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Journal of Global Health Dec 2017Acute lower respiratory tract infections (ALRIs) caused by respiratory syncytial virus (RSV) are a leading cause of hospitalization in infants. Numerous risk factors... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute lower respiratory tract infections (ALRIs) caused by respiratory syncytial virus (RSV) are a leading cause of hospitalization in infants. Numerous risk factors have been identified in the aetiology of severe RSV-associated ALRI necessitating hospitalisation, including prematurity and congenital heart disease. Down syndrome (DS), a common genetic disorder associated with congenital and dysmorphic features, has recently been identified as an independent risk factor for RSV-associated ALRI requiring hospitalisation; however, the disease burden of RSV-associated ALRI in this population has not yet been established. Similarly, the impact of DS as an independent risk factor has not yet been quantified. We aimed therefore to estimate the incidence of admissions in children with DS, and by comparing this with unaffected children, to quantify the risk of DS independent of other risk factors.
METHODS
A systematic review of the existing literature published between 1995 and March 1, 2017 was performed to quantify the incidence of hospitalisation due to RSV-associated ALRI in children with DS. Meta-analyses were performed on extracted data using STATA statistical software, and hospitalisation rates for children with and without DS under the age of 2 were calculated.
FINDINGS
5 articles were ultimately deemed eligible for analyses. Analyses were limited to children under the age of 2 years. We calculated the hospitalisation rate for children with DS in this age group to be 117.6 per 1000 child-years (95% CI 67.4-205.2), vs a rate of 15.2 per 1000 child-years (95% CI 8.3-27.6) in unaffected children. This indicates DS contributes to a 6.8 (95% CI 5.5-8.4) fold increase in the relative risk of hospitalisation for RSV-associated ALRI.
INTERPRETATION
Though limited by a small number of articles, this review found sufficient evidence to conclude DS was a significant independent risk factor for the development of severe RSV-associated ALRI requiring hospitalisation. Further studies are needed to define the impact of DS in conjunction with other comorbidities on the risk of severe RSV infection. Determining benefits of immunoprophylaxis or future vaccines against RSV in this at-risk population is warranted.
Topics: Acute Disease; Child; Down Syndrome; Hospitalization; Humans; Incidence; Respiratory Syncytial Viruses; Respiratory Tract Infections; Risk Factors
PubMed: 29302319
DOI: 10.7189/jogh.07.020413 -
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 -
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 -
Epidemics Jun 2021Due to high burden of respiratory syncytial virus (RSV) in low- and middle-income countries (LMIC), international funding organizations have prioritized the development...
BACKGROUND
Due to high burden of respiratory syncytial virus (RSV) in low- and middle-income countries (LMIC), international funding organizations have prioritized the development of RSV vaccines. Mathematical models of RSV will play an important role in assessing the relative value of these interventions. Our objectives were to provide an overview of the existing RSV modelling literature in LMIC and summarize available results on population-level effectiveness and cost-effectiveness.
METHODS
We searched MEDLINE from 2000 to 2020 for English language publications that employed a mathematical model of RSV calibrated to LMIC. Qualitative data were extracted on study and model characteristics. Quantitative data were collected on key model input assumptions and base case effectiveness and cost-effectiveness estimates for various immunization strategies.
FINDINGS
Of the 283 articles reviewed, 15 met inclusion criteria. Ten studies used modelling techniques to explore RSV transmission and/or natural history, while eight studies evaluated RSV vaccines and/or monoclonal antibodies, three of which included cost-effectiveness analyses. Six studies employed deterministic compartmental models, five studies employed individual transmission models, and four studies used different types of cohort models. Nearly every model was calibrated to at least one middle-income country, while four were calibrated to low-income countries.
INTERPRETATION
The mathematical modelling literature in LMIC has demonstrated the potential effectiveness of RSV vaccines and monoclonal antibodies. This review has demonstrated the importance of accounting for seasonality, social contact rates, immunity from prior infection and maternal antibody transfer. Future models should consider incorporating individual-level risk factors, subtype-specific effects, long-term sequelae of RSV infections, and out-of-hospital mortality.
Topics: Developing Countries; Humans; Models, Theoretical; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus, Human
PubMed: 33662812
DOI: 10.1016/j.epidem.2021.100444 -
BMC Infectious Diseases Oct 2022Respiratory syncytial virus (RSV) and influenza viruses are important global causes of morbidity and mortality. We evaluated the diagnostic accuracy of the Luminex NxTAG... (Meta-Analysis)
Meta-Analysis
Respiratory syncytial virus (RSV) and influenza viruses are important global causes of morbidity and mortality. We evaluated the diagnostic accuracy of the Luminex NxTAG respiratory pathogen panels (RPPs)™ (index) against other RPPs (comparator) for detection of RSV and influenza viruses. Studies comparing human clinical respiratory samples tested with the index and at least one comparator test were included. A random-effect latent class meta-analysis was performed to assess the specificity and sensitivity of the index test for RSV and influenza. Risk of bias was assessed using the QUADAS-2 tool and certainty of evidence using GRADE. Ten studies were included. For RSV, predicted sensitivity was 99% (95% credible interval [CrI] 96-100%) and specificity 100% (95% CrI 98-100%). For influenza A and B, predicted sensitivity was 97% (95% CrI 89-100) and 98% (95% CrI 88-100) respectively; specificity 100% (95% CrI 99-100) and 100% (95% CrI 99-100), respectively. Evidence was low certainty. Although index sensitivity and specificity were excellent, comparators' performance varied. Further research with clear patient recruitment strategies could ascertain performance across different populations.Protocol Registration: Prospero CRD42021272062.
Topics: Humans; Influenza A virus; Influenza B virus; Influenza, Human; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Sensitivity and Specificity
PubMed: 36229786
DOI: 10.1186/s12879-022-07766-9 -
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 -
International Journal of Infectious... Jan 2020The present study provides a comprehensive review of the recently published data on RSV epidemiology in adults and the elderly in Latin America. (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The present study provides a comprehensive review of the recently published data on RSV epidemiology in adults and the elderly in Latin America.
METHODS
A systematic literature search was carried out in Medline, Scielo, Lilacs, and Cochrane Library. The search strategy aimed at retrieving studies focusing on RSV prevalence, burden, risk factors, and the routine clinical practice in the prevention and management of RSV infections in Latin American countries. Only articles published between January 2011 and December 2017 were considered.
RESULTS
Eighteen studies were included. Percentages of RSV detection varied highly across included studies for adult subjects with respiratory infections (0% to 77.9%), influenza-like illness (1.0% to 16.4%) and community-acquired pneumonia (1.3% to 13.5%). Considerable percentages of hospitalization were reported for RSV-infected adults with influenza-like illness (40.9% and 69.9%) and community-acquired pneumonia (91.7%).
CONCLUSIONS
Recent RSV data regarding adult populations in Latin America are scarce. RSV was documented as a cause of illness in adults and the elderly, being identified in patients with acute respiratory infections, influenza-like illness and community-acquired pneumonia. The studies suggest that RSV infections may be a significant cause of hospitalization in adult populations in Latin America, including younger adults.
Topics: Adult; Aged; Aged, 80 and over; Community-Acquired Infections; Female; Hospitalization; Humans; Latin America; Male; Middle Aged; Prevalence; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Risk Factors; Young Adult
PubMed: 31669592
DOI: 10.1016/j.ijid.2019.10.025 -
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 -
The Pediatric Infectious Disease Journal May 2024Acute lower respiratory infection (ALRI) caused by respiratory viruses is among the most common causes of hospitalization and mortality in children. We aimed to identify... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute lower respiratory infection (ALRI) caused by respiratory viruses is among the most common causes of hospitalization and mortality in children. We aimed to identify risk factors for poor outcomes in children <5 years old hospitalized with ALRI caused by respiratory syncytial virus (RSV), influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
METHODS
We searched Embase, Medline and Global Health databases and included observational studies reporting risk factors for poor outcomes (defined as use of supplemental oxygen, mechanical ventilation, intensive care unit admission, prolonged hospital stay and mortality) published between January 2011 and January 2023. Two authors independently extracted data on study characteristics, outcomes and risk factors. Due to limited data, meta-analyses were only conducted for RSV-ALRI poor outcome risk factors using random effects model when there were at least 3 studies.
RESULTS
We included 30 studies. For RSV-related ALRI, significant risk factors based on meta-analysis were: neurological disease [odds ratio (OR): 6.14; 95% confidence intervals (CIs): 2.39-15.77], Down's syndrome (5.43; 3.02-9.76), chronic lung disease (3.64; 1.31-10.09), immunocompromised status (3.41; 1.85-6.29), prematurity (2.98; 1.93-4.59), congenital heart disease (2.80; 1.84-4.24), underlying disease (2.45; 1.94-3.09), age <2 months (2.29; 1.78-2.94), age <6 months (2.08; 1.81-2.39), viral coinfection (2.01; 1.27-3.19), low birth weight (1.88; 1.19-2.95) and being underweight (1.80; 1.38-2.35). For influenza-related ALRI, chronic conditions and age 6-24 months were identified as risk factors for poor outcomes. Cardiovascular disease, immunosuppression, chronic kidney disease, diabetes and high blood pressure were reported as risk factors for mortality due to SARS-CoV-2 associated ALRI.
CONCLUSIONS
These findings might contribute to the development of guidelines for prophylaxis and management of ALRI caused by RSV, influenza and SARS-CoV-2.
Topics: Infant, Newborn; Child; Humans; Infant; Child, Preschool; Influenza, Human; Respiratory Tract Infections; Infant, Premature; Hospitalization; Risk Factors; Respiratory Syncytial Virus, Human; Respiratory Syncytial Virus Infections
PubMed: 38285519
DOI: 10.1097/INF.0000000000004258