Table 1.
Characteristics of studies included in the narrative review
| Reference | Timing of HTS use | Characteristics of patients with CNS samples screened with HTS |
HTS |
Confirmatory assays | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Geographical origin | Number of patients | Immunocompromised patients | Paediatric or adult patients | Age | Diagnosis | Clinical sample analysed | Probable viral cause of CNS disease (number of patients) | Platform | Nucleic acid extraction methods | Report of control use | |||
| Naccache SN et al. Clin Infect Dis. 2015 [33] | Prospective | Europe | 1 | Yes | Adult | 42 yo | Encephalitis | CSF and brain tissue | Novel HAstV-VA1 (1) | HiSeq 2500 | RNA/DNA | Positive control | RT-PCR, in situ hybridization |
| Frémond M-L et al. J Pediatric Infect Dis Soc. 2015 [23] | Prospective | Europe | 1 | Yes | Paediatric | 14 yo | Encephalitis | Brain tissue | Novel HAstV-VA1 (1) | Ion Proton | RNA | No | RT-PCR |
| Salzberg SL et al. Neurol Neuroimmunol Neuroinflamm. 2016 [39] | Prospective | North America | 2 | Yes (1),No (1) | Adult | 44 yo, 67 yo | Encephalitis | Brain tissue | EBV (1) | MiSeq | DNA | No | in situ hybridization |
| Wilson MR et al. Ann Neurol. 2017 [30] | Prospective | Oceania | 1 | Yes | Adult | 34 yo | Chronic meningoencephalitis | CSF and brain tissue | Cache Valley virus (1) | HiSeq 4000 | RNA | Negative control | RT-PCR, viral culture, immunohistochemistry |
| Wilson MR et al. Am J Transplant. 2017 [40] | Prospective | North America | 1 | Yes | Paediatric | 14 yo | Meningoencephalitis | CSF | WNV (1) | HiSeq 2500 | RNA | Negative control | Serology |
| Morfopoulou S et al. Acta Neuropathol. 2017 [41] | Prospective | Europe | 1 | Yes | Paediatric | 1.5 yo | Chronic encephalitis | Brain tissue | Mumps virus (vaccine strain) (1) | NextSeq 500 | RNA | No | RT-PCR, immunohistochemistry, serology |
| Chiu CY et al. Emerg Infect Dis. 2017[42] | Prospective | North America | 1 | Yes | Adult | 68 yo | Encephalitis | CSF | St Louis encephalitis virus (1) | Not specified | RNA/DNA | No | RT-PCR, serology, viral culture |
| Palacios G. et al. N Engl J Med. 2008 [26] | Retrospective | Oceania | 2 | Yes | Adult | 63 yo and 64 yo | Encephalitis | CSF and brain tissue | LCMV-related virus (2) | GSL FLX | RNA | No | RT-PCR, serology |
| Quan PL et al. Emerg Infect Dis. 2010 [47] | Retrospective | North America | 1 | Yes | Paediatric | 15 yo | Encephalitis | Brain tissue | Human astrovirus undetermined (1) | GSL FLX | RNA | No | RT-PCR, immunohistochemistry immunofluorescence |
| Brown JR et al. Clin Infect Dis. 2015 [31] | Retrospective | Europe | 1 | Yes | Paediatric | 1.5 yo | Encephalitis | Brain tissue | Novel HAstV-VA1 (1) | MiSeq | RNA | Positive control | RT-PCR, immunohistochemistry |
| Morfopoulou S et al. N Engl J Med. 2016 [25] | Retrospective | Europe | 1 | Yes | Paediatric | 11 mo | Encephalitis | Brain tissue | Human coronavirus OC43 (1) | HiSeq 2500 | RNA | No | RT-PCR, immunohistochemistry |
| Sato M et al. J Clin Virol. 2016 [24] | Retrospective | Asia | 1 | Yes | Paediatric | 4 yo | Encephalitis | CSF | Novel HAstV-MLB1 (1) | MiSeq | RNA/DNA | No | RT-PCR |
| Lum SH et al. Transpl Infect Dis. 2016 [43] | Retrospective | Europe | 1 | Yes | Paediatric | 4 mo | Encephalitis | Brain tissue | Novel HAstV-VA1 (1) | HiSeq 2500 | RNA | No | RT-PCR |
| Lipowski D et al. J Infect Dis. 2017 [29] | Retrospective | Europe | 3 | Yes | Adult | Median 48 yo (range 27–54 yo) | Encephalitis | CSF and brain tissue | TBEV (3) | HiSeq 1500 | RNA | No | RT-PCR |
| Cordey S et al. Emerg Infect Dis. 2016 [22] | Retrospective | Europe | 1 | No | Adult | 21 yo | Meningitis | CSF | Novel HAstV-MLB2 (1) | HiSeq 2500 | RNA/DNA | No | RT-PCR |
| Benjamin LA et al Emerg Infect Dis. 2011 [46] | Retrospective | Asia | 12 | No | Paediatric | 2 yo, 3 yo Other paediatric patients <16 yo |
Encephalitis | CSF | Parvovirus 4 (2) | GS FLX Titanium | RNA/DNA | No | PCR, serology |
| Perlejewski K et al. J Virol Methods 2015 [35] | Retrospective | Europe | 1 | No | Adult | 60 yo | Encephalitis | CSF | HSV1 (1) | MiSeq | RNA | Negative and positive controls | PCR |
| Guan H et al. J Neurovirol. 2016 [36] | Retrospective | Asia | 4 | No | Adult | Median 43.5 yo (range 31–64 yo) | Meningoencephalitis | CSF | HSV-1 (2), HSV-2 (1), VZV (1) | BGISEQ-100 | DNA | No | PCR |
| Kawada J et al. Sci Rep. 2016 [48] | Retrospective | Asia | 18 | No | Paediatric | Median 3 yo (range 3 mo to 15 yo) | Encephalitis | CSF | Mumps virus (1), coxsackie A9 virus (2) | MiSeq | RNA/DNA | Positive control | RT-PCR |
| Arden KE et al. J Med Virol. 2017 [49] | Retrospective | Oceania | 1 | No | Adult | 51 yo | Encephalitis | CSF | Toscana virus (1) | HiSeq 2500 | RNA | No | None |
| Tan le V et al. MBio. 2013 [28] | Retrospective | Asia | 125 | NA | Paediatric and adult | NA | Encephalitis | CSF | CyCV-VN (2) | FLX genome sequencer | RNA/DNA | No | PCR |
| Phan TG et al. Virology. 2015 [27] | Retrospective | Asia | 62 | NA | Paediatric and adult | Paediatric patients: 2 mo to 12 yo Adult patients: 15 to 72 yo |
Encephalitis | CSF | Gemycirculavirus (3), CyCV-VN (1) | MiSeq | DNA | No | PCR |
| Chan BK et al. PLoS One. 2014 [34] | Retrospective | North America | 7 | NA | NA | NA | Encephalitis | Brain tissue | HSV-1 (3), MeV (2) | HiSeq 2000 | RNA | Negative and positive controls | PCR, RT-PCR |
| Phan TG et al. Arch Virol. 2016 [37] | Retrospective | North America | 53 | NA | Paediatric | 6 yo Other patients: NA |
Encephalitis | CSF | HuCSFDV1 (1) | MiSeq | RNA/DNA | No | PCR |
| Greninger AL et al. Genome Med. 2015 [32] | Prospective | North America | 1 | No | Paediatric | 15 yo | Encephalitis | CSF and brain tissue | None | MiSeq | RNA | Negative control | – |
| Wilson MR et al. Ann Neurol. 2015 [45] | Prospective | North America | 1 | Yes | Adult | 74 yo | Encephalitis | CSF | None | HiSeq 2500 | RNA | Negative control | – |
| Wilson MR et al. N Engl J Med. 2014 [44] | Prospective | North America | 1 | Yes | Paediatric | 14 yo | Meningoencephalitis | CSF | None | MiSeq | DNA | Negative control | – |
| Christopeit M et al. Ann Hematol. 2016 [38] | Prospective | Europe | 1 | Yes | Adult | 65 yo | Encephalitis | CSF | None | Not specified | RNA | Negative and positive controls | – |
| Mongkolrattanothai K et al. J Pediatric Infect Dis Soc. 2017 [50] | Retrospective | North America | 1 | No | Paediatric | 11 yo | Encephalitis | CSF | None | HiSeq | RNA/DNA | Negative and positive controls | – |
HTS, high-throughput sequencing; CNS, central nervous system; CSF, cerebrospinal fluid; y, years old; m, months old; NA, not available. HAstV, human astrovirus; EBV, Epstein-Barr virus; WNV, West Nile virus; LCMV, lymphocytic choriomeningitis virus; TBEV, tick-borne encephalitis virus; CyCV-VN, cyclovirus Viet-Nam; HSV, herpes simplex virus; VZV, varicella zoster virus; MeV, measles virus; HuCSFDV1, CSF-associated densovirus 1.