Table 2.
Burden and diagnostic strategy to identify causes of encephalitis
|
Final aetiology confirmation |
Biological testing used in cause identification |
Sample used in cause identification | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Total (n=664) | Confirmed (n=330) | Probable (n=95) | RT-PCR (n=173) | Serology (n=241) | Culture (n=15) | Rapid diagnostic test (n=16) | NGS (n=5) | CSF (n=301) | Inclusion blood sample (n=51)* | Discharge blood sample (n=21)† | Non-sterile site (n=46)‡ | |
| Infectious causes | ||||||||||||
| Japanese encephalitis virus | 216 (33%) | 207 (63%) | 9 (9%) | 1 (1%) | 214 (89%) | .. | .. | 1 (20%) | 187 (62%) | 9 (18%) | 20 (95%) | .. |
| Dengue virus | 27 (4%) | 21 (6%) | 6 (6%) | 18 (10%) | 14 (6%) | .. | 12 (75%) | .. | 10 (3%) | 17 (33%) | .. | .. |
| Influenza virus | 26 (4%) | 0 | 26 (27%) | 26 (15%) | .. | .. | .. | .. | 0 | .. | .. | 26 (57%) |
| Herpes simplex virus 1 | 24 (4%) | 24 (7%) | 0 | 24 (14%) | .. | .. | .. | .. | 24 (8%) | .. | .. | .. |
| Mycobacterium tuberculosis | 18 (3%) | 12 (4%) | 6 (6%) | 10 (6%) | .. | 2 (13%) | .. | .. | 12 (4%) | .. | .. | 1 (2%) |
| Enterovirus-A71§ | 17 (3%) | 0 | 17 (18%) | 17 (10%) | .. | .. | .. | .. | 0 | .. | .. | 17 (37%) |
| Streptococcus pneumoniae | 17 (3%) | 17 (5%) | 0 | 15 (9%) | .. | 8 (53%) | .. | .. | 17 (6%) | .. | .. | .. |
| Human herpes virus 6 | 13 (2%) | 0 | 13 (14%) | 13 (8%) | .. | .. | .. | .. | 7 (2%) | 6 (12%) | .. | .. |
| Orientia tsutsugamushi | 9 (1%) | 9 (3%) | 0 | 7 (4%) | 8 (3%) | .. | .. | .. | 3 (1%) | 6 (12%) | .. | .. |
| Epstein-Barr virus | 9 (1%) | 0 | 9 (9%) | 9 (5%) | .. | .. | .. | .. | 8 (3%) | 1 (2%) | .. | .. |
| Enterovirus§ | 5 (1%) | 5 (2%) | 0 | 5 (3%) | .. | .. | .. | .. | 5 (2%) | .. | .. | .. |
| Haemophilus influenzae | 4 (1%) | 4 (1%) | 0 | 3 (2%) | .. | 2 (13%) | .. | .. | 4 (1%) | .. | .. | .. |
| Hepatitis A virus | 4 (1%) | 2 (<1%) | 2 (2%) | 2 (1%) | 4 (2%) | .. | .. | 2 (40%) | 2 (1%) | 1 (2%) | 1 (5%) | .. |
| Coinfection | 3 (<1%) | 2 (<1%) | 1 (1%) | 2 (1%) | 1 (<1%) | 0 | .. | 2 (1%) | 1 (2%) | .. | .. | |
| Plasmodium falciparum | 3 (<1%) | 2 (<1%) | 1 (1%) | 2 (1%) | .. | .. | 3 (19%) | 2 (1%) | 1 (2%) | .. | .. | |
| Measles virus | 3 (<1%) | 3 (<1%) | 0 | 2 (1%) | .. | .. | .. | 1 (20%) | 1 (<1%) | 2 (4%) | .. | .. |
| Leptospira spp | 3 (<1%) | 3 (<1%) | 0 | 3 (2%) | .. | .. | .. | .. | 0 | 3 (6%) | .. | .. |
| Rabies virus | 2 (<1%) | 1 (<1%) | 1 (1%) | 1 (1%) | .. | .. | .. | .. | 0 | .. | .. | 1 (2%) |
| Flavivirus¶ | 2 (<1%) | 1 (<1%) | 1 (1%) | 2 (1%) | .. | 1 (7%) | .. | .. | 1 (<1%) | 1 (2%) | .. | .. |
| Neisseria meningitidis | 2 (<1%) | 2 (<1%) | 0 | 2 (1%) | .. | .. | .. | .. | 2 (1%) | .. | .. | .. |
| Mumps virus | 2 (<1%) | 2 (<1%) | 0 | 2 (1%) | .. | .. | .. | .. | 2 (1%) | .. | .. | .. |
| Streptococcus suis | 1 (<1%) | 1 (<1%) | 0 | 1 (<1%) | .. | .. | .. | .. | 1 (<1%) | .. | .. | .. |
| Streptococcus agalactiae | 1 (<1%) | 1 (<1%) | 0 | 1 (<1%) | .. | .. | .. | .. | 1 (<1%) | .. | .. | .. |
| Staphylococcus aureus | 1 (<1%) | 1 (<1%) | 0 | 0 | .. | 1 (7%) | .. | .. | 1 (<1%) | .. | .. | .. |
| Rickettsia spp | 1 (<1%) | 1 (<1%) | 0 | 1 (<1%) | 0 | .. | .. | .. | 1 (<1%) | .. | .. | .. |
| Rubella virus | 1 (<1%) | 1 (<1%) | 0 | 1 (<1%) | .. | .. | .. | .. | 0 | 1 (2%) | .. | .. |
| Varicella zoster virus | 1 (<1%) | 0 | 1 (1%) | 1 (<1%) | .. | .. | .. | .. | 0 | .. | .. | 1 (2%) |
| Adenovirus | 1 (<1%) | 0 | 1 (1%) | 1 (<1%) | .. | .. | .. | .. | 0 | 1 (2%) | .. | .. |
| Listeria monocytogenes | 1 (<1%) | 1 (<1%) | 0 | 1 (<1%) | .. | 1 (7%) | .. | .. | 1 (<1%) | .. | .. | .. |
| Treponema pallidum | 1 (<1%) | 0 | 1 (1%) | 0 | .. | .. | 1 (6%) | .. | 0 | 1 (2%) | .. | .. |
| Rhinovirus | 1 (<1%) | 1 (<1%) | 0 | 0 | .. | .. | .. | 1 (20%) | 1 (<1%) | .. | .. | .. |
| Immune mediated causes | ||||||||||||
| NMDA receptor antibody | 6 (1%) | 6 (2%) | 0 | .. | .. | .. | .. | .. | 6 (2%) | .. | .. | .. |
| Unidentified cause‖ | 239 (36%) | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA | NA |
For biological testing done on each sample to determine the cause of encephalitis, sometimes more than one test led to the diagnosis, so numbers might not add up to total shown in the left column. For cells with 0 in them, this indicates that the test was done with a negative result, whereas the blank cells indicted with .. indicate that the test was not done or does not exist for the pathogen in question. CSF=Cerebrospinal fluid. NA=not applicable. NGS=next-generation sequencing. NMDA=N-methyl-D-aspartate.
Blood obtained on the day of inclusion.
Blood obtained 7–10 days after inclusion or at discharge.
Usually nasopharyngeal, throat, or rectal swabs, or both.
Enterovirus A71 excluded from enteroviruses.
Pan flavivirus RT-PCR positive, undefined species.
Six identified causes were not laboratory confirmed but were only based on clinical data: one child had rabies and five had tuberculosis (appendix 5 p 15). Furthermore, 47 children had multiple identified pathogens (appendix 5 pp 31–32), of which two were confirmed coinfections and one was probable.