Control Of Respiratory Syncytial Virus Infection Research Articles

Respiratory syncytial virus (RSV) prevention: Perception and willingness of expectant parents in the Netherlands

BackgroundRespiratory syncytial virus (RSV) is a leading cause of infant respiratory disease. Recent approval of preventive measures like a long-acting monoclonal antibody and a maternal vaccine signals a potential shift in early-life RSV infection control. However, success hinges on acceptance. MethodsWe conducted a cross-sectional survey among pregnant women and partners in the Netherlands, recruited via healthcare professionals, social media platforms, and the 9-Months Fair. The survey assessed willingness and motivation for maternal RSV vaccination and neonatal RSV immunization, including strategy preferences and informational needs. ResultsIn total 1001 pregnant women (mean age: 31.1 years) and their partners (mean age: 33.2 years) completed the survey. On average, they were 24 weeks pregnant at the time, and 54.6 % had no other children yet. The majority was Dutch-born (95.2 % of women); with 68.3 % of women having completed higher education and with overall strong pro-vaccination attitudes (93.9 % of partners intended to vaccinate their expected newborn). The overall acceptability to vaccination and immunization was high, with 87 % of respondents indicating they would (likely) accept both strategies. A positive attitude towards both methods was associated with previous experience with severity of RSV, intention to vaccinate the newborn and parental vaccination status during childhood and current pregnancy. When the choice was given, the majority of participants, in particular those with children and the intention to breastfeed, favoured maternal vaccination over passive immunization of infants (75.3 % of the pregnant and 71.6 % of the partners). A majority of the respondents cited optimal protection for the child and knowledge of RSV as important factors for accepting RSV prophylaxis. ConclusionsWhile most participants would accept both strategies for RSV protection of their infant, a majority, especially those with other children, favoured maternal vaccination, due to concerns about infant safety and awareness of RSV severity.

Expert consensus on the passive immunization prevention of infant respiratory syncytial virus infection in China

Respiratory syncytial virus (RSV) infection, which has the very heavy disease burdens, is the most common viral pathogen that seriously threatens the health of infants and young children. In order to better guide and standardize the clinical diagnosis, treatment, monitoring and immunization prevention and control of RSV infection in China, the Chinese Preventive Medicine Association jointly organized multidisciplinary experts to form a special working group, drawing on the implementation experience of foreign passive immunization prevention of RSV, integrating the existing evidence and the latest progress as a problem oriented, and putting forward the expert consensus on the passive immunization prevention of infant RSV infection in China in the future. The aim is to answer some professional questions about RSV infection and its immunoprophylaxis, especially passive immunoprophylaxis, in order to provide reference for the practice of immunoprophylaxis for professionals in medical institutions, disease prevention and control institutions and community health service centers at all levels.

Expert consensus on the passive immunization prevention of infant respiratory syncytial virus infection in China

Respiratory syncytial virus (RSV) infection, which has the very heavy disease burdens, is the most common viral pathogen that seriously threatens the health of infants and young children. In order to better guide and standardize the clinical diagnosis, treatment, monitoring and immunization prevention and control of RSV infection in China, the Chinese Preventive Medicine Association jointly organized multidisciplinary experts to form a special working group, drawing on the implementation experience of foreign passive immunization prevention of RSV, integrating the existing evidence and the latest progress as a problem oriented, and putting forward the expert consensus on the passive immunization prevention of infant RSV infection in China in the future. The aim is to answer some professional questions about RSV infection and its immunoprophylaxis, especially passive immunoprophylaxis, in order to provide reference for the practice of immunoprophylaxis for professionals in medical institutions, disease prevention and control institutions and community health service centers at all levels.

Helminth induced monocytosis conveys protection from respiratory syncytial virus infection in mice.

Respiratory syncytial virus (RSV) infection in infants is a major cause of viral bronchiolitis and hospitalisation. We have previously shown in a murine model that ongoing infection with the gut helminth Heligmosomoides polygyrus protects against RSV infection through type I interferon (IFN-I) dependent reduction of viral load. Yet, the cellular basis for this protection has remained elusive. Given that recruitment of mononuclear phagocytes to the lung is critical for early RSV infection control, we assessed their role in this coinfection model. Mice were infected by oral gavage with H. polygyrus. Myeloid immune cell populations were assessed by flow cytometry in lung, blood and bone marrow throughout infection and after secondary infection with RSV. Monocyte numbers were depleted by anti-CCR2 antibody or increased by intravenous transfer of enriched monocytes. H. polygyrus infection induces bone marrow monopoiesis, increasing circulatory monocytes and lung mononuclear phagocytes in a IFN-I signalling dependent manner. This expansion causes enhanced lung mononuclear phagocyte counts early in RSV infection that may contribute to the reduction of RSV load. Depletion or supplementation of circulatory monocytes prior to RSV infection confirms that these are both necessary and sufficient for helminth induced antiviral protection. H. polygyrus infection induces systemic monocytosis contributing to elevated mononuclear phagocyte numbers in the lung. These cells are central to an anti-viral effect that reduces the peak viral load in RSV infection. Treatments to promote or modulate these cells may provide novel paths to control RSV infection in high risk individuals.

Disease Burden Due to Respiratory Syncytial Virus in Indian Pediatric Population: A Literature Review

Respiratory syncytial virus (RSV) is one of the leading causes of lower respiratory tract infections in young children. Globally, there is huge disease burden, high treatment cost, and health impact beyond acute episodes due to RSV which necessitate development and implementation of preventive strategies for the control of RSV infection. The disease burden due to RSV in pediatric population across India is still not clearly understood so this literature review was therefore conducted to gather data on disease burden due to RSV in Indian pediatric population. Systematic literature search was performed using PubMed and Google search with different medical subject headings from 2007 to 2020. Studies performed in Indian pediatric population were selected for review. Literature review revealed that in India, epidemiology of RSV infection is well documented in young children (0-5 years) as compared to children from other age groups. The rates of RSV detection in various studies conducted in younger children (0-5 years) vary from 2.1% to 62.4% in India which is higher as compared to children from other age groups. In India, RSV mainly peaks around rainy to early winter season, that is, during months of June through October while smaller peak was noted during December, January, and February. In 2020, higher RSV-associated disease burden was reported among children (<5 years) in low-income and lower-middle-income countries. Considering significant disease burden due to RSV in young Indian children, availability of RSV vaccine would be crucial to prevent RSV infections in children and its spread in the community.

Regulatory B Lymphocytes Colonize the Respiratory Tract of Neonatal Mice and Modulate Immune Responses of Alveolar Macrophages to RSV Infection in IL-10-Dependant Manner.

Respiratory syncytial virus (RSV) is the prevalent pathogen of lower respiratory tract infections in children. The presence of neonatal regulatory B lymphocytes (nBreg) has been associated with a poor control of RSV infection in human newborns and with bronchiolitis severity. So far, little is known about how nBreg may contribute to neonatal immunopathology to RSV. We tracked nBreg in neonatal BALB/c mice and we investigated their impact on lung innate immunity, especially their crosstalk with alveolar macrophages (AMs) upon RSV infection. We showed that the colonization by nBreg during the first week of life is a hallmark of neonatal lung whereas this population is almost absent in adult lung. This particular period of age when nBreg are abundant corresponds to the same period when RSV replication in lungs fails to generate a type-I interferons (IFN-I) response and is not contained. When neonatal AMs are exposed to RSV in vitro, they produce IFN-I that in turn enhances IL-10 production by nBreg. IL-10 reciprocally can decrease IFN-I secretion by AMs. Thus, our work identified nBreg as an important component of neonatal lungs and pointed out new immunoregulatory interactions with AMs in the context of RSV infection.

Antigenic Fingerprinting of Respiratory Syncytial Virus (RSV)-A-Infected Hematopoietic Cell Transplant Recipients Reveals Importance of Mucosal Anti-RSV G Antibodies in Control of RSV Infection in Humans.

Respiratory syncytial virus (RSV) infection causes significant morbidity in hematopoietic cell transplant (HCT) recipients. However, antibody responses that correlate with recovery from RSV disease are not fully understood. In this study, antibody repertoire in paired serum and nasal wash samples from acutely RSV-A-infected HCT recipients who recovered early (<14 days of RSV shedding) were compared with late-recovered patients (≥14 days of shedding) using gene fragment phage display libraries and surface plasmon resonance. Anti-F serum responses were similar between these 2 groups for antibody repertoires, neutralization titers, anti-F binding antibodies (prefusion and postfusion proteins), antibody avidity, and binding to specific antigenic sites. In contrast, nasal washes from early-recovered individuals demonstrated higher binding to F peptide containing p27. While the serum RSV G antibody repertoires in the 2 groups were similar, the strongest difference between early-recovered and late-recovered patients was observed in the titers of nasal wash antibodies, especially binding to the central conserved domain. Most importantly, a significantly higher antibody affinity to RSV G was observed in nasal washes from early-recovered individuals compared with late-recovered HCT recipients. These findings highlight the importance of mucosal antibodies in resolution of RSV-A infection in the upper respiratory tract.

Respiratory Syncytial Virus Infection Control Challenges with a Novel Polymerase Chain Reaction Assay in a Tertiary Medical Center.

OBJECTIVES To evaluate host characteristics, mode of infection acquisition, and infection control procedures in patients with a positive respiratory syncytial virus (RSV) test result after the introduction of the GenXpert Influenza/RSV polymerase chain reaction (PCR) assay. DESIGN Retrospective cohort study. PATIENTS Adults with a positive PCR test result for RSV who were hospitalized in a tertiary academic medical center between January 2015 and December 2016 were included in this study. Our infection control policy applies contact isolation precautions only for immunocompromised patients. METHODS Patients were identified through 2 databases, 1 consisting of patients isolated because of RSV infection and 1 with automatically collected laboratory results. Baseline and clinical characteristics were collected through a retrospective medical chart review. The rate of and clinical factors associated with healthcare-associated RSV infections were evaluated. RESULTS In total, 108 episodes in 106 patients hospitalized with a positive Xpert RSV test result were recorded during the study period. Among them, 11 episodes were healthcare-associated infections (HAIs) and 97 were community-acquired infections (CAIs). The mean length of hospital stay (LOS, 40.2 vs 11.2 days), the mean number of room switches (3.5 vs 1.7) and ward switches (1.5 vs 0.4), and the mean numbers of contact patients (9.9 vs 3.8) were significantly longer and higher in the HAI group than in the CAI group (P<.0001). Surveillance of microbiology records and clinical data did not reveal evidence for a cluster or an epidemic during the 2-year observation period. CONCLUSIONS The introduction of a rapid molecular diagnostic test systematically applied to patients with influenza-like illness may challenge current infection control policies. In our study, patients with HAIs had a prolonged hospital stay and a high number of contact patients, and they switched rooms and wards frequently. Infect Control Hosp Epidemiol 2017;38:1291-1297.

Age-Specific Profiles of Antibody Responses against Respiratory Syncytial Virus Infection

Respiratory syncytial virus (RSV) is one of the most prevalent causative agents of lower respiratory tract infections worldwide, especially in infants around 3 to 4months old. Infants at such a young age have maternally-transferred passive antibodies against RSV but do not have active immune systems efficient enough for the control of RSV infection. In order to elucidate age-specific profiles of immune responses against RSV protection, antibody responses were examined by using blood samples in both acute and convalescent phases obtained from child patients and adult patients. In addition to the serum neutralization activity, antibody responses to the RSV fusion protein (F protein) were dissected by analyzing levels of total IgG, IgG subclasses, the binding stability, and the levels of antibody for the neutralization epitopes. It was suggested that children's antibody responses against RSV are matured over months and years in at least 5 stages based on 1) levels of the neutralization titer and IgG3 for F protein in the convalescent phase, 2) geometric mean ratios of the neutralization titers and levels of IgG1 and IgG2 for F protein in the convalescent phase compared to those levels in the acute phase, 3) the affinity maturation of IgG for F protein and the cross reactivity of IgG for RSV glycoproteins of groups A and B, 4) levels of neutralization epitope-specific IgG, and 5) augmentation of overall antibody responses due to repetitive RSV infection.

Neutralizing epitopes of RSV and palivizumab resistance in Japan.

Respiratory Syncytial Virus (RSV) is one of the most important viral pathogen related to acute lower respiratory infection in young children. The virus surface envelope contains the G, F, and SH proteins as spike proteins. The F protein is considered to be a major antigenic target for the neutralizing (NT) epitope as only the F protein is essential for cell infection among the three viral envelope proteins, and it is more highly conserved than the G protein. Recently, four antigenic targets related to NT activity have been reported;site I, site II, site IV, and site zero (0). Site II is the target for palivizumab used throughout the world to suppress severe RSV infection as passive immunity in high-risk children since 1998. Under the recent conditions in which indications for palivizumab administered subjects are being expanded, palivizumab-resistant mutations have been confirmed overseas in children with RSV infection, although they remain infrequent. Therefore, continuous genetic analysis of the palivizumab-binding region of the F protein is necessary. In addition, as vaccine development progresses, RSV infection control is expected to improve greatly over the next decade.

The innate immune response to RSV: Advances in our understanding of critical viral and host factors

Respiratory syncytial virus (RSV) causes mild to severe respiratory illness in humans and is a major cause of hospitalizations of infants and the elderly. Both the innate and the adaptive immune responses contribute to the control of RSV infection, but despite successful viral clearance, protective immunity against RSV re-infection is usually suboptimal and infections recur. Poor understanding of the mechanisms limiting the induction of long-lasting immunity has delayed the development of an effective vaccine. The innate immune response plays a critical role in driving the development of adaptive immunity and is thus a crucial determinant of the infection outcome. Advances in recent years have improved our understanding of cellular and viral factors that influence the onset and quality of the innate immune response to RSV. These advances include the identification of a complex system of cellular sensors that mediate RSV detection and stimulate transcriptome changes that lead to virus control and the discovery that cell stress and apoptosis participate in the control of RSV infection. In addition, it was recently demonstrated that defective viral genomes (DVGs) generated during RSV replication are the primary inducers of the innate immune response. Newly discovered host pathways involved in the innate response to RSV, together with the potential generation of DVG-derived oligonucleotides, present various novel opportunities for the design of vaccine adjuvants able to induce a protective response against RSV and similar viruses.

Deep-sequencing of longitudinal samples from RSV-infected adults and infants reveals heterogeneous dynamics of within-host viral diversification

Abstract With high mutation rates, large population sizes, and rapid turnover, RNA viruses can evolve over the course of individual infections. While the dynamics of viral evolution under selective pressures from host immunity has been described for chronic infections, such as those from HIV and HCV, the extent and nature of viral diversification in acute viral infections remains uncharacterized. Here, we investigate the within-host diversification of human respiratory syncytial virus (RSV), a highly prevalent cause of respiratory infections, in healthy adults who were experimentally infected with identical virus and in infants hospitalized with severe manifestations of naturally acquired infections. In aggregate, viral diversification in the adults peaked at day 3, with statistically significant overrepresentation of diversity in the matrix protein 2 (M2) and non-structural protein 2 (NS2) genes. A later peak in diversity at day 10 was attributable to a single study subject, with diversity predominantly in known and predicted B and T cell epitopes. In the infant infections, much less diversity was observed, possibly related to sampling starting at the time of diagnosis and hospitalization, and trended towards overrepresentation in the G surface protein. Our findings raise the possibility of multiple mechanisms for control of RSV infection that vary over the course of an infection and by host, and establish a framework for further investigation into the basis of heterogeneous host response to infection. Moreover, the results have broad implications for investigations into immune response and the use of deep sequencing in viral pathogenicity and the molecular epidemiology of pathogen spread.

Innate IFNs and pro-inflammatory cytokines in local control of Respiratory Syncytial Virus infection of respiratory epithelial cells.

Abstract The host innate response contributes to the severity of disease caused by Respiratory Syncytial Virus (RSV). The primary target of RSV is the airway epithelium. The host becomes infected by inhaling droplets containing viral particles, which then infect small foci of cells. Infected cells then express types I and III interferons (IFN) and pro-inflammatory cytokines to alert neighboring epithelial and myeloid cells of danger. Despite their inherent differences, A549 (carcinoma, type II alveolar epithelium) and BEAS-2B (transformed bronchial epithelium) cells are often used interchangeably to study RSV-epithelial interactions. We compared these two cell lines by infecting them with low MOIs of RSV expressing GFP (rgRSV). We measured expression of types I and III IFNs, interferon stimulated genes (ISGs), pro-inflammatory cytokines and signaling intermediaries. We found that BEAS-2B cells contained rgRSV within foci of ~10–15 cells, but all A549 cells were infected by 48h. Both cell lines highly expressed IFN-β, IFN-λ1 and -λ2, but expression was greater in the A549s. Despite lower levels of IFN expression, BEAS-2Bs expressed higher levels of most classic antiviral ISGs (ISG15, MX1, PKR) and critical TLRs, RLRs and IFN receptors. In contrast, A549 cells expressed higher levels of NF-kB associated genes (CCL2, CCL5, CXCL8). Our data suggests that a balance between expression of NF-kB genes and ISGs may determine local control of RSV infection by respiratory epithelial cells.

Analysis of viral etiology for nasopharyngeal secretions in neonatal pneumonia

Objective To explore the viral etiology spectrum of different age and different seasons for neonatal pneumonia. Methods Medical records of 1 073 cases of neonatal pneumonia in our hospital were retrospectively analyzed, line direct immunofluorescence assay were used to detect nasopharyngeal secretions of newborns, the test results were statistically analyzed. Results In 1 073 cases with neonatal pneumonia, 406 cases were detected positive with virus infected, the positive rate was 37.8%,7 cases were mix infected. 334 cases were infected by respiratory syncytial virus(RSV), which had the highest detection rate, accounting for 82.3%;RSV infection rate in 1-6 month baby was 36.4%, which was higher than the>6-12 month-old baby with RSV infection rate 26.5%, the difference was statistically significant(χ2=12.25,P<0.05);RSV infection rate in winter and spring group was 39.7%, which was significantly higher than that in autumn and winter group(13.6%);PIV3 infection rate in winter and spring group was 1.8%,significantly lower than that in autumn and summer group(9.1%), the difference was statistically significant(χ2=31.27,P<0.05). Conclusion RSV is the most common viral in neonatal pneumonia, more attention should be payed to RSV infection control in small babies and at winter and spring, pay attention to PIV3 infection at autumn and summer. Key words: Virology; Nasopharyngeal secretion; Pneumonia; Infant

Screening for respiratory syncytial virus and isolation strategies in children hospitalized with acute respiratory tract infection.

Nosocomial infection with respiratory syncytial virus (RSV) is an important health risk in pediatric care but is largely preventable by efficient infection control measures. Commonly applied rapid antigen detection tests (RADTs) miss a considerable number of RSV-infected patients. The objective of our analysis was to evaluate whether readily available host parameters are associated with false-negative RADT, and to assess how these parameters could be applied in an optimized RSV isolation strategy.We retrospectively analyzed a cohort of 242 children under the age of 2 years hospitalized with acute respiratory tract infection to identify host parameters associated with false-negative RADT test result. We subsequently simulated the outcome of different isolation strategies based on RADT result and host parameters in view of the overall isolation efficacy.Out of 242 hospitalized patients, 134 (55%) patients were found RSV-positive by RT-PCR, whereas 108 (45%) patients were tested negative. The performance of the RADT was compared with the result obtained by reverse transcription polymerase chain reaction on the identical nasopharyngeal wash. Overall, we found that 85 patients (35%) were tested true positive, 108 (45%) were tested true negative, whereas a false-negative test result was obtained in 49 patients (20%). Duration of respiratory symptoms for >3 days and a respiratory admission diagnosis are associated with false-negative RADT result. In comparison with RADT alone, consideration of these clinical parameters and RADT result can decrease the rate of nonisolated RSV-infected patients from approximately 24% to 8% (65% RSV pretest probability).Consideration of both RADT and clinical parameters associated with false-negative RADT can result in an optimized RSV infection control policy.

Nosocomial RSV infection control and outbreak management

The incidence of nosocomial respiratory syncytial virus (RSV) infection in different areas of the world is not well known. However, it is clear that RSV infection of hospitalized infants with congenital heart disease or following preterm birth is highly relevant. Nosocomial RSV infection in these high-risk group infants often follows a severe course of disease, even resulting in mortality. Transmission of RSV mainly occurs through direct contact, but not through inhalation. Consequently, prevention of nosocomial RSV infection should aim to prevent direct contact between non-infected infants and RSV-infected people. Evidence of the role of gowns, masks and gloves is discussed. The effect and safety of cohorting RSV-infected infants is reviewed. International guidelines with respect to RSV prevention and outbreak management are analysed.

Respiratory syncytial virus: concerns and control.

1. Carol A. McCarthy, MD* 2. Caroline Breese Hall, MD† 1. *Director, Pediatric Infectious Disease, Maine Medical Center; Associate Professor of Pediatrics, University of Vermont College of Medicine, Montpelier, VT 2. †Professor of Pediatrics and of Medicine, The University of Rochester School of Medicine and Dentistry, Rochester, NY After completing this article, readers should be able to: 1. Describe the clinical manifestations of respiratory syncytial virus (RSV) infection. 2. Delineate the infants who are at increased risk for serious RSV infection. 3. Explain why older children and adults who have immunosuppression and the elderly may have significant RSV disease. 4. Explain why timely identification of RSV by antigen detection or culture may be helpful. 5. Describe for whom prophylaxis with immunoglobulin and treatment with antivirals should be considered. RSV is the major pathogen responsible for yearly outbreaks of lower respiratory tract disease in young children. Approximately 75,000 to 125,000 infants in the United States are estimated to be hospitalized yearly because of bronchiolitis or pneumonia from RSV. Although its significance in the young pediatric population has been recognized for more than 40 years, only more recently has RSV been confirmed as an important cause of respiratory tract illness throughout life. Increased understanding of the virus and the host response to it has resulted in expanded therapeutic and preventive options. Although elimination of RSV disease currently does not appear to be a realistic objective, control of RSV infection is possible and is being rigorously pursued. RSV is a member of the Paramyxoviridae family, genus pneumovirus. It was identified initially in chimpanzees that had coryza and was named chimpanzee coryza agent. Subsequently, this virus was isolated from infants who had respiratory symptoms and was renamed respiratory syncytial virus because of the characteristic syncytial pattern observed in tissue culture. It is an enveloped virus that has a single, negative-strand genome of 5×106 kD. The genome encodes 10 mRNAs, each of which codes for an individual protein. Five proteins (F, G, SH, M, M2) are associated with the viral envelope. The F or fusion protein appears to initiate the fusion of viral and cellular membranes. The …

Virus clearance and immunopathology by CD8(+) T cells during infection with respiratory syncytial virus are mediated by IFN-gamma.

CD8(+) T cells (CTL) are important effector cells for virus control and immunopathology after primary infection with respiratory syncytial virus (RSV). To investigate the effector mechanisms involved, we set up an adoptive transfer model, in which effector CTL specific for p82-90 of RSV M2 were generated in vivo, followed by short-term restimulation in vitro and transfusion into infected recipients. A total of 4 x 10(4) donor-derived p82-specific CTL homing to the lung within 4 days after transfusion were sufficient to completely eliminate a virusinoculum of 1.5 x 10(6) pfu. This was accompanied by significant lung pathology. Surprisingly, virus control and immunopathology proceeded unimpaired when donor cells lacking perforin, CD95 ligand or TNF were transfused. By contrast, treatment of recipient mice with a neutralizing antibody against IFN-gamma or transfusion of IFN-gamma-deficient effector CTL largely abolished virus control and significantly reduced CD8(+) T cell-mediated pathology. In IFN-gamma-deficient mice, high-dose primary infection experiments revealed attenuated immunopathology, but only slightly delayedvirus clearance, suggesting that other cells and molecules can partly substitute for the effects of CTL-derived IFN-gamma on virus clearance. These experiments identify IFN-gamma as a key molecule in RSV-induced immunopathology and in CD8(+) T cell-mediated control of RSV infection.