Fulminant Acanthamoeba Encephalitis Diagnosed By Cell-Free DNA in a Renal Transplant Patient: A Case Report.

Granulomatous amoebic encephalitis (GAE) caused by Acanthamoeba spp. is a rare, nearly universally fatal central nervous system infection that predominantly affects immunocompromised individuals, including solid organ transplant (SOT) recipients. Early diagnosis is essential but often delayed due to nonspecific symptoms and the limited sensitivity of conventional diagnostic tests. We describe the case of a 58-year-old man who presented with fever and diarrhea one month after a simultaneous pancreas-kidney transplant. Despite broad-spectrum antimicrobial therapy, he developed status epilepticus and rapid neurologic deterioration. Extensive infectious workup, including cerebrospinal fluid studies, was non-diagnostic, and neuroimaging revealed multifocal infarcts and cerebral edema. Plasma microbial cell-free DNA sequencing identified Acanthamoeba spp., leading to a presumptive diagnosis of GAE that was later confirmed postmortem. This case represents the first reported use of plasma-based next-generation sequencing to diagnose Acanthamoeba GAE and highlights the clinical utility of noninvasive molecular diagnostics in immunocompromised hosts with unexplained encephalopathy. Earlier recognition of rare pathogens using these tools may facilitate more timely interventions and improve outcomes in transplant recipients with rapidly progressive neurologic syndromes.