Influenza viral infections are responsible for respiratory illnesses resulting in substantial morbidity and increased health care utilization and cost [1]. Influenza causes an annual 3 million cases of illness and 250,000 to 500,000 deaths globally [2]. Research has demonstrated substantial mortality associated with influenza-related illnesses in both temperate and subtropical areas of China [3]. The annual influenza-associated excess mortality was 18.0 (range: 10.9–32.7) and 11.3 (range: 7.3–17.8) deaths per 100,000 people in northern and southern cities, respectively [3]. Although only a small proportion of influenza infections required hospitalization, they imposed considerable economic and social burden [4], [5]. Understanding the cost of hospitalization is important in evaluating the economic burden of influenza and the impact of vaccination on a population scale.

Despite extensive research in developed countries, the socio-economic burden of laboratory-confirmed influenza in China has not been well-described. Currently, seasonal influenza vaccination in China is not covered by the national immunization program, instead requiring out-of-pocket payment. Influenza vaccination coverage remains low. A previous study examining production capacity, vaccine supply and annual sales from international and domestic vaccine manufacturers in China concluded the total available influenza vaccines could only cover 1.9% of the Chinese population [6]. Decision making on influenza prevention strategy requires scientific evidence on the cost-effectiveness of influenza vaccination. Data on the economic burden of laboratory-confirmed influenza provides important information for decision makers.

To better understand the economic burden of influenza hospitalization among different age groups in China, we conducted a study estimating the direct medical cost of influenza-related hospitalizations in three hospitals with Severe Acute Respiratory Infections (SARI) surveillance systems. SARI surveillance identified SARI cases in all ages, among which those with laboratory-confirmed influenza infection were recruited. We collected detailed cost data for cases from December 2009 to June 2011 and converted them to 2010 U.S. dollars (USD) [7]. We also identified factors resulted in high-cost hospitalizations.

We retrospectively included 71 influenza-related hospitalizations among 560 SARI cases reported between December 2009 and December 2010. We prospectively recruited 35 influenza-related inpatients among 300 SARI cases reported from January to June 2011. Of the 106 total laboratory-confirmed influenza-related hospitalizations, 60% (64/106) were children younger than 15 years old and 21% (22/106) had underlying medical conditions (Table 1). The proportion of patients with underlying medical conditions was 2%, 44%, and 58% for children, adults, and elderly, respectively. More than 60% (64/106) of influenza patients had complications during hospitalization; most frequently among the elderly (79%). However, there was no statistically significant difference across the age groups. Although 61% (65/106) of influenza patients received antiviral treatment, only 32% of the elderly received antivirals, significantly lower than the other age groups (p<0.05). All patients, regardless of age, received antibiotic treatment. Nearly half (44%) of the children received radiological examination, significantly lower than the overall (61%) and the other two age groups (p<0.05). The median (IQR) length of hospital stay was 6 (6) days. The elderly group had longer length of hospital stay (14 days) than the other age groups (p<0.05).

As shown in Table 2, the mean total direct medical cost of hospitalization was $1,797 with a skewed distribution (range: $80–$27,545). For children, adults, and elderly, the median total direct medical cost (IQR) was $231 ($164), $854 ($890), and $2,263 ($7,803), respectively. Comparing risk groups in the overall population and each age group, the high risk groups had higher costs. Overall, the total direct medical cost incurred by the patients with high risk (with underlying medical conditions) was 6 fold of the cost incurred by low risk patients (without underlying medical conditions). With the exception of antiviral cost, the cost of the other categories or subcategories for the high risk group was approximately 2–13 fold of the cost for the low risk group (p<0.05). For adults, the total cost, therapeutics, and antibiotics cost of the high risk group was approximately 2–3 fold of that of the low risk group (p<0.05). Nursing cost of the high risk elderly group was 3 fold of that of the low risk group (p<0.05). Higher costs were also found in the elderly group in the categories of total cost, diagnostics and therapeutics cost (Table 2). In our study, we had only one child with underlying medical conditions, thus precluding any comparisons from being drawn from this age group.

Comparing patients of different ages in the same risk category, elderly had a higher cost than other age groups. Among low risk, the total direct medical cost in the elderly was 5 and 2 times the cost for children and adults, respectively (p<0.05). Similar trends were observed for clinical examination and laboratory testing cost across the three age groups (p<0.05). Therapeutics cost in the elderly was also significantly higher than the other age groups (p<0.05). Among the high risk, diagnostics cost in the elderly was 3 times the cost in adults (p<0.05).

Regardless of age group or underlying medical conditions, therapeutics and diagnostics were the two largest components of direct medical cost of influenza-related hospitalizations, accounting for of 57% and 23%, respectively (Table 2 and Figure 1). In therapeutics, antiviral cost across age and risk groups was extremely low while antibiotic cost (overall median: $78, IQR: $185) was high. Clinical laboratory testing cost was the majority expenditure (∼84%) in the diagnostics cost, regardless of age group or underlying medical conditions. The clinical laboratory testing cost was much higher than the clinical examination cost (Table 2). Nursing and physician services costs were the lowest in the five categories: 3% and less than 1%, respectively.

Across hospitals, the proportion of each cost category varied. In Hospital A in Sichuan province, diagnostics constituted more than 50% of the total direct medical cost among high risk adult and overall groups. Among the high risk elderly group, the majority of cost was therapeutics while in the low risk elderly group, diagnostics and therapeutics accounted for nearly 50% each of total cost. In Hospital B in Henan province, therapeutics constituted the majority (>77%) of the total direct medical cost in overall high risk population. Therapeutics accounted for a higher proportion of total cost in Hospital C in Shandong province.

This is the first study on the direct medical cost of influenza-related hospitalizations in China. We found the mean cost of influenza-related hospitalization of 6 days (median: 6, IQR: 6) was $1,797. In contrast, the cost of outpatient influenza-like illness (ILI) visits was 71 fold lower ($25.2) in Guangdong province in southern China in 2007 [12]. This suggests that the direct medical costs of influenza-related hospitalization may be a greater source of economic burden to patients and their families than outpatient ILI.

The median direct medical cost of influenza-related hospitalization for children was $231 in our study, much lower than the corresponding cost in the United States ($3,366–$19,444) [10], [13], [14]. This may be due to different levels of economic development and medical care systems. A study analyzing data from 2005 to 2009 in a children’s hospital in Suzhou, Jiangsu province in eastern China, found the mean cost of influenza-related child hospitalizations was $624 [15]. Since it was a specialized hospital and the children had a higher proportion of complications (∼80%) than those in our study (∼60%), the children in the other study may have been sicker and required more expensive care than our population. However, the length of hospital stay was similar in the two studies (7 days in Suzhou. 6 days in this study). Considering the varied cost of living and the diversity of medical care service utilization, the differences observed in these two reports are not unexpected.

Hospitalization due to influenza-related illness incurred a high cost to patients. The overall direct medical cost ($1,797) was 41% of the Chinese annual gross domestic product (GDP) per capita ($4,433) in 2010 [16]. In contrast, hospitalization cost for the same illness ($590) in Hong Kong constituted 1.9% of the GDP per capita ($31,758) in 2010 [16], [17]. The cost of hospitalizing children ($231) was less than for adults or elderly. It constituted 5.2% of the annual GDP per capita. This figure was comparable to the 8.8% ($4,129/$46,702) in a report on children from the U.S. [13], [16].

Underlying medical conditions contributed to a 2–3 fold increase in hospitalization costs for adults and elderly. Annual influenza vaccination is the most effective method for preventing influenza viral infection and its complications [18]. Broader influenza vaccination coverage could decrease hospitalizations. Our findings support a targeted preventive vaccination strategy, focusing on high risk populations with underlying medical conditions in order to reduce economic burden to the society.

In agreement with a previous study [15], we found the majority of direct medical cost in our study hospitals was due to therapeutic treatment (57%) and diagnostic testing (23%). Only a small proportion was incurred through professional services such as physician services (<1%) and nursing (3%). This is drastically different from findings in the U.S., where the majority of hospitalization cost is from room charges and supplies (64%) [10].

Our findings also suggest that standardized clinical management could be optimized to properly guide physicians’ diagnostic testing use and treatment decisions. Laboratory testing was the major diagnostics expenditure in for all three age groups, regardless of underlying medical conditions. Clinical laboratory testing accounted for most of influenza-related hospitalization expenditures because of the high amount of laboratory testing especially the routine blood tests (90%) and blood biochemical tests (91%). Only a small proportion of patients received sputum tests (9%) and immunologic tests (12%) to confirm etiology. Another finding was the low use of antivirals which could be either due to an absence of medicines in the hospital or physician treatment preferences. However, the fact that all patients received antibiotics treatment indicated a potential problem of antibiotic overuse. The Ministry of Health recognized the need to optimize the practices and issued clinical management guidelines in October 2012 [19]. Future studies should investigate the impact of these guidelines on patient treatment, health outcomes and cost.

Our findings should be interpreted given the limitations of the study. We relied on the SARI surveillance system to identify cases; however some patients might not be captured by the system due to suboptimal implementation of the SARI protocol. Since our data was drawn from provincial hospitals, our study might bias toward the selection of relatively more severe cases, who attended provincial rather than more local hospitals. Despite collecting data over two and a half influenza seasons with hospitals in three locations, the size of the study population was small (n = 106) and may not be generalizable to the rest of China. The expenditure and cost composition in more developed cities, such as Beijing and Shanghai may be different from those found in other areas. It is likely that physicians may provide different services based on health insurance status of the patients, but due to inadequate information on health insurance, we were unable to assess its impact.

This study focused on direct medical cost of influenza-related hospitalizations among SARI cases. Future work should include direct non-medical cost and indirect costs including transportation and lost productivity. To accurately measure the annual social and economic burden and impact attributed to influenza infections in China, further investigation is needed on the cost of influenza-related outpatient care and non-SARI influenza-related hospitalizations.