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Projects / Programmes source: ARIS

Tick-transmitted illnesses and their causative agents in Slovenia

Periods
Research activity

Code Science Field Subfield
3.01.00  Medical sciences  Microbiology and immunology   

Code Science Field
3.01  Medical and Health Sciences  Basic medicine 
Keywords
Lyme borreliosis; tick-borne encephalitis; human granulocytic anaplasmosis; Lyme disease boreliae; Borrelia afzelii; Borrelia garinii; epidemiology; clinical presentation; course; outcome; post Lyme borreliosis symptoms; postencephalitic syndrome; etiology; patogenesis; immune responses.
Evaluation (rules)
source: COBISS
Points
7,352.97
A''
1,660.53
A'
2,915.2
A1/2
4,207.64
CI10
27,930
CImax
1,345
h10
70
A1
25.45
A3
6.13
Data for the last 5 years (citations for the last 10 years) on June 19, 2024; A3 for period 2018-2022
Data for ARIS tenders ( 04.04.2019 – Programme tender , archive )
Database Linked records Citations Pure citations Average pure citations
WoS  879  31,394  28,910  32.89 
Scopus  912  40,465  37,732  41.37 
Researchers (45)
no. Code Name and surname Research area Role Period No. of publicationsNo. of publications
1.  16235  PhD Maja Arnež  Microbiology and immunology  Retired researcher  2022 - 2024 
2.  08312  PhD Bojana Beovič  Microbiology and immunology  Researcher  2022 - 2024 
3.  27886  PhD Petra Bogovič  Microbiology and immunology  Researcher  2022 - 2024 
4.  13302  PhD Jože Cimperman  Microbiology and immunology  Retired researcher  2022 - 2024 
5.  37227  Katarina Čurič  Microbiology and immunology  Technical associate  2022 - 2024 
6.  28020  MSc Sergeja Gregorčič  Microbiology and immunology  Technical associate  2022 - 2024 
7.  32097  PhD Martina Jaklič  Microbiology and immunology  Researcher  2022 - 2024 
8.  13300  PhD Matjaž Jereb  Microbiology and immunology  Researcher  2022 - 2024 
9.  34909  Maša Klešnik  Microbiology and immunology  Technical associate  2022 - 2024 
10.  50154  Manja Kordiš  Microbiology and immunology  Technical associate  2022 - 2024 
11.  11330  PhD Tatjana Lejko-Zupanc  Microbiology and immunology  Researcher  2022 - 2024 
12.  34820  Lidija Lepen  Medical sciences  Technical associate  2022 - 2024 
13.  13299  PhD Stanka Lotrič Furlan  Microbiology and immunology  Retired researcher  2022 - 2024 
14.  28753  Milica Lukić  Neurobiology  Technical associate  2022 - 2024 
15.  55349  Eduard Madaras    Technical associate  2022 - 2024 
16.  11348  PhD Mojca Matičič  Microbiology and immunology  Researcher  2022 - 2024 
17.  39764  Matej Mavrič  Microbiology and immunology  Technical associate  2022 - 2024 
18.  50228  Sandra Mihelčič    Technical associate  2022 - 2024 
19.  38342  Mirijam Nahtigal Klevišar  Microbiology and immunology  Technical associate  2022 - 2024 
20.  01161  PhD Marko Noč  Cardiovascular system  Researcher  2022 - 2024 
21.  20254  PhD Katarina Ogrinc  Microbiology and immunology  Researcher  2022 - 2024 
22.  32966  Blaž Pečavar  Microbiology and immunology  Technical associate  2022 - 2024 
23.  28858  Natalija Planinc Strunjaš  Neurobiology  Technical associate  2022 - 2024 
24.  23436  PhD Tina Plankar Srovin  Public health (occupational safety)  Researcher  2022 - 2024 
25.  33996  Petra Podkrajšek    Technical associate  2022 - 2024 
26.  15476  PhD Marko Pokorn  Microbiology and immunology  Researcher  2022 
27.  20473  Mateja Poljanšek    Technical associate  2022 - 2024 
28.  22350  PhD Tereza Rojko  Microbiology and immunology  Researcher  2022 - 2024 
29.  20474  Simona Rojs    Technical associate  2022 - 2024 
30.  33988  PhD Mojca Rožič  Microbiology and immunology  Researcher  2022 - 2024 
31.  22302  PhD Rajko Saletinger  Microbiology and immunology  Researcher  2022 - 2024 
32.  20475  Andreja Sorman    Technical associate  2022 - 2024 
33.  33995  Jadranka Stojnič    Technical associate  2022 - 2024 
34.  13301  PhD Franc Strle  Microbiology and immunology  Head  2022 - 2024 
35.  30270  PhD Klemen Strle  Medical sciences  Researcher  2022 - 2023 
36.  24091  PhD Daša Stupica  Microbiology and immunology  Researcher  2022 - 2024 
37.  11347  PhD Janez Tomažič  Microbiology and immunology  Researcher  2022 - 2024 
38.  50050  Gabriele Turel  Microbiology and immunology  Technical associate  2022 - 2024 
39.  39163  Maša Velušček  Microbiology and immunology  Junior researcher  2022 - 2024 
40.  36368  PhD Marko Vidak  Medical sciences  Researcher  2022 - 2024 
41.  24469  PhD Jerneja Videčnik Zorman  Microbiology and immunology  Researcher  2022 - 2024 
42.  38376  Katarina Vincek  Microbiology and immunology  Technical associate  2022 - 2024 
43.  30546  Tomaž Vovko  Microbiology and immunology  Technical associate  2022 - 2024 
44.  54292  Mateja Zalaznik  Microbiology and immunology  Technical associate  2022 - 2024 
45.  20472  Marija Žitko    Technical associate  2022 - 2024 
Organisations (2)
no. Code Research organisation City Registration number No. of publicationsNo. of publications
1.  0312  University Medical Centre Ljubljana  Ljubljana  5057272000  125 
2.  0381  University of Ljubljana, Faculty of Medicine  Ljubljana  1627066  118 
Abstract
Background: Lyme borreliosis (LB), tick-borne encephalitis (TBE) and human granulocytic anaplasmosis (HGA) are endemic in Slovenia. Main research topics o Determination of the frequency, clinical characteristics and outcome of illness in patients with LB, TBE, or those coinfected with Lyme borreliae, TBE virus and/or Anaplasma phagocytophilum. o Identification of other arthropod-borne diseases (besides LB, TBE and HGA) in Slovenia. We will use novel microbiological and genetic approaches for detection of potential etiological agents. o Elucidation of disease pathogenesis of LB and TBE from acute infection to post-treatment sequelae. We hypothesize that differences in the clinical course of LB and TBE result from altered immune responses driven by host and microbial factors. We will assess these factors using cutting edge microbiological, immunological, and genomic/genetic approaches. Aims 1) To fill key gaps in knowledge on the course and outcome of LB and TBE. 2) To ascertain the frequency and clinical course on coinfections with LB, TBE and/or HGA agents and to test the hypothesis that course of illness in coinfected patients differs. 3) To identify other arthropod-borne diseases, in addition to LB, TBE and HGA, present in Slovenia. 4) To characterize the genetic variability of European B. burgdorferi sensu lato species and its impact on virulence by performing WGS and RFLP and correlating the genotype with clinical findings in patients using GWAS. Persistence will be assessed by culture, PCR and serology before and after treatment. 5) To identify genetic variants within the European TBE virus subtype and their impact on virulence by correlating variants with clinical findings (severity of acute disease and PES) in the same patient. TBE virus genetic variants will be determined by WGS/molecular methods. 6-9) To determine the immune mechanisms in LB and TBE pathogenesis by characterizing patients' transcriptome, immunome (cytokine and antibody profiles), and genetic variants (SNPs) and correlate the results with clinical findings in patients. Cytokines will be assessed by Luminex in sera of patients with LB and TBE and in skin samples of patients with erythema migrans and acrodermatitis chronica atrophicans obtained during active infection and thereafter. Disease-relevant SNPs will be assessed by ImmunoArray. Transcriptome profiles of patients' immune cell subtypes will be assessed by RNAseq. 10) To develop clinically-relevant predictive models using mathematical modelling and biostatistics based on patient's immune response, microbial genotype, host SNP profiles, and the corresponding clinical phenotype: in LB - frequency of dissemination, disease severity, and post-Lyme symptoms; in TBE - severity of acute illness and the presence of postencephalitic syndrome.
Significance for science
Importance for the development of science is depicted according to three research topics proposed in the programme. We expect to substantially improve knowledge by obtaining additional or new data with studies that are part of topic 1, including information on treatment of Lyme borreliosis (LB), influence of different Borrelia species on clinical presentation, laboratory findings and immune response in patients with LB, information on the course and outcome of LB according to age, and in pregnant women and persons with severe immunodeficiency, and on the efficacy of different laboratory approaches for the diagnosis of Lyme neuroborreliosis. The answer to the question "Are arthropode-borne illnesses other than LB, tick-borne encephalitis (TBE) and human granulocytic anaplasmosis (HGA) present in Slovenia" (topic 2) and studies on "Concomittant infections with the agents of LB, TBE and HGA" (topic 1) will bring new knowledge and original data on diseases transmitted by arthopodes/ticks that are limited or absent in the literature. We expect to uncover arthropod-borne illnesses other than LB, TBE and HGA, which have been reported in neighboring countries but not Slovenia. In addition, it is possible that we will identify a "new" illness, in a similar way as we succeded for the first European case of HGA, which we discovered more than 2 decades ago in a prospective study on the etiology of febrile illnesses after a tick bite. We will also gain information on the frequency, clinical characteristics and disease outcome in patients coinfected with Lyme borreliae, TBE virus and/or A. phagocytophilum, the information that is very limited. We also expect to get insight into immune and genetic characteristics in patients with acute skin manifestation of LB (erythema migrans, EM) and those with chronic skin involvement (acrodermatitis chronica atrophicans, ACA) to ascertain factors associated with the development of chronic illness. We will obtain information on the frequency and type of reinfection with B. burgdorferi sensu lato and -based on prospectively acquired data on >13.000 EM patients - on the circumstances in which the clinically manifested reinfections occur, and on clinical, etiological and immunological distinctions in patients with primary and repeat infection. Topic 3 (Elucidation of LB and TBE pathogenesis and post-Lyme and post-TBE symptoms) comprises studies that are novel and relevant in that they are focused on addressing critical issues in human disease by using cutting-edge technology applied to human specimens in combination with clinical information from well-defined patients. This approach differs substantially from the majority of pathogenetic studies to date, which were conducted in cell culture and animal models, the results of which may not be applicable to humans. Acquisition of genetic material of TBE virus which is present in blood in the initial phase of illness will enable correlation of clinical data (severity of acute illness and course and outcome of TBE) with functionally important genetic variants of TBE virus causing the illness in individual patient - the approach has not been tested/reported. We also intend to enlarge knowledge on the inflammatory protein markers and markers of neurological damage at the time of acute TBE and after treatment, and correlate the findings with severity and outcome of the illness, as well as on the causes and mechanisms on the development of TBE in persons who had been vaccinated against TBE. With our genotyping methods we hope to characterize the subtypes of individual Borrelia species, and to identify the borrelial genotypes that are associated with disseminated infection, chronic disease and post-treatment symptoms after Lyme borreliosis. We anticipate that the comprehensive genetic and multiplex protein analyses of patients' skin and blood samples will identify host inflammatory factors that are associated with control of the infection, dissemination, and different clinical outcomes of disease, including post-Lyme symptoms. Furthermore, we expect that we will get insight into host polymorphisms that may predispose patients to more severe disease or to chronic disease. Because the entire study will be conducted in a human system, any identified biomarkers will be directly relevant to patients with LB, and the increased understanding of disease pathogenesis could shape the treatment strategies. This is the first such comprehensive study of pathogenesis in human patients with LB or TBE.
Significance for the country
Direct impact of the programme on the economy and society Topic 1: Lyme borreliosis (LB) and tick-borne encephalitis (TBE) - Comparison of the efficacy, side effects and cost of therapy with different antibiotics may enable optimization of treatment strategies. For example if treatment with less costly antibiotic or for a shorter duration is as effective as more expensive or longer therapy, this will have a direct positive economic impact. - Understanding the course and outcome of early LB in severely immunocompromised patients, and in pregnant women, will enable rational management of these groups of patients, while the assessment of the value of different laboratory approaches for the diagnosis of Lyme neuroborreliosis may lead to optimization of diagnostic approaches. - Data on clinically manifested reinfections with B. burgdorferi sensu lato will make possible a valuable source of information for LB vaccine preparation. - Identification of coinfections with Lyme borreliae, TBE virus, and/or A. phagocytophilum would enable the implementation of a rational approach for diagnostic testing and treatment of coinfected patients. Topic 2: Are arthropode-borne illnesses other than LB, TBE and human granulocytis anaplasmosis (HGA) present in Slovenia? Discovery of an arthropod-borne illness other than LB, TBE and HGA in Slovenia will enable employment of rational public health measures and may have enormous impact on public health not only in Slovenia but also elsewhere. Establishment of a new (bacterial disease) would most probably enable an effective etiological treatment. Topic 3: Elucidation of LB and TBE pathogenesis and post-Lyme and post-TBE symptoms will impact the management of patients, particularly those with post-treatment symptoms after LB and TBE. These groups of patients represent a substantial scientific, medical and practical challenge that has been further augmented by numerous individuals and groups using unscientific and potentially detrimental treatment approaches. Indirect impact of the programme on the society In addition to the direct impact, a successful implementation of the programme will also have substantial indirect influence in several key areas. We envision these areas to include development/enhancement of professional expertise and promotion of professional excelency; improvement, augmentation, and intensification of clinical research; stimulation and facilitation of interdisciplinary international collaboration; and effective promotion of the country through publication of the findings in high ranked journals and by presentation of the findings at international meetings (congresses).
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