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

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)

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

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 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

“This Is Public Health in Italy”. An ASPPH-ASPHER campaign to raise awareness on health prevention and Health in All Policies

Introduction In many European countries, Public Health (PH) and Preventive Medicine are not perceived as important tools 1 2.The general population, especially those working in non-healthcare related fields, underestimates the crucial role of PH policies as food & veterinary safety, energy efficiency, transport regulation, healthcare design and city planning 3-8. The Health in All Policies (HiAP) approach is instrumental in tackling this information gap 9 10. Originally conceived in the EU, HiAP is now included in WHO’s Sustainable Development Goals. In the US, in 2018, the Association of Schools & 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, families, communities, and populations” 11. The Association of Schools of Public Health in the European Region (ASPHER) responded by creating a European campaign to reproduce the American one. An open challenge was set, in which PH Schools – students and staff – were requested to formulate country-specific proposals. The Accademia Lombarda di Sanità Pubblica, coordinating the Schools and Programs of PH of Vita-Salute “San Raffaele” University, Milan, University of Parma, University of Pavia and Politecnico of Milan set up a proposal to increase PH awareness both in the general population and in healthcare workers. Materials and methods The preliminary phase was dedicated to the Project setup and was conducted by the ten new Residents of the Vita-Salute “San Raffaele” University, with the coordination and supervision of the PI and the Schools’ Directors. The working group extensively discussed the need for an appropriate translation of the catchphrase and a new graphic rendering of the TIPH logo. An agreement was finally reached to adapt all the elements of the Campaign, re-elaborating them according to the Italian context. The word “health” has a double meaning in Italian (“salute” and “sanità”). Furthermore, people with limited English proficiency are a large part of the target population. Therefore, the Group opted for a non-literal translation (“Per la salute di tutti”). To further boost the Campaign online, the group created “TIPH – Italy” accounts and pages on the main social media (i.e. Facebook, Twitter, Instagram). Subsequently, the PI assigned tasks to each of the team’s members from the various PH Schools involved. The operational phase is currently underway, and a series of activities are already in schedule. All laws and resolutions enacted by local governments (Lombardy Region and, in a future phase, Emilia Romagna Region) are being thoroughly analysed, to assess their direct or indirect PH impact. Spreading the project will be a key for its success. In the next months, multiple promotional events will be organised, addressing both operators and the public at large. Surveys will be administered before and after the events, both to assess baseline knowledge and attitudes towards PH initiatives, and to verify the interventions’ effectiveness in raising awareness. Running a social media photo contest will be a useful option for targeting younger age groups, following in the steps of the US campaign. Side events will be organised, such as congress, meeting, press conferences, with the purpose of giving the latest updates about the Campaign. Conclusions Italy is a challenging country. A fairly strong National Health Service, with plenty of positive health indicators, coexist with impressive inequalities and contradictions, both in the North-South and in the rich-poor axis. In light of this scenario, stronger recognition of the role and the importance of PH is essential. PH awareness is ultimately directed at informing policymaking and improving community health 12. While the potential impact of TIPH in Italy is still to be fully explored, the basis for its potential success can only lie in the delivery of a culturally appropriate message. TIPH Italy is a wonderful opportunity of making PH accessible to the general population in an effective, yet entertaining way

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