Flowchart illustrating the process of patient selection

@Among 385 lab-confirmed dengue patients in study A, 31 individuals were later included in study B upon hospitalization. Of these, 9 had viremia measurements available in both studies and were consequently analysed in study A. The remaining 22 lacked viremia data in study A but had measurements in study B, leading to their inclusion in study B in the analysis.

#Although study B spanned from 2000 to 2009, daily viremia levels were only measured between 2006 and 2008.

$In study C, one study site in Vietnam did not have daily viremia measurements.

Overall, a random sample of 2340 from 3527 laboratory-confirmed dengue patients had data on viremia kinetics. PCR, polymerase chain reaction.

Baseline characteristics and clinical outcomes

Individual trajectories of measured viremia levels

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, 60 copies/ml for DENV-2, and 600 copies/ml for DENV-4 in the one-step PCR cohort, and 1000 copies/ml in the two-step PCR cohort. 57 measured values that are lower than 1000 copies/ml in the two-step PCR cohort are considered as below the detection limit. Values below the detection limit are visually represented as 1/10 of the corresponding detection limit (on the original scale). DENV, dengue virus; PCR, polymerase chain reaction.

Fitted trends in mean viremia levels

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 (D1, D2, D3, and D4 denote DENV-1, DENV-2, DENV-3, and DENV-4, respectively). Dashed lines indicate fitted viremia levels that are below the detection limit. Viremia levels are shown for age of 10 years, male sex, serotype DENV-1, probable secondary infection, and using the one-step PCR. DENV, dengue virus; PCR, polymerase chain reaction.

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 viremia on a specific day to platelet count from that day to day 10. No fitted trends are made for DENV-4 in LM day 7 since viremia was undetectable in almost all DENV-4 cases from day 7 onwards. The mean platelet counts are shown for age of 10 years, male sex, probable secondary infection, and using the one-step PCR. DENV, dengue virus; LM, landmark; PCR, polymerase chain reaction; U, under the limit of detection.

Probability of occurrence of the two clinical endpoints 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 of viremia on a specific day. No fitted trends are made for DENV-4 in LM day 7 since viremia was undetectable in almost all DENV-4 cases from day 7 onwards. Note that due to the limited number of severe dengue in primary infections (only 1 case in DENV-1) and plasma leakage in primary DENV-4 (see Appendix 4-table 1), the estimated probability of having these outcomes is nearly zero across all viremia levels within these subgroups. The probabilities are shown for age of 10 years, male sex, probable secondary infection, and from Study C. DENV, dengue virus, LM, landmark; PCR, polymerase chain reaction; U, under the limit of detection.

Probability of occurrence of the two clinical endpoints 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.