Diagnosing Balamuthia mandrillaris Encephalitis with Metagenomic Deep Sequencing

Michael R. Wilson, Niraj M. Shanbhag, Michael J. Reid, Neel S. Singhal, Jeffrey M. Gelfand, Hannah A. Sample, Barlas Benkli, Brian D. O'Donovan, Ibne K.M. Ali, M. Kelly Keating, Thelma H. Dunnebacke, Matthew Wood, Andrew Bollen, Joseph L. DeRisi

Research output: Contribution to journalArticle

39 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)722-730
Number of pages9
JournalAnnals of Neurology
Volume78
Issue number5
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

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Balamuthia mandrillaris
High-Throughput Nucleotide Sequencing
Metagenomics
Encephalitis
Meningoencephalitis
Cerebrospinal Fluid
Viruses
Amoeba
Endophthalmitis
Brain
Serology
rRNA Genes
Communicable Diseases
Parasites
Fungi
Immunohistochemistry
Bacteria
Phenotype
Biopsy
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Wilson, M. R., Shanbhag, N. M., Reid, M. J., Singhal, N. S., Gelfand, J. M., Sample, H. A., ... DeRisi, J. L. (2015). Diagnosing Balamuthia mandrillaris Encephalitis with Metagenomic Deep Sequencing. Annals of Neurology, 78(5), 722-730. https://doi.org/10.1002/ana.24499

Diagnosing Balamuthia mandrillaris Encephalitis with Metagenomic Deep Sequencing. / Wilson, Michael R.; Shanbhag, Niraj M.; Reid, Michael J.; Singhal, Neel S.; Gelfand, Jeffrey M.; Sample, Hannah A.; Benkli, Barlas; O'Donovan, Brian D.; Ali, Ibne K.M.; Keating, M. Kelly; Dunnebacke, Thelma H.; Wood, Matthew; Bollen, Andrew; DeRisi, Joseph L.

In: Annals of Neurology, Vol. 78, No. 5, 01.01.2015, p. 722-730.

Research output: Contribution to journalArticle

Wilson, MR, Shanbhag, NM, Reid, MJ, Singhal, NS, Gelfand, JM, Sample, HA, Benkli, B, O'Donovan, BD, Ali, IKM, Keating, MK, Dunnebacke, TH, Wood, M, Bollen, A & DeRisi, JL 2015, 'Diagnosing Balamuthia mandrillaris Encephalitis with Metagenomic Deep Sequencing', Annals of Neurology, vol. 78, no. 5, pp. 722-730. https://doi.org/10.1002/ana.24499
Wilson MR, Shanbhag NM, Reid MJ, Singhal NS, Gelfand JM, Sample HA et al. Diagnosing Balamuthia mandrillaris Encephalitis with Metagenomic Deep Sequencing. Annals of Neurology. 2015 Jan 1;78(5):722-730. https://doi.org/10.1002/ana.24499
Wilson, Michael R. ; Shanbhag, Niraj M. ; Reid, Michael J. ; Singhal, Neel S. ; Gelfand, Jeffrey M. ; Sample, Hannah A. ; Benkli, Barlas ; O'Donovan, Brian D. ; Ali, Ibne K.M. ; Keating, M. Kelly ; Dunnebacke, Thelma H. ; Wood, Matthew ; Bollen, Andrew ; DeRisi, Joseph L. / Diagnosing Balamuthia mandrillaris Encephalitis with Metagenomic Deep Sequencing. In: Annals of Neurology. 2015 ; Vol. 78, No. 5. pp. 722-730.
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