Neonatal scrub typhus with neurological manifestations: a case series from an endemic region

Neonatal scrub typhus is rare, potentially fatal, and easily confused with neonatal sepsis or meningitis, particularly when a typical eschar is absent. We describe the clinical, microbiological, neurological, and outcome features of three affected neonates and discuss the diagnostic and transmission-related implications. Three neonates from Yunnan Province, China, an endemic region for scrub typhus, developed fever on days 14–28 of life. All had multisystem involvement and neurological manifestations, but none had a typical eschar. All three mothers retrospectively reported a diagnosis of scrub typhus during pregnancy, but none of these histories could be independently verified because the original maternal records and laboratory results were unavailable. Two neonates had strong evidence of central nervous system involvement, whereas the third developed seizures during severe systemic illness with major metabolic disturbances. Orientia tsutsugamushi was detected by blood metagenomic next-generation sequencing in one patient and by targeted next-generation sequencing of blood and/or cerebrospinal fluid in the other two. One patient recovered after azithromycin followed by doxycycline; two died after progressive multiorgan dysfunction. One affected infant was a member of a dichorionic diamniotic twin pair; the co-twin remained asymptomatic and had negative blood and cerebrospinal-fluid targeted sequencing. Neonatal scrub typhus can cause life-threatening multisystem disease and may involve the central nervous system. In endemic areas, it should be considered in neonates with unexplained fever, sepsis-like illness, thrombocytopenia, coagulopathy, liver injury, or neurological manifestations even without an eschar. Molecular testing may establish an etiological diagnosis when routine investigations are unrevealing. A retrospectively reported maternal history of scrub typhus during pregnancy is an important epidemiological clue, but the present data do not establish transplacental transmission, and postnatal acquisition cannot be excluded.