Potential immunosuppressive effects of Escherichia coli O157:H7 experimental infection on the bovine host

Background: Enterohaemorrhagic Escherichia coli (EHEC), like E. coli O157:H7 are frequently detected in bovine faecal samples at slaughter. Cattle do not show clinical symptoms upon infection, but for humans the consequences after consuming contaminated beef can be severe. The immune response against EHEC in cattle cannot always clear the infection as persistent colonization and shedding in infected animals over a period of months often occurs. In previous infection trials, we observed a primary immune response after infection which was unable to protect cattle from reinfection. These results may reflect a suppression of certain immune pathways, making cattle more prone to persistent colonization after re-infection. To test this, RNA-Seq was used for transcriptome analysis of recto-anal junction tissue and ileal Peyer's patches in nine Holstein-Friesian calves in response to a primary and secondary Escherichia coli O157: H7 infection with the Shiga toxin (Stx) negative NCTC12900 strain. Non-infected calves served as controls. Results: In tissue of the recto-anal junction, only 15 genes were found to be significantly affected by a first infection compared to 1159 genes in the ileal Peyer's patches. Whereas, re-infection significantly changed the expression of 10 and 17 genes in the recto-anal junction tissue and the Peyer's patches, respectively. A significant downregulation of 69 immunostimulatory genes and a significant upregulation of seven immune suppressing genes was observed. Conclusions: Although the recto-anal junction is a major site of colonization, this area does not seem to be modulated upon infection to the same extent as ileal Peyer's patches as the changes in gene expression were remarkably higher in the ileal Peyer's patches than in the recto-anal junction during a primary but not a secondary infection. We can conclude that the main effect on the transcriptome was immunosuppression by E. coli O157: H7 (Stx(-)) due to an upregulation of immune suppressive effects (7/12 genes) or a downregulation of immunostimulatory effects (69/94 genes) in the ileal Peyer's patches. These data might indicate that a primary infection promotes a re-infection with EHEC by suppressing the immune function

Non-prescription medicines: A process for standards development and testing in community pharmacy

Objective: The objective of the study was to develop and test standards of practice for handling non-prescription medicines. Method: In consultation with pharmacy registering authorities, key professional and consumer groups and selected community pharmacists, standards of practice were developed in the areas of Resource Management; Professional Practice; Pharmacy Design and Environment; and Rights and Needs of Customers. These standards defined and described minimum professional activities required in the provision of non-prescription medicines at a consistent and measurable level of practice. Seven standards were described and further defined by 20 criteria, including practice indicators. The Standards were tested in 40 community pharmacies in two States and after further adaptation, endorsed by all Australian pharmacy registering authorities and major Australian pharmacy and consumer organisations. The consultation process effectively engaged practicing pharmacists in developing standards to enable community pharmacists meet their legislative and professional responsibilities. Main outcome measures: Community pharmacies were audited against a set of standards of practice for handling non-prescription medicines developed in this project. Pharmacies were audited on the Standards at baseline, mid-intervention and post-intervention. Behavior of community pharmacists and their staff in relation to these standards was measured by conducting pseudo-patron visits to participating pharmacies. Results: The testing process demonstrated a significant improvement in the quality of service delivered by staff in community pharmacies in the management of requests involving non-prescription medicines. The use of pseudo-patron visits, as a training tool with immediate feedback, was an acceptable and effective method of achieving changes in practice. Feedback from staff in the pharmacies regarding the pseudo-patron visits was very positive. Conclusion: Results demonstrated the methodology employed was effective in increasing overall compliance with the Standards from a rate of 47.4% to 70.0% (P < 0.01). This project led to a recommendation for the development and execution of a national implementation strategy. © 2007 Springer Science+Business Media, LLC