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Abstract Background Malaria continues to be amongst the most frequent infectious diseases imported to Europe. Whilst European treatment guidelines are based on data from studies carried out in endemic areas, there is a paucity of original prospective treatment data. The objective was to summarize data on treatments to harmonize and optimize treatment for uncomplicated malaria in Europe. Methods A prospective observational multicentre study was conducted, assessing tolerance and efficacy of treatment regimens for imported uncomplicated falciparum malaria in adults amongst European centres of tropical and travel medicine. Results Between December 2003 and 2009, 504 patients were included in 16 centres from five European countries. Eighteen treatment regimens were reported, the top three being atovaquone-proguanil, mefloquine, and artemether-lumefantrine. Treatments significantly differed with respect to the occurrence of treatment changes (p = 0.005) and adverse events (p = 0.001), parasite and fever clearance times (p Conclusions This study highlights the heterogeneity of standards of care within Europe. A consensus discussion at European level is desirable to foster a standardized management of imported falciparum malaria.

Abstract Background Hepatitis C virus (HCV) is a leading cause of chronic liver disease, end-stage cirrhosis, and liver cancer, but little is known about the burden of disease caused by the virus. We summarised burden of disease data presently available for Europe, compared the data to current expert estimates, and identified areas in which better data are needed. Methods Literature and international health databases were systematically searched for HCV-specific burden of disease data, including incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and liver transplantation. Data were collected for the WHO European region with emphasis on 22 countries. If HCV-specific data were unavailable, these were calculated via HCV-attributable fractions. Results HCV-specific burden of disease data for Europe are scarce. Incidence data provided by national surveillance are not fully comparable and need to be standardised. HCV prevalence data are often inconclusive. According to available data, an estimated 7.3–8.8 million people (1.1–1.3%) are infected in our 22 focus countries. HCV-specific mortality, DALY, and transplantation data are unavailable. Estimations via HCV-attributable fractions indicate that HCV caused more than 86000 deaths and 1.2 million DALYs in the WHO European region in 2002. Most of the DALYs (95%) were accumulated by patients in preventable disease stages. About one-quarter of the liver transplants performed in 25 European countries in 2004 were attributable to HCV. Conclusion Our results indicate that hepatitis C is a major health problem and highlight the importance of timely antiviral treatment. However, data on the burden of disease of hepatitis C in Europe are scarce, outdated or inconclusive, which indicates that hepatitis C is still a neglected disease in many countries. What is needed are public awareness, co-ordinated action plans, and better data. European physicians should be aware that many infections are still undetected, provide timely testing and antiviral treatment, and avoid iatrogenic transmission.

Abstract A comparison was made between local malaria transmission and malaria imported by travellers to identify the utility of national and regional annual parasite index (API) in predicting malaria risk and its value in generating recommendations on malaria prophylaxis for travellers. Regional malaria transmission data was correlated with malaria acquired in Latin America and imported into the USA and nine European countries. Between 2000 and 2004, most countries reported declining malaria transmission. Highest API's in 2003/4 were in Surinam (287.4) Guyana (209.2) and French Guiana (147.4). The major source of travel associated malaria was Honduras, French Guiana, Guatemala, Mexico and Ecuador. During 2004 there were 6.3 million visits from the ten study countries and in 2005, 209 cases of malaria of which 22 (11%) were Plasmodium falciparum. The risk of adverse events are high and the benefit of avoided benign vivax malaria is very low under current policy, which may be causing more harm than benefit.

Abstract Background Malaria parasites that carry the DHFR-mutation I164L are not only highly resistant to sulfadoxine-pyrimethamine but also to the new antimalarial drug chlorproguanil-dapsone. The spread of this mutation in Africa would result in a public health disaster since there is a lack of effective alternatives that are both affordable and safe. Up to now, this mutation has only been described in Asian and Latin-American countries. The objective of this study was to assess the prevalence of this mutation in African isolates of Plasmodium falciparum that have been imported into Europe through travellers. Methods TropNetEurop is a network for the surveillance of travel-associated diseases and seems to cover approximately 12% of all malaria cases imported into Europe. Within this network we screened 277 imported African isolates of P. falciparum with the help of PCR- and enzyme-digestion-methods for the antifolate-resistant mutation I164L. Results The I164L mutation was not detected in any of the isolates tested. Discussion Continuous molecular surveillance of mutations in P. falciparum, as it is practised within TropNetEurop, is an essential tool for the understanding and early detection of the spread of antimalarial drug resistance in Africa.

Abstract Background Results from numerous studies point convincingly to correlations between mutations at selected genes and phenotypic resistance to antimalarials in Plasmodium falciparum isolates. In order to move molecular assays for point mutations on resistance-related genes into the realm of applied tools for surveillance, we investigated a selection of P. falciparum isolates that were imported during the year 2001 into Europe to study the prevalence of resistance-associated point mutations at relevant codons. In particular, we tested for parasites which were developing resistance to antifolates and chloroquine. The screening results were used to map the prevalence of mutations and, thus, levels of potential drug resistance in endemic areas world-wide. Results 337 isolates have been tested so far. Prevalence of mutations that are associated with resistance to chloroquine on the pfcrt and pfmdr genes of P. falciparum was demonstrated at high levels. However, the prevalence of mutations associated with resistance to antifolates at the DHFR and DHPS genes was unexpectedly low, rarely exceeding 60% in endemic areas. Conclusions Constant screening of imported isolates will enable TropNetEurop to establish a screening tool for emerging resistance in endemic areas.

Background: Stool DNA testing for early detection of colorectal cancer (CRC) is a non-invasive technology with the potential to supplement established CRC screening tests. The aim of this health technology assessment was to evaluate effectiveness and safety of currently CE-marked stool DNA tests, compared to other CRC tests in CRC screening strategies in an asymptomatic screening population.Methods: The assessment was carried out following the guidelines of the European Network for Health Technology Assessment (EUnetHTA). This included a systematic literature search in MED-LINE, Cochrane and EMBASE in 2018. Manufacturers were asked to provide additional data. Five patient interviews helped assessing potential ethical or social aspects and patients’ experiences and preferences. We assessed the risk of bias using QUADAS-2, and the quality of the body of evidence using GRADE.Results: We identified three test accuracy studies, two of which investigated a multitarget stool DNA test (Cologuard, compared fecal immunochemical test (FIT)) and one a combined DNA stool assay (ColoAlert, compared to guaiac-based fecal occult blood test (gFOBT), Pyruvate Kinase Isoenzyme Type M2 (M2-PK) and combined gFOBT/M2-PK). We found five published surveys on patient satisfaction. No primary study investigating screening effects on CRC incidence or on overall mortality was found. Both stool DNA tests showed in direct comparison higher sensitivity for the detection of CRC and (advanced) adenoma compared to FIT, or gFOBT, respectively, but had lower specificity. However, these comparative results may depend on the exact type of FIT used. The reported test failure rates were higher for stool DNA testing than for FIT. The certainty of evidence was moderate to high for Cologuard studies, and low to very low for the ColoAlert study which refers to a former version of the product and yielded no direct evidence on the test accuracy for ad-vanced versus non-advanced adenoma.Conclusions: ColoAlert is the only stool DNA test currently sold in Europe and is available at a lower price than Cologuard, but reliable evidence is lacking. A screening study including the current product version of ColoAlert and suitable comparators would, therefore, help evaluate the effectiveness of this screening option in a European context.

Individuals with a family history of colorectal cancer (CRC) may benefit from early screening with colonoscopy or immunologic fecal occult blood testing (iFOBT). We systematically evaluated the benefit‐harm trade‐offs of various screening strategies differing by screening test (colonoscopy or iFOBT), interval (iFOBT: annual/biennial; colonoscopy: 10‐yearly) and age at start (30, 35, 40, 45, 50 and 55 years) and end of screening (65, 70 and 75 years) offered to individuals identified with familial CRC risk in Germany. A Markov‐state‐transition model was developed and used to estimate health benefits (CRC‐related deaths avoided, life‐years gained [LYG]), potential harms (eg, associated with additional colonoscopies) and incremental harm‐benefit ratios (IHBR) for each strategy. Both benefits and harms increased with earlier start and shorter intervals of screening. When screening started before age 50, 32‐36 CRC‐related deaths per 1000 persons were avoided with colonoscopy and 29‐34 with iFOBT screening, compared to 29‐31 (colonoscopy) and 28‐30 (iFOBT) CRC‐related deaths per 1000 persons when starting age 50 or older, respectively. For iFOBT screening, the IHBRs expressed as additional colonoscopies per LYG were one (biennial, age 45‐65 vs no screening), four (biennial, age 35‐65), six (biennial, age 30‐70) and 34 (annual, age 30‐54; biennial, age 55‐75). Corresponding IHBRs for 10‐yearly colonoscopy were four (age 55‐65), 10 (age 45‐65), 15 (age 35‐65) and 29 (age 30‐70). Offering screening with colonoscopy or iFOBT to individuals with familial CRC risk before age 50 is expected to be beneficial. Depending on the accepted IHBR threshold, 10‐yearly colonoscopy or alternatively biennial iFOBT from age 30 to 70 should be recommended for this target group. [ABSTRACT FROM AUTHOR]

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Background and objective: The distribution of the newly developed vaccines presents a great challenge in the ongoing SARS-CoV-2 pandemic. Policy makers must decide which subgroups should be vaccinated first to minimize the negative consequences of the pandemic. These decisions must be made upfront and under uncertainty regarding the amount of vaccine doses available at a given time. The objective of the present work was to develop an iterative optimization algorithm, which provides a prioritization order of predefined subgroups. The results of this algorithm should be optimal but also robust with respect to potentially limited vaccine supply. Methods: We present an optimization meta-heuristic which can be used in a classic simulation-optimization setting with a simulation model in a feedback loop. The meta-heuristic can be applied in combination with any epidemiological simulation model capable of depicting the effects of vaccine distribution to the modeled population, accepts a vaccine prioritization plan in a certain notation as input, and generates decision making relevant variables such as COVID-19 caused deaths or hospitalizations as output. We finally demonstrate the mechanics of the algorithm presenting the results of a case study performed with an epidemiological agent-based model. Results: We show that the developed method generates a highly robust vaccination prioritization plan which is proven to fulfill an elegant supremacy criterion: the plan is equally optimal for any quantity of vaccine doses available. The algorithm was tested on a case study in the Austrian context and it generated a vaccination plan prioritization favoring individuals age 65+, followed by vulnerable groups, to minimize COVID-19 related burden. Discussion: The results of the case study coincide with the international policy recommendations which strengthen the applicability of the approach. We conclude that the path-dependent optimum optimum provided by the algorithm is well suited for real world applications, in which decision makers need to develop strategies upfront under high levels of uncertainty. [ABSTRACT FROM AUTHOR]

Objectives: Benefit and cost effectiveness of breast cancer screening are still matters of controversy. Risk-adapted strategies are proposed to improve its benefit-harm and cost-benefit relations. Our objective was to perform a systematic review on economic breast cancer models evaluating primary and secondary prevention strategies in the European health care setting, with specific focus on model results, model characteristics, and risk-adapted strategies.Methods: Literature databases were systematically searched for economic breast cancer models evaluating the cost effectiveness of breast cancer screening and prevention strategies in the European health care context. Characteristics, methodological details and results of the identified studies are reported in evidence tables. Economic model outputs are standardized to achieve comparable cost-effectiveness ratios.Results: Thirty-two economic evaluations of breast cancer screening and seven evaluations of primary breast cancer prevention were included. Five screening studies and none of the prevention studies considered risk-adapted strategies. Studies differed in methodologic features. Only about half of the screening studies modeled overdiagnosis-related harms, most often indirectly and without reporting their magnitude. All models predict gains in life expectancy and/or quality-adjusted life expectancy at acceptable costs. However, risk-adapted screening was shown to be more effective and efficient than conventional screening.Conclusions: Economic models suggest that breast cancer screening and prevention are cost effective in the European setting. All screening models predict gains in life expectancy, which has not yet been confirmed by trials. European models evaluating risk-adapted screening strategies are rare, but suggest that risk-adapted screening is more effective and efficient than conventional screening. [ABSTRACT FROM AUTHOR]

Background: Iodine deficiency is one of the most prevalent causes of intellectual disability and can lead to impaired thyroid function and other iodine deficiency disorders (IDDs). Despite progress made on eradicating iodine deficiency in the last decades in Europe, IDDs are still prevalent. Currently, evidence-based information on the benefit/harm balance of IDD prevention in Europe is lacking. We developed a decision-analytic model and conducted a public health decision analysis for the long-term net benefit of a mandatory IDD prevention program for the German population with moderate iodine deficiency, as a case example for a European country. Methods: We developed a decision-analytic Markov model simulating the incidence and consequences of IDDs in the absence or presence of a mandatory IDD prevention program (iodine fortification of salt) in an open population with current demographic characteristics in Germany and with moderate ID. We collected data on the prevalence, incidence, mortality, and quality of life from European studies for all health states of the model. Our primary net-benefit outcome was quality-adjusted life years (QALYs) predicted over a period of 120 years. In addition, we calculated incremental life years and disease events over time. We performed a systematic and comprehensive uncertainty assessment using multiple deterministic one-way sensitivity analyses. Results: In the base-case analysis, the IDD prevention program is more beneficial than no prevention, both in terms of QALYs and life years. Health gains predicted for the open cohort over a time horizon of 120 years for the German population (82.2 million inhabitants) were 33 million QALYs and 5 million life years. Nevertheless, prevention is not beneficial for all individuals since it causes additional hyperthyroidism (2.7 million additional cases). Results for QALY gains were stable in sensitivity analyses. Conclusions: IDD prevention via mandatory iodine fortification of salt increases quality-adjusted life expectancy in a European population with moderate ID, and is therefore beneficial on a population level. However, further ethical aspects should be considered before implementing a mandatory IDD prevention program. Costs for IDD prevention and treatment should be determined to evaluate the cost effectiveness of IDD prevention. [ABSTRACT FROM AUTHOR]

Background: A recent recalibration of the ONCOTYROL Prostate Cancer Outcome and Policy (PCOP) Model, assuming that latent prostate cancer (PCa) detectable at autopsy might be detectable by screening as well, resulted in considerable worsening of the benefit-harm balance of screening. In this study, we used the recalibrated model to assess the effects of familial risk, quality of life (QoL) preferences, age, and active surveillance.Methods: Men with average and elevated familial PCa risk were simulated in separate models, differing in familial risk parameters. Familial risk was assumed to affect PCa onset and progression simultaneously in the base-case, and separately in scenario analyses. Evaluated screening strategies included one-time screening at different ages, and screening at different intervals and age ranges. Optimal screening strategies were identified depending on age and individual QoL preferences. Strategies were additionally evaluated with active surveillance by biennial re-biopsy delaying treatment of localized cancer until grade progression to Gleason score ≥ 7.Results: Screening men with average PCa risk reduced quality-adjusted life expectancy (QALE) even under favorable assumptions. Men with elevated familial risk, depending on age and disutilities, gained QALE. While for men with familial risk aged 55 and 60 years annual screening to age 69 was the optimal strategy over most disutility ranges, no screening was the preferred option for 65 year-old men with average and above disutilities. Active surveillance greatly reduced overtreatment, but QALE gains by averted adverse events were opposed by losses due to delayed treatment and additional biopsies. The effect of active surveillance on the benefit-harm balance of screening differed between populations, as net losses and gains in QALE predicted for screening without active surveillance in men with average and familial PCa risk, respectively, were both reduced.Conclusions: Assumptions about PCa risk and screen-detectable prevalence significantly affect the benefit-harm balance of screening. Based on the assumptions of our model, PCa screening should focus on candidates with familial predisposition with consideration of individual QoL preferences and age. Active surveillance may require treatment initiation before Gleason score progression to 7. Alternative active surveillance strategies should be evaluated in further modeling studies. [ABSTRACT FROM AUTHOR]

Background. The ONCOTYROL Prostate Cancer Outcome and Policy (PCOP) model is a state-transition microsimulation model evaluating the benefits and harms of prostate cancer (PCa) screening. The natural history and detection component of the original model was based on the 2003 version of the Erasmus MIcrosimulation SCreening ANalysis (MISCAN) model, which was not calibrated to prevalence data. Compared with data from autopsy studies, prevalence of latent PCa assumed by the original model is low, which may bias the model toward screening. Our objective was to recalibrate the original model to match prevalence data from autopsy studies as well and compare benefit-harm predictions of the 2 model versions differing in prevalence. Methods. For recalibration, we reprogrammed the natural history and detection component of the PCOP model as a deterministic Markov state-transition cohort model in the statistical software package R. All parameters were implemented as variables or time-dependent functions and calibrated simultaneously in a single run. Observed data used as calibration targets included data from autopsy studies, cancer registries, and the European Randomized Study of Screening for Prostate Cancer. Compared models were identical except for calibrated parameters. Results. We calibrated 46 parameters. Prevalence from autopsy studies could not be fitted using the original parameter set. Additional parameters, allowing for interruption of disease progression and age-dependent screening sensitivities, were needed. Recalibration to higher prevalence demonstrated a considerable increase of overdiagnosis and decline of screening sensitivity, which significantly worsened the benefit-harm balance of screening. Conclusions. Our calibration suggests that not all cancers are at risk of progression, and screening sensitivity may be lower at older ages. PCa screening models that use calibration to simulate disease progression in the unobservable latent phase are highly sensitive to prevalence assumptions. [ABSTRACT FROM AUTHOR]

Introduction: Urinary and erectile functions were assessed by using self-administered validated questionnaires in patients undergoing radical prostatectomy. Materials and Methods: In a prospective observational study, a total of 253 consecutive patients diagnosed with clinically localised prostate cancer between 2008 and 2009 at the European Prostate Centre Innsbruck were included. Patient-reported outcomes were assessed before radical prostatectomy and 12 months postoperatively using the validated International Consultation on Incontinence Questionnaire (ICIQ) and the International Index of Erectile Function (IIEF). The Wilcoxon signed-rank test and Chi square statistics were used for analysis. Results: The study showed that before radical prostatectomy, urinary incontinence of various severity grades was reported in 18.8, postoperatively in 63.0% (p < 0.001) and erectile dysfunction of various degrees was reported in 39.6 at baseline compared to 80.1% 12 months postoperatively (p < 0.001). Conclusions: This study suggests that radical prostatectomy is associated with a significantly increased risk of urinary incontinence and erectile dysfunction 12 months postoperatively. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In 2009, the European Centre for Disease Prevention and Control initiated the ‘Burden of Communicable Diseases in Europe (BCoDE)’ project to generate evidence-based and comparable burden-of-disease estimates of infectious diseases in Europe. The burden-of-disease metric used was the Disability-Adjusted Life Year (DALY), composed of years of life lost due to premature death (YLL) and due to disability (YLD). To better represent infectious diseases, a pathogen-based approach was used linking incident cases to sequelae through outcome trees. Health outcomes were included if an evidence-based causal relationship between infection and outcome was established. Life expectancy and disability weights were taken from the Global Burden of Disease Study and alternative studies. Disease progression parameters were based on literature. Country-specific incidence was based on surveillance data corrected for underestimation. Non-typhoidal Salmonella spp. and Campylobacter spp. were used for illustration. Using the incidence- and pathogen-based DALY approach the total burden for Salmonella spp. and Campylobacter spp. was estimated at 730 DALYs and at 1,780 DALYs per year in the Netherlands (average of 2005–2007). Sequelae accounted for 56% and 82% of the total burden of Salmonella spp. and Campylobacter spp., respectively. The incidence- and pathogen-based DALY methodology allows in the case of infectious diseases a more comprehensive calculation of the disease burden as subsequent sequelae are fully taken into account. Not considering subsequent sequelae would strongly underestimate the burden of infectious diseases. Estimates can be used to support prioritisation and comparison of infectious diseases and other health conditions, both within a country and between countries. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) is a leading cause of chronic liver disease, end-stage cirrhosis, and liver cancer, but little is known about the burden of disease caused by the virus. We summarised burden of disease data presently available for Europe, compared the data to current expert estimates, and identified areas in which better data are needed. Methods: Literature and international health databases were systematically searched for HCV-specific burden of disease data, including incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and liver transplantation. Data were collected for the WHO European region with emphasis on 22 countries. If HCV-specific data were unavailable, these were calculated via HCV-attributable fractions. Results: HCV-specific burden of disease data for Europe are scarce. Incidence data provided by national surveillance are not fully comparable and need to be standardised. HCV prevalence data are often inconclusive. According to available data, an estimated 7.3-8.8 million people (1.1-1.3%) are infected in our 22 focus countries. HCV-specific mortality, DALY, and transplantation data are unavailable. Estimations via HCV-attributable fractions indicate that HCV caused more than 86000 deaths and 1.2 million DALYs in the WHO European region in 2002. Most of the DALYs (95%) were accumulated by patients in preventable disease stages. About one-quarter of the liver transplants performed in 25 European countries in 2004 were attributable to HCV. Conclusion: Our results indicate that hepatitis C is a major health problem and highlight the importance of timely antiviral treatment. However, data on the burden of disease of hepatitis C in Europe are scarce, outdated or inconclusive, which indicates that hepatitis C is still a neglected disease in many countries. What is needed are public awareness, co-ordinated action plans, and better data. European physicians should be aware that many infections are still undetected, provide timely testing and antiviral treatment, and avoid iatrogenic transmission. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to summarize the current evidence for the cost-effectiveness of primarily human papillomavirus (HPV) -based cervical cancer screening in settings with already established Papanicolaou test (Pap) programs. Emphasis was placed on the German situation with annual Pap screening.Methods: Medical, economic, and health technology assessment (HTA) databases were systematically searched for cost-effectiveness studies comparing HPV to Pap screening. Study data were extracted, standardized, and summarized in cost-effectiveness plots contrasting HPV strategies to Pap screening with 1-, 2-, 3-, and 5-years interval. For each Pap setting, the likelihood of cost-effective HPV screening was assessed depending on willingness-to-pay.Results: We reviewed twelve decision-analytic cost-effectiveness models. Study results showed wide variation due to methodical heterogeneity. Data synthesis revealed that the cost-effectiveness of HPV screening depends on the interval of the established Pap screening strategy. In comparison with Pap screening every 2 years, only 25 percent of the HPV-based screening strategies were cost-effective. However, in comparison with Pap screening every 1, 3, or 5 years, 83 percent, 55 percent, and 92 percent of HPV screening strategies were cost-effective, respectively. Results for settings with annual Pap screening are based on models assuming 100 percent screening coverage.Conclusions: The introduction of HPV-based screening programs is cost-effective if the screening interval of the established Pap program exceeds 2 years. In settings with biennial Pap screening, introduction of HPV-based screening is unlikely to be cost-effective. Results also suggest cost-effectiveness of HPV-based screening in settings with annual Pap screening; however, this finding should be confirmed under realistic screening adherence assumptions. [ABSTRACT FROM AUTHOR]

Background. Dengue fever is the most common arboviral disease in travelers. In countries where dengue virus is endemic, sequential (secondary) infections with different dengue virus serotypes are associated with disease severity. Data on severity and secondary infection rates in a population of travelers are lacking. Methods. Intensified surveillance of dengue fever in travelers was performed within the European Network on Surveillance of Imported Infectious Diseases. Data were collected at 14 European clinical referral centers between 2003 and 2005. Results. A total of 219 dengue virus infections imported from various regions of endemicity were reported. Serological analysis revealed a secondary immune response in 17%. Spontaneous bleeding was observed in 17 (8%) patients and was associated with increased serum alanine and aspartate aminotransferase levels and lower median platelet counts. Two (0.9%) patients fulfilled the World Health Organization (WHO) case definition for dengue hemorrhagic fever. However, 23 (11%) travelers had severe clinical manifestations (internal hemorrhage, plasma leakage, shock, or marked thrombocytopenia). A secondary immune response was significantly associated with both spontaneous bleeding and other severe clinical manifestations. Conclusions. In travelers, severe dengue virus infections are not uncommon but may be missed if the WHO classification is strictly applied. High liver enzyme levels and low platelet counts could serve as indicators of disease severity. [ABSTRACT FROM AUTHOR]

Background: Due to time constraints imposed by pending departure dates of travelers, the application of multiple vaccinations is commonly practiced in pretravel counseling. However, data regarding the tolerability of schedules with simultaneous vaccinations with different products are sparse.Method: In order to investigate effects of this practice, a prospective study was conducted with 1,183 healthy travelers who presented prior to their departure. Standardized questionnaires covering possible side effects were collected during and after vaccination.Results: Results showed an increase of the overall frequency of side effects with an increasing number of simultaneously applied vaccines. In travelers with two or more vaccinations, side effects occurred less frequently than previously published. In double vaccinations, side effects occurred in 36.7% of vaccinees, triple vaccinations in 40.3%, in more than three vaccinations in 50.0%. Subjective rating by the vaccinees showed an excellent tolerability of multiple vaccinations.Conclusion: Multiple vaccines can be given at the same time with limited subjective side effects. These findings may increase the acceptability of vaccinations given in combination to travelers. [ABSTRACT FROM AUTHOR]

Background: Malaria parasites that carry the DHFR-mutation I164L are not only highly resistant to sulfadoxine-pyrimethamine but also to the new antimalarial drug chlorproguanil-dapsone. The spread of this mutation in Africa would result in a public health disaster since there is a lack of effective alternatives that are both affordable and safe. Up to now, this mutation has only been described in Asian and Latin-American countries. The objective of this study was to assess the prevalence of this mutation in African isolates of Plasmodium falciparum that have been imported into Europe through travellers. Methods: TropNetEurop is a network for the surveillance of travel-associated diseases and seems to cover approximately 12% of all malaria cases imported into Europe. Within this network we screened 277 imported African isolates of P. falciparum with the help of PCR- and enzymedigestion-methods for the antifolate-resistant mutation I164L. Results: The I164L mutation was not detected in any of the isolates tested. Discussion: Continuous molecular surveillance of mutations in P. falciparum, as it is practised within TropNetEurop, is an essential tool for the understanding and early detection of the spread of antimalarial drug resistance in Africa. [ABSTRACT FROM AUTHOR]

Background: Results from numerous studies point convincingly to correlations between mutations at selected genes and phenotypic resistance to antimalarials in Plasmodium falciparum isolates. In order to move molecular assays for point mutations on resistance-related genes into the realm of applied tools for surveillance, we investigated a selection of P. falciparum isolates that were imported during the year 2001 into Europe to study the prevalence of resistance-associated point mutations at relevant codons. In particular, we tested for parasites which were developing resistance to antifolates and chloroquine. The screening results were used to map the prevalence of mutations and, thus, levels of potential drug resistance in endemic areas world-wide. Results: 337 isolates have been tested so far. Prevalence of mutations that are associated with resistance to chloroquine on the pfcrt and pfmdr genes of P. falciparum was demonstrated at high levels. However, the prevalence of mutations associated with resistance to antifolates at the DHFR and DHPS genes was unexpectedly low, rarely exceeding 60% in endemic areas. Conclusions: Constant screening of imported isolates will enable TropNetEurop to establish a screening tool for emerging resistance in endemic areas. [ABSTRACT FROM AUTHOR]

This article describes a new method of collecting data by direct mailing via the Internet. Feasibility and capacities were evaluated through a worldwide opinion poll on global future risks of mankind and potential solutions. Within 1 day, a structured questionnaire was sent to 8,859 randomly selected e-mail addresses. One thousand seven hundred and thirteen were remailed properly completed, 90% within 4 days. Most respondents were residents of North America (64%) and Europe (21 %), male (87%), and 30 years old on average. Environmental destruction (52%) was mentioned as the primary problem, followed by violence (45%) and unemployment (45%). Education (71 %) was the most frequently proposed solution to future problems. It is obvious that Internet surveys at this time are not repre sentative of the total population. However, they open new dimensions in the interrogation of experts and opinion leaders, especially considering their efficiency and potential for automation. [ABSTRACT FROM PUBLISHER]

(1) Background: The Austrian supply of COVID-19 vaccine is limited for now. We aim to provide evidence-based guidance to the authorities in order to minimize COVID-19-related hospitalizations and deaths in Austria. (2) Methods: We used a dynamic agent-based population model to compare different vaccination strategies targeted to the elderly (65 ≥ years), middle aged (45–64 years), younger (15–44 years), vulnerable (risk of severe disease due to comorbidities), and healthcare workers (HCW). First, outcomes were optimized for an initially available vaccine batch for 200,000 individuals. Second, stepwise optimization was performed deriving a prioritization sequence for 2.45 million individuals, maximizing the reduction in total hospitalizations and deaths compared to no vaccination. We considered sterilizing and non-sterilizing immunity, assuming a 70% effectiveness. (3) Results: Maximum reduction of hospitalizations and deaths was achieved by starting vaccination with the elderly and vulnerable followed by middle-aged, HCW, and younger individuals. Optimizations for vaccinating 2.45 million individuals yielded the same prioritization and avoided approximately one third of deaths and hospitalizations. Starting vaccination with HCW leads to slightly smaller reductions but maximizes occupational safety. (4) Conclusion: To minimize COVID-19-related hospitalizations and deaths, our study shows that elderly and vulnerable persons should be prioritized for vaccination until further vaccines are available. [ABSTRACT FROM AUTHOR]

Background: Hepatitis C virus (HCV) is a leading cause of chronic liver disease, end-stage cirrhosis, and liver cancer, but little is known about the burden of disease caused by the virus. We summarised burden of disease data presently available for Europe, compared the data to current expert estimates, and identified areas in which better data are needed. Methods: Literature and international health databases were systematically searched for HCV-specific burden of disease data, including incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and liver transplantation. Data were collected for the WHO European region with emphasis on 22 countries. If HCV-specific data were unavailable, these were calculated via HCV-attributable fractions. Results: HCV-specific burden of disease data for Europe are scarce. Incidence data provided by national surveillance are not fully comparable and need to be standardised. HCV prevalence data are often inconclusive. According to available data, an estimated 7.3–8.8 million people (1.1–1.3%) are infected in our 22 focus countries. HCV-specific mortality, DALY, and transplantation data are unavailable. Estimations via HCV-attributable fractions indicate that HCV caused more than 86000 deaths and 1.2 million DALYs in the WHO European region in 2002. Most of the DALYs (95%) were accumulated by patients in preventable disease stages. About one-quarter of the liver transplants performed in 25 European countries in 2004 were attributable to HCV. Conclusion: Our results indicate that hepatitis C is a major health problem and highlight the importance of timely antiviral treatment. However, data on the burden of disease of hepatitis C in Europe are scarce, outdated or inconclusive, which indicates that hepatitis C is still a neglected disease in many countries. What is needed are public awareness, co-ordinated action plans, and better data. European physicians should be aware that many infections are still undetected, provide timely testing and antiviral treatment, and avoid iatrogenic transmission.

Background: Clear evidence on the benefit-harm balance and cost effectiveness of population-based screening for colorectal cancer (CRC) is missing. We aim to systematically evaluate the long-term effectiveness, harms and cost effectiveness of different organized CRC screening strategies in Austria.Methods: A decision-analytic cohort simulation model for colorectal adenoma and cancer with a lifelong time horizon was developed, calibrated to the Austrian epidemiological setting and validated against observed data. We compared four strategies: 1) No Screening, 2) FIT: annual immunochemical fecal occult blood test age 40-75 years, 3) gFOBT: annual guaiac-based fecal occult blood test age 40-75 years, and 4) COL: 10-yearly colonoscopy age 50-70 years. Predicted outcomes included: benefits expressed as life-years gained [LYG], CRC-related deaths avoided and CRC cases avoided; harms as additional complications due to colonoscopy (physical harm) and positive test results (psychological harm); and lifetime costs. Tradeoffs were expressed as incremental harm-benefit ratios (IHBR, incremental positive test results per LYG) and incremental cost-effectiveness ratios [ICER]. The perspective of the Austrian public health care system was adopted. Comprehensive sensitivity analyses were performed to assess uncertainty.Results: The most effective strategies were FIT and COL. gFOBT was less effective and more costly than FIT. Moving from COL to FIT results in an incremental unintended psychological harm of 16 additional positive test results to gain one life-year. COL was cost saving compared to No Screening. Moving from COL to FIT has an ICER of 15,000 EUR per LYG.Conclusions: Organized CRC-screening with annual FIT or 10-yearly colonoscopy is most effective. The choice between these two options depends on the individual preferences and benefit-harm tradeoffs of screening candidates. [ABSTRACT FROM AUTHOR]