This investigation of the epidemiology of HFRS in the ROK during the past 17 years revealed an average disease incidence per 100,000 individuals of 0.83 and a case fatality rate of 1.26%. More than half of all patients were male, and more than 80% were at least 40 years old. The present results were generally consistent with those of a previous study of HFRS epidemiology in the ROK from 2001 to 2010, which reported an incidence rate per 100,000 individuals of 0.81, a case fatality rate of 1.01%, a proportion of males of 57%, and a proportion of patients aged ≥40 years of 82.1% [11]. However, the previous study stratified patients into only two age groups, ≤39 vs. ≥40 years, whereas the present study added a third age group including patients aged ≥70 years.
Interestingly, the present study observed a gradual increase in the number and proportion of patients in this latter group, consistent with a previous study of 17 HFRS-endemic regions throughout China which showed that the proportion of patients aged ≥60 years increased gradually from 8.8% in 2005 to 14.7% in 2010 [15]. In China, the EPI was implemented in 2008 and targets the general population aged 16–60 years in HFRS-endemic regions. The authors observed that in these EPI-targeted regions, the proportion of patients aged 16–60 years decreased from 88.3% in 2007 to 81.6% in 2010, whereas that of patients aged ≥60 years increased from 9.2 to 14.7%. However, in non-EPI targeted regions, the proportion of patients aged ≥60 years also increased from 8.3% in 2007 to 10.3% in 2010. The authors of this Chinese study explained the reasons for this change in age distribution as follows. First, young people from rural areas migrate to urban areas, and the increased engagement of the remaining elderly population in work and increases in the average survival time lead to an increase in the percentage of elderly workers. Second, the EPI significantly reduced the disease incidence among patients aged 16–60 years, which led to a relative increase in the proportion of patients aged ≥60 years [15]. Another study conducted in Yichun City, China from 2005 to 2013 also observed a gradual increase in the proportion of HFRS patients aged ≥60 years in EPI-targeted regions, from 7.2% in 2005 to 21.6% in 2013, as well as a concomitant gradual decrease in the proportion of patients aged 16–60 years [23].
To date, hantavirus immunization initiatives in the ROK have not targeted specific age groups. However, the present study demonstrated gradual increases in both the number and proportion of HFRS patients aged ≥70 years during the past 17 years (Table 2, Fig. 1). Especially, a Poisson regression analysis revealed that the RR of time on the incidence of HFRS was highest among those aged ≥70 years compared to the other age groups (Table 4). This is probably attributable to overall population aging and a gradual decrease in the proportion of young people in rural areas of the ROK. Consequently, elderly residents are increasingly required to work and are more frequently at risk of exposure to hantaviruses; this is in line with the aforementioned explanation proposed by He et al. [15, 25].
In this study, a distinct pattern of seasonal variation in the incidence of HFRS was observed among patients aged ≥70 years (Fig. 2). Particularly, the Poisson regression analysis yielded an RR of 10.029 during the fourth quarter in this age group, which was significantly higher than the RRs of the other age groups (Table 5). Additionally, patients aged ≥70 years also had the highest incidence rate per 100,000 individuals (Fig. 3). Distinct patterns of seasonal variation in the occurrence of HFRS are usually attributable to HTNV infection, which primarily occurs in farming-related rural populations during the autumn harvest period [1, 26]. In contrast, the present study observed more similar proportions of patients aged ≤39 years across the four quarters of the year. In the ROK, this younger population includes soldiers who are predominantly male and perform many outdoor activities regardless of the season. In this study, 83.8% of patients aged ≤39 years were male, and the relatively lower level of seasonal variation in this age group was presumably due to the large number of soldiers. In other words, the increase in the HFRS incidence and the distinct pattern of seasonal variation among individuals aged ≥70 years are presumably due to an increase in the occurrence of HFRS among elderly agriculture workers in rural areas.
As noted previously, the lack of data on the effectiveness of the IHV from well-designed large-scale studies has hindered the active implementation of hantavirus immunization in the ROK [20, 21]. However, recently, a case-control study of Korean soldiers reported an adjusted hantavirus vaccine efficacy of 58.9%; the rate of 78.7% in the high-risk group suggests moderate effectiveness in this population [27]. In addition, He et al. and Liu et al. have reported in previous studies that immunization of high-risk group in general population is effective [15, 23]. Notably, the ROK also contains HFRS-endemic areas, such as Yeoncheon, Paju, and Cheorwon [11, 28, 29], and the present findings demonstrate an increased disease occurrence among elderly people in rural areas. Therefore, an immunization program that targets this high-risk population may be an important factor in controlling future occurrences of HFRS.
This study had some limitations, primarily related to the use of data reported to the KCDC. Specifically, information about the patients’ occupations was lacking, as these details are not necessarily provided when reporting a national notifiable infectious disease to the government of the ROK. Such data would have allowed a more selective determination of the population facing a high risk of HFRS. However, the patients’ occupations were indirectly estimated from factors such as seasonal variation patterns and sex. Still, this limitation is difficult to overcome.
