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author:("Duh, darpa")
1.  Interacting Roles of Immune Mechanisms and Viral Load in the Pathogenesis of Crimean-Congo Hemorrhagic Fever ▿  
Until now, the pathogenesis of Crimean-Congo hemorrhagic fever (CCHF) has not been well described. However, it has been hypothesized that it could be a result of the direct injury of virus-infected tissues in combination with the indirect effects of host immune responses, including cytokines. To shed more light on the role of viral load and cytokines, differential influences of CCHF virus (CCHFV) RNA load, antibody response, and cytokine production on severity and outcome of the disease were studied in sera of 46 patients with confirmed acute CCHF from Kosovo. In this study, viral load proved to be strongly related to the severity and outcome of the disease, with higher viral loads detected in patients with fatal outcomes than in surviving patients. Also, patients with fatal outcome had on average a weaker antibody response, if one was present at all. High levels of interleukin-10 (IL-10), gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) were associated with poor outcome, since detected concentrations were highest in patients with fatal outcome and lowest in patients with moderate disease course. Additionally, a positive linear dependence between viral load and these cytokines was observed. Interestingly, reduced levels of IL-12 were detected in all CCHF patients. Our study favors the hypothesis that CCHF could be a result of a delayed and downregulated immune response caused by IL-10, which leads to an increased replication and spread of CCHFV throughout the body. This consequently triggers increased production of IFN-γ and TNF-α, cytokines mediating vascular dysfunction, disseminated intravascular coagulation, organ failure, and shock.
doi:10.1128/CVI.00530-09
PMCID: PMC2897258  PMID: 20484568
2.  Anaplasma phagocytophilum in ticks in Slovenia 
Parasites & Vectors  2010;3:102.
Ticks act as vectors of many pathogens of domestic animals and humans. Anaplasma phagocytophilum in Europe is transmitted by the ixodid tick vector Ixodes ricinus. A. phagocytophilum causes a disease with diverse clinical signs in various hosts. A great genetic diversity of the groESL operon of A. phagocytophilum has been found in ticks elsewhere. In Slovenia, the variety of the groESL operon was conducted only on deer samples. In this study, the prevalence of infected ticks was estimated and the diversity of A. phagocytophilum was evaluated. On 8 locations in Slovenia, 1924 and 5049 (6973) I. ricinus ticks were collected from vegetation in the years 2005 and 2006, respectively. All three feeding stages of the tick's life cycle were examined. The prevalence of ticks infected with A. phagocytophilum in the year 2005 and in the year 2006 was 0.31% and 0.63%, respectively, and it did not differ considerably between locations. The similarity among the sequences of groESL ranged from 95.6% to 99.8%. They clustered in two genetic lineages along with A. phagocytophilum from Slovenian deer. One sequence formed a separate cluster. According to our study, the prevalence of A. phagocytophilum in ticks is comparable to the findings in other studies in Europe, and it does not vary considerably between locations and tick stages. According to groESL operon analysis, two genetic lineages have been confirmed and one proposed. Further studies on other genes would be useful to obtain more information on genetic diversity of A. phagocytophilum in ticks in Slovenia.
doi:10.1186/1756-3305-3-102
PMCID: PMC2988007  PMID: 21050436
3.  The complete genome sequence of a Crimean-Congo Hemorrhagic Fever virus isolated from an endemic region in Kosovo 
Virology Journal  2008;5:7.
The Balkan region and Kosovo in particular, is a well-known Crimean-Congo hemorrhagic fever (CCHF) endemic region, with frequent epidemic outbreaks and sporadic cases occurring with a hospitalized case fatality of approximately 30%. Recent analysis of complete genome sequences of diverse CCHF virus strains showed that the genome plasticity of the virus is surprisingly high for an arthropod-borne virus. High levels of nucleotide and amino acid differences, frequent RNA segment reassortment and even RNA recombination have been recently described. This diversity illustrates the need to determine the complete genome sequence of CCHF virus representatives of all geographically distinct endemic areas, particularly in light of the high pathogenicity of the virus and its listing as a potential bioterrorism threat. Here we describe the first complete CCHF virus genome sequence of a virus (strain Kosova Hoti) isolated from a hemorrhagic fever case in the Balkans. This virus strain was isolated from a fatal CCHF case, and passaged only twice on Vero E6 cells prior to sequence analysis. The virus total genome was found to be 19.2 kb in length, consisting of a 1672 nucleotide (nt) S segment, a 5364 nt M segment and a 12150 nt L segment. Phylogenetic analysis of CCHF virus complete genomes placed the Kosova Hoti strain in the Europe/Turkey group, with highest similarity seen with Russian isolates. The virus M segments are the most diverse with up to 31 and 27% differences seen at the nt and amino acid levels, and even 1.9% amino acid difference found between the Kosova Hoti and another strain from Kosovo (9553-01). This suggests that distinct virus strains can coexist in highly endemic areas.
doi:10.1186/1743-422X-5-7
PMCID: PMC2266736  PMID: 18197964
4.  Viral Load as Predictor of Crimean-Congo Hemorrhagic Fever Outcome 
Emerging Infectious Diseases  2007;13(11):1769-1772.
We used quantitative real-time reverse transcription–PCR to measure viral load in serum from 24 patients in Kosovo who had acute Crimean-Congo hemorrhagic fever. Viral load correlated with clinical disease and antibodies and could be used as a predictor of disease outcome.
doi:10.3201/eid1311.070222
PMCID: PMC3375790  PMID: 18217568
Crimean-Congo hemorrhagic fever; real-time RT-PCR; viral load; serology; dispatch
5.  Cervids as Babesiae Hosts, Slovenia 
Emerging Infectious Diseases  2005;11(7):1121-1123.
We describe cervids as potential reservoir hosts of Babesia EU1 and B. divergens. Both babesial parasites were found in roe deer. Sequence analysis of 18S rRNA showed 99.7% identity of roe deer Babesia EU1 with the human EU1 strain. B. divergens detected in cervids was 99.6% identical to bovine B. divergens.
doi:10.3201/eid1107.040724
PMCID: PMC3371785  PMID: 16022795
Slovenia; EU1; Babesia divergens; cervids; molecular research
6.  Diversity of Babesia Infecting European Sheep Ticks (Ixodes ricinus) 
Journal of Clinical Microbiology  2001;39(9):3395-3397.
Questing Ixodes ricinus (Acari: Ixodidae) adult and nymphal ticks collected in various parts of Slovenia were tested for the presence of babesial parasites with a PCR assay based on the nuclear small subunit rRNA gene (nss-ribosomal DNA [rDNA]). Thirteen of 135 ticks were found to contain babesial DNA. Sequence determination and analysis of amplified portions of nss-rDNA revealed their identity with Babesia microti and a high degree of homology with Babesia odocoilei and Babesia divergens. The results of this study represent the first genetic evidence of B. microti and B. divergens-like parasites in I. ricinus ticks in Europe.
doi:10.1128/JCM.39.9.3395-3397.2001
PMCID: PMC88357  PMID: 11526189

Results 1-6 (6)