Nonthyroidal illness syndrome and diagnostic utility of CSF mNGS: insights from a case series of neurological scrub typhus

We describe five cases of neurological scrub typhus that highlight two critical, underrecognized aspects of this disease. First, cerebrospinal fluid metagenomic next-generation sequencing (CSF mNGS) accurately identified Orientia tsutsugamushi in all three patients tested, while the conventional Weil-Felix test was negative in every case, establishing mNGS as a pivotal diagnostic tool. Second, we uncovered a high prevalence of thyroid dysfunction, with nonthyroidal illness syndrome (NTIS) present in three of four patients tested, a novel systemic complication linked to severe inflammatory stress. Additional notable findings included frequent hypokalemia, at times severe enough to mimic periodic paralysis, and urban acquisition in two cases, suggesting an expanding epidemiological footprint. All patients improved on doxycycline-based regimens. This series underscores the diagnostic superiority of CSF mNGS and reveals NTIS as a key endocrine manifestation in neurological scrub typhus, urging greater clinical vigilance.