Modeling in Ecology and Epidemiology

Background: Influenza infection causes a huge burden every year, affecting approximately 8% of adults and approximately 25% of children and resulting in approximately 400,000 respiratory deaths worldwide. However, based on the number of reported influenza cases, the actual prevalence of influenza may be greatly underestimated. The purpose of this study was to estimate the incidence rate of influenza and determine the true epidemiological characteristics of this virus.

Methods: The number of influenza cases and the prevalence of ILIs among outpatients in Zhejiang Province were obtained from the China Disease Control and Prevention Information System. Specimens were sampled from some cases and sent to laboratories for influenza nucleic acid testing. Random forest was used to establish an influenza estimation model based on the influenza-positive rate and the percentage of ILIs among outpatients. Furthermore, the moving epidemic method (MEM) was applied to calculate the epidemic threshold for different intensity levels. Joinpoint regression analysis was used to identify the annual change in influenza incidence. The seasonal trends of influenza were detected by wavelet analysis.

Results: From 2009 to 2021, a total of 990,016 influenza cases and 8 deaths were reported in Zhejiang Province. The numbers of estimated influenza cases from 2009 to 2018 were 743,449, 47,635, 89,026, 132,647, 69,218, 190,099, 204,606, 190,763, 267,168 and 364,809, respectively. The total number of estimated influenza cases is 12.11 times the number of reported cases. The APC of the estimated annual incidence rate was 23.33 (95% CI: 13.2 to 34.4) from 2011 to 2019, indicating a constant increasing trend. The intensity levels of the estimated incidence from the epidemic threshold to the very high-intensity threshold were 18.94 cases per 100,000, 24.14 cases per 100,000, 141.55 cases per 100,000, and 309.34 cases per 100,000, respectively. From the first week of 2009 to the 39th week of 2022, there were a total of 81 weeks of epidemics: the epidemic period reached a high intensity in 2 weeks, the epidemic period was at a moderate intensity in 75 weeks, and the epidemic period was at a low intensity in 2 weeks. The average power was significant on the 1-year scale, semiannual scale, and 115-week scale, and the average power of the first two cycles was significantly higher than that of the other cycles. In the period from the 20th week to the 35th week, the Pearson correlation coefficients between the time series of influenza onset and the positive rate of pathogens, including A(H3N2), A (H1N1)pdm2009, B(Victoria) and B(Yamagata), were − 0.089 (p = 0.021), 0.497 (p < 0.001), −0.062 (p = 0.109) and − 0.084 (p = 0.029), respectively. In the period from the 36th week of the first year to the 19th week of the next year, the Pearson correlation coefficients between the time series of influenza onset and the positive rate of pathogens, including A(H3N2), A (H1N1)pdm2009, B(Victoria) and B(Yamagata), were 0.516 (p < 0.001), 0.148 (p < 0.001), 0.292 (p < 0.001) and 0.271 (p < 0.001), respectively.

Conclusion: The disease burden of influenza has been seriously underestimated in the past. An appropriate method for estimating the incidence rate of influenza may be to comprehensively consider the influenza-positive rate as well as the percentage of ILIs among outpatients. The intensity level of the estimated incidence from the epidemic threshold to the very high-intensity threshold was calculated, thus yielding a quantitative standard for judging the influenza prevalence level in the future. The incidence of influenza showed semi-annual peaks in Zhejiang Province, including a main peak from December to January of the next year followed by a peak in summer. Furthermore, the driving factors of the influenza peaks were preliminarily explored. While the peak in summer was mainly driven by pathogens of A(H3N2), the peak in winter was alternately driven by various pathogens. Our research suggests that the government urgently needs to address barriers to vaccination and actively promote vaccines through primary care providers.