STRATEGIES FOR PREVENTION AND TREATMENT OF HEPATITIS C VIRUS INFECTION

Hepatitis C virus (HCV) is the causative agent of Hepatitis C, a serious global health problem which results in liver cirrhosis and hepatocellular carcinoma. Currently there is no effective treatment or vaccine against the virus. Therefore, development of a therapeutic vaccine is of paramount importance. In this project, three alternative approaches were used to control HCV including a DNA vaccine, a recombinant viral vaccine and RNA interference. The first approach was to test the effect of different promoters on the efficacy of a DNA vaccine against HCV. Plasmids encoding HCV-NS3 and E1 antigens were designed under three different promoters, adenoviral E1A, MLP, and CMV ie. The promoter effect on the antigen expression in 293 cells, as well as on the antibody level in immunized BALB/c mice, was evaluated. The results showed that the antigens were successfully expressed from all vectors. The CMV ie promoter induced the highest antigen expression and the highest antibody level. Second, the efficiency of a recombinant adenovirus vaccine encoding HCV-NS3 was compared to that of a HCV-NS3 plasmid vaccine. The results showed that the recombinant adenovirus vaccine induced higher antibody levels as compared to the plasmid vaccine. The relationship between the immune response and miRNA was also evaluated. The levels of mir-181, mir-155, mir-21 and mir-296 were quantified in the sera of immunized animals. mir-181 and mir-21 were found to be upregulated in animals injected with adenoviral vectors. Third, two recombinant adenoviruses encoding siRNAs targeting both the helicase and protease parts of the NS3 region were tested for their ability to inhibit NS3 expression. The results showed that the siRNA against protease was more effective in silencing the HCV-NS3 gene in a HCV replicon cell line. This result confirmed the efficiency of adenovirus for siRNA delivery. These results confirmed that CMV ie is optimum promoter for immune response induction. Adenovirus was shown to be an effective delivery vector for antigens or siRNAs. In addition, miRNAs were proved to be involved in the regulation of immune response.

A research capacity strengthening project for infectious diseases in Honduras: experience and lessons learned

Background: In Honduras, research capacity strengthening (RCS) has not received sufficient attention, but an increase in research competencies would enable local scientists to advance knowledge and contribute to national priorities, including the Millennium Development Goals (MDGs). Objective: This project aimed at strengthening research capacity in infectious diseases in Honduras, focusing on the School of Microbiology of the National Autonomous University of Honduras (UNAH). The primary objective was the creation of a research-based graduate program for the continued training of researchers. Parallel objectives included institutional strengthening and the facilitation of partnerships and networks. Methods: Based on a multi-stakeholder consultation, an RCS workplan was designed and undertaken from 2007 to 2012. Due to unexpected adverse circumstances, the first 2 years were heavily dedicated to implementing the project's flagship, an MSc program in infectious and zoonotic diseases (MEIZ). In addition, infrastructure improvements and demand-driven continuing education opportunities were facilitated; biosafety and research ethics knowledge and practices were enhanced, and networks fostering collaborative work were created or expanded. Results: The project coincided with the peak of UNAH's radical administrative reform and an unprecedented constitutional crisis. Challenges notwithstanding, in September 2009, MEIZ admitted the first cohort of students, all of whom undertook MDG-related projects graduating successfully by 2012. Importantly, MEIZ has been helpful in expanding the School of Microbiology's traditional etiology-based, disciplinary model to infectious disease teaching and research. By fulfilling its objectives, the project contributed to a stronger research culture upholding safety and ethical values at the university. Conclusions: The resources and strategic vision afforded by the project enhanced UNAH's overall research capacity and its potential contribution to the MDGs. Furthermore, increased research activity and the ensuing improvement in performance indicators at the prime Honduran research institution invoke the need for a national research system in Honduras.

Sustaining Health Care Practice Change: The Experience of Best Practice Spotlight Organizations Implementing and Sustaining RNAO Best Practice Guidelines

Sustainability of change for improvement initiatives has been widely reported as a global challenge both within and outside health care settings. The purpose of this study was to examine the extent to which factors related to staff training and involvement, staff behaviour, and clinical leaders’ and senior leaders’ engagement and support impact the long term sustainability of practice changes for BPSO health care organizations who have implemented Registered Nursing Association of Ontario’s (RNAO) Best Practice Guidelines. Semi structured interviews with eleven organizational leaders’ from ten health care organizations were conducted to explore the unique experiences, views and perspectives on factors related to staff, clinical leaders and senior leaders and their involvement and impact on the long term sustainability of clinical practice changes within organizations who had implemented Registered Nursing Association of Ontario’s (RNAO) Best Practice Guidelines (BPGs). The interviews were coded and analyzed using thematic content analysis. Further analysis identified patterns and themes in relation to: 1. The National Health Service (NHS) Sustainability Model which was used as the theoretical framework for this research; and 2. Organizations found to have sustained practice changes longer term verses organizations that did not. Six organizations were found to have sustained practice changes while the remaining four were found to have been unsuccessful in their efforts to sustain the changes. Five major findings in relation to sustainability emerged from this study. First is the importance of early and sustained engagement and frontline staff, managers, and clinical leaders in planning, implementation and ongoing development of BPGs through use of working groups and champions models. Second is the importance of ongoing provision of formal training, tools and resources to all key stakeholders during and after the implementation phase and efforts made to embed changes in current processes whenever possible to ensure sustainability. Third is to ensure staff and management are receptive to the proposed change(s) and/or have been given the necessary background information and rationale so they understand and can support the need for the change. Fourth is the need for early and sustained fiscal and human resources dedicated to supporting BPG implementation and the ongoing use of the BPGs already in place. Fifth is ensuring clinical leaders are trusted, influential, respected and seen as clinical resources by frontline staff. The significance of this study lies in a greater understanding of the influence and impact of factors related to staff on the long term sustainability of implemented practice changes within health care organizations. This study has implications for clinical practice, policy, education and research in relation to sustainability in health care.