Dengue viremia kinetics and effects on platelet count and clinical outcomes: An analysis of 2340 patients from Vietnam
- University of Medicine and Pharmacy at Ho Chi Minh City, Viet Nam
- Oxford University Clinical Research Unit, Viet Nam
- Hospital for Tropical Diseases, Viet Nam
- Center for Global Health, Colorado School of Public Health, United States
- Heidelberg Institute of Global Health (HIGH), Heidelberg University Hospital, Germany
- Centre for Tropical Medicine and Global health, Nuffield Department of Clinical Medicine, University of Oxford, United Kingdom
- World Mosquito Program, Monash University, Australia
Figures
Figure 1
Flowchart illustrating the process of patient selection.
@Among 385 laboratory-confirmed dengue patients in study A, 31 individuals were later included in study B upon hospitalization. Of these, nine had viremia measurements available in both studies and …
Figure 2
Individual trajectories of measured viremia levels for (A) the one-step PCR cohort and (B) the two-step PCR cohort.
The dots represent the measured viremia levels and are connected by lines for each individual patient. The dashed lines indicate the detection limits, which are 300 copies/ml for DENV-1 and DENV-3, …
Figure 3
Fitted trends in mean viremia levels for (A) serotype, (B) immune status, (C) sex, and (D) age.
The colored lines represent the estimated mean viremia levels, and the colored shaded regions represent the corresponding 95% credible intervals. The horizontal lines represent the detection limits …
Figure 4
Fitted trends in mean platelet counts according to viremia levels – results from the supermodel.
The colored lines or dots represent the estimated mean platelet counts. The colored shaded regions and whiskers indicate the corresponding 95% confidence intervals. Each row represents the effect of …
Figure 5
Probability of occurrence of (A) severe dengue and (B) plasma leakage, according to viremia levels – results from the supermodel.
The colored lines or dots represent the probability of the endpoints. The colored shaded regions and whiskers indicate the corresponding 95% confidence intervals. Each column represents the effect …
Figure 6
Probability of occurrence of (A) severe dengue and (B) plasma leakage, according to the rate of decline in viremia.
The colored lines represent the probability of the endpoints. The colored shaded regions indicate the corresponding 95% confidence intervals.
Appendix 3—figure 1
Directed acyclic graph illustrating the presumed causal relationships among variables.
t: illness day t (from days 1 to 7). t + i: after day t (i ≥ 1). Outcome can be platelet count or clinical outcomes (severe dengue or plasma leakage)
Appendix 3—figure 2
Empirical distribution estimation obtained from viremia kinetics model for (A) log-10 viremia and (B) 10th-root viremia.
The figures show the empirical cumulative distribution function of the observed viremia levels (represented by the black curve), along with the empirical cumulative distribution function derived …
Appendix 3—figure 3
Empirical distribution estimation obtained from platelet count model.
The figure shows the empirical cumulative distribution function of the observed platelet counts (represented by the black curve), along with the empirical cumulative distribution function derived …
Appendix 4—figure 1
Distribution of (A) log-10 and (B) 10th-root viremia levels by illness day.
Values below the detection limit are set as 1/2 of the detection limit in each corresponding transformation scale.
Appendix 4—figure 2
Distribution and individual trajectory of platelet count.
The distribution of platelet count is shown with all measurements (A) and by illness day (B). In (B), the line inside each box represents the median, the upper and lower margins of each box indicate …
Appendix 4—figure 3
Difference in log-10 viremia from first measurement for (A) the one-step PCR cohort and (B) the two-step PCR cohort.
The red dots represent values that are higher than the first value. The red and black numbers indicate the number of measurements that are higher and lower than the first value, respectively. The …
Appendix 5—figure 1
Compare fitted trends in mean viremia levels between one- and two-step PCR methods based on (A) log-10 and (B) 10th-root transformations.
The estimated mean viremia levels are represented by colored lines. The 95% credible intervals are shown as colored shaded regions. The horizontal lines indicate the detection limits. Dashed lines …
Appendix 5—figure 2
Fitted trends in mean viremia levels by models based on 10th-root and log-10 viremia transformations for (A) one-step and (B) two-step PCR methods.
The estimated mean viremia levels are represented by colored lines. The 95% confidence intervals are shown as colored shaded regions. The horizontal lines indicate the detection limits. Dashed lines …
Appendix 6—figure 1
Fitted trends in mean platelet counts according to viremia levels by subgroups of the covariates (A) immune status, (B) sex, (C) age, and (D) PCR method – results from the supermodel.
The colored lines or dots represent the estimated mean platelet counts. The colored shaded regions and whiskers indicate the corresponding 95% confidence intervals. The figures show the effect of …
Appendix 7—figure 1
Frequency of the outcomes and regression coefficients for individuals observed on each landmark day that did not have the outcome yet.
Relationship between viremia and outcome. A logistic regression model with covariates viremia level (with linear trend) and the binary variable describing whether the viremia value was undetectable …
Appendix 7—figure 2
Probability of occurrence of the two clinical endpoints according to viremia levels by subgroups of the covariates (A) immune status, (B) sex, (C) age, and (D) study – results from the supermodel.
The colored lines or dots represent the probability of the endpoints. The colored shaded regions and whiskers indicate the corresponding 95% confidence intervals. Each column represents the effect …
Appendix 7—figure 3
Probability of occurrence of (A) severe dengue and (B) plasma leakage according to viremia levels – compare results from the supermodels with and without multiple imputation.
The colored lines or dots represent the probability of the endpoints. The colored shaded regions and whiskers indicate the corresponding 95% confidence intervals. Each column represents the effect …
Appendix 7—figure 4
Probability of occurrence of (A) severe dengue and (B) plasma leakage according to the covariates – results from the supermodel.
The lines and dots represent the probability of the endpoints. The shaded regions and whiskers indicate the corresponding 95% confidence intervals. Note that the probability of severe dengue in the …
Author response image 1
Tables
Table 1
Baseline characteristics and clinical outcomes.
| N* | All patients (N = 2340) | Study A (N = 363) | Study B (N = 622) | Study C (N = 1355) | |
|---|---|---|---|---|---|
| Age, years | 2340 | 13 (10; 18) | 12 (9; 14) | 12 (10; 13) | 16 (10; 25) |
| Sex male | 2340 | 1403 (60) | 195 (54) | 412 (66) | 796 (59) |
| Illness day at enrolment | 2340 | ||||
| 1 | 310 (13) | 59 (16) | 7 (1) | 244 (18) | |
| 2 | 848 (36) | 150 (41) | 155 (25) | 543 (40) | |
| 3 | 1137 (49) | 114 (31) | 455 (73) | 568 (42) | |
| 4 | 45 (2) | 40 (11) | 5 (1) | 0 (0) | |
| Serotype | 2340 | ||||
| DENV-1 | 1264 (54) | 233 (64) | 410 (66) | 621 (46) | |
| DENV-2 | 373 (16) | 48 (13) | 130 (21) | 195 (14) | |
| DENV-3 | 252 (11) | 80 (22) | 82 (13) | 90 (7) | |
| DENV-4 | 451 (19) | 2 (1) | 0 (0) | 449 (33) | |
| Immune status | 2340 | ||||
| Probable primary | 474 (20) | 134 (37) | 124 (20) | 216 (16) | |
| Probable secondary | 1619 (69) | 219 (60) | 464 (75) | 936 (69) | |
| Indeterminate | 247 (11) | 10 (3) | 34 (5) | 203 (15) | |
| Plasma leakage | 2288 | 353 (15) | 43 (13) | 177 (29) | 133 (10) |
| Missing | 52 | 39 | 13 | 0 | |
| Illness day of plasma leakage | 327 | ||||
| 3 | 2 (1) | 0 (0) | 0 (0) | 2 (2) | |
| 4 | 71 (22) | 12 (30) | 35 (23) | 24 (18) | |
| 5 | 107 (33) | 12 (30) | 50 (32) | 45 (34) | |
| 6 | 105 (32) | 12 (30) | 49 (32) | 44 (33) | |
| 7 | 42 (13) | 4 (10) | 20 (13) | 18 (14) | |
| Missing | 26 | 3 | 23 | 0 | |
| Severe dengue | 2340 | 65 (3) | 6 (2) | 40 (6) | 19 (1) |
| Illness day of severe dengue | 65 | ||||
| 3 | 2 (3) | 0 (0) | 2 (5) | 0 (0) | |
| 4 | 13 (20) | 0 (0) | 12 (30) | 1 (5) | |
| 5 | 24 (37) | 2 (33) | 16 (40) | 6 (32) | |
| 6 | 20 (31) | 4 (67) | 7 (18) | 9 (47) | |
| 7 | 6 (9) | 0 (0) | 3 (8) | 3 (16) |
-
Summary statistics are number of patients (%) or median (25th; 75th percentiles).
-
DENV: dengue virus.
-
*
N represents the number of patients with available data (i.e., without missing data).
Appendix 3—table 1
Comparison of the models in Analysis #2a.
| Model | Degrees of freedom | Log-likelihood | AIC | BIC |
|---|---|---|---|---|
| Viremia on the same day | 55 | −502.0 | 1114.1 | 1384.3 |
| Viremia 1 day earlier | 55 | −488.2 | 1086.3 | 1356.6 |
| Viremia 2 days earlier | 55 | −479.0 | 1068.0 | 1338.3 |
| Viremia 3 days earlier | 55 | −452.4 | 1014.9 | 1285.1 |
| Viremia 4 days earlier | 55 | −469.6 | 1049.3 | 1319.5 |
| Viremia 5 days earlier* | 54 | −478.4 | 1064.8 | 1330.1 |
-
*
The model for viremia 5 days earlier had fewer degrees of freedom due to the absence of a binary variable indicating detectable or undetectable viremia values (as all patients had detectable viremia values 5 days earlier).
Appendix 3—table 2
Comparison of the models in Analysis #2b.
| Model | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | Day 7 | Day 8 |
|---|---|---|---|---|---|---|---|
| Same day | 2.0 (24) | –58.7 (145) | –95.9 (220) | –99.7 (227) | –84.9 (198) | –252.6 (533) | –210.5 (449) |
| 1 day earlier | 0.9 (24) | –53.1 (134) | –95.2 (218) | –98.0 (224) | –80.1 (188) | –243.4 (515) | –208.7 (443) |
| 2 days earlier | –56.0 (138) | –88.8 (206) | –94.0 (216) | –80.9 (190) | –232.8 (494) | –205.2 (438) | |
| 3 days earlier | –91.8 (210) | –89.8 (208) | –76.2 (180) | –229.3 (487) | –189.6 (407) | ||
| 4 days earlier | –92.9 (212) | –78.7 (185) | –241.3 (511) | –189.6 (407) | |||
| 5 days earlier | –83.0 (192) | –245.4 (517) | –196.5 (419) |
-
Statistics are log-likelihood (AIC). The highest log-likelihood values (along with the lowest AIC) per column are highlighted in bold. Note that all analyses per each column use the same sample size.
Appendix 4—table 1
Distribution of clinical outcomes by serotype and immune status.
| Severe dengue* | Plasma leakage* | ||||||
|---|---|---|---|---|---|---|---|
| N†† | No(n = 2275) | Yes(n = 65) | No(n = 1935) | Yes(n = 353) | Indeterminate(n = 52) | ||
| DENV-1 | 1264 | 1224 (96.8) | 40 (3.2) | 1028 (81.3) | 200 (15.8) | 36 (2.8) | |
| Probable primary | 356 (28.2) | 355 (99.7) | 1 (0.3) | 307 (86.2) | 35 (9.8) | 14 (3.9) | |
| Probable secondary | 774 (61.2) | 737 (95.2) | 37 (4.8) | 603 (77.9) | 151 (19.5) | 20 (2.6) | |
| Indeterminate | 134 (10.6) | 132 (98.5) | 2 (1.5) | 118 (88.1) | 14 (10.4) | 2 (1.5) | |
| DENV-2 | 373 | 358 (96.0) | 15 (4.0) | 292 (78.3) | 75 (20.1) | 6 (1.6) | |
| Probable primary | 37 (9.9) | 37 (100.0) | 0 (0.0) | 29 (78.4) | 7 (18.9) | 1 (2.7) | |
| Probable secondary | 299 (80.2) | 286 (95.7) | 13 (4.3) | 232 (77.6) | 63 (21.1) | 4 (1.3) | |
| Indeterminate | 37 (9.9) | 35 (94.6) | 2 (5.4) | 31 (83.8) | 5 (13.5) | 1 (2.7) | |
| DENV-3 | 252 | 250 (99.2) | 2 (0.8) | 208 (82.5) | 34 (13.5) | 10 (4.0) | |
| Probable primary | 68 (27.0) | 68 (100.0) | 0 (0.0) | 58 (85.3) | 8 (11.8) | 2 (2.9) | |
| Probable secondary | 165 (65.5) | 163 (98.8) | 2 (1.2) | 132 (80.0) | 25 (15.2) | 8 (4.8) | |
| Indeterminate | 19 (7.5) | 19 (100.0) | 0 (0.0) | 18 (94.7) | 1 (5.3) | 0 (0.0) | |
| DENV-4 | 451 | 443 (98.2) | 8 (1.8) | 407 (90.2) | 44 (9.8) | 0 (0.0) | |
| Probable primary | 13 (2.9) | 13 (100.0) | 0 (0.0) | 13 (100.0) | 0 (0.0) | 0 (0.0) | |
| Probable secondary | 381 (84.5) | 373 (97.9) | 8 (2.1) | 337 (88.5) | 44 (11.5) | 0 (0.0) | |
| Indeterminate | 57 (12.6) | 57 (100.0) | 0 (0.0) | 57 (100.0) | 0 (0.0) | 0 (0.0) | |
-
Summary statistics are n (%).
-
DENV: dengue virus.
-
*
The percentages are computed by the total sample size per row.
-
†
The percentages of immune status are computed by the total sample size within each DENV serotype.
Appendix 5—table 1
p values of parameters in the models of viremia.
| Parameter | p value |
|---|---|
| Age (overall effect) | <0.0001 |
| - All interactions of Age | 0.0015 |
| - Nonlinear effect of Age | <0.0001 |
| Sex (overall effect) | 0.0008 |
| - All interactions of Sex | 0.0011 |
| Serotype (overall effect) | <0.0001 |
| - All interactions of Serotype | <0.0001 |
| Immune status (overall effect) | <0.0001 |
| - All interactions of Immune status | <0.0001 |
| PCR method (overall effect) | <0.0001 |
| - All interactions of PCR method | <0.0001 |
| Day (overall effect) | <0.0001 |
| - All interactions of Day | <0.0001 |
| - Nonlinear effect of Day | <0.0001 |
| Serotype * Immune status | 0.0066 |
| Age * Day | 0.0015 |
| Sex * Day | 0.0011 |
| Serotype * Day | <0.0001 |
| Immune status * Day | <0.0001 |
| PCR * Day | <0.0001 |
-
p values are calculated using the Wald test from the R package ‘aod’. This test computes the Wald chi-squared test for 1 or more coefficients given their variance–covariance matrix from the model.
-
A * B is the interaction between A and B.
-
PCR: polymerase chain reaction.
Appendix 6—table 1
p values of parameters in the supermodel for platelet count.
| Parameter | p value | Parameter | p value |
|---|---|---|---|
| Age (overall effect) | <0.0001 | Age * Day | <0.0001 |
| - All interactions of Age | <0.0001 | Sex * Day | <0.0001 |
| - Nonlinear effect of Age | <0.0001 | Serotype * Day | <0.0001 |
| Sex (overall effect) | <0.0001 | Immune status * Day | <0.0001 |
| - All interactions of Sex | <0.0001 | PCR * Day | <0.0001 |
| Serotype (overall effect) | <0.0001 | Landmark * Day | <0.0001 |
| - All interactions of Serotype | <0.0001 | Viremia * Day | <0.0001 |
| Immune status (overall effect) | <0.0001 | Viremia * Serotype | <0.0001 |
| - All interactions of Immune status | <0.0001 | Viremia * Immune status | 0.0017 |
| PCR method (overall effect) | <0.0001 | Viremia * PCR | <0.0001 |
| - All interactions of PCR method | <0.0001 | Viremia * Landmark | <0.0001 |
| Day (overall effect) | <0.0001 | Serotype * Landmark | 0.0403 |
| - All interactions of Day | <0.0001 | PCR * Landmark | <0.0001 |
| - Nonlinear effect of Day | <0.0001 | Serotype * PCR | <0.0001 |
| Landmark (overall effect) | <0.0001 | Serotype * Immune status | <0.0001 |
| - All interactions of Landmark | <0.0001 | Viremia * Serotype * PCR | 0.2465 |
| - Nonlinear effect of Landmark | <0.0001 | Viremia * Serotype * Day | <0.0001 |
| Viremia (overall effect) | <0.0001 | Viremia * PCR * Day | <0.0001 |
| - All interactions of Viremia | <0.0001 | Viremia * Serotype * Landmark | 0.2601 |
| - Nonlinear effect of Viremia | <0.0001 | Viremia * PCR * Landmark | 0.0846 |
| - Undetectable Viremia | 0.1632 | Viremia * Serotype * Immune status | 0.0589 |
| Serotype * PCR * Day | <0.0001 | ||
| Serotype * PCR * Landmark | 0.1347 | ||
| Viremia * Serotype * PCR * Day | 0.4683 | ||
| Viremia * Serotype * PCR * Landmark | 0.3646 |
-
p values are calculated using the Wald test from the R package ‘aod’. This test computes the Wald chi-squared test for 1 or more coefficients given their variance–covariance matrix from the model. Note that the overall effect of viremia includes the binary variable describing detectable or undetectable viremia, and the term ‘Viremia’ in all interactions also consists of that binary variable.
-
A * B is the interaction between A and B.
-
PCR: polymerase chain reaction.
Appendix 7—table 1
Estimates from models of viremia and clinical outcomes.
| Severe dengue | Plasma leakage | |||
|---|---|---|---|---|
| OR (95% CI) | p | OR (95% CI) | p | |
| Viremia level (log-10 copies/ml)* | <0.001 | <0.001 | ||
| - 7 vs 6 (on day 1) | 2.98 (1.46; 6.10) | 1.94 (1.50; 2.51) | ||
| - 8 vs 7 (on day 1) | 2.27 (1.20; 4.31) | 1.83 (1.44; 2.32) | ||
| - 7 vs 6 (on day 2) | 2.10 (1.32; 3.36) | 1.62 (1.36; 1.94) | ||
| - 8 vs 7 (on day 2) | 1.60 (1.05; 2.44) | 1.53 (1.29; 1.82) | ||
| - 7 vs 6 (on day 3) | 1.51 (1.13; 2.00) | 1.38 (1.20; 1.57) | ||
| - 8 vs 7 (on day 3) | 1.15 (0.84; 1.57) | 1.30 (1.11; 1.52) | ||
| - 7 vs 6 (on day 4) | 1.18 (0.91; 1.54) | 1.26 (1.10; 1.45) | ||
| - 8 vs 7 (on day 4) | 0.90 (0.61; 1.32) | 1.19 (0.98; 1.44) | ||
| - 7 vs 6 (on day 5) | 1.08 (0.75; 1.54) | 1.31 (1.10; 1.57) | ||
| - 8 vs 7 (on day 5) | 0.82 (0.49; 1.37) | 1.24 (0.96; 1.59) | ||
| Undetectable viremia (Yes vs 3 log-10 copies/ml) | 0.48 (0.20; 1.16) | 0.102 | 1.84 (0.51; 6.65) | 0.247 |
| Age (years)* | 0.182 | 0.105 | ||
| - 15 vs 10 | 0.77 (0.50; 1.18) | 1.07 (0.88; 1.31) | ||
| - 20 vs 15 | 0.67 (0.44; 1.04) | 0.95 (0.85; 1.06) | ||
| Sex (Male vs Female) | 1.43 (0.79; 2.61) | 0.011 | 1.10 (0.84; 1.45) | 0.711 |
| Serotype | <0.001 | <0.001 | ||
| - DENV-1 | Ref | Ref | ||
| - DENV-2 | 0.95 (0.44; 2.07) | 1.22 (0.84; 1.77) | ||
| - DENV-3 | 0.35 (0.08; 1.51) | 0.92 (0.54; 1.56) | ||
| - DENV-4 | 2.41 (0.83; 6.98) | 1.19 (0.76; 1.86) | ||
| Immune status | <0.001 | <0.001 | ||
| - Probable primary | 0.02 (0.00; 0.15) | 0.41 (0.27; 0.63) | ||
| - Probable secondary | Ref | Ref | ||
| - Indeterminate | 0.32 (0.04; 2.32) | 0.57 (0.30; 1.11) | ||
| Study | 0.010 | <0.001 | ||
| - Study C | Ref | Ref | ||
| - Study A | 1.36 (0.43; 4.28) | 1.24 (0.80; 1.93) | ||
| - Study B | 2.86 (1.21; 6.80) | 2.68 (1.92; 3.75) | ||
| Landmark (illness day)* | <0.001 | <0.001 | ||
| - 5 vs 3 | 1.38 (0.74; 2.57) | 1.37 (1.06; 1.78) | ||
| - 7 vs 5 | 0.58 (0.17; 2.05) | 1.34 (0.77; 2.35) | ||
| Interaction of viremia† | ||||
| - With age | 0.237 | 0.044 | ||
| - With sex | 0.004 | 0.590 | ||
| - With landmark (illness day) | <0.001 | <0.001 | ||
| - With study | 0.030 | 0.261 | ||
| - With serotype | <0.001 | <0.001 | ||
| - With immune status | <0.001 | 0.001 | ||
| - With serotype * immune status | <0.001 | 0.012 | ||
| - With serotype * landmark | <0.001 | <0.001 | ||
| - With immune status * landmark | <0.001 | 0.014 | ||
| - With serotype * immune status * landmark | <0.001 | 0.005 | ||
| Interaction of serotype and immune status | <0.001 | <0.001 | ||
| Nonlinear trend | ||||
| - Viremia level | 0.031 | 0.272 | ||
| - Age | 0.349 | 0.017 | ||
| - Landmark (illness day) | <0.001 | <0.001 | ||
-
* The model incorporates nonlinear effects of log-10 viremia level, age, and illness day on the endpoints. To facilitate the interpretation of the results, ORs and their corresponding 95% CIs are provided for two selected contrasts of viremia level, age, and landmark illness day.
-
† In the model for plasma leakage, the interactions of viremia include the binary variable describing detectable or undetectable viremia.
-
Given the complexity of the models involving multiple interactions, ORs and 95% CIs are estimated for specific values of the interacting variables: log-10 viremia of 7, age of 10years, male sex, landmark illness day of 3, serotype DENV-1, and probable secondary infection. CI, confidence interval; DENV, dengue virus; OR, odds ratio; Ref, reference.
Appendix 7—table 2
Estimates from models of the rate of decline in viremia and clinical outcomes.
| Severe dengue | Plasma leakage | |||
|---|---|---|---|---|
| OR (95% CI) | p | OR (95% CI) | p | |
| Rate of decline in viremia (per 0.5 log-10 copies/ml increase) | 0.14 (0.06; 0.33) | <0.001 | <0.001 | |
| - DENV-1 – probable primary | 0.23 (0.09; 0.56) | |||
| - DENV-1 – probable secondary | 0.12 (0.05; 0.28) | |||
| - DENV-2 – probable primary | 0.30 (0.11; 0.80) | |||
| - DENV-2 – probable secondary | 0.16 (0.06; 0.38) | |||
| - DENV-3 – probable primary | 0.18 (0.06; 0.54) | |||
| - DENV-3 – probable secondary | 0.09 (0.03; 0.27) | |||
| - DENV-4 – probable primary | 0.78 (0.24; 2.50) | |||
| - DENV-4 – probable secondary | 0.40 (0.16; 1.04) | |||
| Serotype | 0.001 | 0.006 | ||
| - DENV-1 | Ref | Ref | ||
| - DENV-2 | 0.74 (0.39; 1.39) | 1.04 (0.75; 1.45) | ||
| - DENV-3 | 0.21 (0.05; 0.88) | 0.81 (0.54; 1.22) | ||
| - DENV-4 | 8.59 (2.38; 31.03) | 4.84 (2.07; 11.32) | ||
| Immune status | <0.001 | <0.001 | ||
| - Probable primary | Ref | Ref | ||
| - Probable secondary | 63.23 (8.15; 490.31) | 2.77 (1.78; 4.33) | ||
| - Indeterminate | 16.29 (1.77; 150.25) | 1.39 (0.68; 2.82) | ||
| PCR method | <0.001 | <0.001 | ||
| - One-step | Ref | Ref | ||
| - Two-step | 33.32 (10.92; 101.66) | 14.62 (6.98; 30.60) | ||
| Interaction of rate of decline in viremia | ||||
| - With serotype | 0.182 | |||
| - With immune status | 0.017 | |||
| - With PCR | 0.006 | |||
-
The model for severe dengue does not include any interaction term.
-
In the model of plasma leakage, interactions between the rate of decline in viremia and serotype, immune status, and PCR are included. ORs and 95% CIs of the rate of decline in viremia are estimated for the one-step PCR in each subgroup of serotype and probable primary/secondary infection. ORs and 95% CIs of serotype, immune status, and PCR are estimated for the rate of decline in viremia of 1.4 log-10 copies/ml.
-
CI, confidence interval; DENV, dengue virus; OR, odds ratio; PCR, polymerase chain reaction; Ref, reference.
