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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 -
Human Vaccines & Immunotherapeutics Oct 2021Clinical development of Ebola virus vaccines (EVV) was accelerated by the West African Ebola virus epidemic which remains the deadliest in history. To compare and rank... (Meta-Analysis)
Meta-Analysis
Clinical development of Ebola virus vaccines (EVV) was accelerated by the West African Ebola virus epidemic which remains the deadliest in history. To compare and rank the EVV according to their immunogenicity and safety. A total of 21 randomized controlled trial, evaluating seven different vaccines with different doses, and 5,275 participants were analyzed. The rVSVΔG-ZEBOV-GP (2 × 10 ) vaccine was more immunogenic (-score 0.80). For pain, rVSVΔG-ZEBOV-GP (≤10 ) had few events (-score 0.90). For fatigue and headache, the DNA-EBOV (≤ 4 mg) was the best one with -scores of 0.94 and 0.87, respectively. For myalgia, the ChAd3 (10 ) had a lower risk (-score 0.94). For fever, the Ad5.ZEBOV (≤ 8 × 10 ) was the best one (-score 0.80). The best vaccine to be used to stop future outbreak of Ebola is the rVSVDG-ZEBOV-GP vaccine at dose of 2 × 10 PFU.
Topics: Adult; Antibodies, Viral; Ebola Vaccines; Ebolavirus; Hemorrhagic Fever, Ebola; Humans; Network Meta-Analysis; Randomized Controlled Trials as Topic
PubMed: 34270366
DOI: 10.1080/21645515.2021.1932214 -
The Journal of Infectious Diseases Aug 2022Respiratory syncytial virus (RSV) can cause serious illness in those aged <5 years in the United States, but uncertainty remains around which populations receive RSV...
BACKGROUND
Respiratory syncytial virus (RSV) can cause serious illness in those aged <5 years in the United States, but uncertainty remains around which populations receive RSV testing. We conducted a systematic literature review of RSV testing patterns in studies published from 2000 to 2021.
METHODS
Studies of RSV, medically attended RSV lower respiratory tract infections (LRTIs), and bronchiolitis were identified using standard methodology. Outcomes were clinical decisions to test for RSV, testing frequency, and testing incidence proportions in inpatient (IP), emergency department (ED), outpatient (OP), and urgent care settings.
RESULTS
Eighty good-/fair-quality studies, which reported data from the period 1988-2020, were identified. Twenty-seven described the clinical decision to test, which varied across and within settings. Two studies reported RSV testing frequency for multiple settings, with higher testing proportions in IP (n = 2, range: 83%-85%, 1996-2009) compared with ED (n = 1, 25%, 2006-2009) and OP (n = 2, 15%-25%, 1996-2009). Higher RSV testing incidence proportions were observed among LRTI infant populations in the ED (n = 1, 74%, 2007-2008) and OP (n = 2, 54%-69%, 1995-2008). Incidence proportions in LRTI populations were not consistently higher in the IP setting (n = 13). Across studies and time, there was heterogeneity in RSV testing patterns, which may reflect varying detection methods, populations, locations, time periods, and healthcare settings.
CONCLUSIONS
Not all infants and children with LRTI are tested for RSV, highlighting underestimation of RSV burden across all settings.
Topics: Bronchiolitis; Child; Child, Preschool; Humans; Incidence; Infant; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; United States
PubMed: 35968874
DOI: 10.1093/infdis/jiac203 -
BMJ Global Health Feb 2023Respiratory syncytial virus (RSV) is the principal cause of acute lower respiratory infections (ALRI) among infants worldwide, and an important cause of morbidity,...
Impact of breastfeeding on the incidence and severity of respiratory syncytial virus (RSV)-associated acute lower respiratory infections in infants: a systematic review highlighting the global relevance of primary prevention.
BACKGROUND
Respiratory syncytial virus (RSV) is the principal cause of acute lower respiratory infections (ALRI) among infants worldwide, and an important cause of morbidity, hospitalisation and mortality. While infants are universally exposed to RSV, most mortality occurs among normal term infants from low-income and middle-income countries. Breastfeeding has been suggested to have a protective effect against RSV infection. This study aims to determine the association of breastfeeding on the frequency and severity of RSV-associated ALRI among infants.
METHODS
A systematic review was conducted using keywords and Medical Subject Headings on MEDLINE, PubMed, Google Scholar, EMBASE, MedRxiv and Cochrane Central Register of Controlled Trials. Full-text articles published in English from 2000 to 2021 that studied exclusively or partially breastfed infants who developed RSV-associated ALRI <12 months of age were included. Covidence software-based evidence extraction and Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol guidelines were followed. Quality of evidence was analysed using UK National Service Framework grading and the risk-of-bias assessment using Robvis.
RESULTS
Among 1368 studies screened, 217 qualified full-text review and 198 were excluded based on pre-agreed criteria. Nineteen articles published from 12 countries that included 16 787 infants from 31 countries (of which 8 middle-income) were retained for analysis. Results indicate that non-breastfeeding practices pose a significant risk for severe RSV-associated ALRI and hospitalisation. Exclusive breastfeeding for >4-6 months significantly lowered hospitalisation, length of stay, supplemental oxygen demand and admission to intensive care units.
CONCLUSION
In the context of no effective or standardised treatment for established RSV-associated ALRI, available evidence suggest that breastfeeding is associated with lower frequency and severity of RSV-associated ALRI, based on observational studies of variable grades of evidence and risk-of-bias. With both exclusive and partial breastfeeding benefiting infants who develop RSV-associated ALRI, breastfeeding should be promoted globally as an adjunct primary prevention; in addition to emerging immunoprophylaxis and maternal immunisation strategies.
Topics: Female; Infant; Humans; Respiratory Syncytial Viruses; Breast Feeding; Incidence; Respiratory Tract Infections; Primary Prevention
PubMed: 36746518
DOI: 10.1136/bmjgh-2022-009693 -
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 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 -
Human Vaccines & Immunotherapeutics Dec 2022This study comprehensively evaluated and compared three human rabies vaccines. Seven electronic databases were systematically searched. The Cochrane Handbook v5.1.0 was... (Meta-Analysis)
Meta-Analysis
Immunogenicity and safety of human diploid cell vaccine (HDCV) vs. purified Vero cell vaccine (PVRV) vs. purified chick embryo cell vaccine (PCECV) used in post-exposure prophylaxis: a systematic review and meta-analysis.
This study comprehensively evaluated and compared three human rabies vaccines. Seven electronic databases were systematically searched. The Cochrane Handbook v5.1.0 was used to assess the risk of bias. A random-effects model was used to combine individual rates, and network meta-analysis was used for pairwise comparisons. Twenty-seven articles were included, with a total of 18,630 participants. The pooled incidence of the total adverse reaction to HDCV was significantly lower than that of PCECV. HDCV administration resulted in a lower incidence of local pain, fever, and weakness than purified Vero cell vaccine. HDCV caused a lower incidence of local pain and fever than PCECV. No significant difference was observed in terms of the seroconversion rate on day 7 or the rabies virus-neutralizing antibody titer on day 14. HDCV demonstrated superiority in terms of safety compared with the other two rabies vaccines, while the same was not observed in terms of immunogenicity.
Topics: Animals; Antibodies, Viral; Chick Embryo; Chickens; Chlorocebus aethiops; Diploidy; Fever; Humans; Pain; Post-Exposure Prophylaxis; Rabies; Rabies Vaccines; Rabies virus; Vero Cells
PubMed: 35192787
DOI: 10.1080/21645515.2022.2027714 -
The Journal of Infectious Diseases Mar 2022Although global reviews of infant respiratory syncytial virus (RSV) burden exist, none have summarized data from the United States or evaluated how RSV burden estimates... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Although global reviews of infant respiratory syncytial virus (RSV) burden exist, none have summarized data from the United States or evaluated how RSV burden estimates are influenced by variations in study design.
METHODS
We performed a systematic literature review and meta-analysis of studies describing RSV-associated hospitalization rates among US infants and examined the impact of key study characteristics on these estimates.
RESULTS
We reviewed 3328 articles through 14 August 2020 and identified 25 studies with 31 unique estimates of RSV-associated hospitalization rates. Among US infants <1 year of age, annual rates ranged from 8.4 to 40.8 per 1000 with a pooled rate of 19.4 (95% confidence interval [CI], 17.9-20.9). Study type influenced RSV-associated hospitalization rates (P = .003), with active surveillance studies having pooled rates (11.0; 95% CI, 9.8-12.2) that were half that of studies based on administrative claims (21.4; 19.5-23.3) or modeling approaches (23.2; 20.2-26.2).
CONCLUSIONS
Applying our pooled rates to the 2020 US birth cohort suggests that 79 850 (95% CI, 73 680-86 020) RSV-associated infant hospitalizations occur each year. The full range of RSV-associated hospitalization rates identified in our review can better inform future evaluations of RSV prevention strategies. More research is needed to better understand differences in estimated RSV burden across study design.
Topics: Hospitalization; Humans; Infant; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; United States
PubMed: 33346360
DOI: 10.1093/infdis/jiaa752 -
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 -
BMC Medicine Jun 2020Major infectious disease outbreaks are a constant threat to human health. Clinical research responses to outbreaks generate evidence to improve outcomes and outbreak...
BACKGROUND
Major infectious disease outbreaks are a constant threat to human health. Clinical research responses to outbreaks generate evidence to improve outcomes and outbreak control. Experiences from previous epidemics have identified multiple challenges to undertaking timely clinical research responses. This scoping review is a systematic appraisal of political, economic, administrative, regulatory, logistical, ethical and social (PEARLES) challenges to clinical research responses to emergency epidemics and solutions identified to address these.
METHODS
A scoping review. We searched six databases (MEDLINE, Embase, Global Health, PsycINFO, Scopus and Epistemonikos) for articles published from 2008 to July 2018. We included publications reporting PEARLES challenges to clinical research responses to emerging epidemics and pandemics and solutions identified to address these. Two reviewers screened articles for inclusion, extracted and analysed the data.
RESULTS
Of 2678 articles screened, 76 were included. Most presented data relating to the 2014-2016 Ebola virus outbreak or the H1N1 outbreak in 2009. The articles related to clinical research responses in Africa (n = 37), Europe (n = 8), North America (n = 5), Latin America and the Caribbean (n = 3) and Asia (n = 1) and/or globally (n = 22). A wide range of solutions to PEARLES challenges was presented, including a need to strengthen global collaborations and coordination at all levels and develop pre-approved protocols and equitable frameworks, protocols and standards for emergencies. Clinical trial networks and expedited funding and approvals were some solutions implemented. National ownership and community engagement from the outset were a key enabler for delivery. Despite the wide range of recommended solutions, none had been formally evaluated.
CONCLUSIONS
To strengthen global preparedness and response to the COVID-19 pandemic and future epidemics, identified solutions for rapid clinical research deployment, delivery, and dissemination must be implemented. Improvements are urgently needed to strengthen collaborations, funding mechanisms, global and national research capacity and capability, targeting regions vulnerable to epidemics and pandemics. Solutions need to be flexible to allow timely adaptations to context, and research led by governments of affected regions. Research communities globally need to evaluate their activities and incorporate lessons learnt to refine and rehearse collaborative outbreak response plans in between epidemics.
Topics: Betacoronavirus; Biomedical Research; COVID-19; Coronavirus Infections; Delivery of Health Care; Disease Outbreaks; Ebolavirus; Epidemics; Global Health; Health Services Needs and Demand; Humans; Influenza A Virus, H1N1 Subtype; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32586391
DOI: 10.1186/s12916-020-01624-8