Health economic analyses of latent tuberculosis infection screening and preventive treatment among people living with HIV in lower tuberculosis incidence settings: a systematic review [version 1; peer review: awaiting peer review]

INTRODUCTION: In lower tuberculosis (TB) incidence countries (<100 cases/100,000/year), screening and preventive treatment (PT) for latent TB infection (LTBI) among people living with HIV (PLWH) is often recommended, yet guidelines advising which groups to prioritise for screening can be contradictory and implementation patchy. Evidence of LTBI screening cost-effectiveness may improve uptake and health outcomes at reasonable cost. METHODS: Our systematic review assessed cost-effectiveness estimates of LTBI screening/PT strategies among PLWH in lower TB incidence countries to identify model-driving inputs and methodological differences. Databases were searched 1980-2020. Studies including health economic evaluation of LTBI screening of PLWH in lower TB incidence countries (<100 cases/100,000/year) were included. Study quality was assessed using the CHEERS checklist. RESULTS: Of 2,644 articles screened, nine studies were included. Cost-effectiveness estimates of LTBI screening/PT for PLWH varied widely, with universal screening/PT found highly cost-effective by some studies, while only targeting to high-risk groups (such as those from mid/high TB incidence countries) deemed cost-effective by others. Cost-effectiveness of strategies screening all PLWH from studies published in the past five years varied from US$2828 to US$144,929/quality-adjusted life-year gained (2018 prices). Study quality varied, with inconsistent reporting of methods and results limiting comparability of studies. Cost-effectiveness varied markedly by screening guideline, with British HIV Association guidelines more cost-effective than NICE guidelines in the UK. DISCUSSION: Cost-effectiveness studies of LTBI screening/PT for PLWH in lower TB incidence settings are scarce, with large variations in methods and assumptions used, target populations and screening/PT strategies evaluated. The limited evidence suggests LTBI screening/PT may be cost-effective for some PLWH groups but further research is required, particularly on strategies targeting screening/PT to PLWH at higher risk. Standardisation of model descriptions and results reporting could facilitate reliable comparisons between studies, particularly to identify those factors driving the wide disparity between cost-effectiveness estimates. REGISTRATION: PROSPERO CRD42020166338 (18/03/2020)

Prevention and treatment of infectious diseases in migrants in Europe in the era of universal health coverage.

Some subpopulations of migrants to Europe are generally healthier than the population of the country of settlement, but are at increased risk of key infectious diseases, including tuberculosis, HIV, and viral hepatitis, as well as under- immunisation. Infection screening programmes across Europe work in disease silos with a focus on individual diseases at the time of arrival. We argue that European health-care practitioners and policy makers would benefit from developing a framework of universal health care for migrants, which proactively offers early testing and vaccinations by delivering multi-disease testing and catch-up vaccination programmes integrated within existing health systems. Such interventions should be codeveloped with migrant populations to overcome barriers faced in accessing services. Aligning policies with the European Centre for Disease Prevention and Control guidance for health care for migrants, community-based preventive health-care programmes should be delivered as part of universal health care. However, effective implementation needs appropriate funding, and to be underpinned by high-quality evidence

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis - update from 2017 to 2023

Background Antimicrobial resistance (AMR) is a critical global health concern. A previous systematic review showed that migrants in Europe are at increased risk of AMR. Since the COVID-19 pandemic there have been rapid changes in patterns of antibiotic use, AMR, and migration. We aimed to present an updated evidence synthesis on the current distribution of AMR among migrants in Europe. Methods We carried out a systematic review and meta-analysis in accordance with PRISMA guidelines (PROSPERO ID: CRD42022343263). We searched databases (MEDLINE, Embase, PubMed and Scopus) from 18 January 2017 until 18 January 2023 to identify primary data from observational studies reporting any laboratory-confirmed AMR among migrants in the European Economic Area (EEA) and European Union-15 (EU-15) countries using over 7 key search terms for migrants and over 70 terms for AMR and countries in Europe. Outcomes were infection with, or colonisation of AMR bacteria. Methodological quality was assessed using Joanna Briggs Institute Critical Appraisal Checklist for Observational Studies. We meta-analysed the pooled-prevalence of infection and/or colonisation of AMR organisms. Findings Among 630 articles, 21 observational studies met the inclusion criteria and were included in this review. The pooled prevalence for any detected AMR was 28.0% (95% CI 18.0%–41.0%, I2 = 100%) compared to a 25.4% seen in the previous review; gram-negative bacteria 31.0% (95% CI 20.0%–44.0%, I2 = 100%), and methicillin-resistant staphylococcus aureus 10.0% (95% CI 5.0%–16.0%, I2 = 99%). Drug-resistant bacteria were more prevalent in community settings in large migrant populations (pooled prevalence: 41.0%, 95% CI 24.0%–60.0%, I2 = 99%) than in hospitals (21.0%, 95% CI 12.0%–32.0%, I2 = 99%). AMR estimates in ‘other’ migrants were 32.0%, (95% CI 12.0%–57.0%, I2 = 100%) and 28.0% (95% CI 18.0%–38.0%, I2 = 100%) in forced migrants. No firm evidence of AMR acquisition with arrival time or length of stay in the host country was found. Interpretation Studies investigating AMR in migrants are highly heterogenous. However, since the COVID-19 pandemic, migrants may be at higher risk of acquiring resistant bacteria, particularly gram-negative bacteria, within community settings such as refugee camps and detention centres in Europe. Our study highlights the importance of infrastructure and hygiene measures within these settings, to mitigate transmission of resistant pathogens. Policy-makers should screen for AMR in migrants prior to departure from countries of origin, where feasible, and upon arrival to a new country to ensure optimal health screening, infection control and effective treatment

Autonomous Targeting of Infectious Superspreaders Using Engineered Transmissible Therapies

Infectious disease treatments, both pharmaceutical and vaccine, face three universal challenges: the difficulty of targeting treatments to high-risk ‘superspreader’ populations who drive the great majority of disease spread, behavioral barriers in the host population (such as poor compliance and risk disinhibition), and the evolution of pathogen resistance. Here, we describe a proposed intervention that would overcome these challenges by capitalizing upon Therapeutic Interfering Particles (TIPs) that are engineered to replicate conditionally in the presence of the pathogen and spread between individuals — analogous to ‘transmissible immunization’ that occurs with live-attenuated vaccines (but without the potential for reversion to virulence). Building on analyses of HIV field data from sub-Saharan Africa, we construct a multi-scale model, beginning at the single-cell level, to predict the effect of TIPs on individual patient viral loads and ultimately population-level disease prevalence. Our results show that a TIP, engineered with properties based on a recent HIV gene-therapy trial, could stably lower HIV/AIDS prevalence by ∼30-fold within 50 years and could complement current therapies. In contrast, optimistic antiretroviral therapy or vaccination campaigns alone could only lower HIV/AIDS prevalence by <2-fold over 50 years. The TIP's efficacy arises from its exploitation of the same risk factors as the pathogen, allowing it to autonomously penetrate superspreader populations, maintain efficacy despite behavioral disinhibition, and limit viral resistance. While demonstrated here for HIV, the TIP concept could apply broadly to many viral infectious diseases and would represent a new paradigm for disease control, away from pathogen eradication but toward robust disease suppression

Self-Interest versus Group-Interest in Antiviral Control

Antiviral agents have been hailed to hold considerable promise for the treatment and prevention of emerging viral diseases like H5N1 avian influenza and SARS. However, antiviral drugs are not completely harmless, and the conditions under which individuals are willing to participate in a large-scale antiviral drug treatment program are as yet unknown. We provide population dynamical and game theoretical analyses of large-scale prophylactic antiviral treatment programs. Throughout we compare the antiviral control strategy that is optimal from the public health perspective with the control strategy that would evolve if individuals make their own, rational decisions. To this end we investigate the conditions under which a large-scale antiviral control program can prevent an epidemic, and we analyze at what point in an unfolding epidemic the risk of infection starts to outweigh the cost of antiviral treatment. This enables investigation of how the optimal control strategy is moulded by the efficacy of antiviral drugs, the risk of mortality by antiviral prophylaxis, and the transmissibility of the pathogen. Our analyses show that there can be a strong incentive for an individual to take less antiviral drugs than is optimal from the public health perspective. In particular, when public health asks for early and aggressive control to prevent or curb an emerging pathogen, for the individual antiviral drug treatment is attractive only when the risk of infection has become non-negligible. It is even possible that from a public health perspective a situation in which everybody takes antiviral drugs is optimal, while the process of individual choice leads to a situation where nobody is willing to take antiviral drugs

The effectiveness of public health interventions to reduce the health impact of climate change:a systematic review of systematic reviews

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases