SARS Epidemiology Modeling

To the Editor: To assess the effectiveness of intervention measures during the recent severe acute respiratory syndrome (SARS) pandemic, Zhou and Yan (1) used Richards model, a logistic-type model, to fit the cumulative number of SARS cases reported daily in Singapore, Hong Kong, and Beijing. The key to using mathematical models for SARS epidemiology is understanding the models (2). In the Richards model (1), the function F(S) in the model was described as measuring "the effectiveness of intervention measures." The parameters in F(S), namely the maximum cases load K and the exponent of deviation a, depict the actual progression of the epidemic as described by the reported data. In other words, the parameter estimates are used to quantify end results of the intervention measures implemented during the outbreaks. Simply put, the all-important question of "what if?" was not answered by their result. To gauge the effectiveness of intervention measures, one should consider a more complicated model with variable maximum case load and growth rate (r) that highlights the time-varying nature of an epidemic and its dependence on the intervention measures implemented during the epidemic. Predicting the trend of an epidemic from limited data during early stages of the epidemic is often futile and sometimes misleading (3). Nevertheless, early prediction of the magnitude of an epidemic outbreak is immeasurably more important than retrospective studies. But how early is too early? Intuitively, the cumulative case curve will always be S-shaped and well-described by a logistic-type model. The essential factor is the time when the inflection of the cumulative case curve occurs, i.e., the moment when a rapid increase in case numbers is replaced by a slower increase. Since the inflection point, approximated by tm (1), dictates the point in time when the rate of increase of cumulative case numbers reaches its maximum, the moment marks the key turning point when the spread of the disease starts to decline. As long as the data include this inflection point and a time interval shortly after, the curve fitting and predicting future case number will be reasonably accurate. To illustrate this point more precisely, the cumulative SARS case data by onset date in Taiwan were obtained from the SARS databank of Taiwan Center for Disease Control. The data cover the time from February 25, 2003, the onset date of the first confirmed SARS case, to June 15, 2003, the onset date of the last confirmed case; a total of 346 SARS cases were confirmed during the 2003 outbreak in Taiwan (4). The cumulative case data are fitted to the cumulative case function S(t) in Richards model with the initial time t0 = 0 being February 25 and the initial case number S0 = S(0) = 1. Description of the model, as well as the result of the parameter estimation, is shown in Tables A1-​-A6.A6. The estimates for the parameters are r = 0.136 (95% confidence interval [CI] 0.121 to 0.150), K = 343.4 (95% CI 339.7 to 347.1), a = 1.07 (95% CI 0.80 to1.35), and the approximate inflection point at tm = 66.62 (95% CI 63.9 to 69.3) with adjusted r2 >0.998, p < 0.0001 for the goodness-of-fit of the model (Figure). The result indicates that the inflection point occurred on May 3, and the estimate for the maximum case number K = 343.3 is 0.8% off the actual total case numbers. Figure SARS cases, Taiwan, 2003, using Richards model; t = real data. A, confirmed cases; B, estimated cases using the truncated data. Moreover, the case number data are sorted by onset date. Given a mean SARS incubation of 5 days (4–6 days) (5), the inflection point for SARS in Taiwan could be traced back to 5 days before May 3, namely April 28. On April 26, the first SARS patient in Taiwan died. Starting April 28, the government implemented a series of strict intervention measures, including household quarantine of all travelers from affected areas (6). In retrospect, April 28 was indeed the turning point of the SARS outbreak in Taiwan. To address making projections during an ongoing epidemic, we used the same dataset but used various time intervals (all starting February 25) but truncated at various dates around the inflection point of May 3. The resulting parameter estimates are given in Tables A1-​-A6.A6. For the truncated data ending on April 28 before the inflection, an unreasonable estimate of K = 875.8 was obtained. However, if we use the data ending on May 5, May 10, May 15, and May 20, we obtain estimates of K = 204.9, 253.1, 334.2, and 342.1, respectively. These estimates improve as we move further past the inflection time of May 3 (Figure). Moreover, the last estimate, using data from February 25–May 20 only, produces a 1.1% error from the eventual cumulative case number of 346, with 95% CI of 321.5 to 362.6. This retrospective exercise demonstrates that if the cumulative case data used for predictive purpose during an outbreak contain information on the inflection point and approximately 2 weeks afterwards, the estimate for the total case number can be obtained with accuracy, well before the date of the last reported case. This procedure may be immensely useful for deciding future public health policies although correctly determining the true inflection point during a real ongoing epidemic calls for scrutiny and judicious use of the model, as with all mathematical epidemic models.