Table 3.
Neurological symptoms, treatment, and outcome of study population grouped by arbovirus diagnosis
|
Mono-infection (n=98) |
Dual infection (n=50) |
All cases (n=201) |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ZIKV (n=41) | CHIKV (n=55) | DENV (n=2) | p value* | ZIKV + CHIKV co-infection (n=13) | ZIKV + CHIKV (n=33) | CHIKV + DENV (n=4) | p value† | Laboratory evidence of acute arbovirus infection (n=148) | No laboratory evidence of acute arbovirus infection (n=53) | p value‡ | ||
| Time from systemic arbovirus infection to neurological symptom onset (days) | 7 (5–25) | 15 (7–46) | 16 (14–17) | 0·062 | 9 (7–126) | 12 (4–36) | 9 (7–48) | 0·84 | 10 (5–33) | 10 (5–30) | 0·48 | |
| Neurological signs and symptoms | ||||||||||||
| Headache | 25 (61%) | 35 (64%) | 1 (50%) | 0·79 | 6 (46%) | 23 (70%) | 3 (75%) | 0·95 | 93 (63%) | 37 (70%) | 0·36 | |
| Photophobia | 4 (10%) | 5 (9%) | 0 | 0·91 | 1 (8%) | 2 (6%) | 0 | 0·83 | 12 (8%) | 3 (6%) | 0·56 | |
| Altered consciousness | 7 (17%) | 16 (29%) | 0 | 0·17 | 3 (23%) | 12 (36%) | 2 (50%) | 0·28 | 40 (27%) | 13 (25%) | 0·72 | |
| Confusion | 3 (7%) | 16 (29%) | 0 | 0·0081 | 3 (23%) | 9 (27%) | 1 (25%) | 0·40 | 32 (22%) | 10 (19%) | 0·67 | |
| Abnormal behaviour | 2 (5%) | 8 (15%) | 0 | 0·13 | 3 (23%) | 4 (12%) | 0 | 0·41 | 17 (11%) | 6 (11%) | 0·97 | |
| Seizures | 3 (7%) | 6 (11%) | 0 | 0·55 | 1 (8%) | 2 (6%) | 2 (50%) | 0·83 | 15 (10%) | 5 (9%) | 0·88 | |
| Visual changes | 7 (17%) | 11 (20%) | 0 | 0·72 | 2 (15%) | 7 (21%) | 1 (25%) | 0·91 | 28 (19%) | 15 (28%) | 0·15 | |
| Cranial neuropathy of cranial nerve III, IV, or VI | 3 (7%) | 7 (13%) | 0 | 0·61 | 2 (15%) | 1 (3%) | 0 | 0·68 | 13 (9%) | 5 (9%) | 0·89 | |
| Facial weakness | 16 (39%) | 9 (16%) | 1 (50%) | 0·012 | 4 (31%) | 7 (21%) | 0 | 0·79 | 37 (25%) | 13 (25%) | 0·95 | |
| Bulbar symptoms | 9 (22%) | 7 (13%) | 0 | 0·23 | 2 (15%) | 10 (30%) | 0 | 0·19 | 28 (19%) | 16 (30%) | 0·090 | |
| Autonomic dysfunction§ | 7 (17%) | 5 (9%) | 0 | 0·24 | 1 (8%) | 1 (3%) | 0 | 0·21 | 14 (9%) | 7 (13%) | 0·44 | |
| Limb weakness | 31 (76%) | 38 (69%) | 2 (100%) | 0·48 | 9 (69%) | 22 (67%) | 4 (100%) | 0·58 | 106 (72%) | 35 (60%) | 0·45 | |
| Hemiparesis | 1 (2%) | 6 (11%) | 0 | 0·11 | 1 (8%) | 5 (15%) | 0 | 0·42 | 13 (9%) | 5 (9%) | 0·89 | |
| Paraparesis | 6 (15%) | 15 (27%) | 1 (50%) | 0·14 | 2 (15%) | 4 (12%) | 2 (50%) | 0·21 | 30 (20%) | 16 (30%) | 0·14 | |
| Quadriparesis | 24 (61%) | 17 (31%) | 1 (50%) | 0·007 | 6 (46%) | 13 (39%) | 2 (50%) | 0·87 | 63 (43%) | 14 (26%) | 0·038 | |
| Abnormal reflexes | ||||||||||||
| Hyporeflexia or absent reflexes | 25 (61%) | 18 (33%) | 0 | 0·0059 | 7 (54%) | 11 (33%) | 0 | 0·52 | 61 (41%) | 17 (32%) | 0·24 | |
| Hyperreflexia | 3 (7%) | 13 (24%) | 1 (50%) | 0·034 | 2 (15%) | 7 (21%) | 1 (25%) | 0·67 | 27 (18%) | 14 (26%) | 0·21 | |
| Impaired coordination | 8 (20%) | 5 (9%) | 0 | 0·14 | 1 (8%) | 2 (6%) | 0 | 0·22 | 16 (11%) | 3 (6%) | 0·27 | |
| Sensory deficit on examination | 30 (73%) | 33 (60%) | 2 (100%) | 0·18 | 8 (62%) | 21 (64%) | 2 (50%) | 0·76 | 96 (65%) | 35 (66%) | 0·88 | |
| Sensory level | 3 (7%) | 13 (24%) | 1 (50%) | 0·034 | 2 (15%) | 9 (27%) | 2 (50%) | 0·31 | 29 (20%) | 5 (9%) | 0·090 | |
| Sphincter dysfunction | 8 (20%) | 18 (33%) | 1 (100%) | 0·15 | 3 (23%) | 10 (28%) | 2 (50%) | 0·88 | 42 (28%) | 8 (15%) | 0·055 | |
| Unable to walk | 14 (34%) | 16 (29%) | 1 (100%) | 0·60 | 5 (38%) | 10 (30%) | 2 (50%) | 0·87 | 48 (32%) | 14 (26%) | 0·42 | |
| Investigations | ||||||||||||
| White blood cell count (109 cells per L) | 9 (7–11) | 9 (7–11) | 5 (NA) | 0·80 | 11 (8–13) | 11 (7–12) | 11 (6–17) | 0·047 | 10 (7–12) | 8 (5–10) | 0·17 | |
| Platelets (109 cells per L) | 271 (220–321) | 250 (199–316) | 236 (NA) | 0·67 | 259 (203–355) | 251 (187–330) | 237 (117–237) | >0·99 | 251 (216–311) | 265 (200–329) | 0·95 | |
| CSF cell count (106 cells per L) | 1·17 (0·33–4·58) | 3·50 (0·33–14·33) | 98·16 (4·00–192·00) | 0·36 | 2·33 (0·33–8·00) | 1·33 (0·33–17·00) | 2·83 (0·17–8·50) | 0·94 | 2·17 (0·33–13·50) | 1·66 (0·50–9·00) | 0·33 | |
| CSF protein (g/L) | 91 (48–156) | 59 (41–84) | 136 (80–191) | 0·57 | 59 (37–67) | 51 (33–111) | 40 (27–45) | 0·10 | 64 (40–101) | 45 (33–67) | 0·010 | |
| Treatment | ||||||||||||
| Steroids | 12 (29%) | 31 (61%; n=51) | 1 (50%) | 0·0026 | 6 (46%) | 12 (41%; n=29) | 2 (66%; n=3) | 0·68 | 64 (46%; n=139) | 27 (53%; n=51) | 0·40 | |
| Immunoglobulin | 24 (58%) | 12 (24%; n=51) | 0 | 0·00063 | 6 (46%) | 9 (31%; n=29) | 0 (0%; n=3) | 0·71 | 51 (37%; n=139) | 18 (35%; n=51) | 0·86 | |
| Antivirals | 4 (10%) | 5 (9%; n=51) | 0 | >0·99 | 0 | 2 (7%; n=29) | 0 (n=3) | 0·54 | 11 (8%; n=139) | 1 (2%; n=51) | 0·14 | |
| Anticonvulsants | 1 (2%) | 1 (2%; n=51) | 0 | >0·99 | 1 (8%) | 2 (7%; n=29) | 1 (33%; n=3) | 0·36 | 5 (4%; n=139) | 2 (4%; n=51) | 0·92 | |
| Inpatient progress and outcome | ||||||||||||
| Intubated | 1 (3%; n=31) | 1 (2%) | 0 | >0·99 | 2 (17%; n=12) | 3 (9%; n=32) | 0 | 0·087 | 7 (5%; n=136) | 4 (9%; n=47) | 0·40 | |
| Admitted to intensive treatment unit | 3 (9%; n=33) | 1 (2%) | 0 | 0·29 | 2 (17%; n=12) | 3 (9%; n=32) | 0 | 0·27 | 9 (7%; n=138) | 6 (13%; n=46) | 0·28 | |
| Number of days in hospital | 17 (9–23) | 17 (9–22) | 20 (14–25) | 0·94 | 19 (13–23) | 22 (8–29) | 12 (7–17) | 0·34 | 17 (9–24) | 18 (9–27) | 0·73 | |
| Disability at discharge¶ | 37 (93%; n=40) | 47 (92%; n=51) | 2 (100%) | >0·99 | 11 (85%) | 26 (81%; n=32) | 3 (100%; n=3) | 0·15 | 126 (89%; n=141) | 43 (91%; n=47) | 0·92 | |
| Died | 0 | 1 (2%) | 0 | >0·99 | 0 | 0 | 0 | >0·99 | 1 (1%) | 1 (2%) | 0·45 | |
Data are median (IQR) for continuous data and n (%) or n (%; N) evaluable for categorical data. Mono-infection was defined as laboratory test evidence of infection with a single virus; dual infection was defined as evidence of infection with more than one virus on the basis of a positive PCR or IgM test—infection might be concurrent or sequential; co-infection was defined as contemporaneous detection of RNA of more than one virus on PCR testing. Neurological symptom onset was estimated from the patient history (if onset preceded presentation with neurological disease) or was based on the presence of symptoms on examination in hospital (if onset of neurological features and infection were concurrent). Patients with dengue infection were excluded from the mono-infection comparison, because only two were assessed in the study, as well as from the dual-infection comparison, because only four patients were assessed in the study. Where data were not available for all cases, the denominator is indicated. Significant differences remained when we excluded the five patients positive for flavivirus who were classified as having Zika infection on epidemiological grounds. CHIKV=chikungunya virus. DENV=dengue virus. NA=not applicable. ZIKV=Zika virus.
p values comparing Zika mono-infection versus chikungunya mono-infection cases.
p values comparing Zika or chikungunya mono-infection versus Zika and chikungunya dual infection cases.
p values comparing cases with laboratory evidence of acute arbovirus infection with those without.
Symptoms of autonomic dysfunction include fluctuations in blood pressure, arrhythmias, vasomotor dysfunction, and abnormalities in gastrointestinal motility.
Data on neurological disability at discharge was available for 188 (94%) of 199 discharged patients.