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The Lancet. Global Health Jan 2021Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs...
BACKGROUND
Human metapneumovirus is a common virus associated with acute lower respiratory infections (ALRIs) in children. No global burden estimates are available for ALRIs associated with human metapneumovirus in children, and no licensed vaccines or drugs exist for human metapneumovirus infections. We aimed to estimate the age-stratified human metapneumovirus-associated ALRI global incidence, hospital admissions, and mortality burden in children younger than 5 years.
METHODS
We estimated the global burden of human metapneumovirus-associated ALRIs in children younger than 5 years from a systematic review of 119 studies published between Jan 1, 2001, and Dec 31, 2019, and a further 40 high quality unpublished studies. We assessed risk of bias using a modified Newcastle-Ottawa Scale. We estimated incidence, hospital admission rates, and in-hospital case-fatality ratios (hCFRs) of human metapneumovirus-associated ALRI using a generalised linear mixed model. We applied incidence and hospital admission rates of human metapneumovirus-associated ALRI to population estimates to yield the morbidity burden estimates by age bands and World Bank income levels. We also estimated human metapneumovirus-associated ALRI in-hospital deaths and overall human metapneumovirus-associated ALRI deaths (both in-hospital and non-hospital deaths). Additionally, we estimated human metapneumovirus-attributable ALRI cases, hospital admissions, and deaths by combining human metapneumovirus-associated burden estimates and attributable fractions of human metapneumovirus in laboratory-confirmed human metapneumovirus cases and deaths.
FINDINGS
In 2018, among children younger than 5 years globally, there were an estimated 14·2 million human metapneumovirus-associated ALRI cases (uncertainty range [UR] 10·2 million to 20·1 million), 643 000 human metapneumovirus-associated hospital admissions (UR 425 000 to 977 000), 7700 human metapneumovirus-associated in-hospital deaths (2600 to 48 800), and 16 100 overall (hospital and community) human metapneumovirus-associated ALRI deaths (5700 to 88 000). An estimated 11·1 million ALRI cases (UR 8·0 million to 15·7 million), 502 000 ALRI hospital admissions (UR 332 000 to 762 000), and 11 300 ALRI deaths (4000 to 61 600) could be causally attributed to human metapneumovirus in 2018. Around 58% of the hospital admissions were in infants under 12 months, and 64% of in-hospital deaths occurred in infants younger than 6 months, of which 79% occurred in low-income and lower-middle-income countries.
INTERPRETATION
Infants younger than 1 year have disproportionately high risks of severe human metapneumovirus infections across all World Bank income regions and all child mortality settings, similar to respiratory syncytial virus and influenza virus. Infants younger than 6 months in low-income and lower-middle-income countries are at greater risk of death from human metapneumovirus-associated ALRI than older children and those in upper-middle-income and high-income countries. Our mortality estimates demonstrate the importance of intervention strategies for infants across all settings, and warrant continued efforts to improve the outcome of human metapneumovirus-associated ALRI among young infants in low-income and lower-middle-income countries.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Acute Disease; Child, Preschool; Cost of Illness; Female; Global Health; Humans; Infant; Infant, Newborn; Linear Models; Male; Metapneumovirus; Paramyxoviridae Infections; Respiratory Tract Infections
PubMed: 33248481
DOI: 10.1016/S2214-109X(20)30393-4 -
Systematic Reviews Nov 2020Acute bronchiolitis caused by respiratory syncytial virus (RSV) has been associated with greater risk of recurrent wheezing and asthma. However, it is unclear whether... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute bronchiolitis caused by respiratory syncytial virus (RSV) has been associated with greater risk of recurrent wheezing and asthma. However, it is unclear whether this association is causal. RSV-specific monoclonal antibodies have been shown to reduce RSV-related hospitalisations in high-risk infants, but the longer-term follow-up has given conflicting evidence for prevention of recurrent wheeze or asthma.
OBJECTIVE
We performed a systematic review and meta-analysis to determine whether monoclonal antibody prophylaxis against RSV bronchiolitis reduces the risk of subsequent recurrent wheeze or asthma. If so, this may support the hypothesis of causality.
METHODS
Studies were identified via an online database search using Embase, MEDLINE, PubMed, Web of Science and the Cochrane Library. Manufacturers of monoclonal antibodies were contacted directly for unpublished data. The intervention of interest was RSV monoclonal antibody prophylaxis, and the primary outcome measure was recurrent wheeze and/or asthma. Studies were screened according to inclusion/exclusion criteria. Included studies were evaluated for quality and assessed for bias independently by 3 reviewers using the 'Grading of Recommendations Assessment, Development and Evaluation' (GRADE) approach. Results were extracted into 2 × 2 outcome tables and a meta-analysis carried out producing forest plots based on relative risk. Heterogeneity was assessed using the I statistic.
RESULTS
The search identified 141 articles, which, after screening, resulted in eight studies (2 randomised controlled trials), thus including 11,195 infants in the meta-analysis. The overall result demonstrated a non-statistically significant reduction in relative risk of developing recurrent wheeze or asthma (RR 0.60; 95% CI 0.31 to 1.16). Study quality was generally low with evidence of publication bias and statistical heterogeneity. However, sub-group analysis excluding studies deemed to be 'very low' quality showed a relative risk of 0.42 (95% CI 0.22 to 0.80, p = 0.008). A further sub-group analysis for infants aged 32 to < 36 weeks showed a statistically significant relative risk of 0.35 (95% CI 0.14 to 0.86, p = 0.02).
DISCUSSION
We did not identify an overall statistically significant benefit. However, our two sub-group analyses did find statistically significant benefits of monoclonal antibody therapy on the risk of recurrent wheeze and asthma. The main limitation of this study is the lack of high-quality randomised controlled trials, highlighting the need for more research in this field.
Topics: Asthma; Child; Humans; Infant; Randomized Controlled Trials as Topic; Recurrence; Respiratory Sounds; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 33239107
DOI: 10.1186/s13643-020-01527-y -
PloS One 2020The advent of genome amplification assays has allowed description of new respiratory viruses and to reconsider the role played by certain respiratory viruses in... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The advent of genome amplification assays has allowed description of new respiratory viruses and to reconsider the role played by certain respiratory viruses in bronchiolitis. This systematic review and meta-analysis was initiated to clarify the prevalence of respiratory viruses in children with bronchiolitis in the pre-COVID-19 pandemic era.
METHODS
We performed an electronic search through Pubmed and Global Index Medicus databases. We included observational studies reporting the detection rate of common respiratory viruses in children with bronchiolitis using molecular assays. Data was extracted and the quality of the included articles was assessed. We conducted sensitivity, subgroups, publication bias, and heterogeneity analyses using a random effect model.
RESULTS
The final meta-analysis included 51 studies. Human respiratory syncytial virus (HRSV) was largely the most commonly detected virus 59.2%; 95% CI [54.7; 63.6]). The second predominant virus was Rhinovirus (RV) 19.3%; 95% CI [16.7; 22.0]) followed by Human bocavirus (HBoV) 8.2%; 95% CI [5.7; 11.2]). Other reported viruses included Human Adenovirus (HAdV) 6.1%; 95% CI [4.4; 8.0]), Human Metapneumovirus (HMPV) 5.4%; 95% CI [4.4; 6.4]), Human Parainfluenzavirus (HPIV) 5.4%; 95% CI [3.8; 7.3]), Influenza 3.2%; 95% CI [2.2; 4.3], Human Coronavirus (HCoV) 2.9%; 95% CI [2.0; 4.0]), and Enterovirus (EV) 2.9%; 95% CI [1.6; 4.5]). HRSV was the predominant virus involved in multiple detection and most codetections were HRSV + RV 7.1%, 95% CI [4.6; 9.9]) and HRSV + HBoV 4.5%, 95% CI [2.4; 7.3]).
CONCLUSIONS
The present study has shown that HRSV is the main cause of bronchiolitis in children, we also have Rhinovirus, and Bocavirus which also play a significant role. Data on the role played by SARS-CoV-2 in children with acute bronchiolitis is needed.
REVIEW REGISTRATION
PROSPERO, CRD42018116067.
Topics: Bronchiolitis, Viral; Female; Human bocavirus; Humans; Infant; Male; Prevalence; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Rhinovirus
PubMed: 33180855
DOI: 10.1371/journal.pone.0242302 -
Epidemiology and Infection Aug 2020To provide comprehensive information on the epidemiology and burden of respiratory syncytial virus hospitalisation (RSVH) in preterm infants, a pooled analysis was... (Meta-Analysis)
Meta-Analysis
To provide comprehensive information on the epidemiology and burden of respiratory syncytial virus hospitalisation (RSVH) in preterm infants, a pooled analysis was undertaken of seven multicentre, prospective, observational studies from across the Northern Hemisphere (2000-2014). Data from all 320-356 weeks' gestational age (wGA) infants without comorbidity were analysed. RSVH occurred in 534/14 504 (3.7%) infants; equating to a rate of 5.65 per 100 patient-seasons, with the rate in individual wGA groups dependent upon exposure time (P = 0.032). Most RSVHs (60.1%) occurred in December-January. Median age at RSVH was 88 days (interquartile range (IQR): 54-159). Respiratory support was required by 82.0% of infants: oxygen in 70.4% (median 4 (IQR: 2-6) days); non-invasive ventilation in 19.3% (median 3 (IQR: 2-5) days); and mechanical ventilation in 10.2% (median 5 (IQR: 3-7) days). Intensive care unit admission was required by 17.9% of infants (median 6 days (IQR: 2-8) days). Median overall hospital length of stay (LOS) was 5 (IQR: 3-8) days. Hospital resource use was similar across wGA groups except for overall LOS, which was shortest in those born 35 wGA (median 3 vs. 4-6 days for 32-34 wGA; P < 0.001). Strategies to reduce the burden of RSVH in otherwise healthy 32-35 wGA infants are indicated.
Topics: Antiviral Agents; Cohort Studies; Gestational Age; Hospitalization; Humans; Infant; Length of Stay; Multicenter Studies as Topic; Observational Studies as Topic; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 32799945
DOI: 10.1017/S0950268820001661 -
Planta Medica Oct 2020Viruses have a high mutation rate, and, thus, there is a continual emergence of new antiviral-resistant strains. Therefore, it becomes imperative to explore and develop...
Viruses have a high mutation rate, and, thus, there is a continual emergence of new antiviral-resistant strains. Therefore, it becomes imperative to explore and develop new antiviral compounds continually. The search for pharmacological substances of plant origin that are effective against animal viruses, which have a high mortality rate or cause large economic losses, has garnered interest in the last few decades. This systematic review compiles 130 plant species that exhibit antiviral activity on 37 different virus species causing serious diseases in animals. The kind of extract, fraction, or compound exhibiting the antiviral activity and the design of the trial were particularly considered for review. The literature revealed details regarding plant species exhibiting antiviral activities against pathogenic animal virus species of the following families-, and that cause infections, among others, in poultry, cattle, pigs, horses, shrimps, and fish. Overall, 30 plant species exhibited activity against various influenza viruses, most of them causing avian influenza. Furthermore, 30 plant species were noted to be active against Newcastle disease virus. In addition, regarding the pathogens most frequently investigated, this review provides a compilation of 20 plant species active against bovine herpesvirus, 16 against fowlpox virus, 12 against white spot syndrome virus in marine shrimps, and 10 against suide herpesvirus. Nevertheless, some plant extracts, particularly their compounds, are promising candidates for the development of new antiviral remedies, which are urgently required.
Topics: Animal Diseases; Animals; Antiviral Agents; Cattle; Horses; Orthomyxoviridae; Plant Extracts; Plants, Medicinal; Swine; Veterinary Medicine
PubMed: 32777833
DOI: 10.1055/a-1224-6115 -
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