A patient with a 10-day history of fever, weakness, and fatigue, who recently traveled to an area requiring prophylactic malaria treatment and stayed in cheap hostels, presents with pallor, splenomegaly, anemia, leukopenia, and thrombocytopenia, what is the most likely diagnosis?

Most Likely Diagnosis: Visceral Leishmaniasis

The most likely diagnosis is visceral leishmaniasis (option c), given the constellation of prolonged fever (10 days), pancytopenia (anemia, leukopenia, thrombocytopenia), splenomegaly, recent travel to an endemic area with exposure risk (cheap hostels suggesting potential sandfly exposure), and the fact that malaria prophylaxis was taken. 1

Clinical Reasoning

Why Leishmaniasis is Most Likely

• Classic triad present: The patient demonstrates the characteristic presentation of visceral leishmaniasis with chronic fever, splenomegaly, and pancytopenia (Hb 8.2 g/dl, WBC 3.2 x 10⁹/L, platelets 67 x 10⁹/L), which are hallmark features of this disease 1

• Epidemiologic context: Travel history to an endemic area with accommodation in cheap hostels increases sandfly exposure risk, the vector for Leishmania transmission 1

• Duration of symptoms: The 10-day history of fever, weakness, and fatigue fits the subacute-to-chronic presentation typical of visceral leishmaniasis, rather than the acute presentation of other conditions 1

• Normal liver and kidney function: The preservation of hepatic and renal biochemistry despite significant hematologic abnormalities is consistent with early visceral leishmaniasis 1

Why Other Diagnoses are Less Likely

Malaria (option a):

• While malaria commonly presents with fever, splenomegaly, and thrombocytopenia 1, the patient took prophylactic antimalarial treatment, significantly reducing this probability
• Malaria typically presents more acutely (within days to 2 weeks of exposure) rather than the subacute presentation seen here 1
• The profound leukopenia (WBC 3.2) is less characteristic of malaria, which more commonly shows normal or slightly decreased white cell counts 2, 3
• However, malaria cannot be completely excluded and should still be tested for given the overlapping clinical features 1

Thrombotic Thrombocytopenic Purpura (option b):

• TTP would typically present with more severe thrombocytopenia, microangiopathic hemolytic anemia with schistocytes, and evidence of end-organ damage (elevated creatinine, neurological symptoms)
• The normal kidney biochemistry argues strongly against TTP
• Fever in TTP is usually accompanied by neurological changes and renal impairment, which are absent here

Systemic Lupus Erythematosus (option d):

• While SLE can cause pancytopenia and splenomegaly, the acute presentation with prominent fever and recent travel history makes an infectious etiology far more likely
• SLE typically has a more insidious onset with additional features (rash, arthritis, serositis)

Weil's Disease/Leptospirosis (option e):

• Leptospirosis would typically show elevated liver enzymes and renal impairment (both absent here)
• The normal liver and kidney biochemistry effectively rules out Weil's disease 1

Diagnostic Approach

Immediate Testing Required

• Bone marrow or splenic aspirate: Gold standard for visceral leishmaniasis diagnosis, looking for Leishmania amastigotes 1, 4

• Thick and thin blood films: Essential to definitively exclude malaria despite prophylaxis, as breakthrough infections can occur 1, 5

• Rapid diagnostic tests: Can provide quick results for malaria (sensitivity 67.9-100% for P. falciparum) while awaiting microscopy 1

Key Clinical Predictors Supporting Leishmaniasis

• Splenomegaly: Strongly increases likelihood of both malaria (LR+ 5.1-13.6) and visceral leishmaniasis 1
• Thrombocytopenia: Present in this case (67 x 10⁹/L), though this finding is non-specific and seen in multiple tropical diseases 1
• Pancytopenia: The combination of anemia, leukopenia, and thrombocytopenia is particularly characteristic of visceral leishmaniasis 1

Critical Management Considerations

• Do not delay diagnostic workup: Both visceral leishmaniasis and malaria require prompt diagnosis and treatment to prevent progression to severe disease 1

• Consider empiric antimalarial therapy: If malaria cannot be rapidly excluded and the patient deteriorates, empiric treatment should be initiated while awaiting confirmatory testing 5, 6

• Immunocompromised status: Assess for HIV and other immunocompromising conditions, as these increase risk for visceral leishmaniasis reactivation and disseminated disease 1

• Treatment for visceral leishmaniasis: If confirmed, liposomal amphotericin B or miltefosine are first-line therapies, with cure rates of 94-97% 4