{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T05:32:57Z","timestamp":1787031177150,"version":"build-2736575974"},"reference-count":62,"publisher":"American Society of Tropical Medicine and Hygiene","issue":"5","license":[{"start":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T00:00:00Z","timestamp":1778025600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,6]]},"abstract":"<jats:title>ABSTRACT.<\/jats:title>\n                  <jats:p>\n                    The aim for the present study was to analyze clinical features, diagnostic approaches, and therapeutic strategies for visceral leishmaniasis (VL)-associated hemophagocytic lymphohistiocytosis (HLH) in pediatric patients. The clinical characteristics and test results of the children were summarized. Among the four patients, three resided in VL-endemic regions, and one had traveled to a VL-endemic region. All patients presented with recurrent fever (&gt;38.5\u00b0C), hepatosplenomegaly, and decreased hemoglobin (HGB) levels ([78.75 \u00b1 8.50] g\/L) and platelet (PLT) counts ([59.50 \u00b1 17.48] \u00d7 10\n                    <jats:sup>9<\/jats:sup>\n                    \/L). Before a definitive diagnosis could be made, patients exhibited progressive declines in white blood cell counts, HGB levels, and PLT counts, along with elevated triglyceride, serum cytokine (interleukin [IL]-6, IL-10, IL-2R, and tumor necrosis factor \u03b1) levels. Bone marrow aspirate smears revealed hemophagocytosis and\n                    <jats:italic>Leishmania donovani<\/jats:italic>\n                    (LD) bodies in all cases: two were diagnosed via direct identification of LD bodies, one was diagnosed through re-examination of bone marrow smears after confirming a travel history, and one was diagnosed via re-examination prompted by metagenomic next-generation sequencing, which revealed leishmaniasis. All the patients were initially diagnosed with HLH and received HLH-directed immunochemotherapy before VL diagnosis, with suboptimal response. After confirmation of VL, sodium stibogluconate therapy was initiated, resulting in a partial response in all cases. Etiological investigation is critical for HLH diagnosis. For VL-associated HLH, sodium stibogluconate as targeted therapy rapidly controls HLH, facilitates immunosuppression withdrawal, and significantly improves patient outcomes. White blood cell count, HGB level, PLT count, and lactate dehydrogenase level may serve as critical prognostic biomarkers for VL-associated HLH.\n                  <\/jats:p>","DOI":"10.4269\/ajtmh.25-0530","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T19:09:38Z","timestamp":1774552178000},"page":"882-888","source":"Crossref","is-referenced-by-count":1,"title":["Clinical Characteristics and Management of Four Cases of Visceral Leishmaniasis-Associated Hemophagocytic Lymphohistiocytosis"],"prefix":"10.4269","volume":"114","author":[{"given":"Meng","family":"Tian","sequence":"first","affiliation":[{"name":"Department of Clinical Laboratory, Capital Center for Children\u2019s Health, Capital Medical University, Capital Institute of Pediatrics, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Capital Center for Children\u2019s Health, Capital Medical University, Capital Institute of Pediatrics, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzhi","family":"Dai","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Capital Center for Children\u2019s Health, Capital Medical University, Capital Institute of Pediatrics, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijuan","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Capital Center for Children\u2019s Health, Capital Medical University, Capital Institute of Pediatrics, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2795","reference":[{"key":"b1","series-title":"Hematology Am Soc Hematol Educ Program","first-page":"605","article-title":"Hemophagocytic lymphohistiocytosis: Pathogenesis and treatment","volume":"2013","author":"Janka","year":"2013"},{"key":"b2","series-title":"Blood","first-page":"1332","article-title":"Pediatric hemophagocytic lymphohistiocytosis","volume":"135","author":"Canna","year":"2020"},{"key":"b3","series-title":"J Allergy Clin Immunol Pract","first-page":"824","article-title":"Hemophagocytic lymphohistiocytosis: Clinical presentations and diagnosis","volume":"7","author":"Risma","year":"2019"},{"key":"b4","series-title":"Acta Paediatr Scand","first-page":"428","article-title":"Incidence in Sweden and clinical features of familial hemophagocytic lymphohistiocytosis","volume":"80","author":"Henter","year":"1991"},{"key":"b5","series-title":"Eur J Pediatr","first-page":"221","article-title":"Familial hemophagocytic lymphohistiocytosis","volume":"140","author":"Janka","year":"1983"},{"key":"b6","series-title":"Princ Pract Infect Dis","first-page":"3463","article-title":"Leishmania species: Visceral (Kala-Azar), cutaneous, and mucosal leishmaniasis","volume":"2","author":"Magill","year":"2014"},{"key":"b7","article-title":"Global Leishmaniasis Surveillance: 2019-2020, a Baseline for the 2030 Roadmap.","year":"2020"},{"key":"b8","article-title":"Findings from the Global Burden of Disease Study.","year":"2019"},{"key":"b9","series-title":"Chinese J Antibiotics","first-page":"729","article-title":"Interpretation of \u2018Visceral Leishmaniasis Diagnosis and Treatment Guideline\u2019","volume":"2024","author":"Bi","year":"2023"},{"key":"b10","series-title":"Med Vet Entomol","first-page":"123","article-title":"Phlebotomine sand-flies and the spreading of leishmaniases and other diseases of publichealth concern","volume":"27","author":"Maroli","year":"2013"},{"key":"b11","series-title":"Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi","first-page":"329","article-title":"Optimization of the control strategy and research priorities to combat the resurgence of visceral leish-maniasis in China","volume":"36","author":"Zhou","year":"2024"},{"key":"b12","series-title":"Chin J Parasitol Parasit Dis","first-page":"559","article-title":"Prevalence of visceral leishmaniasis in China in 2023","volume":"42","author":"Zhou","year":"2024"},{"key":"b13","series-title":"China CDC Wkly","first-page":"625","article-title":"Visceral leishmaniasis \u2013 China, 2015\u20132019","volume":"2","author":"Zhou","year":"2020"},{"key":"b14","series-title":"Trop Med Infect Dis","first-page":"318","article-title":"Reemergence of visceral leishmaniasis in Henan Province, China","volume":"8","author":"Yang","year":"2023"},{"key":"b15","series-title":"Front Microbiol","first-page":"959901","article-title":"Epidemiological features and spatial-temporal clustering of visceral leishmaniasis in China\u2019s mainland from 2019 to 2021","volume":"13","author":"Li","year":"2022"},{"key":"b16","series-title":"Pediatrics","first-page":"E58","article-title":"Hemophagocytic syndrome: A misleading complication of visceral leishmaniasis in children\u2013A series of 12 cases","volume":"106","author":"Gagnaire","year":"2000"},{"key":"b17","series-title":"Zhonghua Er Ke Za Zhi","first-page":"550","article-title":"Visceral leishmaniasis associated hemophagocytic lymphohistiocytosis: Report of four childhood cases","volume":"49","author":"Guo","year":"2011"},{"key":"b18","series-title":"Pediatr Blood Cancer","first-page":"101","article-title":"Salvage therapy of refractory hemophagocytic lymphohistiocytosis with alemtuzumab","volume":"60","author":"Marsh","year":"2013"},{"key":"b19","series-title":"Pediatr Blood Cancer","first-page":"124","article-title":"HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis","volume":"48","author":"Henter","year":"2007"},{"key":"b20","series-title":"Blood","first-page":"4577","article-title":"Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: Long-term results of the HLH-94 treatment 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lymphohistiocytosis","volume":"135","author":"Canna","year":"2020"},{"key":"b3","series-title":"J Allergy Clin Immunol Pract","first-page":"824","article-title":"Hemophagocytic lymphohistiocytosis: Clinical presentations and diagnosis","volume":"7","author":"Risma","year":"2019"},{"key":"b4","series-title":"Acta Paediatr Scand","first-page":"428","article-title":"Incidence in Sweden and clinical features of familial hemophagocytic lymphohistiocytosis","volume":"80","author":"Henter","year":"1991"},{"key":"b5","series-title":"Eur J Pediatr","first-page":"221","article-title":"Familial hemophagocytic lymphohistiocytosis","volume":"140","author":"Janka","year":"1983"},{"key":"b6","series-title":"Princ Pract Infect Dis","first-page":"3463","article-title":"Leishmania species: Visceral (Kala-Azar), cutaneous, and mucosal leishmaniasis","volume":"2","author":"Magill","year":"2014"},{"key":"b7","article-title":"Global Leishmaniasis Surveillance: 2019-2020, a Baseline for the 2030 Roadmap.","year":"2020"},{"key":"b8","article-title":"Findings from the Global Burden of Disease Study.","year":"2019"},{"key":"b9","series-title":"Chinese J Antibiotics","first-page":"729","article-title":"Interpretation of \u2018Visceral Leishmaniasis Diagnosis and Treatment Guideline\u2019","volume":"2024","author":"Bi","year":"2023"},{"key":"b10","series-title":"Med Vet Entomol","first-page":"123","article-title":"Phlebotomine sand-flies and the spreading of leishmaniases and other diseases of publichealth concern","volume":"27","author":"Maroli","year":"2013"},{"key":"b11","series-title":"Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi","first-page":"329","article-title":"Optimization of the control strategy and research priorities to combat the resurgence of visceral leish-maniasis in China","volume":"36","author":"Zhou","year":"2024"},{"key":"b12","series-title":"Chin J Parasitol Parasit Dis","first-page":"559","article-title":"Prevalence of visceral leishmaniasis in China in 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Zhi","first-page":"550","article-title":"Visceral leishmaniasis associated hemophagocytic lymphohistiocytosis: Report of four childhood cases","volume":"49","author":"Guo","year":"2011"},{"key":"b18","series-title":"Pediatr Blood Cancer","first-page":"101","article-title":"Salvage therapy of refractory hemophagocytic lymphohistiocytosis with alemtuzumab","volume":"60","author":"Marsh","year":"2013"},{"key":"b19","series-title":"Pediatr Blood Cancer","first-page":"124","article-title":"HLH-2004: Diagnostic and therapeutic guidelines for hemophagocytic lymphohistiocytosis","volume":"48","author":"Henter","year":"2007"},{"key":"b20","series-title":"Blood","first-page":"4577","article-title":"Chemoimmunotherapy for hemophagocytic lymphohistiocytosis: Long-term results of the HLH-94 treatment protocol","volume":"118","author":"Trottestam","year":"2011"},{"key":"b21","series-title":"Blood","first-page":"2728","article-title":"Confirmed efficacy of etoposide and dexamethasone in HLH 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