High infant mortality, eschar absence, and universal CNS involvement in scrub typhus-associated HLH: a case series and narrative synthesis of 91 pediatric cases

Background Scrub typhus-associated hemophagocytic lymphohistiocytosis (HLH) is a life-threatening complication of Orientia tsutsugamushi infection. Its clinical features in young infants remain poorly characterized, despite evidence that immune immaturity and atypical presentations may confer particular vulnerability in this age group. Methods We present a case series of three infants with scrub typhus-associated HLH from Yunnan Province, southwestern China, confirmed by molecular diagnostics. Combined with a pooled analysis of published pediatric cases identified through a structured search of 5 databases from inception to December 2025, we analyzed a total of 91 cases. Results Infant mortality was markedly higher than that in older children (44.4% vs. 15.9%). Eschar detection was substantially lower in infants than non-infants (22.2% vs. 66.7%), and central nervous system (CNS) involvement was universal among infants (100% vs. 42.9%). In eschar-negative cases, molecular diagnostics were essential for etiological confirmation. All comparisons are exploratory and hypothesis-generating. Conclusions Scrub typhus-associated HLH in young infants is associated with high mortality, frequent eschar absence, and universal CNS involvement, representing a clinical profile distinct from older children. In endemic areas, early molecular testing should be prioritized in eschar-negative presentations, and empirical doxycycline initiated promptly, with rifampin considered when CNS involvement is confirmed. Prospective multicenter studies are needed to validate these findings.