Acute West Nile Virus Meningoencephalitis Diagnosed Via Metagenomic Deep Sequencing of Cerebrospinal Fluid in a Renal Transplant Patient

Solid organ transplant patients are vulnerable to suffering neurologic complications from a wide array of viral infections and can be sentinels in the population who are first to get serious complications from emerging infections like the recent waves of arboviruses, including West Nile virus, Chikungunya virus, Zika virus, and Dengue virus. The diverse and rapidly changing landscape of possible causes of viral encephalitis poses great challenges for traditional candidate‐based infectious disease diagnostics that already fail to identify a causative pathogen in approximately 50% of encephalitis cases. We present the case of a 14‐year‐old girl on immunosuppression for a renal transplant who presented with acute meningoencephalitis. Traditional diagnostics failed to identify an etiology. RNA extracted from her cerebrospinal fluid was subjected to unbiased metagenomic deep sequencing, enhanced with the use of a Cas9‐based technique for host depletion. This analysis identified West Nile virus (WNV). Convalescent serum serologies subsequently confirmed WNV seroconversion. These results support a clear clinical role for metagenomic deep sequencing in the setting of suspected viral encephalitis, especially in the context of the high‐risk transplant patient population.

[1]  Joseph L. DeRisi,et al.  Identification, Characterization, and In Vitro Culture of Highly Divergent Arenaviruses from Boa Constrictors and Annulated Tree Boas: Candidate Etiological Agents for Snake Inclusion Body Disease , 2012, mBio.

[2]  Bagher Forghani,et al.  In search of encephalitis etiologies: diagnostic challenges in the California Encephalitis Project, 1998-2000. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[3]  J. Pedroso,et al.  Neurological complications of solid organ transplantation , 2017, Arquivos de Neuro-Psiquiatria.

[4]  J. Derisi,et al.  Human Enterovirus 109: a Novel Interspecies Recombinant Enterovirus Isolated from a Case of Acute Pediatric Respiratory Illness in Nicaragua , 2010, Journal of Virology.

[5]  R. Lanciotti,et al.  Transmission of West Nile virus from an organ donor to four transplant recipients. , 2003, The New England journal of medicine.

[6]  Thomas R. Gingeras,et al.  STAR: ultrafast universal RNA-seq aligner , 2013, Bioinform..

[7]  E. Crawford,et al.  Depletion of Abundant Sequences by Hybridization (DASH): using Cas9 to remove unwanted high-abundance species in sequencing libraries and molecular counting applications , 2015, bioRxiv.

[8]  J. Fishman,et al.  Central nervous system syndromes in solid organ transplant recipients. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[9]  J. Derisi,et al.  Analysis of Naturally Occurring Avian Bornavirus Infection and Transmission during an Outbreak of Proventricular Dilatation Disease among Captive Psittacine Birds , 2009, Journal of Virology.

[10]  J. Derisi,et al.  Diagnosing Balamuthia mandrillaris Encephalitis With Metagenomic Deep Sequencing , 2015, Annals of neurology.

[11]  Steven L Salzberg,et al.  Fast gapped-read alignment with Bowtie 2 , 2012, Nature Methods.

[12]  R. DeBiasi,et al.  West Nile virus neuroinvasive disease , 2006, Annals of neurology.

[13]  N. Prasad,et al.  Dengue virus infection in renal allograft recipients: a case series during 2010 outbreak , 2012, Transplant infectious disease : an official journal of the Transplantation Society.

[14]  Zhengwei Zhu,et al.  CD-HIT: accelerated for clustering the next-generation sequencing data , 2012, Bioinform..

[15]  N. M. Vora,et al.  Burden of encephalitis-associated hospitalizations in the United States, 1998–2010 , 2013, Neurology.

[16]  K. Tyler,et al.  Four emerging arboviral diseases in North America: Jamestown Canyon, Powassan, chikungunya, and Zika virus diseases , 2016, Journal of NeuroVirology.

[17]  Serban Nacu,et al.  Fast and SNP-tolerant detection of complex variants and splicing in short reads , 2010, Bioinform..

[18]  J. Derisi,et al.  The complete genome of klassevirus – a novel picornavirus in pediatric stool , 2009, Virology Journal.

[19]  Xiao-jun Huang,et al.  Spectrum of Epstein-Barr Virus–Associated Diseases in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation , 2013, Transplantation.

[20]  G. Palù,et al.  West Nile virus and kidney disease , 2013, Expert review of anti-infective therapy.

[21]  J. Derisi,et al.  PRICE: Software for the Targeted Assembly of Components of (Meta) Genomic Sequence Data , 2013, G3: Genes, Genomes, Genetics.

[22]  Yongan Zhao,et al.  RAPSearch2: a fast and memory-efficient protein similarity search tool for next-generation sequencing data , 2011, Bioinform..

[23]  G. Klintmalm,et al.  West Nile Virus Infection in Kidney and Pancreas Transplant Recipients in the Dallas-Fort Worth Metroplex During the 2012 Texas Epidemic , 2014, Transplantation.

[24]  B. Gazzard,et al.  The significance of Epstein–Barr virus detected in the cerebrospinal fluid of people with HIV infection , 2007, HIV medicine.

[25]  Joseph L DeRisi,et al.  Actionable diagnosis of neuroleptospirosis by next-generation sequencing. , 2014, The New England journal of medicine.

[26]  Abraham Lempel,et al.  A universal algorithm for sequential data compression , 1977, IEEE Trans. Inf. Theory.

[27]  刘启发 Spectrum of Epstein-Barr Virus–Associated Diseases in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation , 2013 .