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DOI: 10.1055/s-0039-1688441
Diagnostic Testing in Central Nervous System Infection
Publication History
Publication Date:
02 August 2019 (online)
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Abstract
Patients with central nervous system (CNS) infection experience very high levels of morbidity and mortality, in part because of the many challenges inherent to the diagnosis of CNS infection and identification of a causative pathogen. The clinical presentation of CNS infection is nonspecific, so clinicians must often order and interpret many diagnostic tests in parallel. This can be a daunting task given the large number of potential pathogens and the availability of different testing modalities. Here, we review traditional diagnostic techniques including Gram stain and culture, serology, and polymerase chain reaction (PCR). We highlight which of these are recommended for the pathogens most commonly tested among U.S. patients with suspected CNS infection. Finally, we describe the newer broad-range diagnostic approaches, multiplex PCR and metagenomic sequencing, which are increasingly used in clinical practice.
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References
- 1 Venkatesan A, Tunkel AR, Bloch KC. , et al; International Encephalitis Consortium. Case definitions, diagnostic algorithms, and priorities in encephalitis: consensus statement of the international encephalitis consortium. Clin Infect Dis 2013; 57 (08) 1114-1128
- 2 Tunkel AR, Glaser CA, Bloch KC. , et al; Infectious Diseases Society of America. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis 2008; 47 (03) 303-327
- 3 Negrini B, Kelleher KJ, Wald ER. Cerebrospinal fluid findings in aseptic versus bacterial meningitis. Pediatrics 2000; 105 (02) 316-319
- 4 Coll MT, Uriz MS, Pineda V. , et al. Meningococcal meningitis with ‘normal’ cerebrospinal fluid. J Infect 1994; 29 (03) 289-294
- 5 Cho TA, Mckendall RR. Clinical approach to the syndromes of viral encephalitis, myelitis, and meningitis. Handb Clin Neurol 2014; 123: 89-121
- 6 Graeff-Teixeira C, da Silva ACA, Yoshimura K. Update on eosinophilic meningoencephalitis and its clinical relevance. Clin Microbiol Rev 2009; 22 (02) 322-348
- 7 Gray LD, Fedorko DP. Laboratory diagnosis of bacterial meningitis. Clin Microbiol Rev 1992; 5 (02) 130-145
- 8 Kanegaye JT, Soliemanzadeh P, Bradley JS. Lumbar puncture in pediatric bacterial meningitis: defining the time interval for recovery of cerebrospinal fluid pathogens after parenteral antibiotic pretreatment. Pediatrics 2001; 108 (05) 1169-1174
- 9 Michael B, Menezes BF, Cunniffe J. , et al. Effect of delayed lumbar punctures on the diagnosis of acute bacterial meningitis in adults. Emerg Med J 2010; 27 (06) 433-438
- 10 Marx GE, Chan ED. Tuberculous meningitis: diagnosis and treatment overview. Tuberc Res Treat 2011; 2011: 798764
- 11 Erdem H, Ozturk-Engin D, Elaldi N. , et al. The microbiological diagnosis of tuberculous meningitis: results of Haydarpasa-1 study. Clin Microbiol Infect 2014; 20 (10) O600-O608
- 12 Bahr NC, Tugume L, Rajasingham R. , et al. Improved diagnostic sensitivity for tuberculous meningitis with Xpert(®) MTB/RIF of centrifuged CSF. Int J Tuberc Lung Dis 2015; 19 (10) 1209-1215
- 13 Peaper DR, Landry ML. Laboratory diagnosis of viral infection. Handb Clin Neurol 2014; 123: 123-147
- 14 Lyons JL, Schaefer PW, Cho TA, Azar MM. Case 34-2017. A 76-year-old man with fever, weight loss, and weakness. N Engl J Med 2017; 377 (19) 1878-1886
- 15 Lanciotti RS, Kerst AJ, Nasci RS. , et al. Rapid detection of West Nile virus from human clinical specimens, field-collected mosquitoes, and avian samples by a TaqMan reverse transcriptase-PCR assay. J Clin Microbiol 2000; 38 (11) 4066-4071
- 16 Bennett JE, Dolin R, Blaser MJ. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. Philadelphia, PA: Elsevier/Saunders; 2015
- 17 CDC. Arboviral diseases, neuroinvasive and non-neuroinvasive 2015 case definition. Available at: https://wwwn.cdc.gov/nndss/conditions/arboviral-diseases-neuroinvasive-and-non-neuroinvasive/case-definition/2015/ . Accessed November 14, 2018
- 18 Murray KO, Garcia MN, Yan C, Gorchakov R. Persistence of detectable immunoglobulin M antibodies up to 8 years after infection with West Nile virus. Am J Trop Med Hyg 2013; 89 (05) 996-1000
- 19 Guven T, Ugurlu K, Ergönül O. , et al. Neurobrucellosis: clinical and diagnostic features. Clin Infect Dis 2013; 56 (10) 1407-1412
- 20 Wright AE, Semple D. On the employment of dead bacteria in the serum diagnosis of typhoid and malta fever, and on an easy method of extemporising a blowpipe flame for making capillary sero-sedimentation tubes. BMJ 1897; 1 (1898): 1214-1215
- 21 Memish ZA, Almuneef M, Mah MW, Qassem LA, Osoba AO. Comparison of the brucella standard agglutination test with the ELISA IgG and IgM in patients with Brucella bacteremia. Diagn Microbiol Infect Dis 2002; 44 (02) 129-132
- 22 Erdem H, Kilic S, Sener B. , et al. Diagnosis of chronic brucellar meningitis and meningoencephalitis: the results of the Istanbul-2 study. Clin Microbiol Infect 2013; 19 (02) E80-E86
- 23 Mitka S, Anetakis C, Souliou E, Diza E, Kansouzidou A. Evaluation of different PCR assays for early detection of acute and relapsing brucellosis in humans in comparison with conventional methods. J Clin Microbiol 2007; 45 (04) 1211-1218
- 24 Araj GF, Lulu AR, Khateeb MI, Saadah MA, Shakir RA. ELISA versus routine tests in the diagnosis of patients with systemic and neurobrucellosis. APMIS 1988; 96 (02) 171-176
- 25 Yagupsky P. Detection of Brucellae in blood cultures. J Clin Microbiol 1999; 37 (11) 3437-3442
- 26 Colmenero JD, Queipo-Ortuño MI, Reguera JM, Baeza G, Salazar JA, Morata P. Real time polymerase chain reaction: a new powerful tool for the diagnosis of neurobrucellosis. J Neurol Neurosurg Psychiatry 2005; 76 (07) 1025-1027
- 27 Canneti B, Cabo-Lopez I, Puy-Nunez A. , et al. Neurological presentations of Bartonella henselae infection. Neurol Sci 2019; 40 (02) 261-268
- 28 Wong MT, Dolan MJ, Lattuada Jr CP. , et al. Neuroretinitis, aseptic meningitis, and lymphadenitis associated with Bartonella (Rochalimaea) henselae infection in immunocompetent patients and patients infected with human immunodeficiency virus type 1. Clin Infect Dis 1995; 21 (02) 352-360
- 29 Bergmans AM, Peeters MF, Schellekens JF. , et al. Pitfalls and fallacies of cat scratch disease serology: evaluation of Bartonella henselae-based indirect fluorescence assay and enzyme-linked immunoassay. J Clin Microbiol 1997; 35 (08) 1931-1937
- 30 Margolis B, Kuzu I, Herrmann M, Raible MD, Hsi E, Alkan S. Rapid polymerase chain reaction-based confirmation of cat scratch disease and Bartonella henselae infection. Arch Pathol Lab Med 2003; 127 (06) 706-710
- 31 Hansmann Y, DeMartino S, Piémont Y. , et al. Diagnosis of cat scratch disease with detection of Bartonella henselae by PCR: a study of patients with lymph node enlargement. J Clin Microbiol 2005; 43 (08) 3800-3806
- 32 Schwartzman WA, Patnaik M, Barka NE, Peter JB. Rochalimaea antibodies in HIV-associated neurologic disease. Neurology 1994; 44 (07) 1312-1316
- 33 Hook III EW. Syphilis. Lancet 2017; 389 (10078): 1550-1557
- 34 Lee JW, Wilck M, Venna N. Dementia due to neurosyphilis with persistently negative CSF VDRL. Neurology 2005; 65 (11) 1838
- 35 Marra CM, Tantalo LC, Sahi SK, Maxwell CL, Lukehart SA. CXCL13 as a cerebrospinal fluid marker for neurosyphilis in HIV-infected patients with syphilis. Sex Transm Dis 2010; 37 (05) 283-287
- 36 Marra CM, Tantalo LC, Maxwell CL, Ho EL, Sahi SK, Jones T. The rapid plasma reagin test cannot replace the Venereal Disease Research Laboratory test for neurosyphilis diagnosis. Sex Transm Dis 2012; 39 (06) 453-457
- 37 Marks M, Lawrence D, Kositz C, Mabey D. Diagnostic performance of PCR assays for the diagnosis of neurosyphilis: a systematic review. Sex Transm Infect 2018; 94 (08) 585-588
- 38 Harding AS, Ghanem KG. The performance of cerebrospinal fluid treponemal-specific antibody tests in neurosyphilis: a systematic review. Sex Transm Dis 2012; 39 (04) 291-297
- 39 Marra CM, Maxwell CL, Dunaway SB, Sahi SK, Tantalo LC. Cerebrospinal fluid treponema pallidum particle agglutination assay for neurosyphilis diagnosis. J Clin Microbiol 2017; 55 (06) 1865-1870
- 40 Krüger H, Reuss K, Pulz M. , et al. Meningoradiculitis and encephalomyelitis due to Borrelia burgdorferi: a follow-up study of 72 patients over 27 years. J Neurol 1989; 236 (06) 322-328
- 41 Koedel U, Fingerle V, Pfister H-W. Lyme neuroborreliosis-epidemiology, diagnosis and management. Nat Rev Neurol 2015; 11 (08) 446-456
- 42 Hansen K, Lebech AM. Lyme neuroborreliosis: a new sensitive diagnostic assay for intrathecal synthesis of Borrelia burgdorferi--specific immunoglobulin G, A, and M. Ann Neurol 1991; 30 (02) 197-205
- 43 Ljøstad U, Skarpaas T, Mygland A. Clinical usefulness of intrathecal antibody testing in acute Lyme neuroborreliosis. Eur J Neurol 2007; 14 (08) 873-876
- 44 Theel ES, Aguero-Rosenfeld ME, Pritt B, Adem PV, Wormser GP. Limitations and confusing aspects of diagnostic testing for neurologic lyme disease in the United States. J Clin Microbiol 2019; 57 (01) e01406-18
- 45 Wilking H, Fingerle V, Klier C, Thamm M, Stark K. Antibodies against Borrelia burgdorferi sensu lato among Adults, Germany, 2008-2011. Emerg Infect Dis 2015; 21 (01) 107-110
- 46 Hammers-Berggren S, Hansen K, Lebech AM, Karlsson M. Borrelia burgdorferi-specific intrathecal antibody production in neuroborreliosis: a follow-up study. Neurology 1993; 43 (01) 169-175
- 47 Bajani MD, Ashford DA, Bragg SL. , et al. Evaluation of four commercially available rapid serologic tests for diagnosis of leptospirosis. J Clin Microbiol 2003; 41 (02) 803-809
- 48 Cole Jr JR, Sulzer CR, Pursell AR. Improved microtechnique for the leptospiral microscopic agglutination test. Appl Microbiol 1973; 25 (06) 976-980
- 49 Desakorn V, Wuthiekanun V, Thanachartwet V. , et al. Accuracy of a commercial IgM ELISA for the diagnosis of human leptospirosis in Thailand. Am J Trop Med Hyg 2012; 86 (03) 524-527
- 50 Nabity SA, Hagan JE, Araújo G. , et al. Prospective evaluation of accuracy and clinical utility of the Dual Path Platform (DPP) assay for the point-of-care diagnosis of leptospirosis in hospitalized patients. PLoS Negl Trop Dis 2018; 12 (02) e0006285
- 51 Bouza E, Dreyer JS, Hewitt WL, Meyer RD. Coccidioidal meningitis. An analysis of thirty-one cases and review of the literature. Medicine (Baltimore) 1981; 60 (03) 139-172
- 52 Drake KW, Adam RD. Coccidioidal meningitis and brain abscesses: analysis of 71 cases at a referral center. Neurology 2009; 73 (21) 1780-1786
- 53 Wheat LJ, Batteiger BE, Sathapatayavongs B. Histoplasma capsulatum infections of the central nervous system. A clinical review. Medicine (Baltimore) 1990; 69 (04) 244-260
- 54 Kassis C, Zaidi S, Kuberski T. , et al. Role of Coccidioides antigen testing in the cerebrospinal fluid for the diagnosis of coccidioidal meningitis. Clin Infect Dis 2015; 61 (10) 1521-1526
- 55 Galgiani JN, Peng T, Lewis ML, Cloud GA, Pappagianis D. ; The National Institute of Allergy and Infectious Diseases Mycoses Study Group. Cerebrospinal fluid antibodies detected by ELISA against a 33-kDa antigen from spherules of Coccidioides immitis in patients with coccidioidal meningitis. J Infect Dis 1996; 173 (02) 499-502
- 56 Bloch KC, Myint T, Raymond-Guillen L. , et al. Improvement in diagnosis of Histoplasma meningitis by combined testing for histoplasma antigen and immunoglobulin G and immunoglobulin M anti-histoplasma antibody in cerebrospinal fluid. Clin Infect Dis 2018; 66 (01) 89-94
- 57 Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. 2018 . Available at: http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf . Accessed April 1, 2019
- 58 Alfonso Y, Fraga J, Jiménez N. , et al. Detection of Toxoplasma gondii in cerebrospinal fluid from AIDS patients by nested PCR and rapid identification of type I allele at B1 gene by RFLP analysis. Exp Parasitol 2009; 122 (03) 203-207
- 59 Cingolani A, De Luca A, Ammassari A. , et al. PCR detection of Toxoplasma gondii DNA in CSF for the differential diagnosis of AIDS-related focal brain lesions. J Med Microbiol 1996; 45 (06) 472-476
- 60 Walker MD, Zunt JR. Neuroparasitic infections: cestodes, trematodes, and protozoans. Semin Neurol 2005; 25 (03) 262-277
- 61 WHO. Guidelines for the diagnosis, prevention and management of cryptococcal disease in HIV-infected adults, adolescents and children: supplement to the 2016 consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Available at: https://www.who.int/hiv/pub/guidelines/cryptococcal-disease/en/ . Accessed April 1, 2019
- 62 Lu H, Zhou Y, Yin Y, Pan X, Weng X. Cryptococcal antigen test revisited: significance for cryptococcal meningitis therapy monitoring in a tertiary chinese hospital. J Clin Microbiol 2005; 43 (06) 2989-2990
- 63 Kabanda T, Siedner MJ, Klausner JD, Muzoora C, Boulware DR. Point-of-care diagnosis and prognostication of cryptococcal meningitis with the cryptococcal antigen lateral flow assay on cerebrospinal fluid. Clin Infect Dis 2014; 58 (01) 113-116
- 64 Tarafdar K, Rao S, Recco RA, Zaman MM. Lack of sensitivity of the latex agglutination test to detect bacterial antigen in the cerebrospinal fluid of patients with culture-negative meningitis. Clin Infect Dis 2001; 33 (03) 406-408
- 65 Karre T, Vetter EA, Mandrekar JN, Patel R. Comparison of bacterial antigen test and gram stain for detecting classic meningitis bacteria in cerebrospinal fluid. J Clin Microbiol 2010; 48 (04) 1504-1505
- 66 Debiasi RL, Tyler KL. Molecular methods for diagnosis of viral encephalitis. Clin Microbiol Rev 2004; 17 (04) 903-925 , table of contents
- 67 Lakeman FD, Whitley RJ. ; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Diagnosis of herpes simplex encephalitis: application of polymerase chain reaction to cerebrospinal fluid from brain-biopsied patients and correlation with disease. J Infect Dis 1995; 171 (04) 857-863
- 68 Tebas P, Nease RF, Storch GA. Use of the polymerase chain reaction in the diagnosis of herpes simplex encephalitis: a decision analysis model. Am J Med 1998; 105 (04) 287-295
- 69 Weil AA, Glaser CA, Amad Z, Forghani B. Patients with suspected herpes simplex encephalitis: rethinking an initial negative polymerase chain reaction result. Clin Infect Dis 2002; 34 (08) 1154-1157
- 70 Mueller NH, Gilden DH, Cohrs RJ, Mahalingam R, Nagel MA. Varicella zoster virus infection: clinical features, molecular pathogenesis of disease, and latency. Neurol Clin 2008; 26 (03) 675-697 , viii
- 71 Steiner I, Kennedy PGE, Pachner AR. The neurotropic herpes viruses: herpes simplex and varicella-zoster. Lancet Neurol 2007; 6 (11) 1015-1028
- 72 Nagel MA, Cohrs RJ, Mahalingam R. , et al. The varicella zoster virus vasculopathies: clinical, CSF, imaging, and virologic features. Neurology 2008; 70 (11) 853-860
- 73 Read SJ, Jeffery KJ, Bangham CR. Aseptic meningitis and encephalitis: the role of PCR in the diagnostic laboratory. J Clin Microbiol 1997; 35 (03) 691-696
- 74 Portolani M, Cermelli C, Meacci M. , et al. Epstein-Barr virus DNA in the cerebrospinal fluid of patients with human immunodeficiency virus infection and central nervous system disorders. New Microbiol 1999; 22 (04) 369-374
- 75 Challoner PB, Smith KT, Parker JD. , et al. Plaque-associated expression of human herpesvirus 6 in multiple sclerosis. Proc Natl Acad Sci U S A 1995; 92 (16) 7440-7444
- 76 Clark DA. Clinical and laboratory features of human herpesvirus 6 chromosomal integration. Clin Microbiol Infect 2016; 22 (04) 333-339
- 77 University of Washington Medicine. Molecular diagnostic (PCR) testing. Available at: http://depts.washington.edu/uwviro/clinical-testing/ . Accessed December 2, 2018
- 78 Green DA, Pereira M, Miko B, Radmard S, Whittier S, Thakur K. Clinical Significance of Human Herpesvirus 6 positivity on the FilmArray meningitis/encephalitis panel. Clin Infect Dis 2018; 67 (07) 1125-1128
- 79 Ho PR, Koendgen H, Campbell N, Haddock B, Richman S, Chang I. Risk of natalizumab-associated progressive multifocal leukoencephalopathy in patients with multiple sclerosis: a retrospective analysis of data from four clinical studies. Lancet Neurol 2017; 16 (11) 925-933
- 80 Pérez-Vélez CM, Anderson MS, Robinson CC. , et al. Outbreak of neurologic enterovirus type 71 disease: a diagnostic challenge. Clin Infect Dis 2007; 45 (08) 950-957
- 81 Mylonakis E, Hohmann EL, Calderwood SB. Central nervous system infection with Listeria monocytogenes. 33 years' experience at a general hospital and review of 776 episodes from the literature. Medicine (Baltimore) 1998; 77 (05) 313-336
- 82 Brouwer MC, van de Beek D, Heckenberg SG, Spanjaard L, de Gans J. Community-acquired Listeria monocytogenes meningitis in adults. Clin Infect Dis 2006; 43 (10) 1233-1238
- 83 Arslan F, Meynet E, Sunbul M. , et al. The clinical features, diagnosis, treatment, and prognosis of neuroinvasive listeriosis: a multinational study. Eur J Clin Microbiol Infect Dis 2015; 34 (06) 1213-1221
- 84 Charlier C, Perrodeau É, Leclercq A. , et al; MONALISA study group. Clinical features and prognostic factors of listeriosis: the MONALISA national prospective cohort study. Lancet Infect Dis 2017; 17 (05) 510-519
- 85 Piquet AL, Cho TA. The clinical approach to encephalitis. Curr Neurol Neurosci Rep 2016; 16 (05) 45
- 86 Le Monnier A, Abachin E, Beretti JL, Berche P, Kayal S. Diagnosis of Listeria monocytogenes meningoencephalitis by real-time PCR for the hly gene. J Clin Microbiol 2011; 49 (11) 3917-3923
- 87 Al-Zaidy SA, MacGregor D, Mahant S, Richardson SE, Bitnun A. Neurological complications of PCR-proven M. pneumoniae infections in children: prodromal illness duration may reflect pathogenetic mechanism. Clin Infect Dis 2015; 61 (07) 1092-1098
- 88 Bitnun A, Ford-Jones EL, Petric M. , et al. Acute childhood encephalitis and Mycoplasma pneumoniae. Clin Infect Dis 2001; 32 (12) 1674-1684
- 89 Waites KB, Xiao L, Paralanov V, Viscardi RM, Glass JI. Molecular methods for the detection of Mycoplasma and ureaplasma infections in humans: a paper from the 2011 William Beaumont Hospital Symposium on molecular pathology. J Mol Diagn 2012; 14 (05) 437-450
- 90 WHO. WHO meeting report of a technical expert consultation: non-inferiority analysis of Xpert MTB/RIF Ultra compared to Xpert MTB/RIF. 2017 . Available at: https://www.who.int/tb/publications/2017/XpertUltra/en/ . Accessed April 1, 2019
- 91 Bahr NC, Nuwagira E, Evans EE. , et al; ASTRO-CM Trial Team. Diagnostic accuracy of Xpert MTB/RIF Ultra for tuberculous meningitis in HIV-infected adults: a prospective cohort study. Lancet Infect Dis 2018; 18 (01) 68-75
- 92 Glaser CA, Honarmand S, Anderson LJ. , et al. Beyond viruses: clinical profiles and etiologies associated with encephalitis. Clin Infect Dis 2006; 43 (12) 1565-1577
- 93 Kupila L, Vuorinen T, Vainionpää R, Hukkanen V, Marttila RJ, Kotilainen P. Etiology of aseptic meningitis and encephalitis in an adult population. Neurology 2006; 66 (01) 75-80
- 94 Popiel M, Perlejewski K, Bednarska A. , et al. Viral etiologies in adult patients with encephalitis in Poland: a prospective single center study. PLoS One 2017; 12 (06) e0178481
- 95 McGill F, Griffiths MJ, Bonnett LJ. , et al; UK Meningitis Study Investigators. Incidence, aetiology, and sequelae of viral meningitis in UK adults: a multicentre prospective observational cohort study. Lancet Infect Dis 2018; 18 (09) 992-1003
- 96 Gable MS, Sheriff H, Dalmau J, Tilley DH, Glaser CA. The frequency of autoimmune N-methyl-D-aspartate receptor encephalitis surpasses that of individual viral etiologies in young individuals enrolled in the California Encephalitis Project. Clin Infect Dis 2012; 54 (07) 899-904
- 97 Leber AL, Everhart K, Balada-Llasat J-M. , et al. Multicenter evaluation of BioFire FilmArray Meningitis/Encephalitis Panel for detection of bacteria, viruses, and yeast in cerebrospinal fluid specimens. J Clin Microbiol 2016; 54 (09) 2251-2261
- 98 Liesman RM, Strasburg AP, Heitman AK, Theel ES, Patel R, Binnicker MJ. Evaluation of a commercial multiplex molecular panel for diagnosis of infectious meningitis and encephalitis. J Clin Microbiol 2018; 56 (04) e01927-17
- 99 Hanson KE, Slechta ES, Killpack JA. , et al. Preclinical assessment of a fully automated multiplex PCR panel for detection of central nervous system pathogens. J Clin Microbiol 2016; 54 (03) 785-787
- 100 Launes C, Casas-Alba D, Fortuny C, Valero-Rello A, Cabrerizo M, Muñoz-Almagro C. Utility of FilmArray meningitis/encephalitis panel during outbreak of brainstem encephalitis caused by enterovirus in Catalonia in 2016. J Clin Microbiol 2016; 55 (01) 336-338
- 101 Messacar K, Breazeale G, Robinson CC, Dominguez SR. Potential clinical impact of the film array meningitis encephalitis panel in children with suspected central nervous system infections. Diagn Microbiol Infect Dis 2016; 86 (01) 118-120
- 102 Graf EH, Farquharson MV, Cárdenas AM. Comparative evaluation of the FilmArray meningitis/encephalitis molecular panel in a pediatric population. Diagn Microbiol Infect Dis 2017; 87 (01) 92-94
- 103 Rhein J, Bahr NC, Hemmert AC. , et al; ASTRO-CM Team. Diagnostic performance of a multiplex PCR assay for meningitis in an HIV-infected population in Uganda. Diagn Microbiol Infect Dis 2016; 84 (03) 268-273
- 104 Chew KL, Lee CK, Cross GB, Lum LHW, Yan B, Jureen R. Culture-confirmed cryptococcal meningitis not detected by Cryptococcus PCR on the Biofire meningitis/encephalitis panel® . Clin Microbiol Infect 2018; 24 (07) 791-792
- 105 Simner PJ, Miller S, Carroll KC. Understanding the promises and hurdles of metagenomic next-generation sequencing as a diagnostic tool for infectious diseases. Clin Infect Dis 2018; 66 (05) 778-788
- 106 Gu W, Miller S, Chiu CY. Clinical metagenomic next-generation sequencing for pathogen detection. Annu Rev Pathol 2019; 14: 319-338
- 107 Wilson MR, Naccache SN, Samayoa E. , et al. Actionable diagnosis of neuroleptospirosis by next-generation sequencing. N Engl J Med 2014; 370 (25) 2408-2417
- 108 Mongkolrattanothai K, Naccache SN, Bender JM. , et al. Neurobrucellosis: unexpected answer from metagenomic next-generation sequencing. J Pediatric Infect Dis Soc 2017; 6 (04) 393-398
- 109 Fan S, Ren H, Wei Y. , et al. Next-generation sequencing of the cerebrospinal fluid in the diagnosis of neurobrucellosis. Int J Infect Dis 2018; 67: 20-24
- 110 Christopeit M, Grundhoff A, Rohde H. , et al. Suspected encephalitis with Candida tropicalis and Fusarium detected by unbiased RNA sequencing. Ann Hematol 2016; 95 (11) 1919-1921
- 111 Wilson MR, Shanbhag NM, Reid MJ. , et al. Diagnosing Balamuthia mandrillaris encephalitis with metagenomic deep sequencing. Ann Neurol 2015; 78 (05) 722-730
- 112 Wilson MR, Zimmermann LL, Crawford ED. , et al. Acute West Nile virus meningoencephalitis diagnosed via metagenomic deep sequencing of cerebrospinal fluid in a renal transplant patient. Am J Transplant 2017; 17 (03) 803-808
- 113 Murkey JA, Chew KW, Carlson M. , et al. Hepatitis E virus-associated meningoencephalitis in a lung transplant recipient diagnosed by clinical metagenomic sequencing. Open Forum Infect Dis 2017; 4 (03) ofx121
- 114 Chan BK, Wilson T, Fischer KF, Kriesel JD. Deep sequencing to identify the causes of viral encephalitis. PLoS One 2014; 9 (04) e93993
- 115 Salzberg SL, Breitwieser FP, Kumar A. , et al. Next-generation sequencing in neuropathologic diagnosis of infections of the nervous system. Neurol Neuroimmunol Neuroinflamm 2016; 3 (04) e251
- 116 Hong DK, Blauwkamp TA, Kertesz M, Bercovici S, Truong C, Banaei N. Liquid biopsy for infectious diseases: sequencing of cell-free plasma to detect pathogen DNA in patients with invasive fungal disease. Diagn Microbiol Infect Dis 2018; 92 (03) 210-213
- 117 Frémond ML, Pérot P, Muth E. , et al. Next-generation sequencing for diagnosis and tailored therapy: a case report of astrovirus-associated progressive encephalitis. J Pediatric Infect Dis Soc 2015; 4 (03) e53-e57
- 118 Piantadosi A, Kanjilal S, Ganesh V. , et al. Rapid detection of Powassan virus in a patient with encephalitis by metagenomic sequencing. Clin Infect Dis 2018; 66 (05) 789-792
- 119 Solomon IH, Spera KM, Ryan SL. , et al. Fatal Powassan encephalitis (deer tick virus, lineage II) in a patient with fever and orchitis receiving rituximab. JAMA Neurol 2018; 75 (06) 746-750
- 120 Morfopoulou S, Brown JR, Davies EG. , et al. Human coronavirus OC43 associated with fatal encephalitis. N Engl J Med 2016; 375 (05) 497-498
- 121 Wilson MR, Suan D, Duggins A. , et al. A novel cause of chronic viral meningoencephalitis: Cache Valley virus. Ann Neurol 2017; 82 (01) 105-114
- 122 Morfopoulou S, Mee ET, Connaughton SM. , et al. Deep sequencing reveals persistence of cell-associated mumps vaccine virus in chronic encephalitis. Acta Neuropathol 2017; 133 (01) 139-147
- 123 Hoffmann B, Tappe D, Höper D. , et al. A variegated squirrel bornavirus associated with fatal human encephalitis. N Engl J Med 2015; 373 (02) 154-162
- 124 Naccache SN, Peggs KS, Mattes FM. , et al. Diagnosis of neuroinvasive astrovirus infection in an immunocompromised adult with encephalitis by unbiased next-generation sequencing. Clin Infect Dis 2015; 60 (06) 919-923
- 125 Lum SH, Turner A, Guiver M. , et al. An emerging opportunistic infection: fatal astrovirus (VA1/HMO-C) encephalitis in a pediatric stem cell transplant recipient. Transpl Infect Dis 2016; 18 (06) 960-964
- 126 Quan PL, Wagner TA, Briese T. , et al. Astrovirus encephalitis in boy with X-linked agammaglobulinemia. Emerg Infect Dis 2010; 16 (06) 918-925
- 127 Chiu CY, Coffey LL, Murkey J. , et al. Diagnosis of fatal human case of St. Louis encephalitis virus infection by metagenomic sequencing, California, 2016. Emerg Infect Dis 2017; 23 (10) 1964-1968
- 128 Piantadosi A, Mukerji SS, Chitneni P. , et al. Metagenomic sequencing of an echovirus 30 genome from cerebrospinal fluid of a patient with aseptic meningitis and orchitis. Open Forum Infect Dis 2017; 4 (03) ofx138
- 129 Kawada J, Okuno Y, Torii Y. , et al. Identification of viruses in cases of pediatric acute encephalitis and encephalopathy using next-generation sequencing. Sci Rep 2016; 6: 33452
- 130 Greninger AL, Naccache SN, Messacar K. , et al. A novel outbreak enterovirus D68 strain associated with acute flaccid myelitis cases in the USA (2012-14): a retrospective cohort study. Lancet Infect Dis 2015; 15 (06) 671-682
- 131 Dyda A, Stelzer-Braid S, Adam D, Chughtai AA, MacIntyre CR. The association between acute flaccid myelitis (AFM) and Enterovirus D68 (EV-D68) - what is the evidence for causation?. Euro Surveill 2018; 23 (03) 17-00310
- 132 Naccache SN, Greninger AL, Lee D. , et al. The perils of pathogen discovery: origin of a novel parvovirus-like hybrid genome traced to nucleic acid extraction spin columns. J Virol 2013; 87 (22) 11966-11977
- 133 Wilson MR, O'Donovan BD, Gelfand JM. , et al. Chronic meningitis investigated via metagenomic next-generation sequencing. JAMA Neurol 2018; 75 (08) 947-955
- 134 Schlaberg R, Chiu CY, Miller S, Procop GW, Weinstock G. ; Professional Practice Committee and Committee on Laboratory Practices of the American Society for Microbiology; Microbiology Resource Committee of the College of American Pathologists. Validation of metagenomic next-generation sequencing tests for universal pathogen detection. Arch Pathol Lab Med 2017; 141 (06) 776-786
- 135 University of California San Francisco Center for Next-Gen Precision Diagnostics. Available at: https://nextgendiagnostics.ucsf.edu/ . Accessed November 14, 2018
- 136 ARUP Laboratories. Explify respiratory pathogens by next-generation sequencing. Available at: https://www.aruplab.com/topics/explify . Accessed November 14, 2018