Hepatitis E Virus–Associated Meningoencephalitis in a Lung Transplant Recipient Diagnosed by Clinical Metagenomic Sequencing

Murkey, Jamie; Chew, Kara W.; Carlson, Margrit; Shannon, Chelsea; Sirohi, Deepika; Sample, Hannah; Wilson, Michael R.; Vespa, Paul; Humphries, Romney M.; Miller, Steve; Klausner, Jeffrey D.; Chiu, Charles Y.

doi:10.1093/ofid/ofx121

Cited by 65 publications

(44 citation statements)

References 15 publications

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“…24,[46][47][48][49][50][51][52] Total RNA is extracted from a patient's CSF, and complementary DNA (cDNA) is generated by reverse transcription with random hexamer primers. The use of mNGS has gained momentum over the past several years, with several notable case reports and case series showcasing mNGS's ability to capture a broad range of infections with a single assay.…”

Section: Research Csf Metagenomic Sequencingmentioning

confidence: 99%

“…The use of mNGS has gained momentum over the past several years, with several notable case reports and case series showcasing mNGS's ability to capture a broad range of infections with a single assay. 24,[46][47][48][49][50][51][52] Total RNA is extracted from a patient's CSF, and complementary DNA (cDNA) is generated by reverse transcription with random hexamer primers. The cDNA is then converted into a library of random fragments, which is then sequenced on a massively parallel scale.…”

Section: Research Csf Metagenomic Sequencingmentioning

confidence: 99%

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Clinicopathology conference: 41‐year‐old woman with chronic relapsing meningitis

Beck

Ramachandran

Khan

et al. 2019

Annals of Neurology

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Section: Research Csf Metagenomic Sequencingmentioning

confidence: 99%

Section: Research Csf Metagenomic Sequencingmentioning

confidence: 99%

Clinicopathology conference: 41‐year‐old woman with chronic relapsing meningitis

Beck

Ramachandran

Khan

et al. 2019

Annals of Neurology

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“…Obstacles to widespread adoption of mNGS include concerns about high costs, long turnaround time, and need for additional data about test performance characteristics. Thus, mNGS is often reserved for use as a late-stage option in diagnostically challenging cases [11][12][13][14][15][16]. Ongoing clinical validation of mNGS testing for a number of syndromes, results are based on did not include special access privileges to the data beyond the license.…”

Section: Introductionmentioning

confidence: 99%

Exploratory analysis of the potential for advanced diagnostic testing to reduce healthcare expenditures of patients hospitalized with meningitis or encephalitis

et al. 2020

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Objective To estimate healthcare expenditures that could be impacted by advanced diagnostic testing for patients hospitalized with meningitis or encephalitis Methods Patients hospitalized with meningitis (N = 23,933) or encephalitis (N = 7,858) in the U.S. were identified in the 2010-2014 Truven Health MarketScan Commercial Claims and Encounters Database using ICD-9-CM diagnostic codes. The database included an average of 40.8 million commercially insured enrollees under age 65 per year. Clinical, demographic and healthcare utilization criteria were used to identify patient subgroups early in their episode who were at risk to have high inpatient expenditures. Healthcare expenditures of patients within each subgroup were bifurcated: those expenditures that remained five days after the patient could be classified into the subgroup versus those that had occurred previously. Results The hospitalization episode rate per 100,000 enrollee-years for meningitis was 13.0 (95% CI: 12.9-13.2) and for encephalitis was 4.3 (95% CI: 4.2-4.4

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“…Metagenomic shotgun sequencing is a method of sequencing all the nucleic acid in a specimen unbiasedly and then matching the sequences to those in databases to identify organisms and their genetic traits (e.g., antibiotic resistance genes and mutations). This approach has the potential to identify a variety of infectious agents, including bacteria, viruses, fungi, and protists, directly from various clinical samples, with applications being described for central nervous system specimens (12)(13)(14)(15)(16), respiratory tract specimens (17,18), blood (19)(20)(21)(22), urine (23,24), bile (25), stool (26), synovial fluid (27), and prosthesis sonicate fluid (28)(29)(30).…”

mentioning

confidence: 99%

Evaluation of the CosmosID Bioinformatics Platform for Prosthetic Joint-Associated Sonicate Fluid Shotgun Metagenomic Data Analysis

Yan

Thoendel

et al. 2019

J Clin Microbiol

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We previously demonstrated that shotgun metagenomic sequencing can detect bacteria in sonicate fluid, providing a diagnosis of prosthetic joint infection (PJI). A limitation of the approach that we used is that data analysis was timeconsuming and specialized bioinformatics expertise was required, both of which are barriers to routine clinical use. Fortunately, automated commercial analytic platforms that can interpret shotgun metagenomic data are emerging. In this study, we evaluated the CosmosID bioinformatics platform using shotgun metagenomic sequencing data derived from 408 sonicate fluid samples from our prior study with the goal of evaluating the platform vis-à-vis bacterial detection and antibiotic resistance gene detection for predicting staphylococcal antibacterial susceptibility. Samples were divided into a derivation set and a validation set, each consisting of 204 samples; results from the derivation set were used to establish cutoffs, which were then tested in the validation set for identifying pathogens and predicting staphylococcal antibacterial resistance. Metagenomic analysis detected bacteria in 94.8% (109/115) of sonicate fluid culture-positive PJIs and 37.8% (37/98) of sonicate fluid culture-negative PJIs. Metagenomic analysis showed sensitivities ranging from 65.7 to 85.0% for predicting staphylococcal antibacterial resistance. In conclusion, the CosmosID platform has the potential to provide fast, reliable bacterial detection and identification from metagenomic shotgun sequencing data derived from sonicate fluid for the diagnosis of PJI. Strategies for metagenomic detection of antibiotic resistance genes for predicting staphylococcal antibacterial resistance need further development.

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Hepatitis E Virus–Associated Meningoencephalitis in a Lung Transplant Recipient Diagnosed by Clinical Metagenomic Sequencing

Cited by 65 publications

References 15 publications

Clinicopathology conference: 41‐year‐old woman with chronic relapsing meningitis

Clinicopathology conference: 41‐year‐old woman with chronic relapsing meningitis

Exploratory analysis of the potential for advanced diagnostic testing to reduce healthcare expenditures of patients hospitalized with meningitis or encephalitis

Evaluation of the CosmosID Bioinformatics Platform for Prosthetic Joint-Associated Sonicate Fluid Shotgun Metagenomic Data Analysis

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