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Optimizing Treatment GLOBAL INFLUENZA PROGRAMME BACKGROUND DOCUMENT STREAM WHO PUBLIC HEALTH RESEARCH a s d AGENDA FOR d 3 v 4 a e n INFLUENZA e c n e h s lt c a ie e nc c h e li to a pub ddress unmet OPTIMIZING TREATMENT 2017 UPDATE Optimizing the treatment of patients WHO/WHE/IHM/GIP/2017.7 © World Health Organization 2017 Some rights reserved. This work is available under the Creative Commons Attribution- NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/ licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. 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The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by WHO in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO be liable for damages arising from its use. OPTIMIZING TREATMENT Optimizing the treatment of patients WHO Public Health Research Agenda for Influenza 2017 Update Contents Abbreviations 4.0 INTRODUCTION 1 Substream 4.1 FACTORS ASSOCIATED WITH PATHOGENESIS AND CLINICAL SEVERITY 1 RESEARCH RECOMMENDATION 4.1.1 Major Progress 4.1.1 Unmet public health needs and research gaps 4.1.1 RESEARCH RECOMMENDATION 4.1.2 Major Progress 4.1.2 Unmet public health needs and research gaps 4.1.2 RESEARCH RECOMMENDATION 4.1.3 Major Progress 4.1.3 Unmet public health needs and research gaps 4.1.3 RESEARCH RECOMMENDATION 4.1.4 Major Progress 4.1.4 Unmet public health needs and research gaps 4.1.4 RESEARCH RECOMMENDATION 4.1.5 Major Progress 4.1.5 Unmet public health needs and research gaps 4.1.5 Substream 4.2 IMPROVE CLINICAL MANAGEMENT OF PATIENTS 9 RESEARCH RECOMMENDATION 4.2.1 Major Progress 4.2.1 Unmet public health needs and research gaps 4.2.1 RESEARCH RECOMMENDATION 4.2.2 Major Progress 4.2.2 Unmet public health needs and research gaps 4.2.2 RESEARCH RECOMMENDATION 4.2.3 Major Progress 4.2.3 Unmet public health needs and research gaps 4.2.3 RESEARCH RECOMMENDATION 4.2.4 Major Progress 4.2.4 Unmet public health needs and research gaps 4.2.4 RESEARCH RECOMMENDATION 4.2.5 Major Progress 4.2.5 Unmet public health needs and research gaps 4.2.5 Substream 4.3 HEALTH-CARE CAPACITY AND RESPONSE 17 RESEARCH RECOMMENDATION 4.3.1 Major Progress 4.3.1 Unmet public health needs and research gaps 4.3.1 RESEARCH RECOMMENDATION 4.3.2 Major Progress 4.3.2 Unmet public health needs and research gaps 4.3.2 RESEARCH RECOMMENDATION 4.3.3 Major Progress 4.3.3 Unmet public health needs and research gaps 4.3.3 RESEARCH RECOMMENDATION 4.3.4 Major Progress 4.3.4 Unmet public health needs and research gaps 4.3.4 RESEARCH RECOMMENDATION 4.3.5 Major Progress 4.3.5 Unmet public health needs and research gaps 4.3.5 RESEARCH RECOMMENDATION 4.3.6 Major Progress 4.3.6 Unmet public health needs and research gaps 4.3.6 REFERENCES 24 Abbrevations AMI Acute Myocardial Infarction ARI Acute Respiratory Infection CAP Community-acquired Pneumonia CC Collaborating Centre CCR5 Chemokine Receptor 5 CDC Centers for Disease Control and Prevention CPT2 Carnitine Palmitoyltransferase II ECMO Extracorporeal Membrane Oxygenation GI Gastrointestinal HA Haemagglutinin HCT Haematopoietic Cell Transplant HDU High-dependency Unit HLA Human Leukocyte Antigen BACKGROUND DOCUMENT HSCT Haematopoietic Stem Cell Transplant ICU Intensive Care Unit STREAM IFITM3 Interferon-inducible Transmembrane 3 OPTIMIZING THE 4 ILI Influenza-like Illness TREATMENT OF PATIENTS IMV Invasive Mechanical Ventilation IRF7 Interferon Regulatory Factor 7 IRVS Invasive Respiratory or Vasopressor Support NAAT Nucleic Acid Amplification-based Test NAIs Neuraminidase Inhibitors NIV Noninvasive Ventilation PCT Procalcitonin POC Point of Care PPE Personal Protective Equipment RCTs Randomized Controlled Trials RSV Respiratory Syncytial Virus RT-PCR Reverse Transcriptase Polymerase Chain Reaction SARI Severe Acute Respiratory Infection TB Tuberculosis WBC White Blood Cell WHO World Health Organization STREAM 4.0 Introduction 4 AMI Acute Myocardial Infarction ARI Acute Respiratory Infection Rapid case identification and improved clinical management can substantially reduce the incidence of CAP Community-acquired Pneumonia severe illness and associated complications of seasonal, novel influenza A and pandemic influenza virus CC Collaborating Centre infections. It may also reduce the risk of influenza virus transmission and mitigate the impact of outbreaks on the health-care system. Optimization of clinical management must be underpinned by a better CCR5 Chemokine Receptor 5 understanding of the pathogenesis of influenza virus infections, advances in rapid laboratory diagnostics, CDC Centers for Disease Control and Prevention development and timely initiation of effective antiviral treatment and other interventions, and prompt CPT2 Carnitine Palmitoyltransferase II access to good-quality health-care services. As summarized below, progress has been made in many aspects of influenza clinical management, particularly from new evidence developed during the 2009 ECMO Extracorporeal Membrane Oxygenation A(H1N1)pdm09 virus pandemic, but there are still many unmet public health needs and unanswered GI Gastrointestinal questions. The following sections provide overviews with selected references that illustrate both HA Haemagglutinin developments and continuing evidence gaps for each of the substreams described in Stream 4 of the 2009 HCT Haematopoietic Cell Transplant WHO Public Health Research Agenda for Influenza. HDU High-dependency Unit HLA Human Leukocyte Antigen Substream 4.1 HSCT Haematopoietic Stem Cell Transplant Factors associated with pathogenesis and clinical severity ICU Intensive Care Unit IFITM3 Interferon-inducible Transmembrane 3 Research recommendation 4.1.1 ILI Influenza-like Illness Investigate the role of virological factors (including replication sites, duration and viral load levels), IMV Invasive Mechanical Ventilation and innate and adaptive immune responses and other host responses in the severity of disease and IRF7 Interferon Regulatory Factor 7 associated complications. IRVS Invasive Respiratory or Vasopressor Support Major Progress 4.1.1 NAAT Nucleic Acid Amplification-based Test Many studies have examined viral replication patterns, and immune and other host responses, in patients NAIs Neuraminidase Inhibitors with serious illness from A(H1N1)pdm09 virus infection. Relevant observations include the finding of more protracted viral replication (measured by quantitative viral RNA detection) in the upper respiratory tract of NIV Noninvasive Ventilation patients with severe illness (To et al., 2010). In this study, the 23 patients who had acute respiratory distress PCT Procalcitonin syndrome (ARDS) or died had a slower decline in nasopharyngeal viral loads, had higher plasma levels of POC Point of Care proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), PPE Personal Protective Equipment myocarditis (21.7%) or viremia (13.0%) than
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