Aetiological role of common respiratory viruses in acute lower respiratory infections in children under five years: A systematic review and meta–analysis

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Abstract

Background

Acute lower respiratory infection (ALRI) remains a major cause of childhood hospitalization and mortality in young children and the causal attribution of respiratory viruses in the aetiology of ALRI is unclear. We aimed to quantify the absolute effects of these viral exposures.

Methods

We conducted a systematic literature review (across 7 databases) of case–control studies published from 1990 to 2014 which investigated the viral profile of 18592 children under 5 years with and without ALRI. We then computed a pooled odds ratio and virus–specific attributable fraction among the exposed of 8 common viruses – respiratory syncytial virus (RSV), influenza (IFV), parainfluenza (PIV), human metapneumovirus (MPV), adenovirus (AdV), rhinovirus (RV), bocavirus (BoV), and coronavirus (CoV).

Findings

From the 23 studies included, there was strong evidence for causal attribution of RSV (OR 9.79; AFE 90%), IFV (OR 5.10; AFE 80%), PIV (OR 3.37; AFE 70%) and MPV (OR 3.76; AFE 73%), and less strong evidence for RV (OR 1.43; AFE 30%) in young children presenting with ALRI compared to those without respiratory symptoms (asymptomatic) or healthy children. However, there was no significant difference in the detection of AdV, BoV, or CoV in cases and controls.

Conclusions

This review supports RSV, IFV, PIV, MPV and RV as important causes of ALRI in young children, and provides quantitative estimates of the absolute proportion of virus–associated ALRI cases to which a viral cause can be attributed.

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Most cited references 45

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Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis

Harish Nair, Eric AF Simões, Igor Rudan … (2013)

Summary Background The annual number of hospital admissions and in-hospital deaths due to severe acute lower respiratory infections (ALRI) in young children worldwide is unknown. We aimed to estimate the incidence of admissions and deaths for such infections in children younger than 5 years in 2010. Methods We estimated the incidence of admissions for severe and very severe ALRI in children younger than 5 years, stratified by age and region, with data from a systematic review of studies published between Jan 1, 1990, and March 31, 2012, and from 28 unpublished population-based studies. We applied these incidence estimates to population estimates for 2010, to calculate the global and regional burden in children admitted with severe ALRI in that year. We estimated in-hospital mortality due to severe and very severe ALRI by combining incidence estimates with case fatality ratios from hospital-based studies. Findings We identified 89 eligible studies and estimated that in 2010, 11·9 million (95% CI 10·3–13·9 million) episodes of severe and 3·0 million (2·1–4·2 million) episodes of very severe ALRI resulted in hospital admissions in young children worldwide. Incidence was higher in boys than in girls, the sex disparity being greatest in South Asian studies. On the basis of data from 37 hospital studies reporting case fatality ratios for severe ALRI, we estimated that roughly 265 000 (95% CI 160 000–450 000) in-hospital deaths took place in young children, with 99% of these deaths in developing countries. Therefore, the data suggest that although 62% of children with severe ALRI are treated in hospitals, 81% of deaths happen outside hospitals. Interpretation Severe ALRI is a substantial burden on health services worldwide and a major cause of hospital referral and admission in young children. Improved hospital access and reduced inequities, such as those related to sex and rural status, could substantially decrease mortality related to such infection. Community-based management of severe disease could be an important complementary strategy to reduce pneumonia mortality and health inequities. Funding WHO.

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Epidemiology and etiology of childhood pneumonia.

Igor Rudan, Cynthia Boschi-Pinto, Zrinka Biloglav … (2008)

Childhood pneumonia is the leading single cause of mortality in children aged less than 5 years. The incidence in this age group is estimated to be 0.29 episodes per child-year in developing and 0.05 episodes per child-year in developed countries. This translates into about 156 million new episodes each year worldwide, of which 151 million episodes are in the developing world. Most cases occur in India (43 million), China (21 million) and Pakistan (10 million), with additional high numbers in Bangladesh, Indonesia and Nigeria (6 million each). Of all community cases, 7-13% are severe enough to be life-threatening and require hospitalization. Substantial evidence revealed that the leading risk factors contributing to pneumonia incidence are lack of exclusive breastfeeding, undernutrition, indoor air pollution, low birth weight, crowding and lack of measles immunization. Pneumonia is responsible for about 19% of all deaths in children aged less than 5 years, of which more than 70% take place in sub-Saharan Africa and south-east Asia. Although based on limited available evidence, recent studies have identified Streptococcus pneumoniae, Haemophilus influenzae and respiratory syncytial virus as the main pathogens associated with childhood pneumonia.

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Viral pneumonia.

David R. Murdoch, Olli Ruuskanen, Nicole Jennings … (2011)

About 200 million cases of viral community-acquired pneumonia occur every year-100 million in children and 100 million in adults. Molecular diagnostic tests have greatly increased our understanding of the role of viruses in pneumonia, and findings indicate that the incidence of viral pneumonia has been underestimated. In children, respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses are the agents identified most frequently in both developed and developing countries. Dual viral infections are common, and a third of children have evidence of viral-bacterial co-infection. In adults, viruses are the putative causative agents in a third of cases of community-acquired pneumonia, in particular influenza viruses, rhinoviruses, and coronaviruses. Bacteria continue to have a predominant role in adults with pneumonia. Presence of viral epidemics in the community, patient's age, speed of onset of illness, symptoms, biomarkers, radiographic changes, and response to treatment can help differentiate viral from bacterial pneumonia. However, no clinical algorithm exists that will distinguish clearly the cause of pneumonia. No clear consensus has been reached about whether patients with obvious viral community-acquired pneumonia need to be treated with antibiotics. Apart from neuraminidase inhibitors for pneumonia caused by influenza viruses, there is no clear role for use of specific antivirals to treat viral community-acquired pneumonia. Influenza vaccines are the only available specific preventive measures. Further studies are needed to better understand the cause and pathogenesis of community-acquired pneumonia. Furthermore, regional differences in cause of pneumonia should be investigated, in particular to obtain more data from developing countries. Copyright © 2011 Elsevier Ltd. All rights reserved.

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Author and article information

Journal

Journal ID (nlm-ta): J Glob Health

Journal ID (iso-abbrev): J Glob Health

Journal ID (publisher-id): JGH

Title: Journal of Global Health

Publisher: Edinburgh University Global Health Society

ISSN (Print): 2047-2978

ISSN (Electronic): 2047-2986

Publication date (Print, pub): June 2015

Publication date (Electronic, pub): 17 June 2015

Volume: 5

Issue: 1

Electronic Location Identifier: 010408

Affiliations

[1 ]Centre for Global Health Research, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, UK

[2 ]Centre for Population Health Sciences, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, UK

[3 ]Centre for Medical Informatics, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, Scotland, UK

[4 ]Public Health Foundation of India, New Delhi, India

[* ]Joint authors in this position.

[† ]Joint authors in this position.

Author notes

Correspondence to: Dr. Harish Nair Centre for Global Health Research Usher Institute of Population Health Sciences and Informatics University of Edinburgh Medical School, Teviot Place, Edinburgh EH8 9AG, UK  Harish.Nair@ 123456ed.ac.uk

Article

Publisher ID: jogh-05-010408

DOI: 10.7189/jogh.05.010408

PMC ID: 4593292

PubMed ID: 26445672

SO-VID: ae1dfd36-03f8-4118-9c73-8fb28d20dc36

License:

This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Aetiological role of common respiratory viruses in acute lower respiratory infections in children under five years: A systematic review and meta–analysis

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Abstract

Background

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European Respiratory Society: COVID-19

Most cited references 45

Global and regional burden of hospital admissions for severe acute lower respiratory infections in young children in 2010: a systematic analysis

Epidemiology and etiology of childhood pneumonia.

Viral pneumonia.

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