key: cord-0966149-slssn6w8 authors: Guo, Fang; Kang, Lei; Xu, Meixian title: A Case of Pediatric Visceral Leishmaniasis-related Hemophagocytic Lymphohistiocytosis diagnosed by mNGS date: 2020-05-18 journal: Int J Infect Dis DOI: 10.1016/j.ijid.2020.05.056 sha: 6d6cf7abe15100faa2d3c6043ce2629165bc15ef doc_id: 966149 cord_uid: slssn6w8 Abstract Background Visceral leishmaniasis-related hemophagocytic lymphohistiocytosis (VL-HLH) is a secondary hemophagocytic syndrome, which can be life-threatening, caused by leishmania and transmitted by infected sandflies. Rapid and accurate identification of leishmania is crucial for clinical strategies. Case report Here, we report an infantile infection in a non-epidemic area of China. The infant was a 9.5-month-old girl with fever, pancytopenia and hepatosplenomegaly, which meet the HLH-2004 standard, and the negative gene results exclude congenital HLH. However, chemotherapy is ineffective and is accompanied by severe infection. Fortunately, she is diagnosed with VL-HLH (visceral leishmaniasis-related hemophagocytic lymphohistiocytosis), as leishmania is detected by next-generation meta-genome sequencing (mNGS) and quickly relieved after treatment with libosomal amphotericin B (L-AMB). Conclusion mNGS can detect leishmania in pediatric HLH, and should be performed as a new detection for VL-HLH, particularly for infants, who may not respond to HLH-2004 regimen. next-generation meta-genome sequencing; bone marrow aspiration Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome, is a disease caused by uncontrollable activation and proliferation of lymphocytes and macrophages (Janka, 2012) . HLH is classified as primary and secondary, and infection is the most common cause of secondary HLH (Janka et al., VL-HLH is very rare in childhood, and the mortality rate is as high as 100% (Gradoni et al., 2017) without early diagnosis and treatment. Here, we report a case of VL-HLH in a 9.5-month-old girl, diagnosed by next-generation meta-genome sequencing (mNGS), while routine tests were negative. In November 2019, a 9.5-month-old girl from handan city of hebei province, who had a fever for 8 days, was admitted to the Hematology Department of Hebei Children's Hospital. The patient had been treated with cefoperazone sulbactam and acyclovir for 5 days in the local hospital due to high fever, but her symptoms did not relieve. Upon admission, the baby's parents complained of high fever, accompanied by hepatosplenomegaly, without rash, cough, jaundice or vomiting. Multiple hematological examinations confirmed leukopenia, anemia and thrombocytopenia. The laboratory testing revealed hypertriglyceridemia (4.1mmol/L), eutrophilic lobulated nuclear granulocyt J o u r n a l P r e -p r o o f The diagnosis of secondary HLH was clear, but the pathogen was unknown. The infant fell ill in winter, and denied sandfly bites and family aggregation diseases. She PCR test with high specificity has improved detection of leishmania, but it is not universalized in China, especially in non-epidemic areas, where bone marrow needs to be sent to special testing institutions. More importantly, the test will be carried out only when leishmaniasis is highly suspected, which is difficult for inexperienced clinicians in non-epidemic areas. To the best of our knowledge, this is the first report of direct detection of As far as we know, this is the first report that mNGS can detect leishmania in pediatric HLH, when leishmane-donovan bodies are not found under the microscope and rk39 test is negative. mNGS can provide an effective basis for early diagnosis of VL-HLH, and should be recommended in clinical practice, particularly for children who are not responsive to HLH-2004 regimen and complicated with severe infection. mNGS should be performed to determine whether there is secondary HLH caused by rare pathogens including VL. Consent for publication: Written informed consent was obtained from the legal guardian of this case report. Funding Source: This report did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. J o u r n a l P r e -p r o o f Ethical Approval: Since the data were anonymous and no threat to patients' rights, the Ethics Committee of Hebei Children's Hospital exempts the need for ethical approval. Competing interests: As the authors of this report, we all declare that there are no known conflicts of competing financial interests or personal relationshipst that could have appeared to influence the work reported in this paper. J o u r n a l P r e -p r o o f Familial and acquired hemophagocytic lymphohistiocytosis Infection-and malignancy-associated hemophagocytic syndromes. 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