What could be causing anemia in a family of four, with partial response to oral iron supplementation and prior treatment with albendazole (anti-parasitic medication)?

Differential Diagnosis: Family-Wide Anemia with Partial Response to Iron

The most likely cause of anemia affecting this entire family is ongoing gastrointestinal blood loss from hookworm infection that was inadequately treated or has recurred, particularly given their geographic history and the variable response to oral iron supplementation. 1

Primary Diagnostic Considerations

Persistent or Recurrent Hookworm Infection

Hookworm remains the leading concern despite albendazole treatment in three family members. 2, 3

• Hookworm (Necator americanus or Ancylostoma duodenale) causes chronic intestinal blood loss leading to iron deficiency anemia, particularly in endemic regions 2
• The variable response to oral iron among family members is characteristic of ongoing blood loss overwhelming iron replacement 1
• Albendazole treatment may have been incomplete or ineffective - single-dose therapy often fails to eradicate heavy infections, and reinfection is common in endemic areas 3
• The mother's lack of treatment creates a potential reservoir for household transmission 4
• Moderate to heavy hookworm infections are most strongly associated with anemia, with treatment impact greatest when albendazole is combined with other interventions 3

Celiac Disease

All family members should be screened for celiac disease, as it accounts for 2-4% of iron deficiency anemia cases and can affect multiple family members due to genetic predisposition. 1

• Celiac disease causes iron malabsorption and is present in up to 4% of patients with unexplained iron deficiency anemia 1
• Testing should include tissue transglutaminase antibody (IgA type) with total IgA levels to exclude IgA deficiency which renders the test unreliable 1
• Family clustering is common due to genetic factors 1
• Small bowel biopsy during upper endoscopy confirms diagnosis 1

Helicobacter pylori Infection

• Can cause iron deficiency through chronic gastritis, reduced acid production, and occult bleeding 1
• Family-wide infection is common due to household transmission 1
• Testing and eradication should be considered, particularly if upper endoscopy is performed 1

Critical Diagnostic Workup

Immediate Laboratory Assessment

Confirm true iron deficiency in all family members with: 1

• Complete blood count with red cell indices (MCV, MCH, RDW)
• Serum ferritin (diagnostic if <12-15 μg/dL; iron deficiency unlikely if >100 μg/dL) 1
• Transferrin saturation (<30% suggests iron deficiency) 1
• C-reactive protein to identify concurrent inflammation that may elevate ferritin 1

Stool Studies

Obtain stool examination for ova and parasites (×3 samples) with specific attention to hookworm eggs. 2, 3

• Quantitative egg counts help assess infection intensity 3
• Consider PCR-based testing if available for higher sensitivity 3
• Examine all four family members, including the mother who did not receive albendazole 4

Celiac Serology

Screen all family members with tissue transglutaminase antibody (IgA) and total IgA levels. 1

Endoscopic Evaluation (Age-Dependent)

For the parents (both in their 40s), bidirectional endoscopy (gastroscopy and colonoscopy) is indicated if initial workup is unrevealing: 1

• Upper endoscopy with small bowel biopsies to exclude celiac disease, gastritis, and occult bleeding sources 1
• Colonoscopy to exclude colonic pathology, though less likely given age and family clustering 1
• The 15-year-old boy may warrant upper endoscopy with small bowel biopsy if celiac serology is positive or symptoms persist 1
• The 12-year-old typically does not require endoscopy unless specific indications arise 1

Treatment Strategy

If Hookworm Confirmed or Highly Suspected

Retreat the entire family, including the mother, with albendazole 400 mg twice daily for 3 days (more effective than single-dose for heavy infections). 4, 3

• Monitor for treatment response with repeat stool examination 2-4 weeks post-treatment 3
• Albendazole combined with iron supplementation shows benefit, though the primary impact comes from parasite eradication 3
• Educate about prevention of reinfection (proper sanitation, wearing shoes) 2

Iron Supplementation Optimization

Continue oral iron supplementation in all family members with confirmed iron deficiency: 1

• Ferrous sulfate 200 mg (65 mg elemental iron) once to three times daily, or equivalent 1
• Adding ascorbic acid 250-500 mg with iron enhances absorption and should be considered given the partial response 1
• Expected hemoglobin rise is 2 g/dL after 3-4 weeks - failure suggests ongoing blood loss, malabsorption, or non-compliance 1
• Continue for 3 months after hemoglobin normalization to replenish stores 1

For Severe Anemia or Malabsorption

If any family member has hemoglobin <10 g/dL or fails oral iron therapy, consider intravenous iron: 5

• Produces significantly greater hemoglobin response (1-2 weeks vs 4-8 weeks for oral iron) 5
• Particularly indicated if celiac disease or other malabsorption is confirmed 5

Follow-Up Monitoring

Reassess hemoglobin and iron indices at 3-4 weeks, then 3 months: 1

• Failure to achieve expected hemoglobin rise indicates ongoing blood loss, malabsorption, or incorrect diagnosis 1
• If iron deficiency recurs after initial correction, proceed with age-appropriate endoscopic evaluation 1
• Monitor at 3-month intervals for the first year, then annually 1

Key Clinical Pitfalls

• Do not assume dietary deficiency or menstruation (in the mother) explains family-wide anemia - this pattern demands investigation for shared environmental or genetic causes 1
• Single-dose albendazole may be inadequate for moderate-heavy hookworm infections - consider extended or repeat treatment 3
• Ferritin may be falsely normal or elevated in the presence of inflammation - use transferrin saturation and clinical context 1
• Do not delay celiac screening - it is easily missed and affects multiple family members 1
• The mother's untreated status may perpetuate household transmission if parasitic infection is present 4, 2