Microbiota Predict Infections and Acute Graft-Versus-Host Disease After Pediatric Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Despite preventive measures, infections continue to pose significant risks to pediatric allogeneic hematopoietic cell transplantation (allo-HCT) recipients. The gut microbiota has been linked to clinical outcomes following adult allo-HCT. This study evaluated whether similar disruptions or differing microbiota patterns were associated with infection risk in pediatric allo-HCT. METHODS: In a prospective observational study, fecal samples were obtained from 74 children before conditioning and upon neutrophil recovery. Microbiome signatures identified through sequencing were examined for their associations with infections or acute graft-versus-host disease (aGVHD) in the first-year post-HCT using Cox proportional hazards analysis. RESULTS: Microbiome disruption in adults, did not predict infection risk in pediatric allo-HCT. Unique microbiota signatures were associated with different infections or aGVHD. A ratio of strict and facultative anaerobes (eg, Lachnoclostridium, Parabacteroides) prior to conditioning predicted bacteremia risk (Cox hazard ratio [HR], 3.89). A distinct ratio of oral (eg, Rothia, Veillonella) to intestinal anaerobes (eg, Anaerobutyricum, Romboutsia) at neutrophil recovery predicted likelihood of bacterial infections (Cox HR, 1.81) and viral enterocolitis (Cox HR, 1.96). CONCLUSIONS: Interactions between medical interventions, pediatric hosts, and microbial communities contribute to microbiota signatures that predict infections. Further multicenter study is necessary to validate the generalizability of these ratios as biomarkers.

Human Astroviruses: A Tale of Two Strains.

Since the 1970s, eight closely related serotypes of classical human astroviruses (HAstV) have been associated with gastrointestinal illness worldwide. In the late 2000s, three genetically unique human astrovirus clades, VA1-VA3, VA2-VA4, and MLB, were described. While the exact disease associated with these clades remains to be defined, VA1 has been associated with central nervous system infections. The discovery that VA1 could be grown in cell culture, supports exciting new studies aimed at understanding viral pathogenesis. Given the association of VA1 with often lethal CNS infections, we tested its susceptibility to the antimicrobial drug, nitazoxanide (NTZ), which we showed could inhibit classical HAstV infections. Our studies demonstrate that NTZ inhibited VA1 replication in Caco2 cells even when added at 12 h post-infection, which is later than in HAstV-1 infection. These data led us to further probe VA1 replication kinetics and cellular responses to infection in Caco-2 cells in comparison to the well-studied HAstV-1 strain. Overall, our studies highlight that VA1 replicates more slowly than HAstV-1 and elicits significantly different cellular responses, including the inability to disrupt cellular junctions and barrier permeability.

How rural and urban parents describe convenience in the context of school-based influenza vaccination: a qualitative study.

BACKGROUND: Seasonal influenza vaccine uptake among school-age children has been low, particularly among rural children, even in jurisdictions in Canada where this immunization is publicly funded. Providing this vaccination at school may be convenient for parents and might contribute to increased vaccine uptake, particularly among rural children. We explore the construct of convenience as an advantage of school based influenza vaccination. We also explore for rural urban differences in this construct. METHODS: Participants were parents of school-aged children from Alberta, Canada. We qualitatively analyzed focus group data from rural parents using a thematic template that emerged from prior work with urban parents. Both groups of parents had participated in focus groups to explore their perspectives on the acceptability of adding an annual influenza immunization to the immunization program that is currently delivered in Alberta schools. Data from within the theme of 'convenience' from both rural and urban parents were then further explored for sub-themes within convenience. RESULTS: Data were obtained from nine rural and nine urban focus groups. The template of themes that had arisen from prior analysis of the urban data applied to the rural data. Convenience was a third level theme under Advantages. Five fourth level themes emerged from within convenience. Four of the five sub-themes were common to both rural and urban participants: reduction of parental burden to schedule, reduction in parental lost time, decrease in parental stress and increase in physical access points for influenza immunization. The fifth subtheme, increases temporal access to influenza immunization, emerged uniquely from the rural data. CONCLUSIONS: Both rural and urban parents perceived that convenience would be an advantage of adding an annual influenza immunization to the vaccinations currently given to Alberta children at school. Improving temporal access to such immunization may be a more relevant aspect of convenience to rural than to urban parents.

School-based influenza vaccination: parents' perspectives.

BACKGROUND: School-age children are important drivers of annual influenza epidemics yet influenza vaccination coverage of this population is low despite universal publicly funded influenza vaccination in Alberta, Canada. Immunizing children at school may potentially increase vaccine uptake. As parents are a key stakeholder group for such a program, it is important to consider their concerns. PURPOSE: We explored parents' perspectives on the acceptability of adding an annual influenza immunization to the immunization program that is currently delivered in Alberta schools, and obtained suggestions for structuring such a program. PARTICIPANTS: Forty-eight parents of children aged 5-18 years participated in 9 focus groups. Participants lived in urban areas of the Alberta Health Services Calgary Zone. FINDINGS: Three major themes emerged: Advantages of school-based influenza vaccination (SBIV), Disadvantages of SBIV, and Implications for program design & delivery. Advantages were perceived to occur for different populations: children (e.g. emotional support), families (e.g. convenience), the community (e.g. benefits for school and multicultural communities), the health sector (e.g. reductions in costs due to burden of illness) and to society at large (e.g. indirect conduit of information about health services, building structure for pandemic preparedness, building healthy lifestyles). Disadvantages, however, might also occur for children (e.g. older children less likely to be immunized), families (e.g. communication challenges, perceived loss of parental control over information, choices and decisions) and the education sector (loss of instructional time). Nine second-level themes emerged within the major theme of Implications for program design & delivery: program goals/objectives, consent process, stakeholder consultation, age-appropriate program, education, communication, logistics, immunizing agent, and clinic process. CONCLUSIONS: Parents perceived advantages and disadvantages to delivering annual seasonal influenza immunizations to children at school. Their input gives a framework of issues to address in order to construct robust, acceptable programs for delivering influenza or other vaccines in schools.