Hepatitis A occurrence and outbreaks in Europe over the past two decades: A systematic review.

Hepatitis A (HA) is a vaccine-preventable liver disease with >170 million new cases occurring yearly. In recent outbreaks in the USA, hospitalization and case-fatality ratios were >60% and ~1%, respectively. In Europe, endemicity persists and outbreaks continue to occur. We performed a systematic literature review to understand the changes in HA occurrence in Europe over the past two decades. PubMed and Embase were systematically searched for peer-reviewed articles published between 1 January 2001 and 14 April 2021 using terms covering HA, 11 selected European countries, outbreaks, outcomes and HA virus circulation. Here, we focus on HA occurrence and outbreaks in the five countries with the largest population and the most comprehensive vaccination recommendations: France, Germany, Italy, Spain and the UK; 118 reports included data for these five European countries. Notification rates (≤9.7/100,000 population) and percentages of men among cases (≤83.0%) peaked in 2017. The number of person-to-person-transmitted cases and outbreaks decreased in children but increased in other risk groups, such as men who have sex with men (MSM). Sexually transmitted outbreaks in MSM clustered around 2017. Travel-related outbreaks were few; the proportion of travel-related cases decreased during the past two decades, while the number of domestic cases increased. Despite the existing risk-based vaccination recommendations, HA transmission shifted in proportions from travelers and children to other risk groups, such as MSM and older age groups. Because a substantial proportion of the European population is susceptible to HA, adherence to existing recommendations should be monitored more closely, and enhanced vaccination strategies should be considered.

Exploring doctors' reasons for not granting a request for euthanasia: a mixed-methods study.

BACKGROUND: In a growing number of jurisdictions, physician-assisted death (PAD) is now an established part of medical care. Although PAD is allowed under certain criteria in The Netherlands, physicians can always refuse a request. The Euthanasia Expertise Centre (EEC) offers PAD to patients whose request was declined in circumstances where their own physician could have satisfied the legal criteria. The number of requests reaching EEC has increased, suggesting the threshold for treating physicians to refer patients to EEC has become lower. AIM: To explore the reasons of physicians for not granting a request for PAD and/or referring a patient to EEC, and any needs physicians may have in handling requests for PAD. DESIGN & SETTING: Survey and interviews among Dutch physicians in The Netherlands. METHOD: A questionnaire was sent to 500 physicians who declined a request for PAD and whose patient subsequently requested PAD at EEC. This was followed by a qualitative study, in which in-depth interviews were held with 21 of the physicians who responded to the survey. RESULTS: Doctors were identified as those who had objections on principle, or with other reasons for refusing a request for PAD and/or to refer the patient to EEC. These reasons were mostly related to concerns about complying with the due care criteria for PAD, or to difficulties with PAD in specific patient groups. In these cases they often valued support from another healthcare professional. CONCLUSION: For patients of physicians with objections on principle against PAD, EEC offered a good solution. Doctors who struggle with whether they can comply with the legal criteria might benefit from peer support.

The changing epidemiology of human monkeypox-A potential threat? A systematic review.

Monkeypox, a zoonotic disease caused by an orthopoxvirus, results in a smallpox-like disease in humans. Since monkeypox in humans was initially diagnosed in 1970 in the Democratic Republic of the Congo (DRC), it has spread to other regions of Africa (primarily West and Central), and cases outside Africa have emerged in recent years. We conducted a systematic review of peer-reviewed and grey literature on how monkeypox epidemiology has evolved, with particular emphasis on the number of confirmed, probable, and/or possible cases, age at presentation, mortality, and geographical spread. The review is registered with PROSPERO (CRD42020208269). We identified 48 peer-reviewed articles and 18 grey literature sources for data extraction. The number of human monkeypox cases has been on the rise since the 1970s, with the most dramatic increases occurring in the DRC. The median age at presentation has increased from 4 (1970s) to 21 years (2010-2019). There was an overall case fatality rate of 8.7%, with a significant difference between clades-Central African 10.6% (95% CI: 8.4%- 13.3%) vs. West African 3.6% (95% CI: 1.7%- 6.8%). Since 2003, import- and travel-related spread outside of Africa has occasionally resulted in outbreaks. Interactions/activities with infected animals or individuals are risk behaviors associated with acquiring monkeypox. Our review shows an escalation of monkeypox cases, especially in the highly endemic DRC, a spread to other countries, and a growing median age from young children to young adults. These findings may be related to the cessation of smallpox vaccination, which provided some cross-protection against monkeypox, leading to increased human-to-human transmission. The appearance of outbreaks beyond Africa highlights the global relevance of the disease. Increased surveillance and detection of monkeypox cases are essential tools for understanding the continuously changing epidemiology of this resurging disease.

One or two doses of hepatitis A vaccine in universal vaccination programs in children in 2020: A systematic review.

BACKGROUND: Hepatitis A virus (HAV) is a global health concern as outbreaks continue to occur. Since 1999, several countries have introduced universal vaccination (UV) of children against HAV according to approved two-dose schedules. Other countries have implemented one-dose UV programs since 2005; the long-term impact of this schedule is not yet known. METHODS: We conducted a systematic literature search in four electronic databases for data published between January 2000 and July 2019 to assess evidence for one-dose and two-dose UV of children with non-live HAV vaccines and describe their global impact on incidence, mortality, and severity of hepatitis A, vaccine effectiveness, vaccine efficacy, and antibody persistence. RESULTS: Of 3739 records screened, 33 peer-reviewed articles and one conference abstract were included. Rapid declines in incidence of hepatitis A and related outcomes were observed in all age groups post-introduction of UV programs, which persisted for at least 14 years for two-dose and six years for one-dose programs according to respective study durations. Vaccine effectiveness was ≥95% over 3-5 years for two-dose programs. Vaccine efficacy was >98% over 0.1-7.5 years for one-dose vaccination. Antibody persistence in vaccinated individuals was documented for up to 15 years (≥90%) and ten years (≥74%) for two-dose and one-dose schedules, respectively. CONCLUSION: Experience with two-dose UV of children against HAV is extensive, demonstrating an impact on the incidence of hepatitis A and antibody persistence for at least 15 years in many countries globally. Because evidence is more limited for one-dose UV, we were unable to draw conclusions on immune response persistence beyond ten years or the need for booster doses later in life. Ongoing epidemiological monitoring is essential in countries implementing one-dose UV against HAV. Based on current evidence, two doses of non-live HAV vaccines are needed to ensure long-term protection.

Systematic Literature Review and Quantitative Analysis of Health Problems Associated with Sexually Transmitted Neisseria gonorrhoeae Infection.

OBJECTIVE: Neisseria gonorrhoeae (Ng) is the second most common sexually transmitted bacterial infection (STI), leading to serious health problems in men, women and newborns. While early antibiotic treatment is effective, infections are increasingly antibiotic-resistant. No systematic reviews present health problems associated with Ng infections or their likelihood of occurrence. The objective, therefore, was to conduct a systematic literature review to address these gaps. METHODS: A systematic literature review was conducted of all studies with an English abstract published since 1950 (Pubmed)/1966 (Embase). The search included patients with a history of/current sexually transmitted Ng infection. Expected outcomes were defined from published reviews of gonorrhoea health problems. Observational studies with a control group were included. A decision tree determined the best quality studies for each outcome, prioritising generalisable populations, laboratory-confirmed diagnosis, clearly defined outcomes, no STI co-infections, adjusted analyses and risk estimates. Where feasible, a meta-analysis was performed; otherwise, the best quality study estimates were identified. FINDINGS: In total, 46 studies were included, and 22 health problems were identified. Of these problems, Ng infection was statistically significantly associated with preterm premature ruptures of membranes, preterm birth, low birth weight, stillbirth, infant death, neonatal ophthalmia, schizophrenia in offspring, pelvic inflammatory disease and subsequent tubal infertility, human immunodeficiency virus and prostate cancer/problems. High-quality evidence was generally lacking, with high heterogeneity across studies, and limited or inconclusive data on other health problems. CONCLUSION: Ng infection is associated with severe health problems in women, men and newborns. More high-quality comparative studies are needed to address the limitations in current knowledge.

Wish for euthanasia persists for at least one year after the request was declined by Euthanasia Expertise Center.

BACKGROUND: Euthanasia Expertise Center (EEC) in the Netherlands provides euthanasia or physician-assisted suicide for patients who meet all requirements of the Dutch Euthanasia Law, but whose treating physician declined their request. Little is known about how life continues for a patient after a request for physician-assisted death (PAD) is also declined by EEC. OBJECTIVE: To follow-up patients whose request for PAD was declined at EEC. METHODS: Between December 2016 and January 2020, 66 patients were prospectively followed for one year after their request was declined. Their general well-being and health, persistence of the wish for PAD, and mortality was measured by means of a questionnaire administered after three, six and 12 months. Furthermore, information was extracted from the patient's medical record. FINDINGS: More than half (58%) of the included patients suffered from an accumulation of old-age complaints. In the year after the request was declined, 15 patients (23%) died, three of whom committed suicide. Almost all patients who were alive after one year, persisted in their wish for PAD. Moreover, they were often not doing well. CONCLUSIONS: Considering that EEC is a last resort for those who were not granted PAD elsewhere, and that the wish for PAD persists, aftercare services should be provided to people whose request has been declined.

A systematic literature review of herpes zoster incidence worldwide.

We conducted a systematic review to characterize the incidence rate of herpes zoster (HZ) in the general population, specifically in individuals ≥50 years of age. A total of 69 publications were included in the review. We found a cumulative incidence of HZ ranging from 2.9-19.5 cases per 1,000 population and an incidence rate of HZ ranging from 5.23-10.9 cases per 1,000 person-years. The cumulative incidence (3.22-11.2 versus 2.44-8.0 cases per 1,000 population) and incidence rates (6.05-12.8 versus 4.30-8.5 cases per 1,000 person-years) were higher in females than males. Studies revealed a trend of increasing incidence of HZ with increasing age and over time. Variations in incidence estimates can be attributed to the various study designs, case ascertainments, age distributions of the population and year of the study. HZ is associated with a substantial disease burden and is expected to increase due to population aging.

Critical appraisal and issues regarding generalisability of comparative effectiveness studies of NOACs in atrial fibrillation and their relation to clinical trial data: a systematic review.

OBJECTIVE: To critically appraise the published comparative effectiveness studies on non-vitamin K antagonist oral anticoagulants (NOACs) in non-valvular atrial fibrillation (NVAF). Results were compared with expectations formulated on the basis of trial results with specific attention to the patient years in each study. METHODS: All studies that compared the effectiveness or safety between at least two NOACs in patients with NVAF were eligible. We performed a systematic literature review in Medline and EMbase to investigate the way comparisons between NOACs were made, search date 23 April 2019. Critical appraisal of the studies was done using among others ISPOR Good Research Practices for comparative effectiveness research. RESULTS: We included 39 studies in which direct comparison between at least two NOACs were made. Almost all studies concerned patient registries, pharmacy or prescription databases and/or health insurance database studies using a cohort design. Corrections for differences in patient characteristics was applied in all but two studies. Eighteen studies matched using propensity scores (PS), 8 studies weighted patients based on the inverse probability of treatment, 1 study used PS stratification and 10 studies applied a proportional hazards model. These studies have some important limitations regarding unmeasured confounders and channelling bias, even though the larger part of the studies were well conducted technically. On the basis of trial results, expected differences are small and a naïve analysis suggests trials with between 7200 and 56 500 patients are needed to confirm the observed differences in bleedings and between 51 800 and 7 994 300 to confirm differences in efficacy. DISCUSSION: Comparisons regarding effectiveness and safety between NOACs on the basis of observational data, even after correction for baseline characteristics, may not be reliable due to unmeasured confounders, channelling bias and insufficient sample size. These limitations should be kept in mind when results of these studies are used to decide on ranking NOAC treatment options.

Hepatitis A epidemiology in Latin American countries: a 2020 view from a systematic literature review.

INTRODUCTION: The World Health Organization recommends vaccination against hepatitis A virus (HAV) for children aged 1 year and older in areas where endemicity has shifted from high to intermediate. There are no recent comprehensive reviews of the epidemiology of HAV infection in Latin America, but seroprevalence and socioeconomic data suggest that, with improved clean water and sanitation systems, countries are transitioning to intermediate endemicity. AREAS COVERED: We conducted a systematic literature review of the epidemiology of HAV infection in 25 countries in the Latin American region, which included gray literature. We compiled data on HAV incidence and prevalence, including the identification of epidemiological changes observed in countries that established pediatric HAV vaccination programs. EXPERT OPINION: We identified 59 relevant articles, including 34 peer-reviewed seroprevalence studies (12 recent studies from Brazil), three incidence studies, and six vaccine impact studies (three from Argentina). Based on the estimated age at midpoint of population immunity in each country, most have a high-intermediate, intermediate, or low-intermediate level of HAV endemicity, suggesting that national childhood immunization may be an appropriate disease prevention strategy. However, recent data were lacking for most countries. Improved data quality and continued epidemiological surveillance are required for this region.

A systematic review of the burden of pertussis disease in infants and the effectiveness of maternal immunization against pertussis.

Introduction Infants too young to be fully immunized are the most vulnerable to severe pertussis disease. To close this susceptibility gap, passive infant immunization through vaccination of pregnant women against pertussis was first introduced in 2011 in the United States and has been extended since then to more than 40 countries. Areas covered We conducted two systematic literature searches to describe the worldwide burden of pertussis disease in infants <6 months of age since 2005, and the effectiveness and impact of maternal pertussis vaccination in preventing infant pertussis since 2011. Expert opinion Pertussis disease incidence rates in infants aged <2-3 months were substantial in all countries with available data, exceeding 1000 cases per 100,000 population during outbreaks. Virtually all pertussis deaths occurred in this age group. Data from Africa, Eastern Mediterranean, and Asia were limited, but suggest a similar or higher disease burden than in Europe or the Americas. Estimates of effectiveness of second/third trimester pertussis vaccination in preventing pertussis disease in <2-3 months old infants were consistently high (69%-93%) across the observational studies reviewed, conducted in various settings with different designs. Maternal vaccination programs appear to be achieving their goal of reducing the burden of disease in very young infants. Plain language summary What is the context? Pertussis, also known as whooping cough, is a highly contagious disease of the respiratory tract. Infants too young to be fully vaccinated are at the highest risk of severe pertussis disease, hospitalization, and death. Vaccinating pregnant women against pertussis with a Tdap vaccine is recommended in more than 40 countries as a safe and effective strategy to protect infants for the first months of life. What is new? This review summarizes recent literature describing the burden of pertussis disease in infants worldwide prior to the introduction of maternal vaccination programs; pertussis disease incidence rates in infants aged <2-3 months were substantial in all countries with available data, exceeding 1000 cases per 100,000 population during outbreaks. Immunization of pregnant women with a Tdap vaccine can prevent about 70-90% of pertussis disease and up to 90.5% of pertussis hospitalizations in infants under 3 months of age. What is the impact? Limited available data suggest that incidence rates of pertussis disease after the introduction of Tdap maternal immunization have declined in infants. Current knowledge supports the implementation of Tdap maternal immunization programs.

Hepatitis B and C prevalence and incidence in key population groups with multiple risk factors in the EU/EEA: a systematic review.

BackgroundPeople living with HIV (PLHIV) and people in prison are population groups with a potentially high risk and/or prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection.AimWe conducted a systematic review in order to find prevalence and incidence estimates in these populations in the European Union/European Economic Area (EU/EEA).MethodsOriginal research articles published between January 2005 and February 2017 were retrieved from PubMed and Embase in February 2017.ResultsFifty-two articles were included, providing 97 estimates of HBV/HCV infection prevalence or incidence. Estimates of HBV infection prevalence ranged between 2.9% and43.4% in PLHIV and 0.0% and 25.2% in people in prison. Estimates of HCV infection prevalence ranged from 2.9% to 43.4% in PLHIV and 0.0% to 25.2% in people in prison. Incidence estimates ranged between 0.0 and 2.5 cases per 100 person-years for HBV infection in PLHIV. No such data was available for people in prison. HCV infection incidence ranged between 0.3 and 0.9 cases per 100 person-years in PLHIV and between 1 and 1.2 cases per 100 person-years in people in prison. Prevalence estimates were generally higher than in the general population, especially for HCV infection and among groups with multiple risk factors.ConclusionsPLHIV, people in prison and groups with multiple risk factors, have a high prevalence of HBV and HCV and may be at ongoing risk of infection. These groups should be among the populations prioritised and targeted for active case finding and prevention programmes in the EU/EEA.

Hepatitis B and C testing strategies in healthcare and community settings in the EU/EEA: A systematic review.

An estimated 9 million individuals are chronically infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) across the European Union/European Economic Area (EU/EEA), many of which are yet to be diagnosed. We performed a systematic review to identify interventions effective at improving testing offer and uptake in the EU/EEA. Original research articles published between 1 January 2008 and 1 September 2017 were retrieved from PubMed and EMBASE. Search strings combined terms for HBV/HCV, intervention, testing and geographic terms (EU/EEA). Out of 8331 records retrieved, 93 studies were selected. Included studies reported on testing initiatives in primary health care (9), hospital (12), other healthcare settings (31) and community settings (41). Testing initiatives targeted population groups such as migrants, drug users, prisoners, pregnant women and the general population. Testing targeted to populations at higher risk yielded high coverage rates in many settings. Implementation of novel testing approaches, including dried blood spot (DBS) testing, was associated with increased coverage in several settings including drug services, pharmacies and STI clinics. Community-based testing services were effective in reaching populations at higher risk for infection, vulnerable and hard-to-reach populations. In conclusion, our review identified several successful testing approaches implemented in healthcare and community settings, including testing approaches targeting groups at higher risk, community-based testing services and DBS testing. Combining a diverse set of testing opportunities within national testing strategies may lead to higher impact both in terms of testing coverage and in terms of reduction, on the undiagnosed fraction.

Vaccination herd effect experience in Latin America: a systematic literature review.

BACKGROUND: National pediatric vaccination programs have been introduced in Latin America (LatAm) to reduce the burden of diseases due to pathogens such as rotavirus, Haemophilus influenzae type b (Hib) and pneumococcus. Vaccination health benefits may extend to unvaccinated populations by reducing pathogen transmission. Understanding herd effect is important for implementation and assessment of vaccination programs. The objective was to conduct a systematic review of published epidemiological evidence of herd effect with Hib, rotavirus and pneumococcal conjugate vaccines (PCV) in LatAm. METHODS: Searches were conducted in PubMed, Virtual Health Library (VHL), SciELO and SCOPUS databases, for studies reporting data on herd effect from Hib, rotavirus and PCV vaccination in LatAm, without age restriction. Searches were limited to articles published in English, Spanish or Portuguese (1990-2016). After screening and full-text review, articles meeting the selection criteria were included to be critically appraised following criteria for observational and interventional studies. The presence of a herd effect was defined as a significant decrease in incidence of disease, hospitalization, or mortality. RESULTS: 3,465 unique articles were identified, and 23 were included (Hib vaccine n = 5, PCV n = 8, rotavirus vaccine n = 10). Most studies included children and/or adolescents (age range varied between studies). Studies in adults, including older adults (aged > 65 years), were limited. Few studies reported statistically significant reductions in disease incidence in age groups not targeted for vaccination. Hib-confirmed meningitis hospitalization decreased in children but herd effect could not be quantified. Some evidence of herd effect was identified for PCV and rotavirus vaccine in unvaccinated children. Evidence for herd effects due to PCV in adults was limited. CONCLUSION: After introduction of Hib, PCV and rotavirus vaccination in LatAm, reductions in morbidity/mortality have been reported in children not targeted for vaccination. However, due to methodological limitations (e.g. short post-vaccination periods and age range studied), there is currently insufficient evidence to quantify the herd effect in adult populations. More research and higher quality surveillance is needed to characterize herd effect of these vaccines in LatAm.

Systematic literature review comparing rapid 3-dose administration of the GSK tick-borne encephalitis vaccine with other primary immunization schedules.

INTRODUCTION: Tick-borne encephalitis (TBE), which is endemic across large regions of Europe and Asia, is most effectively prevented through vaccination. Three-dose primary TBE vaccination schedules are either rapid (0,7,21-days) or conventional (0,28-84-days, 9-12-months). The second dose can also be administered at 14 days for faster priming and sero-protection). Areas covered: We used a three-step selection process to identify 21 publications comparing the immunogenicity and/or safety of different schedules. Expert commentary: Priming with two or three TBE vaccine doses was highly immunogenic. After conventional priming (0-28 days), 95% adults and ≥95% children had neutralization test (NT) titers ≥10 at 14 days post-dose-2 compared with 92% adults and 99% children at 21 days post-dose-3 (rapid schedule). Most subjects retained NT titers ≥10 at day 300. A single booster dose induced a strong immune response in all subjects irrespective of primary vaccination schedule or elapsed time since priming. GMT peaked at 42 days post-dose-1 (i.e., 21 days post-dose 3 [rapid-schedule], or 14-28 days post-dose-2 [conventional-schedule]), and declined thereafter. Adverse events were generally rare and declined with increasing doses. In the absence of data to recommend one particular schedule, the regimen choice will remain at the physician's discretion, based on patient constraints and availability.

Should adults with diabetes mellitus be vaccinated against hepatitis B virus? A systematic review of diabetes mellitus and the progression of hepatitis B disease.

Despite the burden of diabetes mellitus (DM), little is known about the role of this and other metabolic syndromes on the severity of hepatitis B virus (HBV) chronicity and liver disease progression. The value of hepatitis B vaccination and its impact on liver diseases and HCC has been largely demonstrated, adult vaccination coverage is however suboptimal and DM diagnosis represents an opportunity for the HCP to discuss hepatitis B and other adult vaccinations. We performed a systematic literature search to identify studies (January 2000 to January 2017) describing liver disease progression among patients with HBV by DM status. Risk factors were assessed including the relationship between HBV and non-alcoholic steatohepatitis (NASH). Data were extracted systematically and assessed descriptively. Twenty articles described liver disease progression and one article evaluated NASH among subjects with HBV by DM status. Fourteen articles reported that DM as a predictor for the outcome, including delayed seroclearance, cirrhosis, hepatocellular carcinoma, transplant/mortality and death, whereas no association on liver outcomes was found in 7 studies. In summary, our review suggests that DM is associated with the progression of severe liver outcomes in adults with HBV, although more studies are needed to understand the benefits of HBV vaccination in adults with DM and liver-diseases.

The immunogenicity of GSK's recombinant hepatitis B vaccine in children: a systematic review of 30 years of experience.

INTRODUCTION: The World Health Organization recommends hepatitis B virus (HBV) vaccines to be included in national immunization schedules everywhere, and has adopted the strategic goal of halting viral hepatitis as a major public health threat by 2030, under which vaccination plays a major role. Engerix™ B (GSK HepB, GSK, Belgium) was the first recombinant HBV vaccine to be licensed, and marked its 30th anniversary in 2016. Areas covered: We conducted a systematic review of the literature summarizing 30 years of immunogenicity and safety data for GSK HepB in children and adolescents. Expert commentary: Primary 3-dose vaccination of healthy infants and children, including infants born to HBsAg-positive mothers, using the standard 0, 1, 6 month schedule was associated with seroprotection rates ≥96.0%. In high-risk infants, vaccine efficacy at year 5 was 96.0% after 3-dose priming in infancy and immunoglobulin at birth. Lower seroprotection rates were observed in children with severe underlying disease including human immunodeficiency virus infection and cancer. GSK HepB had a clinically acceptable safety profile in all of the populations studied. HBV vaccines have demonstrated long-term impacts on rates of fulminant hepatitis, chronic liver disease and hepatocellular carcinoma. GSK HepB will continue to contribute to global HBV control for the foreseeable future.

The immunogenicity and safety of GSK's recombinant hepatitis B vaccine in adults: a systematic review of 30 years of experience.

INTRODUCTION: Engerix B (GSK HepB, GSK, Belgium) was the first recombinant hepatitis B virus vaccine to be licensed, and marked its 30th anniversary in 2016. Vaccination of adult populations against HBV is usually implemented on a risk-based approach with varying degrees of success. Confirmation of ongoing vaccine effectiveness requires monitoring the performance of HBV immunization as reported in individual studies, using systematic methods. Areas covered: We conducted a systematic review of the literature to summarize 30 years of immunogenicity and safety data for GSK HepB in adult populations. Expert commentary: Primary 3-dose vaccination of healthy individuals is generally associated with seroprotection rates of 90% or more, although seroprotection decreases with older age. Accelerated 0, 1, 2-month or 0, 7 and 21-day schedules require the recommended booster dose to achieve similar rates of seroprotection. Lower rates of seroprotection were also observed in adults with underlying chronic disease and with a weakened immune system. GSK HepB had a clinically acceptable safety profile in all of the populations studied, including individuals with underlying co-morbidities and immunosuppression. GSK HepB will continue to contribute to global HBV control for the foreseeable future. Further investigation is needed into how to optimize seroprotection in less immune-competent groups.

Impact of universal mass vaccination with monovalent inactivated hepatitis A vaccines - A systematic review.

The WHO recommends integration of universal mass vaccination (UMV) against hepatitis A virus (HAV) in national immunization schedules for children aged ≥1 year, if justified on the basis of acute HAV incidence, declining endemicity from high to intermediate and cost-effectiveness. This recommendation has been implemented in several countries. Our aim was to assess the impact of UMV using monovalent inactivated hepatitis A vaccines on incidence and persistence of anti-HAV (IgG) antibodies in pediatric populations. We conducted a systematic review of literature published between 2000 and 2015 in PubMed, Cochrane Library, LILACS, IBECS identifying a total of 27 studies (Argentina, Belgium, China, Greece, Israel, Panama, the United States and Uruguay). All except one study showed a marked decline in the incidence of hepatitis A post introduction of UMV. The incidence in non-vaccinated age groups decreased as well, suggesting herd immunity but also rising susceptibility. Long-term anti-HAV antibody persistence was documented up to 17 y after a 2-dose primary vaccination. In conclusion, introduction of UMV in countries with intermediate endemicity for HAV infection led to a considerable decrease in the incidence of hepatitis A in vaccinated and in non-vaccinated age groups alike.

Risk of new onset autoimmune disease in 9- to 25-year-old women exposed to human papillomavirus-16/18 AS04-adjuvanted vaccine in the United Kingdom.

To assess the risk of autoimmune disease (AD) in 9-25 year-old women within 1 year after the first AS04-HPV-16/18vaccine dose, a retrospective, observational database cohort study was conducted using CPRD GOLD. From CPRD GOLD 4 cohorts (65,000 subjects each) were retrieved: 1 exposed female cohort (received ≥1 AS04-HPV-16/18 vaccine dose between Sep2008-Aug2010) and 3 unexposed cohorts: historical female (Sep2005-Aug2007), concurrent male, and historical male. Co-primary endpoints were confirmed neuroinflammatory/ophthalmic AD and other AD, secondary endpoints were confirmed individual AD. Risk of new onset of AD was compared between cohorts (reference: historical cohort) using Poisson regression. The main analysis using confirmed cases showed no neuroinflammatory/ophthalmic AD cases in the female exposed cohort. Incidence rate ratio (IRR) (95% CI) of other AD was 1.41 (0.86 to 2.31) in female and 1.77 (0.94 to 3.35) in male cohorts when compared to the female and male historical cohort, respectively. Secondary endpoints were evaluated for diseases with >10 cases, which were Crohn's disease (IRR: 1.21 [0.37 to 3.95] for female and 4.22 [0.47 to 38.02] for male cohorts), autoimmune thyroiditis (IRR: 3.75 [1.25 to 11.31] for female and no confirmed cases for male cohorts) and type 1 diabetes (IRR: 0.30 [0.11 to 0.83] for female and 2.46 [1.08 to 5.60] for male cohorts). Analysis using confirmed and non-confirmed cases showed similar results, except for autoimmune thyroiditis in females, IRR: 1.45 (0.79 to 2.64). There was no evidence of an increased risk of AD in women aged 9 to 25 years after AS04-HPV-16/18 vaccination.

The incidence, clearance and persistence of non-cervical human papillomavirus infections: a systematic review of the literature.

BACKGROUND: Human papillomavirus (HPV) vaccines were designed to prevent cervical cancer in women and their provision remains a major public health need. However, HPV is also a major cause of non-cervical anogenital and oropharyngeal cancers and the potential benefit of vaccination likely extends beyond cervical cancer. METHODS: A systematic literature search of PubMed (1995-2014) identified publications assessing the incidence, persistence, and clearance of non-cervical anogenital/oral HPV infections. Comparability with cervical HPV was assessed by identifying articles assessing the same or similar populations. RESULTS: Available data suggest high incidence rates of non-cervical HPV infection in men and women, with HPV-16 predominating in all sites. The incidence of high risk HPV per 100 person-years ranged from 11.4 to 72.9 for penile infections, 6.7-47.9 at other male genital sites, and 4.4-36.7 and 5.3-23.4 for anal infections in men and women, respectively. The incidence per 100 person-years of oral infection with any HPV type ranged from 5.7 to 6.7 in men and 6.8-39.6 in women. Within the limitations of the data, there was a general pattern of higher incidence and clearance of non-cervical genital HPV infections, compared to cervical infections. HIV status, circumcision, number of sex partners and partner HPV status significantly influenced high-risk HPV incidence/clearance at male anogenital sites. Few studies assessed risk factors for oral HPV. CONCLUSIONS: Parallels appear to exist between the epidemiology of cervical and non-cervical HPV infections in terms of incidence, HPV-type distribution, and risk factors for infection. Available data suggest that non-cervical genital HPV infections may occur more frequently, with higher clearance rates, than cervical infections. More extensive studies could provide useful information for estimating vaccine impact, the wider cost-benefit of HPV vaccination, and guiding vaccination policy. TRIAL REGISTRATION: Not applicable, as systematic review of the literature.