scholarly journals 92. Incidence of Respiratory Syncytial Virus Infection among Hospitalized Adults, 2017–2019

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S7-S8
Author(s):  
Angela Branche ◽  
Lisa Saiman ◽  
Edward E Walsh ◽  
Ann R Falsey ◽  
William Sieling ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Census Data ◽  
Vaccine Development ◽  
Respiratory Illness ◽  
Incidence Rates ◽  
Case Definition ◽  
Cardiopulmonary Disease ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Surveillance Area

Abstract Background Respiratory syncytial virus (RSV) infection has been increasingly recognized as an important cause of acute respiratory illness (ARI) and a trigger for exacerbation of underlying cardiopulmonary disease in adults. Incidence of hospitalized RSV infection remains uncertain as adults have not been systematically screened. Previous incidence estimates, derived primarily from modeling studies, have ranged from 84 to 190/100K population in adults >65 years of age. Accurate burden data are critical to inform RSV vaccine development for adults. We used active surveillance among hospitalized adults to determine population-based incidence rates of RSV infection. Methods Hospitalized adults ≥ 18 years old residing in the surveillance area with >2 ARI symptoms or exacerbation of underlying cardiopulmonary disease were screened for eligibility during October 2017–April 2018 and October 2018 to April 2019 in 3 hospitals in Rochester, NY and New York City. Respiratory specimens were tested for RSV using PCR assays. RSV incidence per 100,000 persons (per 2010 US Census data) was adjusted by percent market share for study hospitals in their catchment area. Results In total, 8,217 hospitalized adults residing in the surveillance area that met the surveillance case definition were tested for RSV; 768 (9.4%) were positive. Adults were aged 18–49 (12%), 50–64 (30%), and ≥65 years old (58%); 55% were female. RSV infection incidence varied from year 1 to year 2 and was highest in patients aged ≥65 years old (table). Conclusion This is the largest prospective RSV incidence study to date. Preliminary results indicate that the incidence of RSV infection may be higher than previously reported, especially in urban-dwelling adults >65 years of age. Results confirm the need for vaccines to prevent RSV infections in older adults. Disclosures All Authors: No reported Disclosures.

scholarly journals Respiratory Syncytial Virus Immunoprophylaxis with Palivizumab: 12-Year Observational Study of Usage and Outcomes in Canada

2021 ◽  
Author(s):  
Ian Mitchell ◽  
Abby Li ◽  
Candice L. Bjornson ◽  
Krista L. Lanctot ◽  
Bosco A. Paes ◽  
...  
Keyword(s):  
Risk Factors ◽  
Respiratory Syncytial Virus ◽  
Burden Of Illness ◽  
Respiratory Illness ◽  
Smoking Exposure ◽  
Key Points ◽  
Rsv Infection ◽  
History Of ◽  
Syncytial Virus ◽  
Airway Anomalies

Objective This study aimed to evaluate palivizumab (PVZ) use, trends in indications, and outcomes of respiratory illness hospitalizations (RIH) and respiratory syncytial virus hospitalizations (RSVH). Study Design It involves a large, Canadian prospective (2005–2017) observational multicenter study of children at high risk for RSV infection. Results A total of 25,003 infants (56.3% male) were enrolled at 32 sites; 109,579 PVZ injections were administered. Indications included: prematurity (63.3%); “miscellaneous” (17.8%); hemodynamically significant congenital heart disease (10.5%); bronchopulmonary dysplasia/chronic lung disease (8.4%). The “miscellaneous” group increased over time (4.4% in 2005–2006 to 22.5% in 2016–2017) and included: trisomy 21, airway anomalies, pulmonary disorders, cystic fibrosis, neurological impairments, immunocompromised, cardiac aged >2 years, multiple conditions, and a residual “unclassified” group. Adherence measured by expected versus actual doses plus correct interdose interval was 64.7%. A total of 2,054 RIH occurred (6.9%); 198 (9.6%) required intubation. Three hundred thirty-seven hospitalized children were RSV-positive (overall RSVH 1.6%). Risk factors for RSVH included having siblings, attending daycare, family history of atopy, smoking exposure, and crowded household. Infants with 5 risk factors were 9.0 times (95% CI or confidence interval 4.4–18.2; p < 0.0005) more likely to have RSVH than infants without risk factors. Three adverse events occurred; none were fatal. Conclusion Results are relevant to both clinicians and decision-makers. We confirmed the safety of PVZ. Use of PVZ increased steadily for children with miscellaneous conditions and medical complexity. Medical and social factors pose a risk for severe RIH and RSVH with accompanying burden of illness. A vaccine that protects against RSV is urgently required. Key Points

scholarly journals Accuracy of diagnostic tests for respiratory syncytial virus infection within a paediatric hospital population in Kilifi County, Kenya

2020 ◽  
Vol 5 ◽  
pp. 155
Author(s):  
Marshal M. Mweu ◽  
Nickson Murunga ◽  
Juliet W. Otieno ◽  
D. James Nokes
Keyword(s):  
Respiratory Syncytial Virus ◽  
Diagnostic Tests ◽  
Latent Class ◽  
Respiratory Illness ◽  
Acute Respiratory Illness ◽  
Predictive Values ◽  
Paediatric Hospital ◽  
Rsv Infection ◽  
Hospital Population ◽  
Syncytial Virus

Background: Respiratory syncytial virus (RSV)-induced lower respiratory tract disease is a prominent cause of hospitalisation among children aged <5 years in developing countries. Accurate and rapid diagnostic tests are central to informing effective patient management and surveillance efforts geared towards quantifying RSV disease burden. This study sought to estimate the sensitivity (Se), specificity (Sp) (along with the associated factors) and predictive values of a direct immunofluorescence test (IFAT), and two real-time reverse transcription polymerase chain reaction (rRT-PCR) assays for RSV infection within a paediatric hospital population: a multiplex rRT-PCR (MPX) and Fast-Track Diagnostics® (FTD) Respiratory Pathogens 33 (Resp-33) rRT-PCR. Methods: The study enlisted 1458 paediatrics aged ≤59 months admitted with acute respiratory illness at the Kilifi County Hospital between August 2011 and December 2013. A Bayesian latent class modelling framework was employed to infer the tests’ estimates based on the patients’ diagnostic data from the three tests. Results: The tests posted statistically similar Se estimates: IFAT (93.7%, [90.7; 95.0]), FTD (97.8%, [94.6; 99.4]) and MPX (97.5%, [94.2; 99.3]). As for Sp, FTD registered a lower estimate (97.4%, [96.2; 98.2]) than MPX (99.7%, [99.0; 100.0]) but similar to IFAT (99.0%, [98.2; 99.6]). The negative and positive predictive values were strong (>91%) and closely mimicked the pattern given by the Se and Sp values respectively. None of the examined covariates (age, sex and pneumonia status) significantly influenced the accuracy of the tests. Conclusions: The evaluation found little to choose between the three diagnostic tests. Nonetheless, with its relative affordability, the conventional IFAT continues to hold promise for use in patient care and surveillance activities for RSV infection within settings where children are hospitalised with severe acute respiratory illness.

scholarly journals 998. Forward and Reverse Translational Approaches to Predict Efficacy of the Neutralizing Respiratory Syncytial Virus (RSV) Antibody MK-1654

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S590-S590
Author(s):  
Brian M Maas ◽  
Jos Lommerse ◽  
Nele Plock ◽  
Radha Railkar ◽  
S Y Amy Cheung ◽  
...  
Keyword(s):  
Viral Load ◽  
Respiratory Syncytial Virus ◽  
Tract Infection ◽  
Lower Respiratory Tract ◽  
Incidence Rates ◽  
Independent Contractor ◽  
Phase 3 ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
The Relationship

Abstract Background MK-1654 is a respiratory syncytial virus (RSV) F glycoprotein neutralizing monoclonal antibody (mAb) with an extended half-life in late development to prevent RSV infection in infants. Neutralizing mAbs, like MK-1654, have great potential for prophylaxis against viral infection. However, well-validated approaches for clinical dose and efficacy predictions are lacking. Methods Summary-level literature data from RSV prevention studies were used in a model-based meta-analysis (MBMA) to describe the relationship between RSV incidence rates and serum neutralizing antibody (SNA) titer. The model was validated using viral challenge experiments in cotton rats and phase 3 RSV-A efficacy results in infants for an anti-RSV F mAb, REGN-2222. A phase 2b human RSV challenge study (HCS) in adults was also conducted with MK-1654. Participants (N=70) received 100, 200, 300, or 900 mg of MK-1564 or placebo and were challenged intranasally with RSV 29 days later. RSV viral load and symptomatic infection were monitored. Data from the HCS were compared to model predictions. The MBMA was used to predict efficacy of MK-1654 in a virtual population of pre- and full- term infants. Results The relationship between SNA titer and RSV incidence rate defined using the viral load data from the cotton rat approximated the relationship identified for infants from the clinical MBMA. The MBMA was quantitatively consistent with the phase 3 efficacy results against RSV A for REGN-2222. In the HCS, RSV nasal viral load measured by RT-qPCR and quantitative culture as well as symptomatic infections were decreased in MK-1654 recipients compared to placebo. Incidence rates of RSV infection in the HCS were also consistent with MBMA predictions. The model-based clinical trial simulations for MK-1654 indicated a high probability of substantial efficacy against RSV-associated medically attended lower respiratory tract infection ( &gt;75% for 5 months) for doses ≥75 mg. Conclusion Our MBMA successfully quantified the relationship between RSV SNA and clinically relevant endpoints, including lower respiratory tract infection in infants. MBMA-based efficacy predictions support continued development of the MK-1654 antibody for the prevention of RSV in infants. Disclosures Brian M. Maas, PharmD, Merck & Co., Inc. (Employee, Shareholder) Jos Lommerse, PhD, Certara (Employee, Shareholder)Merck & Co., Inc. (Independent Contractor) Nele Plock, PhD, Certara (Employee, Shareholder)Merck & Co., Inc. (Independent Contractor) Radha Railkar, PhD, Merck & Co., Inc. (Employee, Shareholder) S. Y. Amy Cheung, PhD, Certara (Employee, Shareholder) Luzelena Caro, PhD, Merck & Co., Inc. (Employee, Shareholder) Jingxian Chen, PhD, Merck & Co., Inc. (Employee, Shareholder) Wen Liu, MPH, Merck & Co., Inc. (Employee, Shareholder) Ying Zhang, PhD, Merck & Co., Inc. (Employee, Shareholder) Qinlei Huang, MS, Merck & Co., Inc. (Employee, Shareholder) Wei Gao, PhD, Merck & Co., Inc. (Employee, Shareholder) Li Qin, PhD, Certara (Employee, Shareholder)Merck & Co., Inc. (Independent Contractor) Jie Meng, MSc, Certara (Employee, Shareholder)Merck & Co., Inc. (Independent Contractor) Han Witjes, PhD, Certara (Employee, Shareholder)Merck & Co., Inc. (Independent Contractor) Emilie Schindler, PhD, Certara (Employee, Shareholder)Merck & Co., Inc. (Independent Contractor) Benjamin Guiastrennec, PharmD, PhD, Certara (Employee, Shareholder)Merck & Co., Inc. (Independent Contractor) Francesco Bellanti, PhD, Certara (Employee, Shareholder)Merck & Co., Inc. (Independent Contractor) Daniel Spellman, PhD, Merck & Co., Inc. (Employee, Shareholder) Brad Roadcap, MS, Merck & Co., Inc. (Employee, Shareholder) Amy Espeseth, PhD, Merck & Co., Inc. (Employee, Shareholder) S. Aubrey Stoch, MD, Merck & Co., Inc. (Employee, Shareholder) Eseng Lai, MD, PhD, Merck & Co., Inc. (Employee, Shareholder) Kalpit A. Vora, PhD, Merck & Co., Inc. (Employee, Shareholder) Antonios O. Aliprantis, MD, PhD, Merck & Co., Inc. (Employee, Shareholder) Jeffrey R. Sachs, PhD, Merck & Co., Inc. (Employee, Shareholder)

Association of Viral Load With Disease Severity in Outpatient Children With Respiratory Syncytial Virus Infection

2020 ◽  
Vol 222 (2) ◽  
pp. 298-304 ◽  
Author(s):  
Erika Uusitupa ◽  
Matti Waris ◽  
Terho Heikkinen
Keyword(s):  
Viral Load ◽  
Respiratory Syncytial Virus ◽  
Disease Severity ◽  
Respiratory Infections ◽  
Respiratory Illness ◽  
Lower Viral Load ◽  
Primary Analysis ◽  
Rsv Infection ◽  
Syncytial Virus ◽  
Outpatient Children

Abstract Background There are scarce data on whether viral load affects the severity of respiratory syncytial virus (RSV) disease in outpatient children. Methods We analyzed the association between viral load and disease severity among children who participated in a prospective cohort study of respiratory infections. The children were examined and nasal swabs for the detection of RSV were obtained during each respiratory illness. Quantification of RSV load was based on the cycle threshold (Ct) value. For the primary analysis, the children were divided into 2 groups: higher (Ct &lt; 27) and lower viral load (Ct ≥ 27). Results Among 201 episodes of RSV infection, children with higher viral load had significantly longer median durations of rhinitis (8 vs 6 days; P = .0008), cough (8 vs 6 days; P = .034), fever (2 vs 1 days; P = .018), and any symptom (10 vs 8 days; P = .024) than those with lower viral load. There were statistically significant negative correlations between the Ct values and durations of all measured symptoms. Conclusions Our findings support the concept that viral load drives the severity of RSV disease in children. Reducing the viral load by RSV antivirals might provide substantial benefits to outpatient children.

scholarly journals Respiratory syncytial virus hospitalisations among young children: a data linkage study

2019 ◽  
Vol 147 ◽  
Author(s):  
Namrata Prasad ◽  
E. Claire Newbern ◽  
Adrian A. Trenholme ◽  
Tim Wood ◽  
Mark G. Thompson ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Hospital Discharge ◽  
Active Surveillance ◽  
Data Linkage ◽  
Economic Status ◽  
Linkage Study ◽  
Incidence Rates ◽  
Seasonal Incidence ◽  
Rsv Infection ◽  
Syncytial Virus

Abstract We aimed to provide comprehensive estimates of laboratory-confirmed respiratory syncytial virus (RSV)-associated hospitalisations. Between 2012 and 2015, active surveillance of acute respiratory infection (ARI) hospitalisations during winter seasons was used to estimate the seasonal incidence of laboratory-confirmed RSV hospitalisations in children aged <5 years in Auckland, New Zealand (NZ). Incidence rates were estimated by fine age group, ethnicity and socio-economic status (SES) strata. Additionally, RSV disease estimates determined through active surveillance were compared to rates estimated from hospital discharge codes. There were 5309 ARI hospitalisations among children during the study period, of which 3923 (73.9%) were tested for RSV and 1597 (40.7%) were RSV-positive. The seasonal incidence of RSV-associated ARI hospitalisations, once corrected for non-testing, was 6.1 (95% confidence intervals 5.8–6.4) per 1000 children <5 years old. The highest incidence was among children aged <3 months. Being of indigenous Māori or Pacific ethnicity or living in a neighbourhood with low SES independently increased the risk of an RSV-associated hospitalisation. RSV hospital discharge codes had a sensitivity of 71% for identifying laboratory-confirmed RSV cases. RSV infection is a leading cause of hospitalisation among children in NZ, with significant disparities by ethnicity and SES. Our findings highlight the need for effective RSV vaccines and therapies.

scholarly journals Performance of surveillance case definitions for respiratory syncytial virus infections through the sentinel influenza surveillance system, Portugal, 2010 to 2018

2019 ◽  
Vol 24 (45) ◽  
Author(s):  
Emma Sáez-López ◽  
Pedro Pechirra ◽  
Inês Costa ◽  
Paula Cristóvão ◽  
Patrícia Conde ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Characteristic Curve ◽  
Age Groups ◽  
Case Definition ◽  
Influenza Surveillance ◽  
Surveillance Systems ◽  
The European Union ◽  
Case Definitions ◽  
Rsv Infection ◽  
Syncytial Virus

Background Well-established influenza surveillance systems (ISS) can be used for respiratory syncytial virus (RSV) surveillance. In Portugal, RSV cases are detected through the ISS using the European Union (EU) influenza-like illness (ILI) case definition. Aim To investigate clinical predictors for RSV infection and how three case definitions (EU ILI, a modified EU acute respiratory infection, and one respiratory symptom) performed in detecting RSV infections in Portugal. Methods This observational retrospective study used epidemiological and laboratory surveillance data (October 2010–May 2018). Associations between clinical characteristics and RSV detection were analysed using logistic regression. Accuracy of case definitions was assessed through sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). A 0.05 significance level was accepted. Results The study involved 6,523 persons, including 190 (2.9%) RSV cases. Among 183 cases with age information, RSV infection was significantly more frequent among individuals < 5 years (n = 23; 12.6%) and ≥ 65 years (n = 45; 24.6%) compared with other age groups (p < 0.0001). Cough (odds ratio (OR): 2.4; 95% confidence interval (CI): 1.2–6.5) was the best RSV-infection predictor considering all age groups, while shortness of breath was particularly associated with RSV-positivity among ≤ 14 year olds (OR: 6.7; 95% CI: 2.6–17.4 for 0–4 year olds and OR: 6.7; 95% CI: 1.5–28.8 for 5–14 year olds). Systemic symptoms were significantly associated with RSV-negative and influenza-positive cases. None of the case definitions were suitable to detect RSV infections (AUC = 0.51). Conclusion To avoid underestimating the RSV disease burden, RSV surveillance within the Portuguese sentinel ISS would require a more sensitive case definition than ILI and, even a different case definition according to age.

scholarly journals Immunization of Macaques with Formalin-Inactivated Respiratory Syncytial Virus (RSV) Induces Interleukin-13-Associated Hypersensitivity to Subsequent RSV Infection

2002 ◽  
Vol 76 (22) ◽  
pp. 11561-11569 ◽  
Author(s):  
Rik L. de Swart ◽  
Thijs Kuiken ◽  
Helga H. Timmerman ◽  
Geert van Amerongen ◽  
Bernadette G. van den Hoogen ◽  
...  
Keyword(s):  
T Cells ◽  
Respiratory Syncytial Virus ◽  
Measles Virus ◽  
Vaccine Development ◽  
Neutralizing Antibody ◽  
Airway Hyperreactivity ◽  
Primate Model ◽  
Interleukin 13 ◽  
Rsv Infection ◽  
Syncytial Virus

ABSTRACT Respiratory syncytial virus (RSV) is a major cause of severe respiratory disease in infants and the elderly. RSV vaccine development has been hampered by results of clinical trials in the 1960s, when formalin-inactivated whole-RSV preparations adjuvated with alum (FI-RSV) were found to predispose infants for enhanced disease following subsequent natural RSV infection. We have reproduced this apparently immunopathological phenomenon in infant cynomolgus macaques and identified immunological and pathological correlates. Vaccination with FI-RSV induced specific virus-neutralizing antibody responses accompanied by strong lymphoproliferative responses. The vaccine-induced RSV-specific T cells predominantly produced the Th2 cytokines interleukin-13 (IL-13) and IL-5. Intratracheal challenge with a macaque-adapted wild-type RSV 3 months after the third vaccination elicited a hypersensitivity response associated with lung eosinophilia. The challenge resulted in a rapid boosting of IL-13-producing T cells in the FI-RSV-vaccinated animals but not in the FI-measles virus-vaccinated control animals. Two out of seven FI-RSV-vaccinated animals died 12 days after RSV challenge with pulmonary hyperinflation. Surprisingly, the lungs of these two animals did not show overt inflammatory lesions. However, upon vaccination the animals had shown the strongest lymphoproliferative responses associated with the most pronounced Th2 phenotype within their group. We hypothesize that an IL-13-associated asthma-like mechanism resulted in airway hyperreactivity in these animals. This nonhuman primate model will be an important tool to assess the safety of nonreplicating candidate RSV vaccines.

scholarly journals Severe Morbidity and Mortality Associated With Respiratory Syncytial Virus Versus Influenza Infection in Hospitalized Older Adults

2018 ◽  
Vol 69 (2) ◽  
pp. 197-203 ◽  
Author(s):  
Bradley Ackerson ◽  
Hung Fu Tseng ◽  
Lina S Sy ◽  
Zendi Solano ◽  
Jeff Slezak ◽  
...  
Keyword(s):  
Older Adults ◽  
Respiratory Syncytial Virus ◽  
Disease Burden ◽  
Influenza Infection ◽  
Respiratory Illness ◽  
Morbidity And Mortality ◽  
Chronic Obstructive ◽  
Rsv Infection ◽  
Hospitalized Older Adults ◽  
Syncytial Virus

Abstract Background Respiratory syncytial virus (RSV) is an important cause of serious respiratory illness in older adults. Comparison of RSV and influenza infection in hospitalized older adults may increase awareness of adult RSV disease burden. Methods Hospitalized adults aged ≥60 years who tested positive for RSV or influenza between 1 January 2011 and 30 June 2015 were identified from Kaiser Permanente Southern California electronic medical records. Baseline characteristics, comorbidities, utilization, and outcomes were compared. Results The study included 645 RSV- and 1878 influenza-infected hospitalized adults. Patients with RSV were older than those with influenza (mean, 78.5 vs 77.4 years; P = .035) and more likely to have congestive heart failure (35.3% vs 24.5%; P < .001) and chronic obstructive pulmonary disease (COPD) (29.8% vs 24.3%; P = .006) at baseline. In adjusted analyses, RSV infection was associated with greater odds of length of stay ≥7 days (odds ratio [OR] = 1.5; 95% confidence interval [CI], 1.2–1.8; P < .001); pneumonia (OR = 2.7; 95% CI, 2.2–3.2; P < .001); intensive care unit admission (OR = 1.3; 95% CI, 1.0–1.7; P = .023); exacerbation of COPD (OR = 1.7; 95% CI, 1.3–2.4; P = .001); and greater mortality within 1 year of admission (OR = 1.3; 95% CI, 1.0–1.6; P = .019). Conclusions RSV infection may result in greater morbidity and mortality among older hospitalized adults than influenza. Increased recognition of adult RSV disease burden will be important in the evaluation and use of new RSV vaccines and antivirals.

scholarly journals Palivizumab and prevention of childhood respiratory syncytial viral infection: protocol for a systematic review and meta-analysis of breakthrough infections

BMJ Open ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. e029832
Author(s):  
Shelly Jun ◽  
Meghan Sebastianski ◽  
Robin Featherstone ◽  
Joan Robinson
Keyword(s):  
Systematic Review ◽  
Vaccine Development ◽  
Meta Analysis ◽  
Respiratory Illness ◽  
Sensitivity Analyses ◽  
Cochrane Library ◽  
Secondary Outcome ◽  
New Findings ◽  
Rsv Infection ◽  
Syncytial Virus

IntroductionChildhood respiratory syncytial virus (RSV) infection is a global phenomenon that can lead to fatal respiratory illness. Palivizumab is a drug that is routinely used in affluent countries as a prophylaxis against RSV infection; nevertheless, breakthrough infections are often reported. In light of new findings on potential RSV resistance to palivizumab, an up-to-date synthesis of evidence on effectiveness is needed. Furthering existing reviews, a broadened scope to better reflect effectiveness in a ‘real world’ clinical context is also important. This systematic review and meta-analysis will enhance our understanding of the effectiveness of palivizumab in varying populations of children. Findings from this review will inform recommendations for best practices regarding palivizumab use for childhood RSV infection as well as research priorities in RSV vaccine development.Methods and analysisWe will conduct a systematic review of primary population-based studies that examine the incidence of palivizumab breakthrough infections in children, published between 1997 to present. In collaboration with a research librarian, four electronic databases (MEDLINE, Embase, Cochrane Library, Web of Science) and additional sources will be searched. Study screening and quality assessment will be performed in duplicate. Data will be extracted by one reviewer, with partial and random verification by a second reviewer. The primary outcomes to assess breakthrough RSV infection will be hospitalisation, length of stay and the need for intensive care unit admission and mechanical ventilation in children receiving palivizumab. The secondary outcome will be RSV-associated mortality. We will conduct a meta-analysis using pooled effectiveness data, and include subgroup analyses by patient comorbidities and drug compliance. Sensitivity analyses for risk of bias and study design will also be performed.Ethics and disseminationThis systematic review will only include data from previously published literature and is therefore exempt from ethics approval. Final results will be disseminated through peer-reviewed publication and presented at academic conferences and scientific meetings engaging paediatric researchers and healthcare providers. Should findings from this review necessitate updates to current clinical practice guidelines, we intend to establish a working group to engage relevant health administrators and decision makers.PROSPERO registration numberCRD42019122120.

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