Analysing the link between public transport use and airborne transmission: mobility and contagion in the London underground

Background: The transmission of infectious diseases is dependent on the amount and nature of contacts between infectious and healthy individuals. Confined and crowded environments that people visit in their day-to-day life (such as town squares, business districts, transport hubs, etc) can act as hot-spots for spreading disease. In this study we explore the link between the use of public transport and the spread of airborne infections in urban environments. Methods: We study a large number of journeys on the London Underground, which is known to be particularly crowded at certain times. We use publically available Oyster card data (the electronic ticket used for public transport in Greater London), to infer passengers’ routes on the underground network. In order to estimate the spread of a generic airborne disease in each station, we use and extend an analytical microscopic model that was initially designed to study people moving in a corridor. Results: Comparing our results with influenza-like illnesses (ILI) data collected by Public Health England (PHE) in London boroughs, shows a correlation between the use of public transport and the spread of ILI. Specifically, we show that passengers departing from boroughs with higher ILI rates have higher number of contacts when travelling on the underground. Moreover, by comparing our results with other demographic key factors, we are able to discuss the role that the Underground plays in the spread of airborne infections in the English capital. Conclusions: Our study suggests a link between public transport use and infectious diseases transmission and encourages further research into that area. Results could be used to inform the development of non-pharmacological interventions that can act on preventing instead of curing infections and are, potentially, more cost-effective

Improving Allocative Efficiency in Zimbabwe’s Health Sector: Results from the Health Interventions Prioritization Tool

The country of Zimbabwe has seen some important improvements in key health outcomes since 2009. However, despite progress in some areas of the health sector, the country did not meet its Millennium Development Goals (MDGs) and current progress falls short of the Sustainable Development Goals (SDGs) milestones. As is often the case, the poor and rural populations in Zimbabwe bear a disproportionate burden of disease and health risks. The situation is compounded by national economic challenges and health sector spending inefficiencies that have resulted in households bearing an increasing share of health sector financing, mainly through out-of-pocket expenditures. Households provide approximately 25 percent of health sector financing in Zimbabwe. Again, the poor and rural populations are hardest hit by this economic reality. Zimbabwe was one of the few countries in which HIPtool was piloted at the proof of concept stage. HIPtool enables the mathematical prioritization of interventions based on existing data and a set of criteria. It provides a technical foundation to further develop an essential health benefits package. However, HIPtool, at this stage in development, still has strong limitations, which are outlined along with results in this report

An open label, randomised controlled trial of rifapentine versus rifampicin based short course regimens for the treatment of latent tuberculosis in England: the HALT LTBI pilot study

BACKGROUND: Ending the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks. METHODS: An open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid ('intervention') or a daily combination of rifampicin/isoniazid ('standard'), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded. RESULTS: Fifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7-91.4), compared with 19 of 25 (76.0%, CI 54.9-90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms. CONCLUSION: In this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current treatment. TRIAL REGISTRATION: The trial was funded by the NIHR, UK and registered with ISRCTN ( 26/02/2013-No.04379941 )

An open label, randomised controlled trial of rifapentine versus rifampicin based short course regimens for the treatment of latent tuberculosis in England: the HALT LTBI pilot study.

BACKGROUND: Ending the global tuberculosis (TB) epidemic requires a focus on treating individuals with latent TB infection (LTBI) to prevent future cases. Promising trials of shorter regimens have shown them to be effective as preventative TB treatment, however there is a paucity of data on self-administered treatment completion rates. This pilot trial assessed treatment completion, adherence, safety and the feasibility of treating LTBI in the UK using a weekly rifapentine and isoniazid regimen versus daily rifampicin and isoniazid, both self-administered for 12 weeks. METHODS: An open label, randomised, multi-site pilot trial was conducted in London, UK, between March 2015 and January 2017. Adults between 16 and 65 years with LTBI at two TB clinics who were eligible for and agreed to preventative therapy were consented and randomised 1:1 to receive either a weekly combination of rifapentine/isoniazid ('intervention') or a daily combination of rifampicin/isoniazid ('standard'), with both regimens taken for twelve weeks; treatment was self-administered in both arms. The primary outcome, completion of treatment, was self-reported, defined as taking more than 90% of prescribed doses and corroborated by pill counts and urine testing. Adverse events were recorded. RESULTS: Fifty-two patients were successfully enrolled. In the intervention arm 21 of 27 patients completed treatment (77.8, 95% confidence interval [CI] 57.7-91.4), compared with 19 of 25 (76.0%, CI 54.9-90.6) in the standard of care arm. There was a similar adverse effect profile between the two arms. CONCLUSION: In this pilot trial, treatment completion was comparable between the weekly rifapentine/isoniazid and the daily rifampicin/isoniazid regimens. Additionally, the adverse event profile was similar between the two arms. We conclude that it is safe and feasible to undertake a fully powered trial to determine whether self-administered weekly treatment is superior/non-inferior compared to current treatment. TRIAL REGISTRATION: The trial was funded by the NIHR, UK and registered with ISRCTN ( 26/02/2013-No.04379941 )

Protocol for a cluster randomised control trial evaluating the efficacy and safety of treatment for latent tuberculosis infection in recent migrants within primary care: the CATAPuLT trial.

BACKGROUND: The identification and treatment of LTBI is a key component of the WHO's strategy to eliminate TB. Recent migrants from high TB-incidence countries are recognised to be at risk TB reactivation, and many high-income countries have focused on LTBI screening and treatment programmes for this group. However, migrants are the group least likely to complete the LTBI cascade-of-care. This pragmatic cluster-randomised, parallel group, superiority trial investigates whether a model of care based entirely within a community setting (primary care) will improve treatment completion compared with treatment in specialist TB services (secondary care). METHODS: The CATAPuLT trial (Completion and Acceptability of Treatment Across Primary Care and the community for Latent Tuberculosis) randomised 34 general practices in London, England, to evaluate the efficacy and safety of treatment for LBTI in recent migrants within primary care. GP practices were randomised to either provide management for LTBI entirely within primary care (GPs and community pharmacists) or to refer patients to secondary care. The target recruitment number for individuals is 576. The primary outcome is treatment completion (defined as taking at least 90% of antibiotic doses). The secondary outcomes assess adherence, acceptance of treatment, the incidence of adverse effects including drug-induced liver injury, the rates of active TB, patient satisfaction and cost-effectiveness of LTBI treatment. This protocol adheres to the SPIRIT Checklist. DISCUSSION: The CATAPuLT trial seeks to provide implementation research evidence for a patient-centred intervention to improve treatment completion for LTBI amongst recent migrants to the UK. TRIAL REGISTRATION: NCT03069807, March 2017, registered retrospectively

Tackling TB in migrants arriving at Europe's southern border

Over a quarter of the individuals diagnosed with tuberculosis [TB] in the European Union region are born outside of the area and the proportion has been increasing steadily. Italy is a low TB incidence country with over 50% of TB cases in the foreign-born population primarily due to the high numbers of migrants entering the country via land or sea. As a case study to evaluate the value of screening in newly arrived migrants, the EDETECT-TB project in Italy implemented and evaluated active TB screening in the migrant population at first reception centres to ensure early diagnosis to avoid further spread. Based on a cost-effectiveness analysis from a program provider perspective, a decision tree model allowed the assessment of the value for money of case finding by estimating the cost per case of active TB detected compared with the status quo of no screening. The analysis confirmed that early case detection is a cost-effective intervention in areas with migrants arriving from high TB risk settings. Targeted post-arrival early screening of high TB risk vulnerable new entrants to Italy has a potential role in reducing the spread of TB among migrants

Screening for tuberculosis among high-risk groups attending London Emergency Departments: A prospective observational study.

LTBI screening among high-risk groups at EDs could be implemented to identify those at risk of progression to TB disease. Large-scale studies are required to investigate effective TB disease screening strategies in EDs. https://bit.ly/3bTkoO

Evaluating the equity impact and cost-effectiveness of digital adherence technologies with differentiated care to support tuberculosis treatment adherence in Ethiopia: protocol and analysis plan for the health economics component of a cluster randomised trial

Abstract Background Tuberculosis remains a leading infectious cause of death in resource-limited settings. Effective treatment is the cornerstone of tuberculosis control, reducing mortality, recurrence and transmission. Supporting treatment adherence through facility-based observations of medication taking can be costly to providers and patients. Digital adherence technologies (DATs) may facilitate treatment monitoring and differentiated care. The ASCENT-Ethiopia study is a three-arm cluster randomised trial assessing two DATs with differentiated care for supporting tuberculosis treatment adherence in Ethiopia. This study is part of the ASCENT consortium, assessing DATs in South Africa, the Philippines, Ukraine, Tanzania and Ethiopia. The aim of this study is to determine the costs, cost-effectiveness and equity impact of implementing DATs in Ethiopia. Methods and design A total of 78 health facilities have been randomised (1:1:1) into one of two intervention arms or a standard-of-care arm. Approximately 50 participants from each health facility will be enrolled on the trial. Participants in facilities randomised to the intervention arms are offered a DAT linked to the ASCENT adherence platform for daily adherence monitoring and differentiated response for those who have missed doses. Participants at standard-of-care facilities receive routine care. Treatment outcomes and resource utilisation will be measured for each participant. The primary effectiveness outcome is a composite index of unfavourable end-of-treatment outcomes (lost to follow-up, death or treatment failure) or treatment recurrence within 6 months of end-of-treatment. For the cost-effectiveness analysis, end-of-treatment outcomes will be used to estimate disability-adjusted life years (DALYs) averted. Provider and patient cost data will be collected from a subsample of 5 health facilities per study arm, 10 participants per facility (n = 150). We will conduct a societal cost-effectiveness analysis using Bayesian hierarchical models that account for the individual-level correlation between costs and outcomes as well as intra-cluster correlation. An equity impact analysis will be conducted to summarise equity efficiency trade-offs. Discussion Trial enrolment is ongoing. This paper follows the published trial protocol and describes the protocol and analysis plan for the health economics work package of the ASCENT-Ethiopia trial. This analysis will generate economic evidence to inform the implementation of DATs in Ethiopia and globally. Trial registration Pan African Clinical Trial Registry (PACTR) PACTR202008776694999. Registered on 11 August 2020,  https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=12241