Severe fever with thrombocytopenia syndrome (SFTS) is a viral infection transmitted by tick bites. It is often prevalent during spring to summer and is characterized by fever, thrombocytopenia, hemorrhage, and gastrointestinal symptoms. SFTS was first identified in China in 2009 and was first reported in 2011 in humans ^[1][2][1,2]. In 2012, SFTS cases were reported in South Korea and Japan, and the number of patients has been increasing in East Asia and other regions ^[3][4][3,4]. The cumulative total number of reported patients was 7419 in China in 2016, 335 in South Korea in 2016, and 319 in Japan in 2017.

There are large gaps in the literature regarding differences in mortality rates between countries. For example, the reported mortality rates of those diagnosed with SFTS were 4.8%, 21.8%, and 27% in China, South Korea, and Japan, respectively ^[5][6][7][8][5,6,7,8]. In Japan, the first case was confirmed in Yamaguchi Prefecture, located in the Chugoku region, in 2013; since then, 40 to 90 cases have been reported annually, although they have been limited to the Shizuoka Prefecture in Western Japan [7]. Of the 303 reported cases in the Infectious Diseases Weekly Report from April 2013 to October 2017, 133 cases were analyzed epidemiologically based on patient information ^[7][8][7,8]. One study showed that the mean age of patients was 74 years, with the majority being 60 years or older; the male-to-female ratio was roughly 1:1, and the mortality rate of all cases during the study period was higher than that of other countries [7].

Diverse studies have been conducted to identify the factors associated with the severity of SFTS. For example, in a prospective study involving 2096 patients with SFTS who were treated in hospitals located in Henan Province, China, from April 2011 to October 2017, the mean age at the time of hospital admission was 61.4 years, 59% of those affected were female, and the mortality rate was 16.2% [9]. It was also found that patients had a higher risk of mortality if they exhibited the following characteristics: male sex, older age, delay from symptom onset to hospital admission, diarrhea, dyspnea, hemorrhage, and neurological symptoms [9]. Further, certain laboratory measures such as higher lactate dehydrogenase (LDH), aspartate aminotransferase (AST), blood urea nitrogen (BUN) levels, and elevated neutrophil counts were associated with higher mortality rates [9]. The same study also showed that the viral load in blood samples was a strong predictor of fatal outcomes. Similar results have been reported by studies conducted in Japan ^[7][8][7,8]. Therefore, the factors associated with the severity of SFTS need to be examined in each case, and conservative treatment should be provided appropriately because of the lack of evidence related to the use of antiviral drugs and other intensive treatments ^[7][8][7,8].

The severity and mortality rates of SFTS differ considerably for each country. Specifically, the mortality rate in Japan has been shown to be approximately 30%, indicating a poor prognosis ^[3][7][9][3,7,9]. In contrast, other countries such as China and South Korea have reported lower mortality rates, despite the lack of significant differences in the quality of medical care provided. Further, the rate ranges from low to high among articles published in East Asia, suggesting that there is a wide degree of variability in the data [3].

2. Clinical Presentation and Mortality of Severe Fever with Thrombocytopenia Syndrome

The mean age of all cases was 70.69 years, and the mortality rate was approximately 35 percent, which was mostly consistent with those reported in epidemiological surveys conducted in Japan (27%) ^[8][9][8,9]. ItWe was found the same tendency of higher mortality rates than in other Asian countries. In comparing the alive and dead groups, the dead group was significantly older than the alive group, had a significantly shorter period from symptom onset to hospital admission, and had significantly more hemorrhagic and neurologic symptoms. The chief complaints were fever, malaise, and gastrointestinal symptoms such as diarrhea, appetite loss, and vomiting. The reported case numbers declined after peaking in 2015, and the cases were limited to the West Japan area, mainly in the Chugoku, Shikoku, and Kyushu regions. In addition, the most frequently provided treatment methods were adrenocorticosteroids, antibiotics, and conservative treatments such as fluid transfusion. This research revealed that SFTS cases were mainly observed in the West Japan area. Therefore, one should pay attention to the spread of this disease in the future. According to a survey conducted by the Japan National Institute of Infectious Diseases in 2014, ticks carrying the SFTS virus were identified not only in regions where patients were diagnosed with SFTS (Chugoku, Shikoku, and Kyushu regions) but also in regions where there were no confirmed SFTS cases (Hokkaido, Tohoku, Kanto, and Chubu regions), suggesting that the virus-carrying ticks are widespread across Japan ^{[7][8][10][11]}[7,8,10,11]. In addition, various tick species are known to spread the SFTS virus. Haemaphysalis longicornis as well as Amblyomma testudinarium, Haemaphysalis flava, Haemaphysalis formosensis, Haemaphysalis hystricis, Haemaphysalis kitaokai, Haemaphysalis longicornis, and Haemaphysalis megaspinosa can transmit the SFTS virus to humans ^{[7][8][10][11]}[7,8,10,11]. As these ticks are prevalent in Asia, one must be cautious of the spread of the virus in various areas in Asia. The SFTS virus is transmitted by the ticks through a life cycle involving wild animals, including deer, wild boar, cats, and dogs ^[12][13][12,13]. A survey conducted by the Japan National Institute of Infectious Diseases in 2015 reported that 43.2% of deer and 8.6% of wild boars had confirmed SFTS infections based on PCR tests of the saliva or blood in the Yamaguchi prefecture, where the first patient carrying the SFTS virus was identified ^[8][14][8,14]. In addition, as reported by a survey conducted in the area where the patients with SFTS were newly identified in 2014, the prevalence of anti-SFTS virus antibodies in raccoons, raccoon dogs, and cats increased preceding the identification of the index case, suggesting that the SFTS spread between wild animals was a risk factor for SFTS in humans ^[13][15][16][13,15,16]. A survey by the Ministry of the Environment reported that the habitat area of Japanese deer and wild boars was mainly West Japan, although the area had been spreading northward every year ^{[17][18][19][20]}[17,18,19,20]. A previous study concluded that wildlife habitat area changes also accelerated the spread of infection of Japanese spotted fever and scrub typhus, both of which are related to ticks ^[21][22][23][21,22,23]. The spread of the habitat area of the wild animals may also be associated with the distribution of the ticks carrying the SFTS virus and the differences between regions in terms of case prevalence; therefore, the spread of infection should be studied in the future. This research showed a higher mortality rate (approximately 30%) for SFTS cases reported in Japan than for those reported in China and South Korea ^[5][6][5,6]. According to a report from China, the mortality rate in China was estimated to be 12.2%, which is much lower than that reported in Japan [24]. It is important to note that the data we collected in this research showed a significantly shorter time from symptom onset to hospital admission in the dead group than in the alive group, although these periods were longer in the reports from China [9]. It is also noted that the mean age in Japan shown in this study, 70.69, was higher than those reported in China, 60.5 [24]. We dithoud not considering the difference in mean age between Japan and South Korea because those in South Korea were unknown [5]. Currently, each prefecture in Japan has been working towards raising awareness of SFTS, and the public has gradually come to recognize the disease [25]. However, it is still insufficient, owing to the limited awareness in the regions where cases occur. Therefore, medical professionals tend to consider the possibility of SFTS less frequently than those in other countries. Those who developed severe conditions acutely might have received a quick response from clinicians, but cases with mild to moderate symptoms may not have been fully diagnosed. The undiagnosed disease may also be associated with the fact that patients do not complain about the symptoms because of a lack of awareness of the possibility of SFTS [26]. In terms of the cases treated in the community hospital presented in this research, it wase observed that the patients did not die but achieved remission through conservative treatment provided in the early stage, even though some of them had severe conditions. The use of antiviral drugs can be considered in critical cases of SFTS. In this study, the numbers of patients who received conservative treatment including fluid transfusion, and administered antiviral drugs were significantly higher in the group that was still alive. Previous studies have reported that there was limited evidence supporting active treatment, whereas conservative treatment administered appropriately was the most critical course of action ^[7][17][7,17]. There have been discrepancies between Japan and other Asian countries in diagnosing SFTS and in collecting data related to its prognosis and mortality. In our opinions, this is partly because recognition of SFTS remains low in Japan, and mild to moderate cases may be overlooked. Subsequent studies should investigate the effectiveness of antiviral drugs against SFTS in critically ill patients. Consistent with the results of the overall systematic review, the three cases treated at our hospital primarily had nonspecific symptoms, such as fever, gastrointestinal symptoms, and malaise. Of those, two cases reported no evident episodes of a tick bite, although they were diagnosed with SFTS based on laboratory test abnormalities, including cytopenia, during hospitalization. It took several days to decide to perform the PCR test for a definitive diagnosis. Many patients with SFTS have relatively mild symptoms ^[27][28][27,28]. If there is no need for hospital admission, those patients might not be tested for SFTS and might be provided with outpatient care for the common cold and other similar diseases. This delay in treatment could be one of the reasons for the higher mortality rate compared to that of other countries. The current primary treatment for SFTS is conservative treatment, and no specific treatment protocols have been established. Considering the further need to collect and study additional cases, we believe it is essential to conduct definitive testing appropriately to prevent overlooking those afflicted with the disease [17]. This may be achieved by conducting detailed interviews and physical examinations, including of the living environment, crusted skin regions, blood spots, and more for cold and gastrointestinal symptoms, especially in the West Japan SFTS area [29]. From the perspective of infection prevention, ticks carrying the SFTS virus are widespread in regions without SFTS cases; therefore, the recognition of SFTS needs to be improved nationwide by conducting surveys for SFTS infection in wildlife and predicting the risk of infection in humans ^[30][31][30,31]. BWe believinge that additional scrutiny is particularly important among people with a high risk of infection, such as those working in the forestry and hunting industry.