Biosafety standards for working with Crimean-Congo hemorrhagic fever virus.

In countries from which Crimean-Congo haemorrhagic fever (CCHF) is absent, the causative virus, CCHF virus (CCHFV), is classified as a hazard group 4 agent and handled in containment level (CL)-4. In contrast, most endemic countries out of necessity have had to perform diagnostic tests under biosafety level (BSL)-2 or -3 conditions. In particular, Turkey and several of the Balkan countries have safely processed more than 100 000 samples over many years in BSL-2 laboratories. It is therefore advocated that biosafety requirements for CCHF diagnostic procedures should be revised, to allow the tests required to be performed under enhanced BSL-2 conditions with appropriate biosafety laboratory equipment and personal protective equipment used according to standardized protocols in the countries affected. Downgrading of CCHFV research work from CL-4, BSL-4 to CL-3, BSL-3 should also be considered.

Medical education in Kosova.

BACKGROUND: Kosova, the poorest country in Europe, is an example of the challenges posed by higher education in the developing world. The last 10 years have represented a period of significant reform within both the health care and education systems in Kosova. AIM: This article provides an overview of all levels of the higher medical education in Kosova, with particular emphasis on main issues and challenges. METHODS: This is a descriptive cross-sectional study. Data were collected through review of medical curriculum, student selection, licensure, continuing medical education (CME) and interviews with stakeholders in Medical School and Ministry of Health. RESULTS: Medical education in Kosova is categorised in three levels: undergraduate, postgraduate and CME. Kosova has a short tradition of medical education and has had a turbulent history in higher education during the last two decades. Starting in the academic year 2001/2002, the University of Prishtina adopted the Bologna system, although officially Kosova is not yet a member of Bologna Process. CONCLUSION: Quality assurance and quality control measures are considered core elements in future modernisation of medical education in Kosova. Bologna Declaration provides an opportunity for improvement of current weaknesses in medical education system.

Current situation of Crimean-Congo hemorrhagic fever in Southeastern Europe and neighboring countries: a public health risk for the European Union?

UNLABELLED: Crimean-Congo hemorrhagic fever (CCHF) is the most widespread tick-borne viral infection of humans, occurring across western China through southern Asia, Middle East, and Southeastern Europe (SEE) and in the most of African countries. CCHF virus is maintained through vertical and horizontal transmission in several genera of ticks, mainly in Hyalomma, which spreads the virus to a variety of wild and domestic mammals, which develop a transient viremia without signs of illness. Human infections occur through tick bite or exposure to the blood or other body fluids of an infected animal or of a CCHF patient. In SEE the number of clinical cases of CCHF as well as the areal of the infected ticks continuously rapidly increased after 2000. The aim of this study was to present actual situation of CCHF in SEE. Sources of information include published literature and personal unpublished data. CONCLUSIONS: Based on: 1. Hyaloma's presence in Western EU countries, 2. Changes in climatic conditions and 3. Absence of an active vaccination against CCHF, it can be expected that this disease will continue to present real threat for human health in SEE and Southwestern Europe (SWE).

Molecular epidemiology of Crimean-Congo hemorrhagic fever virus in Kosovo.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a zoonotic agent that causes severe, life-threatening disease, with a case fatality rate of 10-50%. It is the most widespread tick-borne virus in the world, with cases reported in Africa, Asia and Eastern Europe. CCHFV is a genetically diverse virus. Its genetic diversity is often correlated to its geographical origin. Genetic variability of CCHFV was determined within few endemic areas, however limited data is available for Kosovo. Furthermore, there is little information about the spatiotemporal genetic changes of CCHFV in endemic areas. Kosovo is an important endemic area for CCHFV. Cases were reported each year and the case-fatality rate is significantly higher compared to nearby regions. In this study, we wanted to examine the genetic variability of CCHFV obtained directly from CCHF-confirmed patients, hospitalized in Kosovo from 1991 to 2013. We sequenced partial S segment CCHFV nucleotide sequences from 89 patients. Our results show that several viral variants are present in Kosovo and that the genetic diversity is high in relation to the studied area. We also show that variants are mostly uniformly distributed throughout Kosovo and that limited evolutionary changes have occurred in 22 years. Our results also suggest the presence of a new distinct lineage within the European CCHF phylogenetic clade. Our study provide the largest number of CCHFV nucleotide sequences from patients in 22 year span in one endemic area.

Prevalence of Crimean-Congo hemorrhagic fever virus in healthy population, livestock and ticks in Kosovo.

Crimean-Congo hemorrhagic fever (CCHF) is an acute, tick borne disease often associated with hemorrhagic presentations and high case fatality rate. Kosovo is a highly endemic area for CCHF, with a significant case fatality rate. The aim of our study was to determine the prevalence of CCHF in Kosovo. We tested 1105 serum samples from healthy population in both endemic and non-endemic areas in the country. Our results revealed a seroprevalence of 4.0% (range 0-9.3%) which is comparable to the seroprevalence in other countries. We show that seroprevalence is correlated to the disease incidence in each studied municipality. We also tested 401 animal sera (353 cow, 30 sheep, 10 goat and 8 chicken) in four endemic municipalities in Kosovo. We detected specific antibodies in all animals except in chicken. Seroprevalence in cows is comparable to other endemic areas and correlates to the seroprevalence in humans. No CCHF RNA could be detected in 105 tick samples obtained in 2012 and 2013. Sequencing of CCHFV positive ticks from 2001 revealed that the virus is most closely related to viral strains that were detected in CCHF patients from Kosovo. Results suggest that mild CCHF cases are most probably underdiagnosed and consequently that the burden of disease is higher than reported. Our study provides key information for CCHF surveillance and raises awareness for possible imported cases in CCHF non-endemic countries.

Epidemiological, serological and herd immunity of Crimean-Congo haemorrhagic fever in Kosovo.

Crimean-Congo Haemorrhagic Fever (CCHF) is primarily a zoonotic disease, mostly present as sporadic cases, but outbreaks also occur, especially in the family. Disease as endemic form is presents in some countries of Africa, Europe and Asia. In 2001, outbreak of CCHF was registered in Kosova, Albania, Pakistan, Iran, and South Africa. Goal of the research was to establish a pattern of the disease, its natural flow and herd immunity. For this purpose we used epidemiological methods, laboratory confirmation (ELISA, PCR) and t-test and chi2-test for results significance verification. Morbidity rate of the disease for the period of fifteen years (1995-2009) is 0.49 in 100,000 inhabitants, and lethality rate is 26.76 deaths on 100 lab confirmed cases. CCHF in Kosovo is present in 50% of the territory with common characteristics: altitude, hot climate, low bush and farming. Hyper endemic zones are in Central and South West of Kosovo. Seroprevalence in entire healthy population is found to be 24.3%. Presence of the CCHF antibodies was found in 14% of livestock, and in 32.6% of sheep. A phylogenetic aspect of the CCHFvirus isolated in Kosovo is the same as of the virus isolated in Drosdov (Russia).

Brain tumors and epilepsy.

Brain tumors are a common cause of epilepsy. Tumor type and location are determining factors that significantly influence seizure frequency. The aim of this study was to analyze clinical data of patients diagnosed with brain tumors and epilepsy. Data for this study were obtained from patient medical records over a 6-year period (2000-2005). Patient history and findings obtained by diagnostic methods such as electroencephalography, computerized tomography and magnetic resonance were analyzed. Data were analyzed by appropriate statistical methods and the structure, prevalence, mean and standard deviation were calculated. The significance of results was tested by use of t-test and chi2-test. A total of 15 933 patient charts were analyzed. Out of 15 933 patients, 10.8% were diagnosed with epilepsy and 175 (1.09%) patients had brain tumor, 75 (42.86%) of which were significantly associated with epilepsy (P > 0.05). Almost forty-three percent (42.86%) of tumors were epileptogenic, with no significant sex difference (confidence level of 95%). Fifty-seven (32.5%) brain tumor patients were aged 51-60. The mean age of all patients with brain tumors was 41.6 years. Focal sensorimotor seizures were dominant in 40 (53.3%) cases. Among epilepsy cases with known etiology, 75 (6.8%) patients had epileptogenic tumors. Types of seizures in patients with epilepsy were different from seizures provoked by brain tumors. The most common tumor site was temporal region (43.4%). There was no significant difference according to epileptogenesis. Focal sensorimotor seizures were common in patients with frontal and parietal region tumors.

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-gamma), and tumor necrosis factor alpha (TNF-alpha) 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-gamma and TNF-alpha, cytokines mediating vascular dysfunction, disseminated intravascular coagulation, organ failure, and shock.

Collective immunity of the population from endemic zones of hemorrhagic fever with renal syndrome in Kosovo.

Hemorrhagic fever with renal syndrome (HFRS), also known as mice fever is an acute viral zoonosis and it appears in the natural focus after the human contact with Hantaan virus infected mice. The objective (purpose) of this study was to investigate the prevalence of specific antibodies in HFRS, in convalescent persons (collective immunity in endemic hearths). In this project we applied the epidemiological method of studying with retrospective-perspective, the serological method for determination and detecting antibodies from the persons of epidemical focus and statistical methods. The disease diagnosis is based on the epidemiological, clinical and serological records. The collected samples have been sent to referral laboratory in Medical Faculty-Institute of Microbiology Ljubljana for laboratory confirmation. From the results we came to conclusion that in the territory of Republic of Kosovo, the HFRS is still a serious health, economic and biological problem. The lethality rate from HFRS in 1986 was 15.4%, 1986-89 10.8%, from 1995-2006 8.70%. The lowest rates of morbidity, mortality and lethality of HFRS compared with the previous periods of time, prove collective immunity growth in Dukagjini valley. For collective immunity research and to conduct the persistence of antibodies for viral corresponding (relative) antigen, after the disease, the samples were collected in the time period of May-June 2008, with 203 persons that were tested with serological method IIF (Indirect immune fluorescence) from which 187 cases (92.1%) resulted sero-negative and 16 cases (7.9%) resulted sero-positive with HFRS. This proves the collective immunity increase for HFRS. From 13 recovered patients previously diagnosed with HFRS (1986-1989-1995), levels of antibodies were screened in 2008 with IIF. Out of 13 persons, positive antibodies were found in 10 cases, while 3 cases were negative for antibodies (HTN, PUU, and DOB). After 13, 19 and 22 years HTN, PUU and DOB antibodies persisted in level (1:16-1:512). Based on the gathered results, we came to conclusion that it is necessary to compile the National Strategy of Surveillance for the Kosovo Health System for a 5 year period, for avoiding this high risk disease.

Tularemia outbreak investigation in Kosovo: case control and environmental studies.

A large outbreak of tularemia occurred in Kosovo in the early postwar period, 1999-2000. Epidemiologic and environmental investigations were conducted to identify sources of infection, modes of transmission, and household risk factors. Case and control status was verified by enzyme-linked immunosorbent assay, Western blot, and microagglutination assay. A total of 327 serologically confirmed cases of tularemia pharyngitis and cervical lymphadenitis were identified in 21 of 29 Kosovo municipalities. Matched analysis of 46 case households and 76 control households suggested that infection was transmitted through contaminated food or water and that the source of infection was rodents. Environmental circumstances in war-torn Kosovo led to epizootic rodent tularemia and its spread to resettled rural populations living under circumstances of substandard housing, hygiene, and sanitation.