Serotype Replacement after Introduction of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccines in 10 Countries, Europe.

We evaluated invasive pneumococcal disease (IPD) during 8 years of infant pneumococcal conjugate vaccine (PCV) programs using 10-valent (PCV10) and 13-valent (PCV13) vaccines in 10 countries in Europe. IPD incidence declined during 2011-2014 but increased during 2015-2018 in all age groups. From the 7-valent PCV period to 2018, IPD incidence declined by 42% in children <5 years of age, 32% in persons 5-64 years of age, and 7% in persons >65 years of age; non-PCV13 serotype incidence increased by 111%, 63%, and 84%, respectively, for these groups. Trends were similar in countries using PCV13 or PCV10, despite different serotype distribution. In 2018, serotypes in the 15-valent and 20-valent PCVs represented one third of cases in children <5 years of age and two thirds of cases in persons >65 years of age. Non-PCV13 serotype increases reduced the overall effect of childhood PCV10/PCV13 programs on IPD. New vaccines providing broader serotype protection are needed.

Public health considerations for transitioning beyond the acute phase of the COVID-19 pandemic in the EU/EEA.

Many countries, including some within the EU/EEA, are in the process of transitioning from the acute pandemic phase. During this transition, it is crucial that countries' strategies and activities remain guided by clear COVID-19 control objectives, which increasingly will focus on preventing and managing severe outcomes. Therefore, attention must be given to the groups that are particularly vulnerable to severe outcomes of SARS-CoV-2 infection, including individuals in congregate and healthcare settings. In this phase of pandemic management, a strong focus must remain on transitioning testing approaches and systems for targeted surveillance of COVID-19, capitalising on and strengthening existing systems for respiratory virus surveillance. Furthermore, it will be crucial to focus on lessons learned from the pandemic to enhance preparedness and to enact robust systems for the preparedness, detection, rapid investigation and assessment of new and emerging SARS-CoV-2 variants. Filling existing knowledge gaps, including behavioural insights, can help guide the response to future resurgences of SARS-CoV-2 and/or the emergence of other pandemics. Finally, 'vaccine agility' will be needed to respond to changes in people's behaviours, changes in the virus, and changes in population immunity, all the while addressing issues of global health equity.

Human papillomavirus vaccination in the European Union/European Economic Area and globally: a moral dilemma.

While many European Union/European Economic Area (EU/EEA) countries recently expanded human papillomavirus (HPV) vaccination to boys, HPV vaccine supply is currently limited for girls in low- and middle-income countries (LMIC) that are severely affected by HPV.Globally, about 50% of countries have introduced HPV vaccination. Some LMIC with high burden of cervical cancer have not yet introduced HPV vaccination, or are reaching suboptimal vaccination coverage. While WHO issued a call for cervical cancer elimination in 2018, a global shortage of HPV vaccines is currently predicted to last at least until 2024.We reviewed national policies of EU/EEA countries and recommendations of the World Health Organization (WHO) Strategic Advisory Group of Experts on immunisation to discuss current challenges and dose-sparing options. Several EU/EEA countries have extended HPV vaccination to boys and the European Cancer Organisation has issued a resolution for elimination of all HPV-associated cancers in both sexes. The European Centre for Disease Prevention and Control concluded in its 2020 guidance that cost-effectiveness of extending routine vaccination to boys depends on several context-specific factors. The extension of HPV vaccination to boys in EU/EEA countries may affect global availability of vaccines. Temporary dose-sparing options could be considered during the COVID-19 post-pandemic period.

Rapidly increasing cumulative incidence of coronavirus disease (COVID-19) in the European Union/European Economic Area and the United Kingdom, 1 January to 15 March 2020.

The cumulative incidence of coronavirus disease (COVID-19) cases is showing similar trends in European Union/European Economic Area countries and the United Kingdom confirming that, while at a different stage depending on the country, the COVID-19 pandemic is progressing rapidly in all countries. Based on the experience from Italy, countries, hospitals and intensive care units should increase their preparedness for a surge of patients with COVID-19 who will require healthcare, and in particular intensive care.

Potential scenarios for the progression of a COVID-19 epidemic in the European Union and the European Economic Area, March 2020.

Two months after the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the possibility of established and widespread community transmission in the European Union and European Economic Area (EU/EEA) is becoming more likely. We provide scenarios for use in preparedness for a possible widespread epidemic. The EU/EEA is moving towards the 'limited sustained transmission' phase. We propose actions to prepare for potential mitigation phases and coordinate efforts to protect the health of citizens.

Disability weights for infectious diseases in four European countries: comparison between countries and across respondent characteristics.

Background: In 2015, new disability weights (DWs) for infectious diseases were constructed based on data from four European countries. In this paper, we evaluated if country, age, sex, disease experience status, income and educational levels have an impact on these DWs. Methods: We analyzed paired comparison responses of the European DW study by participants' characteristics with separate probit regression models. To evaluate the effect of participants' characteristics, we performed correlation analyses between countries and within country by respondent characteristics and constructed seven probit regression models, including a null model and six models containing participants' characteristics. We compared these seven models using Akaike Information Criterion (AIC). Results: According to AIC, the probit model including country as covariate was the best model. We found a lower correlation of the probit coefficients between countries and income levels (range rs: 0.97-0.99, P < 0.01) than between age groups (range rs: 0.98-0.99, P < 0.01), educational level (range rs: 0.98-0.99, P < 0.01), sex (rs = 0.99, P < 0.01) and disease status (rs = 0.99, P < 0.01). Within country the lowest correlations of the probit coefficients were between low and high income level (range rs = 0.89-0.94, P < 0.01). Conclusions: We observed variations in health valuation across countries and within country between income levels. These observations should be further explored in a systematic way, also in non-European countries. We recommend future researches studying the effect of other characteristics of respondents on health assessment.

Impact of infectious diseases on population health using incidence-based disability-adjusted life years (DALYs): results from the Burden of Communicable Diseases in Europe study, European Union and European Economic Area countries, 2009 to 2013.

Background and aimsThe Burden of Communicable Diseases in Europe (BCoDE) study aimed to calculate disability-adjusted life years (DALYs) for 31 selected diseases in the European Union (EU) and European Economic Area (EEA). Methods: DALYs were estimated using an incidence-based and pathogen-based approach. Incidence was estimated through assessment of data availability and quality, and a correction was applied for under-estimation. Calculation of DALYs was performed with the BCoDE software toolkit without applying time discounting and age-weighting. Results: We estimated that one in 14 inhabitants experienced an infectious disease episode for a total burden of 1.38 million DALYs (95% uncertainty interval (UI): 1.25-1.5) between 2009 and 2013; 76% of which was related to the acute phase of the infection and its short-term complications. Influenza had the highest burden (30% of the total burden), followed by tuberculosis, human immunodeficiency virus (HIV) infection/AIDS and invasive pneumococcal disease (IPD). Men had the highest burden measured in DALYs (60% of the total), adults 65 years of age and over had 24% and children less than 5 years of age had 11%. Age group-specific burden showed that infants (less than 1 year of age) and elderly people (80 years of age and over) experienced the highest burden. Conclusions: These results provide baseline estimates for evaluating infectious disease prevention and control strategies. The study promotes an evidence-based approach to describing population health and assessing surveillance data availability and quality, and provides information for the planning and prioritisation of limited resources in infectious disease prevention and control.

Estimating the annual burden of tick-borne encephalitis to inform vaccination policy, Slovenia, 2009 to 2013.

With an annual incidence between 8 and 15 per 100,000 population in the period from 2009 to 2013, Slovenia has one of the highest notified incidences of tick-borne encephalitis (TBE) in Europe. TBE vaccination coverage remains at about 7.3%. To inform vaccination policy, we used surveillance data from 2009 to 2013 to calculate the overall and age- and sex-specific mean annual TBE incidence. We estimated disability-adjusted life years (DALYs) with 95% uncertainty intervals (UI), using the Burden of Communicable Diseases in Europe approach from the European Centre for Disease Prevention and Control. The mean annual incidence was 11.6 per 100,000 population, peaking in older age groups (50-74 years: 18.5/100,000) while relatively lower among children (5-14 years: 10.2/100,000). We estimated an overall 10.95 DALYs per 100,000 population per year (95% UI: 10.25-11.65). In contrast to the TBE incidence, the disease burden in children aged 5-14 years was higher than in adults aged 50-74 years: 17.31 (95% UI: 14.58-20.08) and 11.58 (95% UI: 10.25-12.91) DALYs per 100,000 stratum-specific population, respectively. In a limited resource setting where prioritisation of TBE vaccination strategies is required, vaccination programmes targeting children may have a higher impact on disease burden.

Risk of hospitalisation and death due to bone fractures after breast cancer: a registry-based cohort study.

BACKGROUND: Bone fractures may have an impact on prognosis of breast cancer. The long-term risks of bone fracture in breast cancer patients have not been thoroughly studied. METHODS: Poisson regression was used to investigate the incidence of hospitalisation due to bone fracture comparing women with and without breast cancer based on Swedish National registers. Cox regression was used to investigate the risk of being hospitalised with bone fracture, and subsequent risk of death, in a regional cohort of breast cancer patients. RESULTS: For breast cancer patients, the 5-year risk of bone fracture hospitalisation was 4.8% and the 30-day risk of death following a bone fracture hospitalisation was 2.0%. Compared with the general population, breast cancer patients had incidence rate ratios of 1.25 (95% CI: 1.23-1.28) and 1.18 (95% CI: 1.14-1.22) for hospitalisation due to any bone fracture and hip fracture, respectively. These ratios remained significantly increased for 10 years. Comorbidities (Charlson Comorbidity Index ⩾1) were associated with the risk of being hospitalised with bone fracture. Women taking aromatase inhibitors were at an increased risk as compared with women taking tamoxifen (HR=1.48; 95% CI: 0.98-2.22). Breast cancer patients hospitalised for a bone fracture showed a higher risk of death (HR=1.83; 95% CI: 1.50-2.22) compared with those without bone fracture. CONCLUSIONS: Women with a previous breast cancer diagnosis are at an increased risk of hospitalisation due to a bone fracture, particularly if they have other comorbidities.

Review of disability weight studies: comparison of methodological choices and values.

INTRODUCTION: The disability-adjusted life year (DALY) is widely used to assess the burden of different health problems and risk factors. The disability weight, a value anchored between 0 (perfect health) and 1 (equivalent to death), is necessary to estimate the disability component (years lived with disability, YLDs) of the DALY. After publication of the ground-breaking Global Burden of Disease (GBD) 1996, alternative sets of disability weights have been developed over the past 16 years, each using different approaches with regards to the panel, health state description, and valuation methods. The objective of this study was to review all studies that developed disability weights and to critically assess the methodological design choices (health state and time description, panel composition, and valuation method). Furthermore, disability weights of eight specific conditions were compared. METHODS: Disability weights studies (1990¿2012) in international peer-reviewed journals and grey literature were identified with main inclusion criteria being that the study assessed DALY disability weights for several conditions or a specific group of illnesses. Studies were collated by design and methods and evaluation of results. RESULTS: Twenty-two studies met the inclusion criteria of our review. There is considerable variation in methods used to derive disability weights, although most studies used a disease-specific description of the health state, a panel that consisted of medical experts, and nonpreference-based valuation method to assess the values for the majority of the disability weights. Comparisons of disability weights across 15 specific disease and injury groups showed that the subdivision of a disease into separate health states (stages) differed markedly across studies. Additionally, weights for similar health states differed, particularly in the case of mild diseases, for which the disability weight differed by a factor of two or more. CONCLUSIONS: In terms of comparability of the resulting YLDs, the global use of the same set of disability weights has advantages, though practical constraints and intercultural differences should be taken into account into such a set.

Effects of an ageing population and the replacement of immune birth cohorts on the burden of hepatitis A in the Netherlands.

BACKGROUND: In populations in which the incidence of hepatitis A virus (HAV) infection has declined due to socio-economic improvements, better sanitation and hygiene, and vaccination, birth cohorts who have long-term immunity through exposure early in life are now being replaced by non-immune cohorts, meaning that more cases in the elderly may occur in future. Our goal was to qualitatively investigate the interaction of this cohort effect and demographic change (population ageing) on the estimated disease burden of HAV infection in the Netherlands. METHODS: We used dynamic MSIR (maternal immunity-susceptible-infectious-recovered) transmission and demographic models to simulate annual HAV incidence over the period 2000-2030, and estimated disease burden using the disability-adjusted life years (DALY) measure and a pre-defined disease progression model. Five scenarios representing different force of infection situations were simulated. RESULTS: The overall disease burden was projected to decrease over the simulation period in the baseline scenario (310 DALYs in 2000 compared with 67 in 2030). This decreasing trend was absent for the 55+ years age group; 23.5% of all new infections were predicted to occur in the 55+ group in 2030, compared with 5.5% in the 55+ group in 2000. CONCLUSIONS: In the absence of further public health interventions and under the assumption of a continued steady decline in the force of infection, the HAV disease burden in the Netherlands is predicted to decrease over the coming decades, but with proportionally more of the burden occurring within the increasingly larger segment of the population represented by elderly persons who are no longer naturally immune.

Effectiveness of 10 and 13-valent pneumococcal conjugate vaccines against invasive pneumococcal disease in European children: SpIDnet observational multicentre study.

BACKGROUND: Pneumococcal conjugate vaccines covering 10 (PCV10) and 13 (PCV13) serotypes have been introduced in the infant immunization schedule of most European countries in 2010-11. To provide additional real-life data, we measured the effectiveness of PCV10 and PCV13 against invasive pneumococcal disease (IPD) in children of 12 European sites (SpIDnet). METHODS: We compared the vaccination status of PCV10 and PCV13 serotype IPD (cases) to that of nonPCV13 serotype IPD (controls) reported in 2012-2018. We calculated pooled effectiveness as (1-vaccination odds ratio)*100, and measured effectiveness over time since booster dose. RESULTS: The PCV13 and PCV10 studies included 2522 IPD cases from ten sites and 486 cases from four sites, respectively. The effectiveness of ≥ 1 PCV13 dose was 84.2% (95 %CI: 79.0-88.1) against PCV13 serotypes (n = 2353) and decreased from 93.1% (87.8-96.1) < 12 months to 85.1% (72.0-92.1) ≥ 24 months after booster dose. PCV13 effectiveness of ≥ 1 dose was 84.7% (55.7-94.7) against fatal PCV13 IPD, 64.5% (43.7-77.6), 83.2% (73.7-89.3) and 85.1% (67.6-93.1) against top serotypes 3, 19A and 1, respectively, and 85.4% (62.3-94.4) against 6C. Serotype 3 and 19A effectiveness declined more rapidly. PCV10 effectiveness of ≥ 1 dose was 84.8% (69.4-92.5) against PCV10 serotypes (n = 370), 27.2% (-187.6 to 81.6) and 85.3% (35.2-96.7) against top serotypes 1 and 7F, 32.5% (-28.3 to 64.5) and -14.4% (-526.5 to 79.1) against vaccine-related serotypes 19A and 6C, respectively. CONCLUSIONS: PCV10 and PCV13 provide similar protection against IPD due to the respective vaccine serotype groups but serotype-specific effectiveness varies by serotype and vaccine. PCV13 provided individual protection against serotype 3 and vaccine-related serotype 6C IPD. PCV10 effectiveness was not significant against vaccine-related serotypes 19A and 6C. PCV13 effectiveness declined with time after booster vaccination. This multinational study enabled measuring serotype-specific vaccine effectiveness with a precision rarely possible at the national level. Such large networks are crucial for the post-licensure evaluation of vaccines.

Breaking the matching in nested case-control data offered several advantages for risk estimation.

OBJECTIVE: To demonstrate the advantage of using weighted Cox regression to analyze nested case-control data in overcoming limitations encountered with traditional conditional logistic regression. STUDY DESIGN AND SETTING: We analyzed data from 1,051 women who were sampled in a case-control study of lung cancer nested within a cohort of breast cancer patients. We investigated how lung cancer risk is associated with radiation therapy and modified by smoking, with both conditional logistic regression and weighted Cox regression models. RESULTS: In contrast to logistic regression, weighted Cox regression exploited the information regarding radiation dose received by each individual lung. The weighted method also mitigated a problem of overmatching apparent in the data and revealed that the risk of radiotherapy-associated lung cancer was modified by smoking (P = 0.026) with a hazard ratio of 4.09 (2.31, 7.24) in unexposed smokers and 8.63 (5.04, 14.79) in smokers receiving doses >13 Gy. The cumulative risk of lung cancer increased steadily with increasing radiotherapy dose in smokers, whereas no such effect was found in nonsmokers. CONCLUSION: The weighted Cox regression makes optimal and versatile use of the information in a nested case-control design, allowing dose-response analysis of exposure to paired organs and enabling the estimation of cumulative risk.

A Software Tool for Estimation of Burden of Infectious Diseases in Europe Using Incidence-Based Disability Adjusted Life Years.

The burden of disease framework facilitates the assessment of the health impact of diseases through the use of summary measures of population health such as Disability-Adjusted Life Years (DALYs). However, calculating, interpreting and communicating the results of studies using this methodology poses a challenge. The aim of the Burden of Communicable Disease in Europe (BCoDE) project is to summarize the impact of communicable disease in the European Union and European Economic Area Member States (EU/EEA MS). To meet this goal, a user-friendly software tool (BCoDE toolkit), was developed. This stand-alone application, written in C++, is open-access and freely available for download from the website of the European Centre for Disease Prevention and Control (ECDC). With the BCoDE toolkit, one can calculate DALYs by simply entering the age group- and sex-specific number of cases for one or more of selected sets of 32 communicable diseases (CDs) and 6 healthcare associated infections (HAIs). Disease progression models (i.e., outcome trees) for these communicable diseases were created following a thorough literature review of their disease progression pathway. The BCoDE toolkit runs Monte Carlo simulations of the input parameters and provides disease-specific results, including 95% uncertainty intervals, and permits comparisons between the different disease models entered. Results can be displayed as mean and median overall DALYs, DALYs per 100,000 population, and DALYs related to mortality vs. disability. Visualization options summarize complex epidemiological data, with the goal of improving communication and knowledge transfer for decision-making.

Infection-related hospitalizations in breast cancer patients: Risk and impact on prognosis.

OBJECTIVES: Infections are a common cause of hospitalization in breast cancer patients. We studied the risk, clinical characteristics and outcomes of infection-related hospitalizations in this patient population. METHODS: A Swedish registry-based study including 8338 breast cancer patients diagnosed between 2001 and 2008, followed prospectively for infection-related hospitalizations until 2010. Standardized incidence ratios (SIRs) were calculated using background rates from the general female population. Associations with clinical characteristics and mortality were analyzed using flexible parametric survival models. RESULTS: In total, 720 patients experienced an infection-related hospitalization during a median follow-up of 4.9 years. Infection rates were highest within the first year of diagnosis (SIR = 5.61, 95% CI; 4.98-6.32), and site-specific risks were most pronounced for sepsis (SIR = 3.14, 95% CI; 2.66-3.71) and skin infections (SIR = 2.80, 95% CI; 2.24-3.50). Older age at diagnosis, comorbidities, markers of tumor aggressiveness, chemotherapy and axillary node dissection were independent predictors of infectious disease risk. Infection-related hospitalizations were also independently associated with overall and breast cancer-specific death. CONCLUSIONS: A significant number of breast cancer patients are hospitalized with an infection following diagnosis, which in turn predicts poor prognosis. The risk profile of infection-related hospitalizations is multifactorial, including patient, tumor and treatment-related factors.

[Survey of the Council of Residents of the Italian Society of Hygiene (SItI) on the smoking habits of physicians training in Hygiene and Preventive Medicine.]. / Indagine della Consulta degli Specializzandi SItI sul fumo di sigaretta tra i medici in formazione nelle scuole di specializzazione in Igiene e Medicina Preventiva: uno studio trasversale.

This study was conducted on a sample of physicians training in Hygiene and Preventive medicine to evaluate their: smoking habits, awareness of the effects of cigarette smoke on health and attitudes regarding antismoking legislation. Data was obtained through administration of an anonymous questionnaire. A total of 220 physicians were interviewed: 27% was found to be a smoker while 45% of smokers stated that they did not want to quit smoking. These results are similar to those obtained for the general population. Amongst the residents of the various schools of specialisation, there are large differences in habits, awareness and attitudes towards smoke: a lack of professional training on the subject is present.

[The evaluation process of public health action: the challenge of epidemiology]. / Valutazione dell'efficacia degli interventi in Sanità Pubblica: il ruolo dell'epidemiologia.

This paper aims to focus the need of a correct use of epidemiology in the evaluation process of public health actions. It has been described the challenge of epidemiology, at first used mainly for aetiological studies but now much more involved in health services research. Then, considering the fact that in public health every act has to be judged on the basis of its suitability and efficacy, but also of the few financial resources available, the authors stated the importance of the identification of the actual role of the epidemiologists in the evaluation processes and, meanwhile, of their specific training programs. It is eventually underlined that public health, though becoming more and more complex, needs measurable and concrete evaluation indexes and criteria which could lead to a correct selection of the targets and of the actions needed.

Prognosis of patients with breast cancer: causes of death and effects of time since diagnosis, age, and tumor characteristics.

PURPOSE: The proportion of women living with a diagnosis of breast cancer in developed countries is increasing. Because breast cancer-specific deaths decrease with time since diagnosis, it is important to assess the burden of other causes of death in women diagnosed with breast cancer. METHODS: Different causes of death within 10 years from diagnosis were assessed in 12,850 women younger than 75 years of age with stage 1 to 3 breast cancer diagnosed in Stockholm and Gotland regions 1990 to 2006. Flexible parametric survival models were used to estimate hazard ratios over time since diagnosis by tumor characteristics and age at diagnosis. RESULTS: The proportion of deaths attributed to breast cancer ranged from 95.0% among women younger than age 45 years at diagnosis to 44.5% among women age 65 to 74 years. The proportions of circulatory system-specific deaths and deaths resulting from other causes increased with older age at diagnosis. Patients with one to three positive lymph nodes were more likely to die as a result of breast cancer during the first 10 years of follow-up compared with women without positive lymph nodes. Women with estrogen receptor (ER) -positive tumors had the same risk of dying as a result of breast cancer 5 years after diagnosis compared with women with ER-negative tumors. CONCLUSION: Lymph node negativity is an important long-term predictor of more favorable prognosis. The nature of the relationship between ER status and risk of dying as a result of breast cancer after 5 years of follow-up requires further investigation. Circulatory system diseases are an important cause of death, especially in women diagnosed with breast cancer at an older age.

Third Italian national survey on knowledge, attitudes, and sexual behaviour in relation to HIV/AIDS risk and the role of health education campaigns.

AIM: The survey, supported by the National Health Institute (ISS), investigates on sources of information for HIV/AIDS and sexual behaviour of the Italian general population. METHODS: The survey was carried out in four different Italian provinces with different geographical, social, and epidemiological patterns of HIV/AIDS: Bari, Milan, Parma, and Perugia. A self-administered questionnaire was used to interview a sample of 2000 people, aged 18-49 years, chosen using a quota-sampling, considering age, sex, and level of education. RESULTS: A total of 1985 persons filled in the questionnaire. Among them, 73.2% reported Ministry of Health as their main source of information and 76.7% TV/radio advertising as their main means of information. Sexually active subjects, experiencing occasional sexual intercourse, were 22.4%; of them 34.6% did not refer a systematic use of condom. Among sexually active people, half (45.7%) reported as irrelevant their risk of infection, 6.9% as high. Being male (OR = 6.175) and having the first sexual intercourse before 18 years (OR = 2.076) were significantly associated with sexual behaviour at risk (males having unsafe sexual intercourses with prostitutes or during partners' menstrual period; both sexes having unsafe occasional sexual intercourses or anal sex), while living in Northern Italy (OR = 0.672) was significantly protective. Subjects with sexual behaviour at risk were about 40%. CONCLUSIONS: The need for further education campaigns, and their consequent evaluations, is relevant. Monitoring sexual behaviour of general population, focusing on risk behaviour rather than risk groups, is fundamental nowadays in preventing HIV.