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      Respiratory syncytial virus hospitalization and mortality: Systematic review and meta‐analysis

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          Background: Respiratory syncytial virus (RSV) is a major public health burden worldwide. We aimed to review the current literature on the incidence and mortality of severe RSV in children globally. Methods: Systematic literature review and meta‐analysis of published data from 2000 onwards, reporting on burden of acute respiratory infection (ARI) due to RSV in children. Main outcomes were hospitalization for severe RSV‐ARI and death. Results: Five thousand two hundred and seventy‐four references were identified. Fifty‐five studies were included from 32 countries. The global RSV‐ARI hospitalization estimates, reported per 1,000 children per year (95% Credible Interval (CrI), were 4.37 (2.98, 6.42) among children <5 years, 19.19 (15.04, 24.48) among children <1 year, 20.01 (9.65, 41.31) among children <6 months and 63.85 (37.52, 109.70) among premature children <1 year. The RSV‐ARI global case‐fatality estimates, reported per 1,000 children, (95% Crl) were 6.21 (2.64, 13.73) among children <5 years, 6.60 (1.85, 16.93) for children <1 year, and 1.04 (0.17, 12.06) among preterm children <1 year. Conclusions: A substantial proportion of RSV‐associated morbidity occurs in the first year of life, especially in children born prematurely. These data affirm the importance of RSV disease in the causation of hospitalization and as a significant contributor to pediatric mortality and further demonstrate gestational age as a critical determinant of disease severity. An important limitation of case‐fatality ratios is the absence of individual patient characteristics of non‐surviving patients. Moreover, case‐fatality ratios cannot be translated to population‐based mortality. Pediatr Pulmonol. 2017;52:556–569. © 2016 The Authors. Pediatric Pulmonology. Published by Wiley Periodicals, Inc.

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          WHO estimates of the causes of death in children.

          Child survival efforts can be effective only if they are based on accurate information about causes of deaths. Here, we report on a 4-year effort by WHO to improve the accuracy of this information. WHO established the external Child Health Epidemiology Reference Group (CHERG) in 2001 to develop estimates of the proportion of deaths in children younger than age 5 years attributable to pneumonia, diarrhoea, malaria, measles, and the major causes of death in the first 28 days of life. Various methods, including single-cause and multi-cause proportionate mortality models, were used. The role of undernutrition as an underlying cause of death was estimated in collaboration with CHERG. In 2000-03, six causes accounted for 73% of the 10.6 million yearly deaths in children younger than age 5 years: pneumonia (19%), diarrhoea (18%), malaria (8%), neonatal pneumonia or sepsis (10%), preterm delivery (10%), and asphyxia at birth (8%). The four communicable disease categories account for more than half (54%) of all child deaths. The greatest communicable disease killers are similar in all WHO regions with the exception of malaria; 94% of global deaths attributable to this disease occur in the Africa region. Undernutrition is an underlying cause of 53% of all deaths in children younger than age 5 years. Achievement of the millennium development goal of reducing child mortality by two-thirds from the 1990 rate will depend on renewed efforts to prevent and control pneumonia, diarrhoea, and undernutrition in all WHO regions, and malaria in the Africa region. In all regions, deaths in the neonatal period, primarily due to preterm delivery, sepsis or pneumonia, and birth asphyxia should also be addressed. These estimates of the causes of child deaths should be used to guide public-health policies and programmes.
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            Respiratory syncytial virus and recurrent wheeze in healthy preterm infants.

            Respiratory syncytial virus (RSV) infection is associated with subsequent recurrent wheeze. Observational studies cannot determine whether RSV infection is the cause of recurrent wheeze or the first indication of preexistent pulmonary vulnerability in preterm infants. The monoclonal antibody palivizumab has shown efficacy in preventing severe RSV infection in high-risk infants. In the double-blind, placebo-controlled MAKI trial, we randomly assigned 429 otherwise healthy preterm infants born at a gestational age of 33 to 35 weeks to receive either monthly palivizumab injections (214 infants) or placebo (215 infants) during the RSV season. The prespecified primary outcome was the total number of parent-reported wheezing days in the first year of life. Nasopharyngeal swabs were taken during respiratory episodes for viral analysis. Palivizumab treatment resulted in a relative reduction of 61% (95% confidence interval, 56 to 65) in the total number of wheezing days during the first year of life (930 of 53,075 days in the RSV-prevention group [1.8%] vs. 2309 of 51,726 days [4.5%] in the placebo group). During this time, the proportion of infants with recurrent wheeze was 10 percentage points lower in patients treated with palivizumab (11% vs. 21%, P=0.01). In otherwise healthy preterm infants, palivizumab treatment resulted in a significant reduction in wheezing days during the first year of life, even after the end of treatment. These findings implicate RSV infection as an important mechanism of recurrent wheeze during the first year of life in such infants. (Funded by Abbott Laboratories and by the Netherlands Organization for Health Research and Development; MAKI Controlled Clinical Trials number, ISRCTN73641710.).
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              Risk factors for respiratory syncytial virus associated with acute lower respiratory infection in children under five years: Systematic review and meta–analysis

              Background Respiratory syncytial virus (RSV) is the most common pathogen identified in young children with acute lower respiratory infection (ALRI) as well as an important cause of hospital admission. The high incidence of RSV infection and its potential severe outcome make it important to identify and prioritise children who are at higher risk of developing RSV–associated ALRI. We aimed to identify risk factors for RSV–associated ALRI in young children. Methods We carried out a systematic literature review across 4 databases and obtained unpublished studies from RSV Global Epidemiology Network (RSV GEN) collaborators. Quality of all eligible studies was assessed according to modified GRADE criteria. We conducted meta–analyses to estimate odds ratios with 95% confidence intervals (CI) for individual risk factors. Results We identified 20 studies (3 were unpublished data) with “good quality” that investigated 18 risk factors for RSV–associated ALRI in children younger than five years old. Among them, 8 risk factors were significantly associated with RSV–associated ALRI. The meta–estimates of their odds ratio (ORs) with corresponding 95% confidence intervals (CI) are prematurity 1.96 (95% CI 1.44–2.67), low birth weight 1.91 (95% CI 1.45–2.53), being male 1.23 (95% CI 1.13–1.33), having siblings 1.60 (95% CI 1.32–1.95), maternal smoking 1.36 (95% CI 1.24–1.50), history of atopy 1.47 (95% CI 1.16–1.87), no breastfeeding 2.24 (95% CI 1.56–3.20) and crowding 1.94 (95% CI 1.29–2.93). Although there were insufficient studies available to generate a meta–estimate for HIV, all articles (irrespective of quality scores) reported significant associations between HIV and RSV–associated ALRI. Conclusions This study presents a comprehensive report of the strength of association between various socio–demographic risk factors and RSV–associated ALRI in young children. Some of these amenable risk factors are similar to those that have been identified for (all cause) ALRI and thus, in addition to the future impact of novel RSV vaccines, national action against ALRI risk factors as part of national control programmes can be expected to reduce burden of disease from RSV. Further research which identifies, accesses and analyses additional unpublished RSV data sets could further improve the precision of these estimates.
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                Author and article information

                Contributors
                colleen.wegzyn@abbvie.com
                Journal
                Pediatr Pulmonol
                Pediatr. Pulmonol
                10.1002/(ISSN)1099-0496
                PPUL
                Pediatric Pulmonology
                John Wiley and Sons Inc. (Hoboken )
                8755-6863
                1099-0496
                14 October 2016
                April 2017
                : 52
                : 4 ( doiID: 10.1002/ppul.v52.4 )
                : 556-569
                Affiliations
                [ 1 ] Department of PediatricsHospital da PUCRS & Biomedical Research Institute Porto AlegreBrazil
                [ 2 ] Department of PediatricsUniversity Medical Center Utrecht UtrechtThe Netherlands
                [ 3 ] Department of Paediatrics and Child Health, Red Cross Childrens Hospital and MRC Unit on Child and Adolescent Health University of Cape Town Cape TownSouth Africa
                [ 4 ]Fundacion INFANT Buenos AiresArgentina
                [ 5 ] Department of PediatricsVanderbilt University Medical Center Nashville Tennessee
                [ 6 ]AbbVie Inc. North Chicago Illinois
                [ 7 ]Doctor Evidence, LLC Santa Monica California
                Author notes
                [*] [* ] Correspondence to: Colleen M. Wegzyn, PharmD, AbbVie Inc., 1 North Waukegan Road, North Chicago, IL 60064‐6075. E‐mail: colleen.wegzyn@ 123456abbvie.com

                Article
                PPUL23570
                10.1002/ppul.23570
                5396299
                27740723
                04a3698a-4cf0-43a0-baa1-d4183cb56371
                © 2016 The Authors. Pediatric Pulmonology Published by Wiley Periodicals, Inc.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 09 February 2016
                : 24 June 2016
                : 18 July 2016
                Page count
                Figures: 1, Tables: 3, Pages: 14, Words: 7221
                Funding
                Funded by: AbbVie Inc
                Categories
                Review
                Reviews
                International Health
                Custom metadata
                2.0
                ppul23570
                April 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.0.9 mode:remove_FC converted:19.04.2017

                Pediatrics
                epidemiology,preterm,infant,morbidity,burden
                Pediatrics
                epidemiology, preterm, infant, morbidity, burden

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