SummaryBackgroundRespiratory syncytial virus (RSV) infection is an important cause of pneumonia mortality in young children. However, clinical data for fatal RSV infection are scarce. We aimed to identify clinical and socioeconomic characteristics of children aged younger than 5 years with RSV-related mortality using individual patient data.MethodsIn this retrospective case series, we developed an online questionnaire to obtain individual patient data for clinical and socioeconomic characteristics of children aged younger than 5 years who died with community-acquired RSV infection between Jan 1, 1995, and Oct 31, 2015, through leading research groups for child pneumonia identified through a comprehensive literature search and existing research networks. For the literature search, we searched PubMed for articles published up to Feb 3, 2015, using the key terms “RSV”, “respiratory syncytial virus”, or “respiratory syncytial viral” combined with “mortality”, “fatality”, “death”, “died”, “deaths”, or “CFR” for articles published in English. We invited researchers and clinicians identified to participate between Nov 1, 2014, and Oct 31, 2015. We calculated descriptive statistics for all variables.FindingsWe studied 358 children with RSV-related in-hospital death from 23 countries across the world, with data contributed from 31 research groups. 117 (33%) children were from low-income or lower middle-income countries, 77 (22%) were from upper middle-income countries, and 164 (46%) were from high-income countries. 190 (53%) were male. Data for comorbidities were missing for some children in low-income and middle-income countries. Available data showed that comorbidities were present in at least 33 (28%) children from low-income or lower middle-income countries, 36 (47%) from upper middle-income countries, and 114 (70%) from high-income countries. Median age for RSV-related deaths was 5·0 months (IQR 2·3–11·0) in low-income or lower middle-income countries, 4·0 years (2·0–10·0) in upper middle-income countries, and 7·0 years (3·6–16·8) in high-income countries.InterpretationThis study is the first large case series of children who died with community-acquired RSV infection. A substantial proportion of children with RSV-related death had comorbidities. Our results show that perinatal immunisation strategies for children aged younger than 6 months could have a substantial impact on RSV-related child mortality in low-income and middle-income countries.FundingBill & Melinda Gates Foundation.
Please cite this paper as: Goka et al. (2013) Influenza A viruses dual and multiple infections with other respiratory viruses and risk of hospitalisation and mortality. Influenza and Other Respiratory Viruses 7(6), 1079–1087. Introduction Recent literature suggests that dual or multiple virus infections may affect disease severity. However, few studies have investigated the effect of co‐infection with influenza A viruses. Objectives To identify the association between influenza A and respiratory viruses co‐infections with disease outcome. Methodology Data for samples from North West England tested between January 2007 and June 2011 was analysed for patterns of co‐infection between influenza A viruses and eight respiratory viruses. Risk of hospitalisation to ICU or general ward in single versus co‐infections was assessed using logistic regression. Results Of the 25 596 samples analysed for respiratory viruses 40·7% (10 501) were positive for any virus. Co‐infections were detected in 4·7% (137/2879) of all patients with influenza A(H1N1)pdm09, and 7·3% (57/779) of those with other influenza A virus infections. Co‐infection between seasonal influenza A viruses and influenza B virus was associated with a significant increase in the risk of admission to ICU/death (OR: 22·0, 95% CI: 2·21–219·8, P = 0·008). Respiratory syncytial virus/influenza A (RSV/Flu A) co‐infection also increased this risk but was not statistically significant. For influenza A(H1N1)pdm09, RSV and AdV co‐infection increased risk of hospitalisation to general ward whereas Flu B increased risk of admission to ICU, but none of these were statistically significant. Conclusion Co‐infection is a significant predictor of disease outcome; combined treatment, introduction of an integrated vaccine for all respiratory viruses and development of multi‐target rapid diagnostic tests is recommended. Integration of respiratory viruses’ co‐infections into public health reports could also contribute to the accumulation of evidence.
Respiratory virus infections cause a significant number of hospitalization and deaths globally. This study investigated the association between single and multiple respiratory virus infections and risk of admission to a general ward, intensive care unit or death in patients aged 0-105 years (mean ± s.d. = 24·4 ± 24·1 years), from North West England, that were tested for respiratory virus infections between January 2007 and June 2012. The majority of infections were in children aged ⩽5 years. Dual or multiple infections occurred in 10·4% (1214/11 715) of patients, whereas single infection occurred in 89·6% (10 501/11 715). Rhinovirus was the most common co-infecting virus (occurring in 69·5%; 844/1214 of co-infections). In a multivariate logistic regression model, multiple infections were associated with an increased risk of admission to a general ward [odds ratio (OR) 1·43, 95% confidence interval (CI) 1·2-1·7, P < 0·0001]. On the other hand, patients with respiratory syncytial virus (RSV) and human parainfluenza virus types 1-3 (hPIV1-3), as a single infection, had a higher risk of being admitted to a general ward (OR 1·49, 95% CI 1·28-1·73, P < 0·0001 and OR 1·34, 95% CI 1·003-1·8, P = 0·05, respectively); admitted to an intensive-care unit or dying (OR 1·5, 95% CI 1·20-2·0, P = 0·001 and OR 1·60, 95% CI 1·02-2·40, P = 0·04, respectively). This result emphasizes the importance of RSV, hPIV and mixed infections and calls for research on vaccines, drugs and diagnostic tests targeting these respiratory viruses.
The influence of co-infections on severe viral respiratory disease is still unclear. The observed conflict in outcomes could be because they were conducted in different seasons and covered different years and periods. It could also be due to bias towards the null, especially in studies where only crude analysis was conducted. Future studies should employ stratified analysis.
The National Institute for Health Research Health Technology Assessment programme.
Mutations in the haemagglutinin (HA), non-structural protein 1 (NS1) and polymerase basic protein 2 (PB2) of influenza viruses have been associated with virulence. This study investigated the association between mutations in these genes in influenza A(H1N1)pdm09 virus and the risk of severe or fatal disease. Searches were conducted on the MEDLINE, EMBASE and Web of Science electronic databases and the reference lists of published studies. The PRISMA and STROBE guidelines were followed in assessing the quality of studies and writing-up. Eighteen (18) studies, from all continents, were included in the systematic review (recruiting patients 0 - 77 years old). The mutation D222G was associated with a significant increase in severe disease (pooled RD: 11 %, 95 % CI: 3.0 % - 18.0 %, p = 0.004) and the risk of fatality (RD: 23 %, 95 % CI: 14.0 %-31.0 %, p = < 0.0001). No association was observed between the mutations HA-D222N, D222E, PB2-E627K and NS1-T123V and severe/fatal disease. The results suggest that no virus quasispecies bearing virulence-conferring mutations in the HA, PB2 and NS1 predominated. However issues of sampling bias, and bias due to uncontrolled confounders such as comorbidities, and viral and bacterial coinfection, should be born in mind. Influenza A viruses should continue to be monitored for the occurrence of virulence-conferring mutations in HA, PB2 and NS1. There are suggestions that respiratory virus coinfections also affect virus virulence. Studies investigating the role of genetic mutations on disease outcome should make efforts to also investigate the role of respiratory virus coinfections.
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