PHWR Public Health Weekly Report

Severe fever with thrombocytopenia syndrome (SFTS) is a recessive hemorrhagic disease caused by the SFTS virus, which is tick-borne [1]. The Ixodidae family of ticks comprises approximately 700 species and is distributed globally. The main vector of domestic SFTS is Haemaphysalis longicornis [2]. It is known that the virus is transmitted from ticks infected with the SFTS virus to the host animal or human body through the salivary gland of the ticks while they suck blood [3]. Human-to-human transmission cases in which an individual is infected, owing to exposure to the blood or bodily fluids of patients with SFTS and transmissions from infected animals, have also been reported [1,4].

SFTS was first reported in China in 2011, and cases have also been reported in Japan, Taiwan, and Vietnam. Since the first report of a patient in 2013 in the Republic of Korea (ROK), 1,697 cases were reported until 2022. Of these patients, 317 died and the cumulative mortality rate was 18.7%. The latency period after exposure is 5 to 14 days. In addition to high fever and thrombocytopenia, digestive and bleeding symptoms develop [5,6]. In severe cases, multiple organ dysfunction or even death may occur [5]. Accordingly, the ROK has classified as a class 4 legal communicable disease since September 23, 2013, and is currently monitoring and classified it as a class 3 legal communicable disease according to the amendment of the Infectious Disease Prevention Act of 2020.

The aim of this investigation was to analyze the 2022 SFTS report and epidemiological survey data to determine the incidence patterns, epidemiological characteristics, and clinical characteristics of patients with SFTS and the associated deaths to explore future prevention and management measures.

Overall, 193 cases of patients with SFTS (190 confirmed patients and 3 SFTS-like illness) reported through the statutory infectious disease monitoring system under the Infectious Disease Control and Prevention Act from January 1 to December 31, 2022, and reflected in the statistics were analyzed according to the month, region, and report date. The patients’ sex, age, occupation, exposure risk factors, symptoms, and underlying diseases were obtained through an epidemiological survey, and risk factors for mortality according to clinical symptoms and underlying diseases were analyzed using univariate analysis and binomial logistic regression. Excel 2016 (Microsoft Office Professional Plus 2016; Microsoft), QGIS 3.22.9, and R version 4.1.2 were used for the analysis. A p-value of <0.05 was considered significant.

1. Patients in SFTS by Month and Region in 2022

Overall, SFTS was reported in 193 patients between January 1 and December 31, 2022, with 40 deaths, resulting in 20.7% SFTS mortality rate in 2022. Most infections occurred between April and November, with the highest number of patients (n=45, 23.3%) and deaths (n=12, 30.0%) reported in October (Figure 1).

Figure 1. Monthly distribution of cases and deaths with severe fever with thrombocytopenia syndrome (SFTS) in the Republic of Korea, 2022

The nationwide incidence of SFTS per 100,000 population was 0.38. According to regions, the most of the infections occurred in Yeongdeok-gun, Gyeongsangbuk-do (n=11.3); followed by Yangyang-gun, Gangwon-do (n=10.8); Inje-gun, Gangwon-do (n=9.3); Soonchang-gun, Jeollabuk-do (n=7.5); and Yeongyang-gun, Gyeongsangbuk-do (n=6.1, Figure 2).

Figure 2. Geographical distribution of cases with severe fever with thrombocytopenia syndrome in the Republic of Korea, 2022

2. Epidemiological Characteristics of Patients with SFTS in 2022

Regarding the general characteristics of the patients, there were no significant differences between the sexes, with 104 male patients (53.9%) and 89 female patients (46.1%). However, there were more deaths among male patients (n=27, 67.5%) than that in female patients (n=13, 32.5%). Five, 38, 53, and 97 patients were aged 20 to 39 years (2.6%), 40 to 59 years (19.7%), 60 to 69 years (27.5%), and 70 years or higher (50.3%), respectively. The highest number of deaths due to SFTS were in the aged 70 years and older (n=24, 60%), followed by those aged 60 to 69 years (n=12, 30.0%) and 40 to 59 years (n=4, 10.0%). The most common occupation were agricultural workers (n=61, 31.6%), followed by clerical workers (n=12, 6.2%) and other (n=37, 19.2%); 61 patients were unemployed (31.6%) and 22 were homemakers (11.4%).

The exposure risk factors were categorized as agricultural work, including farming and garden work, other activities, and unknown activities (duplicate selection was available for agricultural work and other activities). Ninety-six patients were engaged in agricultural work (49.7%) and 87 in other activities (45.1%). The other activities were identified as collecting forest products (n=18); hiking, walking, and camping (n=16); weeding (n=12); and visiting graves and mowing (n=11, Table 1).

Table 1 Epidemiological characteristics of cases and deaths with severe fever with thrombocytopenia syndrome in the Republic of Korea, 2022

Variable	Total (n=193)	Survival (n=153)	Death (n=40)
Sex
Male	104 (53.9)	77 (50.3)	27 (67.5)
Female	89 (46.1)	76 (49.7)	13 (32.5)
Age
20–39	5 (2.6)	5 (3.3)	0 (0.0)
40–59	38 (19.7)	34 (22.2)	4 (10.0)
60–69	53 (27.5)	41 (26.8)	12 (30.0)
≥70	97 (50.3)	73 (47.7)	24 (60.0)
Occupation
Farm-worker	61 (31.6)	47 (30.7)	14 (35.0)
Un-employed	61 (31.6)	47 (30.7)	14 (35.0)
Housewife	22 (11.4)	16 (10.5)	6 (15.0)
Office worker	12 (6.2)	11 (7.2)	1 (2.5)
Others	37 (19.2)	32 (20.9)	5 (12.5)
Risk factora)
Farmworksb)	96 (49.7)	77 (50.3)	19 (47.5)
Other activities except farmworks	87 (45.1)	69 (45.1)	18 (45.0)
Unknown	19 (9.8)	15 (9.8)	4 (10.0)

Values are presented as number (%). ^a)Farmworks and other activities can be duplicated. ^b)Farmworks included farming and gardening..

3. Clinical Characteristics and Underlying Diseases of Patients with SFTS in 2022

Regarding systemic clinical symptoms, 169 patients had a fever (87.6%) and 122 experienced fatigue (63.2%). With respect to digestive system symptoms, 64 patients complained of diarrhea (33.2%) and 42 had abdominal pain (21.8%). Regarding neurological symptoms, 46 patients reported loss of consciousness (23.8%) and 27 complained of slurred speech (14.0%). Regarding bleeding symptoms, seven reported hematuria (3.6%) and seven complained of bleeding from the gums (3.6%).

In the case of the deceased, 35 patients had a fever (87.5%) and 26 experienced fatigue (65.0%) regarding systemic symptoms. With respect to digestive system symptoms, 16 reported diarrhea (40.0%) and 10 complained of abdominal pain (25.0%). Only four experienced coughing (10.0%). In terms of neurological symptoms, 11 had loss of consciousness (27.5%), and seven complained of slurred speech (17.5%). Regarding bleeding symptoms, five had hematuria (12.5%), three reported bloody stool (7.5%), and three complained of bleeding from the gums (7.5%). Univariate analysis to confirm the risk of death according to clinical symptoms showed a significant prevalence of hematuria (adjusted odds ratio [aOR], 10.8; 95% confidence interval [CI], 2.01–57.9) (Table 2).

Table 2 Clinical characteristics of cases and deaths with severe fever with thrombocytopenia syndrome in the Republic of Korea, 2022

Symptomsa)	Case (n=193)	Survival (n=153)	Death (n=40)	p-value	Odds ratio	95% confidence interval
General symptoms
Fever	169 (87.6)	134 (87.6)	35 (87.5)	0.99	0.99	0.35–2.85
Fatigue	122 (63.2)	96 (62.7)	26 (65.0)	0.79	1.10	0.53–2.28
Muscle pain	76 (39.4)	61 (39.9)	15 (37.5)	0.79	0.91	0.44–1.85
Headache	57 (29.5)	47 (30.7)	10 (25.0)	0.48	0.75	0.34–1.66
Joint pains	22 (11.4)	19 (12.4)	3 (7.5)	0.39	0.57	0.16–2.04
Lymph node enlargement	4 (2.1)	3 (2.0)	1 (2.5)	0.83	1.28	0.13–12.7
Gastrointestinal symptoms
Diarrhea	64 (33.2)	48 (31.4)	16 (40.0)	0.30	1.46	0.71–2.99
Abdominal pain	42 (21.8)	32 (20.9)	10 (25.0)	0.58	1.26	0.56–2.85
Nausea	30 (15.5)	23 (15.0)	7 (17.5)	0.70	1.20	0.47–3.03
Vomiting	27 (14.0)	24 (15.7)	3 (7.5)	0.28	0.44	0.12–1.53
Jaundice	9 (4.7)	9 (5.9)	0 (0.0)	0.99	-	0.00–Inf
Respiratory symptoms
Cough	14 (7.3)	10 (6.5)	4 (10.0)	0.46	1.59	0.47–5.36
Sputum	2 (1.0)	2 (1.3)	0 (0.0)	0.99	-	0.00–Inf
Neurologic symptoms
Decreased level of consciousness	46 (23.8)	35 (22.9)	11 (27.5)	0.54	1.28	0.58–2.82
Slurred speech	27 (14.0)	20 (13.1)	7 (17.5)	0.47	1.41	0.55–3.62
Convulsions	14 (7.3)	11 (7.2)	3 (7.5)	0.95	1.68	0.28–3.95
Bleeding tendency
Hematuria	7 (3.6)	2 (1.3)	5 (12.5)	0.006	10.8	2.01–57.9
Bleeding gums	7 (3.6)	4 (2.6)	3 (7.5)	0.16	3.02	0.65–14.1
Melena	6 (3.1)	3 (2.0)	3 (7.5)	0.09	4.05	0.79–20.9

Values are presented as number (%). ^a)Multiple choices. Inf=infinite..

One hundred and seven patients had underlying conditions (55.4%); 83 had cardiovascular diseases (43.0%), including hypertension; 45 had diabetes (23.3%); 9 had cancer (4.7%), and 5 had liver diseases (2.6%). Among the deceased, 30 had underlying conditions (75.0%), 21 had cerebro-cardiovascular diseases (52.5%), 17 had diabetes (42.5%), 4 had cancer (10.0%), and 2 had liver diseases (5.0%). Univariate analysis confirmed a significant risk of death in accordance with underlying diseases (aOR, 2.96; 95% CI, 1.35–6.48). Binomial logistic regression analysis was also performed for variables including cerebro-cardiovascular diseases, diabetes, cancer, and liver diseases to confirm the effect of underlying diseases on mortality, and diabetes was found to have a significant effect (aOR, 2.75; 95% CI, 1.19–6.37) (Table 3).

Table 3 Underlying disease of cases and deaths with severe fever with thrombocytopenia syndrome in the Republic of Korea, 2022

Underlying diseasesa)	Case (n=193)	Survival (n=153)	Death (n=40)	p-value	Odds ratio	95% confidence interval
Yes	107 (55.4)	77 (50.3)	30 (75.0)	0.007	2.96	1.35–6.48
Cardiovascular disease	83 (43.0)	62 (40.5)	21 (52.5)	0.58	1.25	0.57–2.75
Diabetes	45 (23.3)	28 (18.3)	17 (42.5)	0.018	2.75	1.19–6.37
Cancer	9 (4.7)	5 (3.3)	4 (10.0)	0.43	2.20	0.31–15.7
Liver disease	5 (2.6)	3 (2.0)	2 (5.0)	0.58	1.77	0.24–13.2

Values are presented as number (%). ^a)Multiple choices..

In this investigation, the 2022 SFTS report and epidemiological survey data were analyzed to identify epidemiological and clinical characteristics of the affected patients and deaths. The review of the monthly incidence of SFTS in 2022 showed that the first case emerged in April. From 2013 to 2015, the first case emerged in May. However, from 2016 to 2022, the first case emerged in April, except for that in 2017, and in 2023, the first case was reported on April 5th [7]. Climate factors and the monthly incidence of SFTS have been reported to be correlated, and follow-up studies will be necessary because the trend of infectious diseases caused by climate change may vary [8].

There were no deaths among patients younger than 40 years of age, and the mortality rates were 10.5% for those between the ages of 40 and 59 years, 22.6% for those between the ages of 60 to 69 years, and 24.7% for those aged 70 years or higher. This finding was consistent with those of previous studies showing that 90.0% of deaths were among those aged 60 years or higher and that the risk of death increases with age [5].

Excluding those who were unemployed, most patients were engaged in agricultural work (31.6%), which was associated with the highest risk for exposure (49.7%). These results are consistent with those of previous research, which showed that agricultural workers are at high risk and suggested the need for continuing education for older agricultural workers [9]. Many patients appeared to be unemployed, with the rate of unemployment by age ranging from 21.1% among those aged 40 to 59 years, 26.4% for those aged 60 to 69 years, and 40.2% among those aged 70 years or higher. Many of the older patients were estimated to be unemployed, and it should be investigated whether such reports were made for convenience during the input process of the epidemiological survey. It is also necessary to consider revising the epidemiological survey for more accurate job group classification and analysis.

In addition to agricultural work, hiking, walking, and camping were identified as significant risk factors for exposure. In terms of exposure in confirmed cases, 17 cases were attributed to exposure due to hiking, walking, and camping in 2021. Similar findings were reported for 16 cases in 2022; therefore, a review of publicity materials is planned to prevent tick-borne diseases among individuals engaging in outdoor activities.

Although the risk of death was significantly higher if a patient experienced hematuria, additional studies are needed to confirm this because there were only few such cases. Since many patients report a fever, fatigue, digestive system symptoms, and neurological symptoms, medical institutions should consider SFTS and administer treatment accordingly if a patient has engaged in outdoor activities and complains of the above clinical symptoms.

Patients with underlying diseases had a 2.96-fold higher risk of death (95% CI, 1.35–6.48) than those without underlying conditions; this finding was consistent with those of previous studies [10]. The risk of death in patients with diabetes was 2.75-fold higher (95% CI, 1.19–6.37); this finding was consistent with those of previous studies showing that SFTS infection along with underlying diseases such as diabetes increases oxidative stress, worsening the prognosis [11,12]. Further research is needed on the extent and developmental mechanisms of underlying conditions corresponding to high-risk groups.

Finally, SFTS management requires a ‘One Health’ approach, because cases of transmission from animals to humans have been reported abroad [1,4], and there is a risk of transmission. To this end, the human-animal SFTS monitoring system has been established and operational, and there are plans for it to be continuously pursued and managed.

Since SFTS is an infectious disease with a high mortality rate without vaccines or treatment to date, it is necessary to avoid exposure to ticks. As shown in this study, older agricultural workers and individuals engaging in outdoor activities from April to November, when SFTS occurs, are at high risk, and they are recommended to wear appropriate work attire and use tick repellents. After outdoor activities, it is crucial to take a bath or shower and thoroughly check that there is no Ixodidae on the body. It is also essential to visit a medical institution for diagnostic tests and early treatment when fever and digestive system symptoms appear within 14 days of outdoor activities.

Ethics Statement: Not applicable.

Funding Source: None.

Acknowledgments: None.

Conflict of Interest: The authors have no conflicts of interest to declare.

Author Contributions: Conceptualization: JC, JH, HL, KH. Data curation: JC, JH. Formal analysis: JC, JH, HL, KH. Investigation: JC, JH. Methodology: JC, KH. Project administration: HL, KH. Resources: JC, JH. Supervision: HL, KH. Visualization: JC. Writing – original draft: JC. Writing – review & editing: HL, KH.