Table 1_Scrub typhus triggers hemophagocytic lymphohistiocytosis in children: metagenomic next-generation sequencing enables rapid diagnosis.docx

Common clinical findings included eschar (66.7%), lymphadenopathy (100%), hepatomegaly (58.3%), and splenomegaly (66.7%). Notably, four patients (33.3%) were initially misdiagnosed as having Kawasaki disease. All patients met the HLH-2004 criteria, with prominent hyperferritinemia (median: 5,355 ng/mL) and elevated sCD25 (median: 5,065 U/mL).

Peripheral blood mNGS confirmed the diagnosis of scrub typhus in all patients (median sequence reads: 333). Cerebrospinal fluid (CSF) mNGS was positive for Orientia tsutsugamushi in four out of five patients tested, and cytokine profiling revealed elevated levels of IL-6, IL-10, and IFN-γ. Basic CSF parameters, including white blood cell count, protein, and glucose, are reported for all patients who underwent lumbar puncture.

Severe complications included pulmonary hemorrhage (n = 3) and shock (n = 3). All patients survived following targeted antibiotic and immunomodulatory therapy.</p>Conclusion<p>Scrub typhus is a significant trigger for secondary HLH in children from endemic areas. mNGS may facilitate rapid etiological diagnosis and timely targeted therapy. CSF mNGS and cytokine analysis may be considered in severe cases, though further validation is warranted.

We also acknowledge that our study demonstrates feasibility rather than superiority of mNGS over conventional diagnostic methods.</p>