After the first cases of swine-origin influenza A were described in Mexico and the United States in April 2009, pandemic influenza A (H1N1) 2009 spread throughout the world. [1], [2] The first case of pandemic (H1N1) 2009 in the Republic of Korea (ROK) was identified in a person returning from Mexico on May 2, 2009, and virus activity subsequently increased rapidly. [3]–[6].

Because of the high rates of incidence, the medical costs of pandemic (H1N1) 2009 have been considerable. [7]–[9] In order to prevent the spread of pandemic (H1N1) 2009, the government was not performed only the health policy, such as quarantine, isolation, and campaign for hygiene, but also the government was responsible for stockpiling antivirals and developing and producing vaccines. [3], [10] Pandemic (H1N1) 2009 would become a significant burden in both healthcare and socioeconomic system.

On the other hands, the government was conducted surveillance system for investment the scale occurred influenza. However, the surveillance may have been under-reporting, because the surveillance was included serological confirmed patients. Therefore, efforts are needed to estimate the exact socioeconomic burden of pandemic (H1N1) 2009.

Although several studies have been conducted to estimate disease the burden or medical costs of pandemic (H1N1) 2009, these studies focused on disease severity, effective vaccination, or community mitigation strategies. [11]–[16] Due to limitations of representative national statistics, estimation on economic impact of pandemic (H1N1) 2009 has not been conducted.

The purpose of this study was to determine the socioeconomic burden of seasonal influenza (2007–2008 [May 2007 to April 2008] and 2008–2009 seasons [May 2008 to April 2009]) and pandemic (H1N1) 2009 (2009–2010 influenza season [May 2009 to April 2010]) in the ROK and to compare medical costs and socioeconomic burden of pandemic (H1N1) 2009 with those of seasonal influenza.

During the 2009–2010 season (week 17, 2009 through week 16, 2010), a total of 266 fatal cases were reported (Figure 1). Outpatient visits and antiviral prescriptions peaked at week 43. Vaccinations against pandemic (H1N1) 2009 began on October 27, 2009, when the number of outpatient visits peaked (746,290/week).

Inpatient visits during the 2009–2010 season (123,035) increased 15- to 20-fold compared with two previous seasons, and outpatient visits (4,609,026) increased 10-fold (Table 2). The number of visits per person during the 2009–2010 season was not increased compared with two previous seasons. During the 2009–2010 season, total medical costs of inpatients increased 20-fold and those costs of outpatients increased 50-fold. In both inpatient and outpatient, the medical costs of all subcategory during the 2009–2010 season increased compared with two previous seasons. The proportion of each subcategory among inpatient medical costs was not different among seasons (P-value  = 0.598); whereas, the proportion of each subcategory among outpatient differed significantly (P-value <0.001). The mean cost per visit differed significantly across seasons for both inpatients and outpatients. Among the subcategory of medical cost, the mean diagnostic cost per visit in the 2009–2010 season was significantly increased compared with two previous seasons.

We estimated the socioeconomic costs of influenza consisted of direct costs (direct medical and non-medical costs), indirect costs (productivity losses of morbidity, caregiver, and premature mortality), and costs associated with prevention strategies (execution of the budget and protective equipment) (Table 3). We varied the return fare for outpatients and inpatients, the duration of sick leave, and the probability of purchasing and the price of preventative equipment. Based on results of the Monte Carlo simulation, the socioeconomic burden for pandemic (H1N1) 2009 was estimated at US$1,581.3 million, and those of seasonal influenza were US$44.7 million in 2007–2008 season and US$42.3 million in 2008–2009 season. Indirect costs were the largest proportion of total costs. In 2009–2010 season, 56.0% of total costs were indirect costs, consisting primarily of productivity losses of caregivers (30.0%) and morbidity (outpatient: 24.3%, inpatient 0.62%). In 2007–2008 and 2008–2009 seasons, the cost of productivity losses due to morbidity was the largest component.

Inpatient visits, outpatient visits, and total medical costs increased significantly in the 2009–2010 season compared to two previous seasons in the ROK. The 2009–2010 medical costs (US$291.7 million) accounted for 1.24% of the 2009 total national healthcare expenditures (US$23.48 billion). In contrast, 2007–2008 medical costs (US$7.17 million) accounted for only 0.04% of 2007 national healthcare expenditures (US$19.25 billion), and 2008–2009 medical costs (US$7.90 million) were about 0.04% of 2008 national healthcare expenditures (US$20.67 billion). These findings demonstrate the significance of pandemic (H1N1) 2009 as a major public health concern in the ROK. [24].

Compared with the 2007–2008 season, outpatient diagnostic costs were 773 times higher in the 2009–2010 season, and the mean diagnostic cost per outpatient visit was 58.8 times higher. In addition to the increased number of influenza cases, the higher medical costs during the 2009–2010 season may be due to the increased use of diagnostic tests including real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Although laboratory tests can confirm influenza cases, clinical judgment by physicians is important in the identification of influenza. On October 30 (week 43) 2009, the government recommended antivirals administration who met the case definition of influenza-like illness, without laboratory confirmation. However, diagnostic costs did not decrease after that time.

Besides public fears about the pandemic, other factors may be associated with the increased diagnostic testing. First, in the ROK, medical cost consist those covered by insurer and those covered by patients (coinsurance) due to the National Health Insurance program. Before March 2010, the National Health Insurance program covered 40–50% of the cost for RT-PCR testing, suggesting overutilization of these tests because they were relatively inexpensive for the patient. After March 2010(week 11), the patient covered up to 100% of real-time RT-PCR costs, decreasing its proportion of diagnostic costs. Second, most schools and workplaces required negative diagnostic test results for suspected cases during the pandemic, despite government recommendations. Therefore, suspected cases visited clinics and were examined laboratory tests to obtain a medical certificate and not to get treatment. The medical cost breakdown did not differ significantly among age groups, suggesting that age groups not incurred greater diagnostic costs (data not shown).

In this study, total 2009–2010 socioeconomic costs (US$1,581.3 million) accounted for 0.19% of the 2009 gross domestic product (US$832.9 billion). In contrast, total 2007–2008 socioeconomic costs (US$44.7 million) accounted for only 0.005% of the 2008 gross domestic product. In the 2007–2008 and 2008–2009 seasons, indirect costs were the largest proportion of total costs. Specifically, 56.0% of 2009–2010 costs were indirect costs, consisting primarily of productivity losses of caregivers (30.0%) and adult outpatients (24.3%). In the pandemic's early stage, public health officials recommended that students and employees with influenza rest at home for a week, whereas the mean sick leave was <1 to 4.3 days for typical seasonal influenza. [20], [25] This longer sick leave may have contributed to the high indirect costs for pandemic (H1N1) 2009.

The ROK has several national surveillance systems including pneumonia and influenza surveillance and sentinel surveillance for influenza-like illness known as the Korea Influenza Surveillance Scheme. [9] However, the ROK does not have a hospital-based surveillance system for emerging diseases, such as the Emerging Infections Program in the United States, which collects data about susceptibility, clinical course, treatment efficacy, and outcomes. [26] Therefore, little information on these data was available in the early stages of the pandemic in the ROK. Although the severity of pandemic (H1N1) 2009 was similar to that of typical seasonal influenza, early response strategies in the ROK (e.g., confirmation testing, social distancing) were not effectively changed because of limited national data regarding clinical characteristics.

Our study has some limitations. First, we could not include costs incurred by asymptomatic patients or those not admitted to the hospital in calculating influenza-related costs. We considered preventative actions taken by the general population and execution of the budget (including an improved response system) and its promotion to the general population. Second, the rapid antigen test for influenza was also widely used in the ROK. However, the National Health Insurance Corporation did not cover this test; therefore, we could not acquire data regarding its use or include these costs in our analysis. Third, we estimated outpatient sick leave based on the first clinic visit only and assumed no recurrence or infection with other influenza strains. Therefore, the diagnostic and productivity costs may also be underestimated. In addition, misclassification and underreporting may affect our study. When pneumonia occurs as a complication of influenza, influenza cases may be coded as pneumonia (ICD-10-CM codes: J12–J18). However, misclassification or underreporting of influenza may have been lower in the 2009–2010 season (when confirmation tests were widely used), resulting in overestimated differences in medical costs. We found that the number of pneumonia cases and fatal cases in the 2009–2010 season were similar to numbers reported in previous seasons (Table S1). Therefore, misclassification did not appear to have affected our results. Mortality data were obtained from death certificates for the 2007–2008 and 2008–2009 seasons. When several disease codes can be used as cause of death, the most severe disease is generally used on a death certificate. Therefore, influenza mortality may be misclassified/underreported, underestimating the costs of premature mortality. Because in 2009–2010 season the KCDC mortality surveillance data was used, the costs of premature mortality of 2009–2010 season could not compare with those of previous season.

Because of this potential underestimation in influenza-associated costs, the true socioeconomic burden of pandemic (H1N1) 2009 may exceed our estimate. Although a conservative formula was used, we found that total costs and average costs per visit of pandemic (H1N1) 2009 were significantly higher than those of typical seasonal influenza.

In conclusion, medical and socioeconomic costs of pandemic (H1N1) 2009 were considerably higher than costs of the previous two influenza seasons, primarily because of longer sick leave and high diagnostic costs. Therefore, government policies such as risk communication concerning sick leave and diagnostic testing could be modified to reduce the socioeconomic burden in similar situations. In addition, a surveillance system for clinical characteristics (e.g., susceptibility, treatment efficacy, adverse drug reactions, and severity) in the early stages of an outbreak is needed.