Diagnosing Balamuthia mandrillaris Encephalitis With Metagenomic Deep Sequencing
Michael R. Wilson MD, Niraj M. Shanbhag MD, PhD, Michael J. Reid MD, Neel S. Singhal MD, PhD, Jeffrey M. Gelfand MD, MAS, Hannah A. Sample BS, Barlas Benkli BA, Brian D. O’Donovan MS, Ibne K.M. Ali PhD, M. Kelly Keating DVM, Thelma H. Dunnebacke PhD, Matthew D. Wood MD, PhD, Andrew Bollen MD, and Joseph L. DeRisi PhDAnnals of Neurology, 2015Abstract:
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
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.