Naturally acquired adaptive immunity to Streptococcus pneumoniae is impaired in rheumatoid arthritis patients.

OBJECTIVES: Patients with rheumatoid arthritis (RA) have an increased susceptibility to infections, including those caused by Streptococcus pneumoniae. Why RA is associated with increased susceptibility to S. pneumoniae is poorly understood. This study aims to assess the effects of RA and B-cell depletion therapy on naturally acquired antibody responses to 289 S. pneumoniae protein antigens using a novel protein array. METHODS: IgG responses to S. pneumoniae were characterised in serum from RA patients and disease controls (myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)) using whole-cell ELISA, a flow cytometry opsonisation assay and an S. pneumoniae protein array. For the RA patients, results were compared before and after B-cell depletion therapy. RESULTS: Compared to a well-characterised disease control group of ME/CFS patients, RA patients had reduced antibody responses to multiple S. pneumoniae protein antigens, with significant IgG recognition of approximately half the number of antigens along with reduced median strengths of these responses. Reduction in multiple array antigen-specific responses also correlated with reduced IgG opsonisation of S. pneumoniae. Although B-cell depletion therapy with rituximab did not reduce overall IgG recognition of S. pneumoniae in the RA group, it was associated with marked disruption of pre-existing IgG repertoire to protein antigens in individual patients. CONCLUSION: These data show RA is associated with major disruption of naturally acquired adaptive immunity to S. pneumoniae, which can be assessed rapidly using a protein antigen array and is likely to contribute towards the increased incidence of pneumonia in patients with RA

Microbes and marginalisation: ‘Facing’ antimicrobial resistance in bedridden patients in a peri-urban area of Thailand

Reducing human-microbial encounters through improved infection prevention and control (IPC) is widely acknowledged to be critical for reducing the emergence, transmission and burden of antimicrobial resistance (AMR). However, despite its centrality in the Global Action Plan (GAP) on AMR and adoption as a goal in National Action Plans around the world, there has been limited progress on reducing the incidence of antimicrobial resistant infections globally. In this paper, we argue that closer attention to different faces of AMR could propel progress in this area, with a focus on bedridden people situated in liminal spaces in the Thai health system and suburban economy. Our ethnographic fieldwork followed the cases of 16 bedridden people through the eyes of their carers and medical staff. We 'descended into the ordinary' to encounter individuals living - and dying - in the shadows of the labour-intensive suburbs of Bangkok. Here, AMR and IPC protocols are operationalised in the context of competing priorities and pragmatic decision-making. Focussing on three ethnographic vignettes, we use the analytic frames of precarity and care to consider how particular (bedridden) bodies are differentially exposed to AMR infections in the context of economic, social, and political arrangements that structure embodied vulnerabilities and forms and foci of care. Whilst the political work of calculating the burden of AMR may be oriented around galvanising support through a sense of magnitude and generalised risk, this research serves as a reminder that the faces of AMR include those who disproportionately shoulder the global burden of AMR, making it at once exceptional and ordinary

Effectiveness of malaria chemoprevention in the first two years of life in Cameroon and Côte d'Ivoire compared to standard of care: study protocol for a population-based prospective cohort impact evaluation study.

BACKGROUND: Perennial malaria chemoprevention (PMC) is a chemoprevention strategy endorsed by the World Health Organization (WHO) and is increasingly being adopted by National Malaria Programmes. PMC aims to reduce morbidity and mortality caused by malaria and anaemia in in young children through provision of antimalarial drugs at routine contact points with the local health system. This study aims to evaluate the impact of the programmatically-implemented country-tailored PMC programmes targeting children up to two years of age using sulfadoxine-pyrimethamine (SP) on the incidence of malaria and anaemia in children in Cameroon and Côte d'Ivoire. METHODS: We will assess the impact of PMC using passive and active monitoring of a prospective observational cohort of children up to 36 months of age at recruitment in selected study sites in Cameroon and Côte d'Ivoire. The primary and secondary outcomes include malaria, anaemia and malnutrition incidence. We will also conduct a time-series analysis of passively detected malaria and anaemia cases comparing the periods before and after PMC introduction. This study is powered to detect a 30% and 40% reduction of malaria incidence compared to the standard of care in Cameroon and Côte d'Ivoire, respectively. DISCUSSION: This multi-country study aims to provide evidence of the effectiveness of PMC targeting children in the first two years of life on malaria and anaemia and will provide important information to inform optimal operationalization and evaluation of this strategy. TRIAL REGISTRATION: Cameroon - NCT05889052; Côte d'Ivoire - NCT05856357

The prioritisation of curable sexually transmitted infections among pregnant women in Zambia and Papua New Guinea: Qualitative insights.

Curable sexually transmitted infections (STIs) are neglected in public health policy, services and society at large. Effective interventions are available for some STI but seem not to be prioritised at global, regional or local levels. Zambia and Papua New Guinea (PNG) have a high burden of STIs among pregnant women but little is known about the prioritisation of STI treatment and care among this group. We undertook a qualitative study to explore how STIs are prioritised among pregnant women in local health systems in Zambia and PNG. Semi-structured interviews were conducted with 19 key informants-health care workers providing antenatal care, and policy and programme advisers across the two countries. Audio recordings were transcribed and translated into English and stored, managed, and coded in NVivo v12. Analysis used deductive and inductive thematic analysis. Findings were coded against the World Health Organization health system building blocks. Participants spoke about the stigma of STIs at the community level. They described a broad understanding of morbidity associated with undiagnosed and untreated STIs in pregnant women. The importance of testing and treating STIs in pregnancy was well recognised but many spoke of constraints in providing these services due to stock outs of test kits for HIV and syphilis and antibiotics. In both settings, syndromic management remains the mainstay for treating curable STIs. Clinical practice and treatment were not in alignment with current STI guidelines in either country, with participants recognising the need for mentorship and in-service training, as well as the availability of commodities to support their clinical practice. Local disruptions to screening and management of syphilis, HIV and other curable STIs were widely reported in both countries. There is a need to galvanise priority at national and regional levels to ensure ongoing access to supplies needed to undertake STI testing and treatment

Immune-related adverse events in patients treated with immunotherapy for locally advanced or metastatic NSCLC in real-world settings: a systematic review and meta-analysis

Introduction: Randomized clinical trials (RCTs) represent the mainstay for the approval of new treatments. However, stringent inclusion criteria often cause them to depart from the daily clinical practice. Real-world (RW) evidence have a complementing role, filling the gap between the efficacy of a treatment and its effectiveness. Immune checkpoint inhibitors (ICIs) have changed the treatment scenario for non-small cell lung cancer (NSCLC); immune-related adverse events (irAEs) could become life-threatening events, when not timely managed. We performed a systematic review and meta-analysis on the RW impact of irAEs through the years. Methods: The systematic review focused on irAEs occurred in locally advanced or metastatic NSCLC patients, treated with ICIs in a RW setting. We queried two electronic databases (Embase and Medline) from 1996 to August 2022. We then conducted a meta-analysis dividing the results in two cohorts (2015-2018 and 2019-2021). We described the prevalence of patients with irAEs of any or severe grade (G). Estimates were expressed as proportions up to the second decimal point (effect size, ES). IrAEs of interest were those involving the skin, the liver, the endocrine system or the gastro-intestinal system. Results: Overall, 21 RW studies on 5,439 patients were included in the quantitative and qualitative synthesis. The prevalence of G≥3 irAEs was slightly lower in the 2015-2018 subgroup, while the prevalence of irAEs of any grade was similar for both periods. Overall, we observed a higher ES for gastrointestinal, hepatic and lung irAEs, while a lower ES was reported for skin or endocrine irAEs. Endocrine irAEs were reported in 10 out of 21 studies, with a slight increase in the most recent studies, while cutaneous toxicities were mostly reported in two studies lead within the first time-period. Pulmonary, gastrointestinal, and hepatic toxicities, showed a more heterogeneous distribution of ES over time. Discussion: Our findings showed that the frequency of irAEs remained stable across the two calendar periods examined in our meta-analysis. This finding suggests that RW data might not be able to identify a potential learning curve in detection and management of irAEs

Health impact of policies to reduce agriculture-related air pollutants in the UK: The relative contribution of change in PM2.5 exposure and diets to morbidity and mortality.

Food systems can negatively impact health outcomes through unhealthy diets and indirectly through ammonia emissions originating from agricultural production, which contribute to air pollution and consequently cardiovascular and respiratory health outcomes. In the UK, ammonia emissions from agriculture have not declined in the same way as other air pollutants in recent years. We applied a novel integrated modelling framework to assess the health impacts from six ammonia reduction scenarios to 2030: two agriculture scenarios - a "Current trends" scenario projecting current mitigation measures to reflect a low ambition future, and "High ambition mitigation" based on measures included in the Climate Change Committee's Balanced Pathway to Net Zero; three dietary scenarios - a "Business as usual" based on past trajectories, "Fiscal" applying 20% tax on meat and dairy and 20% subsidy on fruit and vegetables, and "Innovation" applying a 30% switch to plant-based alternatives; one combination of "High ambition mitigation" and "Innovation". Compared to "Current trends", the "High ambition mitigation" scenario would result in a reduction in premature mortality of 13,000, increase life years by 90,000 and reduce incidence of respiratory diseases by 270,000 cases over a 30 year period. Compared to Business as Usual, the dietary scenarios would reduce the number of premature deaths by 65,000 and 550,000-600,000 life years gained over 30 years, with most of the benefits gained by reducing ischemic heart disease (incidence reduction: 190,000). The "High ambition combination" would lead to 67,000 deaths averted, 536,000 incidence reductions and 650,000 life-years gained. For all scenarios, older age groups and those living in lower income households would experience the greatest benefits, because of higher underlying mortality rates or higher levels of risk factors. Our study shows that combining mitigation policies targeting agricultural production systems with diet-related policies would lead to significant reductions in emissions and improvement in health outcomes

Faith and Intimate Partner Violence in Rural South Africa

Intimate partner violence (IPV) is the most common form of violence against women and is associated with risk factors at the individual, interpersonal and societal level. Women often resort to various coping mechanisms to manage their daily lives due to the complex nature by which these factors interact. We qualitatively interviewed a cohort of rural women participating in a microfinance “plus” program in South Africa where women received loans for small-scale business ventures and received training sessions on gender norms. Our findings detailed women’s experiences of IPV and the role of faith as a coping mechanism for navigating economic hardship and abuse. Belief in a higher power was predominant in almost every interview, offering a sense of purpose and optimism for the future amid precarious circumstances. Interventions for violence prevention need to consider the important role that faith can play in strengthening women’s sense of self and preventing IPV

Pandemic preparedness: why humanities and social sciences matter.

Whilst many lessons were learned from the COVID-19 pandemic, ongoing reflection is needed to develop and maintain preparedness for future outbreaks. Within the field of infectious disease and public health there remain silos and hierarchies in interdisciplinary work, with the risk that humanities and social sciences remain on the epistemological peripheries. However, these disciplines offer insights, expertise and tools that contribute to understanding responses to disease and uptake of interventions for prevention and treatment. In this Perspective, using examples from our own cross-disciplinary research and engagement programme on vaccine hesitancy in South Africa and the United Kingdom (UK), we propose closer integration of expertise, research and methods from humanities and social sciences into pandemic preparedness

Treat All versus targeted strategies to select HBV-infected people for antiviral therapy in The Gambia, west Africa: a cost-effectiveness analysis.

BACKGROUND: Global elimination of hepatitis B virus (HBV) requires expanded uptake of antiviral therapy, potentially by simplifying testing algorithms, especially in resource-limited countries. We evaluated the effectiveness, cost-effectiveness, and budget impact of three strategies that determine eligibility for anti-HBV treatment, as compared with the WHO 2015 treatment eligibility criteria, in The Gambia. METHODS: We developed a microsimulation model of natural history using data from the Prevention of Liver Fibrosis and Cancer in Africa programme (known as PROLIFICA) in The Gambia, for an HBV-infected cohort of individuals aged 20 years. The algorithms included in the model were a conventional strategy using the European Association for the Study of the Liver (EASL) 2017 criteria, a simplified algorithm using hepatitis B e antigen and alanine aminotransferase (the Treatment Eligibility in Africa for the Hepatitis B Virus [TREAT-B] score), a Treat All approach for all HBV-infected individuals, and the WHO 2015 criteria. Outcomes to measure effectiveness were disability-adjusted life years (DALYs) and years of life saved (YLS), which were used to calculate incremental cost-effectiveness ratios (ICERs) with the WHO 2015 criteria as the base-case scenario. Costs were assessed from a modified social perspective. A budget impact analysis was also done. We tested the robustness of results with a range of sensitiviy analyses including probabilistic sensitivity analysis. FINDINGS: Compared with the WHO criteria, TREAT-B resulted in 4877 DALYs averted and Treat All resulted in 9352 DALYs averted, whereas the EASL criteria led to an excess of 795 DALYs. TREAT-B was cost-saving, whereas the ICER for Treat All (US$2149 per DALY averted) was higher than the cost-effectiveness threshold for The Gambia (0·5 times the country's gross domestic product per capita:$352). These patterns did not change when YLS was the outcome. In a modelled cohort of 5000 adults (aged 20 years) with chronic HBV infection from The Gambia, the 5-year budget impact was $1·14 million for Treat All,$0·66 million for TREAT-B, $1·03 million for the WHO criteria, and$1·16 million for the EASL criteria. Probabilistic sensitivity analysis indicated that among the Treat All, EASL, and TREAT-B algorithms, Treat All would become the most preferred strategy only with a willingness-to-pay threshold exceeding approximately $72 000 per DALY averted or$110 000 per YLS. INTERPRETATION: Although the Treat All strategy might be the most effective, it is unlikely to be cost-effective in The Gambia. A simplified strategy such as TREAT-B might be a cost-saving alternative. FUNDING: UK Research and Innovation (Medical Research Council). TRANSLATION: For the French translation of the abstract see Supplementary Materials section

Ozone-related acute excess mortality projected to increase in the absence of climate and air quality controls consistent with the Paris Agreement.

Short-term exposure to ground-level ozone in cities is associated with increased mortality and is expected to worsen with climate and emission changes. However, no study has yet comprehensively assessed future ozone-related acute mortality across diverse geographic areas, various climate scenarios, and using CMIP6 multi-model ensembles, limiting our knowledge on future changes in global ozone-related acute mortality and our ability to design targeted health policies. Here, we combine CMIP6 simulations and epidemiological data from 406 cities in 20 countries or regions. We find that ozone-related deaths in 406 cities will increase by 45 to 6,200 deaths/year between 2010 and 2014 and between 2050 and 2054, with attributable fractions increasing in all climate scenarios (from 0.17% to 0.22% total deaths), except the single scenario consistent with the Paris Climate Agreement (declines from 0.17% to 0.15% total deaths). These findings stress the need for more stringent air quality regulations, as current standards in many countries are inadequate