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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 -
Indian Journal of Public Health 2023The coronavirus disease 2019 (COVID-19) pandemic has changed the epidemiology of respiratory syncytial virus (RSV) infection which accounts for most bronchiolitis and... (Meta-Analysis)
Meta-Analysis Review
The impact of coronavirus disease 2019 pandemic on bronchiolitis (lower respiratory tract infection) due to respiratory syncytial virus: A systematic review and meta-analysis.
The coronavirus disease 2019 (COVID-19) pandemic has changed the epidemiology of respiratory syncytial virus (RSV) infection which accounts for most bronchiolitis and viral pneumonias in infants. This systematic review and meta-analysis aimed to quantitatively assess the effect of the COVID-19 pandemic on RSV-associated bronchiolitis among hospitalized infants. The study protocol was registered in the PROSPERO database (CRD42022314000) and was designed based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines updated in May 2020. The meta-analysis component was modified appropriately to synthesize the pooled proportion of infants having RSV-associated bronchiolitis before the COVID-19 pandemic in 2019 and during the pandemic with 95% confidence interval (CI). We identified and screened 189 articles and systematically reviewed 50 full texts. Eight qualified studies from Europe and China, including 109,186 symptomatic cases of bronchiolitis before the pandemic in 2019 and 61,982 cases in 2020-2021 were pooled by random-effects meta-analysis. The quantitative analysis included laboratory-confirmed RSV infection in 7691 infants with bronchiolitis reported before the pandemic in 2019. Meanwhile, during the pandemic, 4964 bronchiolitis cases were associated with RSV infection. The pooled proportion of RSV-associated bronchiolitis cases before the pandemic in 2019 was 16.74% (95% CI 11.73, 22.43%, 95% prediction interval 0.032, 34.16). The pooled proportion of confirmed RSV cases during the pandemic in 2020/2021 was 19.20% (95% CI 12.01, 27.59%, 95% prediction interval 0.046, 42.35). There was an increase in RSV activity after the relaxation of stringent public health measures during the COVID-19 pandemic.
Topics: Infant; Humans; Pandemics; COVID-19; India; Respiratory Syncytial Virus, Human; Bronchiolitis; Respiratory Syncytial Virus Infections; Respiratory Tract Infections
PubMed: 37459026
DOI: 10.4103/ijph.ijph_1334_22 -
BMC Pediatrics Jun 2023To undertake a systematic review of studies describing the proportion of children admitted to a paediatric intensive care unit (PICU) for respiratory syncytial virus... (Meta-Analysis)
Meta-Analysis
BACKGROUND
To undertake a systematic review of studies describing the proportion of children admitted to a paediatric intensive care unit (PICU) for respiratory syncytial virus (RSV) and/or bronchiolitis who were born preterm, and compare their outcomes in PICU with children born at term.
METHODS
We searched Medline, Embase and Scopus. Citations and references of included articles were searched. We included studies published from the year 2000 onwards, from high-income countries, that examined children 0-18 years of age, admitted to PICU from the year 2000 onwards for RSV and/or bronchiolitis. The primary outcome was the percentage of PICU admissions born preterm, and secondary outcomes were observed relative risks of invasive mechanical ventilation and mortality within PICU. We used the Joanna Briggs Institute Checklist for Analytical Cross-Sectional Studies to assess risk of bias.
RESULTS
We included 31 studies, from 16 countries, including a total of 18,331 children. Following meta-analysis, the pooled estimate for percentage of PICU admissions for RSV/bronchiolitis who were born preterm was 31% (95% confidence interval: 27% to 35%). Children born preterm had a greater risk of requiring invasive ventilation compared to children born at term (relative risk 1.57, 95% confidence interval 1.25 to 1.97, I = 38%). However, we did not observe a significant increase in the relative risk for mortality within PICU for preterm-born children (relative risk 1.10, 95% confidence interval: 0.70 to 1.72, I = 0%), although the mortality rate was low across both groups. The majority of studies (n = 26, 84%) were at high risk of bias.
CONCLUSIONS
Among PICU admissions for bronchiolitis, preterm-born children are over-represented compared with the preterm birth rate (preterm birth rate 4.4% to 14.4% across countries included in review). Preterm-born children are at higher risk of mechanical ventilation compared to those born at term.
Topics: Infant, Newborn; Child; Humans; Pregnancy; Female; Cross-Sectional Studies; Premature Birth; Bronchiolitis; Parturition; Respiratory Syncytial Virus, Human; Critical Care
PubMed: 37386478
DOI: 10.1186/s12887-023-04150-7 -
The Journal of Infectious Diseases Nov 2023Adding additional specimen types (eg, serology or sputum) to nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) increases respiratory... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Adding additional specimen types (eg, serology or sputum) to nasopharyngeal swab (NPS) reverse transcription polymerase chain reaction (RT-PCR) increases respiratory syncytial virus (RSV) detection among adults. We assessed if a similar increase occurs in children and quantified underascertainment associated with diagnostic testing.
METHODS
We searched databases for studies involving RSV detection in persons <18 years using ≥2 specimen types or tests. We assessed study quality using a validated checklist. We pooled detection rates by specimen and diagnostic tests and quantified performance.
RESULTS
We included 157 studies. Added testing of additional specimens to NP aspirate (NPA), NPS, and/or nasal swab (NS) RT-PCR resulted in statistically nonsignificant increases in RSV detection. Adding paired serology testing increased RSV detection by 10%, NS by 8%, oropharyngeal swabs by 5%, and NPS by 1%. Compared to RT-PCR, direct fluorescence antibody tests, viral culture, and rapid antigen tests were 87%, 76%, and 74% sensitive, respectively (pooled specificities all ≥98%). Pooled sensitivity of multiplex versus singleplex RT-PCR was 96%.
CONCLUSIONS
RT-PCR was the most sensitive pediatric RSV diagnostic test. Adding multiple specimens did not substantially increase RSV detection, but even small proportional increases could result in meaningful changes in burden estimates. The synergistic effect of adding multiple specimens should be evaluated.
Topics: Adult; Child; Humans; Respiratory Syncytial Virus Infections; Sensitivity and Specificity; Respiratory Syncytial Virus, Human; Viruses; Diagnostic Techniques and Procedures; Nasopharynx; Reverse Transcriptase Polymerase Chain Reaction
PubMed: 37285396
DOI: 10.1093/infdis/jiad185 -
BMC Infectious Diseases May 2023As countries move towards or achieve measles elimination status, serosurveillance is an important public health tool. However, a major challenge of serosurveillance is...
Comparison of measles IgG enzyme immunoassays (EIA) versus plaque reduction neutralization test (PRNT) for measuring measles serostatus: a systematic review of head-to-head analyses of measles IgG EIA and PRNT.
BACKGROUND
As countries move towards or achieve measles elimination status, serosurveillance is an important public health tool. However, a major challenge of serosurveillance is finding a feasible, accurate, cost-effective, and high throughput assay to measure measles antibody concentrations and estimate susceptibility in a population. We conducted a systematic review to assess, characterize, and - to the extent possible - quantify the performance of measles IgG enzyme-linked assays (EIAs) compared to the gold standard, plaque reduction neutralization tests (PRNT).
METHODS
We followed the PRISMA statement for a systematic literature search and methods for conducting and reporting systematic reviews and meta-analyses recommended by the Cochrane Screening and Diagnostic Tests Methods Group. We identified studies through PubMed and Embase electronic databases and included serologic studies detecting measles virus IgG antibodies among participants of any age from the same source population that reported an index (any EIA or multiple bead-based assays, MBA) and reference test (PRNT) using sera, whole blood, or plasma. Measures of diagnostic accuracy with 95% confidence intervals (CI) were abstracted for each study result, where reported.
RESULTS
We identified 550 unique publications and identified 36 eligible studies for analysis. We classified studies as high, medium, or low quality; results from high quality studies are reported. Because most high quality studies used the Siemens Enzygnost EIA kit, we generate individual and pooled diagnostic accuracy estimates for this assay separately. Median sensitivity of the Enzygnost EIA was 92.1% [IQR = 82.3, 95.7]; median specificity was 96.9 [93.0, 100.0]. Pooled sensitivity and specificity from studies using the Enzygnost kit were 91.6 (95%CI: 80.7,96.6) and 96.0 (95%CI: 90.9,98.3), respectively. The sensitivity of all other EIA kits across high quality studies ranged from 0% to 98.9% with median (IQR) = 90.6 [86.6, 95.2]; specificity ranged from 58.8% to 100.0% with median (IQR) = 100.0 [88.7, 100.0].
CONCLUSIONS
Evidence on the diagnostic accuracy of currently available measles IgG EIAs is variable, insufficient, and may not be fit for purpose for serosurveillance goals. Additional studies evaluating the diagnostic accuracy of measles EIAs, including MBAs, should be conducted among diverse populations and settings (e.g., vaccination status, elimination/endemic status, age groups).
Topics: Humans; Neutralization Tests; Measles; Immunoenzyme Techniques; Measles virus; Sensitivity and Specificity; Antibodies, Viral; Immunoglobulin G
PubMed: 37259032
DOI: 10.1186/s12879-023-08199-8 -
The Journal of Infectious Diseases Mar 2024Previous studies reported inconsistent findings regarding the association between respiratory syncytial virus (RSV) subgroup distribution and timing of RSV season. We...
BACKGROUND
Previous studies reported inconsistent findings regarding the association between respiratory syncytial virus (RSV) subgroup distribution and timing of RSV season. We aimed to further understand the association by conducting a global-level systematic analysis.
METHODS
We compiled published data on RSV seasonality through a systematic literature review, and unpublished data shared by international collaborators. Using annual cumulative proportion (ACP) of RSV-positive cases, we defined RSV season onset and offset as ACP reaching 10% and 90%, respectively. Linear regression models accounting for meteorological factors were constructed to analyze the association of proportion of RSV-A with the corresponding RSV season onset and offset.
RESULTS
We included 36 study sites from 20 countries, providing data for 179 study-years in 1995-2019. Globally, RSV subgroup distribution was not significantly associated with RSV season onset or offset globally, except for RSV season offset in the tropics in 1 model, possibly by chance. Models that included RSV subgroup distribution and meteorological factors explained only 2%-4% of the variations in timing of RSV season.
CONCLUSIONS
Year-on-year variations in RSV season onset and offset are not well explained by RSV subgroup distribution or meteorological factors. Factors including population susceptibility, mobility, and viral interference should be examined in future studies.
Topics: Humans; Respiratory Syncytial Virus, Human; Linear Models; Seasons; Viral Interference
PubMed: 37249267
DOI: 10.1093/infdis/jiad192 -
Jornal de Pediatria 2023To identify and assess the current evidence available about the costs of managing hospitalized pediatric patients diagnosed with Respiratory Syncytial Virus (RSV) and... (Review)
Review
OBJECTIVE
To identify and assess the current evidence available about the costs of managing hospitalized pediatric patients diagnosed with Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3) in upper-middle-income countries.
METHODS
The authors conducted a systematic review across seven key databases from database inception to July 2022. Costs extracted were converted into 2022 International Dollars using the Purchasing Power Parity-adjusted. PROSPERO identifier: CRD42020225757.
RESULTS
No eligible study for PIV3 was recovered. For RSV, cost analysis and COI studies were performed for populations in Colombia, China, Malaysia, and Mexico. Comparing the total economic impact, the lowest cost per patient at the pediatric ward was observed in Malaysia ($ 347.60), while the highest was in Colombia ($ 709.66). On the other hand, at pediatric ICU, the lowest cost was observed in China ($ 1068.26), while the highest was in Mexico ($ 3815.56). Although there is no consensus on the major cost driver, all included studies described that the medications (treatment) consumed over 30% of the total cost. A high rate of inappropriate prescription drugs was observed.
CONCLUSION
The present study highlighted how RSV infection represents a substantial economic burden to health care systems and to society. The findings of the included studies suggest a possible association between baseline risk status and expenditures. Moreover, it was observed that an important amount of the cost is destinated to treatments that have no evidence or support in most clinical practice guidelines.
Topics: Humans; Child; Infant; Developing Countries; Financial Stress; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Parainfluenza Virus 3, Human; Hospitalization
PubMed: 37247828
DOI: 10.1016/j.jped.2023.05.003 -
Influenza and Other Respiratory Viruses May 2023Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in young children. We aimed to analyze the factors affecting the estimation of... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in young children. We aimed to analyze the factors affecting the estimation of RSV-related disease burden, and to provide evidence to help establish a surveillance system.
METHODS
We searched the English- and Chinese-language databases for articles published between January 1, 2010 and June 2, 2022. The quality of the included articles was assessed using the Agency for Healthcare Research and Quality scale. Random-effects models were used for data synthesis and subgroup analyses. This review was registered in the Prospective Register of Systematic Reviews (PROSPERO: CRD42022372972).
RESULTS
We included 44 studies (149,321,171 participants), all of which were of medium or high quality. The pooled RSV-related disease incidence, hospitalization rate, in-hospital mortality, and overall mortality rates in children aged 5 years and younger were 9.0 per 100 children per year (95% confidence interval [CI]: 7.0-11.0), 1.7 per 100 children per year (95% CI: 1.3-2.1), 0.5 per 100 children per year (95% CI: 0.4-0.5), and 0.05 per 100 children per year (95% CI: 0.04-0.06), respectively. Age, economics, surveillance types, case definition, and data source were all recognized as influencing factors.
CONCLUSIONS
A standardized and unified RSV surveillance system is required. Case definition and surveillance types should be fully considered for surveillance of different age groups.
Topics: United States; Child; Humans; Child, Preschool; Incidence; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human; Respiratory Tract Infections; Hospitalization
PubMed: 37223668
DOI: 10.1111/irv.13145 -
The Journal of Infectious Diseases Nov 2023There is no immunization campaign that currently exist for respiratory syncytial virus (RSV). Seroprevalence studies are critical for assessing epidemiological dynamics...
BACKGROUND
There is no immunization campaign that currently exist for respiratory syncytial virus (RSV). Seroprevalence studies are critical for assessing epidemiological dynamics before and during an immunization program. A systematic literature review was conducted to summarize the evidence from seroprevalence studies on RSV.
METHODS
A systematic search of age-dependent RSV seroprevalence was conducted using the PubMed database and EMBASE. Age-dependent force of infections (FoI) and the decay rate of immunity were estimated. A mixture finite model was used, estimating the age-dependent disease state and the antibody concentrations in susceptible and infected or recovered populations.
RESULTS
Twenty-one studies were identified from 15 countries, with studies using enzyme-linked immunosorbent assay being the most represented. Using a catalytic model, the age-dependent force of infection was estimated to be the lowest in infants aged 6 months to 1 year and increased in older age groups. The proportion ever-infected/recovered was estimated to be above 90% by 3 years of age.
CONCLUSIONS
The number of seroprevalence studies covering a broad range of ages are limited. The age-dependent FoI indicated that the risk of infection was greatest among those aged >5 years. Additional data using valid assays are required to describe the transmission dynamics of RSV infection.
Topics: Infant; Humans; Aged; Child, Preschool; Respiratory Syncytial Virus Infections; Seroepidemiologic Studies; Respiratory Syncytial Virus, Human; Antibodies, Viral; Enzyme-Linked Immunosorbent Assay
PubMed: 37161934
DOI: 10.1093/infdis/jiad147 -
Influenza and Other Respiratory Viruses Feb 2023Respiratory syncytial virus (RSV) is responsible for over 30 million lower respiratory tract infections (LRTIs) and 3 million hospitalizations worldwide each year.... (Review)
Review
Respiratory syncytial virus (RSV) is responsible for over 30 million lower respiratory tract infections (LRTIs) and 3 million hospitalizations worldwide each year. Despite the risk RSV poses to young children, older adults, and individuals with comorbidities or suppressed immunity, there is limited understanding of RSV symptom presentation across these at-risk groups, and there is no vaccine for RSV. We conducted two systematic literature reviews (SLRs) of studies that document signs and symptoms (S&S) of RSV in (1) children aged ≤5 years and (2) immunocompromised adolescents and adults, and adults at high risk for severe RSV due to age or comorbidities. Symptom duration and hospital length of stay (LOS) were explored. Electronic database searches were performed following PRISMA guidelines. Studies captured RSV S&S across community and hospital settings. Clinicians and caregivers reported ( = 25 studies) nasal discharge/congestion, cough, shortness of breath, feeding abnormalities, and fever in ≥40% of children across studies and settings. Median hospital stays for children ranged from 2 days in the United States to 7.5 days in China. High-risk adults with RSV ( = 6 studies) commonly (≥40% of adults) reported cough, sputum, dyspnea, and fever/feverishness. Median length of hospital stay in adults ranged from 6 to 15 days across studies. Caregivers and clinicians reported similar RSV S&S in young children, including upper and lower respiratory and systemic symptoms. In high-risk and immunocompromised adults, the most frequent (in multiple publications) and commonly reported RSV S&S were primarily LRTI symptoms. RSV symptoms could last for weeks and are variable based on geography.
Topics: Child; Humans; Infant; Child, Preschool; Aged; Adolescent; Respiratory Syncytial Virus Infections; Cough; Respiratory Syncytial Virus, Human; Hospitalization; Respiratory Tract Infections
PubMed: 36824394
DOI: 10.1111/irv.13100