INTRODUCTION
Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne zoonotic infectious disease. The causative agent is a bandavirus (Dabie bandavirus), commonly known as severe fever with thrombocytopenia syndrome virus (SFTSV). This virus is also referred to as “Huaiyangshan banyangvirus,” “SFTS bunyavirus,” or “SFTS phlebovirus.” It belongs to the genus Phlebovirus within the family Phenuiviridae of the order Buyavirales.1 Since the first isolation and report of SFTSV in China in 2009, the virus has been documented in several other countries in Asia.2
Severe fever with thrombocytopenia syndrome virus is primarily transmitted to humans through the bite of the tick Haemaphysalis longicornis, which is widely distributed in East Asia. Transmission can also occur through contact with blood, saliva, nasal discharge, or urine from infected animals.3–6 Additionally, SFTSV can be found in various vertebrate reservoirs, including in mammals, such as carnivores, rodents, ungulates, and insectivores, and in birds.4,5,7
The clinical presentation of SFTS often resembles an acute undifferentiated febrile illness, with signs and symptoms overlapping with other tropical diseases, such as rickettsiosis.8 This overlap can delay diagnosis and treatment, increasing the risk of mortality. Despite the availability of an antiviral proven to be effective against SFTSV infection, awareness of the disease remains limited, primarily because of its recent discovery and the relative low number of documented cases. With its high case fatality rates (CFRs) from delayed treatment in high-risk groups, broad host range, and wide geographic distribution, SFTS is an emerging viral disease that poses an alarming public health risk. Increased awareness and information about the disease are essential for effective prevention and management. This review focuses on epidemiological characteristics of SFTSV infection in humans.
SEARCH STRATEGY
We accessed articles published until February 14, 2024 through PubMed and Scopus. We included research articles that focused on the epidemiology and characteristics of SFTSV infection. Exclusion was applied to review articles, correspondences, perspectives, letters, book chapters, nonhuman studies, and non-English publications. No formal review protocol was registered for this review. The search strategy is shown in Supplemental Table 1.
RESULTS
A total of 2,925 articles were initially identified. After removing duplicates and excluded articles, 73 articles met the inclusion criteria. Additionally, 3 more articles were identified through direct search, bringing the total to 76 articles for this review. The screening process is shown in Figure 1. Supplemental Table 2 provides a summary of all included studies.
Screening process. SFTS = severe fever with thrombocytopenia syndrome.
Citation: The American Journal of Tropical Medicine and Hygiene 112, 5; 10.4269/ajtmh.24-0616
Epidemiology of SFTS.
Severe fever with thrombocytopenia syndrome is endemic to East Asia, including China, South Korea, and Japan.9–11 Although the first case of SFTS was described in 2009, several clusters of patients with symptoms like those of SFTS in China (most were clinically diagnosed with human anaplasmosis) were retrospectively tested positive for SFTSV antibody and RNA.12,13 Thus, the disease may have been emerging in these areas long before the identification of SFTS. Following the emergence of SFTS in 2009, it was rapidly reported to neighboring provinces in China, South Korea, and Japan, with infections also reported in Myanmar, Thailand, Vietnam, and Pakistan.10,14–17 Figure 2 illustrates the epidemiological map of SFTS.
Epidemiological maps of severe fever with thrombocytopenia syndrome. (A) China. (B) South Korea. (C) Japan.
Citation: The American Journal of Tropical Medicine and Hygiene 112, 5; 10.4269/ajtmh.24-0616
East Asia.
China.
The distribution of SFTS in China is primarily concentrated in the central and eastern regions of the country.10,18,19 Patterns of SFTS distribution in China have been observed to occur in clusters, particularly in provinces such as Jiangsu, Liaoning, Shandong, Zhejiang, Anhui, Henan, and Hubei.10,13,20–23 These clusters often share similar hilly and mountainous landscapes.10 Between 2010 and 2019, China reported a total of 13,824 SFTS cases, with 64.4% of them being laboratory confirmed.23 The seroprevalence of SFTSV in China ranges from 0.3% to 20.2%, with many infections remained undiagnosed or asymptomatic.12,24–40 The incidence of SFTS has significantly increased, and its distribution areas have expanded over the years.10,18,23,41–45 The average incidence of SFTS varies greatly across different regions, ranging from less than 0.1 to 4.2 cases per 100,000 population.10,18,20,41,44–51 In certain areas, the incidence can be exceptionally high, reaching up to 127.6 cases per 100,000 population.43 Although the disease is predominantly found in hilly and mountainous areas, the highest incidences and seroprevalences have been reported in coastal and island regions, such as the Dachen Islands off the coast of Zhejiang.27,33,43 The seroprevalence of SFTSV on Dachen Islands was approximately 3.0–4.8%, exceeding that of several mainland areas.27,33
South Korea.
The seroprevalence of SFTSV in humans in South Korea ranged from 0.2% to 5.9%.11,52–57 The seroprevalence was higher on islands than on the mainland as evidenced by the rates on Jeju Island (2.4%) and Mui Island (5.9%).56,57 Among veterinary hospital staff, the seroprevalence ranged from approximately 1.9% to 3.9%.58 The overall incidence of SFTS was 0.1 cases per 100,000 population, with most cases reported in the eastern and southern regions, including Jeju Island.59,60 In the northeastern province of Gangwon, a highly prevalent region, the incidence ranged from 0.3 to 8.0 per 100,000 population.60,61 On Jeju Island, the incidence was sometimes reported to be the highest in South Korea, reaching 1.3 cases per 100,000 population.60 This high incidence on Jeju Island can be attributed to the predominantly agricultural occupations of the island’s inhabitants as well as the wide range of farmlands and natural habitats suitable for tick habitation.57
Japan.
Seroprevalence of SFTSV in Japan ranged from 0.0% to 4.2%.9,62–67 Samples from donated blood showed seroprevalence rates as low as 0.0%, indicating a low rate of infection among the general population.63,66 However, higher seroprevalence rates were found in veterinarian personnel, ranging from 2.2% to 4.2%.65,66 The incidence of SFTS in Japan was fewer than 0.1 cases per 100,000 population.68,69 Cases were predominantly reported from the western part of Japan, attributed to its mountainous areas.63,68
Other regions in Asia.
Severe fever with thrombocytopenia syndrome virus infections have also been reported in various regions outside the Far East. In Myanmar, studies conducted in two cities revealed that 3.3% of patients suspected of having rickettsiosis were infected with SFTS.14 In Vietnam, seroprevalence studies showed that 3.6% of residents showed evidence of past exposure to SFTSV.15 Additionally, sporadic reports of SFTSV infection have also been reported in Thailand, where affected patients lived in urban and suburban areas and had no history of travel to forested area before the onset of symptoms.16 Reports from Pakistan indicate a wide range of seroprevalence among farmers: from 2.5% to 46.7%.17
Epidemiological characteristics of SFTSV infection.
Severe fever with thrombocytopenia syndrome cases in endemic areas are typically heightened during April and December.10,13,19,20,22,23,41,42,50,59,60,68–75 Severe fever with thrombocytopenia syndrome virus seropositivity rates are higher in rural areas compared with urban settings.52 The majority of confirmed SFTS cases are farmers, with seroprevalence rates among farmers higher than in the general population because of more frequent exposure to ticks.12,13,18,20,23,31,42,45,46,53,67,68,71,74–78 Agricultural activities as well as longer working hours on farmlands are associated with SFTSV seropositivity.34
As a tick-borne disease, environmental exposures that increase the risk of tick bites—such as engaging in outdoor activities and working or residing in areas with vegetation, such as forested regions, tea plantations, and hilly areas—pose risks for SFTSV infection.13,21,24,31,38,39,43,46,68–70,72,76–79 The presence of animals that are susceptible for SFTSV infection, such as rats and cats, as well as high densities of goats and cattle in living areas further increase the risk of SFTSV infection.13,18,21,25,26,34,38,41,72,77,79 The seroprevalences observed in wild and domesticated animals were 45.7–66.8% in goats, 13.2–36.7% in cattle, 33.1% in cats, 7.4–29.5% in dogs, 25.0% in wild boar, 25.0% in deer, 3.2–4.7% in pigs, 3.2–4.4% in rodents, 2.7% in hedgehogs, 1.7% in geese, and 1.2–9.6% in chickens.8,9,29,34,65 In coastal areas of China, living on islands is associated with SFTSV seropositivity and higher incidence rates.33,43 This high incidence on islands may be because of the dense forest environments, such as on Dachen Island, which provide a suitable habitat for ticks and intensify the transmission of SFTSV to animals and humans.33,43
Direct contact with animals and livestock is associated with SFTSV infection, with some infected people, particularly among veterinarian personnel, having directly contacted the body fluids of cats and dogs.31,69 Person-to-person transmission of SFTSV is possible through direct contact with infected patients’ body fluids, such as blood, or through exposure to corpses.7,19,22,80 Face-to-face exposures within 50 cm or exposure times of 30 minutes or longer with the patient increase the risk of transmission.81 Seroprevalence rates are higher among family members or individuals living in the same household as the index patient compared with those who did not have such close contact.19,25,82 The transmission modes of SFTSV are shown in Figure 3.
Transmission modes of severe fever with thrombocytopenia syndrome virus. (A) Tick bite. (B) Contact with infected animal’s blood and body fluid. (C) Contact with patient’s blood and body fluid.
Citation: The American Journal of Tropical Medicine and Hygiene 112, 5; 10.4269/ajtmh.24-0616
The incidence and fatality rates of SFTS typically increase with age, with most cases occurring in elderly individuals, likely reflecting the distribution of elderly populations in rural areas.12,13,17–21,23,27,38,41,42,45,46,51–53,56,59,67,68,70,71,73,74 The incidence rate in individuals over 40 years old is notably higher, suggesting that older individuals are more susceptible to severe clinical symptoms requiring medical attention compared with younger individuals.51 However, the seroprevalence of SFTSV does not differ significantly by age group, indicating that the higher incidence in elderly individuals may be attributed to the more severe clinical symptoms experienced by this demographic.51 Despite increasing incidence, the CFRs have been decreasing in recent years in China and South Korea.23,31,41,59,61,71,74,83 This decline in CFRs is attributed to several factors, including the expansion of surveyed populations from only hospitalized patients to nationwide populations in recent years along with improved diagnostic methods and an increase in the use of plasma exchange and ribavirin treatments.59,83,84 These advancements also enhance the ability to recognize early-stage infections, contributing to better management and outcomes.84
Gender may also play a role in SFTS risk, with some studies indicating a higher prevalence in females compared with males, possibly because of factors such as increased tick exposure during agricultural activities, heightened susceptibility to developing the disease after infection, or reporting biases owing to more frequent doctor visits after symptom onset.10,17,23,41,53,83 Conversely, some studies have suggested that male gender is associated with SFTS because of longer periods spent in farming areas, which subsequently heighten the risk of tick exposure.34,48 Variations in sample composition and the geographic regions from which data were collected may account for these differences.23 For instance, a study in Liaoning, China had a higher proportion of male than female samples,48 whereas in Henan, China, more females were involved in tea farming, which may influence the gender ratio of SFTSV infections in that area.8,10 Characteristics of SFTSV infection are presented in Table 1.
Characteristics of SFTSV infection
| Type of Case/Population | Risk Factors of SFTS |
|---|---|
| Farmers |
|
| Veterinary staffs |
|
| Secondary SFTS cases |
|
SFTS = severe fever with thrombocytopenia syndrome.
CONCLUSION
The incidence of SFTS shows an increasing trend and the spread to wider geographic areas. High incidence rates are observed in rural and island regions, particularly in China and South Korea. Most infected people are elderly farmers who are frequently exposed to ticks through contact with domesticated animals or vegetations. The virus can spread through the saliva, nasal discharge, urine, and blood of infected animals and humans, putting veterinarians, health care workers, and close contacts at risk. A One Health approach, including surveillance of both humans and animals in endemic regions and raising awareness about preventive measures, is important.
Supplemental Materials
ACKNOWLEDGMENTS
We extend our heartfelt gratitude to the highly respected faculty members Watcharapong Piyaphanee, Wasin Matsee, and Udomsak Silachamroon. Their commitment to fostering an environment of academic excellence and their encouragement significantly contributed to the publication of this review. The APC was funded by ROHTO Pharmaceutical Co., Ltd. The sponsor had no involvement in the study design, literature review, or interpretation of the findings presented in this manuscript.
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