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      Respiratory Virus–Associated Severe Acute Respiratory Illness and Viral Clustering in Malawian Children in a Setting With a High Prevalence of HIV Infection, Malaria, and Malnutrition

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          Abstract

          Background

          We used data from 4 years of pediatric severe acute respiratory illness (SARI) sentinel surveillance in Blantyre, Malawi, to identify factors associated with clinical severity and coviral clustering.

          Methods

          From January 2011 to December 2014, 2363 children aged 3 months to 14 years presenting to the hospital with SARI were enrolled. Nasopharyngeal aspirates were tested for influenza virus and other respiratory viruses. We assessed risk factors for clinical severity and conducted clustering analysis to identify viral clusters in children with viral codetection.

          Results

          Hospital-attended influenza virus–positive SARI incidence was 2.0 cases per 10 000 children annually; it was highest among children aged <1 year (6.3 cases per 10 000), and human immunodeficiency virus (HIV)–infected children aged 5–9 years (6.0 cases per 10 000). A total of 605 SARI cases (26.8%) had warning signs, which were positively associated with HIV infection (adjusted risk ratio [aRR], 2.4; 95% confidence interval [CI], 1.4–3.9), respiratory syncytial virus infection (aRR, 1.9; 95% CI, 1.3–3.0) and rainy season (aRR, 2.4; 95% CI, 1.6–3.8). We identified 6 coviral clusters; 1 cluster was associated with SARI with warning signs.

          Conclusions

          Influenza vaccination may benefit young children and HIV-infected children in this setting. Viral clustering may be associated with SARI severity; its assessment should be included in routine SARI surveillance.

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          Most cited references31

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          Global, regional, and national causes of child mortality in 2000-13, with projections to inform post-2015 priorities: an updated systematic analysis.

          Trend data for causes of child death are crucial to inform priorities for improving child survival by and beyond 2015. We report child mortality by cause estimates in 2000-13, and cause-specific mortality scenarios to 2030 and 2035. We estimated the distributions of causes of child mortality separately for neonates and children aged 1-59 months. To generate cause-specific mortality fractions, we included new vital registration and verbal autopsy data. We used vital registration data in countries with adequate registration systems. We applied vital registration-based multicause models for countries with low under-5 mortality but inadequate vital registration, and updated verbal autopsy-based multicause models for high mortality countries. We used updated numbers of child deaths to derive numbers of deaths by causes. We applied two scenarios to derive cause-specific mortality in 2030 and 2035. Of the 6·3 million children who died before age 5 years in 2013, 51·8% (3·257 million) died of infectious causes and 44% (2·761 million) died in the neonatal period. The three leading causes are preterm birth complications (0·965 million [15·4%, uncertainty range (UR) 9·8-24·5]; UR 0·615-1·537 million), pneumonia (0·935 million [14·9%, 13·0-16·8]; 0·817-1·057 million), and intrapartum-related complications (0·662 million [10·5%, 6·7-16·8]; 0·421-1·054 million). Reductions in pneumonia, diarrhoea, and measles collectively were responsible for half of the 3·6 million fewer deaths recorded in 2013 versus 2000. Causes with the slowest progress were congenital, preterm, neonatal sepsis, injury, and other causes. If present trends continue, 4·4 million children younger than 5 years will still die in 2030. Furthermore, sub-Saharan Africa will have 33% of the births and 60% of the deaths in 2030, compared with 25% and 50% in 2013, respectively. Our projection results provide concrete examples of how the distribution of child causes of deaths could look in 15-20 years to inform priority setting in the post-2015 era. More evidence is needed about shifts in timing, causes, and places of under-5 deaths to inform child survival agendas by and beyond 2015, to end preventable child deaths in a generation, and to count and account for every newborn and every child. Bill & Melinda Gates Foundation. Copyright © 2015 Elsevier Ltd. All rights reserved.
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            Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis

            Summary Background The global burden of disease attributable to respiratory syncytial virus (RSV) remains unknown. We aimed to estimate the global incidence of and mortality from episodes of acute lower respiratory infection (ALRI) due to RSV in children younger than 5 years in 2005. Methods We estimated the incidence of RSV-associated ALRI in children younger than 5 years, stratified by age, using data from a systematic review of studies published between January, 1995, and June, 2009, and ten unpublished population-based studies. We estimated possible boundaries for RSV-associated ALRI mortality by combining case fatality ratios with incidence estimates from hospital-based reports from published and unpublished studies and identifying studies with population-based data for RSV seasonality and monthly ALRI mortality. Findings In 2005, an estimated 33·8 (95% CI 19·3–46·2) million new episodes of RSV-associated ALRI occurred worldwide in children younger than 5 years (22% of ALRI episodes), with at least 3·4 (2·8–4·3) million episodes representing severe RSV-associated ALRI necessitating hospital admission. We estimated that 66 000–199 000 children younger than 5 years died from RSV-associated ALRI in 2005, with 99% of these deaths occurring in developing countries. Incidence and mortality can vary substantially from year to year in any one setting. Interpretation Globally, RSV is the most common cause of childhood ALRI and a major cause of admission to hospital as a result of severe ALRI. Mortality data suggest that RSV is an important cause of death in childhood from ALRI, after pneumococcal pneumonia and Haemophilus influenzae type b. The development of novel prevention and treatment strategies should be accelerated as a priority. Funding WHO; Bill & Melinda Gates Foundation.
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              Global burden of childhood pneumonia and diarrhoea

              Summary Diarrhoea and pneumonia are the leading infectious causes of childhood morbidity and mortality. We comprehensively reviewed the epidemiology of childhood diarrhoea and pneumonia in 2010–11 to inform the planning of integrated control programmes for both illnesses. We estimated that, in 2010, there were 1·731 billion episodes of diarrhoea (36 million of which progressed to severe episodes) and 120 million episodes of pneumonia (14 million of which progressed to severe episodes) in children younger than 5 years. We estimated that, in 2011, 700 000 episodes of diarrhoea and 1·3 million of pneumonia led to death. A high proportion of deaths occurs in the first 2 years of life in both diseases—72% for diarrhoea and 81% for pneumonia. The epidemiology of childhood diarrhoea and that of pneumonia overlap, which might be partly because of shared risk factors, such as undernutrition, suboptimum breastfeeding, and zinc deficiency. Rotavirus is the most common cause of vaccine-preventable severe diarrhoea (associated with 28% of cases), and Streptococcus pneumoniae (18·3%) of vaccine-preventable severe pneumonia. Morbidity and mortality from childhood pneumonia and diarrhoea are falling, but action is needed globally and at country level to accelerate the reduction.
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                Author and article information

                Journal
                J Infect Dis
                J. Infect. Dis
                jid
                jinfdis
                The Journal of Infectious Diseases
                Oxford University Press
                0022-1899
                1537-6613
                01 December 2016
                13 September 2016
                : 214
                : 11
                : 1700-1711
                Affiliations
                [1 ] Malawi-Liverpool-Wellcome Trust
                [2 ] Department of Paediatrics, Queen Elizabeth Central Hospital , Blantyre, Malawi
                [3 ] Institute of Infection and Global Health
                [4 ] Institute of Ageing and Chronic Disease, Faculty of Health and Life Sciences, University of Liverpool
                [5 ] Liverpool School of Tropical Medicine
                [6 ] Division of Infection and Immunity, University College London , United Kingdom
                [7 ] World Bank , Hanoi, Vietnam
                [8 ] Medical Research Council–Gambia , Banjul
                [9 ] Influenza Division, Centers for Disease Control and Prevention (CDC)–South Africa , Johannesburg
                [10 ] Influenza Division, CDC, Atlanta, Georgia
                Author notes
                [a]

                D. E. and R. S. H. contributed equally to the study.

                Correspondence: D. Everett, Institute of Infection and Global Health, University of Liverpool, Liverpool, UK ( deaneve@ 123456liverpool.ac.uk ).
                Article
                jiw426
                10.1093/infdis/jiw426
                5341080
                27630199
                36d206c3-dcf3-49aa-9e77-af2d9176f688
                © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@ 123456oup.com .

                This article is made available via the PMC Open Access Subset for unrestricted re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the COVID-19 pandemic or until permissions are revoked in writing. Upon expiration of these permissions, PMC is granted a perpetual license to make this article available via PMC and Europe PMC, consistent with existing copyright protections.

                History
                : 21 June 2016
                : 2 September 2016
                Funding
                Funded by: CDC
                Award ID: 5U01CK000146-04
                Categories
                Major Articles and Brief Reports
                Viruses

                Infectious disease & Microbiology
                children,sari,africa,viral coinfection,influenza
                Infectious disease & Microbiology
                children, sari, africa, viral coinfection, influenza

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