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The Lancet. Global Health Jun 2024Respiratory syncytial virus (RSV) represents a substantial global health challenge, with a disproportionately high disease burden in low-income and middle-income...
BACKGROUND
Respiratory syncytial virus (RSV) represents a substantial global health challenge, with a disproportionately high disease burden in low-income and middle-income countries. RSV exhibits seasonality in most areas globally, and a comprehensive understanding of within-country variations in RSV seasonality could help to define the timing of RSV immunisation programmes. This study focused on China, and aimed to describe the geographical distribution of RSV seasonality, identify distinct RSV transmission zones, and evaluate the potential suitability of a seasonal RSV prevention strategy.
METHODS
We did a systematic analysis of RSV seasonality in China, with use of data on RSV activity extracted from a systematic review of studies published on Embase, MEDLINE, Web of Science, China National Knowledge Infrastructure, Wanfang Data, Chongqing VIP Information, and SinoMed, from database inception until May 5, 2023. We included studies of any design in China reporting at least 25 RSV cases, which aggregated RSV case number by calendar month or week at the province level, and with data covering at least 12 consecutive months before the year 2020 (prior to the COVID-19 pandemic). Studies that used only serology for RSV testing were excluded. We also included weekly data on RSV activity from open-access online databases of the Taiwan National Infection Disease Statistics System and Hong Kong Centre for Health Protection, applying the same eligiblity requirements. Across all datasets, we excluded data on RSV activity from Jan 1, 2020, onwards. We estimated RSV seasonal epidemic onset and duration using the annual average percentage (AAP) approach, and summarised seasonality at the provincial level. We used Pearson's partial correlation analysis to assess the correlation between RSV season duration and the latitude and longitude of the individual provinces. To define transmission zones, we used two independent approaches, an infant-passive-immunisation-driven approach (the moving interval approach, 6-month interval) and a data-driven approach (k-means), to identify groups of provinces with similar RSV seasonality. The systematic review was registered on PROSPERO, CRD42022376993.
FINDINGS
A total of 157 studies were included along with the two online datasets, reporting data on 194 596 RSV cases over 442 study-years (covering the period from Jan 1, 1993 to Dec 31, 2019), from 52 sites in 23 provinces. Among 21 provinces with sufficient data (≥100 reported cases), the median duration of RSV seasonal epidemics was 4·6 months (IQR 4·1-5·4), with a significant latitudinal gradient (r=-0·69, p<0·0007), in that provinces on or near the Tropic of Cancer had the longest epidemic duration. We found no correlation between longitude and epidemic duration (r=-0·15, p=0·53). 15 (71%) of 21 provinces had RSV epidemics from November to March. 13 (62%) of 21 provinces had clear RSV seasonality (epidemic duration ≤5 months). The moving interval approach categorised the 21 provinces into four RSV transmission zones. The first zone, consisting of five provinces (Fujian, Guangdong, Hong Kong, Taiwan, and Yunnan), was assessed as unsuitable for seasonal RSV immunisation strategies; the other three zones were considered suitable for seasonal RSV immunisation strategies with the optimal start month varying between September (Hebei), October (Anhui, Chongqing, Henan, Hubei, Jiangsu, Shaanxi, Shandong, Shanghai, Sichuan, and Xinjiang), and November (Beijing, Gansu, Guizhou, Hunan, and Zhejiang). The k-means approach identified two RSV transmission zones, primarily differentiated by whether the province was on or near the Tropic of Cancer (Fujian, Guangdong, Hong Kong, Taiwan, Yunan, and Hunan) or not (the remaining 15 provinces).
INTERPRETATION
Although substantial variations in RSV seasonality were observed across provinces of China, our study identified distinct transmission zones with shared RSV circulating patterns. These findings could have important implications for decision making on RSV passive immunisation strategy. Furthermore, the methodological framework in this study for defining RSV seasons and identifying RSV transmission zones is potentially applicable to other countries or regions.
FUNDING
Nanjing Medical University.
TRANSLATION
For the Chinese translation of the abstract see Supplementary Materials section.
Topics: Humans; Respiratory Syncytial Virus Infections; China; Seasons; Respiratory Syncytial Virus, Human
PubMed: 38670132
DOI: 10.1016/S2214-109X(24)00090-1 -
Immunity, Inflammation and Disease Apr 2024Respiratory syncytial virus (RSV) is the world's leading cause of viral acute lower respiratory infections (ALRI) in infants. WHO has identified maternal RSV vaccination...
BACKGROUND
Respiratory syncytial virus (RSV) is the world's leading cause of viral acute lower respiratory infections (ALRI) in infants. WHO has identified maternal RSV vaccination a priority and candidate vaccines are in development; however, vaccine hesitancy remains an impediment to successful implementation of maternal immunization. This study, the largest antenatal survey conducted to-date, aimed to examine maternal RSV awareness, likely acceptance of RSV vaccination in pregnancy, and attitudes to maternal vaccination.
METHODS
Pregnant women of all gestations attending antenatal clinic of a university maternity hospital in Ireland were invited to participate. An information leaflet provided, consent obtained, and survey administered examining RSV awareness, willingness to avail of antenatal RSV vaccination, factors influencing acceptability and preferred sources of assistance. Research Ethics Committee (REC) approval obtained, and general data protection regulation (GDPR) guidelines followed.
RESULTS
528 women completed the survey. A large proportion (75.6%) had never heard of RSV, yet 48.5% would still avail of a vaccine, 45.8% were undecided and only 5.3% would not. The main factor making vaccination acceptable to women (76.4%) was that it protects their infant from illness (p < .001, CV 0.336 for association with acceptance) and general practitioner (GP) was the preferred guidance source in decision-making (57.7%).
CONCLUSIONS
Despite low levels of maternal awareness of RSV, pregnant women in Ireland are open to availing of antenatal vaccination. Maternal immunization strategies need to focus on infant's protection from RSV-associated ALRI along with vaccine safety, and build on an interdisciplinary collaboration of maternal, neonatal, primary care and public health services.
Topics: Humans; Female; Ireland; Pregnancy; Respiratory Syncytial Virus Infections; Health Knowledge, Attitudes, Practice; Adult; Respiratory Syncytial Virus Vaccines; Vaccination; Patient Acceptance of Health Care; Pregnancy Complications, Infectious; Surveys and Questionnaires; Young Adult; Vaccination Hesitancy; Pregnant Women; Respiratory Syncytial Virus, Human; Adolescent
PubMed: 38661110
DOI: 10.1002/iid3.1257 -
Influenza and Other Respiratory Viruses Apr 2024Nonpharmaceutical interventions (NPIs) targeted at SARS-CoV-2 have remarkably affected the circulation of other respiratory pathogens, including respiratory syncytial...
BACKGROUND
Nonpharmaceutical interventions (NPIs) targeted at SARS-CoV-2 have remarkably affected the circulation of other respiratory pathogens, including respiratory syncytial virus (RSV). This study aimed to assess the changes in epidemiological and clinical characteristics of RSV infections in hospitalized children before and during the pandemic in Suzhou, China.
METHODS
We prospectively enrolled children aged < 18 years who were hospitalized in Soochow University Affiliated Children's Hospital with acute lower respiratory infection (ALRIs) from January 2018 to July 2022. Changes in epidemiological and clinical characteristics of RSV infections were analyzed.
RESULTS
Compared with the same period in 2018-2019, the difference in the overall positive rate of RSV was not statistically significant in 2020, while it increased significantly in 2021 (11.8% [662/5621] vs. 20.8% [356/1711], p < 0.001) and 2022 (9.0% [308/3406] vs. 18.9% [129/684], p < 0.001). Specifically, the positive rates declined considerably from October to December 2020 but sharply increased during the summer of 2021. Compared to prepandemic period, RSV infections were more frequently observed in older children during the pandemic. RSV-positive children exhibited milder clinical characteristics during the COVID-19 pandemic, including decreased proportion of patients with hospital stay ≥ 11 days (10.3% vs. 6.7%, p < 0.05), less requirement for oxygen therapy (13.7% vs. 6.9%, p < 0.001), and fewer cases of polypnea (12.2% vs. 9.7%, p < 0.05) and wheeze (50.1% vs. 42.9%, p < 0.001).
CONCLUSIONS
The implementation of multilayered NPIs targeted at COVID-19 has affected the activity of RSV. Ongoing monitoring of RSV is warranted as the changing RSV epidemiology can provide valuable insights for future healthcare system planning.
Topics: Humans; Respiratory Syncytial Virus Infections; COVID-19; Child, Preschool; Male; Female; Infant; Child; China; Prospective Studies; Hospitalization; SARS-CoV-2; Adolescent; Respiratory Syncytial Virus, Human; Child, Hospitalized; Infant, Newborn
PubMed: 38653953
DOI: 10.1111/irv.13291 -
Frontiers in Immunology 2024The respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections associated with numerous hospitalizations. Recently, intramuscular...
The respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections associated with numerous hospitalizations. Recently, intramuscular (i.m.) vaccines against RSV have been approved for elderly and pregnant women. Noninvasive mucosal vaccination, e.g., by inhalation, offers an alternative against respiratory pathogens like RSV. Effective mucosal vaccines induce local immune responses, potentially resulting in the efficient and fast elimination of respiratory viruses after natural infection. To investigate this immune response to an RSV challenge, low-energy electron inactivated RSV (LEEI-RSV) was formulated with phosphatidylcholine-liposomes (PC-LEEI-RSV) or 1,2-dioleoyl-3-trimethylammonium-propane and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DD-LEEI-RSV) for vaccination of mice intranasally. As controls, LEEI-RSV and formalin-inactivated-RSV (FI-RSV) were used i.m. vaccination. The RSV-specific immunogenicity of the different vaccines and their protective efficacy were analyzed. RSV-specific IgA antibodies and a statistically significant reduction in viral load upon challenge were detected in mucosal DD-LEEI-RSV-vaccinated animals. Alhydrogel-adjuvanted LEEI-RSV i.m. showed a Th2-bias with enhanced IgE, eosinophils, and lung histopathology comparable to FI-RSV. These effects were absent when applying the mucosal vaccines highlighting the potential of DD-LEEI-RSV as an RSV vaccine candidate and the improved performance of this mucosal vaccine candidate.
Topics: Animals; Respiratory Syncytial Virus Vaccines; Respiratory Syncytial Virus Infections; Mice; Vaccines, Inactivated; Female; Th2 Cells; Antibodies, Viral; Immunity, Mucosal; Mice, Inbred BALB C; Immunization; Respiratory Syncytial Virus, Human; Vaccination; Respiratory Syncytial Viruses; Viral Load; Immunoglobulin A
PubMed: 38646538
DOI: 10.3389/fimmu.2024.1382318 -
Journal of Clinical Virology : the... Jun 2024Rapid and accurate detection of viral respiratory infections is important for infection control measures. This study compares the analytical and clinical performance of... (Comparative Study)
Comparative Study
Evaluation of the analytical and clinical performance of two RT-PCR based point-of-care tests; Cepheid Xpert® Xpress CoV-2/Flu/RSV plus and SD BioSensor STANDARD™ M10 Flu/RSV/SARS-CoV-2.
BACKGROUND
Rapid and accurate detection of viral respiratory infections is important for infection control measures. This study compares the analytical and clinical performance of the Xpert® Xpress CoV-2/Flu/RSV plus test ("Xpert", Cepheid) and the STANDARD™ M10 Flu/RSV/SARS-CoV-2 test ("M10", SD Biosensor). Both tests are quadruplex RT-PCR assays for rapid diagnosis of SARS-CoV-2, influenza A/B and RSV.
STUDY DESIGN
Analytical sensitivities were determined by limit of detection for SARS-CoV-2, influenza A, influenza B and RSV, respectively. Additionally, the clinical performance of the Xpert and the M10 tests was evaluated against standard-of-care RT-PCR by testing of 492 clinical specimens.
RESULTS
The analytical sensitivities for Xpert versus M10 test was 10, 50, 50 and 300 versus 300, 200, 800 and 1500 copies/mL for SARS-CoV-2, influenza A, influenza B and RSV, respectively. Clinical sensitivity for the Xpert test was superior across all four pathogens compared to the M10 test. Xpert showed clinical sensitivity of 100 % in all Ct-ranges for all four pathogens whereas M10 showed clinical sensitivity of 100 % in the 25-30 Ct-range, 84-100 % in the 30-35 Ct-range and 47-67 % in the >35 Ct-range across the four pathogens. Translating into real-life clinical sensitivity, the Xpert would detect 100 % of all four pathogens, whereas M10 would detect 92.1, 92.4, 84.8 and 94.7 % for SARS-CoV-2, influenza A, influenza B and RSV.
CONCLUSION
This study demonstrates improved analytical and clinical performance of Xpert Xpress CoV-2/Flu/RSV plus compared to STANDARD M10 Flu/RSV/SARS-CoV-2, which is important for ensuring accuracy of diagnosis at all stages of a respiratory infection.
Topics: Humans; Sensitivity and Specificity; COVID-19; Influenza, Human; SARS-CoV-2; Influenza B virus; Influenza A virus; Respiratory Syncytial Virus Infections; Point-of-Care Testing; COVID-19 Nucleic Acid Testing; Reverse Transcriptase Polymerase Chain Reaction; Respiratory Syncytial Virus, Human
PubMed: 38643722
DOI: 10.1016/j.jcv.2024.105674 -
Nature Communications Apr 2024Respiratory Syncytial Virus (RSV) is a leading cause of acute respiratory tract infection, with the greatest impact on infants, immunocompromised individuals, and older...
Respiratory Syncytial Virus (RSV) is a leading cause of acute respiratory tract infection, with the greatest impact on infants, immunocompromised individuals, and older adults. RSV prevalence decreased substantially in the United States (US) following the implementation of COVID-19-related non-pharmaceutical interventions but later rebounded with abnormal seasonality. The biological and epidemiological factors underlying this altered behavior remain poorly defined. In this retrospective cohort study from 2009 to 2023 in Chicago, Illinois, US, we examined RSV epidemiology, clinical severity, and genetic diversity. We found that changes in RSV diagnostic platforms drove increased detections in outpatient settings post-2020 and that hospitalized adults infected with RSV-A were at higher risk of intensive care admission than those with RSV-B. While population structures of RSV-A remained unchanged, RSV-B exhibited a genetic shift into geographically distinct clusters. Mutations in the antigenic regions of the fusion protein suggest convergent evolution with potential implications for vaccine and therapeutic development.
Topics: Infant; Humans; United States; Aged; Respiratory Syncytial Virus Infections; Retrospective Studies; Pandemics; COVID-19; Respiratory Syncytial Virus, Human
PubMed: 38643200
DOI: 10.1038/s41467-024-47757-9 -
BMC Infectious Diseases Apr 2024Palivizumab has proven effective in reducing hospitalizations, preventing severe illness, improving health outcomes, and reducing healthcare costs for infants at risk of...
AIM
Palivizumab has proven effective in reducing hospitalizations, preventing severe illness, improving health outcomes, and reducing healthcare costs for infants at risk of respiratory syncytial virus (RSV) infection. We aim to assess the value of palivizumab in preventing RSV infection in high-risk infants in Colombia, where RSV poses a significant threat, causing severe respiratory illness and hospitalizations.
METHODS
We conducted a decision tree analysis to compare five doses of palivizumab with no palivizumab. The study considered three population groups: preterm neonates (≤ 35 weeks gestational age), infants with bronchopulmonary dysplasia (BPD), and infants with hemodynamically significant congenital heart disease (CHD). We obtained clinical efficacy data from IMpact-RSV and Cardiac Synagis trials, while we derived neonatal hospitalization risks from the SENTINEL-1 study. We based hospitalization and recurrent wheezing management costs on Colombian analyses and validated them by experts. We estimated incremental cost-effectiveness ratios and performed 1,000 Monte Carlo simulations for probabilistic sensitivity analyses.
RESULTS
Palivizumab is a dominant strategy for preventing RSV infection in preterm neonates and infants with BPD and CHD. Its high efficacy (78% in preventing RSV in preterm infants), the substantial risk of illness and hospitalization, and the high costs associated with hospitalization, particularly in neonatal intensive care settings, support this finding. The scatter plots and willingness-to-pay curves align with these results.
CONCLUSION
Palivizumab is a cost-saving strategy in Colombia, effectively preventing RSV infection in preterm neonates and infants with BPD and CHD by reducing hospitalizations and lowering healthcare costs.
Topics: Infant; Infant, Newborn; Humans; Palivizumab; Respiratory Syncytial Virus Infections; Cost-Benefit Analysis; Colombia; Antiviral Agents; Infant, Premature; Antibodies, Monoclonal, Humanized; Respiratory Syncytial Virus, Human; Heart Defects, Congenital; Hospitalization
PubMed: 38641577
DOI: 10.1186/s12879-024-09300-5 -
Vaccine May 2024Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) vaccines have been long overdue. Structure-based vaccine design created a new momentum in the last...
Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) vaccines have been long overdue. Structure-based vaccine design created a new momentum in the last decade, and the first RSV vaccines have finally been approved in older adults and pregnant individuals. These vaccines are based on recombinant stabilized pre-fusion F glycoproteins administered as soluble proteins. Multimeric antigenic display could markedly improve immunogenicity and should be evaluated in the next generations of vaccines. Here we tested a new virus like particles-based vaccine platform which utilizes the direct fusion of an immunogen of interest to the structural human immunodeficient virus (HIV) protein Gag to increase its surface density and immunogenicity. We compared, in mice, the immunogenicity of RSV-F or hMPV-F based immunogens delivered either as soluble proteins or displayed on the surface of our VLPs. VLP associated F-proteins showed better immunogenicity and induced superior neutralizing responses. Moreover, when combining both VLP associated and soluble immunogens in a heterologous regimen, VLP-associated immunogens provided added benefits when administered as the prime immunization.
Topics: Animals; Antibodies, Neutralizing; Mice; Metapneumovirus; Vaccines, Virus-Like Particle; Female; Viral Fusion Proteins; Antibodies, Viral; Mice, Inbred BALB C; gag Gene Products, Human Immunodeficiency Virus; Respiratory Syncytial Virus, Human; Immunogenicity, Vaccine; Humans; Respiratory Syncytial Virus Vaccines; Recombinant Fusion Proteins; Respiratory Syncytial Virus Infections; Viral Vaccines
PubMed: 38641492
DOI: 10.1016/j.vaccine.2024.04.048 -
JAMA Network Open Apr 2024Respiratory syncytial virus (RSV) resurgences have been noted following the COVID-19 pandemic in many countries. Recent findings suggest that the 2021 and 2022 RSV...
IMPORTANCE
Respiratory syncytial virus (RSV) resurgences have been noted following the COVID-19 pandemic in many countries. Recent findings suggest that the 2021 and 2022 RSV seasons were more severe than in past seasons, and age distribution may have shifted toward older children in the younger than 5 years age group.
OBJECTIVES
To estimate age-specific changes in RSV hospital-based burden of disease before and after the COVID-19 pandemic and to compare incidence by Medicaid use.
DESIGN, SETTING, AND PARTICIPANTS
This retrospective cohort study included children younger than 5 years diagnosed with RSV and bronchiolitis at 50 US children's hospitals in 10 US geographic regions. The included participants had an encounter in intensive care, inpatient, emergency, or observational units, between June 1, 2015, and March 31, 2023.
EXPOSURES
Diagnosis of RSV, bronchiolitis, or both at encounter.
MAIN OUTCOME AND MEASURES
Incidence rate ratio of hospital use within each care unit before vs after the COVID-19 pandemic. It was hypothesized a priori that incidence of hospital use would increase overall in 2021 and 2022 compared with 2015 to 2019 and that the increase would be greater among children 12 months and older.
RESULTS
Of 924 061 study participants (median [IQR] age, 8 (5-16) months; 535 619 [58.0%] male), 348 077 (37.7%) were diagnosed with RSV. Of these, 187 850 (54.0%) were hospitalized. Incidence rate ratios of hospitalization increased for all ages in 2021 and 2022 compared with 2015 to 2019. Children aged 24 to 59 months were 4.86 (95% CI, 4.75-4.98) times as likely to be hospitalized in 2022 compared with 2015 to 2019, whereas infants aged 0 to 5 months were 1.77 (95% CI, 1.74-1.80) times as likely. Medicaid patients were more likely to be hospitalized than non-Medicaid patients regardless of year.
CONCLUSIONS AND RELEVANCE
Hospitalizations for RSV and bronchiolitis demonstrated atypical seasonality in 2021 and 2022, with an overall increase in RSV encounters. Postpandemic RSV hospitalization increased for all ages, but especially among older children, whereas bronchiolitis hospitalization was decreased or unchanged compared with earlier seasons. These findings suggest some of the observed increase in RSV hospital use may be due to increased testing.
Topics: Child, Preschool; Female; Humans; Infant; Male; Bronchiolitis; Cost of Illness; COVID-19; Hospitals, Pediatric; Pandemics; Respiratory Syncytial Viruses; Retrospective Studies; United States
PubMed: 38635270
DOI: 10.1001/jamanetworkopen.2024.7125 -
Frontiers in Immunology 2024Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause...
BACKGROUND
Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause of LRTI in the elderly. The available treatments and FDA-approved vaccines for RSV only lessen the severity of the infection and are recommended for infants and elderly people.
METHODS
We focused on developing a broad-spectrum vaccine that activates the immune system to directly combat RSV. The objective of this study is to identify CD4 and CD8 T-cell epitopes using an immunoinformatics approach to develop RSV vaccines. The efficacy of these peptides was validated through and studies involving healthy and diseased animal models.
RESULTS
For each major histocompatibility complex (MHC) class-I and II, we found three epitopes of RSV proteins including F, G, and SH with an antigenic score of >0.5 and a projected SVM score of <5. Experimental validation of these peptides on female BALB/c mice was conducted before and after infection with the RSV A2 line 19f. We found that the 3RVMHCI (CD8) epitope of the F protein showed significant results of white blood cells (19.72 × 10 cells/μl), neutrophils (6.01 × 10 cells/μl), lymphocytes (12.98 × 10 cells/μl), IgG antibodies (36.9 µg/ml), IFN-γ (86.96 ng/L), and granzyme B (691.35 pg/ml) compared to control at the second booster dose of 10 µg. Similarly, 4RVMHCII (CD4) of the F protein substantially induced white blood cells (27.08 × 10 cells/μl), neutrophils (6.58 × 10 cells/μl), lymphocytes (16.64 × 10 cells/μl), IgG antibodies (46.13 µg/ml), IFN-γ (96.45 ng/L), and granzyme B (675.09 pg/ml). studies showed that 4RVMHCII produced a significant level of antibodies in sera on day 45 comparable to mice infected with the virus. 4RVMHCII also induced high IFN-γ and IL-2 secretions on the fourth day of the challenge compared to the preinfectional stage.
CONCLUSION
In conclusion, epitopes of the F protein showed considerable immune response and are suitable for further validation.
Topics: Aged; Animals; Child; Child, Preschool; Female; Humans; Infant; Mice; Antibodies, Viral; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Epitopes, T-Lymphocyte; Granzymes; Immunoglobulin G; Peptides; Respiratory Syncytial Virus Infections; Respiratory Syncytial Virus, Human
PubMed: 38629077
DOI: 10.3389/fimmu.2024.1349749