Respiratory Syncytial Virus: Diagnosis, Treatment and Prevention

Eiland, Lea S.

doi:10.5863/1551-6776-14.2.75

Cited by 51 publications

(50 citation statements)

References 58 publications

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“…The most interesting results, however, obtained in the current study were those related to the clinical parameters. Infants with RSV-disease typically develop clinical manifestations such as bronchiolitis and pneumonia symptoms of which include wheezing, crackles, rhonchi, tachypnea, nasal flaring, and intercostal muscle retractions [ 59 , 60 ]. In our study, the neonatal lambs developed respiratory distress (forced expiration, abdominal breathing and wheeze) following RSV-infection consistent with previous reports [ 1 , 18 ].…”

Section: Discussionmentioning

confidence: 99%

Kinetics of Respiratory Syncytial Virus (RSV) Memphis Strain 37 (M37) Infection in the Respiratory Tract of Newborn Lambs as an RSV Infection Model for Human Infants

et al. 2015

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RationaleRespiratory syncytial virus (RSV) infection in preterm and newborn infants can result in severe bronchiolitis and hospitalization. The lamb lung has several key features conducive to modeling RSV infection in human infants, including susceptibility to human strains of RSV such as the A2, Long, and Memphis Strain 37 (M37). In this study, the kinetics of M37 infection was investigated in newborn lambs in order to better define clinical, viral, physiological, and immunological parameters as well as the pathology and lesions.MethodsNewborn lambs were nebulized with M37 hRSV (6 mL of 1.27 x 107 FFU/mL), monitored daily for clinical responses, and respiratory tissues were collected from groups of lambs at days 1, 3, 4, 6, and 8 post-inoculation for the assessment of viral replication parameters, lesions and also cellular, immunologic and inflammatory responses.ResultsLambs had increased expiratory effort (forced expiration) at days 4, 6, and 8 post-inoculation. Nasal wash lacked RSV titers at day 1, but titers were present at low levels at days 3 (peak), 4, and 8. Viral titers in bronchoalveolar lavage fluid (BALF) reached a plateau at day 3 (4.6 Log10 FFU/mL), which was maintained until day 6 (4.83 Log10 FFU/mL), and were markedly reduced or absent at day 8. Viral RNA levels (detected by RT-qPCR) in BALF were indistinguishable at days 3 (6.22 ± 0.08 Log10 M37 RNA copies/mL; mean ± se) and 4 (6.20 ± 0.16 Log10 M37 RNA copies/mL; mean ± se) and increased slightly on day 6 (7.15 ± 0.2 Log10 M37 RNA copies/mL; mean ± se). Viral antigen in lung tissue as detected by immunohistochemistry was not seen at day 1, was present at days 3 and 4 before reaching a peak by day 6, and was markedly reduced by day 8. Viral antigen was mainly present in airways (bronchi, bronchioles) at day 3 and was increasingly present in alveolar cells at days 4 and 6, with reduction at day 8. Histopathologic lesions such as bronchitis/bronchiolitis, epithelial necrosis and hyperplasia, peribronchial lymphocyte infiltration, and syncytial cells, were consistent with those described previously for lambs and infants.ConclusionThis work demonstrates that M37 hRSV replication in the lower airways of newborn lambs is robust with peak replication on day 3 and sustained until day 6. These findings, along with the similarities of lamb lung to those of infants in terms of alveolar development, airway branching and epithelium, susceptibility to human RSV strains, lesion characteristics (bronchiolitis), lung size, clinical parameters, and immunity, further establish the neonatal lamb as a model with key features that mimic RSV infection in infants.

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Section: Discussionmentioning

confidence: 99%

Kinetics of Respiratory Syncytial Virus (RSV) Memphis Strain 37 (M37) Infection in the Respiratory Tract of Newborn Lambs as an RSV Infection Model for Human Infants

et al. 2015

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“…Two hRSV subtypes have been identified, A and B, with the subtype A mostly associated to outbreaks during winter in countries with temperate climates (24, 25). hRSV is transmitted by direct contact or aerosol particles and once in the airways it replicates in mucosal epithelial cells, starting in the upper respiratory tract and then continuing to the lower respiratory tract (26). When hRSV arrives to the lower respiratory tract, viral antigen recognition by innate immune cells induce an inflammatory response, a process that is the result of complex interactions between the pathogen and host factors (27, 28).…”

Section: Characteristics and Pathogenesis Of Hrsvmentioning

confidence: 99%

Cytokines in the Respiratory Airway as Biomarkers of Severity and Prognosis for Respiratory Syncytial Virus Infection: An Update

et al. 2019

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The human respiratory syncytial virus (hRSV) is one of the most important causes of upper and lower respiratory tract infections in children and the main cause of bronchiolitis worldwide. Disease manifestations caused by hRSV may vary from mild to severe, occasionally requiring admission and hospitalization in intensive care units. Despite the high morbidity rates associated to bronchiolitis, treatment options against hRSV are limited and there are no current vaccination strategies to prevent infection. Importantly, the early identification of high-risk patients can help improve disease management and prevent complications associated with hRSV infection. Recently, the characterization of pro- and anti-inflammatory cytokine patterns produced during hRSV-related inflammatory processes has allowed the identification of potential prognosis biomarkers. A suitable biomarker should allow predicting the severity of the infection in a simple and opportune manner and should ideally be obtained from non-invasive samples. Among the cytokines associated with hRSV disease severity, IL-8, interferon-alpha (IFN-alpha), and IL-6, as well as the Th2-type cytokines thymic stromal lymphopoietin (TSLP), IL-3, and IL-33 have been highlighted as molecules with prognostic value in hRSV infections. In this review, we discuss current studies that describe molecules produced by patients during hRSV infection and their potential as biomarkers to anticipate the severity of the disease caused by this virus.

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“…Therefore, prevention of RSV infection in high-risk infants is critical. In the absence of a vaccine, the only effective method for preventing severe RSV infection is prophylaxis with palivizumab (Synagis ® , AbbVie GK, Tokyo, Japan) [ 4 , 5 ]. Palivizumab is a humanized, anti-RSV monoclonal antibody (IgG1), exhibiting potent neutralizing and fusion-inhibiting activity via selective binding to the fusion protein of RSV subtypes A and B [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Palivizumab Prophylaxis Against Respiratory Syncytial Virus Infection in Children with Immunocompromised Conditions or Down Syndrome: A Multicenter, Post-Marketing Surveillance in Japan

2017

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ObjectiveThe aim of this study was to assess the safety and effectiveness of palivizumab for the prevention of lower respiratory tract infection (LRI) caused by respiratory syncytial virus (RSV) in children with immunocompromised conditions or Down syndrome.MethodsIn this multicenter, post-marketing surveillance study (December 2013 to December 2015), children aged ≤24 months with immunocompromised conditions or Down syndrome (without hemodynamically significant congenital heart disease) receiving palivizumab immunoprophylaxis during two RSV seasons were observed until 30 days after the final palivizumab injection. Safety [adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs), serious ADRs (SADRs)] and effectiveness (frequency, incidence, and duration of hospitalization due to RSV infections) were assessed.ResultsOf 304 patients receiving palivizumab, 167 (54.9%) had immunocompromised conditions, and 138 (45.4%) had Down syndrome; 260 (85.5%) completed palivizumab immunoprophylaxis. The annual mean (±standard deviation) number of doses was 5.3 (±2.4) per season. Overall, 220 AEs occurred in 99 patients (32.6%), including 89 SAEs in 53 patients (17.4%). Of these, 33 AEs in 25 patients (8.22%) were considered ADRs, and 13 ADRs in 11 patients (3.62%) were considered SADRs. In four patients, five SADRs (nephroblastoma and asthma in the same patient, septic shock, device-related infection, and drug-induced liver injury) were previously unreported; however, none were considered drug-related. During the observation period, five RSV infections occurred and two patients required hospitalization.ConclusionPalivizumab was generally safe and effective for the prevention of LRI caused by RSV in newborns, infants, and children with immunocompromised conditions or Down syndrome up to the age of 24 months.Electronic supplementary materialThe online version of this article (doi:10.1007/s40272-017-0264-y) contains supplementary material, which is available to authorized users.

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Respiratory Syncytial Virus: Diagnosis, Treatment and Prevention

Cited by 51 publications

References 58 publications

Kinetics of Respiratory Syncytial Virus (RSV) Memphis Strain 37 (M37) Infection in the Respiratory Tract of Newborn Lambs as an RSV Infection Model for Human Infants

Kinetics of Respiratory Syncytial Virus (RSV) Memphis Strain 37 (M37) Infection in the Respiratory Tract of Newborn Lambs as an RSV Infection Model for Human Infants

Cytokines in the Respiratory Airway as Biomarkers of Severity and Prognosis for Respiratory Syncytial Virus Infection: An Update

Palivizumab Prophylaxis Against Respiratory Syncytial Virus Infection in Children with Immunocompromised Conditions or Down Syndrome: A Multicenter, Post-Marketing Surveillance in Japan

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