Molecular Diagnosis and IL-1 Blockade: Redefining Pediatric Leishmaniasis Management

To the Editors: In their recent perspective on human leishmaniasis, Abbasi et al1 highlighted the ongoing transition from microscopy-based to molecular and immunomodulatory approaches. This conceptual shift is particularly relevant in pediatric visceral leishmaniasis (VL), where low parasitic burden and immune dysregulation frequently obscure the diagnosis and complicate management. We report the case of a 22-month-old previously healthy girl presenting with persistent fever, pallor and marked splenomegaly. Laboratory investigations revealed pancytopenia, hyperferritinemia and hypertriglyceridemia, fulfilling the hemophagocytic lymphohistiocytosis (HLH)-2004 criteria. Bone-marrow aspirate demonstrated preserved cellularity, but repeated microscopic evaluations failed to identify amastigotes, and Leishmania serology remained negative. Given the epidemiologic background, VL was still strongly suspected. Quantitative polymerase chain reaction (PCR) performed on peripheral blood detected Leishmania infantum DNA, establishing a diagnosis that conventional techniques had missed. This case exemplifies the diagnostic evolution described by Abbasi et al1: molecular assays have emerged as the reference standard, achieving >90% sensitivity and >95% specificity, as confirmed by recent meta-analyses.2,3 In pediatric settings, where invasive sampling may be risky or uninformative, exclusive reliance on microscopy can lead to critical therapeutic delays. High-dose methylprednisolone (30 mg/kg/day intravenously for 3 consecutive days, followed by a gradual taper) was initiated, resulting in only a partial clinical response. The subsequent addition of anakinra (4 mg/kg/day for at least 15 days) effectively attenuated the interleukin (IL)-1-driven hyperinflammatory state, stabilizing the patient and preventing progression to multi-organ dysfunction.4 Following molecular confirmation, and given the disease severity and poor response to steroid pulses, liposomal amphotericin B was administered according to the center for disease control and prevention immunosuppressed-dose regimen for visceral leishmaniasis (4 mg/kg/day intravenous on days 1–5, 10, 17, 24, 31 and 38; total ≈40 mg/kg), rather than the conventional schedule.5 Fever resolved within 72 hours of combined anakinra and amphotericin therapy, followed by progressive hematologic recovery. The patient was discharged after 2 weeks, with normalized counts, negative follow-up PCR, and complete clinical remission. This clinical experience underscores 3 pivotal messages. First, in febrile children with HLH and epidemiologic exposure, early molecular testing should be prioritized: PCR not only detects low-level parasitemia missed by microscopy or serology but also enables dynamic monitoring of treatment response. Second, targeted IL-1 blockade represents a safe and rational strategy to modulate hyperinflammation in VL-associated HLH, bridging the critical interval until parasitic control is achieved. Third, liposomal amphotericin B remains the cornerstone of therapy, with the immunosuppressed-dose regimen ensuring effective parasite clearance even in unstable hosts. Molecular diagnostics and selective cytokine inhibition redefine the management of Leishmania-triggered HLH, bridging traditional parasitology and precision immunotherapy, a direction that resonates with the translational vision of modern pediatric infectious diseases. Acknowledgments The authors thank the patient and his family for their consent and cooperation in sharing this case for educational purposes.