Respiratory Syncytial Virus Disease In Infants Research Articles

A Phase 1b/2a Single Ascending Dose Study of a Half-life Extended RSV Neutralizing Antibody, Clesrovimab, in Healthy Preterm and Full-term Infants.

Clesrovimab is an investigational monoclonal antibody with an extended half-life targeting site IV of the respiratory syncytial virus (RSV) fusion protein for the prevention of RSV disease in infants. In this phase 1b/2a, double-blind study,183 healthy preterm and full-term infants 2 weeks to 8 months of age were randomized 4:1 within 5 panels (preterm: 20, 50, 75 or 100-mg, full-term: 100 mg) to receive one dose of clesrovimab or placebo. The objectives were to evaluate safety, pharmacokinetics, serum neutralizing antibodies (SNA), and anti-drug antibodies (ADA). The incidence of RSV-associated endpoints [medically-attended lower respiratory tract infection (MALRI), hospitalization, and acute respiratory infection (ARI)] were also evaluated through 150 days postdose. The most common adverse event (AE) through day 14 was irritability; no treatment-related serious AEs were reported. Clesrovimab serum concentrations displayed a geometric mean apparent half-life of 44.9 days. Of participants receiving clesrovimab, 51 (36.7%) developed ADA with no apparent impact in pharmacokinetics. SNA titers increased in a dose-dependent manner at day 150. The incidences of RSV-associated endpoints were lower in infants treated with clesrovimab compared with placebo. Clesrovimab was generally well tolerated and exhibited an extended half-life compared to typical IgG1 antibodies supporting its ongoing development in late-stage trials. Clinicaltrials.gov, NCT03524118.

Activation of STAT3-mediated ciliated cell survival protects against severe infection by respiratory syncytial virus.

Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia, mostly in infants. To identify molecular targets of intervention during RSV infection in infants, we investigated how age regulates RSV interaction with the bronchial epithelium barrier. Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium. In contrast, adult bronchial epithelium showed no barrier damage and limited RSV infection. Single nuclear RNA-Seq revealed age-related insufficiency of an antiapoptotic STAT3 activation response to RSV infection in infant ciliated cells, which was exploited to facilitate virus spread via the extruded apoptotic ciliated cells carrying RSV. Activation of STAT3 and blockade of apoptosis rendered protection against severe RSV infection in infant bronchial epithelium. Lastly, apoptotic inhibitor treatment of a neonatal mouse model of RSV infection mitigated infection and inflammation in the lung. Taken together, our findings identify a STAT3-mediated antiapoptosis pathway as a target to battle severe RSV disease in infants.

First real-world data on universal respiratory syncytial virus prophylaxis with Nirsevimab in infants.

Respiratory Syncytial Virus (RSV) predominantly affects young children, with a peak incidence in temperate regions of the northern hemisphere from October to May. Children under 24 months of age are particularly vulnerable because of the immaturity of their lungs and immune systems, often leading to severe respiratory infections. The World Health Organization (WHO) recognizes RSV as a global health priority. Recently, Nirsevimab, a long-acting monoclonal antibody (mAb), was authorised to prevent RSV disease in infants. Our narrative review brings together the effectiveness data of Nirsevimab available in the literature, highlighting the strengths and weaknesses of the published studies and the prevention opportunities represented by the new preparation. All reviewed studies provide evidence for the effectiveness of immunisation with Nirsevimab in real-world settings, beyond the controlled conditions of clinical trials, and highlight its safety and feasibility. Nirsevimab significantly reduces RSV hospitalisations and Intensive Care Unit (ICU) admissions. High coverage and high efficacy of immunisation have been reported, although supply issues and variability in studies present challenges. Continued research and surveillance are critical to understanding the long-term effectiveness of Nirsevimab. Overall, available data provide valuable insights into the efficacy, safety, and impact of immunisation with Nirsevimab in preventing severe RSV infections in infants, highlighting its potential to reduce the burden of RSV-related hospitalisations and improve paediatric health outcomes.

Respiratory syncytial virus vaccination during pregnancy for improving infant outcomes.

Respiratory syncytial virus vaccination during pregnancy for improving infant outcomes.

Early Estimate of Nirsevimab Effectiveness for Prevention of Respiratory Syncytial Virus-Associated Hospitalization Among Infants Entering Their First Respiratory Syncytial Virus Season - New Vaccine Surveillance Network, October 2023-February 2024.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among infants in the United States. In August 2023, CDC's Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, for infants aged <8 months to protect against RSV-associated lower respiratory tract infection during their first RSV season and for children aged 8-19 months at increased risk for severe RSV disease. In phase 3 clinical trials, nirsevimab efficacy against RSV-associated lower respiratory tract infection with hospitalization was 81% (95% CI = 62%-90%) through 150 days after receipt; post-introduction effectiveness has not been assessed in the United States. In this analysis, the New Vaccine Surveillance Network evaluated nirsevimab effectiveness against RSV-associated hospitalization among infants in their first RSV season during October 1, 2023-February 29, 2024. Among 699 infants hospitalized with acute respiratory illness, 59 (8%) received nirsevimab ≥7 days before symptom onset. Nirsevimab effectiveness was 90% (95% CI = 75%-96%) against RSV-associated hospitalization with a median time from receipt to symptom onset of 45 days (IQR = 19-76 days). The number of infants who received nirsevimab was too low to stratify by duration from receipt; however, nirsevimab effectiveness is expected to decrease with increasing time after receipt because of antibody decay. Although nirsevimab uptake and the interval from receipt of nirsevimab were limited in this analysis, this early estimate supports the current nirsevimab recommendation for the prevention of severe RSV disease in infants. Infants should be protected by maternal RSV vaccination or infant receipt of nirsevimab.

Nirsevimab: A Review.

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections in people of all ages and is the leading cause of hospitalization among infants in the United States. The year 2023 was exciting for RSV prevention. The Food and Drug Administration (FDA) approved 3 new tools for preventing severe lower respiratory tract RSV infections in infants, young children, and elderly persons. In May 2023, the FDA approved 2 vaccines, RSVpreF3 (Arexvy™, GSK) and RSVpreF (Abrysvo™, Pfizer), for adults ages 60 years or older to be given as a single-dose intramuscular injection. July 2023 brought the approval of the first long-acting monoclonal antibody nirsevimab (Beyfortus™, Sanofi and AstraZeneca) for the prevention of RSV disease in infants and young children. Then in August, the FDA approved a vaccine (Abrysvo™, Pfizer) to be given to pregnant women to protect their newborns through passive immunity. This article focuses on nirsevemab that has been recommended by the Advisory Committee on Immunization Practices (ACIP) and American Academy of Pediatrics (AAP) to be administered for all infants <8 months of age and for children 8 to 19 months of age who are at increased risk for severe RSV disease.

Fall 2023 ACIP Update on Meningococcal, RSV, COVID-19, and Other Pediatric Vaccines.

The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts that provides advice to the Centers for Disease Control and Prevention, normally meets 3 times per year to develop US vaccine recommendations. The ACIP met October 25 to 26, 2023, to discuss meningococcal vaccines, mpox vaccines, respiratory syncytial virus (RSV) vaccines, influenza vaccines, coronavirus disease 2019 (COVID-19) vaccines, and the combined pediatric and adult immunization schedules for 2024. The ACIP also held special meetings on September 12 and September 22 to discuss COVID-19 2023-2024 vaccine recommendations and RSV immunization in pregnant women. This update summarizes the proceedings of these meetings that are most relevant to the pediatric population. Major updates for pediatric clinicians include recommendations for XBB monovalent COVID-19 immunization for the 2023-2024 respiratory season, the recently licensed pentavalent meningococcal conjugate vaccine and mpox vaccination in high-risk young adults, and discussion regarding the parallel strategies of protection against RSV disease in infants via maternal immunization during pregnancy or direct prophylaxis of infants with nirsevimab.

Approach to prevention of respiratory syncytial virus disease in infants by passive immunization.

To support family physicians in discussing respiratory syncytial virus (RSV) immunizations with patients. Information was obtained through a literature review on the burden of RSV disease in infants; observational studies; randomized controlled trials; evidence presented by review agencies; product monographs; and National Advisory Committee on Immunization statements. There are now 3 options available for preventing severe RSV disease in infants: the monoclonal antibody palivizumab, the long-acting monoclonal antibody nirsevimab, and the new RSVpreF vaccine administered during pregnancy. Only a small number of infants at high risk of severe RSV disease are eligible for palivizumab. Nirsevimab has received Health Canada authorization for all infants and RSVpreF has received authorization for all pregnant women and pregnant people. There are multiple considerations for the use of each product, including authorization; availability; timing of administration; health status and social determinants of health of the infant; efficacy and effectiveness; safety; patient preference; and cost. The National Advisory Committee on Immunization has recently issued guidance on the use of RSV immunization products for infants. Family doctors should be aware of the indications, relative benefits, and recommendations for the 3 RSV immunization products to have informed discussions with patients, taking into account the preferences and circumstances of the pregnant woman or pregnant person or of the parent and infant.

Direct long-acting antibodies: updating the language of RSV prevention to reflect the evolution of mAbs.

The language of medicine is constantly evolving, typically to better describe a new understanding of disease, adjust to changing social sensibilities, or simply to reflect a new drug class or category. We address the need for an updated language around monoclonal antibodies, or "mAbs" - a widely used medical term, but one which is now too general to accurately reflect the range of mAb pharmaceuticals, their effects, and the intended patients. The question of "what should we call a monoclonal antibody immunisation against respiratory syncytial virus (RSV) to ensure accurate understanding of the product?" was the basis for a virtual advisory panel in May 2022. The panel was convened by Sanofi with the intention of reviewing appropriate language in terminology in the context of mAb-based prophylaxis for RSV. The panel comprised several global experts on RSV and vaccination, a trained linguist specialising in doctor-patient interactions and medical language, and several experts in marketing and communications. We suggest the term "Direct Long-acting Antibody" (DLA) for a specific sub-class of mAbs for use in prevention of RSV disease in infants. This terminology should differentiate from other mAbs, which are generally not used as therapies in infants. This change will more accurately convey the specific mode of action of a mAb in infants, and how it could impact the prevention of communicable diseases: this class of mAbs is not an active treatment, but rather will offer direct and rapid protection lasting at least 5 months.

Host Responses to Respiratory Syncytial Virus Infection.

Respiratory syncytial virus (RSV) infections are a constant public health problem, especially in infants and older adults. Virtually all children will have been infected with RSV by the age of two, and reinfections are common throughout life. Since antigenic variation, which is frequently observed among other respiratory viruses such as SARS-CoV-2 or influenza viruses, can only be observed for RSV to a limited extent, reinfections may result from short-term or incomplete immunity. After decades of research, two RSV vaccines were approved to prevent lower respiratory tract infections in older adults. Recently, the FDA approved a vaccine for active vaccination of pregnant women to prevent severe RSV disease in infants during their first RSV season. This review focuses on the host response to RSV infections mediated by epithelial cells as the first physical barrier, followed by responses of the innate and adaptive immune systems. We address possible RSV-mediated immunomodulatory and pathogenic mechanisms during infections and discuss the current vaccine candidates and alternative treatment options.

WHO preferred product characteristics for monoclonal antibodies for passive immunization against respiratory syncytial virus (RSV) disease in infants – Key considerations for global use

World Health Organization (WHO) preferred product characteristics describe preferences for product attributes that would help optimize value and use to address global public health needs, with a particular focus on low- and middle-income countries. Having previously published preferred product characteristics for both maternal and paediatric respiratory syncytial virus (RSV) vaccines, WHO recently published preferred product characteristics for monoclonal antibodies to prevent severe RSV disease in infants. This article summarizes the key attributes from the preferred product characteristics and discusses key considerations for future access and use of preventive RSV monoclonal antibodies.

Overview of the respiratory syncytial virus vaccine candidate pipeline in Canada.

A vaccine for respiratory syncytial virus (RSV) has been actively sought for over 60 years due to the health impacts of RSV disease in infants, but currently the only available preventive measure in Canada and elsewhere is limited to passive immunization for high-risk infants and children with a monoclonal antibody. RSV vaccine development has faced many challenges, including vaccine-induced enhancement of RSV disease in infants. Several key developments in the last decade in the fields of cellular immunology and protein structure have led to new products entering late-stage clinical development. As of July 2019, RSV vaccine development is being pursued by 16 organizations in 121 clinical trials. Five technologies dominate the field of RSV vaccine development, four active immunizing agents (live-attenuated, particle-based, subunit-based and vector-based vaccines) and one new passive immunizing agent (monoclonal antibody). Phase 3 clinical trials of vaccine candidates for pregnant women, infants, children and older adults are under way. The next decade will see a dramatic transformation of the RSV prevention landscape.

2781. Statistical Modeling to Predict Maternal RSV Vaccine Efficacy from Neutralizing Titers

BackgroundIn the United States, respiratory syncytial virus (RSV) is the leading cause of respiratory-related hospitalization in infants. The well-studied efficacy of the prophylactic monoclonal antibody, palivizumab, at preventing RSV disease in the highest risk infants provides proof of mechanism that serum neutralizing antibody protects against RSV. The expense and burden of monthly antibody injections limit the utility of palivizumab, leaving a large unmet medical need. Maternal immunization, with transplacental transfer of antibodies to the fetus, is an alternative, highly practical approach to protect many more infants.MethodsLevels of protection by known palivizumab serum concentrations provide a basis for predicting maternal RSV vaccine efficacy in infants based on serum neutralizing antibody titers elicited in vaccine clinical trials, using statistical modeling to compensate for differences between palivizumab prophylaxis and maternal immunization. The model adjusts for the dependency of maternal vaccine responses on pre-immunization RSV neutralizing titers, exponential decay of maternal antibodies in infants, and exponentially decreasing airway resistance (reducing RSV disease risk) as infants grow.ResultsThe rates of severe RSV disease by age projected from the model match the pattern of US infant hospitalization for RSV, with a peak at 1.5 months of age. The model relates vaccine-elicited increases in maternal RSV neutralizing titers to predicted reductions in severe RSV disease in infants from 0 to 6 months of age.ConclusionStatistical modeling of maternal RSV vaccine efficacy based on elicited RSV neutralizing titers provides a rational basis for decision-making during RSV vaccine development.Disclosures All authors: No reported disclosures.

2755. Phase 1/2, First-in-Human Study of the Safety, Tolerability, and Immunogenicity of an RSV Prefusion F-Based Subunit Vaccine Candidate

BackgroundThe respiratory syncytial virus (RSV) fusion glycoprotein (F) is a molecule that fuses the viral and host cell membranes during virus entry as it rearranges from a meta-stable prefusion to a stable postfusion conformation. Using structure-guided design, Pfizer engineered a prefusion RSV F subunit vaccine antigen with stable and well-characterized conformational homogeneity.MethodsWe report results of a 1,182 subject, first-in-human, phase 1/2, placebo-controlled, randomized, observer-blind, dose-finding study to describe the safety, tolerability, and immunogenicity of the Pfizer RSV vaccine candidate in healthy men and non-pregnant women from 18 to 85 years of age. The study compares three dosages of the vaccine candidate, with and without aluminum hydroxide, and also compares immunization with the RSV vaccine candidate alone or concomitantly with influenza vaccine. The study is ongoing to collect antibody persistence and additional safety data.ResultsThe data, which are currently available for the 18- to 49-year-old subgroup, demonstrate an excellent safety and tolerability profile. Immunization with the various formulations of the vaccine candidate elicited RSV 50% neutralization titer geometric mean fold rises (GMFRs) of 10.6–17.2 for subgroup A and 10.4–19.8 for subgroup B, measured one month after immunization, with evidence of a dose–response.ConclusionThe 10- to 20-fold increases in neutralizing antibody titers elicited by this vaccine with a stable prefusion F antigen represent a step change relative to the historical performance of vaccine candidates, such as Wyeth’s PFP, with F antigens that were not stabilized in the prefusion conformation (Simoes et al., Vaccine 20:954–60, 2002). The data strongly support development of this vaccine candidate to prevent RSV disease in infants, by immunizing pregnant women, and to prevent RSV disease in older adults, by direct immunization.Disclosures All authors: No reported disclosures.

Pathogenesis of Respiratory Syncytial Virus Infection in BALB/c Mice Differs Between Intratracheal and Intranasal Inoculation.

Human respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract disease requiring hospitalization in infants. There are no market-approved vaccines or antiviral agents available, but a growing number of vaccines and therapeutics are in (pre)clinical stages of development. Reliable animal models are crucial to evaluate new vaccine concepts, but in vivo RSV research is hampered by the lack of well-characterized animal models that faithfully mimic the pathogenesis of RSV infection in humans. Mice are frequently used in RSV infection and vaccination studies. However, differences in the use of mouse strains, RSV subtypes, and methodology often lead to divergent study outcomes. To our knowledge, a comparison between different RSV inoculation methods in mice has not been described in the literature, even though multiple methods are being used across different studies. In this study, we evaluated various pathological and immunological parameters in BALB/c mice after intratracheal or intranasal inoculation with RSV-A2. Our study reveals that intranasal inoculation induces robust pathology and inflammation, whereas this is not the case for intratracheal inoculation. As immunopathology is an important characteristic of RSV disease in infants, these data suggest that in mice intranasal inoculation is a more appropriate method to study RSV infection than intratracheal inoculation. These findings will contribute to the rational experimental design of future in vivo RSV experiments.

Transplacental transfer of maternal respiratory syncytial virus (RSV) antibody and protection against RSV disease in infants in rural Nepal

BackgroundRespiratory syncytial virus (RSV) is the most important viral cause of pneumonia in children. RSV-specific antibody (ab) protects infants from disease, and may be increased by a potential strategy of maternal RSV vaccination. ObjectivesTo describe the effect of RSV antibody on RSV infection risk in infants in a resource-limited setting. Study designIn a prospective study in Nepal, women were enrolled during pregnancy and maternal and infant cord blood were collected at birth. Weekly surveillance for respiratory illness was performed from birth to 180days. Nasal swabs were tested for RSV by PCR and serum was tested using an RSV antibody microneutralization assay. Antibody concentrations at time of RSV infection were estimated based on a decay rate of 0.026 log2/day. ResultsCord:maternal RSV antibody transfer ratio was 1.03 (0.88–1.19), with RSV antibody concentration of log2 11.3 and log2 11.7 in 310 paired maternal and infant samples, respectively. Cord blood RSV antibody was log2 12.1 versus 11.6 in those with or without RSV infection (P=0.86). Among infants with RSV infection, estimated RSV antibody concentration at time of infection did not differ in infants with upper (n=8; log2 10.7) versus lower respiratory tract infection (n=21; log2 9.8; P=0.37). Cord blood RSV antibody concentrations did not correlate with age at primary RSV infection (R=0.11; P=0.57). ConclusionsTransplacental transfer of RSV antibody from mother to the fetus was highly efficient in mother-infant pairs in rural Nepal, though higher antibody concentrations were not protective against earlier or more severe RSV infection in infants.

Induction and Antagonism of Antiviral Responses in Respiratory Syncytial Virus-Infected Pediatric Airway Epithelium

Airway epithelium is the primary target of many respiratory viruses. However, virus induction and antagonism of host responses by human airway epithelium remains poorly understood. To address this, we developed a model of respiratory syncytial virus (RSV) infection based on well-differentiated pediatric primary bronchial epithelial cell cultures (WD-PBECs) that mimics hallmarks of RSV disease in infants. RSV is the most important respiratory viral pathogen in young infants worldwide. We found that RSV induces a potent antiviral state in WD-PBECs that was mediated in part by secreted factors, including interferon lambda 1 (IFN-λ1)/interleukin-29 (IL-29). In contrast, type I IFNs were not detected following RSV infection of WD-PBECs. IFN responses in RSV-infected WD-PBECs reflected those in lower airway samples from RSV-hospitalized infants. In view of the prominence of IL-29, we determined whether recombinant IL-29 treatment of WD-PBECs before or after infection abrogated RSV replication. Interestingly, IL-29 demonstrated prophylactic, but not therapeutic, potential against RSV. The absence of therapeutic potential reflected effective RSV antagonism of IFN-mediated antiviral responses in infected cells. Our data are consistent with RSV nonstructural proteins 1 and/or 2 perturbing the Jak-STAT signaling pathway, with concomitant reduced expression of antiviral effector molecules, such as MxA/B. Antagonism of Jak-STAT signaling was restricted to RSV-infected cells in WD-PBEC cultures. Importantly, our study provides the rationale to further explore IL-29 as a novel RSV prophylactic. Most respiratory viruses target airway epithelium for infection and replication, which is central to causing disease. However, for most human viruses we have a poor understanding of their interactions with human airway epithelium. Respiratory syncytial virus (RSV) is the most important viral pathogen of young infants. To help understand RSV interactions with pediatric airway epithelium, we previously developed three-dimensional primary cell cultures from infant bronchial epithelium that reproduce several hallmarks of RSV infection in infants, indicating that they represent authentic surrogates of RSV infection in infants. We found that RSV induced a potent antiviral state in these cultures and that a type III interferon, interleukin IL-29 (IL-29), was involved. Indeed, our data suggest that IL-29 has potential to prevent RSV disease. However, we also demonstrated that RSV efficiently circumvents this antiviral immune response and identified mechanisms by which this may occur. Our study provides new insights into RSV interaction with pediatric airway epithelium.

WHO consultation on Respiratory Syncytial Virus Vaccine Development Report from a World Health Organization Meeting held on 23–24 March 2015

Respiratory syncytial virus (RSV) is a globally prevalent cause of lower respiratory infection in neonates and infants. Despite its disease burden, a safe and effective RSV vaccine has remained elusive. In recent years, improved understanding of RSV biology and innovations in immunogen design has resulted in the advancement of multiple vaccine candidates into the clinical development pipeline. Given the growing number of vaccines in clinical trials, the rapid pace at which they are being tested, and the likelihood that an RSV vaccine will reach the commercial market in the next 5–10 years, consensus and guidance on clinical development pathways and licensure routes are needed now, before large-scale efficacy trials commence. In pursuit of this aim, the World Health Organization convened the first RSV vaccine consultation in 15 years on the 23rd and 24th of March, 2015 in Geneva, Switzerland. The meeting's primary objective was to provide guidance on clinical endpoints and development pathways for vaccine trials with a focus on considerations of low- and middle-income countries. Meeting participants reached consensus on candidate case definitions for RSV disease, considerations for clinical efficacy endpoints, and the clinical development pathway for active and passive immunization trials in maternal and pediatric populations. The strategic focus of this meeting was on the development of high quality, safe and efficacious RSV preventive interventions for global use and included: (1) maternal/passive immunization to prevent RSV disease in infants less than 6 months; (2) pediatric immunization to prevent RSV disease in infants and young children once protection afforded by maternal immunization wanes.

SP-A1, SP-A2 and SP-D gene polymorphisms in severe acute respiratory syncytial infection in Chilean infants

Respiratory syncytial virus (RSV) is the principal pathogen that causes acute lower respiratory tract infection (ALRI) in infants. Severe RSV-ALRI has been associated with the host genetic susceptibility. To assess whether severe RSV disease in infants is associated with certain single nucleotide polymorphism (SNP) into the gene of SP-A1, SP-A2 and SP-D, a prospective study was performed among blood donors and RSV-infected infants aged <or=6 months, considering their severity, according to a strict scoring system. Allele and genotype frequencies were compared using χ2-test. Association studies and haplotype analysis were tested by using Armitagës trend test and Unphased 3.0 program.A total of 118 RSV-infected infants and 104 blood donors were enrolled into the study; 59 infants had a severe respiratory disease, 34 children developed a moderate illness and 25 had a mild disease. There was no difference in the allelic and genotypic frequencies of SP-A1, but intragenic haplotypes showed significant differences among infected infants and blood donors (p=0.0021). 1A0 variant of SP-A2 was the most frequent allele in all groups. Thr11 allele of SP-D is significantly higher in RSV infants (p=0.028), as given by its higher frequency in severe disease (p=0.046). Heterozygous Thr11/Met11 was significantly more common in infected infants (p=0.037), because it has higher frequency in critically ill children (p=0.017). Thr160 allele was significantly higher in severe infants compared with blood donors (p=0.046) and infants with mild disease (p=0.018). Thr11-Thr160-Ser270 haplotype was significantly more common in RSV-infants, due to severe (p=0.00000034) and moderate disease (p=0.000009). Differences were also found among severe and mild disease (p=0.026). Differences found with other authors, indicate the need for local studies to identify genetic biomarkers of severity.

Severe respiratory syncytial virus (RSV) infection in infants with neuromuscular diseases and immune deficiency syndromes

Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract infection (LRTI) in infants and children. There is growing evidence of severe RSV disease in infants with neuromuscular diseases and immune deficiency syndromes. Factors predisposing to a more severe course of RSV disease in neuromuscular diseases include the impaired ability to clear secretions from the airways due to ineffective cough, respiratory muscle weakness, high prevalence of gastro-oesophageal reflux and swallowing dysfunction which leads to aspiration. Similarly, pulmonary disease is a common presenting feature and complication of T-cell immunodeficiency. Infants with severe congenital and acquired immune deficiency syndromes may demonstrate prolonged viral shedding in RSV LRTI and are reported to have increased morbidity and mortality associated with RSV infection. Although not indicated in most guideline statements, palivizumab prophylaxis for these uncommon underlying conditions is under consideration by clinicians. Prospective studies are needed to determine the burden of RSV disease in these children.