Global respiratory syncytial virus-associated mortality in young children (RSV GOLD): a retrospective case series
University Medical Center Utrecht1, Boston Children's Hospital2, Kenya Medical Research Institute3, University of Warwick4, Pwani University College5, University of the Witwatersrand6, Centers for Disease Control and Prevention7, Tohoku University8, Research Institute for Tropical Medicine9, University of Michigan10, Johns Hopkins University11, Nationwide Children's Hospital12, Ohio State University13, University of Jordan14, Vanderbilt University Medical Center15, University of Virginia16, McMaster University17, University of Colorado Boulder18, The Chinese University of Hong Kong19, Royal Children's Hospital20, University of Melbourne21, Aga Khan University22, University of Nottingham23, McGill University Health Centre24, University of Sheffield25, Utrecht University26, University of Edinburgh27
TL;DR: The results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries.
About: This article is published in The Lancet Global Health.The article was published on 2017-10-01 and is currently open access. It has received 180 citations till now. The article focuses on the topics: Child mortality.
Citations
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University Medical Center Utrecht1, PATH2, University of the Witwatersrand3, Carlos III Health Institute4, University of Washington5, National Institutes of Health6, University of Texas at Austin7, Seattle Children's Research Institute8, Nationwide Children's Hospital9, Johns Hopkins University10, University of Colorado Denver11, World Health Organization12, Rochester General Health System13, University of Edinburgh14, King's College London15, University of Padua16, University of Manchester17, Medicines and Healthcare Products Regulatory Agency18, Pontifícia Universidade Católica do Rio Grande do Sul19
TL;DR: This Review provides a comprehensive overview of RSV vaccine candidates and mAbs in clinical development to prevent one of the most common and severe infectious diseases in young children and older adults worldwide.
Abstract: The global burden of disease caused by respiratory syncytial virus (RSV) is increasingly recognised, not only in infants, but also in older adults (aged ≥65 years). Advances in knowledge of the structural biology of the RSV surface fusion glycoprotein have revolutionised RSV vaccine development by providing a new target for preventive interventions. The RSV vaccine landscape has rapidly expanded to include 19 vaccine candidates and monoclonal antibodies (mAbs) in clinical trials, reflecting the urgency of reducing this global health problem and hence the prioritisation of RSV vaccine development. The candidates include mAbs and vaccines using four approaches: (1) particle-based, (2) live-attenuated or chimeric, (3) subunit, (4) vector-based. Late-phase RSV vaccine trial failures highlight gaps in knowledge regarding immunological protection and provide lessons for future development. In this Review, we highlight promising new approaches for RSV vaccine design and provide a comprehensive overview of RSV vaccine candidates and mAbs in clinical development to prevent one of the most common and severe infectious diseases in young children and older adults worldwide.
308 citations
TL;DR: It is found that extremely preterm children receive comparable repertoires of IgG as term children, albeit at lower absolute concentrations and consequent shorter half-life, and neutralization of the clinically important respiratory syncytial virus was also comparable until three months of age.
Abstract: All circulating immunoglobulin G (IgG) antibodies in human newborns are of maternal origin1 and transferred across the placenta to provide passive immunity until newborn IgG production takes over 15 weeks after birth2. However, maternal IgG can also negatively interfere with newborn vaccine responses3. The concentration of IgG increases sharply during the third trimester of gestation and children delivered extremely preterm are believed to largely lack this passive immunity1,2,4. Antibodies to individual viruses have been reported5–12, but the global repertoire of maternal IgG, its variation in children, and the epitopes targeted are poorly understood. Here, we assess antibodies against 93,904 epitopes from 206 viruses in 32 preterm and 46 term mother–child dyads. We find that extremely preterm children receive comparable repertoires of IgG as term children, albeit at lower absolute concentrations and consequent shorter half-life. Neutralization of the clinically important respiratory syncytial virus (RS-virus) was also comparable until three months of age. These findings have implications for understanding infectious disease susceptibility, vaccine development, and vaccine scheduling in newborn children. A longitudinal survey of maternal antiviral antibodies in newborns provides a blueprint for understanding infectious disease susceptibility and vaccine development, and inform vaccine scheduling in newborn children.
81 citations
TL;DR: Infants with severe RSV bronchiolitis have lower nasal viral load, CXCL10 (C‐X‐C motif chemokine ligand 10)/IP‐10, and type‐I IFN levels than moderately ill children, but enhanced MUC5AC (mucin‐5AC) and IL17A gene expression in nasal cells.
Abstract: Rationale: Respiratory syncytial virus (RSV) bronchiolitis is a major cause of morbidity and mortality in infancy. Severe disease is believed to result from uncontrolled viral replication, an exces...
66 citations
TL;DR: RSV disease is one of the major remaining common tractable challenges in infectious diseases and the era of vaccines and antivirals for RSV is on the near horizon.
Abstract: Respiratory syncytial virus (RSV) is the most common single cause of respiratory hospitalisation of infants and is the second largest cause of lower respiratory infection mortality worldwide. In adults, RSV is an under-recognised cause of deterioration in health, particularly in frail elderly persons. Infection rates typically rise in late autumn and early winter causing bronchiolitis in infants, common colds in adults and insidious respiratory illness in the elderly. Virus detection methods optimised for use in children have low detection rate in adults, highlighting the need for better diagnostic tests. There are many vaccines under development, mostly based on the surface glycoprotein F which exists in two conformations (prefusion and postfusion). Much of the neutralising antibody appears to be to the prefusion form. Vaccines being developed include live attenuated, subunit, particle based and live vectored agents. Different vaccine strategies may be appropriate for different target populations: at-risk infants, school-age children, adult caregivers and the elderly. Antiviral drugs are in clinical trial and may find a place in disease management. RSV disease is one of the major remaining common tractable challenges in infectious diseases and the era of vaccines and antivirals for RSV is on the near horizon.
65 citations
Cites background from "Global respiratory syncytial virus-..."
...Despite this, health inequality means that only 24% of children in low-income and lower middle-income countries have access to paediatric intensive care, an important reason for the differences in mortality.(11) In adults, there are 8482 deaths per year attributable to RSV in the UK, with 93% of those occurring in adults aged more than 65 years....
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...inferred RSV-associated deaths than those that might be established by direct testing and viral detection.(11) In a study from the...
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...Furthermore, at least 28% of RSV-associated mortality occurred in children with severe comorbidities (such as congenital heart disease) in low-income countries.(11) Despite this, health inequality means that only 24% of children in low-income and lower middle-income countries have access to paediatric intensive care, an important reason for the differences in mortality....
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TL;DR: The findings, limited to exposure and immunoprophylaxis studies, do not support basing policy decisions on an assumption that prevention of RSV-LRTI will reduce recurrent chronic wheezing illnesses.
56 citations
References
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TL;DR: The Global Burden of Diseases, Injuries, and Risk Factors Study 2010 aimed to estimate annual deaths for the world and 21 regions between 1980 and 2010 for 235 causes, with uncertainty intervals (UIs), separately by age and sex, using the Cause of Death Ensemble model.
11,809 citations
University of Edinburgh1, University of Glasgow2, Johns Hopkins University3, University of Colorado Boulder4, University of the Witwatersrand5, International Military Sports Council6, Aga Khan University7, Medical Research Council8, King George's Medical University9, Kenya Medical Research Institute10, International Centre for Diarrhoeal Disease Research, Bangladesh11, Centers for Disease Control and Prevention12, Tribhuvan University13, University of Bergen14, University of Barcelona15, Utrecht University16, Emory University17, All India Institute of Medical Sciences18, University of Liverpool19, Boston Children's Hospital20, National Institute of Virology21, University of Zambia22, University of Health Sciences Antigua23, National Health Laboratory Service24, Chinese Center for Disease Control and Prevention25, Austral University26, University of Michigan27, Vanderbilt University28, University of New South Wales29, University of Auckland30, University of Otago31, Universidad del Valle de Guatemala32, University of Jordan33, University of Maryland, Baltimore34, National Scientific and Technical Research Council35, Research Institute for Tropical Medicine36, Pwani University College37, University of Cape Town38, University of Warwick39, Academy of Medical Sciences, United Kingdom40, Tohoku University41, École normale supérieure de Lyon42, John E. Fogarty International Center43, Charité44, Universidad Nacional de Asunción45, Tehran University of Medical Sciences46, Robert Koch Institute47, University of London48, University of New Mexico49, Capital Medical University50, Alaska Native Tribal Health Consortium51, Innlandet Hospital Trust52, Columbia University53, Mahidol University54, University of Pretoria55, Thailand Ministry of Public Health56, Peking Union Medical College57, Nagasaki University58, Public Health Foundation of India59
TL;DR: In this paper, the authors estimated the incidence and hospital admission rate of RSV-associated acute lower respiratory infection (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions.
1,470 citations
University of Edinburgh1, Public Health Foundation of India2, University of Colorado Denver3, National Center for Immunization and Respiratory Diseases4, University of Melbourne5, Johns Hopkins University6, Centers for Disease Control and Prevention7, Medical Research Council8, Kenya Medical Research Institute9, University of Barcelona10, Health Protection Agency11, Alaska Native Tribal Health Consortium12, Research Institute for Tropical Medicine13, Boston Children's Hospital14, University of the Witwatersrand15, All India Institute of Medical Sciences16, Aga Khan University17, Universidad de Ciencias Medicas18, Universidade Federal de Goiás19, University of Buenos Aires20, United Nations Development Programme21, Universidad del Valle de Guatemala22, University of Liverpool23, Bill & Melinda Gates Foundation24, International Centre for Diarrhoeal Disease Research, Bangladesh25
TL;DR: The data suggest that although 62% of children with severe ALRI are treated in hospitals, 81% of deaths happen outside hospitals, which suggests community-based management of severe disease could be an important complementary strategy to reduce pneumonia mortality and health inequities.
597 citations
TL;DR: It was estimated that < or =510 RSV-associated deaths occurred annually during the study period, fewer than previously estimated.
Abstract: A 1985 estimate that 4500 respiratory syncytial virus (RSV)-associated deaths occur annually among US children has not been updated using nationally representative data. Thus, 1979-1997 multiple cause-of-death records for children <5 years old listing bronchiolitis, pneumonia, or any respiratory tract disease were examined. Deaths among children associated with any respiratory disease declined from 4631 in 1979 to 2502 in 1997. During the 19-year study period, 1806 bronchiolitis-associated deaths occurred (annual mean, 95 deaths; range, 66-127 deaths). Of these deaths, 1435 (79%) occurred among infants <1 year old. Congenital heart disease, lung disease, or prematurity was listed in death records of 179 (9.9%), 99 (5.5%), and 76 (4.2%) children dying with bronchiolitis, respectively. By applying published proportions of children hospitalized for bronchiolitis or pneumonia who were RSV-infected to bronchiolitis and pneumonia deaths, it was estimated that < or =510 RSV-associated deaths occurred annually during the study period, fewer than previously estimated.
462 citations