A highly potent extended half-life antibody as apotential RSV vaccine surrogate for all infants5/29/2017 Zhu Q, McLellan JS, Kallewaard NL, Ulbrandt ND, Palaszynski S, Zhang J, Moldt B, Khan A, Svabek C, McAuliffe JM, Wrapp D, Patel NK, Cook KE, Richter BWM, Ryan PC, Yuan AQ, Suzich JA.
Most children with severe RSV infection were previously healthy term children. Palivizumab, the only approved agent for RSV prophylaxis, is limited to high-risk infants, and the cost associated with the requirement for dosing throughout the RSV season makes its use impractical for all infants. This paper describes the development of a monoclonal antibody as potential RSV prophylaxis for all infants with a single intramuscular dose. MEDI8897 has >50-fold higher activity than palivizumab. More than threefold increased half-life. Considering the half-life its use may be an option to protect all infants from RSV disease with once-per-RSV-season dosing.
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Heikkinen T, Ojala E, Waris M.
We analyzed the burden of RSV in a prospective cohort study of children aged ≤13 years during two consecutive respiratory seasons in Turku, Finland (2231 child-seasons of follow-up). Of 6001 medically attended respiratory infections, 302 (5%) were caused by RSV. Per 1000 children, the average annual RSV incidence rates among children aged <3, 3-6, and 7-13 years were 275, 117, and 46, respectively. In children aged <3 years, acute otitis media developed in 58%, and 66% of children in this age group received antibiotics. The mean duration of RSV illness was longest (13.0 days) and the rate of parental work absenteeism highest (136 days per 100 children with RSV) in children aged <3 years. The burden of RSV is particularly great among outpatient children aged <3 years, and young children are an important target group for the development of RSV vaccines and antivirals. Mazur NI, Bont L, Cohen AL, Cohen C, Gottberg A von, Groome MJ, Hellferscee O, Klipstein-Grobusch K, Mekgoe O, Naby F, Moyes J, Tempia S, Treurnicht FK, Venter M, Walaza S, Wolter N, Madhi SA; for the South African Severe Acute Respiratory Illness (SARI) Surveillance Group
It is still not clear why some children have life-threatening RSV disease. Molecular diagnostics enable sensitive detection of respiratory viruses but their clinical significance remains unclear in pediatric lower respiratory tract infections (LRTI). We aimed to determine whether viral coinfections increase life-threatening disease in a large cohort. As part of the Severe Acute Respiratory Illness (SARI) hospitalization sentinal surveillance conducted in South Africa from February 2009-December 2013, molecular testing for respiratory viruses was performed in 2.322 HIV-uninfected children with RSV-associated LRTI. We found that RSV and any viral coinfection compared to RSV monoinfection is not associated with more severe disease (OR:0.74, 95%CI 0.39-1.4). However, increased life-threatening disease in RSV-adenovirus (aOR: 3.4, 95%CI: 1.6-7.2, p=0.001)and RSV-Influenza coinfection (aOR: 2.1, 95%CI 1.0-4.5, p=0.05) warrants further study. Geoghegan S, Erviti A,Caballero MT, Vallone F, Zanone1 SM, Ves Losada J, Bianchi A, Acosta PL, Talarico LB, Ferretti A, Grimaldi LA, Sancilio A, Dueñas K, Sastre G, Rodriguez A, Ferrero F, Barboza E, Fernández Gago G, Nocito C, Flamenco E, Rodriguez Perez A, Rebec B, Ferolla M, Libster R, Karron RA, Berge E, Polack FP.
Respiratory syncytial virus (RSV) infection during infancy causes enormous mortality in the developing world. However, a good proportion of the mortality data have been derived from studies measuring excess mortality during RSV epidemics. Much of RSV-related deaths probably occur in the community due to lack of access to care. To understand individual characteristics of community-based and hospital-based deaths a prospective multicentre study was performed in Argentina. In hospitalized patients, case fatality was 0.9%. RSV infection explained about 50% of all deaths among infants presenting with lower respiratory tract illness. Death was related to bacterial sepsis and pneumothorax. This study is one of the first to provide insight into clinical characteristics of children dying from RSV and the mechanisms eventually preceding death.  We are very proud to announce that our board member, Dr. Federico Martinón Torres and his team, designed a new clinical scale for infants with acute respiratory infection, the ReSVinet scale. Our scale is based on seven parameters (feeding intolerance, medical intervention, respiratory difficulty, respiratory frequency, apnoea, general condition, fever) that were assigned different values (from 0 to 3) for a total of 20 points. 170 children under two years of age with ARI were assessed independently by three pediatricians using this scale.
We invite you to read the full report by downloading the file via the link below We are delighted to inform you that the report of our successful ReSViNET meeting in Zeist (2-3 March 2016) is published in “Journal of Global Health”. We invite you to read the full report by downloading the file via the link below.  Steenhuijsen Piters WAA de, Heinonen S, Hasrat R, Bunsow E, Smith B, Suarez-Arrabal MC, Chaussabel D, Cohen DM, Sanders EAM, Ramilo O, Bogaert D, Mejias A.
From 2010-2014 we conducted a prospective observational study during 4 consecutive RSV seasons at Nationwide Children’s Hospital, Columbus, Ohio, USA. Previously healthy children <2 years of age with a first episode of RSV infection were enrolled either at the outpatient clinics (‘outpatients’) or within 24h [17-39h] (median [IQR]) of admission in the pediatric ward or the pediatric intensive care unit (PICU) (‘inpatients’). Asymptomatic healthy controls were enrolled during routine primary care visits or elective surgery not involving the respiratory tract. For study criteria see Supplementary methods E1. In addition to the need for hospitalization, RSV disease severity was assessed using a clinical disease severity score (CDSS), and by the need for supplemental oxygen, PICU admission and length of stay.(16) Pisesky A, Benchimol EI, Wong CA, Hui C, Crowe M, Belair MA, Pojsupap S, Karnauchow T, O'Hearn K, Yasseen AS, McNally JD.
One in hundred children without comorbidity are hospitalized for RSV lower respiratory tract illness. This is the conclusion from a study performed of a nine year period in Ontario, Canada. Among 1.6 million children 8.7% were born prematurely or suffered congenital heart disease, bronchopulmonary dysplasia or Down syndrome. The incidence of RSV-related admission among these children was 10.2 per 1000 in the first year of life. This was 2.5 times lower than in children with comorbidity. The incidence of RSV-related admissions varied over time between 6,3 and 12 per 1000 showing the critical importance of doing this study over a period of several years. The incidence rates in this report are comparable to those found in a prospective population-based study from the United States (11 per 1000, Hall, NEJM 2007) and the Netherlands (8 per 1000, Zomer, Eur Respir J 2014). DeVincenzo JP, McClure MW, Symons JA, Fathi H, Westland C, Chanda S, Lambkin‑Williams R, Smith P, Qingling Zhang Q, Beigelman L, Blatt LM, Fry J.
Nucleoside analogue for RSV ALS-008176 is a potent oral inhibitor of viral replication when administered early after viral challenge of 62 healthy adults. This is the conclusion by DeVincenzo and colleagues from Alios BioPharma and Retroscreen Virology. Treatment was started after confirmation of RSV infection or 6 days after inoculation. Treatment was administered every 12 hours for 5 days. Robust and surprisingly rapid inhibition of viral replication was observed within 12 hours after treatment. No rebound viral replication was observed. Infection-related mucous production was almost fully prevented by ALS-008176. No evidence of toxicity was observed during or after a 5 day treatment. Safety and tolerability of single and multiple doses of ALS-008176 is currently tested in infants with RSV bronchiolitis. Mazur NI,Martinón-Torres F, Baraldi E, Fauroux B, Greenough A, Heikkinen T, Manzoni P, Mejias A, Nair H, Papadopoulos NG, Polack FP, Ramilo O, Sharland M, Stein R, Madhi SA, Bont L, in collaboration with Respiratory Syncytial Virus Network (ReSViNET)
Respiratory syncytial virus (RSV) is a major worldwide cause of morbidity and mortality in children under five years of age. Evidence-based management guidelines suggest that there is no effective treatment for RSV lower respiratory tract infection (LRTI) and that supportive care, ie, hydration and oxygenation, remains the cornerstone of clinical management. However, RSV treatments in development in the past decade include 10 vaccines and 11 therapeutic agents in active clinical trials. Maternal vaccination is particularly relevant because the most severe disease occurs within the first 6 months of life, when children are unlikely to benefit from active immunisation. We must optimise the implementation of novel RSV therapeutics by understanding the target populations, showing safety, and striving for acceptable pricing in the context of this worldwide health problem. In this Review, we outline the limitations of RSV LRTI management, the drugs in development, and the remaining challenges related to study design, regulatory approval, and implementation. |
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January 2019
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