Table 3.
Positive mNGS results of the four types of CNS infection (73/180).
| Results of mNGS | Confirmatory data | |||
|---|---|---|---|---|
| Pathogen | SSRN | Coverage, % | Depth | |
| Viral encephalitis and/or meningitis (n = 23), SSRN ≥ 2 | ||||
| Herpes simplex virus 1 (n = 9) | 2,764 (2–27639) | 57.9066 (0.0412–91) | 2.99 (1–7.5) | PCR (n = 5), Positive HSV antibody (CLIA) (n = 9) |
| Herpes simplex virus 2 (n = 1) | 4,311 | 90 | 6.5 | Positive HSV antibody (CLIA) |
| Varicella-zoster virus (n = 5) | 77 (6–3626) | 4.3204 (0.2258–95.6227) | 1 (1–2.47) | Skin herpes zoster (n = 4), PCR (n = 1) |
| Epstein-Barr virus (n = 6) | 124.5 (4–3807) | 6.8258 (0.1022–71.6965) | 1 (1–2.39) | PCR (n = 3); Neuropathology (n = 1, DLBCL); Positive EBV antibody (n = 4) |
| Cytomegalovirus (n = 1) | 4 | 0.081 | 1 | CSF cytomegalovirus IgG (122.0 U/mL) |
| Human adenovirus B1 (n = 1) | 2,467 | 62.309 | 9.84 | Clinical evidence |
| Tuberculous meningitis (n = 12), GSRN ≥ 1 | ||||
| Mycobacterium tuberculosis complex | 4 (1–1046) | ND | ND | Xpert MTB/RIF (n = 3); A. TB or T-SPOT.TB (n = 4); Tuberculosis antibody (n = 1); Clinical evidence (n = 4) |
| Bacterial meningitis (n = 24), SSRN ≥ 5 or 10 | ||||
| Streptococcus pneumoniae (n = 10) | 2,488 (19–34711) | 6.0112 (0.2236–66.8601) | 1.31 (1–4.56) | Smear/culture (n = 4), |
| Streptococcus pyogenes (n = 1) | 453 | 3.7 | 1 | Smear |
| Streptococcus intermedius (n = 1) | 592 | 5.2651 | 1 | Clinical evidence |
| Klebsiella pneumoniae (n = 3) | 15 (12–70) | 0.0241 (0.0127–0.2979) | 1 (1–1.59) | Culture (n = 3) |
| Listeria monocytogenes (n = 2) | 43.5 (36–51) | 0.1167 (0.0418–0.1915) | 1.01 (1–1.02) | Culture (n = 2) |
| Nocardia farcinica (n = 1) | 277 | 0.2631 | 1.16 | Clinical evidence |
| Brucella (n = 1) | 18 (GSRN) | ND | ND | RBPT(+) and SAT(+) |
| Stenotrophomonas maltophilia (n = 1) | 288 | 0.7879 | 1 | Clinical evidence |
| Haemophilus influenzae (n = 1) | 12 | 0.1478 | 1 | Clinical evidence |
| Escherichia coli (n = 1) | 58 | 1.2399 | 1 | Culture |
| Aggregatibacter aphrophilus (n = 1) | 256 | 0.7625 | 4.61 | Clinical evidence |
| Neisseria meningitidis (n = 1) | 4543 | 44.2621 | 1.82 | Clinical evidence |
| Fungal meningitis (n = 14), SSRN or GSRN≥2 | ||||
| C. neoformans s.l. (n = 10) | 40.5 (2–177203) | 0.01445 (0.0019–71) | 1 (1–24) | India ink staining or culture for fungi |
| C. gattii s.l. (n = 5) | 334 (7–71743) | 0.1885 (0.0136–20) | 1.02 (1–8.7) | India ink staining or culture for fungi |
| Aspergillus (n = 4) | 6 (3–9) (GSRN) | ND | ND | Histopathology |
CLIA, chemiluminescence immunoassay; CNS, central nerve system; DLBCL, diffused large b-cell lymphoma; GSRN, genus-specific reads number; mNGS, metagenomic next-generation sequencing; PCR, polymerase chain reaction; RBPT, rose bengal plate agglutination test; SAT, serum agglutination test; s.l., sensu lato; SSRN, species-specific read number.
Positive HSV antibody: a 4-fold or more increase in CSF virus-specific antibody titer, or CSF virus-specific IgM antibody.
Positive EBV antibody: VCA (viral capsid antigens)-IgG ≥1:640, EA (early antigens)-IgG ≥1: 160, or EBNA (EB nuclear antigens) ≥1: 2; [Proposed Guidelines for Diagnosing Chronic Active Epstein-Barr Virus Infection].
Clinical evidence: patient's history, clinical presentation, imaging finding, routine laboratory CSF results and response to antibiotic treatment.