Estimation of the reproduction number of pandemic influenza A(H1N1) 2009 from national data of antiviral agent prescription

Abstract

Background: The WHO announced the emergence of Pandemic Influenza A(H1N1) 2009 (H1N1p) on April 24, 2009 and declared pandemic on June 11. Many studies were performed to estimate the reproduction number of H1N1p, however the majority of these studies focused on confirmed cases in the early stage of pandemic. The Korea CDC recommended doctors to prescribe antiviral agents to the patients with acute febrile respiratory illness (AFRI) without confirmation. All pharmacies and designated hospitals were required to report their daily consumption of the antiviral agents to Korea CDC via an internet-based antiviral agent management program. The objective of the present study was to estimate the reproductive number of H1N1p using national data of antiviral agent prescription in Korea during the pandemic.Methods: The study subjects were patients who were prescribed antiviral agents from the national stockpile from August 21, 2009 to April 30, 2010. The daily numbers of incident patients were estimated based on the amount of prescribed antiviral agents by reflecting the time-lag between symptom onset and prescription of an antiviral agent, the proportion of antiviral agent prescription, and the proportion of confirmed H1N1p cases among AFRI patients. In the present study, two different approaches were used to estimate the reproduction number. The first method was an estimation based on the cumulative number of cases, that was simple deterministic approach. The reproduction number was derived from the growth rate in exponential distribution. The intrinsic growth rate of the epidemic was estimated using Poisson regression over a given time interval. The second method was a real-time estimation to estimate the daily reproduction number, assuming the Weibull distribution of generation time.Results: Approximately 3,087,788 people (6.2% of total population in Korea) were prescribed antiviral agents. The antiviral agent prescription rate was higher in children and adolescents (3 to 19 years old) than in other groups. Also, the rate was higher in urban areas than in rural areas. The estimated number of patients rose from mid-October, peaked on October 28, and decreased starting in mid-November. Using the simple deterministic approach, the reproduction numbers were estimated to be 1.44 (mean generation interval, Tc=2), 1.55 (Tc=2.5) and 1.66 (Tc=3) from October 14 to 28. The daily reproduction number increased to 1.5 on October 10, peaked to 1.6 on October 24, and decreased to one at the end of October. In November, the reproduction number fluctuated below one.Conclusions: The reproduction number estimated from the amount of prescribed antiviral agents was similar to or lower than those from previous studies. The daily reproduction number increased three weeks before the peak in the estimated number of patients. The reproduction numbers estimated in the present study reflect the national level transmission of H1N1p during the period with the highest level of activity. Aditionally, the methods used in the present study can be applied in epidemics in which there are too many patients to count on a daily basis.