Severe Fever With Thrombocytopenia Syndrome Research Articles

Immune escape mechanisms of severe fever with thrombocytopenia syndrome virus.

Severe fever with thrombocytopenia syndrome (SFTS), which is caused by SFTS virus (SFTSV), poses a serious threat to global public health, with high fatalities and an increasing prevalence. As effective therapies and prevention strategies are limited, there is an urgent need to elucidate the pathogenesis of SFTS. SFTSV has evolved several mechanisms to escape from host immunity. In this review, we summarize the mechanisms through which SFTSV escapes host immune responses, including the inhibition of innate immunity and evasion of adaptive immunity. Understanding the pathogenesis of SFTS will aid in the development of new strategies for the treatment of this disease.

Susceptibility of Type I Interferon Receptor Knock-Out Mice to Heartland Bandavirus (HRTV) Infection and Efficacy of Favipiravir and Ribavirin in the Treatment of the Mice Infected with HRTV.

Heartland bandavirus (HRTV) is an emerging tick-borne virus that is distributed in the United States and that causes febrile illness with thrombocytopenia and leukocytopenia. It is genetically close to Dabie bandavirus, which is well known as severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV). The mortality rate of human HRTV infection is approximately 10%; however, neither approved anti-HRTV agents nor vaccines exist. An appropriate animal model should be developed to evaluate the efficacy of antiviral agents and vaccines against HRTV. The susceptibility of IFNAR−/− mice with HRTV infection was evaluated using subcutaneous, intraperitoneal, and retro-orbital inoculation routes. IFNAR−/− mice intraperitoneally infected with HRTV showed the most severe clinical signs, and the 50% lethal dose was 3.2 × 106 TCID50. Furthermore, to evaluate the utility of a novel lethal IFNAR−/− mice model, IFNAR−/− mice were orally administered favipiravir, ribavirin, or a solvent for 5 days immediately after a lethal dose of HRTV inoculation. The survival rates of the favipiravir-, ribavirin-, and solvent-administered mice were 100, 33, and 0%, respectively. The changes in bodyweights and HRTV RNA loads in the blood of favipiravir-treated IFNAR−/− mice were the lowest among the three groups, which suggests that favipiravir is a promising drug candidate for the treatment of patients with HRTV infection.

Overview of the immunological mechanism underlying severe fever with thrombocytopenia syndrome (Review)

Severe fever with thrombocytopenia syndrome (SFTS) has been acknowledged as an emerging infectious disease that is caused by the SFTS virus (SFTSV). The main clinical features of SFTS on presentation include fever, thrombocytopenia, leukocytopenia and gastrointestinal symptoms. The mortality rate is estimated to range between 5-30% in East Asia. However, SFTSV infection is increasing on an annual basis globally and is becoming a public health problem. The transmission cycle of SFTSV remains poorly understood, which is compounded by the pathogenesis of SFTS not being fully elucidated. Since the mechanism underlying the host immune response towards SFTSV is also unclear, there are no effective vaccines or specific therapeutic agents against SFTS, with supportive care being the only realistic option. Therefore, it is now crucial to understand all aspects of the host-virus interaction following SFTSV infection, including the antiviral states and viral evasion mechanisms. In the present review, recent research progress into the possible host immune responses against SFTSV was summarized, which may be useful in designing novel therapeutics against SFTS.

High levels of C-reactive protein-to-albumin ratio (CAR) are associated with a poor prognosis in patients with severe fever with thrombocytopenia syndrome in early stage.

C‐reactive protein‐to‐albumin ratio (CAR) can be used to assess the prognosis of various diseases. This study aimed to evaluate the relationship between CAR on the prognosis of patients with severe fever with thrombocytopenia syndrome (SFTS). This study included 155 SFTS patients from the Public Health Clinical Center of Dalian from January to December 2021. They were divided into survival and deceased groups based on the clinical prognosis. The independent risk factors for poor prognosis of SFTS patients at an early stage were determined by Cox regression. The efficacy of CAR prediction was assessed by the receiver operating characteristic (ROC) curve. A total of 155 patients were included in this study, with an average age of 61.98± 11.70 years, including 77 males and 65 females. The mortality rate of the patients enrolled in this study was 14.19%. Multivariate Cox regression indicated that CAR (hazard ratio = 2.585, 95% confidence interval [CI] 1.405–4.753, p = 0.002) could be an independent predictor for prognosis in SFTS patients at an early stage. CAR had an AUC of 0.781 (95% CI, 0.665–0.898, p = 0.000), a cutoff value of 0.57, a sensitivity of 0.77, and a specificity of 0.80, with better predictive efficacy, compared to neutrophil‐to‐lymphocyte ratio (NLR). High levels of CAR are associated with poor prognosis in SFTS patients, and CAR can be used as an independent predictor for SFTS patients.

Effects of corticosteroid treatment in patients with severe fever with thrombocytopenia syndrome: A single-center retrospective cohort study

ObjectivesTo evaluate the effect and safety of corticosteroid (CS) treatment in patients with severe fever with thrombocytopenia syndrome (SFTS). MethodsPatients with and without CS were retrospectively compared by Cox regression and 1:1 propensity score matching analysis to evaluate the effects of CS on mortality and secondary infections in patients with SFTS. ResultsA total of 467 patients with SFTS were enrolled in the cohort study, there were 52 fatal cases and 415 nonfatal cases, the overall fatality rate was 11.1%. The mortality was observed in 36/144 (25%) and 16/323 (5%) patients in the CS-treated and non-CS-treated groups, respectively (P < 0.001). Multi variate Cox regression analysis showed that the difference was not statistically significant for CS treatment in fatality (P > 0.05, aHR 0.767, 95% CI 0.360-1.634). Difference in survival time between the CS-treated and non-CS-treated groups after propensity score matching had no statistical significance (Log-rank test P = 0.390), whereas there was a significant difference in secondary infections between the CS-treated and non-CS-treated groups (P = 0.007). ConclusionAlthough the CS treatment had no impact on fatality in patients with SFTS, it increased the risk of secondary infections. Administration of CS in patients with SFTS should be carefully considered and evaluated the balance between therapeutic efficacy and adverse effects.

Clinical features and significance of coagulation dysfunction in severe fever with thrombocytopenia syndrome

To analyze the changes of coagulation function in severe fever with thrombocytopenia syndrome (SFTS) and its relationship with thrombocytopenia, and to explore its value as an early predictor of the severity of SFTS. The clinical data of 428 SFTS patients (70 deaths and 358 survivors) admitted to the Department of Infectious Disease at Wuhan Union Hospital from January 2014 to July 2020 were retrospectively analyzed. The differences of coagulation parameters and disseminated intravascular coagulation (DIC) scores between the two groups were compared. The results showed that abnormal coagulation function was commonly presented in SFTS patients. Bleeding was more frequent in mortality group (41.4% vs. 26.5%). The D-dimer levels in mortality patients were significantly higher above normal range. Activated partial thrombin time (APTT) and thrombin time (TT) were significantly prolonged. The levels of prothrombin time (PT), TT, APTT, international standardized ratio (INR) and D-dimer between mortality group and survival group started to separate from day 5-6. The difference of fibrinogen (FIB) level developed on day 7-8, while platelet counts between the two groups were significant different from day 9-10. The mortality rate increased according to the increase of baseline DIC score. When DIC score reached 6, the mortality rate surged to 66.67%. Excessive platelet consumption is mediated by significant coagulation abnormalities during disease course, and coagulation parameters are more sensitive than platelet count as an early predictor of severe SFTS.

Seroprevalence of Severe Fever with Thrombocytopenia Syndrome Virus in Mui Island, Rural Area, Incheon, South Korea

The rural areas are the main outbreak sites of severe fever with thrombocytopenia syndrome (SFTS). To identify the seroprevelance of SFTS in rural island, we conducted a serosurveillance study of SFTS virus (SFTSV) of the general public in Mui Island, a representative rural island of Incheon, South Korea. A total of 203 participants (female 127, male 76, 30 to 97 years old, median 67) without symptoms or signs of SFTS were collected via a convenience sampling. Nested reverse transcription PCR was conducted for both the S and M segments of SFTSV gene. Indirect immunofluorescence assay was also performed for immunoglobulin G (IgG) and immunoglobulin M (IgM) against SFTSV. Only 1 participant (0.5%) was positive to SFTSV gene without IgM against SFTSV. In addition, 12 participants (5.9%) were positive to IgG against SFTSV. Seropositive rate of IgG against SFTSV was higher in age group >65 than ≤65 (9.6% vs. 1.1%, OR 9.202; 95% CI, 1.165–72.692; p=0.026) and was not statistically significant according to sex, occupation and duration of residence in Mui Island. This study suggests that SFTSV readily have infected humans in the rural island of Incheon, South Korea. Therefore, reinforced surveillance about SFTS is needed, focusing on medically vulnerable area such as an island.

The Endless Wars: Severe Fever With Thrombocytopenia Syndrome Virus, Host Immune and Genetic Factors

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging arboviral infectious disease with a high rate of lethality in susceptible humans and caused by severe fever with thrombocytopenia syndrome bunyavirus (SFTSV). Currently, neither vaccine nor specific antiviral drugs are available. In recent years, given the fact that both the number of SFTS cases and epidemic regions are increasing year by year, SFTS has become a public health problem. SFTSV can be internalized into host cells through the interaction between SFTSV glycoproteins and cell receptors and can activate the host immune system to trigger antiviral immune response. However, SFTSV has evolved multiple strategies to manipulate host factors to create an optimal environment for itself. Not to be discounted, host genetic factors may be operative also in the never-ending winning or losing wars. Therefore, the identifications of SFTSV, host immune and genetic factors, and their interactions are critical for understanding the pathogenic mechanisms of SFTSV infection. This review summarizes the updated pathogenesis of SFTS with regard to virus, host immune response, and host genetic factors to provide some novel perspectives of the prevention, treatment, as well as drug and vaccine developments.

Nonstructural Protein NSs Activates Inflammasome and Pyroptosis through Interaction with NLRP3 in Human Microglial Cells Infected with Severe Fever with Thrombocytopenia Syndrome Bandavirus.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne febrile disease caused by SFTS virus (SFTSV), or Dabie bandavirus, in the Phenuiviridae family. Clinically neurological disorders in SFTS have been commonly reported, but their neuropathogenesis has rarely been studied. Microglia are a type of neuroglia accounting for 10 to 12% of all cells in the brain. As resident immune cells, microglial cells are the first line of immune defense present in the central nervous system (CNS). Here, we report that SFTSV was able to infect microglial cells and stimulate interleukin 1β (IL-1β) secretion in the brains of infected neonatal BALB/c mice. We characterized the cell death induced in infected human microglial HMC3 cells, also susceptible to SFTSV, and found that the NOD-like receptor protein 3 (NLRP3) inflammasome was activated, leading to secretion of IL-1β and pyroptosis. Knockdown of NLRP3 or inhibition of the NLRP3 inflammasome activation suppressed the viral replication, suggesting that the activation of the NLRP3 inflammasome may support SFTSV replication in microglial cells. Viral nonstructural protein NSs, a known modulator of immune responses, interacted and colocalized with NLRP3 for the inflammasome activation. It appeared that the N-terminal fragment, amino acids 1 to 66, of NSs was critical to promote the assembly of the inflammasome complex by interacting with NLRP3 for its activation in microglial cells. Our findings provide evidence that SFTSV may cause neurological disorders through infecting microglia and activating the inflammasome through its nonstructural protein NSs for neural cell death and inflammation. This study may have revealed a novel mechanism of SFTSV NSs in dysregulating host response. IMPORTANCE Encephalitis or encephalopathy during severe fever with thrombocytopenia syndrome (SFTS) is considered a critical risk factor leading to high mortality, but there have been no studies to date on the pathogenesis of encephalitis or encephalopathy caused by SFTS virus. Here, we report that SFTSV infection can active the NLRP3 inflammasome and induce IL-1β secretion in the brains of infected newborn mice. In infected human HMC3 microglia, SFTSV activated the NLRP3 inflammasome via the viral nonstructural protein NSs through interaction with its N-terminal fragment. Notably, our findings suggest that the activation of the NLRP3 inflammasome may promote SFTSV replication in infected microglial cells. This study may reveal a novel mechanism by SFTSV to dysregulate host responses through its nonstructural protein, which could help us understand viral neuropathogenesis in SFTS patients.

Epidemiological characteristics of severe fever with thtrombocytopenia syndrome in China, 2011-2021

Objective: To analyze the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in China from 2011 to 2021, and provide evidence for the prevention and control of SFTS. Methods: The incidence data of SFTS were collected from the National Disease Reporting Information System of Chinese Center for Disease Control and Prevention for a descriptive epidemiological analysis and Cochran-Armitage trend test was used to evaluate the association between age and the morbidity rate and case fatality rate (CFR) of SFTS. Results: From 2011 to 2021, a total of 18 902 laboratory confirmed cases of SFTS, including 966 deaths, were reported in 533 counties (districts) of 154 prefecture-level cities in 27 provinces. The annual average morbidity rate was 0.125/100 000, and the annual average CFR was 5.11%. From 2011 to 2021 the overall morbidity rate of SFTS was in increase with an average annual percentage change (AAPC) of 14.80% (P=0.001). Most cases (99.23%) occurred in 7 provinces, including Shandong, Henan, Anhui, Hubei, Liaoning, Zhejiang and Jiangsu, with 70.28% of the cases in 11 prefecture-level cities. The average annual CFRs in the 7 provinces varied greatly from 1.30% to 11.27%. In 2011, SFTS cases were reported in 108 counties (districts) of 51 prefecture-level cities in 13 provinces, but SFTS cases were reported in 277 counties (districts) of 88 prefecture-level cities in 19 provinces in 2021, the disease spread from central area to the northeast and from the west and the south. SFTS mainly occurred in summer and autumn in both southern and northern China, and 96.63% of the cases were reported from April to October, and the incidence peak was during May-June. The cases mainly occurred in age group 50-74 years (69.46%), and the deaths mainly occurred in age group ≥60 years (79.71%). Both the morbidity rate and the CFR increased with age. The morbidity rate increased from 0.040/100 000 in age group 0-4 years to 4.480/100 000 in age group ≥80 years in males (χ²=13 185.21, P<0.001) and from 0.038/100 000 in age group 0-4 years to 3.318/100 000 in age group ≥80 years in females (χ²=12 939.83, P<0.001); the CFR increased from 0.70% in age group 30-34 years to 11.58% in age group ≥80 years in males (χ²=115.70, P<0.001) and from 1.56% in age group 35-39 years to 8.98% in age group ≥80 years in females (χ²=103.42, P<0.001). Conclusion: From 2011 to 2021, the incidence of SFTS increased in China, and the spread and obvious spatiotemporal distribution of SFTS were observed. The reported CFR varied greatly with area, and both the morbidity and mortality risk were high in the elderly.

Stability and Bifurcation Analysis of a Discrete Severe Fever with Thrombocytopenia Syndrome Model

Severe fever with thrombocytopenia syndrome (SFTS) is an acute tick-borne disease caused by SFTS virus (SFTSV). In this paper, we use difference equations to establish a discrete tick-borne disease model with systemic and transovarial transmission. Using the method of the next generation of matrix, we get the basic reproduction number [Formula: see text] to determine whether SFTS will die out. Furthermore, we analyze the existence and stability of equilibrium points by [Formula: see text]. In addition, the transcritical bifurcation property at the disease-free equilibrium point is discussed by deriving a equation describing the flow on the center manifold. Finally, we perform numerical simulations to verify the theoretical results.

Clinical Characteristics and Immune Status of Patients with Severe Fever with Thrombocytopenia Syndrome.

Severe fever with thrombocytopenia syndrome (SFTS) is a novel infectious disease caused by bunya virus. The purpose of this study was to investigate the clinical characteristics of SFTS patients and their virus-related immune disorders in vivo. Patients with SFTS admitted to Nanjing Drum Tower Hospital from 2017 to 2020 were retrospectively analyzed, and divided into survival group and death group according to the 28-day survival. Clinical characteristics and laboratory examination results of SFTS patients were recorded, and dynamic changes of immune function and inflammatory factors were statistically analyzed. Prolonged activated prothrombin time (APTT) (p = 0.001), high viral load (p = 0.001), and elevated human leukocyte antigen DR (HLA-DR) level (p = 0.002) were independent prognostic risk factors for SFTS patients. Compared to the survival group, the nonsurvival group was more prone to hemorrhagic and neurological symptoms (p < 0.05). Natural kill (NK) cell count, interleukin-10, interferon-α, and tumor necrosis factor-α scores in the nonsurvival group continued to increase after admission, while CD3+ T, CD4+ T, and CD8+ T cell counts continued to decrease. CD3+ T lymphocyte count was negatively correlated with viral load (R = 0.3883, p < 0.001), CD4+ T lymphocyte count was negatively correlated with viral load (R = 0.28933, p < 0.001), CD8+ T lymphocyte count was negatively correlated with viral load (R = 0.781, p < 0.001), and HLA-DR was positively correlated with viral load (R = 0.489, p < 0.001). High viral load, prolonged APTT time, and elevated HLA-DR level are independent prognostic risk factors for SFTS patients. The T lymphocyte subsets of SFTS patients continue to decrease after infection, and the number of T lymphocyte subsets can reflect the severity of the disease.

Severe Fever with Thrombocytopenia Syndrome, a Viral Hemorrhagic Fever, Endemic to Japan: Achievements in and Directions for Medical Research.

Severe fever with thrombocytopenia syndrome (SFTS), a novel infectious disease caused by a novel bunyavirus and with a high case fatality rate (CFR), was reported by Chinese scientists in 2011. The causative virus, Dabie bandavirus also known as the SFTS virus (SFTSV), belongs to the genus Bandavirus (formerly named Phlebovirus) of the family Phenuiviridae (formerly named Bunyaviridae). SFTS was also reported to be endemic in South Korea and Japan in 2013. SFTSV circulates between some species of ticks and animals in nature. Humans are infected with SFTSV through bites from ticks such as Haemaphysalis longicornis and Amblyomma testidinarium. Domesticated animals, such as cats and dogs, are also infected with SFTSV and shown SFTS-like symptoms with a high CFR, likely having been infected through tick bites in the living environment. Furthermore, there have been cases of patients with SFTS who were infected with SFTSV through close contact with sick cats or dogs. The CFR in patients with SFTS is approximately 30% in Japan. There is always a risk of SFTSV infection in human populations living in endemic areas. Therefore, the development of specific therapies and vaccines is urgently needed to reduce the number of fatal SFTS cases.

Infection Route Impacts the Pathogenesis of Severe Fever with Thrombocytopenia Syndrome Virus in Ferrets.

The threat of severe fever with thrombocytopenia syndrome (SFTS) to public health has been increasing due to the rapid spread of the ticks that carry the causative viral agent. The SFTS virus (SFTSV) was first identified in China and subsequently detected in neighboring countries, including South Korea, Japan, and Vietnam. In addition to the tick-mediated infection, human-to-human transmission has been recently reported with a high mortality rate; however, differential study of the pathogen has been limited by the route of infection. In this study, we investigated the pathogenic potential of SFTSV based on the infection route in aged ferrets, which show clinical signs similar to that of human infections. Ferrets inoculated with SFTSV via the intramuscular and subcutaneous routes show clinical signs comparable to those of severe human infections, with a mortality rate of 100%. Contrastingly, intravascularly infected ferrets exhibit a comparatively lower mortality rate of 25%, although their early clinical signs are similar to those observed following infection via the other routes. These results indicate that the infection route could influence the onset of SFTS symptoms and the pathogenicity of SFTSV. Thus, infection route should be considered in future studies on the pathogenesis of SFTSV infection.

Expansion of granulocytic myeloid-derived suppressor cells in patients with severe fever with thrombocytopenia syndrome.

Severe fever with thrombocytopenia syndrome (SFTS), caused by novel bunyavirus (SFTSV), is a hemorrhagic fever with a high mortality rate of over 10%. We have previously shown that granulocytic myeloid-derived suppressor cell (gMDSC) might affect arginine metabolism, which was associated with decreased platelet count and T lymphocyte dysfunction in this disease. The study was designed to investigate the expression of the gMDSCs subsets in SFTS patients, and to evaluate its association with disease severity. A prospective study was performed on 166 confirmed SFTSV infected patients. Sequential blood samples were collected during hospitalization and after recovery. SFTSV RNA was quantified by real-time RT-PCR. The gMDSCs and NK cells were determined by flow cytometry analysis, which were associated with disease severity. Elevation of the activated gMDSC was observed in SFTS patients at the acute phase, with a significantly higher level of gMDSC attained in 79 severe and 29 fatal SFTS patients than in the mild patients. The NK cells were depleted at the early infection and not restored to normal level until 4 months after the disease. The expansion of gMDSC was accompanied by the elevated expressions of CD3-ζ of NK and Arginase-1, in contrast with the decreased reactive oxygen species(ROS) in gMDSC. The levels of NK, CD3-ζ of NK, viral load, and platelet count were significantly associated with the level of gMDSC. Expansion of gMDSC was demonstrated in SFTS, which was associated with severe disease and suppressed antiviral NK cell via other mechanisms than Arginase-1 or ROS.

The role of selenium in severe fever with thrombocytopenia syndrome: an integrative analysis of surveillance data and clinical data

ObjectivesSelenium deficiency can be associated with increased susceptibility to some viral infections and even more severe diseases. In this study, we aimed to examine whether this association applies to severe fever with thrombocytopenia syndrome (SFTS). MethodAn observational study was conducted based on the data of 13,305 human SFTS cases reported in mainland China from 2010 to 2020. The associations among incidence, case fatality rate of SFTS, and crop selenium concentration at the county level were explored. The selenium level in a cohort of patients with SFTS was tested, and its relationship with clinical outcomes was evaluated. ResultsThe association between selenium-deficient crops and the incidence rate of SFTS was confirmed by multivariate Poisson analysis, with an estimated incidence rate ratio (IRR, 95% confidence interval [CI]) of 4.549 (4.215−4.916) for moderate selenium-deficient counties and 16.002 (14.706−17.431) for severe selenium-deficient counties. In addition, a higher mortality rate was also observed in severe selenium-deficient counties with an IRR of 1.409 (95% CI: 1.061−1.909). A clinical study on 120 patients with SFTS showed an association between serum selenium deficiency and severe SFTS (odds ratio, OR: 2.94; 95% CI: 1.00–8.67) or fatal SFTS (OR: 7.55; 95% CI: 1.14–50.16). ConclusionSelenium deficiency is associated with increased susceptibility to SFTS and poor clinical outcomes.

Development of a Scoring System to Differentiate Severe Fever with Thrombocytopenia Syndrome from Scrub Typhus.

Severe fever with thrombocytopenia syndrome (SFTS) and scrub typhus are disorders with similar clinical features; therefore, differentiating between them is difficult. We retrospectively collected data from 183 SFTS and 178 scrub typhus patients and validated an existing scoring system to develop a more sensitive, specific, and objective scoring system. We first applied the scoring systems proposed by Kim et al. to differentiate SFTS from scrub typhus. Multivariable logistic regression revealed that altered mental status, leukopenia, prolonged activated partial thromboplastin time (aPTT), and normal C-reactive protein (CRP) level (≤1.0 mg/dL) were significantly associated with SFTS. We changed the normal CRP level from ≤1.0 mg/dL to ≤3.0 mg/dL and replaced altered mental status with the creatine kinase (CK) level. The modified scoring system showed 97% sensitivity and 96% specificity for SFTS (area under the curve (AUC): 0.983) and a higher accuracy than the original scoring system (p = 0.0308). This study’s scoring system had 97% sensitivity and 98% specificity for SFTS (AUC: 0.992) and a higher accuracy than Kim et al.’s original scoring system (p = 0.0308). Our scoring system that incorporated leukopenia, prolonged aPTT, normal CRP level (≤3.0 mg/dL), and elevated CK level (>1000 IU/L) easily differentiated SFTS from scrub typhus in an endemic area.

Meteorological factors and tick density affect the dynamics of SFTS in jiangsu province, China.

This study aimed to explore whether the transmission routes of severe fever with thrombocytopenia syndrome (SFTS) will be affected by tick density and meteorological factors, and to explore the factors that affect the transmission of SFTS. We used the transmission dynamics model to calculate the transmission rate coefficients of different transmission routes of SFTS, and used the generalized additive model to uncover how meteorological factors and tick density affect the spread of SFTS. In this study, the time-varying infection rate coefficients of different transmission routes of SFTS in Jiangsu Province from 2017 to 2020 were calculated based on the previous multi-population multi-route dynamic model (MMDM) of SFTS. The changes in transmission routes were summarized by collecting questionnaires from 537 SFTS cases in 2018-2020 in Jiangsu Province. The incidence rate of SFTS and the infection rate coefficients of different transmission routes were dependent variables, and month, meteorological factors and tick density were independent variables to establish a generalized additive model (GAM). The optimal GAM was selected using the generalized cross-validation score (GCV), and the model was validated by the 2016 data of Zhejiang Province and 2020 data of Jiangsu Province. The validated GAMs were used to predict the incidence and infection rate coefficients of SFTS in Jiangsu province in 2021, and also to predict the effect of extreme weather on SFTS. The number and proportion of infections by different transmission routes for each year and found that tick-to-human and human-to-human infections decreased yearly, but infections through animal and environmental transmission were gradually increasing. MMDM fitted well with the three-year SFTS incidence data (P<0.05). The best intervention to reduce the incidence of SFTS is to reduce the effective exposure of the population to the surroundings. Based on correlation tests, tick density was positively correlated with air temperature, wind speed, and sunshine duration. The best GAM was a model with tick transmissibility to humans as the dependent variable, without considering lagged effects (GCV = 5.9247E-22, R2 = 96%). Reported incidence increased when sunshine duration was higher than 11 h per day and decreased when temperatures were too high (>28°C). Sunshine duration and temperature had the greatest effect on transmission from host animals to humans. The effect of extreme weather conditions on SFTS was short-term, but there was no effect on SFTS after high temperature and sunshine hours. Different factors affect the infection rate coefficients of different transmission routes. Sunshine duration, relative humidity, temperature and tick density are important factors affecting the occurrence of SFTS. Hurricanes reduce the incidence of SFTS in the short term, but have little effect in the long term. The most effective intervention to reduce the incidence of SFTS is to reduce population exposure to high-risk environments.

Distribution of Severe Fever with Thrombocytopenia Syndrome Virus and Antiviral Antibodies in Wild and Domestic Animals in Oita Prefecture, Japan.

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging life-threatening infectious disease caused by the tickborne SFTS virus (SFTSV), first identified in China in 2009 and then in Japan in 2013. Human SFTS cases were reported to be concentrated in western Japan, but the epidemiological conditions of SFTSV infection in a specific region are still obscure. We performed an epidemiological study of SFTSV in Oita Prefecture on the island of Kyushu, located in western Japan. For our research, we collected sera from wild and domestic animals (deer, wild boars, raccoons, cats, and dogs) and ticks from January 2010 to November 2020 in Oita. The anti-SFTSV antibody positivity rate of deer in 2014 was significantly higher than that in 2011 (65% versus 27%, P < 0.001). The anti-SFTSV antibody positivity rates of deer, wild boars, raccoons, wild dogs, domestic dogs, and domestic cats were 55%, 12%, 27%, 1.8%, 0.53%, and 1.4%, respectively. Moreover, RT-PCR could not detect SFTSV in any tick sample. Of the six areas of Oita Prefecture, only the Eastern area showed no incidence or possibility of SFTSV infection among wild and domestic animals, ticks, and human beings. Further investigation is required to assess whether local seroepidemiology in animals will help assess the risk of SFTSV infections in inhabitants.

Seasonal activity of Haemaphysalis longicornis and Haemaphysalis flava (Acari: Ixodida), vectors of severe fever with thrombocytopenia syndrome (SFTS) virus, and their SFTS virus harboring rates in Gyeonggi Province, South Korea.

Seasonal activity of ticks, including disease vectors of fatal severe fever with thrombocytopenia syndrome (SFTS) virus, was monitored using CO2-bait traps from April to November in 2019 and 2020 in a rural area in Gyeonggi-do, South Korea. Traps were deployed for 24h once a month in four vegetation types: grassland, grave, mountain trail, and shrubs. A total of 4516 ticks were caught, all of which belong to the genus Haemaphysalis; larvae, nymphs, and adults were 41.9, 39.5, and 18.6%, respectively. The nymphs and adults belonged to two tick species, H. longicornis and H. flava, and H. longicornis was dominant, comprising 97.9% of the two stages collected. Larvae were identified only to the genus level due to difficulty of morphological distinction between species. For H. longicornis, nymph numbers peaked between April and June, followed by adults between June and July. Haemaphysalis larvae showed clear peaks in August. In general, H. longicornis nymphs and adults were most abundant in grassland, whereas larvae were so in the grave area. Collected ticks were pooled and subjected to PCR analysis to estimate SFTS virus harboring rate. In 2019, only one SFTS virus-positive sample was detected in June. However, a total of 18 SFTS-virus positive samples were detected from August to October in 2020.