnostic approach must prioritize helminth infections because they account for 19-80% of eosinophilia in returning travelers and migrants, and missing Strongyloides can be fatal if immunosuppression is later required. 3, 2

Immediate Laboratory Testing

• Three concentrated stool microscopy specimens collected on separate days (single sample sensitivity is only 50% for many helminths) 2, 4
• Strongyloides serology is non-negotiable because this parasite persists lifelong and causes fatal hyperinfection syndrome in immunocompromised patients, even decades after exposure 1, 3, 2
• Schistosomiasis serology if any freshwater swimming occurred in Africa (lakes, rivers), as acute schistosomiasis (Katayama syndrome) presents with fever, splenomegaly, and marked eosinophilia during the pre-patent period when stool tests are still negative 1, 2
• Complete blood count with differential to calculate absolute eosinophil count 4
• Blood cultures should be obtained given fever and splenomegaly to exclude bacterial sepsis or enteric fever 1

Essential History Elements

Document these specific exposures with exact timing:

• Freshwater swimming in Africa (schistosomiasis risk—cercariae penetrate skin during water contact) 1, 2
• Walking barefoot on soil or sand in tropical/subtropical regions (hookworm, Strongyloides larvae penetrate skin) 1, 2
• Raw or undercooked meat consumption: beef (T. saginata), pork (T. solium), fish (various flukes) 1, 2
• Unwashed vegetables or contaminated water (geohelminths: Ascaris, Trichuris, hookworm) 1, 2
• Exact countries visited and duration to match geographic distribution of specific helminths 1

Understanding Timing and Serology

Eosinophilia may be transient during tissue migration phases and can resolve when parasites reach the gut lumen, potentially causing false-negative stool tests during peak eosinophilia. 1, 2 This is why you cannot rely on a single negative stool test.

• Most serological tests do not become positive until 4-12 weeks after infection, so early serology may be falsely negative 1
• Katayama syndrome (acute schistosomiasis) occurs 4-8 weeks post-exposure with fever, urticaria, hepatosplenomegaly, and marked eosinophilia—during the pre-patent period when stool microscopy is negative, requiring serological diagnosis 1, 2, 4
• Serology shows cross-reactivity: filarial serology may be positive in strongyloidiasis; Strongyloides serology may cross-react with filariasis 1, 2

Additional Targeted Testing Based on Clinical Presentation

If Respiratory Symptoms Present

• Chest radiograph to identify migratory pulmonary infiltrates (Loeffler's syndrome from Ascaris, hookworm, or Strongyloides larval migration through lungs) 1, 2
• Fever, urticaria, wheeze, dry cough occurring 1-2 weeks post-exposure suggests larval migration 2

If Hepatosplenomegaly Prominent

• Abdominal ultrasound for suspected hepatosplenic schistosomiasis, particularly in migrants with chronic exposure 2
• Hepatosplenomegaly with portal hypertension suggests chronic schistosomiasis, more common in migrants than travelers 1, 2

If Gastrointestinal Symptoms

• Stool culture for bacterial pathogens (Salmonella, Shigella, Campylobacter, Yersinia) and C. difficile to exclude superinfection 1, 2
• Test for Vibrio species if large volume rice water stools or exposure to brackish water/raw shellfish 1

Critical Pitfalls to Avoid

• Never assume a single negative stool test excludes helminth infection—three samples are required for adequate sensitivity 1, 2
• Never use corticosteroids empirically for eosinophilia without excluding Strongyloides—this risks fatal hyperinfection syndrome 2, 5
• Always screen for Strongyloides before initiating immunosuppression in patients from endemic areas, regardless of symptoms 1, 2, 5
• Recognize that eosinophilia may resolve when parasites reach gut lumen, creating false reassurance despite active infection 1, 2

When Empirical Treatment is Justified

If clinical presentation strongly suggests Katayama syndrome (freshwater exposure in Africa 4-8 weeks prior, fever, urticarial rash, hepatosplenomegaly, marked eosinophilia), empiric treatment may be justified based on clinical presentation while awaiting serology results. 4

Referral Threshold

Consult tropical medicine specialist if: 2

• Recent travel (within past year) to tropical/subtropical regions with eosinophilia
• Eosinophilia ≥1.5 × 10⁹/L at any point (should not be managed in primary care) 3
• Persistently negative stool examinations despite high clinical suspicion
• Any evidence of end-organ damage (cardiac, pulmonary, neurologic) requires urgent specialist evaluation 3