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      Risk Factors for Mortality from Acute Lower Respiratory Infections (ALRI) in Children under Five Years of Age in Low and Middle-Income Countries: A Systematic Review and Meta-Analysis of Observational Studies

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          Abstract

          Objective

          To evaluate risk factors for death from acute lower respiratory infections (ALRI) in children in low- and middle-income countries.

          Design

          Systematic review and meta-analysis.

          Study selection

          Observational studies reporting on risk factors for death from ALRI in children below five years in low- and middle income countries.

          Data sources

          Medline, Embase, Global Health Library, Lilacs, and Web of Science to January 2014

          Risk of bias assessment

          Quality In Prognosis Studies tool with minor adaptations to assess the risk of bias; funnel plots and Egger's test to evaluate publication bias.

          Results

          Out of 10655 papers retrieved, 77 studies from 39 countries (198359 children) met the inclusion criteria. Host and disease characteristics more strongly associated with ALRI mortality were: diagnosis of very severe pneumonia as per WHO definition (odds ratio 9.42, 95% confidence interval 6.37‒13.92); age below two months (5.22, 1.70‒16.03); diagnosis of Pneumocystis Carinii (4.79, 2.67 ‒ 8.61), chronic underlying diseases (4.76, 3.27‒ 6.93); HIV/AIDS (4.68, 3.72‒5.90); and severe malnutrition (OR 4.27, 3.47‒5.25). Socio-economic and environmental factors significantly associated with increased odds of death from ALRI were: young maternal age (1.84, 1.03‒3.31); low maternal education (1.43, 1.13‒1.82); low socio-economic status (1.62, 1.32‒2.00); second-hand smoke exposure (1.52, 1.20 to 1.93); indoor air pollution (3.02, 2.11‒4.31). Immunisation (0.46, 0.36‒0.58) and good antenatal practices (0.50, 0.31‒0.81) were associated with decreased odds of death.

          Conclusions

          Host and disease characteristics as well as socio-economic and environmental determinants affect the risk of death from ALRI in children. Together with the prevention and treatment of chronic diseases, interventions to modify underlying risk factors such as poverty, lack of female education, and poor environmental conditions, should be considered among the strategies to reduce ALRI mortality in children in low- and middle-income countries.

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          Most cited references15

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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

          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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            Indoor air pollution from unprocessed solid fuel use and pneumonia risk in children aged under five years: a systematic review and meta-analysis.

            Reduction of indoor air pollution (IAP) exposure from solid fuel use is a potentially important intervention for childhood pneumonia prevention. This review updates a prior meta-analysis and investigates whether risk varies by etiological agent and pneumonia severity among children aged less than 5 years who are exposed to unprocessed solid fuels. Searches were made of electronic databases (including Africa, China and Latin America) without language restriction. Search terms covered all sources of IAP and wide-ranging descriptions of acute lower respiratory infections, including viral and bacterial agents. From 5317 studies in the main electronic databases (plus 307 African and Latin American, and 588 Chinese studies, in separate databases), 25 were included in the review and 24 were suitable for meta-analysis. Due to substantial statistical heterogeneity, random effects models were used. The overall pooled odds ratio was 1.78 (95% confidence interval, CI: 1.45-2.18), almost unchanged at 1.79 (95% CI: 1.26-2.21) after exclusion of studies with low exposure prevalence (< 15%) and one high outlier. There was evidence of publication bias, and the implications for the results are explored. Sensitivity subanalyses assessed the impact of control selection, adjustment for confounding, exposure and outcome assessment, and age, but no strong effects were identified. Evidence on respiratory syncytial virus was conflicting, while risk for severe or fatal pneumonia was similar to or higher than that for all pneumonia. Despite heterogeneity, this analysis demonstrated sufficient consistency to conclude that risk of pneumonia in young children is increased by exposure to unprocessed solid fuels by a factor of 1.8. Greater efforts are now required to implement effective interventions.
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              Malnutrition as an underlying cause of childhood deaths associated with infectious diseases in developing countries.

              Recent estimates suggest that malnutrition (measured as poor anthropometric status) is associated with about 50% of all deaths among children. Although the association between malnutrition and all-cause mortality is well documented, the malnutrition-related risk of death associated with specific diseases is less well described. We reviewed published literature to examine the evidence for a relation between malnutrition and child mortality from diarrhoea, acute respiratory illness, malaria and measles, conditions that account for over 50% of deaths in children worldwide. MEDLINE was searched for suitable review articles and original reports of community-based and hospital-based studies. Findings from cohort studies and case-control studies were reviewed and summarized. The strongest and most consistent relation between malnutrition and an increased risk of death was observed for diarrhoea and acute respiratory infection. The evidence, although limited, also suggests a potentially increased risk for death from malaria. A less consistent association was observed between nutritional status and death from measles. Although some hospital-based studies and case-control studies reported an increased risk of mortality from measles, few community-based studies reported any association. The risk of malnutrition-related mortality seems to vary for different diseases. These findings have important implications for the evaluation of nutritional intervention programmes and child survival programmes being implemented in settings with different disease profiles.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2015
                30 January 2015
                : 10
                : 1
                : e0116380
                Affiliations
                [1 ]WHO Collaborating Centre for Maternal and Child Health, Institute for Maternal and Child Health IRCCS Burlo Garofolo, Trieste, Italy
                [2 ]Department of Medicine, Surgery, and Health Science, University of Trieste, Trieste, Italy
                INDEPTH Network, GHANA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: ML MS. Performed the experiments: MS ML MCP GB. Analyzed the data: MS. Contributed reagents/materials/analysis tools: ML MS. Wrote the paper: MS ML. Interpreted the data: MS ML MCP GB. Critically revised the manuscript for important intellectual content: MS ML MCP GB. Approved the final version: MS ML MCP GB.

                Article
                PONE-D-14-34112
                10.1371/journal.pone.0116380
                4312071
                25635911
                cb98af93-ce62-4a14-9321-f18f3fa03d0e
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 30 July 2014
                : 6 December 2014
                Page count
                Figures: 6, Tables: 1, Pages: 17
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper and its Supporting Information files. Data for this systematic review were extracted from published papers.

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