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.

"Using behavioral insights to inform the COVID-19 vaccine response in Kosovo[1]: Population perceptions and interventions".

Objective: Understand population perceptions in Kosovo[1] regarding COVID-19 vaccination to inform the pandemic response. Methods: Five rounds of a cross-sectional survey in representative samples of adults during 2020-2021. Analysis includes descriptive statistics, hierarchical cluster analysis, segmentation and logistic regressions. Results: Self-reported intention to vaccinate increased after the introduction of COVID-19 vaccines in Kosovo.[1] In less than one year, vaccination intentions increased from 36% to 66% of those unvaccinated. Predictors for vaccine intentions included gender, age, trust in health authorities. Segmentation analysis identified population segments that had high vaccine nintentions but low uptake, informing messages and campaign initiatives designed to translate intentions into behavior. Conclusion: Identifying people's perceptions and behavior is essential to support evidence-based policy making, especially during outbreak response. Innovation: BI is an innovative focus of research in Kosovo [1] where little BI data had been collected prior, and provided a unique understanding of population views, attitudes and behaviors related to COVID-19. These findings were not only essential for an evidence-based pandemic response but also laid the foundation for future broad application of BI to inform interventions that seek to enable, support and promote health-related behaviurs in Kosovo[1].

Prevalence of SARS-CoV-2 Antibodies in Kosovo-Wide Population-Based Seroepidemiological Study.

BACKGROUND: Seroprevalence studies have proven to be an important tool in tracking the progression of the coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to measure the seroprevalence of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the general population of Kosovo by gender, age group and region and among asymptomatic people. METHOD: The Institute of Public Health of Kosovo conducted a cross-sectional population-based survey, aligned with the protocols of the WHO Unity Studies, from the beginning of May to the end of June 2021. RESULTS: The survey covered a total of 2204 people with a response rate of 91.8% (41.9% [923] males and 51.2% [1281] females). In May to June 2021, the prevalence of antibodies in the overall population (IgG antibodies ≥ 1.1) was 37.0%. Seroprevalence was 34.4% in men and 38.9% in women (p < 0.05), with the highest percentage (48.7%) found in the 60-69 years' age group. The overall prevalence of acute IgM antibodies (IgM ≥ 1.1) was 1% (95% CI: 0.7%-1.5%), with no significant difference between genders and the highest prevalence among participants of 60-69 years of age (1.6%; 95% CI: 0.7%-3.6%). CONCLUSION: A high prevalence of antibodies against SARS-CoV-2 was found in Kosovo before the start of the vaccination campaign. However, the results of the survey suggested that, by the end of June 2021, a desirable level of protection from the SARS-CoV-2 virus had not been reached.

Evaluation of parents' attitudes and practices related to antibiotic use for their children in Kosovo: a cross-sectional survey.

BACKGROUND: Self-medication and lack of patient adherence contribute to antibiotic misuse. This article describes parents' attitudes and practices regarding use of antibiotics by their children in Kosovo. METHODS: A cross-sectional survey was conducted during data collection. We surveyed a total of 453 parents of children aged 0-15 years, who had experiences with using antibiotics for their children. Correlation tests and regression analysis were used to explore the relationship between variables. RESULTS: Our findings showed that 42.2% of parents strongly agreed or agreed with the use of antibiotics as a means to cure a cold or flu in their child more quickly. In addition, 29.8% were not aware of antibiotic side effects. Non-compliance with antibiotic treatment was 35.8%, and 28.9% of surveyed parents suggested that they had pressured their pediatricians to prescribe antibiotics for their children. A total of 10.15% of parents had no information on antibiotic resistance, and 34.38% of parents responded that they did not believe that self-medication with antibiotics could lead to resistance. Regression analysis results indicated that gender and age group have a significant influence on the parents' decision that an antibiotic should be used in children with high fever (p < 0.001). CONCLUSIONS: Our findings suggest that antibiotic management by parents in Kosovo is not satisfactory, and more attention should be given to their knowledge of the side effects of antibiotics, bacterial resistance and reduction in the self-medication. Health education, adequate measures and interventions are needed to overcome this situation and ensure rational use of antibiotics in Kosovo.

Key lessons learnt from COVID-19 intra-action reviews in the Republic of Moldova, Montenegro, Kosovo and North Macedonia 2020-2021: a qualitative study.

OBJECTIVES: Our study described how the WHO intra-action review (IAR) methodology was operationalised and customised in three Western Balkan countries and territories and the Republic of Moldova and analysed the common key findings to inform analyses of the lessons learnt from the pandemic response. DESIGN: We extracted data from the respective IAR reports and performed a qualitative thematic content analysis to identify common (between countries and territories) and cross-cutting (across the response pillars) themes on best practices, challenges and priority actions. The analysis involved three stages, namely: extraction of data, initial identification of emerging themes and review and definition of the themes. SETTING: IARs were conducted in the Republic of Moldova, Montenegro, Kosovo and the Republic of North Macedonia between December 2020 and November 2021. The IARs were conducted at different time points relative to the respective pandemic trajectories (14-day incidence rate ranging from 23 to 495 per 100 000). RESULTS: Case management was reviewed in all the IARs, while the infection prevention and control, surveillance and country-level coordination pillars were reviewed in three countries. The thematic content analysis identified four common and cross-cutting best practices, seven challenges and six priority recommendations. Recommendations included investing in sustainable human resources and technical capacities developed during the pandemic, providing continuous capacity-building and training (with regular simulation exercises), updating legislation, improving communication between healthcare providers at all levels of healthcare and enhancing digitalisation of health information systems. CONCLUSIONS: The IARs provided an opportunity for continuous collective reflection and learning with multisectoral engagement. They also offered an opportunity to review public health emergency preparedness and response functions in general, thereby contributing to generic health systems strengthening and resilience beyond COVID-19. However, success in strengthening the response and preparedness requires leadership and resource allocation, prioritisation and commitment by the countries and territories themselves.

A National Cross-Sectional Study from the Republic of Kosovo on Lot Quality Assurance Sampling (LQAS) to Evaluate the Vaccination Status of Children Between 12 and 24 Months of Age During 2018 to 2020.

BACKGROUND In the Republic of Kosovo, full vaccination status in children under age 2 years includes: 1 dose of Bacillus Calmette-Guerin (BCG) hepatitis B virus (HBV) vaccine; 3 doses of diphtheria, tetanus, pertussis, hepatitis B, polio, and Haemophilus influenzae type b (DTaP-HB-IPV-Hib) vaccine; 3 doses of inactivated polio vaccine (IPV); and 1 dose of measles, mumps, and rubella (MMR) vaccine. Lot quality assurance sampling (LQAS) is a method used to assess the performance of health quality indicators. MATERIAL AND METHODS A national cross-sectional study with children aged between 12 and 24 months from Kosovo was performed between 2018 and 2020. The vaccination status of children was assessed with lot quality assurance sampling (LQAS) using randomized samples. RESULTS Among 430 children, more than 90% had completed the full immunization schedule. Delays in children's immunizations were observed. Most vaccinations showed short delays of less than 1 month, followed by delays of up to 3 months. The main reason for vaccination delay was the COVID-19 pandemic, following by child's illness at the scheduled time of vaccination or the parents were too busy to take the child to the vaccination site. Meanwhile, child age was the only parameter that showed difference among non-vaccinated and fully vaccinated (P<0.001). CONCLUSIONS LQAS analysis showed that between 2018 and 2020 lack of full immunization was due to delay caused by the parent not taking the child to the vaccination site, which may be prevented by improving information given to parents and the use of vaccination reminders.

Characterization of Biomarker Levels in Crimean-Congo Hemorrhagic Fever and Hantavirus Fever with Renal Syndrome.

Hemorrhagic fever with renal syndrome (HFRS) and Crimean-Congo hemorrhagic fever (CCHF) are important viral hemorrhagic fevers (VHF), especially in the Balkan region. Infections with Dobrava or Puumala orthohantavirus and Crimean-Congo hemorrhagic fever orthonairovirus can vary from a mild, nonspecific febrile illness, to a severe disease with a fatal outcome. The pathogenesis of both diseases is poorly understood, but it has been suggested that a host's immune mechanism might influence the pathogenesis of the diseases and survival. The aim of our study is to characterize cytokine response in patients with VHF in association with the disease progression and viral load. Forty soluble mediators of the immune response, coagulation, and endothelial dysfunction were measured in acute serum samples in 100 HFRS patients and 70 CCHF patients. HFRS and CCHF patients had significantly increased levels of IL-6, IL-12p70, IP-10, INF-γ, TNF-α, GM-CSF, MCP-3, and MIP-1b in comparison to the control group. Interestingly, HFRS patients had higher concentrations of serum MIP-1α, MIP-1ß, which promote activation of macrophages and NK cells. HFRS patients had increased concentrations of IFN-γ and TNF-α, while CCHF patients had significantly higher concentrations of IFN-α and IL-8. In both, CCHF and HFRS patients' viral load significantly correlated with IP-10. Patients with fatal outcome had significantly elevated concentrations of IL-6, IFN-α2 and MIP-1α, while GRO-α, chemokine related to activation of neutrophils and basophils, was downregulated. Our study provided a comprehensive characterization of biomarkers released in the acute stages of CCHF and HFRS.

Motors of influenza vaccination uptake and vaccination advocacy in healthcare workers: A comparative study in six European countries.

BACKGROUND: Annual vaccination is the most effective way to prevent and control the health and economic burden caused by seasonal influenza. Healthcare workers (HCWs) play a crucial role in vaccine acceptance and advocacy for their patients. This study explored the drivers of HCWs' vaccine acceptance and advocacy in six European countries. METHODS: Healthcare workers (mainly general practitioners, specialist physicians, and nurses) voluntarily completed a questionnaire in Bulgaria (N = 485), Czech Republic (N = 518), Kosovo (N = 466), Poland (N = 772), Romania (N = 155), and the United Kingdom (N = 80). Twelve-item scales were used to analyse sentiment clusters for influenza vaccination acceptance and engagement with vaccination advocacy. Past vaccination behaviour and patient recommendation were also evaluated. All data were included in a single analysis. RESULTS: For vaccination acceptance, the main cluster (engaged sentiment: 68%) showed strong positive attitudes for influenza vaccination. A second cluster (hesitant sentiment: 32%) showed more neutral attitudes. Cluster membership was predicted by country of origin and age. The odds ratio for past vaccination in the engaged cluster was 39.6 (95% CI 12.21-128.56) although this varied between countries. For vaccination advocacy, the main cluster (confident sentiment: 73%) showed strong positive attitudes towards advocacy; a second cluster (diffident sentiment: 27%) showed neutral attitudes. Cluster membership was predicted by country of origin, age and profession, with specialist physicians being the least likely to belong to the confident sentiment cluster. HCWs characterised by confident advocacy sentiments were also more likely recommend flu vaccination. Again, this association was moderated by country of origin. CONCLUSIONS: These data show that there is room to improve both vaccination acceptance and advocacy rates in European HCWs, which would be expected to lead to higher rates of HCW vaccination. Benefits that could be expected from such an outcome are improved advocacy and better control of morbidity and mortality related to seasonal influenza infection.

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.

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.