Systematic review of fever, febrile convulsions and serious adverse events following administration of inactivated trivalent influenza vaccines in children.

In 2010, increased febrile convulsions (FC) occurred after administration of inactivated trivalent influenza vaccine (TIV) in Australia. We systematically reviewed the rates of fever, FC and serious adverse events (SAEs) after TIV, focussing on published and unpublished clinical trial data from 2005 to 2012, and performed meta-analysis of fever rates. From 4,372 records in electronic databases, 18 randomised controlled trials (RCTs), 14 non-randomised clinical trials, six observational studies and 12 registered trials (five RCTs and seven non-randomised) were identified. In published RCTs, fever ≥ 38 °C rates after first dose of non-adjuvanted TIV were 6.7% and 6.9% for children aged 6­35 months and ≥ 3 years, respectively. Analysis of RCTs by vaccine manufacturer showed pooled fever estimates up to 5.1% with Sanofi or GlaxoSmithKline vaccines; bioCSL vaccines were used in two non-randomised clinical trials and one unpublished RCT and were associated with fever in 22.5­37.1% for children aged 6­35 months. In RCTs, FCs occurred at a rate of 1.1 per 1,000 vaccinated children. While most TIVs induced acceptably low fever rates, bioCSL influenza vaccines were associated with much higher rates of fever in young children. Future standardised study methodology and access to individual level data would be illuminating.

Immunologic methods and correlates of protection.

Studies of natural rotavirus (RV) infection in children have shown that protection against subsequent RV disease occurs (1). Assessment of humoral immune responses has included study of the importance of circulating vs intestinal antibodies (Abs), serotype-specific vs group-specific Abs, and RV-specific immunoglobulins IgA, IgM, and IgG (1). Following natural RV infection, RV-specific IgM, followed by IgA and IgG, appear in serum and duodenal fluid or stool of young children (2). Protection against subsequent RV infection is predicted by the quantity of virus-specific IgA in the feces and serum (3, 4). In addition, virus-specific antibody-secreting cells (ASC) of the IgA, IgM, and IgG isotypes have been detected in the blood of infants following RV infection (5), although correlation between the presence of ASCs and protection against subsequent disease has not been studied. Serum neutralizing antibodies (nAbs) occur after natural RV infection in children, and are serotype-specific (4,6). Overall, protection against subsequent RV infection is correlated with higher titers of nAb (4). Protection against infection has been correlated with homotypic nAb to the G1 serotype (4); however, other studies suggest that protection is not dependent on serotype-specific nAb (7).

Sources of pertussis infection in young infants: a review of key evidence informing targeting of the cocoon strategy.

BACKGROUND: The relative contribution of different categories of contact in transmitting pertussis to very young infants, who experience the most severe morbidity, is the most important single factor determining the likely benefit of pertussis vaccination of their close contacts (the "cocooning" strategy). OBJECTIVE: To identify, evaluate the quality of and summarise existing data on potential sources of infant pertussis infection in high income countries, focussing on infants under 6 months old. DATA SOURCES: Online databases MEDLINE and EMBASE. Additional studies were identified from the reference lists of relevant articles. Study selection and analysis: Study quality was evaluated by standardised criteria, based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement. Pooled estimates of the proportion of pertussis cases attributable to various contact sources were calculated using data from the highest quality studies. RESULTS: Nine studies met the inclusion criteria; seven included data on contacts of hospitalised infants less than 6 months old. Case definitions and methods of contact ascertainment were variable. Most identified sources were from the household, of which 39% (95%CI 33-45%) were mothers, 16% (95%CI 12-21%) fathers, and 5% (95%CI 2-10%) grandparents. Estimates for siblings (16-43%) and non-household contacts (4-22%) were more heterogeneous. For 32-52% of infant cases, no source was identified. Asymptomatic pertussis infection was found in 8-13% of contacts evaluated. CONCLUSIONS: These data suggest that the greatest potential impact of pertussis vaccination of adults to prevent severe disease in young infants comes from vaccinating mothers, followed by fathers, with grandparents having a minor role. Siblings varied in importance and, given recent data regarding waning immunity in vaccinated children, need further study. Non-household sources are also well documented, highlighting the potential limitations of the cocoon strategy to prevent severe infant disease.

Varicella vaccination in Australia.

Varicella zoster virus (VZV) causes both chickenpox and herpes zoster and is responsible for a significant disease burden, including hospitalizations and deaths, in Australian children and adults. Varicella vaccine has been available in Australia for 5 years; however, from November 2005, it will be funded for use in all susceptible children at 18 months and 10-13 years of age under the National Immunisation Program. Experience with universal varicella vaccination of children in the USA over the last 10 years has shown that the vaccine is safe and highly effective in reducing varicella-related disease. This review summarizes the epidemiology of VZV-related disease in Australia, the use of varicella vaccine and the international experience with vaccine efficacy and safety. The potential impact of varicella vaccination on the incidence of herpes zoster is also discussed.

Specific attachment of aqueous-based microcapsules to macrophages, B cells, and dendritic cells in vitro.

Microcapsules were previously prepared composed of aqueous anionic polymers (e.g. alginate) and aqueous amines (e.g. spermine) and it was found that the aqueous-based microcapsules enhanced rotavirus-specific immune responses after oral or parenteral immunization of mice. In these studies, one has modified the amine moiety of aqueous-based microcapsules to bind covalently to avidin and the avidin-bearing microcapsules were linked to biotinylated antibodies specific for surface markers on murine macrophages, dendritic cells, or B cells. Using fluorescence flow cytometry, it was found that antibody-coated microcapsules bound specifically to antigen-presenting cells (APC) in vitro. The availability of APC-specific microcapsules should allow for the uptake of antigens by specific APC, and further one's understanding of the relative capacities of different APC to induce antigen-specific immune responses.

Nosocomial respiratory syncytial virus infections: the cost-effectiveness and cost-benefit of infection control.

OBJECTIVE: To determine the cost-effectiveness and cost-benefit of an infection control program to reduce nosocomial respiratory syncytial virus (RSV) transmission in a large pediatric hospital. DESIGN: RSV nosocomial infection (NI) was studied for 8 years, before and after intervention with a targeted infection control program. The cost-effectiveness of the intervention was calculated, and cost-benefit was estimated by a case-control comparison. SETTING: Children's Hospital of Philadelphia, a 304-bed pediatric hospital. PATIENTS: All inpatients with RSV infection, both community- and hospital-acquired. INTERVENTION: Consisted of early recognition of patients with respiratory symptoms, confirmation of RSV infection by laboratory testing, establishing cohorts of patients and nursing staff, gown and glove barrier precautions, and monitoring and education of staff. OUTCOME MEASURES: The incidence density of RSV NI before and after the intervention was calculated as the rate per 1000 patient days-at-risk for infection. Intervention costs included laboratory testing, isolation, and administration of the program. The cost of RSV NI was estimated by comparing hospital charges for 30 cases and matched uninfected controls. RESULTS: A total of 148 patients acquired NI (88 before and 60 after the intervention). The Mantel-Haenszel stratified relative risk for NI in the period before the infection control program, compared with the postintervention period, was.61 (95% confidence interval:.53-.69). By applying the preintervention stratum-specific rates of infection to the days-at-risk in the postintervention period, an estimated 100 NIs would have been expected, which in comparison to the 60 NIs observed, yielded an estimated program effectiveness of 10 RSV NIs prevented per season. The total cost of the program per season was $15 627 or $1,563/NI prevented. In comparison, the mean cost to the hospital was $9,419/case of RSV NI, resulting in a cost-benefit ratio of 1:6. CONCLUSIONS: A targeted infection control intervention was cost-effective in reducing the rate of RSV NI. For every dollar spent on the program, approximately $6 was saved.

Primary murine small intestinal epithelial cells, maintained in long-term culture, are susceptible to rotavirus infection.

We describe a method for long-term culture of primary small intestinal epithelial cells (IEC) from suckling mice. IEC were digested from intestinal fragments as small intact units of epithelium (organoids) by using collagenase and dispase. IEC proliferated from organoids on a basement-membrane-coated culture surface and remained viable for 3 weeks. Cultured IEC had the morphologic and functional characteristics of immature enterocytes, notably sustained expression of cytokeratin and alkaline phosphatase. Few mesenchymal cells were present in the IEC cultures. IEC were also cultured from adult BALB/c mice and expressed major histocompatibility complex (MHC) class II antigens for at least 48 h in vitro. Primary IEC supported the growth of rhesus rotavirus (RRV) to a greater extent than a murine small intestinal cell line, m-IC(cl2). Cell-culture-adapted murine rotavirus strain EDIM infected primary IEC and m-IC(cl2) cells to a lesser extent than RRV. Wild-type EDIM did not infect either cell type. Long-term culture of primary murine small intestinal epithelial cells provides a method to study (i) virus-cell interactions, (ii) the capacity of IEC to act as antigen-presenting cells using a wide variety of MHC haplotypes, and (iii) IEC biology.

Lyme disease and seventh nerve paralysis in children.

PURPOSE: This study was undertaken to determine the frequency of Lyme disease (LD) as a cause of transient facial nerve palsy (FNP) in children. Acute onset FNP in children has been primarily associated with acute otitis media (AOM). Recently, LD has emerged in regions where the deer-tick vector is present and has been associated with multiple cranial neuropathies. PATIENTS AND METHODS: Fifty children with transient FNP were evaluated and treated at our institution over a 5.5-year period. RESULTS: The rank of etiologies confirmed LD to now be the most common (50%), followed by AOM (12%), varicella (6%), Herpes zoster (4%), and coxsackievirus (2%). Thirteen children (26%) had idiopathic FNP consistent with Bell's palsy. CONCLUSION: We conclude that transient FNP in children is most commonly caused by LD for regions with endemic infections caused by Borrelia burgdorferi.