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The Lancet. Respiratory Medicine Aug 2020Although a positive association has been established, it is unclear whether lower respiratory tract infections (LRTIs) with respiratory syncytial virus (RSV) cause... (Meta-Analysis)
Meta-Analysis
Assessing the strength of evidence for a causal effect of respiratory syncytial virus lower respiratory tract infections on subsequent wheezing illness: a systematic review and meta-analysis.
BACKGROUND
Although a positive association has been established, it is unclear whether lower respiratory tract infections (LRTIs) with respiratory syncytial virus (RSV) cause chronic wheezing illnesses. If RSV-LRTI were causal, we would expect RSV-LRTI prevention to reduce the incidence of chronic wheezing illnesses in addition to reducing acute disease. We aimed to evaluate the strength of evidence for a causal effect of RSV-LRTI on subsequent chronic wheezing illness to inform public health expectations for RSV vaccines.
METHODS
We did a systematic review and meta-analysis of observational studies evaluating the association between RSV-LRTI and subsequent wheezing illness (exposure studies) and studies evaluating the association between RSV immunoprophylaxis and subsequent wheezing illness (immunoprophylaxis studies). Exposure studies were included if the exposure group members had an LRTI with laboratory-confirmed RSV and if the exposure ascertainment period began before 2 years of age and ended before 5 years of age. We required a wash-out period of more than 30 days between the index RSV-LRTI and the outcome measurement to allow for resolution of the acute illness. Comparisons between RSV-LRTI and non-RSV-LRTI were not included. Immunoprophylaxis studies were included if they measured the association with subsequent wheezing illness relative to a control group, either in a randomised controlled trial (RCT) or an observational design. For the immunoprophylaxis drugs in question, we required evidence of efficacy in targeting RSV-LRTI from at least one RCT to ensure biological plausibility. All variations of wheezing illness were combined into a single outcome that refers broadly to asthma or any other respiratory illness with wheezing symptoms. Ovid MEDLINE and Embase databases were searched from inception up to Aug 28, 2018. We evaluated whether data from exposure studies could provide evidence against the most viable non-causal theory that RSV-LRTI is a marker of respiratory illness susceptibility rather than a causal factor. Additionally, we tested whether RSV immunoprophylaxis reduces the odds of subsequent wheezing illnesses. We used a random-effects modelling framework and, to accommodate studies providing multiple correlated estimates, robust variance estimation meta-regressions. Meta-regression coefficients (b) quantify differences between exposure and comparator groups on the log odds ratio (log OR) scale.
FINDINGS
From 14 235 records we identified 57 eligible articles that described 42 studies and provided 153 effect estimates. 35 studies estimated the direct effect of RSV-LRTI on wheezing illnesses (exposure studies) and eight evaluated the effect of RSV immunoprophylaxis (immunoprophylaxis studies). Exposure studies that adjusted for genetic influences yielded a smaller mean adjusted OR estimate (aOR 2·45, 95% CI 1·23-4·88) compared with those that did not (4·17, 2·36-7·37), a significant difference (b 0·53, 95% CI 0·04-1·02). Infants who were not protected with RSV immunoprophylaxis tended to have higher odds of subsequent wheezing illness, as we would expect if RSV-LRTI were causal, but the effect was not significant (OR 1·21, 95% CI 0·73-1·99). There was generally a high threat of confounding bias in the observational studies. Additionally, in both the observational studies and immunoprophylaxis RCTs, there was high risk of bias due to missing outcome data.
INTERPRETATION
Our findings, limited to exposure and immunoprophylaxis studies, do not support basing policy decisions on an assumption that prevention of RSV-LRTI will reduce recurrent chronic wheezing illnesses.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Antiviral Agents; Humans; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections
PubMed: 32763206
DOI: 10.1016/S2213-2600(20)30109-0 -
Journal of Clinical Virology : the... Aug 2020Respiratory syncytial virus (RSV) immunoprophylaxis (IP) has been shown to reduce RSV hospitalization rates in high-risk infants; however, it is unclear whether RSV IP...
Respiratory syncytial virus (RSV) immunoprophylaxis (IP) has been shown to reduce RSV hospitalization rates in high-risk infants; however, it is unclear whether RSV IP is associated with increased risk of non-RSV disease, particularly non-RSV hospitalizations. We conducted a systematic literature review to understand the occurrences of non-RSV disease and/or non-RSV hospitalizations in published studies of RSV IP. Cochrane, Embase, and PubMed databases were searched and reviewed to summarize data regarding the incidence of RSV and non-RSV respiratory disease among RSV IP recipients and controls in randomized and non-randomized studies. Independent investigators screened and selected studies for inclusion. Risk-of-bias assessment was conducted to assess strength/validity of the data using the Jadad scoring system and Downs and Black quality assessment tool, where appropriate. Twenty studies were included for review (5 randomized controlled trials [RCTs]; 15 non-randomized studies). RCTs of RSV IP demonstrated reductions in RSV hospitalizations and all-cause hospitalizations, with no increase in hospitalizations for non-RSV disease. Non-randomized studies also demonstrated reduced RSV hospitalizations in RSV IP recipients but had mixed results in assessments of hospitalizations for non-RSV disease. When RSV IP recipients and controls were more similar in disease severity risk, results of non-randomized studies aligned more closely with RCTs. Observations of increased non-RSV hospitalization rates among RSV IP recipients in some non-randomized studies could be primarily explained by differences in the clinical characteristics between RSV IP recipients and controls.
Topics: Databases, Factual; Hospitalization; Humans; Incidence; Infant; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 32512375
DOI: 10.1016/j.jcv.2020.104339 -
The Journal of Infectious Diseases Oct 2020Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection (ALRI) in young children aged <5 years. (Meta-Analysis)
Meta-Analysis
Cost of Respiratory Syncytial Virus-Associated Acute Lower Respiratory Infection Management in Young Children at the Regional and Global Level: A Systematic Review and Meta-Analysis.
BACKGROUND
Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection (ALRI) in young children aged <5 years.
METHODS
We aimed to identify the global inpatient and outpatient cost of management of RSV-ALRI in young children to assist health policy makers in making decisions related to resource allocation for interventions to reduce severe morbidity and mortality from RSV in this age group. We searched 3 electronic databases including Global Health, Medline, and EMBASE for studies reporting cost data on RSV management in children under 60 months from 2000 to 2017. Unpublished data on the management cost of RSV episodes were collected through collaboration with an international working group (RSV GEN) and claim databases.
RESULTS
We identified 41 studies reporting data from year 1987 to 2017, mainly from Europe, North America, and Australia, covering the management of a total of 365 828 RSV disease episodes. The average cost per episode was €3452 (95% confidence interval [CI], 3265-3639) and €299 (95% CI, 295-303) for inpatient and outpatient management without follow-up, and it increased to €8591(95% CI, 8489-8692) and €2191 (95% CI, 2190-2192), respectively, with follow-up to 2 years after the initial event.
CONCLUSIONS
Known risk factors (early and late preterm birth, congenital heart disease, chronic lung disease, intensive care unit admission, and ventilator use) were associated with €4160 (95% CI, 3237-5082) increased cost of hospitalization. The global cost of inpatient and outpatient RSV ALRI management in young children in 2017 was estimated to be approximately €4.82 billion (95% CI, 3.47-7.93), 65% of these in developing countries and 55% of global costs accounted for by hospitalization. We have demonstrated that RSV imposed a substantial economic burden on health systems, governments, and the society.
Topics: Child; Cost of Illness; Databases, Factual; Global Health; Health Policy; Heart Diseases; Hospitalization; Humans; Intensive Care Units; Lung Diseases; Morbidity; Premature Birth; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Risk Factors
PubMed: 32227101
DOI: 10.1093/infdis/jiz683 -
PloS One 2020Data on the variation in the medical resource utilization rate of Human Respiratory Syncytial Virus (HRSV) infected children by gestational age have recently been made... (Comparative Study)
Comparative Study Meta-Analysis
Comparison of health care resource utilization among preterm and term infants hospitalized with Human Respiratory Syncytial Virus infections: A systematic review and meta-analysis of retrospective cohort studies.
INTRODUCTION
Data on the variation in the medical resource utilization rate of Human Respiratory Syncytial Virus (HRSV) infected children by gestational age have recently been made available. This review aimed to determine whether prematurity is independently associated with the use of medical resources in hospitalized children for HRSV infections.
METHODS
We conducted this systematic review on cohort studies published on the medical resources use in preterm and full-term patients hospitalized for confirmed HRSV infections. We searched PubMed, Embase, and Global Index medicus for eligible studies. The standardized mean difference (SMD) and Risk Ratio (RR) with their 95% confidence intervals (95% CI) were estimated as summary statistics with random effects meta-analysis. The overall results were adjusted to the common confounders by stratified analyses.
RESULTS
A total of 14 articles (20 studies) were included. Compared to full-term, preterm hospitalized with HRSV infections had more frequent intensive care unit admission (RR = 2.6, 95% CI = 1.9-3.5), increased length of stay in hospital (SMD = 0.6, 95% CI = 0.5-0.8) and intensive care unit (SMD = 0.6, 95% CI = 0.4-0.8) and increased case fatality rate (RR = 6.9, 95% CI = 2.0-23.8). Mechanical ventilation utilization was more frequent in preterm children ≤ 2 years (RR = 15.5, 95% CI = 8.9-26.4) and those who did not receive prophylaxis against HRSV (RR = 15.9, 95% CI = 9.1-27.9)] than in full-term children. No differences were identified in the frequency of emergency department visits, oxygen utilization, and the age at the first HRSV episode between preterm and full-term infants.
CONCLUSIONS
Regardless of gestational age, preterm infants hospitalized for HRSV infections, especially those ≤ 2 years, have an increased frequency of use of health resources and poor outcomes compared to full-term infants. HRSV vaccine development programs for pregnant women should be accelerated.
CLINICAL TRIALS REGISTRATION
Review registration PROSPERO, CRD42019124375.
Topics: Child Health Services; Delivery of Health Care; Gestational Age; Hospitalization; Humans; Infant; Infant, Premature; Infant, Premature, Diseases; Patient Acceptance of Health Care; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Retrospective Studies
PubMed: 32084214
DOI: 10.1371/journal.pone.0229357 -
Frontiers in Immunology 2019Due to their overall immunocompromised state, lung transplant recipients (LTRs) are at increased risk for the development of viral respiratory infections compared to the...
Due to their overall immunocompromised state, lung transplant recipients (LTRs) are at increased risk for the development of viral respiratory infections compared to the general population. Such respiratory infections often lead to poor transplant outcomes. We performed a systematic review of the last 30 years of medical literature to summarize the impact of specific respiratory viruses on LTRs. After screening 2,150 articles for potential inclusion, 39 manuscripts were chosen for final review. We found evidence for an association of respiratory viruses including respiratory syncytial virus (RSV), parainfluenza virus, and influenza viruses with increased morbidity following transplant. Through the literature search, we also documented associations of RSV and adenovirus infections with increased mortality among LTRs. We posit that the medical literature supports aggressive surveillance for respiratory viruses among this population.
Topics: Humans; Immunocompromised Host; Lung Transplantation; Orthomyxoviridae; Paramyxoviridae; Respiratory Syncytial Virus, Human; Respiratory Tract Infections
PubMed: 31921130
DOI: 10.3389/fimmu.2019.02861 -
Journal of Global Health Dec 2019Respiratory syncytial virus (RSV) is the leading cause of viral pneumonia and bronchiolitis, especially in younger children. The burden of RSV infection in adults,... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Respiratory syncytial virus (RSV) is the leading cause of viral pneumonia and bronchiolitis, especially in younger children. The burden of RSV infection in adults, particularly in the older age group, is increasingly recognised. However, RSV disease burden and molecular epidemiology in the World Health Organization (WHO) Western Pacific Region (WPR) has not been reviewed systematically. The aim of this systematic review is to investigate the epidemiological aspects of RSV (incidence, prevalence, seasonality and hospitalisation status) and the associated molecular data in the WPRO countries.
METHODS
A systematic search was conducted in international literature databases (MEDLINE, EMBASE, Scopus and Web of Science) to identify RSV-related publications from January 2000 to October 2017 in the WPR countries.
RESULTS
A total of 196 studies from 15 WPR countries were included. The positivity rate for RSV among respiratory tract infection patients was 16.73% (95% confidence interval (CI) = 15.12%-18.4%). The RSV-positive cases were mostly found in hospitalised compared with outpatients (18.28% vs 11.54%, < 0.001), and children compared with adults (20.72% vs 1.87%, < 0.001). The seasonality of RSV in the WPR countries follows the latitude, with the peak of RSV season occurring in the winter in temperate countries, and during the rainy season in tropical countries. The molecular epidemiology pattern of RSV in WPR countries was similar to the global pattern, with NA1 (RSV A) and BA (RSV B) being the predominant genotypes.
CONCLUSIONS
The available data on RSV are limited in several countries within the WPR, with most data focusing on children and hospitalised patients. Further studies and surveillance, incorporating laboratory testing, are needed to determine the burden of RSV infection in the WPR countries.
Topics: Hospitalization; Humans; Incidence; Pacific Islands; Prevalence; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Seasons
PubMed: 31893034
DOI: 10.7189/jogh.09.020431 -
International Journal of Infectious... Jan 2020The present study provides a comprehensive review of the recently published data on RSV epidemiology in adults and the elderly in Latin America. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The present study provides a comprehensive review of the recently published data on RSV epidemiology in adults and the elderly in Latin America.
METHODS
A systematic literature search was carried out in Medline, Scielo, Lilacs, and Cochrane Library. The search strategy aimed at retrieving studies focusing on RSV prevalence, burden, risk factors, and the routine clinical practice in the prevention and management of RSV infections in Latin American countries. Only articles published between January 2011 and December 2017 were considered.
RESULTS
Eighteen studies were included. Percentages of RSV detection varied highly across included studies for adult subjects with respiratory infections (0% to 77.9%), influenza-like illness (1.0% to 16.4%) and community-acquired pneumonia (1.3% to 13.5%). Considerable percentages of hospitalization were reported for RSV-infected adults with influenza-like illness (40.9% and 69.9%) and community-acquired pneumonia (91.7%).
CONCLUSIONS
Recent RSV data regarding adult populations in Latin America are scarce. RSV was documented as a cause of illness in adults and the elderly, being identified in patients with acute respiratory infections, influenza-like illness and community-acquired pneumonia. The studies suggest that RSV infections may be a significant cause of hospitalization in adult populations in Latin America, including younger adults.
Topics: Adult; Aged; Aged, 80 and over; Community-Acquired Infections; Female; Hospitalization; Humans; Latin America; Male; Middle Aged; Prevalence; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Risk Factors; Young Adult
PubMed: 31669592
DOI: 10.1016/j.ijid.2019.10.025 -
The Lancet. Global Health Aug 2019Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in...
BACKGROUND
Influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus are the most common viruses associated with acute lower respiratory infections in young children (<5 years) and older people (≥65 years). A global report of the monthly activity of these viruses is needed to inform public health strategies and programmes for their control.
METHODS
In this systematic analysis, we compiled data from a systematic literature review of studies published between Jan 1, 2000, and Dec 31, 2017; online datasets; and unpublished research data. Studies were eligible for inclusion if they reported laboratory-confirmed incidence data of human infection of influenza virus, respiratory syncytial virus, parainfluenza virus, or metapneumovirus, or a combination of these, for at least 12 consecutive months (or 52 weeks equivalent); stable testing practice throughout all years reported; virus results among residents in well-defined geographical locations; and aggregated virus results at least on a monthly basis. Data were extracted through a three-stage process, from which we calculated monthly annual average percentage (AAP) as the relative strength of virus activity. We defined duration of epidemics as the minimum number of months to account for 75% of annual positive samples, with each component month defined as an epidemic month. Furthermore, we modelled monthly AAP of influenza virus and respiratory syncytial virus using site-specific temperature and relative humidity for the prediction of local average epidemic months. We also predicted global epidemic months of influenza virus and respiratory syncytial virus on a 5° by 5° grid. The systematic review in this study is registered with PROSPERO, number CRD42018091628.
FINDINGS
We initally identified 37 335 eligible studies. Of 21 065 studies remaining after exclusion of duplicates, 1081 full-text articles were assessed for eligibility, of which 185 were identified as eligible. We included 246 sites for influenza virus, 183 sites for respiratory syncytial virus, 83 sites for parainfluenza virus, and 65 sites for metapneumovirus. Influenza virus had clear seasonal epidemics in winter months in most temperate sites but timing of epidemics was more variable and less seasonal with decreasing distance from the equator. Unlike influenza virus, respiratory syncytial virus had clear seasonal epidemics in both temperate and tropical regions, starting in late summer months in the tropics of each hemisphere, reaching most temperate sites in winter months. In most temperate sites, influenza virus epidemics occurred later than respiratory syncytial virus (by 0·3 months [95% CI -0·3 to 0·9]) while no clear temporal order was observed in the tropics. Parainfluenza virus epidemics were found mostly in spring and early summer months in each hemisphere. Metapneumovirus epidemics occurred in late winter and spring in most temperate sites but the timing of epidemics was more diverse in the tropics. Influenza virus epidemics had shorter duration (3·8 months [3·6 to 4·0]) in temperate sites and longer duration (5·2 months [4·9 to 5·5]) in the tropics. Duration of epidemics was similar across all sites for respiratory syncytial virus (4·6 months [4·3 to 4·8]), as it was for metapneumovirus (4·8 months [4·4 to 5·1]). By comparison, parainfluenza virus had longer duration of epidemics (6·3 months [6·0 to 6·7]). Our model had good predictability in the average epidemic months of influenza virus in temperate regions and respiratory syncytial virus in both temperate and tropical regions. Through leave-one-out cross validation, the overall prediction error in the onset of epidemics was within 1 month (influenza virus -0·2 months [-0·6 to 0·1]; respiratory syncytial virus 0·1 months [-0·2 to 0·4]).
INTERPRETATION
This study is the first to provide global representations of month-by-month activity of influenza virus, respiratory syncytial virus, parainfluenza virus, and metapneumovirus. Our model is helpful in predicting the local onset month of influenza virus and respiratory syncytial virus epidemics. The seasonality information has important implications for health services planning, the timing of respiratory syncytial virus passive prophylaxis, and the strategy of influenza virus and future respiratory syncytial virus vaccination.
FUNDING
European Union Innovative Medicines Initiative Respiratory Syncytial Virus Consortium in Europe (RESCEU).
Topics: Female; Global Health; Humans; Influenza A virus; Influenza, Human; Male; Metapneumovirus; Paramyxoviridae Infections; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 31303294
DOI: 10.1016/S2214-109X(19)30264-5 -
The Journal of Infectious Diseases Oct 2020Respiratory syncytial virus-associated acute respiratory infection (RSV-ARI) constitutes a substantial disease burden in older adults aged ≥65 years. We aimed to... (Meta-Analysis)
Meta-Analysis
Respiratory syncytial virus-associated acute respiratory infection (RSV-ARI) constitutes a substantial disease burden in older adults aged ≥65 years. We aimed to identify all studies worldwide investigating the disease burden of RSV-ARI in this population. We estimated the community incidence, hospitalization rate, and in-hospital case-fatality ratio (hCFR) of RSV-ARI in older adults, stratified by industrialized and developing regions, using data from a systematic review of studies published between January 1996 and April 2018 and 8 unpublished population-based studies. We applied these rate estimates to population estimates for 2015 to calculate the global and regional burdens in older adults with RSV-ARI in the community and in hospitals for that year. We estimated the number of in-hospital deaths due to RSV-ARI by combining hCFR data with hospital admission estimates from hospital-based studies. In 2015, there were about 1.5 million episodes (95% confidence interval [CI], .3 million-6.9 million) of RSV-ARI in older adults in industrialized countries (data for developing countries were missing), and of these, approximately 14.5% (214 000 episodes; 95% CI, 100 000-459 000) were admitted to hospitals. The global number of hospital admissions for RSV-ARI in older adults was estimated at 336 000 hospitalizations (uncertainty range [UR], 186 000-614 000). We further estimated about 14 000 in-hospital deaths (UR, 5000-50 000) related to RSV-ARI globally. The hospital admission rate and hCFR were higher for those aged ≥65 years than for those aged 50-64 years. The disease burden of RSV-ARI among older adults is substantial, with limited data from developing countries. Appropriate prevention and management strategies are needed to reduce this burden.
Topics: Aged; Aged, 80 and over; Cost of Illness; Databases, Factual; Developed Countries; Global Burden of Disease; Global Health; Hospitalization; Humans; Incidence; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 30880339
DOI: 10.1093/infdis/jiz059 -
Influenza and Other Respiratory Viruses Nov 2018The epidemiology of human respiratory syncytial virus (HRSV) infection has not yet been systematically investigated in Africa. This systematic review and meta-analysis... (Meta-Analysis)
Meta-Analysis
AIM
The epidemiology of human respiratory syncytial virus (HRSV) infection has not yet been systematically investigated in Africa. This systematic review and meta-analysis are to estimate the prevalence of HRSV infections in people with acute respiratory tract infections (ARTI) in Africa.
METHOD
We searched PubMed, EMBASE, Africa Journal Online, and Global Index Medicus to identify observational studies published from January 1, 2000, to August 1, 2017. We used a random-effects model to estimate the prevalence across studies. Heterogeneity (I ) was assessed via the chi-square test on Cochran's Q statistic. Review registration: PROSPERO CRD42017076352.
RESULTS
A total of 67 studies (154 000 participants) were included. Sixty (90%), seven (10%), and no studies had low, moderate, and high risk of bias, respectively. The prevalence of HRSV infection varied widely (range 0.4%-60.4%). The pooled prevalence was 14.6% (95% CI 13.0-16.4, I = 98.8%). The prevalence was higher in children (18.5%; 95% CI 15.8-21.5) compared to adults (4.0%; 95% CI 2.2-6.1) and in people with severe respiratory tract infections (17.9%; 95% CI 15.8-20.1) compared to those with benign forms (9.4%; 95% CI 7.4-11.5); P-values <0.0001. The HRSV prevalence was not associated with sex, subregion in Africa, setting, altitude, latitude, longitude, and seasonality.
CONCLUSION
This study suggests a high prevalence of HRSV in people with ARTI in Africa, particularly among children and people with severe clinical form. All innovative strategies to curb the burden should first focus on children which present the highest HRSV-related burden.
Topics: Adult; Africa; Age Factors; Aged; Aged, 80 and over; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Observational Studies as Topic; Prevalence; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Young Adult
PubMed: 29908103
DOI: 10.1111/irv.12584