Perspectives from the 2nd International Post-Tuberculosis Symposium: mobilising advocacy and research for improved outcomes.

In 2020, it was estimated that there were 155 million survivors of TB alive, all at risk of possible post TB disability. The 2nd International Post-Tuberculosis Symposium (Stellenbosch, South Africa) was held to increase global awareness and empower TB-affected communities to play an active role in driving the agenda. We aimed to update knowledge on post-TB life and illness, identify research priorities, build research collaborations and highlight the need to embed lung health outcomes in clinical TB trials and programmatic TB care services. The symposium was a multidisciplinary meeting that included clinicians, researchers, TB survivors, funders and policy makers. Ten academic working groups set their own goals and covered the following thematic areas: 1) patient engagement and perspectives; 2) epidemiology and modelling; 3) pathogenesis of post-TB sequelae; 4) post-TB lung disease; 5) cardiovascular and pulmonary vascular complications; 6) neuromuscular & skeletal complications; 7) paediatric complications; 8) economic-social and psychological (ESP) consequences; 9) prevention, treatment and management; 10) advocacy, policy and stakeholder engagement. The working groups provided important updates for their respective fields, highlighted research priorities, and made progress towards the standardisation and alignment of post-TB outcomes and definitions.

En 2020, il est estimé qu'il y a 155 millions de survivants de la TB dans le monde, tous exposés à un risque d'invalidité post-TB. Le deuxième Symposium International Post-Tuberculose (Stellenbosch, Afrique du Sud) a été organisé dans le but de sensibiliser davantage à l'échelle mondiale et de permettre aux communautés touchées par la TB de contribuer activement à la mise en œuvre de l'agenda. De plus, nous avons entrepris de mettre à jour les connaissances sur la vie et les maladies post-TB, de déterminer les domaines de recherche prioritaires, d'établir des partenariats de recherche et de souligner l'importance d'intégrer les résultats sur la santé pulmonaire dans les essais cliniques et les services de soins de la TB. Le symposium était une réunion de travail pluridisciplinaire rassemblant des praticiens, des chercheurs, des personnes ayant survécu à la TB, des donateurs, des décideurs politiques et d'autres acteurs clés. Dix groupes de travail académiques ont établi leurs propres objectifs et ont abordé les sujets thématiques suivants : 1) engagement et perspectives des patients ; 2) épidémiologie et modélisation ; 3) pathogénie des séquelles post-TB ; 4) maladie pulmonaire post-TB (PTLD, pour l'anglais «post-TB lung disease ¼) ; 5) complications cardiovasculaires et vasculaires pulmonaires ; 6) complications neuromusculaires et squelettiques ; 7) complications pédiatriques ; 8) conséquences économiques, sociales et psychologiques (ESP, pour l'anglais «economic-social and psychological¼) ; 9) prévention, traitement et gestion ; 10) plaidoyer, politique et engagement des parties prenantes. Les groupes de travail académiques ont apporté des mises à jour significatives dans leurs domaines respectifs, ont mis en évidence les priorités de recherche et ont avancé vers la normalisation et l'harmonisation des résultats et des définitions de la post-TB.

Systematic assessment of the reliability of quantitative PCR assays targeting IS900 for the detection of Mycobacterium avium ssp. paratuberculosis presence in animal and environmental samples.

Mycobacterium avium ssp. paratuberculosis (MAP) is the bacterium responsible for causing Johne's Disease (JD), which is endemic to dairy cattle and also incriminated in the etiology of Crohn's disease. The difficulty in diagnosing asymptomatic cows for JD makes this disease hard to control. JD is considered a priority under the One Health approach to prevent the spread of the causative agent to humans. Environmental screening is a strategic approach aimed at identifying dairy herds with animals infected with MAP. It serves as the initial step toward implementing more intensive actions to control the disease. Quantitative polymerase chain reaction (qPCR) technology is widely used for diagnosis. Given that genome sequencing is now much more accessible than ever before, it is possible to target regions of the MAP genome that allow for the greatest diagnostic sensitivity and specificity. The aim of this study was to identify among the published qPCR assays targeting IS900 the more cost-effective options to detect MAP and to validate them in the diagnostic context of JD disease. MAP IS900 is a prime target because it is a multicopy genetic element. A total of 136 publications have reported on the use of IS900 qPCR assays over the past 3 decades. Among these records, 29 used the SYBR Green chemistry and TaqMan technology was used in 107 reports. Aside from the 9 reports using commercial assays, 72 TaqMan reports cited previously published work, leaving us with 27 TaqMan qPCR designs. Upon closer examination, 5 TaqMan designs contained mismatches in primer or probe sequences. Additionally, others exhibited high similarity to environmental microorganisms or non-MAP mycobacteria. We assessed the performance of 6 IS900 qPCR designs and their sensitivity when applied to clinical or environmental samples, which varied from 4 to 56 fold overall. Additionally, we provide recommendations for testing clinical and environmental samples, as certain strategies used previously should be avoided due to poor qPCR design (e.g., the presence of mismatches) or a lack of specificity.

Bovine Herpes Virus Type 1 (BoHV-1) seroprevalence, risk factor and Bovine Viral Diarrhoea (BVD) co-infection analysis from Ireland.

Surveillance of endemic pathogens is essential for disease control, providing an evidence base for policy and advice. Bovine Herpes Virus Type 1 (BoHV-1), the causative agent of Infectious Bovine Rhinotracheitis (IBR), has been found to have high seroprevalence within the Irish cattle population. The aim of the present study was to establish seroprevalence levels for culled cattle in Ireland aged < 30 months and to establish whether BVD exposure and other factors was associated with BoHV-1 exposure. We employed random effects logit models coupled with repeated bootstrap sampling to provide robust estimates. The final dataset contained results for 5273 animals tested over two study years, 2018 and 2020. The animal-level seroprevalence of BoHV-1 was 21.43% (1130/5273; 95%CI: 20.32-22.53%). Univariable analysis suggested that BoHV-1 seropositivity risk was associated with BVDV serodiagnosis status, age, sex, year sampled, herd type, herd-size, and metrics of movement into the herd. Final random-effects multivariable models suggested increased risk associated with increasing herd size of the last herd, movements made by animals during the previous year, and the year the animal was sampled. Despite BVDV status and sex being retained in the final model, repeated bootstrap sampling of the regression model to estimate biased-corrected 95%CI suggested that these associations were not robust. The overall apparent prevalence of BoHV-1 exposure for culled cattle in Ireland declined in 2020 relative to 2018 (from 23.32 to 17.61%). Herd-size and the movement of animals were found to be important factors associated with animal-level risk, but there was less statistical support for sex-based or BVDV status associations.

Design and testing the validity of an inexpensive and accessible sham dry needling protocol.

OBJECTIVE: To use a simple method of needle blunting to produce a placebo dry needling protocol which is indistinguishable from the sensations felt during therapeutic dry needling. METHODS: A randomised cross-over design was used to compare the perception of needle skin penetration, pain experienced and types of sensations experienced following a single placebo dry needling and a single therapeutic dry needling application. RESULTS: There were no significant differences in the proportions of patients reported ability to perceive needle penetration (p = 0.646), description of needling sensations (p = 0.3) or pain rating (p = 0.405) when comparing placebo needling to therapeutic dry needling. CONCLUSION: Needle tip bending creates a simple, cost-effective and effective placebo needle for use in comparisons with therapeutic dry needling. This offers researchers a viable alternative to expensive and inappropriate acupuncture sham devices when conducting dry needling trials.

Relationship between ambient temperature at sampling and the interferon gamma test result for bovine tuberculosis in cattle.

Bovine tuberculosis (bTB) is a disease of significant economic and zoonotic importance, therefore, optimising tests for the identification of Mycobacterium bovis infected cattle is essential. The Interferon Gamma (IFN-γ) Release Assay (IGRA) can diagnose M. bovis infected cattle at an early stage, is easy to perform and can be used alongside skin tests for confirmatory purposes or to increase diagnostic sensitivity. It is known that IGRA performance is sensitive to environmental conditions under which samples are taken and transported. In this study, the association between the ambient temperature on the day of bleeding and the subsequent IGRA result for bTB was quantified using field samples from Northern Ireland (NI). Results of 106,434 IGRA results (2013-2018) were associated with temperature data extracted from weather stations near tested cattle herds. Model dependent variables were the levels of IFN-γ triggered by avian purified protein derivative (PPDa), M. bovis PPD (PPDb), their difference (PPD(b-a)) as well as the final binary outcome (positive or negative for M. bovis infection). IFN-γ levels after both PPDa and PPDb stimulation were lowest at the extremes of the temperature distribution for NI. The highest IGRA positive probability (above 6%) was found on days with moderate maximum temperatures (6-16 °C) or moderate minimum temperatures (4-7 °C). Adjustment for covariates did not lead to major changes in the model estimates. These data suggest that IGRA performance can be affected when samples are taken at high or low temperatures. Whilst it is difficult to exclude physiological factors, the data nonetheless supports the temperature control of samples from bleeding through to laboratory to help mitigate post-collection confounders.

Post-TB health and wellbeing.

TB affects around 10.6 million people each year and there are now around 155 million TB survivors. TB and its treatments can lead to permanently impaired health and wellbeing. In 2019, representatives of TB affected communities attending the '1st International Post-Tuberculosis Symposium´ called for the development of clinical guidance on these issues. This clinical statement on post-TB health and wellbeing responds to this call and builds on the work of the symposium, which brought together TB survivors, healthcare professionals and researchers. Our document offers expert opinion and, where possible, evidence-based guidance to aid clinicians in the diagnosis and management of post-TB conditions and research in this field. It covers all aspects of post-TB, including economic, social and psychological wellbeing, post TB lung disease (PTLD), cardiovascular and pericardial disease, neurological disability, effects in adolescents and children, and future research needs.

Characterizing individual trainee learning curves in surgical training: Challenges and opportunities.

The surgical learning curve is an observable and measurable phenomenon. In the era of competency-based approaches to surgical training, monitoring the trajectory of individual trainee competence attainment could represent a meaningful method of formative and summative assessment. While technology can assist this approach, a number of significant barriers to the implementation of such assessment methods remain, including: accurate data collection, standard setting, and reliable assessment. Translating individual learning curve data into quantifiable case minimum targets in training poses further difficulties, and may not be possible for all procedures, particularly those that are less frequently performed and assessed. In spite of these challenges, significant benefits could be realized through an individualized approach to competency assessment using trainee learning curve data. Tracking competence acquisition against criterion-referenced standards could allow for targeted training and remediation, conforming with modern theories of adult education and empowering trainees to take control of their own learning. Learning curve data could also be used to assess the effects of educational interventions such as simulation-based training on subsequent competence acquisition rates. Ultimately, the individual learning curves of trainees could be used to inform personalised decisions regarding entrustment, credentialing, and certification, allowing training programmes to move beyond minimum operative experience targets as a crude proxy measure of competence.

Identification, validation and biological characterisation of novel glioblastoma tumour microenvironment subtypes: implications for precision immunotherapy.

BACKGROUND: New precision medicine therapies are urgently required for glioblastoma (GBM). However, to date, efforts to subtype patients based on molecular profiles have failed to direct treatment strategies. We hypothesised that interrogation of the GBM tumour microenvironment (TME) and identification of novel TME-specific subtypes could inform new precision immunotherapy treatment strategies. MATERIALS AND METHODS: A refined and validated microenvironment cell population (MCP) counter method was applied to >800 GBM patient tumours (GBM-MCP-counter). Specifically, partition around medoids (PAM) clustering of GBM-MCP-counter scores in the GLIOTRAIN discovery cohort identified three novel patient clusters, uniquely characterised by TME composition, functional orientation markers and immune checkpoint proteins. Validation was carried out in three independent GBM-RNA-seq datasets. Neoantigen, mutational and gene ontology analysis identified mutations and uniquely altered pathways across subtypes. The longitudinal Glioma Longitudinal AnalySiS (GLASS) cohort and three immunotherapy clinical trial cohorts [treatment with neoadjuvant/adjuvant anti-programmed cell death protein 1 (PD-1) or PSVRIPO] were further interrogated to assess subtype alterations between primary and recurrent tumours and to assess the utility of TME classifiers as immunotherapy biomarkers. RESULTS: TMEHigh tumours (30%) displayed elevated lymphocyte, myeloid cell immune checkpoint, programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 transcripts. TMEHigh/mesenchymal+ patients featured tertiary lymphoid structures. TMEMed (46%) tumours were enriched for endothelial cell gene expression profiles and displayed heterogeneous immune populations. TMELow (24%) tumours were manifest as an 'immune-desert' group. TME subtype transitions upon recurrence were identified in the longitudinal GLASS cohort. Assessment of GBM immunotherapy trial datasets revealed that TMEHigh patients receiving neoadjuvant anti-PD-1 had significantly increased overall survival (P = 0.04). Moreover, TMEHigh patients treated with adjuvant anti-PD-1 or oncolytic virus (PVSRIPO) showed a trend towards improved survival. CONCLUSIONS: We have established a novel TME-based classification system for application in intracranial malignancies. TME subtypes represent canonical 'termini a quo' (starting points) to support an improved precision immunotherapy treatment approach.

The role of altruism vs self-interest in COVID-19 vaccination uptake in the United Kingdom.

OBJECTIVES: The aim of the present study was to explore self-interest, kin altruism and non-kin altruism reasons that influence people to vaccinate against COVID-19. STUDY DESIGN: This was a cross-sectional study using a fully repeated measures design. METHODS: Participants (N = 178) answered questions on perceived threat and likelihood of infection, vaccination status and opinion on mandatory vaccination. Participants also rated a set of statements that asked how likely these would influence them and others to vaccinate against COVID-19. Statements reflected self-interest, kin altruism or non-kin altruism. RESULTS: Just more than half of the sample (50.8%) reported the likelihood of infection as somewhat or extremely likely, and almost three-fourths (74.2%) reported that COVID-19 posed a minor or moderate threat to their physical health. Almost three-fourths (74.3%) of the sample were vaccinated, with just more than half (56.2%) in favour of mandatory vaccination. A 2 (self/other) × 3 (self-interest/kin altruism/non-kin altruism) fully repeated measures analysis of variance showed that kin-altruistic reasons were rated most highly, regardless of whether this was regarding oneself or others. Participants rated others as having greater self-interest reasons for vaccination compared with oneself, whereas non-kin altruism reasons for vaccination were rated higher for oneself, compared with others. CONCLUSION: Highlighting the benefits of vaccination for close relatives and vulnerable others in the population would be a useful strategy for government to use when urging the public to vaccinate against COVID-19.

Understanding public attitudes to death talk and advance care planning in Northern Ireland using health behaviour change theory: a qualitative study.

OBJECTIVES: Advance care planning is a key preparatory step in ensuring high-quality palliative and end of life care, and should be considered as a process, beginning with community-level conversations among lay persons. There is, however, indication that death talk among community-dwelling adults is not occurring, and there is a dearth of research examining why this is the case. This study aims to provide the first examination of barriers and facilitators to talking about death and dying among the general population in a UK region (Northern Ireland), and to provide a novel application of health behaviour change theory towards developing a theoretical understanding of the sources of this behaviour. METHODS: The study involved qualitative analysis of responses (n = 381 participants) to two open-ended questions within a cross-sectional online survey, with recruitment via social media of adults currently living in Northern Ireland. Reflexive thematic analysis was conducted on open text responses per question, with the barriers and facilitators mapped on to health behaviour change models (the Behaviour Change Wheel COM-B and the Theoretical Domains Framework). RESULTS: The findings evidence a myriad of barriers and facilitators to engaging in death talk, with themes aligning to areas such as lack of acceptance of death in social contexts and fear of upsetting self or others, and a need to improve interpersonal communication skills for facilitating conversations and improve knowledge of the existing services around death and dying. A theoretical understanding of the drivers of death talk is presented with findings mapped across most components of the COM-B Behaviour Change Model and the Theoretical Domains Framework. CONCLUSIONS: This study contributes to a small but emergent research area examining barriers and facilitators to talking about death and dying. Findings from this study can be used to inform new public health programmes towards empowering adults to have these conversations with others in their community towards upstreaming advance care planning.

Bringing families to the table: meaningful inclusion of families/significant others in adult eating disorder programmes.

In Ireland, traditionally, most public Adult Mental Health Services (AMHSs) had a small cohort of service users with eating disorders (EDs) in their service. However, over the last 5 years, the National Clinical Programmes have been encouraging Mental Health Services to develop ED programmes in each catchment area. This has culminated in a model of care for EDs for children and adults. It appears that in relation to AMHSs, meaningful inclusion of families/significant other(s) in ED programmes is somewhat inconsistent. This paper will discuss the possible impact of excluding or minimising family/significant other(s)' inclusion. It will also outline a suggested approach of including families/significant other(s) in a meaningful way in an out-patient ED programme.

Risk factors associated with poorer experiences of end-of-life care and challenges in early bereavement: Results of a national online survey of people bereaved during the COVID-19 pandemic.

BACKGROUND: Experiences of end-of-life care and early bereavement during the COVID-19 pandemic are poorly understood. AIM: To identify clinical and demographic risk factors for sub-optimal end-of-life care and pandemic-related challenges prior to death and in early bereavement, to inform clinical practice, policy and bereavement support. DESIGN: Online national survey of adults bereaved in the UK (deaths between 16 March 2020 and 2 January 2021), recruited via media, social media, national associations and organisations. SETTING/PARTICIPANTS: 711 participants, mean age 49.5 (SD 12.9, range 18-90). 628 (88.6%) were female. Mean age of the deceased was 72.2 (SD 16.1, range miscarriage to 102 years). 311 (43.8%) deaths were from confirmed/suspected COVID-19. RESULTS: Deaths in hospital/care home increased the likelihood of poorer experiences at the end of life; for example, being unable to visit or say goodbye as wanted (p < 0.001). COVID-19 was also associated with worse experiences before and after death; for example, feeling unsupported by healthcare professionals (p < 0.001), social isolation/loneliness (OR = 0.439; 95% CI: 0.261-0.739), and limited contact with relatives/friends (OR = 0.465; 95% CI: 0.254-0.852). Expected deaths were associated with a higher likelihood of positive end-of-life care experiences. The deceased being a partner or child also increased the likelihood of positive experiences, however being a bereaved partner strongly increased odds of social isolation/loneliness, for example, OR = 0.092 (95% CI: 0.028-0.297) partner versus distant family member. CONCLUSIONS: Four clear risk factors were found for poorer end-of-life care and pandemic-related challenges in bereavement: place, cause and expectedness of death, and relationship to the deceased.

Mapping end-of-life and anticipatory medications in palliative care patients using a longitudinal general practice database.

OBJECTIVE: End-of-life and anticipatory medications (AMs) have been widely used in various health care settings for people approaching end-of-life. Lack of access to medications at times of need may result in unnecessary hospital admissions and increased patient and family distress in managing palliative care at home. The study aimed to map the use of end-of-life and AM in a cohort of palliative care patients through the use of the Population Level Analysis and Reporting Data Space and to discuss the results through stakeholder consultation of the relevant organizations. METHODS: A retrospective observational cohort study of 799 palliative care patients in 25 Australian general practice health records with a palliative care referral was undertaken over a period of 10 years. This was followed by stakeholders' consultation with palliative care nurse practitioners and general practitioners who have palliative care patients. RESULTS: End-of-life and AM prescribing have been increasing over the recent years. Only a small percentage (13.5%) of palliative care patients received medications through general practice. Stakeholders' consultation on AM prescribing showed that there is confusion about identifying patients needing medications for end-of-life and mixed knowledge about palliative care referral pathways. SIGNIFICANCE OF RESULTS: Improved knowledge and information around referral pathways enabling access to palliative care services for general practice patients and their caregivers are needed. Similarly, the increased utility of screening tools to identify patients with palliative care needs may be useful for health care practitioners to ensure timely care is provided.

Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

Exploring what is important to patients with regards to quality of life after experiencing a lower limb reconstructive procedure: a qualitative evidence synthesis.

BACKGROUND: Patient reported outcome measures (PROMs) are used to understand the impact of lower limb reconstruction surgery on patients' quality of life (QOL). Existing measures have not been developed to specifically capture patient experiences amongst adults with lower limb conditions that require reconstruction surgery. This review aimed to synthesise qualitative evidence to identify what is important to patients requiring, undergoing, or following reconstructive surgery for lower limb conditions. METHODS: MEDLINE, Embase, PsychINFO and Cinahl were searched from inception until November 2020. Studies were included if they employed qualitative research methods, involved patients requiring, undergoing or following lower limb reconstruction and explored patients' experiences of care, treatment, recovery and QOL. Mixed methods studies that did not separately report qualitative findings, mixed population studies that were not separately reported and studies in languages other than English were excluded. Included studies were analysed using thematic synthesis. The Critical Appraisal Skills Programme qualitative studies checklist was used to undertake quality assessment. RESULTS: Nine studies met the inclusion criteria. The thematic synthesis identified two overarching themes: (1) areas of living key to QOL for lower limb reconstruction patients and (2) moving towards a new normal. The way in which lower limb reconstruction affects an individual's QOL and their recovery is complex and is influenced by a range of inter-related factors, which will affect patients to varying degrees depending on their individual circumstances. We identified these factors as: pain, daily functioning and lifestyle, identity, income, emotional wellbeing, support, the ability to adapt and adjust and the ability to move forwards. CONCLUSIONS: The way patients' QOL is affected after a lower limb reconstruction is complex, may change over time and is strongly linked to their recovery. These findings will aid us in developing a conceptual framework which identifies the outcomes important to patients and those that should be included in a PROM. Further research is then required to establish whether the range of factors we identified are captured by existing PROMs. Depending on the outcome of this work, a new PROM for patients following lower limb reconstruction may be required.

Highly pathogenic avian influenza virus H5N6 (clade 2.3.4.4b) has a preferable host tropism for waterfowl reflected in its inefficient transmission to terrestrial poultry.

Highly-pathogenic avian influenza virus (HPAIV) H5N6 (clade 2.3.4.4b) incurred into Europe in late 2017 and was predominantly detected in wild birds, with very few terrestrial poultry cases. Pekin ducks directly-infected with a UK virus (H5N6-2017) were donors of infection to investigate contact transmission to three recipient species: Ducks, chickens and turkeys. H5N6-2017 transmission to ducks was 100% efficient, but transmission to in-contact galliforme species was infrequent and unpredictable, thereby reflecting the European 2017-2018 H5N6 epidemiology. Although only two of 28 (7%) infected ducks died, the six turkeys and one chicken which became infected all died and displayed systemic H5N6-2017 dissemination, while pathogenesis in ducks was generally milder. Analysis of H5N6-2017 progeny in the contacts revealed no emergent polymorphisms in an infected duck, but the galliforme species included changes in the polymerase (PB2 A199T, PA D347A), matrix (M1 T218A) and neuraminidase genes (T88I). H5N6-2017 environmental contamination was associated with duck shedding.

IRF5 regulates airway macrophage metabolic responses.

Interferon regulatory factor 5 (IRF5) is a master regulator of macrophage phenotype and a key transcription factor involved in expression of proinflammatory cytokine responses to microbial and viral infection. Here, we show that IRF5 controls cellular and metabolic responses. By integrating ChIP sequencing (ChIP-Seq) and assay for transposase-accessible chromatin using sequencing (ATAC)-seq data sets, we found that IRF5 directly regulates metabolic genes such as hexokinase-2 (Hk2). The interaction of IRF5 and metabolic genes had a functional consequence, as Irf5-/- airway macrophages but not bone marrow-derived macrophages (BMDMs) were characterized by a quiescent metabolic phenotype at baseline and had reduced ability to utilize oxidative phosphorylation after Toll-like receptor (TLR)-3 activation, in comparison to controls, ex vivo. In a murine model of influenza infection, IRF5 deficiency had no effect on viral load in comparison to wild-type controls but controlled metabolic responses to viral infection, as IRF5 deficiency led to reduced expression of Sirt6 and Hk2. Together, our data indicate that IRF5 is a key component of AM metabolic responses following influenza infection and TLR-3 activation.