Avian, inter-pandemic, and pandemic influenza in Vietnam

The burden and behaviour of influenza in Southeast Asia is poorly characterised, leading to uncertainty about the importance of influenza as a local health problem and the role of Southeast Asia in the global epidemiology of influenza. Prospective community-based studies have provided fundamental insights into the epidemiology of influenza in temperate regions; therefore a household-based cohort study was established with the aim of determining the intensity and characteristics of influenza transmission in a semi-rural tropical setting. The primary results of the cohort study are presented, along with the results of a survey of social contact patterns in the cohort and a mathematical model of the spread of pandemic influenza A/H1N1/2009 in Vietnam that utilises data from the cohort. Highly pathogenic avian influenza A/H5N1 remains endemic in poultry in parts of Southeast Asia and continues to infect humans. Marked familial clustering of human H5N1 cases has led to speculation that susceptibility to H5N1 infection may have a host genetic component. The epidemiological data that led to the hypothesis of genetic susceptibility to H5N1 is summarised, whilst the evidence for a role of host genetics in susceptibility to influenza in general is systematically reviewed. A genome-wide case-control genetic association study was conducted in Vietnam and Thailand to test the hypothesis of genetic susceptibility to H5N1 infection, and the results are presented. This work provides new data and understanding of the patterns and determinants of inter-pandemic, pandemic, and avian influenza epidemiology. The cohort study has added to the body of knowledge that is accruing on the burden and epidemiology of influenza in the tropics by providing community level data that were previously absent. The genetics study has provided the first direct evidence of genetic loci associated with susceptibility to H5N1 and opens new avenues of research to test these findings and their relevance to the pathogenesis of H5N1 and other types of influenza

Dimethyl fumarate in patients admitted to hospital with COVID-19 (RECOVERY):a randomised, controlled, open-label, platform trial

Background Dimethyl fumarate (DMF) is an anti-inflammatory drug that has been proposed as a treatment for patients hospitalised with COVID-19Methods This randomised, controlled, open-label platform trial (Randomised Evaluation of COVID-19 Therapy [RECOVERY]), is assessing multiple possible treatments in patients hospitalised for COVID-19. In this initial assessment of DMF, performed at 27 UK hospitals, eligible and consenting adults were randomly allocated (1:1) to either usual standard of care alone or usual standard of care plus DMF 120mg twice daily for 2 days followed by 240mg twice daily for 8 days, or until discharge if sooner. The primary outcome was clinical status on day 5 measured on a seven-point ordinal scale, assessed using a proportional odds model. Secondary outcomes were time to sustained improvement in clinical status, time to discharge, day 5 peripheral blood oxygenation, day 5 C-reactive protein, and improvement in day 10 clinical status. The trial is registered with ISRCTN (50189673) and clinicaltrials.gov (NCT04381936).Findings Between 2 March 2021 and 18 November 2021, 713 patients were enrolled in the DMF evaluation, of whom 356 were randomly allocated to receive usual care plus DMF, and 357 to usual care alone. 95% of patients were receiving corticosteroids as part of routine care. There was no evidence of a beneficial effect of DMF on clinical status at day 5 (common odds ratio of unfavourable outcome 1.12; 95% CI 0.85-1.46; p=0.42). There was no significant effect of DMF on any secondary outcome. As expected, DMF caused flushing and gastrointestinal symptoms, each in around 6% of patients, but no new adverse effects were identified.Interpretation In adults hospitalised with COVID-19, DMF was not associated with an improvement in clinical outcomes

Modernising epidemic science: enabling patient-centred research during epidemics

Background: Emerging and epidemic infectious disease outbreaks are a significant public health problem and global health security threat. As an outbreak begins, epidemiological investigations and traditional public health responses are generally mounted very quickly. However, patient-centred research is usually not prioritised when planning and enacting the response. Instead, the clinical research response occurs subsequent to and separate from the public health response, and is inadequate for evidence-based decision-making at the bedside or in the offices of public health policymakers.Discussion: The deficiencies of the clinical research response to severe acute respiratory syndrome, pandemic influenza, Middle East respiratory syndrome coronavirus and Ebola virus demonstrate that current research models do not adequately inform and improve the quality of clinical care or public health response. Three suggestions for improvements are made. First, integrate the data and sample collection needs for clinical and public health decision-making within a unified framework, combined with a risk-based, rather than a discipline-based, approach to ethical review and consent. Second, develop clinical study methods and tools that are specifically designed to meet the epidemiological and contextual challenges of emerging and epidemic infectious diseases. Third, invest in investigator-led clinical research networks that are primed and incentivised to respond to outbreak infections, and which can call on the support and resources of a central centre of excellence.Conclusions: It is crucial that the field of epidemic science matures to place patients at the heart of the response. This can only be achieved when patient-centred research is integrated in the outbreak response from day one and practical steps are taken to reduce the barriers to the generation of reliable and useful evidence

An evidence-based framework for priority clinical research questions for COVID-19

Background On 31 December, 2019, the World Health Organization China Country Office was informed of cases of pneumonia of unknown aetiology. Since then, there have been over 75000 cases globally of the 2019 novel coronavirus (COVID-19), 2000 deaths, and over 14000 cases recovered. Outbreaks of novel agents represent opportunities for clinical research to inform real-time public health action. In 2018, we conducted a systematic review to identify priority research questions for Severe Acute Respiratory Syndrome-related coronavirus (SARS-CoV) and Middle East Respiratory Syndrome-related coronavirus (MERS-CoV). Here, we review information available on COVID-19 and provide an evidenced-based framework for priority clinical research in the current outbreak. Methods Three bibliographic databases were searched to identify clinical studies published on SARS-CoV and MERS-CoV in the outbreak setting. Studies were grouped thematically according to clinical research questions addressed. In February 2020, available information on COVID19 was reviewed and compared to the results of the SARS-CoV and MERS-CoV systematic review. Results From the research objectives for SARS-CoV and MERS-CoV, ten themes in the literature were identified: Clinical characterisation, prognosis, diagnosis, clinical management, viral pathogenesis, epidemiological characterisation, infection prevention and control/transmission, susceptibility, psychosocial, and aetiology. For COVID19, some information on clinical presentation, diagnostic testing, and aetiology is available but many clinical research gaps have yet to be filled. Conclusions Based on a systematic review of other severe coronaviruses, we summarise the state of clinical research for COVID-19, highlight the research gaps, and provide recommendations for the implementation of standardised protocols. Databased on internationally standardised protocols will inform clinical practice real-time

Involve those, who are managing these outbreaks – Identifying barriers and facilitators to the implementation of clinical management guidelines for High-Consequence Infectious Diseases in Uganda

Prior research highlighting the complexity of clinical management guidelines (CMG) implementation, has suggested that limited access to treatments and equipment [1] and substantial issues regarding availability, inclusivity, quality, and applicability [2–6] hinder the implementation of CMGs in Low- and Middle-Income Countries (LMICs). This in-depth case study of Uganda – coincidentally occurring during the 2022 Sudan Virus Disease outbreak – aimed to explore contextual and supplementary factors which hinder or facilitate CMG development and implementation. Using thematic network analysis [7–9] the research describes five thematic topics, that emerged from interviews with 43 healthcare personnel, as barriers to the implementation of CMGs in Uganda, namely: (1) deficient content and slow updates of CMGs; (2) limited pandemic preparedness and response infrastructure; (3) slow dissemination and lack of training; (4) scarce resources and healthcare disparities and (5) patient outcomes. The study displays how insufficient training, patchy dissemination and slow updating exacerbate many of the underlying difficulties in LMIC contexts, by illustrating how these issues are related to resource constraints, healthcare disparities, and limited surveillance and referral infrastructure. Key recommendations to enhance CMG implementation are provided, underscoring the necessity of integrating local stakeholders to ensure guidelines are reflective of the reality of the local health system, applicable and inclusive of resource-constrained settings, available as “living guidance” that is disseminated widely and supported by cascading hands-on training. Findings offer valuable insights for LMICs to improve high consequence infectious disease outbreak responses and for organizations involved in guideline development and funding

The Breadth of Viruses in Human Semen.

Zika virus RNA is frequently detected in the semen of men after Zika virus infection. To learn more about persistence of viruses in genital fluids, we searched PubMed for relevant articles. We found evidence that 27 viruses, across a broad range of virus families, can be found in human semen