Browsing by Author "Poljak, Mario (55142297400)"

Previous multicenter/multinational studies were evaluated to determine the frequency of the absence of cerebrospinal fluid pleocytosis in patients with central nervous system infections, as well as the clinical impact of this condition. It was found that 18% of neurosyphilis, 7.9% of herpetic meningoencephalitis, 3% of tuberculous meningitis, 1.7% of Brucella meningitis, and 0.2% of pneumococcal meningitis cases did not display cerebrospinal fluid pleocytosis. Most patients were not immunosuppressed. Patients without pleocytosis had a high rate of unfavorable outcomes and thus this condition should not be underestimated. © 2017 The Author(s)

Cervical cancer is an important public health care problem in Europe. The overall incidence rate of cervical cancer in Europe is 10.6 per 100,000. However, within Europe, the incidence rates significantly differ, being lower in Western Europe where prevention programs are better developed. Significantly higher are the incidence and mortality rates in Central and Eastern Europe, being in close correlation to the intensity of organized screening. Human papillomavirus (HPV) vaccines are being delivered to the low-incidence populations that already have extensive screening programs, whereas the high-incidence countries have not implemented the vaccination programs yet. The resolution of the problem of cervical cancer control in Europe will be a matter of the implementation of public health care programs across the whole continent. © 2012 AACR.

The burden of cervical cancer in central and eastern Europe is generally higher compared to western or northern Europe due to a history of mostly opportunistic cervical cancer screening practices and due to the strong influence of political and economic changes in post-communist transition. This article describes the current cervical cancer screening practices, organizational plans for the future, and main obstacles that need to be overcome in 16 countries in central and eastern Europe: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, the Czech Republic, Estonia, Hungary, Latvia, Lithuania, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia and The former Yugoslav Republic of Macedonia. Unfortunately, only a few countries have managed to establish an organized and well-functioning cervical cancer screening program in recent years, whereas most countries in the region are still struggling with implementation-related issues of organized cervical cancer screening. Encouragingly, even in the countries where only opportunistic screening is performed, well-prepared plans and strategies have been established for switching to organized screening in the near future.

This paper summarises the position of ESGO and EFC on cervical screening based on existing guidelines and opinions of a team of lead experts. HPV test is replacing cytology as this offers greater protection against cervical cancer and allows longer screening intervals. Only a dozen of HPV tests are considered as clinically validated for screening. The lower specificity of HPV test dictates the use of triage tests that can select women for colposcopy. Reflex cytology is currently the only well validated triage test; HPV genotyping and p16 immunostaining may be used in the future, although methylation assays and viral load also look promising. A summary of quality assurance benchmarks is provided, and the importance to audit the screening histories of women who developed cancer is noted as a key objective. HPV-based screening is more cost-effective than cytology or cotesting. HPV-based screening should continue in the post-vaccination era. Only a fraction of the female population is vaccinated, and this varies across countries. A major challenge will be to personalise screening frequency according to vaccination status. Still the most important factor for successful prevention by screening is high population coverage and organised screening. Screening with self-sampling to reach under-screened women is promising. © 2020, Cancer Research UK.

This paper summarises the position of ESGO and EFC on cervical screening based on existing guidelines and opinions of a team of lead experts. HPV test is replacing cytology as this offers greater protection against cervical cancer and allows longer screening intervals. Only a dozen of HPV tests are considered as clinically validated for screening. The lower specificity of HPV test dictates the use of triage tests that can select women for colposcopy. Reflex cytology is currently the only well validated triage test; HPV genotyping and p16 immunostaining may be used in the future, although methylation assays and viral load also look promising. A summary of quality assurance benchmarks is provided, and the importance to audit the screening histories of women who developed cancer is noted as a key objective. HPV-based screening is more cost-effective than cytology or cotesting. HPV-based screening should continue in the post-vaccination era. Only a fraction of the female population is vaccinated, and this varies across countries. A major challenge will be to personalise screening frequency according to vaccination status. Still the most important factor for successful prevention by screening is high population coverage and organised screening. Screening with self-sampling to reach under-screened women is promising. © 2020, Cancer Research UK.

Background European guidelines recommend treatment of chronic hepatitis B virus infection (CHB) with the nucleos(t)ide analogs (NAs) entecavir or tenofovir. However, many European CHB patients have been exposed to other NAs, which are associated with therapy failure and resistance. The CAPRE study was performed to gain insight in prevalence and characteristics of NA resistance in Europe. Methods A survey was performed on genotypic resistance testing results acquired during routine monitoring of CHB patients with detectable serum hepatitis B virus DNA in European tertiary referral centers. Results Data from 1568 patients were included. The majority (73.8%) were exposed to lamivudine monotherapy. Drug-resistant strains were detected in 52.7%. The most frequently encountered primary mutation was M204V/I (48.7%), followed by A181T/V (3.8%) and N236T (2.6%). In patients exposed to entecavir (n = 102), full resistance was present in 35.3%. Independent risk factors for resistance were age, viral load, and lamivudine exposure (P <. 001). Conclusions These findings support resistance testing in cases of apparent NA therapy failure. This survey highlights the impact of exposure to lamivudine and adefovir on development of drug resistance and cross-resistance. Continued use of these NAs needs to be reconsidered at a pan-European level. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America.

The purpose of this study was to describe the current practice of mentorship in clinical microbiology (CM) and infectious diseases (ID) training, to identify possible areas for improvement and to assess the factors that are associated with satisfactory mentorship. An international cross-sectional survey containing 35 questions was answered by 317 trainees or specialists who recently completed clinical training. Overall, 179/317 (56%) trainees were satisfied with their mentors, ranging from 7/9 (78%) in non-European countries, 39/53 (74%) in Northern Europe, 13/22 (59%) in Eastern Europe, 61/110 (56%) in Western Europe, 37/76 (49%) in South-Western Europe to 22/47 (47%) in South-Eastern Europe. However, only 115/317 (36%) respondents stated that they were assigned an official mentor during their training. In multivariable logistic regression analysis, the satisfaction of trainees was significantly associated with having a mentor who was a career model (OR 6.4, 95%CI 3.5–11.7), gave constructive feedback on work performance (OR 3.3, 95%CI 1.8–6.2), and knew the family structure of the mentee (OR 5.5, 95%CI 3.0–10.1). If trainees felt overburdened, 70/317 (22%) felt that they could not talk to their mentors. Moreover, 67/317 (21%) stated that they could not talk to their mentor when unfairly treated and 59/317 (19%) felt uncertain. Training boards and authorities responsible for developing and monitoring CM&ID training programmes should invest in the development of high-quality mentorship programmes for trainees in order to contribute to the careers of the next generation of professionals. © 2019, The Author(s).

We present a review of the current implementation status of vaccination against human papillomaviruses (HPV) and available data concerning the burden of HPV infection and HPV type-specific distribution in 16 central and eastern European countries: Albania, Bosnia and Herzegovina, Bulgaria, Croatia, the Czech Republic, Estonia, Montenegro, Poland, Romania, Serbia, Slovakia, Slovenia, and The Former Yugoslav Republic of Macedonia. At least one current HPV prophylactic vaccine is registered in all central and eastern European countries except Montenegro. Six counties-Bulgaria, the Czech Republic, Latvia, Romania, Slovenia, and Former Yugoslav Republic of Macedonia-have integrated the HPV vaccination into their national immunization program and currently provide routine vaccination free of charge to the primary target population. Ten countries have not integrated HPV vaccination into the national immunization program. The key reasons for lack of implementation of HPV vaccination into the national immunization program are the high vaccine cost and negative public perception. Vaccination of males is not recommended in any country in the region.

Reiner RC Jr, Hay SI. Mapping geographical inequalities in childhood diarrhoeal morbidity and mortality in low-income and middle-income countries, 2000–17: analysis for the Global Burden of Disease Study 2017. Lancet 2020; 395: 1779–801—In this Article, the author byline has been amended to Local Burden of Disease Diarrhoea Collaborators. This correction has been made to the online version as of June 4, 2020, and the printed version is correct. © 2020 Elsevier Ltd

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The European HIV Drug Resistance Guidelines Panel, established to make recommendations to clinicians and virologists, felt that sufficient new information has become available to warrant an update of its recommendations, explained in both pocket guidelines and this full paper. The Panel makes the following recommendations concerning the indications for resistance testing: for HIV-1 (i) test earliest sample for protease and reverse transcriptase drug resistance in drug-naive patients with acute or chronic infection; (ii) test protease and reverse transcriptase drug resistance at virologic failure, and other drug targets (integrase and envelope) if such drugs were part of the failing regimen; (iii) consider testing for CCR5 tropism at virologic failure or when a change of therapy has to be made in absence of detectable viral load, and in the latter case test DNA or last detectable plasma RNA; (iv) consider testing earliest detectable plasma RNA when a successful nonnucleoside reverse transcriptase inhibitor-containing therapy was inappropriately interrupted; (v) genotype source patient when postexposure prophylaxis is considered; for HIV-2, (vi) consider resistance testing where treatment change is needed after treatment failure. The Panel recommends genotyping in most situations, using updated and clinically evaluated interpretation systems. It is mandatory that laboratories performing HIV resistance tests take part regularly in external quality assurance programs, and that they consider storing samples in situations where resistance testing cannot be performed as recommended. Similarly, it is necessary that HIV clinicians and virologists take part in continuous education and discuss problematic clinical cases. Indeed, resistance test results should be used in the context of all other clinically relevant information for predicting therapy response.

Background. Human immunodeficiency virus type 1 (HIV-1) subtype CRF01-AE originated in Africa and then passed to Thailand, where it established a major epidemic. Despite the global presence of CRF01-AE, little is known about its subsequent dispersal pattern. Methods. We assembled a global data set of 2736 CRF01-AE sequences by pooling sequences from public databases and patient-cohort studies. We estimated viral dispersal patterns, using statistical phylogeographic analysis run over bootstrap trees estimated by the maximum likelihood method. Results. We show that Thailand has been the source of viral dispersal to most areas worldwide, including 17 of 20 sampled countries in Europe. Japan, Singapore, Vietnam, and other Asian countries have played a secondary role in the viral dissemination. In contrast, China and Taiwan have mainly imported strains from neighboring Asian countries, North America, and Africa without any significant viral exportation. Discussion. The central role of Thailand in the global spread of CRF01-AE can be probably explained by the popularity of Thailand as a vacation destination characterized by sex tourism and by Thai emigration to the Western world. Our study highlights the unique case of CRF01-AE, the only globally distributed non-B clade whose global dispersal did not originate in Africa. © 2014 The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.

Objectives: The aim of this survey was to describe the current status of HIV care in the countries of Central and Eastern Europe and to investigate how close the region is to achieving the UNAIDS 2020 target of 90–90–90. Methods: In 2014, data were collected from 24 Central and Eastern European countries using a 38-item questionnaire. Results: All countries reported mandatory screening of blood and organ donors for HIV. Other groups subjected to targeted screening included people who inject drugs (PWID) (15/24, 62.5%), men who have sex with men (MSM) (14/24, 58.3%), and sex workers (12/24, 50.0%). Only 14 of the 24 countries (58.3%) screened pregnant women. The percentages of late presentation and advanced disease were 40.3% (range 14–80%) and 25.4% (range 9–50%), respectively. There was no difference between countries categorized by income or by region in terms of the percentages of persons presenting late or with advanced disease. The availability of newer antiretroviral drugs (rilpivirine, etravirine, darunavir, maraviroc, raltegravir, dolutegravir) tended to be significantly better with a higher country income status. Ten countries reported initiating antiretroviral therapy (ART) regardless of CD4+ T cell count (41.7%), five countries (20.8%) used the threshold of <500 cells/μl, and nine countries (37.5%) used the threshold of <350 cells/μl. Initiation of ART regardless of the CD4+ T cell count was significantly more common among high-income countries than among upper-middle-income and lower-middle-income countries (100% vs. 27.3% and 0%, respectively; p = 0.001). Drugs were provided free of charge in all countries and mostly provided by governments. There were significant discrepancies between countries regarding the follow-up of people living with HIV. Conclusions: There are major disparities in the provision of HIV care among sub-regions in Europe, which should be addressed. More attention in terms of funding, knowledge and experience sharing, and capacity building is required for the resource-limited settings of Central and Eastern Europe. The exact needs should be defined and services scaled up in order to achieve a standard level of care and provide an adequate and sustainable response to the HIV epidemic in this region. © 2018 The Authors

The Balkans is a gateway between Europe, Asia, and the African continent, a fact with potential important consequences on the epidemiology of HIV-1 infection in the region. The duration of the HIV-1 epidemics in many countries of the Balkans is similar to the one in the Western European countries. However, striking differences exist in several countries of the region in both the epidemic situation and, even more so, in our knowledge about it. In particular, the molecular epidemiology of HIV in the Balkans is largely unknown. In order to gain some preliminary insight into HIV-1 diversity in the region, we reviewed the available molecular epidemiology data about HIV-1 diversity in 10 countries of the region: Albania, Bulgaria, Croatia, Greece, Montenegro, Romania, Slovenia, Serbia, Turkey, and Hungary, a neighboring country to four Balkan countries. The data were obtained either from published studies or in direct communication with the participating members. The existing molecular epidemiology data revealed a broad diversity in subtype distribution among Balkan countries. In several countries, subtype B is predominant (e.g. Serbia, Slovenia, and Hungary), while in others the proportion of non-B subtypes is much larger (Albania subtype A, Romania subtype F). In some areas, HIV-1 subtype distribution is marked by divergence between different risk groups or transmission routes (e.g. Croatia). Recently, HIV-1/AIDS epidemics in Eastern Europe have been among the fastest growing in the world. Many major contributing factors for the breakout and spread of these epidemics are present in many of the Balkan countries, as reflected through the process of social transition, wars, unemployment, extensive drug use, high sexual risk behavior, as well as other factors. Yet, in the Balkan countries the prevalence rate of HIV-1 infection is low, under 0.1 percent. Concomitantly, the molecular epidemiology of HIV-1 in the Balkans has not been thoroughly studied so far. The review and analysis of the available data indicate a broad diversity of circulating HIV-1 subtypes in the region, with the predominance of non-B clades in some countries, underscoring the need for an ongoing surveillance of HIV-1 diversity. The setup of a collaborative network might provide important information for the better management and control of the HIV-1 epidemic in the area.

Background: Understanding HIV-1 subtype distribution and epidemiology can assist preventive measures and clinical decisions. Sequence variation may affect antiviral drug resistance development, disease progression, evolutionary rates and transmission routes.Results: We investigated the subtype distribution of HIV-1 in Europe and Israel in a representative sample of patients diagnosed between 2002 and 2005 and related it to the demographic data available. 2793 PRO-RT sequences were subtyped either with the REGA Subtyping tool or by a manual procedure that included phylogenetic tree and recombination analysis. The most prevalent subtypes/CRFs in our dataset were subtype B (66.1%), followed by sub-subtype A1 (6.9%), subtype C (6.8%) and CRF02_AG (4.7%). Substantial differences in the proportion of new diagnoses with distinct subtypes were found between European countries: the lowest proportion of subtype B was found in Israel (27.9%) and Portugal (39.2%), while the highest was observed in Poland (96.2%) and Slovenia (93.6%). Other subtypes were significantly more diagnosed in immigrant populations. Subtype B was significantly more diagnosed in men than in women and in MSM > IDUs > heterosexuals. Furthermore, the subtype distribution according to continent of origin of the patients suggests they acquired their infection there or in Europe from compatriots.Conclusions: The association of subtype with demographic parameters suggests highly compartmentalized epidemics, determined by social and behavioural characteristics of the patients. © 2013 Abecasis et al.; licensee BioMed Central Ltd.

Background: Understanding HIV-1 subtype distribution and epidemiology can assist preventive measures and clinical decisions. Sequence variation may affect antiviral drug resistance development, disease progression, evolutionary rates and transmission routes.Results: We investigated the subtype distribution of HIV-1 in Europe and Israel in a representative sample of patients diagnosed between 2002 and 2005 and related it to the demographic data available. 2793 PRO-RT sequences were subtyped either with the REGA Subtyping tool or by a manual procedure that included phylogenetic tree and recombination analysis. The most prevalent subtypes/CRFs in our dataset were subtype B (66.1%), followed by sub-subtype A1 (6.9%), subtype C (6.8%) and CRF02_AG (4.7%). Substantial differences in the proportion of new diagnoses with distinct subtypes were found between European countries: the lowest proportion of subtype B was found in Israel (27.9%) and Portugal (39.2%), while the highest was observed in Poland (96.2%) and Slovenia (93.6%). Other subtypes were significantly more diagnosed in immigrant populations. Subtype B was significantly more diagnosed in men than in women and in MSM > IDUs > heterosexuals. Furthermore, the subtype distribution according to continent of origin of the patients suggests they acquired their infection there or in Europe from compatriots.Conclusions: The association of subtype with demographic parameters suggests highly compartmentalized epidemics, determined by social and behavioural characteristics of the patients. © 2013 Abecasis et al.; licensee BioMed Central Ltd.

Background: HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe. Methods: This study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence. Results: At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32-3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by analysing drug-naïve patients (29.5% vs 21.2%, P = 0.032). Strong correlation was observed between sP120T and rtM204I/V (P < 0.001), and their co-presence determined an increased HBV-DNA. At least one NA-induced immune-escape mutation occurred in 28.6% of patients, and their selection correlated with genotype-A (OR[95%CI]:2.03[1.32-3.10],P = 0.001). Finally, stop-codons are present in 8.4% of patients also at HBsAg-positions 172 and 182, described to enhance viral oncogenic-properties. Conclusions: Immune-escape mutations and stop-codons develop in a large fraction of NA-exposed patients from Europe. This may represent a potential threat for horizontal and vertical HBV transmission also to vaccinated persons, and fuel drug-resistance emergence. © 2018 The Author(s).