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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 -
Human Vaccines & Immunotherapeutics Nov 2017The aim of this systematic review was to examine the etiology of community-acquired pneumonia (CAP) among Chinese children younger than 5 y and provide evidence for... (Review)
Review
BACKGROUND
The aim of this systematic review was to examine the etiology of community-acquired pneumonia (CAP) among Chinese children younger than 5 y and provide evidence for further cost-effectiveness analyses for vaccine development, diagnostic strategies and empirical treatments.
METHODS
The literature review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Data were obtained by searching PubMed, Embase, Web-of Science, and the Chinese databases Wanfang Data and China National Knowledge Infrastructure. All CAP etiological studies on children under 5 y of age from China published in Chinese and English between the years of 2001 and 2015 were included. A total of 48 studies were included in the final review, comprising 100 151 hospitalized children with CAP episodes. Heterogeneity and the percentage of variation between studies was analyzed based on Q statistic and I indices, respectively. Random effect models were used to calculate the weighted average rate in all analyses.
RESULTS
The most frequently detected bacterial agents were Klebsiella pneumoniae (5.4%), Streptococcus pneumoniae (5.2%), Escherichia coli (5.2%), Staphylococcus aureus (3.9%), Haemophilus influenza (3.6%) and Haemophilus parainfluenzae (3.3%). The most frequently detected viruses were human rhinovirus (20.3%, in just 2 studies), respiratory syncytial virus (RSV, 17.3%), human bocavirus (9.9%), parainfluenza virus (5.8%), human metapneumovirus (3.9%) and influenza (3.5%). Mycoplasma pneumoniae and Chlamydophila pneumoniae were identified in 9.5% and 2.9%, respectively, of children under 5 y of age with CAP.
CONCLUSION
This article provides the most comprehensive analysis to date of the factors contributing to CAP in children under 5 y of age. S. pneumoniae, H. influenzae and influenza were the most common vaccine-preventable diseases in children. Corresponding, vaccines should be introduced into Chinese immunization programs, and further economic evaluations should be conducted. RSV is common in Chinese children and preventative measures could have a substantial impact on public health. These data also have major implications for diagnostic strategies and empirical treatments.
Topics: Child, Hospitalized; Child, Preschool; China; Community-Acquired Infections; Female; Haemophilus Infections; Haemophilus influenzae; Humans; Immunization Programs; Infant; Male; Mycoplasma pneumoniae; Pneumonia; Pneumonia, Mycoplasma; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Staphylococcus aureus; Streptococcus pneumoniae; Viruses
PubMed: 28922613
DOI: 10.1080/21645515.2017.1371381 -
Jornal de Pediatria 2017The aim of this review was to address advances in management and treatment of acute viral bronchiolitis in infants. (Review)
Review
OBJECTIVE
The aim of this review was to address advances in management and treatment of acute viral bronchiolitis in infants.
SOURCES
A systematic review search was made including all articles published in English between 2010 and 2017, and available in the electronic databases PubMed and Cochrane Central Register of Controlled Trials (CENTRAL) and specialized register of the Acute Respiratory Infections Group (Cochrane review group). The following MESH terms in English were included, using different Boolean operators for the search strategy: "bronchiolitis, viral," "diagnosis," "epidemiology," "etiology," "therapy," "virology," "prevention and control," "respiratory syncytial virus, human." Additional filters were used.
SUMMARY OF FINDINGS
Few effective interventions are recommended for the management of RSV bronchiolitis in young infants. The main goal is to ensure an adequate oxygen supplementation and fluid balance whenever deemed necessary. Hypertonic saline nebulization is helpful only for hospitalized infants. Numerous antiviral drugs and specific vaccines for RSV are under evaluation and foretell advances in disease management in the near future.
CONCLUSION
A number of promising new technologies are advancing in the field. Until new interventions became feasible, early detection and modification of preventable risk factors is essential to improve outcomes.
Topics: Acute Disease; Bronchiolitis, Viral; Humans; Infant, Newborn; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 28859915
DOI: 10.1016/j.jped.2017.07.003 -
Lancet (London, England) Sep 2017We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI)... (Review)
Review
Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study.
BACKGROUND
We have previously estimated that respiratory syncytial virus (RSV) was associated with 22% of all episodes of (severe) acute lower respiratory infection (ALRI) resulting in 55 000 to 199 000 deaths in children younger than 5 years in 2005. In the past 5 years, major research activity on RSV has yielded substantial new data from developing countries. With a considerably expanded dataset from a large international collaboration, we aimed to estimate the global incidence, hospital admission rate, and mortality from RSV-ALRI episodes in young children in 2015.
METHODS
We estimated the incidence and hospital admission rate of RSV-associated ALRI (RSV-ALRI) in children younger than 5 years stratified by age and World Bank income regions from a systematic review of studies published between Jan 1, 1995, and Dec 31, 2016, and unpublished data from 76 high quality population-based studies. We estimated the RSV-ALRI incidence for 132 developing countries using a risk factor-based model and 2015 population estimates. We estimated the in-hospital RSV-ALRI mortality by combining in-hospital case fatality ratios with hospital admission estimates from hospital-based (published and unpublished) studies. We also estimated overall RSV-ALRI mortality by identifying studies reporting monthly data for ALRI mortality in the community and RSV activity.
FINDINGS
We estimated that globally in 2015, 33·1 million (uncertainty range [UR] 21·6-50·3) episodes of RSV-ALRI, resulted in about 3·2 million (2·7-3·8) hospital admissions, and 59 600 (48 000-74 500) in-hospital deaths in children younger than 5 years. In children younger than 6 months, 1·4 million (UR 1·2-1·7) hospital admissions, and 27 300 (UR 20 700-36 200) in-hospital deaths were due to RSV-ALRI. We also estimated that the overall RSV-ALRI mortality could be as high as 118 200 (UR 94 600-149 400). Incidence and mortality varied substantially from year to year in any given population.
INTERPRETATION
Globally, RSV is a common cause of childhood ALRI and a major cause of hospital admissions in young children, resulting in a substantial burden on health-care services. About 45% of hospital admissions and in-hospital deaths due to RSV-ALRI occur in children younger than 6 months. An effective maternal RSV vaccine or monoclonal antibody could have a substantial effect on disease burden in this age group.
FUNDING
The Bill & Melinda Gates Foundation.
Topics: Child, Preschool; Developing Countries; Global Health; Hospital Mortality; Hospitalization; Humans; Incidence; Infant; Infant, Newborn; Models, Statistical; Respiratory Syncytial Viruses; Respiratory Tract Infections; Risk Factors
PubMed: 28689664
DOI: 10.1016/S0140-6736(17)30938-8 -
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 -
Clinical Microbiology Reviews Apr 2017Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response... (Review)
Review
Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response to RSV comes from animal models and studies. Here, we provide a comprehensive description of the human immune response to RSV infection, based on a systematic literature review of research on infected humans. There is an initial strong neutrophil response to RSV infection in humans, which is positively correlated with disease severity and mediated by interleukin-8 (IL-8). Dendritic cells migrate to the lungs as the primary antigen-presenting cell. An initial systemic T-cell lymphopenia is followed by a pulmonary CD8 T-cell response, mediating viral clearance. Humoral immunity to reinfection is incomplete, but RSV IgG and IgA are protective. B-cell-stimulating factors derived from airway epithelium play a major role in protective antibody generation. Gamma interferon (IFN-γ) has a strongly protective role, and a Th2-biased response may be deleterious. Other cytokines (particularly IL-17A), chemokines (particularly CCL-5 and CCL-3), and local innate immune factors (including cathelicidins and IFN-λ) contribute to pathogenesis. In summary, neutrophilic inflammation is incriminated as a harmful response, whereas CD8 T cells and IFN-γ have protective roles. These may represent important therapeutic targets to modulate the immunopathogenesis of RSV infection.
Topics: Cytokines; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; T-Lymphocytes
PubMed: 28179378
DOI: 10.1128/CMR.00090-16 -
Pediatric Pulmonology Apr 2017Respiratory syncytial virus (RSV) is a major public health burden worldwide. We aimed to review the current literature on the incidence and mortality of severe RSV in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Respiratory syncytial virus (RSV) is a major public health burden worldwide. We aimed to review the current literature on the incidence and mortality of severe RSV in children globally.
METHODS
Systematic literature review and meta-analysis of published data from 2000 onwards, reporting on burden of acute respiratory infection (ARI) due to RSV in children. Main outcomes were hospitalization for severe RSV-ARI and death.
RESULTS
Five thousand two hundred and seventy-four references were identified. Fifty-five studies were included from 32 countries. The global RSV-ARI hospitalization estimates, reported per 1,000 children per year (95% Credible Interval (CrI), were 4.37 (2.98, 6.42) among children <5 years, 19.19 (15.04, 24.48) among children <1 year, 20.01 (9.65, 41.31) among children <6 months and 63.85 (37.52, 109.70) among premature children <1 year. The RSV-ARI global case-fatality estimates, reported per 1,000 children, (95% Crl) were 6.21 (2.64, 13.73) among children <5 years, 6.60 (1.85, 16.93) for children <1 year, and 1.04 (0.17, 12.06) among preterm children <1 year.
CONCLUSIONS
A substantial proportion of RSV-associated morbidity occurs in the first year of life, especially in children born prematurely. These data affirm the importance of RSV disease in the causation of hospitalization and as a significant contributor to pediatric mortality and further demonstrate gestational age as a critical determinant of disease severity. An important limitation of case-fatality ratios is the absence of individual patient characteristics of non-surviving patients. Moreover, case-fatality ratios cannot be translated to population-based mortality. Pediatr Pulmonol. 2017;52:556-569. © 2016 The Authors. Pediatric Pulmonology. Published by Wiley Periodicals, Inc.
Topics: Child; Child Health Services; Child, Preschool; Global Health; Hospitalization; Humans; Incidence; Infant; Infant, Newborn; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses
PubMed: 27740723
DOI: 10.1002/ppul.23570 -
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 -
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 -
Journal of Global Health Dec 2015Respiratory syncytial virus (RSV) is the most important cause of acute respiratory tract infection (ARTI) related morbidity and mortality worldwide. However, the disease... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Respiratory syncytial virus (RSV) is the most important cause of acute respiratory tract infection (ARTI) related morbidity and mortality worldwide. However, the disease burden due to RSV has not been systematically summarized in China.
METHOD
A systematic search was performed in the Chinese BioMedical Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang database and PubMed to identify available published RSV studies in China.
RESULTS
A total of 489 641 patients with ARTIs from 135 studies were included in the analysis. Among patients with ARTIs, RSV accounted for 18.7% (95% confidence interval CI 17.1-20.5%). The prevalence of RSV was highest in infants (26.5%, 95% CI 23.7-29.5%) and lowest in those aged ≥16 years (2.8%, 95% CI 1.3-6.1). A higher prevalence of RSV was seen in inpatients (22%, 95% CI 19.9-24.2%) than in outpatients (14%, 95% CI 9.6-19.9%). RSV type A accounted for 63.1% (95% CI 52.3-72.8%) of all RSV infections. RSV infections occurred mainly in winter and spring. The most common clinical manifestations were cough, production of sputum, wheezing and fever.
CONCLUSION
RSV is the leading cause of viral ARTIs in China, particularly in infants and young children. Our findings are valuable for guiding the selection of appropriate therapies for ARTIs and implementation of preventive measures against RSV infections. Our data further supports the development of a successful RSV vaccine as a high priority.
Topics: Adult; Child; Child, Preschool; China; Hospitalization; Humans; Infant; Prevalence; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Seasons
PubMed: 26682049
DOI: 10.7189/jogh.05.020417