Respiratory syncytial virus (RSV) is a major worldwide cause of morbidity and mortality in children under five years of age. Evidence-based management guidelines suggest that there is no effective ...treatment for RSV lower respiratory tract infection (LRTI) and that supportive care, ie, hydration and oxygenation, remains the cornerstone of clinical management. However, RSV treatments in development in the past decade include 10 vaccines and 11 therapeutic agents in active clinical trials. Maternal vaccination is particularly relevant because the most severe disease occurs within the first 6 months of life, when children are unlikely to benefit from active immunisation. We must optimise the implementation of novel RSV therapeutics by understanding the target populations, showing safety, and striving for acceptable pricing in the context of this worldwide health problem. In this Review, we outline the limitations of RSV LRTI management, the drugs in development, and the remaining challenges related to study design, regulatory approval, and implementation.
Respiratory syncytial virus (RSV) is the main viral cause of hospitalization in infants and young children worldwide. More than 3 million severe cases and close to 100 000 pediatric deaths every ...year, half of them at home, demand effective interventions to mitigate disease burden. Addressing this challenge is not easy, however, in part because more than 90% of severe cases and 99% of fatalities due to RSV occur in the developing world. In fact, severe cases in industrialized countries almost exclusively affect high-risk groups that represent only a subset of those burdened by serious illness in developing nations. Congenital heart disease, neuromuscular disorders, chronic lung illness, and/or Down syndrome are almost ubiquitous in fatal cases in industrialized countries. On the other hand, secondary bacterial infections and pneumothoraces, in addition to the aforementioned comorbid conditions, seem to be critical contributors to poor outcomes in developing country hospitals.
In 1967, infants and toddlers immunized with a formalin-inactivated vaccine against respiratory syncytial virus (RSV) experienced an enhanced form of RSV disease characterized by high fever, ...bronchopneumonia, and wheezing when they became infected with wild-type virus in the community. Hospitalizations were frequent, and two immunized toddlers died upon infection with wild-type RSV. The enhanced disease was initially characterized as a "peribronchiolar monocytic infiltration with some excess in eosinophils." Decades of research defined enhanced RSV disease (ERD) as the result of immunization with antigens not processed in the cytoplasm, resulting in a nonprotective antibody response and CD4(+) T helper priming in the absence of cytotoxic T lymphocytes. This response to vaccination led to a pathogenic Th2 memory response with eosinophil and immune complex deposition in the lungs after RSV infection. In recent years, the field of RSV experienced significant changes. Numerous vaccine candidates with novel designs and formulations are approaching clinical trials, defying our previous understanding of favorable parameters for ERD. This review provides a succinct analysis of these parameters and explores criteria for assessing the risk of ERD in new vaccine candidates.
Abstract Recognition of the acute and chronic burden of respiratory syncytial virus (RSV) lower respiratory tract infections (LRTI) sparked a wave of initiatives to develop preventive and therapeutic ...products against the pathogen in recent years. RSV is a leading cause of hospitalization in infants in industrialized and developing countries, has been causally linked to recurrent wheezing during childhood, associated with pediatric asthma, and is an important cause of mortality in the first months of life in the developing world. Significant changes in the epidemiology, clinical manifestations, and severe consequences of LRTI may emerge in the next decade with the advent of novel preventive strategies against RSV. This manuscript outlines some of these changes and discusses potential scenarios based on the current literature and experiences with other pathogens.
The landscape of infant bronchiolitis and viral pneumonia may be altered by preventive interventions against respiratory syncytial virus under evaluation today. Pediatric wards in 2018 in developing ...countries may differ from those attended by future generation pediatricians who may not witness the packed emergency rooms, lack of available beds, or emergency situations that all physicians caring for children with RSV experience every year. In this review, we describe and discuss different prevention strategies under evaluation to protect pediatric patients. Then, we outline a number of potential challenges, benefits, and concerns that may result from successful interventions after licensure.
This is a Brighton Collaboration Case Definition of the term “Vaccine Associated Enhanced Disease” to be utilized in the evaluation of adverse events following immunization. The Case Definition was ...developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2 vaccines and other emerging pathogens. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected Expert Reviewers prior to submission.
A vaccine containing an RNA molecule encoding the SARS-CoV-2 spike protein was tested in a trial in which two injections were given 3 weeks apart. After the second injection, Covid-19 developed in ...162 patients receiving placebo, with a median follow-up of 2 months, and in 8 patients receiving the vaccine. Side effects were mainly mild-to-moderate injection-site pain and swelling.
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