Diagnosing Balamuthia mandrillaris Encephalitis With Metagenomic Deep Sequencing.
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.


CONCLUSIONS
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.
Department of Biochemistry and Biophysics, University of California, San Francisco, CA.|Department of Neurology, University of California, San Francisco, CA.
Michael R
MR
Wilson
Department of Neurology, University of California, San Francisco, CA.
Niraj M
NM
Shanbhag
Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, CA.
Michael J
MJ
Reid
Department of Neurology, University of California, San Francisco, CA.
Neel S
NS
Singhal
Department of Neurology, University of California, San Francisco, CA.
Jeffrey M
JM
Gelfand
Department of Neurology, University of California, San Francisco, CA.
Hannah A
HA
Sample
Koc University, Istanbul, Turkey.
Barlas
B
Benkli
Department of Biochemistry and Biophysics, University of California, San Francisco, CA.
Brian D
BD
O'Donovan
Free-Living and Intestinal Amebas Laboratory, Centers for Disease Control and Prevention, Atlanta, GA.
Ibne K M
IK
Ali
Infectious Diseases Pathology Branch, Centers for Disease Control and Prevention, Atlanta, GA.
M Kelly
MK
Keating
California Department of Public Health, Viral and Rickettsial Disease Laboratory, Richmond, CA.
Thelma H
TH
Dunnebacke
Department of Pathology, Division of Neuropathology, University of California, San Francisco, CA.
Matthew D
MD
Wood
Department of Pathology, Division of Neuropathology, University of California, San Francisco, CA.
Andrew
A
Bollen
Department of Biochemistry and Biophysics, University of California, San Francisco, CA.|Howard Hughes Medical Institute, Chevy Chase, MD.
Joseph L
JL
DeRisi
D000368:Aged; D000562:Amebiasis / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics*; D000818:Animals; D059611:Balamuthia mandrillaris / Q000235:genetics*; D001921:Brain / Q000382:microbiology; D016054:DNA, Protozoan / Q000235:genetics; D005260:Female; D023281:Genomics; D006801:Humans; D008590:Meningoencephalitis / Q000134:cerebrospinal fluid / Q000175:diagnosis* / Q000235:genetics*; D016133:Polymerase Chain Reaction; D017423:Sequence Analysis, RNA / Q000379:methods*; D014822:Vitreous Body / Q000382:microbiology
D016054:DNA, Protozoan