Acute West Nile Virus Meningoencephalitis Diagnosed Via Metagenomic Deep Sequencing of Cerebrospinal Fluid in a Renal Transplant Patient

Abstract

Solid organ transplant patients are vulnerable to suffering neurologic complications from a wide array of viral infections and can be sentinels in the population who are first to get serious complications from emerging infections like the recent waves of arboviruses, including West Nile virus, Chikungunya virus, Zika virus, and Dengue virus. The diverse and rapidly changing landscape of possible causes of viral encephalitis poses great challenges for traditional candidate-based infectious disease diagnostics that already fail to identify a causative pathogen in approximately 50% of encephalitis cases. We present the case of a 14-year-old girl on immunosuppression for a renal transplant who presented with acute meningoencephalitis. Traditional diagnostics failed to identify an etiology. RNA extracted from her cerebrospinal fluid was subjected to unbiased metagenomic deep sequencing, enhanced with the use of a Cas9-based technique for host depletion. This analysis identified West Nile virus (WNV). Convalescent serum serologies subsequently confirmed WNV seroconversion. These results support a clear clinical role for metagenomic deep sequencing in the setting of suspected viral encephalitis, especially in the context of the high-risk transplant patient population.

Keywords: basic (laboratory) research/science; clinical research/practice; diagnostic techniques and imaging; genetics; genomics; infection and infectious agents; infectious disease; kidney (allograft) function/dysfunction; kidney transplantation/nephrology; viral: Epstein-Barr Virus (EBV); viral: West Nile, infection and infectious agents.

Figure 1

Neuroimaging. A, Axial T2‐weighted/fluid attenuated inversion recovery (FLAIR) brain MRI demonstrating symmetric hyperintensities in the basal ganglia and thalami (arrows). B and C, Pre‐ (B) and Post‐ (C) contrast T1‐weighted cervical spine MRI demonstrating leptomeningeal enhancement (arrows).