What is the likely cause of a patient's symptoms with elevated eosinophils, hemoptysis, and travel history, with a negative QuantiFERON-TB Gold Plus test and no history of eating raw or undercooked food?

Differential Diagnosis with Negative QuantiFERON and No Raw Food Exposure

With a negative QuantiFERON-TB Gold Plus test and no history of consuming raw or undercooked food, the most likely diagnoses remain helminth infections acquired through other routes (soil contact, contaminated water, or steamed vegetables washed in contaminated water), particularly Strongyloides, hookworm, Ascaris, or Schistosomiasis if there was any freshwater exposure during travel. 1

Understanding the Negative TB Test

The negative QuantiFERON-TB Gold Plus effectively rules out tuberculosis as the cause of this patient's symptoms, though false-negatives can occur in 14-29% of active TB cases, particularly in immunocompromised patients. 1, 2, 3 However, given the clinical context with elevated eosinophils (which is uncommon in TB), the negative test is reliable here. 1

Most Likely Parasitic Causes

Loeffler's Syndrome (Larval Migration)

• This is the leading consideration given the hemoptysis, cough, and elevated eosinophils. 1
• Caused by larval migration through lungs during acute infection with Ascaris, hookworm, or Strongyloides. 1
• Incubation period is 1-2 weeks after exposure, presenting with fever, urticaria, wheeze, dry cough, and rarely hemoptysis. 1
• Critical point: Diagnosis is clinical because symptoms occur during the prepatent period when stool microscopy will be negative. 1
• Migratory pulmonary infiltrates may appear on chest X-ray. 1

Strongyloidiasis

• This is the most critical diagnosis to exclude because it can persist lifelong and cause fatal hyperinfection syndrome if the patient becomes immunocompromised. 1, 4, 5
• Transmission occurs through skin contact with contaminated soil (walking barefoot) or contaminated water. 1
• Strongyloides serology is essential even with negative stool studies, as stool sensitivity is limited. 1, 4

Schistosomiasis (Katayama Syndrome)

• Incubation period 2-9 weeks after freshwater exposure in endemic areas (Africa, occasionally SE Asia, South America). 1
• Presents with high-grade eosinophilia (>5 × 10⁹/L), fever, dry cough, urticarial rash, and hemoptysis. 1
• Even without reported swimming, contaminated water used to wash vegetables or incidental contact can transmit infection. 1
• Serology and stool/urine microscopy have low sensitivity during acute Katayama syndrome. 1

Hookworm and Ascaris

• Worldwide distribution, transmitted through contaminated soil or food washed in contaminated water. 1
• Can cause Loeffler's syndrome during larval migration phase. 1

Recommended Diagnostic Workup

Immediate Testing

• Three separate concentrated stool specimens for ova and parasites (though likely negative during prepatent period). 1, 4
• Strongyloides serology and culture - this is non-negotiable given the risk of future hyperinfection. 1, 4, 5
• Schistosomiasis serology if any possibility of freshwater exposure in endemic areas. 1
• Review pending chest X-ray for migratory pulmonary infiltrates. 1

Additional Serology Based on Travel History

• Filaria serology if travel to endemic regions (W. bancrofti, Brugia species). 1
• Toxocara serology if soil exposure in endemic areas. 1

Empirical Treatment Recommendation

Given the clinical presentation of hemoptysis, cough, and elevated eosinophils during the likely prepatent period when diagnostic tests may be negative, empirical treatment is justified. 1, 4

First-Line Empirical Therapy

• Albendazole 400 mg twice daily for 3 days PLUS Ivermectin 200 μg/kg as a single dose. 1, 4
• This combination covers Strongyloides, hookworm, and Ascaris during the prepatent period. 1, 4

If Schistosomiasis Suspected

• Praziquantel 40 mg/kg as a single dose, repeated at 6-8 weeks (immature schistosomules are relatively resistant to single-dose treatment). 1
• Consider adding prednisolone 20 mg daily for 5 days if symptoms are severe, as steroids reduce symptom duration in Katayama syndrome. 1

Critical Warning

Do NOT initiate corticosteroids before excluding Strongyloides, as steroids can precipitate fatal hyperinfection syndrome. 4, 5, 6 If steroids are needed for severe symptoms, ensure Strongyloides treatment is given first. 4, 6

Follow-Up Strategy

• Repeat complete blood count 2-4 weeks post-treatment to assess eosinophil count decrease. 4
• Repeat praziquantel at 6-8 weeks if schistosomiasis was treated to ensure eradication of immature forms. 1, 4
• Repeat stool microscopy 4-6 weeks after treatment when adult worms would have matured and eggs become detectable. 1
• Strongyloides serology should be repeated 6-12 months post-treatment to confirm cure. 1

Common Pitfalls to Avoid

• Do not assume negative stool studies exclude helminth infection during the acute/prepatent phase. 1
• Do not assume "cooked food only" excludes parasitic infection - vegetables washed in contaminated water, soil contact, or freshwater exposure are alternative routes. 1
• Do not wait for positive diagnostic tests to initiate treatment when clinical presentation strongly suggests Loeffler's syndrome. 1
• Do not overlook Strongyloides screening - this parasite requires specific attention due to lifelong persistence risk. 1, 4, 5