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Ann Neurol. 2015 Nov;78(5):722-30. doi: 10.1002/ana.24499. Epub 2015 Aug 24.

Diagnosing Balamuthia mandrillaris Encephalitis With Metagenomic Deep Sequencing.

Author information

  • 1Department of Biochemistry and Biophysics, University of California, San Francisco, CA.
  • 2Department of Neurology, University of California, San Francisco, CA.
  • 3Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, CA.
  • 4Koc University, Istanbul, Turkey.
  • 5Free-Living and Intestinal Amebas Laboratory, Centers for Disease Control and Prevention, Atlanta, GA.
  • 6Infectious Diseases Pathology Branch, Centers for Disease Control and Prevention, Atlanta, GA.
  • 7California Department of Public Health, Viral and Rickettsial Disease Laboratory, Richmond, CA.
  • 8Department of Pathology, Division of Neuropathology, University of California, San Francisco, CA.
  • 9Howard Hughes Medical Institute, Chevy Chase, MD.



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.


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.


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.


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.

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