Non-invasive assessment of disease progression and neuroprotective effects of dietary coconut oil supplementation in the ALS SOD1G93A mouse model: A 1H-magnetic resonance spectroscopic study.

Amyotrophic Lateral Sclerosis (ALS) is an incurable neurodegenerative disease primarily characterized by progressive degeneration of motor neurons in the motor cortex, brainstem and spinal cord. Due to relatively fast progression of ALS, early diagnosis is essential for possible therapeutic intervention and disease management. To identify potential diagnostic markers, we investigated age-dependent effects of disease onset and progression on regional neurochemistry in the SOD1G93A ALS mouse model using localized in vivo magnetic resonance spectroscopy (MRS). We focused mainly on the brainstem region since brainstem motor nuclei are the primarily affected regions in SOD1G93A mice and ALS patients. In addition, metabolite profiles of the motor cortex were also assessed. In the brainstem, a gradual decrease in creatine levels were detected starting from the pre-symptomatic age of 70 days postpartum. During the early symptomatic phase (day 90), a significant increase in the levels of the inhibitory neurotransmitter γ- aminobutyric acid (GABA) was measured. At later time points, alterations in the form of decreased NAA, glutamate, glutamine and increased myo-inositol were observed. Also, decreased glutamate, NAA and increased taurine levels were seen at late stages in the motor cortex. A proof-of-concept (PoC) study was conducted to assess the effects of coconut oil supplementation in SODG93A mice. The PoC revealed that the coconut oil supplementation together with the regular diet delayed disease symptoms, enhanced motor performance, and prolonged survival in the SOD1G93A mouse model. Furthermore, MRS data showed stable metabolic profile at day 120 in the coconut oil diet group compared to the group receiving a standard diet without coconut oil supplementation. In addition, a positive correlation between survival and the neuronal marker NAA was found. To the best of our knowledge, this is the first study that reports metabolic changes in the brainstem using in vivo MRS and effects of coconut oil supplementation as a prophylactic treatment in SOD1G93A mice.

Hepatitis C: The beginning of the end-key elements for successful European and national strategies to eliminate HCV in Europe.

Hepatitis C virus (HCV) infection is a major public health problem in the European Union (EU). An estimated 5.6 million Europeans are chronically infected with a wide range of variation in prevalence across European Union countries. Although HCV continues to spread as a largely "silent pandemic," its elimination is made possible through the availability of the new antiviral drugs and the implementation of prevention practices. On 17 February 2016, the Hepatitis B & C Public Policy Association held the first EU HCV Policy Summit in Brussels. This summit was an historic event as it was the first high-level conference focusing on the elimination of HCV at the European Union level. The meeting brought together the main stakeholders in the field of HCV: clinicians, patient advocacy groups, representatives of key institutions and regional bodies from across European Union; it served as a platform for one of the most significant disease elimination campaigns in Europe and culminated in the presentation of the HCV Elimination Manifesto, calling for the elimination of HCV in Europe by 2030. The launch of the Elimination Manifesto provides a starting point for action in order to make HCV and its elimination in Europe an explicit public health priority, to ensure that patients, civil society groups and other relevant stakeholders will be directly involved in developing and implementing HCV elimination strategies, to pay particular attention to the links between hepatitis C and social marginalization and to introduce a European Hepatitis Awareness Week.

Safety profile of the 9-valent human papillomavirus vaccine: assessment in prior quadrivalent HPV vaccine recipients and in men 16 to 26 years of age.

A 9-valent HPV (9vHPV) vaccine has been developed to protect against HPV type 6/11/16/18/31/33/45/52/58-related infection and disease. Previous safety analyses from 7 clinical trials conducted in 9vHPV vaccine recipients 9-26 years of age, including comparisons of 9vHPV and quadrivalent HPV (qHPV) vaccines in girls and women 16-26 years of age, showed that the 9vHPV vaccine was generally well tolerated. Additional safety analyses were conducted to include the results of new clinical studies. The safety profile of the 9vHPV vaccine in prior qHPV vaccine recipients (n = 3756 from 1 randomized controlled trial and 2 open-label extension studies) and young men (n = 248 9vHPV and n = 248 qHPV vaccine recipients from 1 randomized controlled trial) was evaluated. Vaccine was administered as a 3-dose regimen (at Day 1 and Months 2 and 6), and adverse events (AEs) were monitored. The most common AEs were injection-site events (91.1% and 79.0% in prior qHPV vaccine recipients and young men, respectively), the majority of which were mild. Discontinuations due to an AE were rare (0.2% and 0.0% among prior qHPV vaccine recipients and young men, respectively). In young men, the AE profile of the 9vHPV vaccine was generally similar to that of the qHPV vaccine. Overall, the 9vHPV vaccine was generally well tolerated in prior qHPV vaccine recipients and in young men, with an AE profile generally consistent with that previously reported with the broader clinical program.

The Disease Burden of Hepatitis C in Belgium : An update of a realistic disease control strategy.

BACKGROUND: This manuscript serves as an update to position papers published in 2014 based on the available Belgian hepatitis C virus (HCV) epidemiological data. METHODS: Building on the current standard of care (2015 : 900 ≥ F3 patients treated with 70-85% SVR), four new scenarios were developed to achieve the goals of near viral elimination and prevention of HCV associated morbidity and mortality by 2026 and 2031. Increases in treatment efficacy were assumed in 2016 (90% SVR) and 2017 (95% SVR). RESULTS: Scenario 1: Treating 6,670 patients annually by 2018 (≥ F0 beginning in 2017) and diagnosing 3,790 patients annually by 2020, a 90% reduction in viremic cases and advanced outcomes was observed by 2026. Scenario 2: Treating 4,300 patients annually by 2018 (≥ F0 beginning in 2020) without increasing the number diagnosed, a 90% reduction in viremic cases and 85%-95% reduction in advanced outcomes was observed by 2031. Scenario 3: Treating 5,000 ≥ F2 patients annually by 2018, and diagnosing 3,620 patients annually by 2020, a 90% reduction in advanced outcomes and 50% reduction in viremic cases was observed by 2026. Scenario 4: Treating 3,100 ≥ F2 patients annually by 2018 without increasing the number diagnosed, a 90%-95% reduction in advanced outcomes and 55% reduction in viremic cases was observed by 2031. CONCLUSIONS: Scenario 2 would provide the most favorable balance of outcomes (90% reduction in viremic prevalence and advanced outcomes) and realistic requirements for implementation (gradual increase in treatment, delayed incorporation of patients with no/mild fibrosis).

The disease burden of hepatitis C in Belgium: development of a realistic disease control strategy.

BACKGROUND: Novel direct antiviral agents (DAAs) will become available soon with higher sustained viral response (SVR), fewer side-effects and higher compliance. Our aim was to evaluate different realistic strategies to control the projected increase in HCV-related disease burden in Belgium. METHODS: Based on literature review, expert opinions and historical assumptions, HCV-disease progression and mortality in Belgium was modeled to 2030. Strategies exploring the impact of increased treatment, treatment delay, and treatment restrictions were developed. RESULTS: Although the overall HCV prevalence is decreasing in Belgium, the burden of advanced stage HCV, including cirrhosis and hepatocellular carcinoma (HCC), is expected to increase under current treatment and cure rates. By increasing SVR to 90% from 2016 onward and the number of treated cases (from 710 to 2,050), in 2030 the cases with cirrhosis, decompensated cirrhosis and HCC would be significantly lower than in 2013. This strategy was found most efficient when applied to F2-F4 cases. To obtain comparable outcomes with F0-F4 cases, 3,490 patients should be treated. A two year delayed access to the DAAs increased HCV related morbidity and mortality by 15% relative to our strategy. CONCLUSIONS: Considering the evolving burden of HCV disease and the need for efficacious usage of healthcare resources, primary application of new DAAs in Belgium should focus on patients with significant and advanced fibrosis (F2-F4), providing these new drugs without delay upon availability and increasing access to therapy.

Current and future health and economic impact of hepatitis C in Belgium.

BACKGROUND AND STUDY AIMS: Chronic hepatitis C virus (HCV) infection is a serious global health problem affecting 150 million individuals worldwide. Although infection rates are decreasing, an aging population with progressing disease is expected to result in increased burden of advanced stage disease with high associated costs. This analysis describes the current and projected future economic impact of HCV sequelae in Belgium. METHODS: A previously described and validated model was populated with Belgian inputs and calibrated to project the current and future health and economic burden of HCV. Monte Carlo and sensitivity analyses were run to quantify uncertainty. All estimates exclude the cost of antiviral therapy. RESULTS: Costs associated with HCV were projected to peak in 2026 at Euro126M (Euro30M-Euro257M), while decompensated cirrhosis and hepatocellular carcinoma costs were projected to increase until 2031 and 2034. The projected 2014-2030 cumulative cost of HCV under current conditions was Euro1,850M. Scenarios to reduce the burden of HCV could result in Euro70M-Euro400M in cumulative cost savings. Starting treatment (1,000 patients) in 2015 could result in Euro150M cost savings. The lifetime cost of HCV increases with life expectancy, with highest future costs projected among young females with early stage disease. CONCLUSIONS: The economic burden of HCV and advanced stage disease were projected to further increase. Cost reductions are possible with timely interventions aimed at minimizing the health burden of advanced stage disease.

A cohesive European policy for hepatitis B vaccination, are we there yet?

Despite the availability of safe and effective hepatitis B virus (HBV) vaccines for more than 30 years, the burden of hepatitis B disease is still substantial. In 1992, the WHO recommended the inclusion of HBV vaccination in all national vaccination programmes. As of 2012, 47 of the 53 European countries (89%) had implemented a universal hepatitis B vaccination programme. The most recent countries to follow the recommendation were Ireland (in 2008) and the Netherlands (in 2011). Still, six countries (Denmark, Finland, Iceland, Norway, Sweden and the UK) adopt risk-group-targeted vaccination only, instead of adding a universal vaccination programme. However, changing demography, increasing immigration and the current vaccine costs make the cost­benefit ratios in these remaining low endemicity countries strongly in favour of universal HBV vaccination. Global efforts, including a cohesive European vaccination policy, are essential to control and prevent hepatitis B.

Rotavirus vaccination in Europe: drivers and barriers.

Rotavirus gastroenteritis is a vaccine-preventable disease that confers a high medical and economic burden in more developed countries and can be fatal in less developed countries. Two vaccines with high efficacy and good safety profiles were approved and made available in Europe in 2006. We present an overview of the status of rotavirus vaccination in Europe. We discuss the drivers (including high effectiveness and effect of universal rotavirus vaccination) and barriers (including low awareness of disease burden, perception of unfavourable cost-effectiveness, and potential safety concerns) to the implementation of universal rotavirus vaccination in Europe. By February, 2014, national universal rotavirus vaccination had been implemented in Belgium, Luxembourg, Austria, Finland, Greece, Luxembourg, Norway, and the UK. Four other German states have issued recommendations and reimbursement is provided by sickness funds. Other countries were at various stages of recommending or implementing universal rotavirus vaccination.

The state of hepatitis B and C in the Mediterranean and Balkan countries: report from a summit conference.

The burden of disease due to chronic viral hepatitis constitutes a global threat. In many Balkan and Mediterranean countries, the disease burden due to viral hepatitis remains largely unrecognized, including in high-risk groups and migrants, because of a lack of reliable epidemiological data, suggesting the need for better and targeted surveillance for public health gains. In many countries, the burden of chronic liver disease due to hepatitis B and C is increasing due to ageing of unvaccinated populations and migration, and a probable increase in drug injecting. Targeted vaccination strategies for hepatitis B virus (HBV) among risk groups and harm reduction interventions at adequate scale and coverage for injecting drug users are needed. Transmission of HBV and hepatitis C virus (HCV) in healthcare settings and a higher prevalence of HBV and HCV among recipients of blood and blood products in the Balkan and North African countries highlight the need to implement and monitor universal precautions in these settings and use voluntary, nonremunerated, repeat donors. Progress in drug discovery has improved outcomes of treatment for both HBV and HCV, although access is limited by the high costs of these drugs and resources available for health care. Egypt, with the highest burden of hepatitis C in the world, provides treatment through its National Control Strategy. Addressing the burden of viral hepatitis in the Balkan and Mediterranean regions will require national commitments in the form of strategic plans, financial and human resources, normative guidance and technical support from regional agencies and research.

Measles outbreak in Europe: susceptibility of infants too young to be immunized.

As women vaccinated against measles transfer low amounts of antibodies, an increasing number of infants lack early protection through maternal antibodies until being immunised themselves. This paper reviews the literature on disease burden of measles in the population too young to be immunized according to the respective national recommendations during recent outbreaks in EU and EEA/EFTA countries. In addition, specific control strategies adopted to protect this young population are reviewed. Pubmed, Unbound Medline, Web of Knowledge and the Eurosurveillance database were searched using MESH terms: measles and epidemiology, measles and infants, prevalence of measles, measles and outbreaks and measles and epidemic. Additionally, data from Euvac.net and ECDC were consulted. Databases were searched from January 2001 to September 2011. Fifty-three papers were included in the analysis. The percentage of all measles cases during outbreaks affecting young infants ranged from 0.25% to 83.0%. Specific control strategies were adopted: e.g. administration of the first or second vaccine dose earlier than recommended. Infants younger than 12 months are often involved in measles outbreaks, and advancing the first vaccine dose could reduce the burden of disease. However, immunization before 9 months of age is not systematically recommended because of dysmature humoral immune responses of infants. High coverage and timely administration of the recommended series of vaccines are the most important measures to decrease measles incidence and measles circulation and protect vulnerable infants from infection.

The health and economic burden of chickenpox and herpes zoster in Belgium.

Varicella-zoster virus causes chickenpox (CP) and after reactivation herpes zoster (HZ). Vaccines are available against both diseases warranting an assessment of the pre-vaccination burden of disease. We collected data from relevant Belgian databases and performed five surveys of CP and HZ patients. The rates at which a general practitioner is visited at least once for CP and HZ are 346 and 378/100 000 person-years, respectively. The average CP and HZ hospitalization rates are 5·3 and 14·2/100 000 person-years respectively. The direct medical cost for HZ is about twice as large as the direct medical cost for CP. The quality-adjusted life years lost for ambulatory CP patients consulting a physician is more than double that of those not consulting a physician (0·010 vs. 0·004). In conclusion, both diseases cause a substantial burden in Belgium.

Introduction of human papillomavirus vaccination in Belgium, Luxembourg and the Netherlands.

AIMS: To document progress with human papillomavirus (HPV) vaccine introduction in three closely related European countries, one with organized (the Netherlands) and two with opportunistic cervical cancer screening (Belgium and Luxembourg). METHODS: Experts involved in cervical cancer screening and national immunization programs from the three countries were contacted to provide information on the decision-making process concerning the introduction of HPV vaccine. Sales statistics were obtained from Intercontinental Marketing Services. RESULTS: Advisory boards in all three countries advised organized HPV vaccination of girls of 12 years with variable catch-up policies. In Belgium, the national health authority partially reimburses the HPV vaccine for girls of 12-15 years (recently extended until 18 years). In Luxembourg, 12-year-old girls are invited for free vaccination, but the HPV vaccine is also free of charge for female adolescents of 13-17 years. The number of vaccines reimbursed in Belgium in December 2007 to May 2008 corresponds with the amount required to fully vaccinate 29% of the female population aged 12-15 years. In Luxembourg, between March and November 2008, the immunization program delivered a quantity of HPV vaccines which theoretically covered 29% of females aged 12-17 years. In the Netherlands, nationwide HPV vaccination of girls of 12 years will start in September 2009. The sales of HPV vaccines (all ages combined) were by far the lowest in the Netherlands. CONCLUSION: Up to the end of 2008, HPV vaccination efforts reached less than a third of the target population in Belgium and Luxembourg. If the latest trend continues, the current policy is expected to reach to most half of the target population. Well-planned introduction of vaccination combined with an organized screening program and active surveillance are crucial for the program to achieve and monitor its desired aims. Such surveillance should include linkage between vaccination, screening and cancer registries.

Introduction of human papillomavirus (HPV) vaccination in Belgium, 2007-2008.

This paper documents the progress of human papillomavirus (HPV) vaccine introduction in Belgium. Information on vaccine use is based on sales statistics and reimbursement claims. From November 2007 to November 2008, the National Institute for Health and Disability Insurance reimbursed the HPV vaccine for girls aged between 12-15 years. In December 2008, the age limit was extended to include girls up to the age of 18. In November 2008, the total number of HPV vaccines sold exceeded 530,000 doses. The number of vaccines reimbursed in Belgium, for the period November 2007-November 2008, corresponds to the amount required to fully vaccinate 44% of all girls aged between 12-15 years. However, the trend was decreasing over the last 10 months. By the current reimbursement policy, we can expect that maximum half of the target population can be reached. In Flanders (one of the three Communities in Belgium), the intention is to start, from September 2010, with a free school-based HPV immunisation for girls in the first year of secondary school (12 years of age), complemented with vaccination by a physician of choice. This strategy ensures a higher HPV vaccine coverage which is expected to be as high as the current coverage in the hepatitis B vaccination programme (approximately 80%) offered to boys and girls in the same age group and under the same circumstances.

Has the time come to control hepatitis A globally? Matching prevention to the changing epidemiology.

For the first time a global meeting on hepatitis A virus (HAV) infection as vaccine preventable disease was organized at the end of 2007. More than 200 experts from 46 countries gathered to investigate the changing global HAV epidemiology reflecting the increasing numbers of persons at risk for severe clinical disease and mortality from HAV infection. The benefits of childhood and adult hepatitis A (HepA) vaccination strategies and the data needed by individual countries and international health organizations to assess current HepA prevention strategies were discussed. New approaches in preventing HAV infection including universal HepA vaccination were considered. This introductory paper summarizes the major findings of the meeting and describes the changing epidemiology of HAV infections and the impact of HepA vaccination strategies in various countries. Implementation of HepA vaccination strategies should take into account the level of endemicity, the level of the socio-economic development and sanitation, and the risk of outbreaks. A stepwise strategy for introduction of HepA universal immunisation of children was recommended. This strategy should be based on accurate surveillance of cases and qualitative documentation of outbreaks and their control, secure political support on the basis of high-quality results, and comprehensive cost-effectiveness studies. The recognition of the need for increased global attention towards HepA prevention is an important outcome of this meeting.

Hepatitis B virus, hepatitis C virus and other blood-borne infections in healthcare workers: guidelines for prevention and management in industrialised countries.

The Viral Hepatitis Prevention Board (VHPB) convened a meeting of international experts from the public and private sectors in order to review and evaluate the epidemiology of blood-borne infections in healthcare workers, to evaluate the transmission of hepatitis B and C viruses as an occupational risk, to discuss primary and secondary prevention measures and to review recommendations for infected healthcare workers and (para)medical students. This VHPB meeting outlined a number of recommendations for the prevention and control of viral hepatitis in the following domains: application of standard precautions, panels for counselling infected healthcare workers and patients, hepatitis B vaccination, restrictions on the practice of exposure-prone procedures by infected healthcare workers, ethical and legal issues, assessment of risk and costs, priority setting by individual countries and the role of the VHPB. Participants also identified a number of terms that need harmonization or standardisation in order to facilitate communication between experts.

Recommendations for the use of the 23-valent polysaccharide pneumococcal vaccine in adults: a Belgian consensus report.

A multidisciplinary expert panel, appointed by the High Council for Public Health, evaluated the scientific evidence on which the recommendations for the appropriate use of the pneumococcal vaccine was based and reviewed the studies that became available since previous reports. The conclusions of the working group, presented in this manuscript, resulted in an update of the Belgian recommendations for pneumococcal vaccination.

Economic evaluations of pneumococcal vaccination strategies in adults. A summary of the results.

With the view to re-evaluate the current evidence about the efficiency of adult pneumococcal vaccination, we searched the Medline database to collect recent full economic evaluations on this topic. We included a literature review based on studies published up to June 2001 and 5 other studies published between July 2001 and April 2004. Based on these articles' results, pneumococcal vaccination of the elderly aged between 65 and 75 years is found to be relatively cost-effective for the health care payer. There is also evidence that vaccination of HIV+ patients and of young military personnel may be justifiable on the basis of economic evaluation including direct medical costs only. Conclusions about universal vaccination of younger adults (< 65 years) and of high-risk groups could not be drawn because of controversial results. An accurate assessment of the efficiency of adult pneumococcal vaccination is however hard to achieve given the difficulties in collecting valid input data (e.g. for the incidence and mortality of the disease) and given the remaining uncertainties about the vaccine efficacy for non-invasive disease. Finally, by lack of data, none of the studies estimated the impact of vaccination on antimicrobial resistance.

The difficult quest for data on "vanishing" vaccine-preventable infections in Europe: the case of measles in Flanders (Belgium).

We aimed to describe the impact of vaccination on the epidemiology of measles infection in Flanders (Belgium), to document probable vaccination coverage based on this evidence, compare these epidemiological data with those generated by a mathematical model and estimate the costs of morbidity from measles. In contrast to previous analyses, we included the costs of long-term care for sequelae due to encephalitis and subacute sclerosing panencephalitis (SSPE). We estimated the direct health care costs per average measles case at 227, 212, 210, 200 and 194 for the age groups of 0-4, 5-9, 10-14, 15-19 and > or=20 years, respectively. Excluding long-term care lowers these estimates by 22-51%, depending on the age group. By including indirect time costs, we arrive at total costs per measles case of 320, 305, 210, 200 and 625, respectively. In addition to registering vaccination coverage more rigorously in the future, it seems necessary to undertake seroprevalence studies to document the age-specific immunity to measles. By using such information, current vaccination strategies can be adapted to prevent future outbreaks and to help eliminate measles from Europe in an efficient way. We noted throughout that many of the data sources are flawed. Better and accessible data bases are required to improve the reliability of similar studies in the future.

Vaccination coverage estimates by EPI cluster sampling survey of children (18-24 months) in Flanders, Belgium.

UNLABELLED: A random cluster sample according to the EPI cluster sampling technique was conducted in 1999 in Flanders (North Belgium) to ascertain the vaccination coverage of 18 to 24-mo-old children. Polio is the only mandatory vaccine. Diphtheria-tetanus-pertussis (DTP), Haemophilus influenzae type b (Hib), hepatitis B (HB) and measles-mumps-rubella (MMR) are included in the recommended schedule of vaccinations. For Hib and HB, a minimal cost was charged. Professional interviewers conducted interviews with the parents of 1110 children randomly selected in 89 municipalities. Analysis was conducted on the results of 1005 children. The coverage level (95% confidence interval) for the full schedule was 96% (95-97) for polio, 89% (87-91) for DTP, 78% (74-82) for Hib, 68% (64-72) for HB and 83% (81-87) for MMR. The vaccinations were administered by the regional children's health organization (70%), paediatricians (17%) and GPs (11%). No sociodemographic factors could be associated with vaccination coverage. One province showed significantly (p < 0.01) lower vaccination coverage levels compared with those of the other four provinces for DTP (91% vs 82%), Hib (78% vs 53%), HB (73% vs 46%) and MMR (87% vs 66%). CONCLUSION: There is a need for more and better information about vaccination for parents as well as for the healthcare providers.