Respiratory Syncytial Virus-Associated Neurologic Complications in Children: A Systematic Review and Aggregated Case Series.

OBJECTIVES: To describe the features and frequency of respiratory syncytial virus (RSV)-associated severe acute neurologic disease in children. STUDY DESIGN: We performed a systematic review of the literature to identify reports of severe acute neurologic complications associated with acute RSV infection in children aged <15 years (PROSPERO Registration CRD42019125722). Main outcomes included neurologic, clinical, and demographic features of cases and the frequency of disease. We aggregated available case data from the published literature and from the Australian Acute Childhood Encephalitis (ACE) study. RESULTS: We identified 87 unique studies from 26 countries describing a spectrum of RSV-associated severe acute neurologic syndromes including proven encephalitis, acute encephalopathy, complex seizures, hyponatremic seizures, and immune-mediated disorders. The frequency of RSV infection in acute childhood encephalitis/encephalopathy was 1.2%-6.5%. We aggregated data from 155 individual cases with RSV-associated severe acute neurologic complications; median age was 11.0 months (IQR 2.0-21.5), most were previously healthy (71/104, 68%). Seizure was the most frequently reported neurologic feature (127/150, 85%). RSV was detected in the central nervous system of 12 cases. Most children recovered (81/122, 66%); however, some reports described partial recovery (33/122, 27%) and death (8/122, 7%). CONCLUSIONS: RSV-associated neurologic complications have been widely reported, but there is substantial heterogeneity in the design and quality of existing studies. The findings from our study have implications for the investigation, management, and prevention of RSV-associated neurologic complications. Further, this systematic review can inform the design of future studies aiming to quantify the burden of childhood RSV-associated neurologic disease.

The immunogenicity and safety of respiratory syncytial virus vaccines in development: A systematic review.

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccine candidates in development, but a systematic review on immunogenicity and safety of vaccine is lacking. METHODS: This systematic review of RSV vaccine clinical trials was undertaken using four databases. Searches were conducted using both controlled vocabulary terms such as "Respiratory Syncytial Virus, Human," "Respiratory Syncytial Virus Infections," "Respiratory Syncytial Virus Vaccines," "Immunization," "Immunization Programs" and "Vaccines" and corresponding text word terms. The included studies were limited to clinical trials published from January 2000 to 31 December 2020. RSV infection case was defined as RSV-associated medically attended acute respiratory illness (MAARI) or RSV infection by serologically confirmed test (Western blot) during the RSV surveillance period. We calculated the relative risk of each vaccine trial with RSV infection case. RESULTS: Of 6306 publications, 38 were included and data were extracted covering four major types of RSV vaccine candidates, these being live-attenuated/chimeric (n = 14), recombinant-vector (n = 6), subunit (n = 12) and nanoparticle vaccines (n = 6). For RSV infection cases, nine trials were involved and none of them showed a vaccine-related increased MAARI during RSV surveillance season. CONCLUSION: LID ∆M2-2, MEDI M2-2, RSVcps2 and LID/∆M2-2 /1030s (live-attenuated) were considered the most promising vaccine candidates in infant and children. In the elderly, a nanoparticle F vaccine candidate and Ad26.RSV.preF were considered as two potential effective vaccines. A promising maternal vaccine candidate is still lacking.

Australian caregivers' perceptions of influenza vaccination in pregnancy: A mixed methods exploration.

BACKGROUND: Pregnant women and their unborn children are at high risk from both pandemic and seasonal influenza. AIM: To explore views about influenza vaccination during pregnancy, in a pandemic and immediate post-pandemic context, among mothers and other carers of young children. METHODS: In a mixed methods study, caregivers from 16 childcare centres in Sydney, Australia, were surveyed in November and December 2009, and interviews were conducted with caregivers from six childcare centres between June 2009 and May 2011. FINDINGS: Emerging themes from 41 interviews conducted with mothers included: 'pregnancy as a protected state', 'risk negotiation' and 'centrality of healthcare worker interaction'. Of 972 surveys distributed, 431 were completed (a response rate of 44%). Respondents perceived pandemic influenza risks to be greater for pregnant women than for their unborn children. Only 2% (9/383) of women reported being vaccinated against swine flu during pregnancy and 45% (168/383) indicated intent to receive swine flu vaccination in a future pregnancy. DISCUSSION: The low rates of maternal influenza vaccination revealed in this study contrast to recent gains in vaccine uptake. Vaccination decision-making in pregnancy can be complex and contextually driven for some women. Healthcare workers, including midwives, have a key role in addressing women's concerns about maternal influenza vaccination in both pandemic and interpandemic periods. CONCLUSIONS: Policy makers need to be cognisant of women's concerns and develop resources for both pregnant women and healthcare workers as part of both future pandemic planning and seasonal vaccination efforts.

Much ado about flu: A mixed methods study of parental perceptions, trust and information seeking in a pandemic.

BACKGROUND: Effective public health messaging is essential in both the planning phase and duration of a pandemic. OBJECTIVES: This study aimed to gain an understanding of parental information seeking, trusted sources and needs in relation to pandemic influenza A 2009 (pH1N1) to inform future policy planning and resource development. PATIENTS/METHODS: We conducted a mixed methods study; parents from 16 childcare centres in Sydney, Australia, were surveyed between 16 November and 9 December 2009, and interviews were conducted with participants from six childcare centres between June 2009 and May 2011. RESULTS: From 972 surveys distributed, 431 were completed; a response rate of 44%. Most parents (90%) reported that doctors were "trusted a lot" as a source of influenza information, followed by nurses (59%), government (56%) and childcare centres (52%). Less trusted sources included media (7% selected "trusted a lot"), antivaccination groups (6%) and celebrities (1%). Parents identified a range of key search terms for influenza infection and vaccine. From 42 in-depth interviews, key themes were as follows: "Action trigger," "In an emergency, think Emergency," "Fright to hype" and "Dr Google and beyond." Parents relied heavily on media messages, but cynicism emerged when the pandemic was milder than expected. Parents viewed a range of information sources as trustworthy, including doctors, authoritative hospital or government websites, and childcare centres and schools. CONCLUSIONS: A user-centred orientation is vital for pandemic communications including tailored information provision, via trusted sources based on what parents want to know and how they can find it.