Diagnosing Balamuthia mandrillaris Encephalitis With Metagenomic Deep Sequencing

Abstract

Objective: Identification of a particular cause of meningoencephalitis can be challenging owing to the myriad bacteria, viruses, fungi, and parasites that can produce overlapping clinical phenotypes, frequently delaying diagnosis and therapy. Metagenomic deep sequencing (MDS) approaches to infectious disease diagnostics are known for their ability to identify unusual or novel viruses and thus are well suited for investigating possible etiologies of meningoencephalitis.

Methods: We present the case of a 74-year-old woman with endophthalmitis followed by meningoencephalitis. MDS of her cerebrospinal fluid (CSF) was performed to identify an infectious agent.

Results: Sequences aligning to Balamuthia mandrillaris ribosomal RNA genes were identified in the CSF by MDS. Polymerase chain reaction subsequently confirmed the presence of B. mandrillaris in CSF, brain tissue, and vitreous fluid from the patient's infected eye. B. mandrillaris serology and immunohistochemistry for free-living amoebas on the brain biopsy tissue were positive.

Interpretation: The diagnosis was made using MDS after the patient had been hospitalized for several weeks and subjected to costly and invasive testing. MDS is a powerful diagnostic tool with the potential for rapid and unbiased pathogen identification leading to early therapeutic targeting.

Figure 1

Neuroimaging and neuropathology. (A) Axial T2‐weighted/fluid‐attenuated inversion recovery (FLAIR) brain magnetic resonance imaging (MRI) demonstrating multiple hyperintensities (arrows), which correspond to areas of restricted diffusion on diffusion weighted imaging (not shown). (B) Axial T2‐weighted/FLAIR brain MRI demonstrating progression in the size and number of hyperintensities (arrows) visualized in the MRI in (A). (C) Postcontrast axial T1‐weighted brain MRI demonstrating multiple ring enhancing lesions (white arrow) and basilar meningitis (yellow arrow) as well as severe hydrocephalus. (D) Periodic acid‐Schiff stained section of brain parenchyma shows necrotizing vasculitis, chronic inflammatory cells, and a population of amoebic trophozoites that closely resemble macrophages (arrows); 400×. The majority of the tissue showed a robust necrotizing vasculitis with mixed inflammation, including macrophages and numerous eosinophils. (E) Immunohistochemistry for free‐living amoebas highlights numerous B. mandrillaris trophozoites; 400 × (courtesy of M.K.K., CDC).