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The Journal of Infectious Diseases Mar 2024Respiratory syncytial virus (RSV) is a widespread respiratory pathogen, and RSV-related acute lower respiratory tract infections are the most common cause of respiratory...
BACKGROUND
Respiratory syncytial virus (RSV) is a widespread respiratory pathogen, and RSV-related acute lower respiratory tract infections are the most common cause of respiratory hospitalization in children <2 years of age. Over the last 2 decades, a number of severity scores have been proposed to quantify disease severity for RSV in children, yet there remains no overall consensus on the most clinically useful score.
METHODS
We conducted a systematic review of English-language publications in peer-reviewed journals published since January 2000 assessing the validity of severity scores for children (≤24 months of age) with RSV and/or bronchiolitis, and identified the most promising scores. For included articles, (1) validity data were extracted, (2) quality of reporting was assessed using the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis checklist (TRIPOD), and (3) quality was assessed using the Prediction Model Risk Of Bias Assessment Tool (PROBAST). To guide the assessment of the validity data, standardized cutoffs were employed, and an explicit definition of what we required to determine a score was sufficiently validated.
RESULTS
Our searches identified 8541 results, of which 1779 were excluded as duplicates. After title and abstract screening, 6670 references were excluded. Following full-text screening and snowballing, 32 articles, including 31 scores, were included. The most frequently assessed scores were the modified Tal score and the Wang Bronchiolitis Severity Score; none of the scores were found to be sufficiently validated according to our definition. The reporting and/or design of all the included studies was poor. The best validated score was the Bronchiolitis Score of Sant Joan de Déu, and a number of other promising scores were identified.
CONCLUSIONS
No scores were found to be sufficiently validated. Further work is warranted to validate the existing scores, ideally in much larger datasets.
Topics: Child; Humans; Bronchiolitis; Consensus; Hospitalization; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Respiratory Syncytial Virus Infections
PubMed: 37797314
DOI: 10.1093/infdis/jiad436 -
Frontiers in Immunology 2023The virus neutralization assay is a principal method to assess the efficacy of antibodies in blocking viral entry. Due to biosafety handling requirements of viruses... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The virus neutralization assay is a principal method to assess the efficacy of antibodies in blocking viral entry. Due to biosafety handling requirements of viruses classified as hazard group 3 or 4, pseudotyped viruses can be used as a safer alternative. However, it is often queried how well the results derived from pseudotyped viruses correlate with authentic virus. This systematic review and meta-analysis was designed to comprehensively evaluate the correlation between the two assays.
METHODS
Using PubMed and Google Scholar, reports that incorporated neutralisation assays with both pseudotyped virus, authentic virus, and the application of a mathematical formula to assess the relationship between the results, were selected for review. Our searches identified 67 reports, of which 22 underwent a three-level meta-analysis.
RESULTS
The three-level meta-analysis revealed a high level of correlation between pseudotyped viruses and authentic viruses when used in an neutralisation assay. Reports that were not included in the meta-analysis also showed a high degree of correlation, with the exception of lentiviral-based pseudotyped Ebola viruses.
CONCLUSION
Pseudotyped viruses identified in this report can be used as a surrogate for authentic virus, though care must be taken in considering which pseudotype core to use when generating new uncharacterised pseudotyped viruses.
Topics: Viral Pseudotyping; Ebolavirus
PubMed: 37790941
DOI: 10.3389/fimmu.2023.1184362 -
Influenza and Other Respiratory Viruses Sep 2023Despite the growing recognition of a potentially significant respiratory syncytial virus (RSV) disease burden in adults, relevant evidence in the United Kingdom (UK) is... (Review)
Review
Despite the growing recognition of a potentially significant respiratory syncytial virus (RSV) disease burden in adults, relevant evidence in the United Kingdom (UK) is limited. This systematic literature review (SLR) aimed to identify the disease burden of RSV in UK adults, including certain high-risk subgroups and existing evidence gaps. Published studies (2011 onwards) reporting epidemiological, economic and clinical burden outcomes in UK adults (≥15 years) with RSV were identified from indexed databases, including MEDLINE, Embase and the Cochrane library. High-risk groups included elderly (≥65 years), immunocompromised, co-morbid and co-infected patients. Outcomes included RSV incidence/prevalence, mortality, clinical presentation and direct/indirect resource use/costs. Twenty-eight publications on 28 unique studies were identified, mostly in general/respiratory indicator ( = 17), elderly ( = 10) and immunocompromised ( = 6) cohorts. Main outcomes reported in the general/respiratory indicator cohort were RSV infection incidence (seasonal/annual: 0.09-17.9%/6.6-15.1%), mortality (8,482 deaths/season) and direct resource use (including mean general practitioner [GP] episodes/season: 487,247). Seasonal/annual incidence was 14.6-26.5%/0.7-16% in high-risk cohorts. Attributed to RSV in the elderly were 7,915 deaths/season and 175,070 mean GP episodes/season. Only two studies reported on co-morbid cohorts. Clinical burden outcomes were only reported in general and immunocompromised patients, and no evidence was found in any cohort on indirect economic burden or RSV complications. Evidence captured suggests that RSV may have a substantial burden in UK adults. However, available data were limited and highly heterogenous, with further studies needed to characterise the burden of RSV in adults and to validate our findings.
Topics: Aged; Humans; Adult; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections; Cost of Illness; Databases, Factual; Evidence Gaps
PubMed: 37744994
DOI: 10.1111/irv.13188 -
Paediatric Respiratory Reviews Mar 2024Bronchiolitis is a leading cause of infant hospitalization, linked to respiratory syncytial virus (RSV) and rhinovirus (RV). Guidelines lack specific viral testing for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Bronchiolitis is a leading cause of infant hospitalization, linked to respiratory syncytial virus (RSV) and rhinovirus (RV). Guidelines lack specific viral testing for bronchiolitis management. To establish effective management strategies, it is crucial to assess whether specific respiratory virus types are correlated with distinct examination features.
METHODS
Through a systematic search of three databases, 21 studies were qualitatively analyzed, with 18 used for meta-analysis. Various outcomes like wheezing on auscultation, fever, atopic traits, and infection severity were evaluated.
RESULTS
RSV-positive bronchiolitis was associated with a higher need for oxygen supplementation (OR 1.78, 95% CI 1.04-3.02) in 5 studies, while RV-positive bronchiolitis was more frequently linked to personal history of eczema (OR 0.60, 95% CI 0.41-0.88) in 6 studies. No significant differences were observed in the other outcomes examined.
CONCLUSIONS
Bronchiolitis caused by RSV or RV presents with similar clinical features. Despite the associations between RSV-positive bronchiolitis and need for oxygen supplementation, and RV-positive bronchiolitis and a history of eczema, our study shows that viral etiology of bronchiolitis cannot be determined solely based on clinical presentation. Tailored management strategies, informed by accurate viral testing, seem crucial in clinical practice for enhancing patient outcomes in severe bronchiolitis.
Topics: Infant; Humans; Bronchiolitis; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Hospitalization; Rhinovirus; Eczema; Respiratory Sounds
PubMed: 37743159
DOI: 10.1016/j.prrv.2023.09.003 -
PLoS Medicine Jul 2023Respiratory syncytial virus (RSV) infections are among the primary causes of death for children under 5 years of age worldwide. A notable challenge with many of the...
BACKGROUND
Respiratory syncytial virus (RSV) infections are among the primary causes of death for children under 5 years of age worldwide. A notable challenge with many of the upcoming prophylactic interventions against RSV is their short duration of protection, making the age profile of key interest to the design of prevention strategies.
METHODS AND FINDINGS
We leverage the RSV data collected on cases, hospitalizations, and deaths in a systematic review in combination with flexible generalized additive mixed models (GAMMs) to characterize the age burden of RSV incidence, hospitalization, and hospital-based case fatality rate (hCFR). Due to the flexible nature of GAMMs, we estimate the peak, median, and mean incidence of infection to inform discussions on the ideal "window of protection" of prophylactic interventions. In a secondary analysis, we reestimate the burden of RSV in all low- and middle-income countries. The peak age of community-based incidence is 4.8 months, and the mean and median age of infection is 18.9 and 14.7 months, respectively. Estimating the age profile using the incidence coming from hospital-based studies yields a slightly younger age profile, in which the peak age of infection is 2.6 months and the mean and median age of infection are 15.8 and 11.6 months, respectively. More severe outcomes, such as hospitalization and in-hospital death have a younger age profile. Children under 6 months of age constitute 10% of the population under 5 years of age but bear 20% to 29% of cases, 28% to 39% of hospitalizations, and 38% to 50% of deaths. On an average year, we estimate 28.23 to 31.34 million cases of RSV, between 2.95 to 3.35 million hospitalizations, and 16,835 to 19,909 in-hospital deaths in low, lower- and upper middle-income countries. In addition, we estimate 17,254 to 23,875 deaths in the community, for a total of 34,114 to 46,485 deaths. Globally, evidence shows that community-based incidence may differ by World Bank Income Group, but not hospital-based incidence, probability of hospitalization, or the probability of in-hospital death (p ≤ 0.01, p = 1, p = 0.86, 0.63, respectively). Our study is limited mainly due to the sparsity of the data, especially for low-income countries (LICs). The lack of information for some populations makes detecting heterogeneity between income groups difficult, and differences in access to care may impact the reported burden.
CONCLUSIONS
We have demonstrated an approach to synthesize information on RSV outcomes in a statistically principled manner, and we estimate that the age profile of RSV burden depends on whether information on incidence is collected in hospitals or in the community. Our results suggest that the ideal prophylactic strategy may require multiple products to avert the risk among preschool children.
Topics: Humans; Child, Preschool; Infant; Respiratory Syncytial Viruses; Developing Countries; Hospital Mortality; Respiratory Syncytial Virus Infections; Hospitalization; Respiratory Syncytial Virus, Human; Respiratory Tract Infections
PubMed: 37459352
DOI: 10.1371/journal.pmed.1004250 -
Indian Journal of Public Health 2023The coronavirus disease 2019 (COVID-19) pandemic has changed the epidemiology of respiratory syncytial virus (RSV) infection which accounts for most bronchiolitis and... (Meta-Analysis)
Meta-Analysis Review
The impact of coronavirus disease 2019 pandemic on bronchiolitis (lower respiratory tract infection) due to respiratory syncytial virus: A systematic review and meta-analysis.
The coronavirus disease 2019 (COVID-19) pandemic has changed the epidemiology of respiratory syncytial virus (RSV) infection which accounts for most bronchiolitis and viral pneumonias in infants. This systematic review and meta-analysis aimed to quantitatively assess the effect of the COVID-19 pandemic on RSV-associated bronchiolitis among hospitalized infants. The study protocol was registered in the PROSPERO database (CRD42022314000) and was designed based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines updated in May 2020. The meta-analysis component was modified appropriately to synthesize the pooled proportion of infants having RSV-associated bronchiolitis before the COVID-19 pandemic in 2019 and during the pandemic with 95% confidence interval (CI). We identified and screened 189 articles and systematically reviewed 50 full texts. Eight qualified studies from Europe and China, including 109,186 symptomatic cases of bronchiolitis before the pandemic in 2019 and 61,982 cases in 2020-2021 were pooled by random-effects meta-analysis. The quantitative analysis included laboratory-confirmed RSV infection in 7691 infants with bronchiolitis reported before the pandemic in 2019. Meanwhile, during the pandemic, 4964 bronchiolitis cases were associated with RSV infection. The pooled proportion of RSV-associated bronchiolitis cases before the pandemic in 2019 was 16.74% (95% CI 11.73, 22.43%, 95% prediction interval 0.032, 34.16). The pooled proportion of confirmed RSV cases during the pandemic in 2020/2021 was 19.20% (95% CI 12.01, 27.59%, 95% prediction interval 0.046, 42.35). There was an increase in RSV activity after the relaxation of stringent public health measures during the COVID-19 pandemic.
Topics: Infant; Humans; Pandemics; COVID-19; India; Respiratory Syncytial Virus, Human; Bronchiolitis; Respiratory Syncytial Virus Infections; Respiratory Tract Infections
PubMed: 37459026
DOI: 10.4103/ijph.ijph_1334_22 -
BMC Pediatrics Jun 2023To undertake a systematic review of studies describing the proportion of children admitted to a paediatric intensive care unit (PICU) for respiratory syncytial virus... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To undertake a systematic review of studies describing the proportion of children admitted to a paediatric intensive care unit (PICU) for respiratory syncytial virus (RSV) and/or bronchiolitis who were born preterm, and compare their outcomes in PICU with children born at term.
METHODS
We searched Medline, Embase and Scopus. Citations and references of included articles were searched. We included studies published from the year 2000 onwards, from high-income countries, that examined children 0-18 years of age, admitted to PICU from the year 2000 onwards for RSV and/or bronchiolitis. The primary outcome was the percentage of PICU admissions born preterm, and secondary outcomes were observed relative risks of invasive mechanical ventilation and mortality within PICU. We used the Joanna Briggs Institute Checklist for Analytical Cross-Sectional Studies to assess risk of bias.
RESULTS
We included 31 studies, from 16 countries, including a total of 18,331 children. Following meta-analysis, the pooled estimate for percentage of PICU admissions for RSV/bronchiolitis who were born preterm was 31% (95% confidence interval: 27% to 35%). Children born preterm had a greater risk of requiring invasive ventilation compared to children born at term (relative risk 1.57, 95% confidence interval 1.25 to 1.97, I = 38%). However, we did not observe a significant increase in the relative risk for mortality within PICU for preterm-born children (relative risk 1.10, 95% confidence interval: 0.70 to 1.72, I = 0%), although the mortality rate was low across both groups. The majority of studies (n = 26, 84%) were at high risk of bias.
CONCLUSIONS
Among PICU admissions for bronchiolitis, preterm-born children are over-represented compared with the preterm birth rate (preterm birth rate 4.4% to 14.4% across countries included in review). Preterm-born children are at higher risk of mechanical ventilation compared to those born at term.
Topics: Infant, Newborn; Child; Humans; Pregnancy; Female; Cross-Sectional Studies; Premature Birth; Bronchiolitis; Parturition; Respiratory Syncytial Virus, Human; Critical Care
PubMed: 37386478
DOI: 10.1186/s12887-023-04150-7 -
The Journal of Infectious Diseases Nov 2023Adding additional specimen types (eg, serology or sputum) to nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) increases respiratory... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adding additional specimen types (eg, serology or sputum) to nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) increases respiratory syncytial virus (RSV) detection among adults. We assessed if a similar increase occurs in children and quantified underascertainment associated with diagnostic testing.
METHODS
We searched databases for studies involving RSV detection in persons <18 years using ≥2 specimen types or tests. We assessed study quality using a validated checklist. We pooled detection rates by specimen and diagnostic tests and quantified performance.
RESULTS
We included 157 studies. Added testing of additional specimens to NP aspirate (NPA), NPS, and/or nasal swab (NS) RT-PCR resulted in statistically nonsignificant increases in RSV detection. Adding paired serology testing increased RSV detection by 10%, NS by 8%, oropharyngeal swabs by 5%, and NPS by 1%. Compared to RT-PCR, direct fluorescence antibody tests, viral culture, and rapid antigen tests were 87%, 76%, and 74% sensitive, respectively (pooled specificities all ≥98%). Pooled sensitivity of multiplex versus singleplex RT-PCR was 96%.
CONCLUSIONS
RT-PCR was the most sensitive pediatric RSV diagnostic test. Adding multiple specimens did not substantially increase RSV detection, but even small proportional increases could result in meaningful changes in burden estimates. The synergistic effect of adding multiple specimens should be evaluated.
Topics: Adult; Child; Humans; Respiratory Syncytial Virus Infections; Sensitivity and Specificity; Respiratory Syncytial Virus, Human; Viruses; Diagnostic Techniques and Procedures; Nasopharynx; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 37285396
DOI: 10.1093/infdis/jiad185 -
BMC Infectious Diseases May 2023As countries move towards or achieve measles elimination status, serosurveillance is an important public health tool. However, a major challenge of serosurveillance is...
Comparison of measles IgG enzyme immunoassays (EIA) versus plaque reduction neutralization test (PRNT) for measuring measles serostatus: a systematic review of head-to-head analyses of measles IgG EIA and PRNT.
BACKGROUND
As countries move towards or achieve measles elimination status, serosurveillance is an important public health tool. However, a major challenge of serosurveillance is finding a feasible, accurate, cost-effective, and high throughput assay to measure measles antibody concentrations and estimate susceptibility in a population. We conducted a systematic review to assess, characterize, and - to the extent possible - quantify the performance of measles IgG enzyme-linked assays (EIAs) compared to the gold standard, plaque reduction neutralization tests (PRNT).
METHODS
We followed the PRISMA statement for a systematic literature search and methods for conducting and reporting systematic reviews and meta-analyses recommended by the Cochrane Screening and Diagnostic Tests Methods Group. We identified studies through PubMed and Embase electronic databases and included serologic studies detecting measles virus IgG antibodies among participants of any age from the same source population that reported an index (any EIA or multiple bead-based assays, MBA) and reference test (PRNT) using sera, whole blood, or plasma. Measures of diagnostic accuracy with 95% confidence intervals (CI) were abstracted for each study result, where reported.
RESULTS
We identified 550 unique publications and identified 36 eligible studies for analysis. We classified studies as high, medium, or low quality; results from high quality studies are reported. Because most high quality studies used the Siemens Enzygnost EIA kit, we generate individual and pooled diagnostic accuracy estimates for this assay separately. Median sensitivity of the Enzygnost EIA was 92.1% [IQR = 82.3, 95.7]; median specificity was 96.9 [93.0, 100.0]. Pooled sensitivity and specificity from studies using the Enzygnost kit were 91.6 (95%CI: 80.7,96.6) and 96.0 (95%CI: 90.9,98.3), respectively. The sensitivity of all other EIA kits across high quality studies ranged from 0% to 98.9% with median (IQR) = 90.6 [86.6, 95.2]; specificity ranged from 58.8% to 100.0% with median (IQR) = 100.0 [88.7, 100.0].
CONCLUSIONS
Evidence on the diagnostic accuracy of currently available measles IgG EIAs is variable, insufficient, and may not be fit for purpose for serosurveillance goals. Additional studies evaluating the diagnostic accuracy of measles EIAs, including MBAs, should be conducted among diverse populations and settings (e.g., vaccination status, elimination/endemic status, age groups).
Topics: Humans; Neutralization Tests; Measles; Immunoenzyme Techniques; Measles virus; Sensitivity and Specificity; Antibodies, Viral; Immunoglobulin G
PubMed: 37259032
DOI: 10.1186/s12879-023-08199-8 -
The Journal of Infectious Diseases Mar 2024Previous studies reported inconsistent findings regarding the association between respiratory syncytial virus (RSV) subgroup distribution and timing of RSV season. We...
BACKGROUND
Previous studies reported inconsistent findings regarding the association between respiratory syncytial virus (RSV) subgroup distribution and timing of RSV season. We aimed to further understand the association by conducting a global-level systematic analysis.
METHODS
We compiled published data on RSV seasonality through a systematic literature review, and unpublished data shared by international collaborators. Using annual cumulative proportion (ACP) of RSV-positive cases, we defined RSV season onset and offset as ACP reaching 10% and 90%, respectively. Linear regression models accounting for meteorological factors were constructed to analyze the association of proportion of RSV-A with the corresponding RSV season onset and offset.
RESULTS
We included 36 study sites from 20 countries, providing data for 179 study-years in 1995-2019. Globally, RSV subgroup distribution was not significantly associated with RSV season onset or offset globally, except for RSV season offset in the tropics in 1 model, possibly by chance. Models that included RSV subgroup distribution and meteorological factors explained only 2%-4% of the variations in timing of RSV season.
CONCLUSIONS
Year-on-year variations in RSV season onset and offset are not well explained by RSV subgroup distribution or meteorological factors. Factors including population susceptibility, mobility, and viral interference should be examined in future studies.
Topics: Humans; Respiratory Syncytial Virus, Human; Linear Models; Seasons; Viral Interference
PubMed: 37249267
DOI: 10.1093/infdis/jiad192