The incubation periods of Dengue viruses

Abstract

Dengue viruses are major contributors to illness and death globally. Here we analyze the extrinsic and intrinsic incubation periods (EIP and IIP), in the mosquito and human, respectively. We identified 146 EIP observations from 8 studies and 204 IIP observations from 35 studies. These data were fitted with censored Bayesian time-to-event models. The best-fitting temperature-dependent EIP model estimated that 95% of EIPs are between 5 and 33 days at 25°C, and 2 and 15 days at 30°C, with means of 15 and 6.5 days, respectively. The mean IIP estimate was 5.9 days, with 95% expected between days 3 and 10. Differences between serotypes were not identified for either incubation period. These incubation period models should be useful in clinical diagnosis, outbreak investigation, prevention and control efforts, and mathematical modeling of dengue virus transmission.

Figure 1. Extrinsic incubation period models.

(A–D) Vertical lines indicate the observed censored EIP observations (black for interval-censored and grey for right-censored) at each temperature (with added variability in temperature to improve visualization for observations at the same temperature). Thick solid lines and shaded areas indicate the mean and middle 95%, respectively, of the distribution for each fitted model (red: exponential; blue: Weibull; orange: gamma; and black: log-normal). (E) The lines indicate the predicted probability density for each model at 30°C.

Figure 2. EIP model sensitivity to right-censored observations.

The log-normal model is shown as in Figure 1D. The dotted and dashed lines are the comparable predicted mean and middle 95% range, respectively, for the model when the right-censored data is omitted.

Figure 3. Intrinsic incubation period models and datasets.

The thick solid lines indicate the estimated probability distributions using the complete dataset. The dashed and dotted lines indicate the estimate distributions using the pre-1940 and post-1970 subsets, respectively.

Figure 4. Intrinsic incubation period models.

The vertical bars are a histogram of the uncensored IIP data. Horizontal grey lines indicate interval-censored observations from the pre-1940 dataset (those which extend outside of the plot area are labeled with the interval maximum). The curves are the estimated IIPs for each model when fitted to the pre-1940 dataset.