Fever After Tick Bite (FATB) Study; Determining the Etiology of Tick-Borne Human Infections in Northern Europe
试验速览
- 阶段
- 不适用
- 状态
- 撤回
- 发起方
- 入组人数
- 310
- 试验地点
- 1
- 主要终点
- Proportion of subjects developing other serious, non-neurological symptoms or disease after a tick bite.
研究概览
简要总结
The proposed study is a collaboration between Microbiology, SU/Sahlgrenska and the Infectious Diseases clinic at SU/Östra as well as several Infectious Diseases clinics throughout Sweden aiming at improving microbiological diagnostic assays regarding the early identification of tick-borne microorganisms (including as of yet unidentified pathogens) capable of causing human disease using modern diagnostic tools.
At the initial study visit (day 0) plasma, serum, urine, saliva, and PBMCs (and tick, if available) will be collected from patients developing fever within two weeks after a tick bite. Additional follow-up samples will be obtained after 9 and 30 days as well as after 6 months. The initial samples will be analyzed using (a) directed multiplex PCR analysis for Tick-Borne Encephalitis (TBE), Borrelia, Anaplasma, Neoerlichia, Rickettsia, Coxiella, Tularemia, and Babesiosis in plasma, whole blood and urine, (b) conventional IgM and IgG serology for TBE, (c) "Next Generation Sequencing" (NGS) for the detection of bacterial 16s rRNA as well as unknown viruses, (d) potential biomarkers, and (e) host genetic factors. Among patients where initial sampling indicates the presence of a potential pathogen or in patients developing neurological symptoms, a lumbar puncture will be performed and CSF will be further analyzed. Samples will also be evaluated regarding potential microbiological factors predisposing for severity of infection.
The primary objective of the study is to improve diagnostic tools in the initial early phase of infections caused by tick-borne pathogens, especially TBE prior to the affliction of the central nervous system, and to attempt to identify which factors impact the course of infection as it is believed that approximately 75% of infected individuals resolve their infection in this first phase whereas others develop meningoencephalitis with significant subsequent neurological sequelae. Secondary objectives of the study include investigating for the presence of and treating other tick-borne pathogens, setting the stage for coming clinical trials evaluating novel anti-viral therapies for TBE.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Only
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent
- •Male and female patients ≥18 years of age
- •Medical history of tick bite within past 2 weeks
- •Documented or medical history of fever (≥38°C) within past 2 weeks
排除标准
- •Inability or unwillingness to provide informed consent or abide by the requirements of the study
- •Presence of urinary tract symptoms
- •Presence of non-tick related, infectious agent causing fever, e.g. a respiratory virus
- •Presence of other medical, non-infectious cause of fever
结局指标
主要结局
Proportion of subjects developing other serious, non-neurological symptoms or disease after a tick bite.
时间窗: Up to six months after the tick bite.
The proportion of subjects developing other serious, non-neurological symptoms or disease in each of the following etiological categories: Tick-Borne Encephalitis Virus (TBEV), Borrelia, Anaplasma, Neoerlichia, Rickettsia, Coxiella burnetii, Tularemia, and/or Babesia.
Etiology of fever (≥38°C) developing within 2 weeks after a tick bite.
时间窗: Up to two weeks after the tick bite.
Number of participants with detectable Tick-Borne Encephalitis Virus (TBEV), Borrelia, Anaplasma, Neoerlichia, Rickettsia, Coxiella burnetii, Tularemia, and/or Babesia infections.
Proportion of subjects developing neurological symptoms after a tick bite.
时间窗: Up to six months after the tick bite.
The proportion of subjects developing neurological symptoms in each of the following etiological categories: Tick-Borne Encephalitis Virus (TBEV), Borrelia, Anaplasma, Neoerlichia, Rickettsia, Coxiella burnetii, Tularemia, and/or Babesia.
次要结局
- Impact of body mass index (BMI) of subjects on the risk of development of neurological symptoms.(Up to six months after the tick bite.)
- Impact of gender of subjects on the risk of development of neurological symptoms.(Up to six months after the tick bite.)
- Impact of waist circumference of subjects on the risk of development of neurological symptoms.(Up to six months after the tick bite.)
- Impact of body mass index of subjects developing other serious, non-neurological symptoms or disease.(Up to six months after the tick bite.)
- Impact of age of subjects developing other serious, non-neurological symptoms or disease.(Up to six months after the tick bite.)
- Prospective evaluation of the specificity and sensitivity of early evaluation of plasma concentrations of the neurological marker T-tau in relation to the likelihood of developing neurological symptoms.(Up to six months after the tick bite.)
- Impact of gender of subjects developing other serious, non-neurological symptoms or disease.(Up to six months after the tick bite.)
- Prospective evaluation of the utility of Next Generation Sequencing (NGS) for the detection of unknown viruses and of bacterial 16s rRNA vs. directed Multiplex PCR(Up to 30 days after the tick bite.)
- Prospective evaluation of the specificity and sensitivity of early evaluation of 25-hydroxy vitamin D (25(OH)D) concentrations in relation to the likelihood of developing neurological symptoms.(Up to six months after the tick bite.)
- Prospective evaluation of the impact of host genetic polymorphisms in the IFNL4 gene in relation to the likelihood of developing neurological symptoms.(Up to six months after the tick bite.)
- Prospective evaluation of the association between presence or absence of immunosuppression in relation to the likelihood of developing neurological symptoms.(Up to six months after the tick bite.)
- Impact of age of subjects on the risk of development of neurological symptoms.(Up to six months after the tick bite.)
- Prospective evaluation of the specificity and sensitivity of TBEV-RNA and TBE IgM serology in the early phase of infection, i.e. up to 30 days after the tick bite.(Up to 30 days after the tick bite.)
- Prospective evaluation of the specificity and sensitivity of PCR for Borrelia DNA in plasma/serum as well as Borrelia IgM serology in the early phase of infection, i.e. up to 30 days after the tick bite.(Up to 30 days after the tick bite.)
- Prospective evaluation of the specificity and sensitivity of early evaluation of plasma concentrations of the neurological markers NFL in relation to the likelihood of developing neurological symptoms.(Up to six months after the tick bite.)
- Prospective evaluation of the impact of host genetic polymorphisms in the ITPA gene in relation to the likelihood of developing neurological symptoms.(Up to six months after the tick bite.)
- Prospective evaluation of the impact of prior vaccination against Yellow Fever on frequency and outcome of TBEV infection.(From time of prior vaccination until six months after the tick bite.)
- Impact of waist circumference of subjects developing other serious, non-neurological symptoms or disease.(Up to six months after the tick bite.)
- Prospective evaluation of the specificity and sensitivity of early evaluation of plasma concentrations of the neurological marker GFAp in relation to the likelihood of developing neurological symptoms.(Up to six months after the tick bite.)
- Prospective evaluation of the impact of prior vaccination against TBE on frequency and outcome of TBEV infection.(From time of prior vaccination until six months after the tick bite.)
- Prospective evaluation of the specificity and sensitivity of TBEV-RNA in urine vs. plasma/whole blood in the early phase of TBE infection, i.e. up to 30 days after the tick bite.(Up to 30 days after the tick bite.)
- Prospective evaluation of the specificity and sensitivity of early evaluation of plasma concentrations of IP-10 (aka CXCL10) in relation to the likelihood of developing neurological symptoms.(Up to six months after the tick bite.)
- Prospective evaluation of the impact of prior vaccination against Japanese Encephalitis on frequency and outcome of TBEV infection.(From time of prior vaccination until six months after the tick bite.)
- Prospective evaluation of peripheral blood mononuclear cells (PBMCs) analyzed by FACS, in relation to the likelihood of developing neurological symptoms.(Up to six months after the tick bite.)