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

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

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

Addressing challenges for clinical research responses to emerging epidemics and pandemics: a scoping review.

BACKGROUND: Major infectious disease outbreaks are a constant threat to human health. Clinical research responses to outbreaks generate evidence to improve outcomes and outbreak control. Experiences from previous epidemics have identified multiple challenges to undertaking timely clinical research responses. This scoping review is a systematic appraisal of political, economic, administrative, regulatory, logistical, ethical and social (PEARLES) challenges to clinical research responses to emergency epidemics and solutions identified to address these. METHODS: A scoping review. We searched six databases (MEDLINE, Embase, Global Health, PsycINFO, Scopus and Epistemonikos) for articles published from 2008 to July 2018. We included publications reporting PEARLES challenges to clinical research responses to emerging epidemics and pandemics and solutions identified to address these. Two reviewers screened articles for inclusion, extracted and analysed the data. RESULTS: Of 2678 articles screened, 76 were included. Most presented data relating to the 2014-2016 Ebola virus outbreak or the H1N1 outbreak in 2009. The articles related to clinical research responses in Africa (n = 37), Europe (n = 8), North America (n = 5), Latin America and the Caribbean (n = 3) and Asia (n = 1) and/or globally (n = 22). A wide range of solutions to PEARLES challenges was presented, including a need to strengthen global collaborations and coordination at all levels and develop pre-approved protocols and equitable frameworks, protocols and standards for emergencies. Clinical trial networks and expedited funding and approvals were some solutions implemented. National ownership and community engagement from the outset were a key enabler for delivery. Despite the wide range of recommended solutions, none had been formally evaluated. CONCLUSIONS: To strengthen global preparedness and response to the COVID-19 pandemic and future epidemics, identified solutions for rapid clinical research deployment, delivery, and dissemination must be implemented. Improvements are urgently needed to strengthen collaborations, funding mechanisms, global and national research capacity and capability, targeting regions vulnerable to epidemics and pandemics. Solutions need to be flexible to allow timely adaptations to context, and research led by governments of affected regions. Research communities globally need to evaluate their activities and incorporate lessons learnt to refine and rehearse collaborative outbreak response plans in between epidemics

Time to reconsider the role of ribavirin in Lassa fever

Ribavirin is the only available Lassa fever treatment. The rationale for using ribavirin is based on one clinical study conducted in the early 1980s. However, reanalysis of previous unpublished data reveals that ribavirin may actually be harmful in some Lassa fever patients. An urgent reevaluation of ribavirin is therefore needed

Lack of Evidence for Ribavirin Treatment of Lassa Fever in Systematic Review of Published and Unpublished Studies

Ribavirin has been used widely to treat Lassa fever in West Africa since the 1980s. However, few studies have systematically appraised the evidence for its use. We conducted a systematic review of published and unpublished literature retrieved from electronic databases and gray literature from inception to March 8, 2022. We identified 13 studies of the comparative effectiveness of ribavirin versus no ribavirin treatment on mortality outcomes, including unpublished data from a study in Sierra Leone provided through a US Freedom of Information Act request. Although ribavirin was associated with decreased mortality rates, results of these studies were at critical or serious risk for bias when appraised using the ROBINS-I tool. Important risks for bias related to lack of control for confounders, immortal time bias, and missing outcome data. Robust evidence supporting the use of ribavirin in Lassa fever is lacking. Well-conducted clinical trials to elucidate the effectiveness of ribavirin for Lassa fever are needed