What is already known about this topic?
What does this article add?
Background
Methods
Ethical considerations
Study design
Case definitions for dengue
Serology for dengue viral infection
Measurement of biomarkers
Composite indices
Statistical analysis
Results
Patient characteristics
All | Severe Dengue | Non-severe Dengue |
p-value | ||||
---|---|---|---|---|---|---|---|
n
| No. (% or IQR) |
n
| No. (% or IQR) |
n
| No. (% or IQR) | ||
Gender | 365 | 0.003
a
| |||||
Male
| 215 (58.90%) | 22 | 6 (2.80%) | 343 | 209 (97.20%) | ||
Female
| 150 (41.10%) | 22 | 16 (10.70%) | 343 | 134 (89.30%) | ||
Age (y), median (IQR)
| 364 | 28 (23 - 36) | 22 | 31 (23 - 36) | 342 | 28 (23 - 36) | 0.660
b
|
BMI, median (IQR)
| 353 | 24 (21 - 28) | 18 | 25 (21 - 29) | 335 | 24 (21 - 28) | 0.700
b
|
Co-morbids present | 365 | 55 (15.10%) | 22 | 8 (36.40%) | 343 | 47 (13.70%) | 0.009
a
|
DM
| 365 | 12 (3.30%) | 22 | 3 (13.60%) | 343 | 9 (2.60%) | 0.003
a
|
Hypertension
| 365 | 16 (4.40%) | 22 | 3 (13.60%) | 343 | 13 (3.80%) | 0.006
a
|
Other co-morbids
| 365 | 49 (13.40%) | 22 | 6 (27.30%) | 343 | 43 (12.50%) | 0.100
a
|
Number of co-morbids | 365 | 22 | 343 | 0.003
c
| |||
0
| 308 (84.40%) | 22 | 14 (63.60%) | 343 | 294 (85.70%) | ||
1
| 41 (11.20%) | 22 | 5 (22.70%) | 343 | 36 (10.50%) | ||
2
| 12 (3.30%) | 22 | 2 (9.10%) | 343 | 10 (2.90%) | ||
3
| 4 (1.10%) | 22 | 1 (4.50%) | 343 | 3 (0.90%) | ||
More than 1 co-morbids present | 365 | 16 (4.40%) | 22 | 3 (13.60%) | 343 | 13 (3.80%) | 0.006
a
|
All | Severe Dengue | Non-severe Dengue |
p-value | ||||
---|---|---|---|---|---|---|---|
n
| No. (% or IQR) |
n
| No. (% or IQR) |
n
| No. (% or IQR) | ||
Duration of febrile phase (d)
| 360 | 4.8 (3.8 - 5.8) | 21 | 5 (4.1 - 7.3) | 339 | 4.8 (3.8 - 5.8) | 0.170
b
|
Phase at admission, febrile | 360 | 230 (63.90%) | 21 | 16 (76.20%) | 339 | 214 (63.10%) | 0.250
a
|
Day of presentation (d)
| 361 | 4.3 (3.2 - 5.3) | 22 | 4.2 (3.1 - 5.1) | 339 | 4.3 (3.2 - 5.4) | 0.570
b
|
NS1 Ag | 356 | 288 (80.90%) | 22 | 20 (90.90%) | 334 | 268 (80.20%) | 0.270
a
|
High-titre IgG | 360 | 160 (44.40%) | 22 | 11 (50.00%) | 338 | 149 (44.10%) | 0.660
a
|
Admission Hct, median (IQR), % | 365 | 42 (39 - 46) | 22 | 41 (37 - 43) | 343 | 42 (39 - 46) | 0.160
b
|
Admission CK, median (IQR), IU/L | 354 | 208 (103 - 409) | 19 | 212 (116 - 300) | 335 | 207 (103 - 424) | 0.760
b
|
Admission AST, median (IQR), IU/L | 364 | 79 (47 - 135) | 22 | 231 (97 - 564) | 342 | 75 (47 - 128) | < 0.001
b
|
Admission ALT, median (IQR), IU/L | 365 | 51 (29 - 100) | 22 | 122 (49 - 230) | 343 | 49 (28 - 91) | 0.003
b
|
Nadir WBC, median (IQR), ×103/μL | 364 | 2.5 (1.9 - 3.6) | 22 | 2.8 (2 - 3.8) | 342 | 2.5 (1.9 - 3.6) | 0.540
b
|
Nadir Platelet, median (IQR), ×103/μL | 364 | 41 (21 - 67) | 22 | 27 (10 - 49) | 342 | 42 (22 - 67) | 0.020
b
|
Nadir Serum Albumin, median (IQR), g/L | 326 | 32 (30 - 36) | 21 | 27 (23 - 29) | 305 | 33 (30 - 36) | < 0.001
b
|
Peak CK, median (IQR), IU/L | 103 | 429 (199 - 1044) | 10 | 404 (171 - 766) | 93 | 431 (206 - 1118) | 0.430
b
|
Peak AST, median (IQR), IU/L | 338 | 123 (74 - 243) | 21 | 585 (144 - 1098) | 37 | 116 (73 - 223) | < 0.001
b
|
Peak ALT, median (IQR), IU/L | 340 | 86 (41 - 175) | 22 | 225 (107 - 403) | 318 | 81 (39 - 162) | < 0.001
b
|
Severe vs non-severe dengue
Diagnostic value of CK, AST and ALT for identifying severe dengue
Markers | AUC (95% CI) |
---|---|
CK | 0.52 (0.40 - 0.64) |
AST | 0.78 (0.68 - 0.89) |
ALT | 0.69 (0.56 - 0.81) |
Hct | 0.59 (0.47 - 0.71) |
AST2/ALT | 0.83 (0.73 - 0.92) |
AST/ALT | 0.77 (0.67 - 0.87) |
AST x ALT | 0.74 (0.62 - 0.86) |
AST2 x ALT | 0.76 (0.64 - 0.87) |
AST x √ALT | 0.76 (0.64 - 0.87) |
√AST x ALT | 0.72 (0.60 - 0.84) |
AST/√ALT | 0.83 (0.73 - 0.92) |
√AST/ALT | 0.42 (0.30 - 0.55) |
AST2/√ALT | 0.81 (0.71 - 0.90) |
AST2/ALT3
| 0.52 (0.41 - 0.63) |
AST3/ALT | 0.81 (0.72 - 0.91) |
AST3/√ALT | 0.80 (0.69 - 0.90) |
AST3/ALT2
| 0.83 (0.73 - 0.93) |
AST4/ALT3
| 0.82 (0.73 - 0.92) |
Cutoff | Sensitivity % (95% CI) | Specificity% (95% CI) | PPV (95% CI) | NPV (95% CI) | Diagnostic accuracy (95% CI) | LR+ (95% CI) | LR– (95% CI) |
---|---|---|---|---|---|---|---|
> 98.1 | 95.5 (77.2 - 99.9) | 40.5 (35.3 - 45.9) | 9.3 (6.2 - 13.9) | 99.3 (96.1 - 99.9) | 43.8 (38.8 - 49.0) | 1.6 (1.6 - 1.6) | 0.1 (0.02 - 0.8) |
> 402.5 | 59.1 (36.4 - 79.3) | 92.4 (89.1 - 95.0) | 33.3 (20.6 - 49.0) | 97.2 (94.8 - 98.5) | 90.4 (87.0 - 93.0) | 7.8 (6.5 - 9.3) | 0.4 (0.4 - 0.6) |
> 653.2 | 40.9 (20.7 - 63.7) | 97.4 (95.1 - 98.8) | 50.0 (29.0 - 71.0) | 96.3 (93.7 - 97.8) | 94.0 (91.0 - 96.0) | 15.6 (9.2 - 26.6) | 0.6 (0.5 - 0.7) |
> 1193 | 31.8 (13.9 - 54.9) | 99.4 (97.9 - 99.9) | 77.8 (45.3 - 93.7) | 95.8 (93.2 - 97.4) | 95.3 (92.7 - 97.1) | 54.6 (11.2 - 264.9) | 0.7 (0.6 - 0.8) |
Correlation and predictive associations between markers
n | Spearman r (95% CI) |
p
|
R
2
| |
---|---|---|---|---|
Admission CK - Admission AST | 364 | 0.37 (0.27 - 0.46) | <0.001 | 0.13a
|
Admission CK - Peak AST | 206 | 0.28 (0.15 - 0.41) | <0.001 | 0.07a
|
Peak CK - Admission AST | 104 | 0.29 (0.09 - 0.46) | 0.003 | 0.06a
|
Peak CK - Peak AST | 92 | 0.22 (0.03 - 0.39) | 0.020 | 0.06a
|
Admission CK - Admission ALT | 364 | 0.26 (0.16 - 0.35) | <0.001 | 0.02b
|
Admission CK - Peak ALT | 216 | 0.11 (−0.02 - 0.24) | 0.110 | 0.01b
|
Peak CK - Admission ALT | 217 | 0.25 (0.06 - 0.42) | 0.010 | 0.05c
|
Peak CK - Peak ALT | 217 | 0.12 (−0.08 - 0.32) | 0.240 | 0.02c
|
Admission CK - Admission Hct | 364 | 0.24 (0.14 - 0.33) | <0.001 | 0.01c
|
Admission CK - Nadir Platelet | 363 | −0.22 (−0.32 - -0.12) | <0.001 | 0.01c
|
Admission CK - Nadir Serum Albumin | 326 | −0.04 (−0.15 - 0.07) | 0.500 | 0.001c
|
Peak CK - Admission Hct | 104 | 0.03 (−0.17 - 0.22) | 0.800 | 0.004c
|
Peak CK - Nadir Platelet | 104 | −0.10 (−0.29 - 0.09) | 0.300 | 0.01c
|
Peak CK - Nadir Serum Albumin | 104 | 0.06 (−0.13 - 0.25) | 0.540 | 0.01c
|
Admission AST - Admission ALT | 365 | 0.86 (0.82 - 0.88) | <0.001 | 0.79b
|
Admission AST - Peak ALT | 217 | 0.68 (0.60 - 0.75) | <0.001 | 0.54b
|
Peak AST - Admission ALT | 206 | 0.66 (0.57 - 0.73) | <0.001 | 0.45a
|
Peak AST - Peak ALT | 189 | 0.92 (0.89 - 0.94) | <0.001 | 0.66b
|
Admission Hct - Nadir Platelet | 365 | −0.14 (−0.24 - -0.03) | 0.009 | 0.06c
|
Admission Hct - Nadir Serum Albumin | 327 | 0.19 (0.08 - 0.29) | 0.001 | 0.03c
|
Nadir Serum Albumin - Nadir Platelet | 327 | 0.52 (0.43 - 0.60) | <0.001 | 0.14b
|
Admission AST - Admission Hct | 365 | 0.05 (−0.06 - 0.15) | 0.380 | 0.006c
|
Admission AST - Nadir Platelet | 365 | −0.34 (−0.43 - -0.25) | <0.001 | 0.04b
|
Admission AST - Nadir Serum Albumin | 327 | −0.32 (−0.41 - -0.21) | <0.001 | 0.09c
|
Peak AST - Admission Hct | 206 | −0.02 (−0.15 - 0.12) | 0.800 | 0.01c
|
Peak AST - Nadir Platelet | 206 | −0.38 (−0.49 - -0.26) | <0.001 | 0.08c
|
Peak AST - Nadir Serum Albumin | 200 | −0.29 (−0.41 - -0.16) | <0.001 | 0.09c
|
Admission ALT - Admission Hct | 365 | 0.09 (−0.06 - 0.15) | 0.080 | 0.003c
|
Admission ALT - Nadir Platelet | 365 | −0.19 (−0.43 - -0.25) | <0.001 | 0.03c
|
Admission ALT - Nadir Serum Albumin | 327 | −0.16 (−0.41 - -0.21) | 0.003 | 0.04c
|
Peak ALT - Admission Hct | 217 | −0.02 (−0.06 - 0.15) | 0.810 | 0.01c
|
Peak ALT - Nadir Platelet | 217 | −0.17 (−0.43 - -0.25) | 0.020 | 0.01c
|
Peak ALT - Nadir Serum Albumin | 209 | −0.13 (−0.41 - -0.21) | 0.050 | 0.03c
|