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Journal of Global Health Jul 2022This systematic review aimed to describe common aetiologies of severe and non-severe community acquired pneumonia among children aged 1 month to 9 years in low- and...
BACKGROUND
This systematic review aimed to describe common aetiologies of severe and non-severe community acquired pneumonia among children aged 1 month to 9 years in low- and middle-income countries.
METHODS
We searched the MEDLINE, EMBASE, and PubMed online databases for studies published from January 2010 to August 30, 2020. We included studies on acute community-acquired pneumonia or acute lower respiratory tract infection with ≥1 year of continuous data collection; clear consistent case definition for pneumonia; >1 specimen type (except empyema studies where only pleural fluid was required); testing for >1 pathogen including both viruses and bacteria. Two researchers reviewed the studies independently. Results were presented as a narrative summary. Quality of evidence was assessed with the Quality Assessment Tool for Quantitative Studies. The study was registered on PROSPERO [CRD42020206830].
RESULTS
We screened 5184 records; 1305 duplicates were removed. The remaining 3879 titles and abstracts were screened. Of these, 557 articles were identified for full-text review, and 55 met the inclusion criteria - 10 case-control studies, three post-mortem studies, 11 surveillance studies, eight cohort studies, five cross-sectional studies, 12 studies with another design and six studies that included patients with pleural effusions or empyema. Studies which described disease by severity showed higher bacterial detection (Streptococcus pneumoniae, Staphylococcus aureus) in severe vs non-severe cases. The most common virus causing severe disease was respiratory syncytial virus (RSV). Pathogens varied by age, with RSV and adenovirus more common in younger children. Influenza and atypical bacteria were more common in children 5-14 years than younger children. Malnourished and HIV-infected children had higher rates of pneumonia due to bacteria or tuberculosis.
CONCLUSIONS
Several viral and bacterial pathogens were identified as important targets for prevention and treatment. Bacterial pathogens remain an important cause of moderate to severe disease, particularly in children with comorbidities despite widespread PCV and Hib vaccination.
Topics: Child; Community-Acquired Infections; Cross-Sectional Studies; Developing Countries; Humans; Infant; Pneumonia; Respiratory Syncytial Viruses; Vaccination
PubMed: 35866332
DOI: 10.7189/jogh.12.10009 -
Nutrients Jan 2021Vitamin D is an essential component of immune function and childhood deficiency is associated with an increased risk of acute lower respiratory infections (ALRIs)....
Vitamin D is an essential component of immune function and childhood deficiency is associated with an increased risk of acute lower respiratory infections (ALRIs). Globally, the leading childhood respiratory pathogens are , respiratory syncytial virus and the influenza virus. There is a growing body of evidence describing the innate immunomodulatory properties of vitamin D during challenge with respiratory pathogens, but recent systematic and unbiased synthesis of data is lacking, and future research directions are unclear. We therefore conducted a systematic PubMed literature search using the terms "vitamin D" and "" or "Respiratory Syncytial Virus" or "Influenza". A priori inclusion criteria restricted the review to in vitro studies investigating the effect of vitamin D metabolites on human innate immune cells (primary, differentiated or immortalised) in response to stimulation with the specified respiratory pathogens. Eleven studies met our criteria. Despite some heterogeneity across pathogens and innate cell types, vitamin D modulated pathogen recognition receptor (PRRs: Toll-like receptor 2 (TLR2), TLR4, TLR7 and nucleotide-binding oligomerisation domain-containing protein 2 (NOD2)) expression; increased antimicrobial peptide expression (LL-37, human neutrophil peptide (HNP) 1-3 and β-defensin); modulated autophagosome production reducing apoptosis; and modulated production of inflammatory cytokines (Interleukin (IL) -1β, tumour necrosis factor-α (TNF-α), interferon-ɣ (IFN-ɣ), IL-12p70, IFN-β, Regulated on Activation, Normal T cell Expressed (RANTES), IL-10) and chemokines (IL-8 and C-X-C motif chemokine ligand 10 (CXCL10)). Differential modulation of PRRs and IL-1β was reported across immune cell types; however, this may be due to the experimental design. None of the studies specifically focused on immune responses in cells derived from children. In summary, vitamin D promotes a balanced immune response, potentially enhancing pathogen sensing and clearance and restricting pathogen induced inflammatory dysregulation. This is likely to be important in controlling both ALRIs and the immunopathology associated with poorer outcomes and progression to chronic lung diseases. Many unknowns remain and further investigation is required to clarify the nuances in vitamin D mediated immune responses by pathogen and immune cell type and to determine whether these in vitro findings translate into enhanced immunity and reduced ALRI in the paediatric clinical setting.
Topics: Child; Child, Preschool; Cytokines; Humans; Immunity, Innate; Immunomodulation; Infant; Influenza A virus; Influenza, Human; Pneumonia, Pneumococcal; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Respiratory Tract Infections; Streptococcus pneumoniae; Vitamin D
PubMed: 33478006
DOI: 10.3390/nu13010276 -
European Journal of Pediatrics Jan 2023Infections with respiratory syncytial virus (RSV) can cause severe disease. In young children, RSV is the most common cause of lower respiratory tract illness and...
UNLABELLED
Infections with respiratory syncytial virus (RSV) can cause severe disease. In young children, RSV is the most common cause of lower respiratory tract illness and life-threatening infections most commonly occur in the first years of life. In adults, elderly and immunocompromised people are most vulnerable. Recently there has been an acceleration in the development of candidate RSV vaccines, monoclonal antibodies and therapeutics which are expected to become available in Europe within the next 2-10 years. Understanding the true burden of childhood RSV disease will become very important to support public health authorities and policy makers in the assessment of new therapeutic opportunities against RSV disease. A systematic literature search was performed to map local data on the burden of RSV disease and to evaluate available RSV surveillance systems. A group of 9 paediatric infectious diseases specialists participated in an expert panel. The purpose of this meeting was to evaluate and map the burden associated with RSV infection in children, including patient pathways and the epidemiological patterns of virus circulation in Belgium. Sources of information on the burden of RSV disease in Belgium are very limited. For the outpatient setting, it is estimated that 5-10% of young patients seen in primary care are referred to the hospital. Around 3500 children between 0 and 12 months of age are hospitalized for RSV-bronchiolitis every year and represent the majority of all hospitalizations. The current Belgian RSV surveillance system was evaluated and found to be insufficient. Knowledge gaps are highlighted and future perspectives and priorities offered.
CONCLUSION
The Belgian population-based RSV surveillance should be improved, and a hospital-led reporting system should be put in place to enable the evaluation of the true burden of RSV disease in Belgium and to improve disease management in the future.
WHAT IS KNOWN
• RSV bronchiolitis is a very important cause of infant hospitalization. • The burden of disease in the community is poorly studied and underestimated.
WHAT IS NEW
• This expert opinion summarizes knowledge gaps and offers insights that allow improvement of local surveillance systems in order to establish a future-proof RSV surveillance system.
Topics: Humans; Infant; Infant, Newborn; Belgium; Bronchiolitis; Hospitalization; Population Surveillance; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 36371521
DOI: 10.1007/s00431-022-04698-z -
BMC Public Health Dec 2023A significant proportion of the global respiratory syncytial virus (RSV) associated morbidity is accounted for by infants aged 0 to 6 months, who are particularly...
BACKGROUND
A significant proportion of the global respiratory syncytial virus (RSV) associated morbidity is accounted for by infants aged 0 to 6 months, who are particularly vulnerable to severe disease. In 2015, 44% of global hospitalisations in infants in this age group were secondary to RSV. The objective of this systematic review is to appraise and synthesise the local evidence of RSV infection morbidity among Australian infants aged 0 to 6 months and to assess the implications for future immunisation strategies.
METHODS
Electronic databases (Medline, Embase, Pubmed and Global Health) were searched for full-text articles published between 2000 and 2023 in English language. Studies that examined markers of RSV disease morbidity in infants aged 0 to 6 months in Australia who had laboratory confirmed RSV infection were eligible for inclusion. The outcomes of interest were incidence, prevalence, testing rate, positivity rate, mortality, emergency department visits, community health visits, hospitalisation, intensive care unit admission, supplementary oxygen use, mechanical ventilation, risk factors for disease severity and monoclonal antibody use.
RESULTS
The database search identified 469 studies. After removal of duplicates and full-text review, 17 articles were eligible for inclusion. This review was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Synthesis without meta-analysis guidelines.
CONCLUSIONS
Qualitative analysis of the included studies showed that Australian infants aged 0 to 6 months have higher rates of RSV testing, positivity and incidence; and more likely to develop severe disease that requires hospitalisation, intensive care unit admission or respiratory support, compared to children and adults of all ages. Aboriginal and Torres Strait Islander infants aged 0 to 6 months demonstrated higher rates of RSV infection and hospitalisation, compared to non-Indigenous infants. Age-related trends persisted in geographic areas with varying seasonal transmission of RSV, and during the SARS-CoV-2 pandemic. Passive immunisation strategies targeting infants in their first 6 months of life, either via vaccination of pregnant women or administration of long-acting monoclonal antibody during infancy, could effectively reduce RSV disease burden in Australia.
Topics: Pregnancy; Infant; Child; Adult; Humans; Female; Respiratory Syncytial Virus Infections; Australia; Communicable Diseases; Antibodies, Monoclonal; Respiratory Syncytial Virus, Human; Hospitalization; Prevalence
PubMed: 38129854
DOI: 10.1186/s12889-023-17474-x -
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 -
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 -
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 -
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