Subclinical Tuberculosis Disease-A Review and Analysis of Prevalence Surveys to Inform Definitions, Burden, Associations, and Screening Methodology.

While it is known that a substantial proportion of individuals with tuberculosis disease (TB) present subclinically, usually defined as bacteriologically-confirmed but negative on symptom screening, considerable knowledge gaps remain. Our aim was to review data from TB prevalence population surveys and generate a consistent definition and framework for subclinical TB, enabling us to estimate the proportion of TB that is subclinical, explore associations with overall burden and program indicators, and evaluate the performance of screening strategies. We extracted data from all publicly available prevalence surveys conducted since 1990. Between 36.1% and 79.7% (median, 50.4%) of prevalent bacteriologically confirmed TB was subclinical. No association was found between prevalence of subclinical and all bacteriologically confirmed TB, patient diagnostic rate, or country-level HIV prevalence (P values, .32, .4, and .34, respectively). Chest Xray detected 89% (range, 73%-98%) of bacteriologically confirmed TB, highlighting the potential of optimizing current TB case-finding policies.

Transition to retirement impact on health and lifestyle habits: analysis from a nationwide Italian cohort.

BACKGROUND: Retirement is a life-course transition likely to affect, through different mechanisms, behavioural risk factors' patterns and, ultimately, health outcomes. We assessed the impact of transitioning to retirement on lifestyle habits and perceived health status in a nationwide cohort of Italian adults. METHODS: We analysed data from a large cohort of Italian adults aged 55-70, derived from linking six waves of the Participation, Labour, Unemployment Survey (PLUS), a national survey representative of the Italian workforce population, conducted between 2010 and 2018. We estimated relative-risk ratios (RRR) of transition to retirement and their corresponding 95% confidence intervals (CIs) for selected behavioural risk factors and health outcomes using multivariable logistic regression models. We used propensity score matching (PSM) to account for potential confounders. RESULTS: We included 5169 subjects in the study population, of which 1653 retired between 2010 and 2018 (exposed, 32%). Transition to retirement was associated with a 36% increased probability of practising sports (RRR 1.36, 95% CI 1.12-1.64). No statistically significant changes were reported for smoking habit (current smoker RRR: 1.18, 95% CI 0.94-1.46) and BMI (overweight/obese RRR: 0.96, 95% CI 0.81-1.15). Overall, retiring was associated with improved self-rated health status (RRR 1.26, 95% CI 1.02-1.58). CONCLUSION: Individual data-linkage of multiple waves of the PLUS can offer great insight to inform healthy ageing policies in Italy and Europe. Transition to retirement has an independent effect on perceived health status, physical activity and selected behavioural risk factors. It should be identified as a target moment for preventive interventions, with particular reference to primary prevention so as to promote health and wellbeing in older ages.

The natural history of untreated pulmonary tuberculosis in adults: a systematic review and meta-analysis.

Stages of tuberculosis disease can be delineated by radiology, microbiology, and symptoms, but transitions between these stages remain unclear. In a systematic review and meta-analysis of studies of individuals with untreated tuberculosis who underwent follow-up (34 cohorts from 24 studies, with a combined sample of 139 063), we aimed to quantify progression and regression across the tuberculosis disease spectrum by extracting summary estimates to align with disease transitions in a conceptual framework of the natural history of tuberculosis. Progression from microbiologically negative to positive disease (based on smear or culture tests) in participants with baseline radiographic evidence of tuberculosis occurred at an annualised rate of 10% (95% CI 6·2-13·3) in those with chest x-rays suggestive of active tuberculosis, and at a rate of 1% (0·3-1·8) in those with chest x-ray changes suggestive of inactive tuberculosis. Reversion from microbiologically positive to undetectable disease in prospective cohorts occurred at an annualised rate of 12% (6·8-18·0). A better understanding of the natural history of pulmonary tuberculosis, including the risk of progression in relation to radiological findings, could improve estimates of the global disease burden and inform the development of clinical guidelines and policies for treatment and prevention.

Quantifying progression and regression across the spectrum of pulmonary tuberculosis: a data synthesis study.

BACKGROUND: Prevalence surveys show a substantial burden of subclinical (asymptomatic but infectious) tuberculosis, from which individuals can progress, regress, or even persist in a chronic disease state. We aimed to quantify these pathways across the spectrum of tuberculosis disease. METHODS: We created a deterministic framework of untreated tuberculosis disease with progression and regression between three states of pulmonary tuberculosis disease: minimal (non-infectious), subclinical (asymptomatic but infectious), and clinical (symptomatic and infectious). We obtained data from a previous systematic review of prospective and retrospective studies that followed and recorded the disease state of individuals with tuberculosis in a cohort without treatment. These data were considered in a Bayesian framework, enabling quantitative estimation of tuberculosis disease pathways with rates of transition between states and 95% uncertainty intervals (UIs). FINDINGS: We included 22 studies with data from 5942 individuals in our analysis. Our model showed that after 5 years, 40% (95% UI 31·3-48·0) of individuals with prevalent subclinical disease at baseline recover and 18% (13·3-24·0) die from tuberculosis, with 14% (9·9-19·2) still having infectious disease, and the remainder with minimal disease at risk of re-progression. Over 5 years, 50% (40·0-59·1) of individuals with subclinical disease at baseline never develop symptoms. For those with clinical disease at baseline, 46% (38·3-52·2) die and 20% (15·2-25·8) recover from tuberculosis, with the remainder being in or transitioning between the three disease states after 5 years. We estimated the 10-year mortality of people with untreated prevalent infectious tuberculosis to be 37% (30·5-45·4). INTERPRETATION: For people with subclinical tuberculosis, classic clinical disease is neither an inevitable nor an irreversible outcome. As such, reliance on symptom-based screening means a large proportion of people with infectious disease might never be detected. FUNDING: TB Modelling and Analysis Consortium and European Research Council.

Estimating the contribution of subclinical tuberculosis disease to transmission: An individual patient data analysis from prevalence surveys.

Background: Individuals with bacteriologically confirmed pulmonary tuberculosis (TB) disease who do not report symptoms (subclinical TB) represent around half of all prevalent cases of TB, yet their contribution to Mycobacterium tuberculosis (Mtb) transmission is unknown, especially compared to individuals who report symptoms at the time of diagnosis (clinical TB). Relative infectiousness can be approximated by cumulative infections in household contacts, but such data are rare. Methods: We reviewed the literature to identify studies where surveys of Mtb infection were linked to population surveys of TB disease. We collated individual-level data on representative populations for analysis and used literature on the relative durations of subclinical and clinical TB to estimate relative infectiousness through a cumulative hazard model, accounting for sputum-smear status. Relative prevalence of subclinical and clinical disease in high-burden settings was used to estimate the contribution of subclinical TB to global Mtb transmission. Results: We collated data on 414 index cases and 789 household contacts from three prevalence surveys (Bangladesh, the Philippines, and Viet Nam) and one case-finding trial in Viet Nam. The odds ratio for infection in a household with a clinical versus subclinical index case (irrespective of sputum smear status) was 1.2 (0.6-2.3, 95% confidence interval). Adjusting for duration of disease, we found a per-unit-time infectiousness of subclinical TB relative to clinical TB of 1.93 (0.62-6.18, 95% prediction interval [PrI]). Fourteen countries across Asia and Africa provided data on relative prevalence of subclinical and clinical TB, suggesting an estimated 68% (27-92%, 95% PrI) of global transmission is from subclinical TB. Conclusions: Our results suggest that subclinical TB contributes substantially to transmission and needs to be diagnosed and treated for effective progress towards TB elimination. Funding: JCE, KCH, ASR, NS, and RH have received funding from the European Research Council (ERC) under the Horizon 2020 research and innovation programme (ERC Starting Grant No. 757699) KCH is also supported by UK FCDO (Leaving no-one behind: transforming gendered pathways to health for TB). This research has been partially funded by UK aid from the UK government (to KCH); however, the views expressed do not necessarily reflect the UK government's official policies. PJD was supported by a fellowship from the UK Medical Research Council (MR/P022081/1); this UK-funded award is part of the EDCTP2 programme supported by the European Union. RGW is funded by the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), EDTCP (RIA208D-2505B), UK MRC (CCF17-7779 via SET Bloomsbury), ESRC (ES/P008011/1), BMGF (OPP1084276, OPP1135288 and INV-001754), and the WHO (2020/985800-0).

Current understandings of the impact of mandatory vaccination laws in Europe.

Vaccinations are among the most successful preventive tools to protect collective health. In response to alarming vaccines preventable diseases (VPDs) outbreaks resurgence, decreased vaccination coverage and vaccine refusal, several European countries have recently revised their vaccination policies introducing or extending mandatory vaccinations. This review examines the health, political and ethical aspects of mandatory vaccination.The authors first clarify terms and definitions and propose a conceptual framework of mandatory policies. Second, they describe the current status of mandatory childhood immunization programmes in Europe, assessing selected mandatory laws. Third, as the authors conduct a systematic review of the literature (retrieving from Medline 17 relevant records between 2010 and 2020), they take an analytical approach to measure the impact of mandatory vaccination policies on both VPDs control and immunization coverage, but also on population attitudes toward vaccines. 40% of European countries currently have mandatory vaccination policies; however, policies vary widely and, although there is evidence of increased vaccine uptake, their impact on informed adherence to preventive behaviors is scant.Although mandatory vaccination policies might be needed to protect collective health in times of emergency, public health goals of VPD prevention and health promotion should primarily be pursued through health education and population empowerment.

The Use of Digital Technologies to Support Vaccination Programmes in Europe: State of the Art and Best Practices from Experts' Interviews.

Digitalisation offers great potential to improve vaccine uptake, supporting the need for effective life-course immunisation services. We conducted semi-structured in-depth interviews with public health experts from 10 Western European countries (Germany, Greece, Italy, Luxembourg, Malta, the Netherlands, Norway, Poland, Portugal, and the United Kingdom) to assess the current level of digitalisation in immunisation programmes and retrieve data on interventions and best practices. Interviews were performed using an ad hoc questionnaire, piloted on a sample of national experts. We report a mixed level of digital technologies deployment within vaccination services across Europe: Some countries are currently developing eHealth strategies, while others have already put in place robust programmes. Institutional websites, educational videos, and electronic immunisation records are the most frequently adopted digital tools. Webinars and dashboards represent valuable resources to train and support healthcare professionals in immunisation services organisation. Text messages, email-based communication, and smartphone apps use is scattered across Europe. The main reported barrier to the implementation of digital-based programmes is the lack of resources and shared standards. Our study offers a comprehensive picture of the European context and shows the need for robust collaboration between states and international institutions to share best practices and inform the planning of digital intervention models with the aim of countering vaccine hesitancy and increasing vaccine uptake.

Effectiveness of email-based reminders to increase vaccine uptake: a systematic review.

BACKGROUND: In times of vaccine hesitancy and decreasing immunization coverage, it is crucial to exploit the potential of digital solutions to support immunization programmes and ultimately increase vaccine uptake. Scant evidence exists on the impact of email-based immunization reminders. In particular, while email communication is exponentially increasing at the global level, its use for health communication is still sporadic and limited data exists on its application to immunization programmes. The objective of this study is to systematically retrieve and critically appraise the available literature on the effectiveness of email-based reminders to increase vaccine uptake, with the ultimate aim to inform and encourage its integration in the implementation of immunization programmes. METHODS: We conducted a systematic review of literature following the PRISMA. We included studies providing quantitative comparative data on any measure of vaccine uptake. We extracted data on study design, study population, vaccine type and details of email-based interventions; data were pooled by type of comparison (no reminders, traditional reminders, other digital reminders). RESULTS: Eleven studies were included, 90% with experimental study designs. While email communication succeeds in increasing vaccine uptake when compared with no intervention, weak and heterogeneous data exist supporting the superiority of email reminders, as compared to traditional methods or other digital reminders. Encouraging evidence report the effectiveness of reminder methods combining different strategies and tailored to target populations' preferences. CONCLUSIONS: Theoretically, email communication offers many advantages: it is cheaper and faster, it can be automated and linked to electronic immunization registries, and reach people on the move. As we urge the need for further research to prove email communication impact on vaccine uptake in different settings, we underline the importance of identifying how to best integrate email communication in vaccine delivery equipping immunization programmes with technical infrastructures and normative frameworks suitable to embrace innovation.

Does the use of personal electronic health records increase vaccine uptake? A systematic review.

BACKGROUND: Although Personal Electronic Health Records (PEHR) have been identified as innovative tools enabling the provision of patient-centered care and prevention, evidence on the impact of their use is scant. With PEHRs being more and more marketed as easily implementable and cost-effective instruments to provide people with direct control on their health, the question on whether their use might be associated with the priority to improve vaccine coverage arises. METHODS: We conducted a systematic review following the PRISMA guidelines to retrieve, quantitatively pool and critically appraise the effectiveness of PEHR access on vaccine uptake. Analysis on PEHR effectiveness were carried out for the following comparison strata: i) PEHR access vs no intervention (standard care, no access to PEHR), ii) PEHR access only vs access to PEHR with additional features (e.g. health education materials, active reminders). RESULTS: Of 3114 identified citations, 8 studies were included, the majority published in the US and before 2015; 62% were randomized trials, the rest having an observational study design. Evidence suggests a moderate positive impact of PEHR access in increasing vaccine uptake, with data available for influenza and pneumococcal vaccines, diabetic patients and childhood immunization. Pooled data report the addition of digital communication features, i.e. the delivery of educational messages, reminders and availability of scheduling features might increase vaccine uptake, as compared to PEHR access alone. However, evidence is not conclusive. CONCLUSION: While immunization programs are struggling to achieve optimal coverage targets, it seems the potential of PEHRSs supporting informed adherence to vaccines recommendations is neither fully exploited nor explored. Which factors mediate the association between PEHRs access and vaccine uptake? Which PEHRs' design and functional components can maximize their impact? On which target populations? Which PEHR models works better for high-risk populations? Our findings can only partially answer those questions and further experimental research is needed.

COVID-19 mortality rate in nine high-income metropolitan regions.

We analyzed the spread of the COVID-19 epidemic in 9 metropolitan regions of the world with similar socio-demographic characteristics, daytime commuting population and business activities: the New York State, Bruxelles-Capital, the Community of Madrid, Catalonia, the Île-de-France Region, the Greater London county, Stockholms län, Hovedstaden (Copenhagen) and the Lombardy Region. The Lombardy region reported the highest COVID-19 crude mortality rate (141.0 x 100,000) 70-days after the onset of the epidemic, followed by the Community of Madrid (132.8 x 100,000) New York State (120.7 x 100,000). The large variation in COVID-19 mortality and case-fatality rates for COVID-19 in different age strata suggested a more accurate analysis and interpretation of the epidemic dynamics after standardization of the rates by age. The share of elder populations (>70 years) over total population varies widely in the considered study settings, ranging from 6.9% in Catalonia to 17.0% in Lombardy. When taking age distribution into consideration the highest standardized mortality rate was observed in the State of New York (257.9 x 100,000); with figures in most of the European regions concentrated between 123.3 x 100,000 in Greater London and 177.7 x 100,000 in Bruxelles-Capital, lower in French and Danish regions. We also report and critical appraise, when available, COVID-19 mortality figures in capital cities, nursing homes, as well as excess mortality at country level. Our data raise awareness on the need for a more in-depth epidemiological analysis of the current COVID-19 public health emergency that further explores COVID-19 mortality determinants associated with health services delivery, community-level healthcare, testing approaches and characteristics of surveillance systems, including classification of COVID-19 deaths.

The spread of COVID-19 in six western metropolitan regions: a false myth on the excess of mortality in Lombardy and the defense of the city of Milan.

We analyzed the spread of the COVID-19 epidemic in 6 metropolitan regions with similar demographic characteristics, daytime commuting population and business activities: the New York metropolitan area, the Île-de-France region, the Greater London county, Bruxelles-Capital, the Community of Madrid and the Lombardy region. The highest mortality rates 30-days after the onset of the epidemic were recorded in New York (81.2 x 100,000) and Madrid (77.1 x 100,000). Lombardy mortality rate is below average (41.4 per 100,000), and it is the only situation in which the capital of the region (Milan) has not been heavily impacted by the epidemic wave. Our study analyzed the role played by containment measures and the positive contribution offered by the hospital care system. (www.actabiomedica.it).

The campaign "This Is Public Health" in Italy, set up by a team of Public Health Schools in Northern Italy.

Despite the great effort to raise awareness among health promotion, nowadays Public Health policies are not often recognized as important tools. For this reason, the Health in All Policies (HiAP) approach is instrumental in tackling this information gap. In 2018, the US Association of Schools and Programs of Public Health (ASPPH) launched an international campaign called "This is Public Health" (TIPH), whose aim was "to brand public health and raise awareness of how it affects individuals, communities and populations". The Association of Schools of Public Health in the European Region (ASPHER), in coordination with ASPPH, decided to create a European campaign to support and to reproduce the American one, by opening a challenge among the European Public Health Schools. The Schools and Programs of PH of Vita-Salute "San Raffaele" University, Milan, University of Parma, University of Pavia and Politecnico of Milan won this bid. In this "briefing on" we present a report on the Italian project for raising awareness of Public Health among general population and health care personell.