In a 35‑year‑old woman with 10‑day fever, fatigue, recent travel to India, prophylactic malaria treatment, pallor, splenomegaly, anemia, leukopenia, thrombocytopenia and normal hepatic and renal function, which is the most likely diagnosis: visceral leishmaniasis, malaria, systemic lupus erythematosus, or thrombotic thrombocytopenic purpura?

Visceral Leishmaniasis (Kala-Azar)

The most likely diagnosis is visceral leishmaniasis (option a). This patient presents with the classic triad of chronic fever, splenomegaly, and pancytopenia following travel to an endemic region (India), which is pathognomonic for kala-azar 1, 2.

Clinical Reasoning

Why Visceral Leishmaniasis is the Answer

The patient demonstrates all hallmark features of visceral leishmaniasis:

• Chronic fever for 10 days – VL characteristically presents with fever (present in 64% of patients), with a median symptom duration of 28 days before diagnosis 1
• Marked splenomegaly – found in 58% of VL patients and a defining clinical feature 1
• Pancytopenia affecting all cell lines – anemia (Hb 8.2), leukopenia (WBC 3.2), and thrombocytopenia (platelets 67) is the characteristic hematologic signature of VL 1, 3, 4, 2
• Travel to India – the Indian subcontinent is a major endemic region for L. donovani, the causative organism 5
• Staying in cheap hostels – increases exposure risk to sandfly vectors in endemic areas 5
• Normal hepatic and renal function – typical for VL, which primarily causes hematologic abnormalities rather than organ failure 1

Why the Other Options Are Incorrect

Malaria (option b) is less likely because:

• The patient took prophylactic antimalarial treatment 1
• Malaria typically causes acute rather than 10-day chronic fever 1
• While malaria can cause splenomegaly and thrombocytopenia, the profound pancytopenia affecting all three cell lines is more characteristic of VL 1, 3
• The differential diagnosis for VL specifically includes malaria, but the chronic presentation and complete pancytopenia favor leishmaniasis 6, 1

Systemic Lupus Erythematosus (option c) is unlikely because:

• No mention of typical SLE features (arthritis, rash, photosensitivity, renal involvement, or autoantibodies) 7
• While SLE can cause cytopenias, the combination of chronic fever, marked splenomegaly, and travel history to an endemic region makes VL far more likely 7
• SLE would be a diagnosis of exclusion after ruling out infectious causes in this epidemiologic context 7

Thrombotic Thrombocytopenic Purpura (option d) is excluded by:

• Normal renal function (TTP causes acute kidney injury) 8
• Absence of neurologic symptoms or microangiopathic hemolytic anemia features 8
• The presence of leukopenia (TTP does not typically cause leukopenia) 8

Diagnostic Approach

The IDSA/ASTMH guidelines emphasize that VL should be suspected in patients with:

• Chronic fever, splenomegaly, and pancytopenia 6, 1
• History of travel or residence in endemic areas (Mediterranean basin, Indian subcontinent, East Africa, Latin America) 1, 5
• The clinical manifestations are not specific, requiring high index of suspicion in the appropriate epidemiologic context 1

Critical diagnostic steps include:

• Bone marrow aspirate or biopsy for direct visualization of amastigotes and PCR testing for Leishmania species 6, 7
• rK39 rapid diagnostic test (primary diagnostic method for VL) 2
• Blood PCR for Leishmania infantum or L. donovani 7

Clinical Pitfalls to Avoid

• Do not dismiss VL based on malaria prophylaxis – the prophylactic treatment protects against malaria but not leishmaniasis 1
• Recognize that untreated VL is potentially fatal – death results from progressive wasting, superinfection, or hemorrhage, making prompt diagnosis essential 1
• The broad differential diagnosis includes malaria, typhoid fever, miliary tuberculosis, lymphoma, and other causes of fever with splenomegaly, but the epidemiologic context and complete pancytopenia are key distinguishing features 6, 1