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ObjectiveLyme disease is a tick-borne disease of increasing incidence and public concern across the Northern Hemisphere. However, the socio-demographics and geographic distribution of the population affected in England and Wales are poorly understood. Therefore, the proposed study was designed to describe the demographics and distribution of laboratory-confirmed cases of Lyme disease from a national testing laboratory.DesignAn ecological study of routinely collected laboratory surveillance data.SettingPublic Health England’s national Lyme disease testing laboratory.Participants3986 laboratory-confirmed cases of Lyme disease between 2013 and 2016.ResultsIn England and Wales, the incidence of laboratory-confirmed Lyme disease rose significantly over the study period from 1.62 cases per 100 000 in 2013 to 1.95 cases per 100 000 in 2016. There was a bimodal age distribution (with peaks at 6–10 and 61–65 years age bands) with a predominance of male patients. A significant clustering of areas with high Lyme disease incidence was located in southern England. An association was found between disease incidence and socioeconomic status, based on the patient’s resident postcode, with more cases found in less deprived areas. Cases were disproportionately found in rural areas compared with the national population distribution.ConclusionsThese results suggest that Lyme disease patients originate from areas with higher socioeconomic status and disproportionately in rural areas. Identification of the Lyme disease hotspots in southern England, alongside the socio-demographics described, will enable a targeted approach to public health interventions and messages.

Background Lyme disease is a tick-borne disease of increasing global importance. There is scant information on Lyme disease patient demographics in England and Wales, and how they interact with the National Health Service (NHS). Our aims were to explore the demographic characteristics of Lyme disease patients within the Hospital Episode Statistics (HES) and Patient Episode Database for Wales (PEDW), and to describe patient pathways. Methods Data from 1st January 1998 to 31st December 2015 was retrieved from the two administrative hospital datasets (HES and PEDW), based on patients coded with Lyme disease. Information was collected on demographic characteristics, home address and case management. Incidence rates were calculated, and demographics compared to the national population. Results Within HES and PEDW, 2361 patients were coded with Lyme disease. There was a significant increase ( p  < 0.01) in incidence from 0.08 cases/100,000 in 1998, to 0.53 cases/100,000 in 2015. There was a bimodal age distribution, patients were predominantly female, white and from areas of low deprivation. New cases peaked annually in August, with higher incidence rates in southern central and western England. Within hospital admission data ( n  = 2066), most cases were either referred from primary care (28.8%, n  = 596) or admitted via accident and emergency (A&E) (29.5%, n  = 610). This population entering secondary care through A&E suggest a poor understanding of the recommended care pathways for symptoms related to Lyme disease by the general population. Conclusions These data can be used to inform future investigations into Lyme disease burden, and patient management within the NHS. They provide demographic information for clinicians to target public health messaging or interventions.

Background Primary care is likely to see the highest number of Lyme disease patients. Despite this, there is limited published data regarding Lyme disease patients accessing primary care in the UK. We aim to describe trends in the incidence of a new diagnosis, and demographics of patients identified in a primary care electronic health database. Methods A descriptive epidemiological study of Lyme disease coded patients in UK primary care. 3725 patients coded for Lyme disease during 1998–2016 were identified within The Health Improvement Network (THIN). Incidence rates and the demographics of cases identified were described. Poisson regression was used to analyse socio-demographic characteristics of the cases. Results There was an increase in annual crude incidence rates, peaking in 2015 at 5.47 (95% CI 4.85–6.14) cases per 100,000 population per year. Multivariable analysis showed there were significant differences in the ages of those affected, incidence of a new diagnosis rose as deprivation levels improved, and that there was a higher incidence of cases living in rural areas compared to urban areas. There was no significant difference between sexes for the UK. Cases were significantly more likely to identify with being white compared to the national population. Conclusions An increasing incidence of patients newly coded with Lyme disease related Read codes was identified using data from a UK national primary care database. By comparing these incidence figures with national laboratory-confirmed surveillance data, a multiplication factor of 2.35 (95%CI 1.81–2.88) can be calculated in order to estimate the annual number of cases seen in primary care. The significant socio-demographic variables associated with a Lyme disease diagnosis likely reflect a complex interplay of socio-economic issues, which needs to be further explored. Future work is needed to examine the treatment and management of patients within this database.

The possibility of HIV-1 eradication has been limited by the existence of latently infected cellular reservoirs. Studies to examine control of HIV latency and potential reactivation have been hindered by the small numbers of latently infected cells found in vivo. Major conceptual leaps have been facilitated by the use of latently infected T cell lines and primary cells. However, notable differences exist among cell model systems. Furthermore, screening efforts in specific cell models have identified drug candidates for \"anti-latency\" therapy, which often fail to reactivate HIV uniformly across different models. Therefore, the activity of a given drug candidate, demonstrated in a particular cellular model, cannot reliably predict its activity in other cell model systems or in infected patient cells, tested ex vivo. This situation represents a critical knowledge gap that adversely affects our ability to identify promising treatment compounds and hinders the advancement of drug testing into relevant animal models and clinical trials. To begin to understand the biological characteristics that are inherent to each HIV-1 latency model, we compared the response properties of five primary T cell models, four J-Lat cell models and those obtained with a viral outgrowth assay using patient-derived infected cells. A panel of thirteen stimuli that are known to reactivate HIV by defined mechanisms of action was selected and tested in parallel in all models. Our results indicate that no single in vitro cell model alone is able to capture accurately the ex vivo response characteristics of latently infected T cells from patients. Most cell models demonstrated that sensitivity to HIV reactivation was skewed toward or against specific drug classes. Protein kinase C agonists and PHA reactivated latent HIV uniformly across models, although drugs in most other classes did not.

To investigate the effectiveness of community-based mental health interventions by professionally trained, lay counsellors in low- and middle-income countries. We searched PubMed®, Cochrane Central Register of Controlled Trials, PROSPERO and EBSCO databases and professional section publications of the United States National Center for PTSD for randomized controlled trials of mental health interventions by professionally trained, lay counsellors in low- and middle-income countries published between 2000 and 2019. Studies of interventions by professional mental health workers, medical professionals or community health workers were excluded because there are shortages of these personnel in the study countries. Additional data were obtained from study authors. The primary outcomes were measures of post-traumatic stress disorder, depression, anxiety and alcohol use. To estimate effect size, we used a random-effects meta-analysis model. We identified 1072 studies, of which 19 (involving 20 trials and 5612 participants in total) met the inclusion criteria. Hedges' for the aggregate effect size of the interventions by professionally trained, lay counsellors compared with mostly either no intervention or usual care was -0.616 (95% confidence interval: -0.866 to -0.366). This result indicates a significant, medium-sized effect. There was no evidence of publication bias or any other form of bias across the studies and there were no extreme outliers among the study results. The use of professionally trained, lay counsellors to provide mental health interventions in low- and middle-income countries was associated with significant improvements in mental health symptoms across a range of settings.

Expanding the US Food and Drug Administration–approved indications for immune checkpoint inhibitors in patients with cancer has resulted in therapeutic success and immune-related adverse events (irAEs). Neurologic irAEs (irAE-Ns) have an incidence of 1%–12% and a high fatality rate relative to other irAEs. Lack of standardized disease definitions and accurate phenotyping leads to syndrome misclassification and impedes development of evidence-based treatments and translational research. The objective of this study was to develop consensus guidance for an approach to irAE-Ns including disease definitions and severity grading. A working group of four neurologists drafted irAE-N consensus guidance and definitions, which were reviewed by the multidisciplinary Neuro irAE Disease Definition Panel including oncologists and irAE experts. A modified Delphi consensus process was used, with two rounds of anonymous ratings by panelists and two meetings to discuss areas of controversy. Panelists rated content for usability, appropriateness and accuracy on 9-point scales in electronic surveys and provided free text comments. Aggregated survey responses were incorporated into revised definitions. Consensus was based on numeric ratings using the RAND/University of California Los Angeles (UCLA) Appropriateness Method with prespecified definitions. 27 panelists from 15 academic medical centers voted on a total of 53 rating scales (6 general guidance, 24 central and 18 peripheral nervous system disease definition components, 3 severity criteria and 2 clinical trial adjudication statements); of these, 77% (41/53) received first round consensus. After revisions, all items received second round consensus. Consensus definitions were achieved for seven core disorders: irMeningitis, irEncephalitis, irDemyelinating disease, irVasculitis, irNeuropathy, irNeuromuscular junction disorders and irMyopathy. For each disorder, six descriptors of diagnostic components are used: disease subtype, diagnostic certainty, severity, autoantibody association, exacerbation of pre-existing disease or de novo presentation, and presence or absence of concurrent irAE(s). These disease definitions standardize irAE-N classification. Diagnostic certainty is not always directly linked to certainty to treat as an irAE-N (ie, one might treat events in the probable or possible category). Given consensus on accuracy and usability from a representative panel group, we anticipate that the definitions will be used broadly across clinical and research settings.

SARS-CoV-2 Delta and Omicron are globally relevant variants of concern. Although individuals infected with Delta are at risk of developing severe lung disease, infection with Omicron often causes milder symptoms, especially in vaccinated individuals 1 , 2 . The question arises of whether widespread Omicron infections could lead to future cross-variant protection, accelerating the end of the pandemic. Here we show that without vaccination, infection with Omicron induces a limited humoral immune response in mice and humans. Sera from mice overexpressing the human ACE2 receptor and infected with Omicron neutralize only Omicron, but not other variants of concern, whereas broader cross-variant neutralization was observed after WA1 and Delta infections. Unlike WA1 and Delta, Omicron replicates to low levels in the lungs and brains of infected animals, leading to mild disease with reduced expression of pro-inflammatory cytokines and diminished activation of lung-resident T cells. Sera from individuals who were unvaccinated and infected with Omicron show the same limited neutralization of only Omicron itself. By contrast, Omicron breakthrough infections induce overall higher neutralization titres against all variants of concern. Our results demonstrate that Omicron infection enhances pre-existing immunity elicited by vaccines but, on its own, may not confer broad protection against non-Omicron variants in unvaccinated individuals. Infection with Omicron after vaccination produces cross-neutralizing antibodies to other variants of concern, whereas this induces a limited response to non-Omicron variants in unvaccinated individuals.

Tools that can be used to collect behavioural data during pandemics are needed to inform policy and practice. The objective of this project was to develop the Your COVID-19 Risk tool in response to the global spread of COVID-19, aiming to promote health behaviour change. We developed an online resource based on key behavioural evidence-based risk factors related to contracting and spreading COVID-19. This tool allows for assessing risk and provides instant support to protect individuals from infection. The Risk Estimation Questions assessed users’ location, age, gender, work environment, day-to-day behaviours currently performed, and conditions under which these behaviours would change. Users were also asked to estimate how often they keep their distance from others in public and regularly wash their hands, and the procedures they follow to do so. A multidisciplinary research team of more than 150 international experts developed the tool. Over 60,000 users in more than 150 countries have assessed their risk and provided data. The majority of respondents reported that they almost always keep their distance from others in public places, and most participants reported washing their hands after touching public or shared surfaces or when entering buildings. The tool, data, and results were openly shared to support government and health agencies developing behaviour change interventions. This tool creates a blueprint for similar digital infrastructure that can be replicated and used in future pandemics.

Allergic disorders, characterized by Th2 immune responses to environmental substances, are increasingly common in children in Western societies. Multiple studies indicate that breastfeeding, early complementary introduction of food allergens, and antibiotic avoidance in the first year of life reduces allergic outcomes in at-risk children. Why the benefit of these practices is restricted to early life is largely unknown. We identified a preweaning interval during which dietary antigens are assimilated by the colonic immune system. This interval is under maternal control via temporal changes in breast milk, coincides with an influx of naive T cells into the colon, and is followed by the development of a long-lived population of colonic peripherally derived Tregs (pTregs) that can be specific for dietary antigens encountered during this interval. Desynchronization of mothers and offspring produced durable deficits in these pTregs, impaired tolerance to dietary antigens introduced during and after this preweaning interval, and resulted in spontaneous Th2 responses. These effects could be rescued by pTregs from the periweaning colon or by Tregs generated in vitro using periweaning colonic antigen-presenting cells. These findings demonstrate that mothers and their offspring are synchronized for the development of a balanced immune system.

Crimean–Congo haemorrhagic fever (CCHF) is a widely distributed and potentially fatal tick-borne viral disease with no licensed specific treatments or vaccines. In 2019, WHO published an advanced draft of a research and development roadmap for CCHF that prioritised the development and deployment of the medical countermeasures most needed by CCHF-affected countries. This Personal View presents updated CCHF research and development priorities and is the product of broad consultation with a working group of 20 leading experts in 2023–24. The strategic goals, milestones, and timelines have been revised and expanded to reflect scientific advances since 2019, including the identification of antibodies with therapeutic potential and the progression of four vaccine candidates through phase 1 clinical trials. This update emphasises the need for a One Health approach to manage CCHF, from integrated cross-sectoral surveillance to novel interventions that target ticks and their vertebrate hosts to reduce CCHF virus transmission to humans. The overarching vision for rapid diagnostics and specific therapeutics by 2028, followed by options to limit CCHF virus transmission and control disease by 2030, is deliberately ambitious and will only be achieved through coordinated international action from affected countries, funders, scientists, product developers, manufacturers, regulators, national authorities, and policy makers.