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Expert Review of Anti-infective Therapy Jun 2017Influenza-Like Illness is a leading cause of hospitalization in children. Disease burden due to influenza and other respiratory viral infections is reported on a... (Review)
Review
Influenza-Like Illness is a leading cause of hospitalization in children. Disease burden due to influenza and other respiratory viral infections is reported on a population level, but clinical scores measuring individual changes in disease severity are urgently needed. Areas covered: We present a composite clinical score allowing individual patient data analyses of disease severity based on systematic literature review and WHO-criteria for uncomplicated and complicated disease. The 22-item ViVI Disease Severity Score showed a normal distribution in a pediatric cohort of 6073 children aged 0-18 years (mean age 3.13; S.D. 3.89; range: 0 to 18.79). Expert commentary: The ViVI Score was correlated with risk of antibiotic use as well as need for hospitalization and intensive care. The ViVI Score was used to track children with influenza, respiratory syncytial virus, human metapneumovirus, human rhinovirus, and adenovirus infections and is fully compliant with regulatory data standards. The ViVI Disease Severity Score mobile application allows physicians to measure disease severity at the point-of care thereby taking clinical trials to the next level.
Topics: Adenoviridae; Adolescent; Anti-Bacterial Agents; Child; Child, Preschool; Clinical Trials as Topic; Coinfection; Female; Humans; Infant; Influenza A virus; Influenza B virus; Male; Metapneumovirus; Mobile Applications; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Rhinovirus; Severity of Illness Index
PubMed: 28277820
DOI: 10.1080/14787210.2017.1295847 -
The Journal of Pediatrics Dec 2021To describe the features and frequency of respiratory syncytial virus (RSV)-associated severe acute neurologic disease in children.
OBJECTIVES
To describe the features and frequency of respiratory syncytial virus (RSV)-associated severe acute neurologic disease in children.
STUDY DESIGN
We performed a systematic review of the literature to identify reports of severe acute neurologic complications associated with acute RSV infection in children aged <15 years (PROSPERO Registration CRD42019125722). Main outcomes included neurologic, clinical, and demographic features of cases and the frequency of disease. We aggregated available case data from the published literature and from the Australian Acute Childhood Encephalitis (ACE) study.
RESULTS
We identified 87 unique studies from 26 countries describing a spectrum of RSV-associated severe acute neurologic syndromes including proven encephalitis, acute encephalopathy, complex seizures, hyponatremic seizures, and immune-mediated disorders. The frequency of RSV infection in acute childhood encephalitis/encephalopathy was 1.2%-6.5%. We aggregated data from 155 individual cases with RSV-associated severe acute neurologic complications; median age was 11.0 months (IQR 2.0-21.5), most were previously healthy (71/104, 68%). Seizure was the most frequently reported neurologic feature (127/150, 85%). RSV was detected in the central nervous system of 12 cases. Most children recovered (81/122, 66%); however, some reports described partial recovery (33/122, 27%) and death (8/122, 7%).
CONCLUSIONS
RSV-associated neurologic complications have been widely reported, but there is substantial heterogeneity in the design and quality of existing studies. The findings from our study have implications for the investigation, management, and prevention of RSV-associated neurologic complications. Further, this systematic review can inform the design of future studies aiming to quantify the burden of childhood RSV-associated neurologic disease.
Topics: Adolescent; Child; Child, Preschool; Diagnostic Tests, Routine; Female; Humans; Incidence; Infant; Male; Nervous System Diseases; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 34181989
DOI: 10.1016/j.jpeds.2021.06.045 -
Influenza and Other Respiratory Viruses Jul 2016Respiratory syncytial virus (RSV) causes a significant public health burden, and outbreaks among vulnerable patients in hospital settings are of particular concern. We... (Review)
Review
Respiratory syncytial virus (RSV) causes a significant public health burden, and outbreaks among vulnerable patients in hospital settings are of particular concern. We reviewed published and unpublished literature from hospital settings to assess: (i) nosocomial RSV transmission risk (attack rate) during outbreaks, (ii) effectiveness of infection control measures. We searched the following databases: MEDLINE, EMBASE, CINAHL, Cochrane Library, together with key websites, journals and grey literature, to end of 2012. Risk of bias was assessed using the Cochrane risk of bias tool or Newcastle-Ottawa scale. A narrative synthesis was conducted. Forty studies were included (19 addressing research question one, 21 addressing question two). RSV transmission risk varied by hospital setting; 6-56% (median: 28·5%) in neonatal/paediatric settings (n = 14), 6-12% (median: 7%) in adult haematology and transplant units (n = 3), and 30-32% in other adult settings (n = 2). For question two, most studies (n = 13) employed multi-component interventions (e.g. cohort nursing, personal protective equipment (PPE), isolation), and these were largely reported to be effective in reducing nosocomial transmission. Four studies examined staff PPE; eye protection appeared more effective than gowns and masks. One study reported on RSV prophylaxis for patients (RSV-Ig/palivizumab); there was no statistical evidence of effectiveness although the sample size was small. Overall, risk of bias for included studies tended to be high. We conclude that RSV transmission risk varies widely during hospital outbreaks. Although multi-component control strategies appear broadly successful, further research is required to disaggregate the effectiveness of individual components including the potential role of palivizumab prophylaxis.
Topics: Animals; Cross Infection; Humans; Infection Control; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 26901358
DOI: 10.1111/irv.12379 -
Current Molecular Pharmacology 2020Nipah virus (NiV) and Hendra virus (HeV) of genus Henipavirus are the deadliest zoonotic viruses, which cause severe respiratory ailments and fatal encephalitis in...
BACKGROUND
Nipah virus (NiV) and Hendra virus (HeV) of genus Henipavirus are the deadliest zoonotic viruses, which cause severe respiratory ailments and fatal encephalitis in humans and other susceptible animals. The fatality rate for these infections had been alarmingly high with no approved treatment available to date. Viral attachment and fusion with host cell membrane is essential for viral entry and is the most essential event of viral infection. Viral attachment is mediated by interaction of Henipavirus attachment glycoprotein (G) with the host cell receptor: Ephrin B2/B3, while viral fusion and endocytosis are mediated by the combined action of both viral glycoprotein (G) and fusion protein (F).
CONCLUSION
This review highlights the mechanism of viral attachment, fusion and also explains the basic mechanism and pathobiology of this infection in humans. The drugs and therapeutics used either experimentally or clinically against NiV and HeV infection have been documented and classified in detail. Some amino acid residues essential for the functionality of G and F proteins were also emphasized. Therapeutic designing to target and block these residues can serve as a promising approach in future drug development against NiV and HeV.
Topics: Animals; Antiviral Agents; Drug Design; Hendra Virus; Henipavirus Infections; Humans; Nipah Virus; Virus Internalization
PubMed: 31657692
DOI: 10.2174/1874467212666191023123732 -
Health Technology Assessment... Dec 2008To systematically review the effectiveness and cost-effectiveness of palivizumab for the prevention of respiratory syncytial virus (RSV) in children and examine... (Review)
Review
OBJECTIVES
To systematically review the effectiveness and cost-effectiveness of palivizumab for the prevention of respiratory syncytial virus (RSV) in children and examine prognostic factors to determine whether subgroups can be identified with important differences in cost-effectiveness.
DATA SOURCES
Bibliographic databases were searched from inception to March 2007 for literature on the effectiveness and cost-effectiveness of prophylaxis with palivizumab.
REVIEW METHODS
The literature was systematically reviewed and current economic evaluations were analysed to identify which parameters were driving the different cost-effectiveness estimates. A probabilistic decision-analytical model was built to assess the cost-effectiveness of prophylaxis with palivizumab for children at risk of RSV infection and the parameters populated with the best estimates thought most applicable to the UK. We also constructed a new model, the Birmingham Economic Evaluation (BrumEE). Cost-effectiveness analyses were undertaken from both NHS and societal perspectives.
RESULTS
Two randomised controlled trials (RCTs) were identified. Prophylaxis with palivizumab for preterm infants without chronic lung disease (CLD) or children with CLD resulted in a 55% reduction in RSV hospital admission: 4.8% (48/1002) in the palivizumab group and 10.6% (53/500) in the no prophylaxis group (p = 0.0004). Prophylaxis with palivizumab was associated with a 45% reduction in hospitalisation rate RSV among children with coronary heart disease (CHD). Hospitalisation rates for RSV were 5.3% (34/639) in the palivizumab group and 9.7% (63/648) in the no prophylaxis group (p = 0.003). Of existing economic evaluations, 3 systematic reviews and 18 primary studies were identified. All the systematic reviews concluded that the potential costs of palivizumab were far in excess of any potential savings achieved by decreasing hospital admission rates, and that the use of palivizumab was unlikely to be cost-effective in all children for whom it is recommended, but that its continued use for particularly high-risk children may be justified. The incremental cost-effectiveness ratios (ICERs) of the primary studies varied 17-fold for life-years gained (LYG), from 25,800 pounds/LYG to 404,900 pounds/LYG, and several hundred-fold for quality-adjusted life-years (QALYs), from 3200 pounds/QALY to 1,489,700 pounds/QALY for preterm infants without CLD or children with CLD. For children with CHD, the ICER varied from 5300 pounds/LYG to 7900 pounds/LYG and from 7500 pounds/QALY to 68,700 pounds/QALY. An analysis of what led to the discrepant ICERs showed that the assumed mortality rate for RSV infection was the most important driver. The results of the BrumEE confirm that palivizumab does not reach conventional levels of cost-effectiveness in any of the licensed indications if used for all eligible children.
CONCLUSIONS
Prophylaxis with palivizumab is clinically effective for the reducing the risk of serious lower respiratory tract infection caused by RSV infection and requiring hospitalisation in high-risk children, but if used unselectively in the licensed population, the ICER is double that considered to represent good value for money in the UK. The BrumEE shows that prophylaxis with palivizumab may be cost-effective (based on a threshold of 30,000 pounds/QALY) for children with CLD when the children have two or more additional risk factors. Future research should initially focus on reviewing systematically the major uncertainties for patient subgroups with CLD and CHD and then on primary research to address the important uncertainties that remain.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antiviral Agents; Evidence-Based Medicine; Humans; Infant; Infant, Newborn; Palivizumab; Preventive Medicine; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; United Kingdom
PubMed: 19049692
DOI: 10.3310/hta12360 -
The Pediatric Infectious Disease Journal Jul 2016Studies have explored the risk for and impact of respiratory syncytial virus (RSV) infection requiring hospitalization among healthy preterm infants born at 29-35 weeks... (Review)
Review
BACKGROUND
Studies have explored the risk for and impact of respiratory syncytial virus (RSV) infection requiring hospitalization among healthy preterm infants born at 29-35 weeks of gestational age not given RSV immunoprophylaxis. We performed a systematic review and qualitative synthesis of these studies.
METHODS
Two experienced reviewers used prespecified inclusion/exclusion criteria to screen titles/abstracts and full-text studies using MEDLINE, Embase, BIOSIS and Cochrane Library (January 1, 1985, to November 6, 2014). We abstracted data on risk factors for RSV hospitalization, incidence and short- and long-term outcomes of RSV hospitalization. Using standard procedures, we assessed study risk of bias and graded strength of evidence (SOE).
RESULTS
We identified 4754 records and reviewed 27. Important risk factors for RSV hospitalization included young age during the RSV season, having school-age siblings and day-care attendance, with odds ratios >2.5 in at least one study (high SOE). Incidence rates for RSV hospitalizations ranged from 2.3% to 10% (low SOE). Length of hospital stays ranged from 3.8 to 6.1 days (low SOE). Recurrent wheezing rates ranged from 20.7% to 42.8% 1 to 2 years after RSV hospitalization (low SOE).
CONCLUSIONS
Young chronological age and some environmental risk factors are important clinical indicators of an increased risk of RSV hospitalization in healthy preterm infants 32 to 35 weeks of gestational age. SOE was low for estimates of incidence of RSV hospitalizations, in-hospital resource use and recurrent wheezing in this population. Studies were inconsistent in study characteristics, including weeks of gestational age, age during RSV season and control for confounding factors.
Topics: Gestational Age; Hospitalization; Humans; Incidence; Infant, Premature; Infant, Premature, Diseases; Palivizumab; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Risk Factors; Seasons; Treatment Outcome
PubMed: 27093166
DOI: 10.1097/INF.0000000000001163 -
PharmacoEconomics Mar 2021Several vaccine and antibody candidates are currently in development for the prevention of lower respiratory tract infections caused by the respiratory syncytial virus...
Assessment of the Effects of Active Immunisation against Respiratory Syncytial Virus (RSV) using Decision-Analytic Models: A Systematic Review with a Focus on Vaccination Strategies, Modelling Methods and Input Data.
BACKGROUND
Several vaccine and antibody candidates are currently in development for the prevention of lower respiratory tract infections caused by the respiratory syncytial virus (RSV).
METHODS
We searched MEDLINE, Embase, and SCOPUS and included model-based evaluations of RSV vaccinations. Two reviewers performed the selection, data extraction, and quality evaluation with EVIDEM. Cost-effectiveness (CE) estimates were converted to $US purchasing power parity (PPP), year 2018 values. Potential economic and epidemiological outcomes were summarised for maternal, infant, children, and elderly vaccinations. The PROSPERO identifier is CRD42019122570.
RESULTS
In total, 22 model-based studies were reviewed. On average, a potential 27% reduction in RSV hospitalisations in infants was projected for maternal vaccination and 50% for direct infant immunisation. The CE of maternal vaccination was $US1766-5857 PPP 2018/disability-adjusted life-years (DALYs) for Global Alliance for Vaccines and Immunisation (Gavi)-eligible countries. For England, the maximum cost-effective price of maternal vaccination was estimated at $US81.5 PPP 2018. Infant vaccination was associated with higher CE ratios in low- and high-income settings. Vaccination of neonates born before the RSV season was the most cost effective in high-income settings. Higher values for vaccine effectiveness, duration of protection, and vaccine uptake increased the benefits. Due to indirect effects, the vaccination of school-age children and a cocooning strategy were effective alternatives to protect infants, and the vaccination of children aged < 5 years had a beneficial impact on the elderly.
CONCLUSION
RSV vaccines with anticipated characteristics may reduce a sizeable proportion of the RSV burden. The results are subject to uncertainty because of the limited epidemiological and clinical data. Data on RSV incidence and hospitalisation risk for granular age strata should be prioritised to facilitate the evaluation of RSV interventions and decision making.
Topics: Aged; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Pregnancy; Quality-Adjusted Life Years; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human; Vaccination
PubMed: 33462760
DOI: 10.1007/s40273-020-00991-7 -
The Pediatric Infectious Disease Journal May 2021Human metapneumovirus (hMPV) has been associated with upper and lower respiratory tract infections (LRTI) in children and adults. This systematic review evaluated the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Human metapneumovirus (hMPV) has been associated with upper and lower respiratory tract infections (LRTI) in children and adults. This systematic review evaluated the epidemiology of hMPV-associated LRTI, including severe acute respiratory infection (SARI) hospitalization or clinically diagnosed severe pneumonia, in African children under 5 years of age.
METHODS
We searched Science Direct, PubMed, Cochrane Central, Scopus, and WHO regional databases using the terms "("Human metapneumovirus" AND "Africa") OR ("hMPV" AND "Africa")" up to September 17, 2020. Other sources included ClinicalTrials.gov to obtain unpublished data. Studies were included if children were less than 5 years of age and hospitalized with hMPV-associated LRTI, SARI or if clinically diagnosed with severe pneumonia in the community. The main outcomes were prevalence of hMPV identified among children with hospitalized LRTI or SARI. We further calculated odds ratios for hMPV in cases with LRTI compared with non-LRTI controls. Pooled results were calculated using a random-effects model.
RESULTS
Thirty studies were eligible for inclusion in the review. The prevalence of hMPV-LRTI/SARI among hospitalized and severe pneumonia cases was 4.7% [95% confidence interval (CI): 3.9-5.6, I2 = 95.0]. The case-control studies indicated that hMPV was 2.0-fold (95% CI: 0.9-4.4) more likely to be identified in LRTI cases (10.3%) than controls (6.0%). Three of 5 studies reported hMPV-associated LRTI case fatality risk, with a pooled estimate of 1.3% (95% CI: 0.3-2.9; I2 = 49).
CONCLUSIONS
hMPV was associated with approximately 5% of LRTI/SARI hospitalizations or severe pneumonia cases in Africa.
Topics: Africa; Child, Preschool; Hospitalization; Humans; Infant; Metapneumovirus; Paramyxoviridae Infections; Pneumonia; Prevalence; Respiratory Tract Infections
PubMed: 33480663
DOI: 10.1097/INF.0000000000003041 -
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 -
Reviews in Medical Virology Jan 2014Respiratory syncytial virus is the most common respiratory virus infection in early childhood, causing a wide range of illness from mild colds to life-threatening croup,... (Review)
Review
Respiratory syncytial virus is the most common respiratory virus infection in early childhood, causing a wide range of illness from mild colds to life-threatening croup, bronchiolitis and pneumonia that may require intensive care. Exactly which parameters contribute to the seasonality of RSV (and other respiratory viruses, such as influenza) and their comparative significance are the subject of ongoing intensive debate. This review article summarises the specific contributions and correlations between the incidence of RSV and various climate parameters. This systematic review of the literature specifically focuses on these climate associations and have been stratified by study site latitudes: tropical (0-23.5°N or S), subtropical (23.5-40°N or S) and temperate latitudes (>40°N or S). Correlations between RSV incidence and temperature and relative humidity are particularly variable and inconsistent amongst the tropical regions. In subtropical and temperate regions, RSV incidence is more consistently positively correlated with lower temperatures and higher relative humidity. Although there is some variation with the diagnostic methods used in these studies, most used immunofluorescent viral antigen testing to diagnose RSV infection. Statistically, most studies used some form of regression analysis, which assumes no dependence between data taken at different time points. A few used the autoregressive integrated moving average approach, which may be more realistic for an infectious agent as the total number of cases usually evolves in a time-dependent manner during a typical seasonal epidemic.
Topics: Climate; Humans; Humidity; Incidence; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Seasons; Temperature
PubMed: 24421259
DOI: 10.1002/rmv.1771