Risk Factors for Bunyavirus-Associated Severe Fever with Thrombocytopenia Syndrome,China

Background

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging disease that is caused by a novel bunyavirus, referred to as SFTS virus. During January 2011 to December 2011 we conducted a case-control study in Henan, Hubei and Shandong Provinces of China to determine the risk factors for SFTS.

Methods

Case-patients were identified in hospitals and reported to provincial Centers for Disease Control and Prevention while being notified electronically to the National Surveillance System. Controls were randomly selected from a pool of patients admitted to the same hospital ward within one week of the inclusion of the cases. They were matched by age (+/−5 years) and gender.

Results

A total of 422 patients participated in the study including 134 cases and 288 matched controls. The median age of the cases was 58.8 years, ranging from 47.6 to 70.1 years; 54.5% were male. No differences in demographics were observed between cases and controls; however, farmers were frequent and more common among cases (88.8%) than controls (58.7%). In multivariate analysis, the odds for SFTS was 2.4∼4.5 fold higher with patients who reported tick bites or presence of tick in the living area. Other independent risk factors included cat or cattle ownership and reported presence of weeds and shrubs in the working environment.

Conclusions

Our findings support the hypothesis that ticks are important vectors of SFTS virus. Further investigations are warranted to understand the detailed modes of transmission of SFTS virus while vector management, education on tick bites prevention and personal hygiene management should be implemented for high-risk groups in high incidence areas.     

Age Is a Critical Risk Factor for Severe Fever with Thrombocytopenia Syndrome

Background

Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease in East Asia. SFTS is a tick borne hemorrhagic fever caused by SFTSV, a new bunyavirus named after the syndrome. We investigated the epidemiology of SFTS in Laizhou County, Shandong Province, China.

Methods

We collected serum specimens of all patients who were clinically diagnosed as suspected SFTS cases in 2010 and 2011 in Laizhou County. The patients'' serum specimens were tested for SFTSV by real time fluorescence quantitative PCR (RT-qPCR). We collected 1,060 serum specimens from healthy human volunteers by random sampling in Laizhou County in 2011. Healthy persons'' serum specimens were tested for specific SFTSV IgG antibody by ELISA.

Results

71 SFTS cases were diagnosed in Laizhou County in 2010 and 2011, which resulted in the incidence rate of 4.1/100,000 annually. The patients ranged from 15 years old to 87 years old and the median age of the patients were 59 years old. The incidence rate of SFTS was significantly higher in patients over 40 years old and fatal cases only occurred in patients over 50 years old. 3.3% (35/1,060) of healthy people were positive to SFTSV IgG antibody. The SFTSV antibody positive rate was not significantly different among people at different age groups.

Conclusion

Our results revealed that seroprevalence of SFTSV in healthy people in Laizhou County was not significantly different among age groups, but SFTS patients were mainly elderly people, suggesting that age is the critical risk factor or determinant for SFTS morbidity and mortality.     

家养动物体表蜱中发热伴血小板减少综合征布尼亚病毒分离及鉴定

为了解发热伴血小板减少综合征布尼亚病毒(SFTSV)的传播机制,采集了山东疫区家养牛、羊和狗等动物体表蜱,分类鉴定后,通过Real-time PCR筛查、病毒分离培养和基因组序列分析等方法分离鉴定蜱中的病毒。所采集的蜱,以长角血蜱为主,占91.4%。其中3头SFTSV核酸检测阳性,阳性率为2.14%,并在其中一份羊体表蜱标本中分离到SFTSV病毒,命名为SDLZTick12。序列分析显示与我国在不同省份患者标本中分离的病毒全基因序列具有高度同源性,且病毒的抗原性和生长特性与人源病毒相同。本研究首次在山东疫区蜱中分离到新型布尼亚病毒,并与人源病毒进行了系统比较研究,提示蜱可能为该新病原体的传播媒介,对疾病的防控具有重要的指导意义。     

Interstadial and Infestation Level-dependent Variation in the Transmission Efficiency of Borrelia Burgdorferi from Mice to Ixodes Ricinus Ticks

The efficiency with which the spirochaete Borrelia burgdorferi sensu stricto was transmitted from laboratory mice to larval and nymphal Ixodes ricinus ticks was assessed, using the polymerase chain reaction. The transmission efficiency to nymphs was significantly greater than to larvae when both fed together on the same host. Increased tick infestation levels of mice were correlated with significantly greater engorgement weights and higher B. burgdorferi transmission coefficients from mice to nymphs. These observations indicate that both the feeding success of ticks and the transmission coefficients from host to tick may be influenced by the tick infestation level of an infected host. The infestation level and the relative numbers of each life stage of the tick are factors which should be considered in the design of transmission experiments.     

江苏省冬小麦湿渍害的风险区划

选取能较好反映冬小麦春季湿渍害特征的3个气象因子:旬降雨量、旬日照时数和旬雨日,计算了江苏省1960—2008期间历年3—5月这3个因子的逐旬统计值,分析了这些因子与冬小麦气候产量的关系,研究结果表明:(1)春季旬降雨量、旬雨日和旬日照时数对江苏省冬小麦气候产量有显著影响;(2)通径分析显示,旬降雨量和旬日照对气候产量有直接影响,而旬雨日对气候产量有间接影响;(3)构建了一个湿渍害判别指数Q用来判别湿渍害发生年份,并结合江苏省各地湿渍害年发生频率和冬小麦气候减产率,建立了冬小麦湿渍害风险指数模型;(4)利用所建风险指数模型对江苏省冬小麦的湿渍害风险进行了区划和评估,并提出了各风险区的防御对策。     

Landscape features predict the current and forecast the future geographic spread of Lyme disease

Lyme disease, the most prevalent vector-borne disease in North America, is increasing in incidence and geographic distribution as the tick vector, Ixodes scapularis, spreads to new regions. We re-construct the spatial-temporal invasion of the tick and human disease in the Midwestern US, a major focus of Lyme disease transmission, from 1967 to 2018, to analyse the influence of spatial factors on the geographic spread. A regression model indicates that three spatial factors—proximity to a previously invaded county, forest cover and adjacency to a river—collectively predict tick occurrence. Validation of the predictive capability of this model correctly predicts counties invaded or uninvaded with 90.6% and 98.5% accuracy, respectively. Reported incidence increases in counties after the first report of the tick; based on this modelled relationship, we identify 31 counties where we suspect I. scapularis already occurs yet remains undetected. Finally, we apply the model to forecast tick establishment by 2021 and predict 42 additional counties where I. scapularis will probably be detected based upon historical drivers of geographic spread. Our findings leverage resources dedicated to tick and human disease reporting and provide the opportunity to take proactive steps (e.g. educational efforts) to prevent and limit transmission in areas of future geographic spread.     

Spatiotemporal Dynamics of Hand-Foot-Mouth Disease and Its Relationship with Meteorological Factors in Jiangsu Province,China

Hand, foot and mouth disease (HFMD) is an important public health issue in mainland China, including Jiangsu Province. The main purpose of this study was to depict the epidemiological characteristics of HFMD and evaluate the effects of meteorological variables on its dynamics via spatiotemporal analytic methods, which is essential for formulating scientific and effective prevention and control strategies and measures. In total, 497,910 cases of HFMD occurred in the 2009-2013 period, with an average annual incidence of 126.3 per 100,000 in Jiangsu. Out of these, 87.7% were under 5 years old with a male-to-female incidence ratio of 1.4. The dominant pathogens of the laboratory-confirmed cases were EV71 and CoxA16, accounting for 44.8% and 30.6% of all cases, respectively. Two incidence peaks were observed in each year, the higher occurring between April and June, the lower between November and December. The incidence ranged between 16.8 and 233.5 per 100,000 at the county level. The incidence in the South of the province was generally higher than that in the northern regions. The most likely spatiotemporal cluster detected by space–time scan analysis occurred in May-June of 2012 in the southern region. Average temperature and rainfall were positively correlated with HFMD incidence, while the number of days with rainfall ≥ 0.1mm, low temperature, high temperature and hours of sunshine were negatively related. Particularly, relative humidity had no relationship. In conclusion, the prevalence of HFMD in Jiangsu Province has an obvious feature of seasonality. The etiological composition changed dynamically and might be a latent driving force for the temporal variation of the incidence of HFMD. A moderately warm environment promotes the transmission of the HFMD viruses, while particularly cold and hot climate conditions restrain their transmission.     

The climatic factors affecting dengue fever outbreaks in southern Taiwan: an application of symbolic data analysis

Background

Dengue fever is a leading cause of severe illness and hospitalization in Taiwan. This study sought to elucidate the linkage between dengue fever incidence and climate factors.

Results

The result indicated that temperature, accumulated rainfall, and sunshine play an important role in the transmission cycles of dengue fever. A predictive model equation plots dengue fever incidence versus temperature, rainfall, and sunshine, and it suggests that temperature, rainfall, and sunshine are significantly correlated with dengue fever incidence.

Conclusions

The data suggests that climate factors are important determinants of dengue fever in southern Taiwan. Dengue fever viruses and the mosquito vectors are sensitive to their environment. Temperature, rainfall and sunshine have well-defined roles in the transmission cycle. This finding suggests that control of mosquito by climatic factor during high temperature seasons may be an important strategy for containing the burden of dengue fever.

     

Thresholds for disease persistence in models for tick-borne infections including non-viraemic transmission,extended feeding and tick aggregation

Lyme disease and Tick-Borne Encephalitis (TBE) are two emergent tick-borne diseases transmitted by the widely distributed European tick Ixodes ricinus. The life cycle of the vector and the number of hosts involved requires the development of complex models which consider different routes of pathogen transmission including those occurring between ticks that co-feed on the same host. Hence, we consider here a general model for tick-borne infections. We assumed ticks feed on two types of host species, one competent for viraemic transmission of infection, the second incompetent but included a third transmission route through non-viraemic transmission between ticks co-feeding on the same host. Since a blood meal lasts for several days these routes could lead to interesting nonlinearities in transmission rates, which may have important effects.We derive an explicit formula for the threshold for disease persistence in the case of viraemic transmission, also for the case of viraemic and non-viraemic transmission. From this formula, the effect of parameters on the persistence of infection can be determined. When only viraemic transmission occurs, we confirm that, while the density of the competent host has always a positive effect on infection persistence, the density of the incompetent host may have either a positive effect, by amplifying tick population, or a negative ("dilution") effect, by wasting tick bites on an incompetent host. With non-viraemic transmission, the "dilution" effect becomes less relevant. On the other hand, if the nonlinearity due to extended feeding is included, the dilution effect always occurs, but often at unrealistically high host densities. Finally, we incorporated the effects of tick aggregation on the hosts and correlation of tick stages and found that both had an important effect on infection persistence, if non-viraemic transmission occurred.     

基于生态位和模糊数学的冬小麦适宜性评价

为定量评价气象、土壤等要素对作物生长的影响,利用江苏省及周边40个气象站1980—2010年日气象资料,选取影响冬小麦品种生长发育的主要气象(如气温、降水、日照时数等)和土壤(如土壤厚度、有机质和p H值等)生态因子,基于生态位理论和模糊数学的方法,依据冬小麦生长对生态各因子的响应关系建立各生态因子适宜度模型,借助GIS空间插值和空间分析,计算江苏省冬小麦品种的种植适宜度并进行等级划分。结果表明:从单要素看,研究区气温适宜度和日照时数适宜度都由北往南逐渐降低,降水适宜度由南往北逐渐降低;大部分地区土壤厚度和土壤有机质适宜,但大部分地区的p H值适宜度较低;从气候适宜度看,江苏省气候适宜度的范围为0.68—0.81,中北部大部分区域适宜度大于0.73,全省的气候适宜度均适合种植冬小麦,大体上呈现由北往南逐渐减小的变化;从土壤适宜度看,全省中部、南部与西北部大部分区域适宜度大于0.70,适合种植冬小麦。从综合适宜度看,全省大部分地区适宜度为0.50—0.86,适宜于冬小麦生长。综合考虑农业气候资源和土壤资源对江苏省冬小麦品种种植的综合适宜性进行评价,评价结果为充分利用江苏省农业生态资源、指导及科学制定冬小麦品种区域种植规划提供科学依据;按作物品种分生育期多角度的精细化研究方法和建立的各因子的适宜度模型可为今后作物区域适宜性评价提供一种新的思路,对同类研究具有一定的借鉴作用。     

Integrated Assessment of Behavioral and Environmental Risk Factors for Lyme Disease Infection on Block Island,Rhode Island

Peridomestic exposure to Borrelia burgdorferi-infected Ixodes scapularis nymphs is considered the dominant means of infection with black-legged tick-borne pathogens in the eastern United States. Population level studies have detected a positive association between the density of infected nymphs and Lyme disease incidence. At a finer spatial scale within endemic communities, studies have focused on individual level risk behaviors, without accounting for differences in peridomestic nymphal density. This study simultaneously assessed the influence of peridomestic tick exposure risk and human behavior risk factors for Lyme disease infection on Block Island, Rhode Island. Tick exposure risk on Block Island properties was estimated using remotely sensed landscape metrics that strongly correlated with tick density at the individual property level. Behavioral risk factors and Lyme disease serology were assessed using a longitudinal serosurvey study. Significant factors associated with Lyme disease positive serology included one or more self-reported previous Lyme disease episodes, wearing protective clothing during outdoor activities, the average number of hours spent daily in tick habitat, the subject’s age and the density of shrub edges on the subject’s property. The best fit multivariate model included previous Lyme diagnoses and age. The strength of this association with previous Lyme disease suggests that the same sector of the population tends to be repeatedly infected. The second best multivariate model included a combination of environmental and behavioral factors, namely hours spent in vegetation, subject’s age, shrub edge density (increase risk) and wearing protective clothing (decrease risk). Our findings highlight the importance of concurrent evaluation of both environmental and behavioral factors to design interventions to reduce the risk of tick-borne infections.     

Persistence of Pathogens with Short Infectious Periods in Seasonal Tick Populations: The Relative Importance of Three Transmission Routes

Background

The flaviviruses causing tick-borne encephalitis (TBE) persist at low but consistent levels in tick populations, despite short infectious periods in their mammalian hosts and transmission periods constrained by distinctly seasonal tick life cycles. In addition to systemic and vertical transmission, cofeeding transmission has been proposed as an important route for the persistence of TBE-causing viruses. Because cofeeding transmission requires ticks to feed simultaneously, the timing of tick activity may be critical to pathogen persistence. Existing models of tick-borne diseases do not incorporate all transmission routes and tick seasonality. Our aim is to evaluate the influence of seasonality on the relative importance of different transmission routes by using a comprehensive mathematical model.

Methodology/Principal Findings

We developed a stage-structured population model that includes tick seasonality and evaluated the relative importance of the transmission routes for pathogens with short infectious periods, in particular Powassan virus (POWV) and the related “deer tick virus,” emergent encephalitis-causing flaviviruses in North America. We used the next generation matrix method to calculate the basic reproductive ratio and performed elasticity analyses. We confirmed that cofeeding transmission is critically important for such pathogens to persist in seasonal tick populations over the reasonable range of parameter values. At higher but still plausible rates of vertical transmission, our model suggests that vertical transmission can strongly enhance pathogen prevalence when it operates in combination with cofeeding transmission.

Conclusions/Significance

Our results demonstrate that the consistent prevalence of POWV observed in tick populations could be maintained by a combination of low vertical, intermediate cofeeding and high systemic transmission rates. When vertical transmission is weak, nymphal ticks support integral parts of the transmission cycle that are critical for maintaining the pathogen. We also extended the model to pathogens that cause chronic infections in hosts and found that cofeeding transmission could contribute to elevating prevalence even in these systems. Therefore, the common assumption that cofeeding transmission is not relevant in models of chronic host infection, such as Lyme disease, could lead to underestimating pathogen prevalence.     

Clinical laboratory parameters and fatality of Severe fever with thrombocytopenia syndrome patients: A systematic review and meta-analysis

BackgroundSevere fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease with high case fatality rate. Unfortunately, no vaccine or antiviral specifically targeting SFTS virus (SFTSV) are available for the time being. Our objective was to investigate the association between clinical laboratory parameters and fatality of SFTS patients.MethodsThe systematic review was conducted in accordance with The Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines. We searched (from inception to 24th February 2022) Web of Science, PubMed, National Knowledge Infrastructure databases and Wan Fang Data for relevant researchers on SFTS. Studies were eligible if they reported on laboratory parameters of SFTS patients and were stratified by clinical outcomes. A modified version of Newcastle-Ottawa scale was used to evaluate the quality of included studies. Standardized mean difference (SMD) was used to evaluate the association between laboratory parameters and outcomes. The between-study heterogeneity was evaluated quantitatively by standard Chi-square and the index of heterogeneity (I²). Heterogeneity was explored by subgroup and sensitivity analyses, and univariable meta-regression. Publication bias was determined using funnel plots and Egger’s test.ResultsWe identified 34 relevant studies, with over 3300 participants across three countries. The following factors were strongly (SMD>1 or SMD<-0.5) and significantly (P<0.05) associated mortality: thrombin time (TT) (SMD = 1.53), viral load (SMD = 1.47), activated partial-thromboplastin time (APTT) (SMD = 1.37), aspartate aminotransferase (AST) (SMD = 1.19), lactate dehydrogenase (LDH) (SMD = 1.13), platelet count (PLT) (SMD = -0.47), monocyte percentage (MON%) (SMD = -0.47), lymphocyte percentage (LYM%) (SMD = -0.46) and albumin (ALB) (SMD = -0.43). Alanine aminotransferase, AST, creatin phosphokinase, LDH, PLT, partial-thromboplastin time and viral load contributed to the risk of dying of SFTS patients in each subgroup analyses. Sensitivity analysis demonstrated that the results above were robust.Conclusions/significanceThe abnormal levels of viral load, PLT, coagulation function and liver function, significantly increase the risk of SFTS mortality, suggesting that SFTS patients with above symptoms call for special concern.     

Effect of deer density on tick infestation of rodents and the hazard of tick-borne encephalitis. II: population and infection models

Tick-borne encephalitis is an emerging vector-borne zoonotic disease reported in several European and Asiatic countries with complex transmission routes that involve various vertebrate host species other than a tick vector. Understanding and quantifying the contribution of the different hosts involved in the TBE virus cycle is crucial in estimating the threshold conditions for virus emergence and spread. Some hosts, such as rodents, act both as feeding hosts for ticks and reservoirs of the infection. Other species, such as deer, provide important sources of blood for feeding ticks but they do not support TBE virus transmission, acting instead as dead-end (i.e., incompetent) hosts. Here, we introduce an eco-epidemiological model to explore the dynamics of tick populations and TBE virus infection in relation to the density of two key hosts. In particular, our aim is to validate and interpret in a robust theoretical framework the empirical findings regarding the effect of deer density on tick infestation on rodents and thus TBE virus occurrence from selected European foci. Model results show hump-shaped relationships between deer density and both feeding ticks on rodents and the basic reproduction number for TBE virus. This suggests that deer may act as tick amplifiers, but may also divert tick bites from competent hosts, thus diluting pathogen transmission. However, our model shows that the mechanism responsible for the dilution effect is more complex than the simple reduction of tick burden on competent hosts. Indeed, while the number of feeding ticks on rodents may increase with deer density, the proportion of blood meals on competent compared with incompetent hosts may decrease, triggering a decline in infection. As a consequence, using simply the number of ticks per rodent as a predictor of TBE transmission potential could be misleading if competent hosts share habitats with incompetent hosts.     

Botanical Soceity of Edinburgh

Background: Economic activities are substantial factors in alien plant establishment and invasions. Climate also plays an important role in the distribution of alien species.

Aims: We evaluate the relationship between alien species density and both climatic and socio-economic factors at the scale of provinces located in a latitudinal-bioclimatic gradient in Chile.

Methods: We used generalised linear models with backward selection to evaluate the relative importance of each parameter (human population, gross domestic product, length of traffic routes, crop cover, abandoned crop cover, artificial plantations, protected areas, annual rainfall and temperature) on species density. We compared the average species density among climate types.

Results: Alien density was higher for provinces located in the most populated areas with Mediterranean and temperate oceanic climates (south-central Chile) and decreased for less populated provinces in the north and the southernmost parts (desert and sub-Antarctic wetlands). Human population, length of traffic routes and annual rainfall significantly explained the variation in alien species density in Chile.

Conclusions: Although human population still increases, the results can be used especially in high priority conservation areas where traffic routes and human settlements can be objectively reduced or managed, to reduce the potential increase in the number of alien species.     

No Detection of Severe Fever with Thrombocytopenia Syndrome Virus from Ixodid Ticks Collected in Seoul

Larvae, nymphs, and adult stages of 3 species of ixodid ticks were collected by tick drag methods in Seoul during June-October 2013, and their infection status with severe fever with thrombocytopenia syndrome (SFTS) virus was examined using RT-PCR. During the period, 732 Haemaphysalis longicornis, 62 Haemaphysalis flava, and 2 Ixodes nipponensis specimens were collected. Among the specimens of H. longicornis, the number of female adults, male adults, nymphs, and larvae were 53, 11, 240, and 446, respectively. Ticks were grouped into 63 pools according to the collection site, species, and developmental stage, and assayed for SFTS virus. None of the pools of ticks were found to be positive for SFTS virus gene.     

Correlation Between HLA-A,B and DRB1 Alleles and Severe Fever with Thrombocytopenia Syndrome

ObjectiveSevere fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever caused by a tick-borne bunyavirus (SFTSV) in East Asian countries. The role of human leukocyte antigen (HLA) in resistance and susceptibility to SFTSV is not known. We investigated the correlation of HLA locus A, B and DRB1 alleles with the occurrence of SFTS.MethodsA total of 84 confirmed SFTS patients (patient group) and 501 unrelated non-SFTS patients (healthy individuals as control group) from Shandong Province were genotyped by PCR-sequence specific oligonucleotide probe (PCR-SSOP) for HLA-A, B and DRB1 loci.Allele frequency was calculated and compared using χ² test or the Fisher''s exact test. A corrected P value was calculated with a bonferronis correction. Odds Ratio (OR) and 95% confidence intervals (CI) were calculated by Woolf’s method.ResultsA total of 11 HLA-A, 23 HLA-B and 12 HLA-DRB1 alleles were identified in the patient group, whereas 15 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles were detected in the control group. The frequencies of A*30 and B*13 in the SFTS patient group were lower than that in the control group (P = 0.0341 and 0.0085, Pc = 0.5115 and 0.252). The ORs of A*30 and B*13 in the SFTS patient group were 0.54 and 0.49, respectively. The frequency of two-locus haplotype A*30-B*13 was lower in the patient group than in the control group(5.59% versus 12.27%, P = 0.037,OR = 0.41, 95%CI = 0.18–0.96) without significance(Pc>0.05). A*30-B*13-DRB1*07 and A*02-B*15-DRB1*04 had strong associations with SFTS resistance and susceptibility respectively (Pc = 0.0412 and 0.0001,OR = 0.43 and 5.07).ConclusionThe host HLA class I polymorphism might play an important role with the occurrence of SFTS. Negative associations were observed with HLA-A*30, HLA-B*13 and Haplotype A*30-B*13, although the associations were not statistically significant. A*30-B*13-DRB1*07 had negative correlation with the occurrence of SFTS; in contrast, haplotype A*02-B*15-DRB1*04 was positively correlated with SFTS.     

Severe fever with thrombocytopenia syndrome and its pathogen SFTSV

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in East Asia with case fatality up to 50%. SFTS is caused by SFTSV, a tick borne bunyavirus. In endemic area in China 1%–3% population was infected with SFTSV, but age is critical risk factor for hospitalization and death of SFTS patients.