What is the significance of elevated eosinophil count in hookworm infection and how is it treated?

Eosinophil Count and Percentage in Hookworm Infection

Hookworm infection typically causes significant eosinophilia with counts often exceeding 3,000 eosinophils/mm³ of blood, which requires prompt treatment with albendazole 400 mg as a single dose to prevent potential complications. 1

Significance of Eosinophilia in Hookworm Infection

Epidemiology and Pathophysiology

• Hookworm (Ancylostoma duodenale and Necator americanus) is one of the most common helminth infections causing eosinophilia in returning travelers and migrants, with diagnosis rates varying from 19%-80% 1, 2
• Normal eosinophil counts are typically below 0.5 × 10⁹/L, but during hookworm infection, counts can increase dramatically to a mean of 3,008 ± 456 eosinophils/mm³ (compared to pre-infection levels of 524 ± 29 eosinophils/mm³) 3
• Eosinophilia occurs as part of the immune response to larval migration through the lungs (Loeffler's syndrome) and intestinal phases of infection 1

Clinical Significance

• Eosinophilia in hookworm infection serves as an important diagnostic marker but may also contribute to both protective and pathological responses 4, 5
• Hookworm-induced eosinophilia is characterized by:
  • Increased percentage of hypodense eosinophils (from 34% to 80% during infection) 3
  • Enhanced superoxide production (from 56 to 97 nmol O₂/10⁶ cells) 3
  • Increased chemotactic response to inflammatory stimuli 3, 6
• Persistent eosinophilia, especially at high levels (>1.5 × 10⁹/L for more than 3 months), can cause significant end-organ damage affecting the heart, lungs, and central nervous system 1, 2

Clinical Presentation

Symptoms Associated with Hookworm Infection

• Initial skin penetration may cause a transient itchy rash called "ground itch" 1
• During larval migration through the lungs, patients may develop:
  • Fever, urticaria, wheeze, dry cough, and rarely hemoptysis (Loeffler's syndrome) 1
  • Migratory pulmonary infiltrates visible on chest radiograph 1
• Intestinal phase symptoms include:
  • Nausea, vomiting, diarrhea, and abdominal pain 1
  • Heavy infections may result in iron-deficiency anemia, particularly in young children 1

Diagnostic Approach

Laboratory Findings

• Peripheral blood eosinophilia (>0.5 × 10⁹/L) is a key finding 1
• Concentrated stool microscopy is the primary diagnostic test for detecting hookworm eggs 1
• Serological tests may be useful but may not become positive until 4-12 weeks after infection 2

Diagnostic Pitfalls

• Many people with helminth infection do not have eosinophilia, so testing for eosinophilia alone is not an adequate screening strategy 1, 2
• Stool microscopy may be negative during the tissue migration phase when eosinophilia is present 2
• Serological tests may exhibit cross-reactivity between different helminth species 2

Treatment Recommendations

First-Line Treatment

• Albendazole 400 mg as a single dose is the recommended treatment for hookworm infection 1, 7
• Alternative treatment: Mebendazole 500 mg as a single dose 1, 7
• For patients with asymptomatic eosinophilia aged >24 months with suspected helminth infection, empirical treatment with albendazole 400 mg plus ivermectin 200 μg/kg as single doses is recommended 1

Management of Loeffler's Syndrome

• For patients with significant respiratory symptoms due to larval migration:
  • Consider empirical treatment with single-dose ivermectin 200 μg/kg and albendazole 400 mg 1
  • Consider retreatment one month after resolution of pulmonary symptoms to ensure adult worms are treated 1
  • Use caution with steroids, which may cause hyperinfection in concurrent strongyloidiasis 1

Follow-up

• Monitor eosinophil counts after treatment to confirm resolution 1
• If eosinophilia persists ≥1.5 × 10⁹/L for more than 3 months with no identified cause after treatment, referral to a hematologist is recommended 1, 2

Special Considerations

Immunological Effects

• Hookworm infection alters the host's innate immune response, potentially modulating dendritic cell maturation and contributing to T-cell hyporesponsiveness 4
• Eosinophils in hookworm infection show increased activation of major cell surface markers and may act as antigen-presenting cells in addition to their effector functions 4, 8
• Eosinophils may produce IL-10 during helminth infections, which can expand IL-10+ myeloid dendritic cells and CD4+ IL-10+ T lymphocytes that inhibit inducible NO synthase expression 5

Potential Complications

• Heavy hookworm infections can lead to iron deficiency anemia due to intestinal blood loss 1
• Persistent untreated eosinophilia may lead to end-organ damage affecting the heart, lungs, and central nervous system 1