Evasion of the Interferon-Mediated Antiviral Response by Filoviruses

The members of the filoviruses are recognized as some of the most lethal viruses affecting human and non-human primates. The only two genera of the Filoviridae family, Marburg virus (MARV) and Ebola virus (EBOV), comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central Africa, with case fatality rates ranging from 25 to 90%. Fatal outcomes have been associated with a late and dysregulated immune response to infection, very likely due to the virus targeting key host immune cells, such as macrophages and dendritic cells (DCs) that are necessary to mediate effective innate and adaptive immune responses. Despite major progress in the development of vaccine candidates for filovirus infections, a licensed vaccine or therapy for human use is still not available. During the last ten years, important progress has been made in understanding the molecular mechanisms of filovirus pathogenesis. Several lines of evidence implicate the impairment of the host interferon (IFN) antiviral innate immune response by MARV or EBOV as an important determinant of virulence. In vitro and in vivo experimental infections with recombinant Zaire Ebola virus (ZEBOV), the best characterized filovirus, demonstrated that the viral protein VP35 plays a key role in inhibiting the production of IFN-α/β. Further, the action of VP35 is synergized by the inhibition of cellular responses to IFN-α/β by the minor matrix viral protein VP24. The dual action of these viral proteins may contribute to an efficient initial virus replication and dissemination in the host. Noticeably, the analogous function of these viral proteins in MARV has not been reported. Because the IFN response is a major component of the innate immune response to virus infection, this chapter reviews recent findings on the molecular mechanisms of IFN-mediated antiviral evasion by filovirus infection

Evaluation of the UK Public Health Skills and Knowledge Framework (PHSKF): Implications for international competency frameworks

Background: The value of competency frameworks for developing the public health workforce is widely acknowledged internationally. However, there is a lack of formal evaluations of such frameworks. In the UK, the Public Health Skills and Knowledge Framework (PHSKF) is a key tool for the public health workforce across the UK, and this study presents the evaluation of the PHSKF 2016 version, with the aim of reflecting on implications for international public health competency frameworks.Methods: A sequential explanatory design was employed. An online survey (n = 298) was completed with stakeholders across the four UK nations and different sectors. This was followed by 18 telephone interviews with stakeholders and survey completers. Quantitative results were analysed descriptively; qualitative transcripts were analysed with thematic analysis.Results: Most respondents had used the PHSKF occasionally or rarely, and most users found it useful (87%) and easy to use (82%). Main purposes of use included team/workforce development (e.g. setting of standards) and professional development (e.g. identify professional development opportunities). Some positive experiences emerged of uses of the PHSKF to support organisational redevelopments. However, 23% of respondents had never used the framework. Areas for improvement included greater clarity on purpose and audience, the need for more support from employers and for clear career progression opportunities, and stronger links with other competency frameworks.Conclusions: The development of a digital version of the PHSKF, together with improving buy-in from the workforce and employers could make an important contribution towards UK public health workforce development. Further evaluation and shared learning internationally of the implementation of public health competency frameworks would support global public health workforce development

Children from Baffin Island have a disproportionate burden of tuberculosis in Canada: data from the Children's Hospital of Eastern Ontario (1998-2008)

<p>Abstract</p> <p>Background</p> <p>The Children's Hospital of Eastern Ontario (CHEO) provides services to children in Baffin Island, through the Baffin Island Pediatric Health Initiative. Tuberculosis (TB) remains a major public health problem in that region. The objective of our study was to describe the origin and clinical characteristics of patients with TB disease at CHEO, since the inception of the Baffin Island Pediatric Health Initiative.</p> <p>Methods</p> <p>All charts with a discharge diagnosis of TB disease during the first 10 years of the Baffin Island program were reviewed. Patients meeting a pre-determined case definition were included in analyses. A standard medical record abstraction form was used for patient data collection.</p> <p>Results</p> <p>Twenty patients met our case definition. Seven (35%) were Canadian-born children from Baffin Island. Seven resided in Ontario, 4 in Quebec, and 2 were visiting from other countries. All 7 children residing in Ontario were born in African countries. Endothoracic disease occurred in 16 patients (80%), including 9 with primary pulmonary TB, and 3 with sputum smear positive "adult-type" disease. Extrathoracic disease was present in 6 children (30%), including 3 with CNS disease. Three children had disease in 2 separate sites.</p> <p>Conclusions</p> <p>While Baffin Island makes up 1% of the hospital catchment population, they contributed 35% of TB patients, and the only TB death. While TB in foreign-born children is due in part to epidemics abroad, the problem in Baffin Island is a reflection of disease burden and transmission within Canada.</p

Exploring Public Health's roles and limitations in advancing food security in British Columbia

OBJECTIVES: This research analyzes the roles and limitations of Public Health in British Columbia in advancing food security through the integration of food security initiatives into its policies and programs. It asks the question, can Public Health advance food security? If so, how, and what are its limitations? METHODS: This policy analysis merges findings from 38 key informant interviews conducted with government and civil society stakeholders involved in the development of food security initiatives, along with an examination of relevant documents. The Population Health Template is used to delineate and analyze Public Health roles in food security. RESULTS: Public Health was able to advance food security in some ways, such as the adoption of food security as a core public health program. Public Health's leadership role in food security is constrained by a restricted mandate, limited ability to collaborate across a wide range of sectors and levels, as well as internal conflict within Public Health between Food Security and Food Protection programs. CONCLUSIONS: Public Health has a role in advancing food security, but it also faces limitations. As the limitations are primarily systemic and institutional, recommendations to overcome them are not simple but, rather, require movement toward embracing the determinants of health and regulatory pluralism. The results also suggest that the historic role of Public Health in food security remains salient today

Community capacity to acquire, assess, adapt, and apply research evidence: a survey of Ontario's HIV/AIDS sector

<p>Abstract</p> <p>Background</p> <p>Community-based organizations (CBOs) are important stakeholders in health systems and are increasingly called upon to use research evidence to inform their advocacy, program planning, and service delivery. To better support CBOs to find and use research evidence, we sought to assess the capacity of CBOs in the HIV/AIDS sector to acquire, assess, adapt, and apply research evidence in their work.</p> <p>Methods</p> <p>We invited executive directors of HIV/AIDS CBOs in Ontario, Canada (n = 51) to complete the Canadian Health Services Research Foundation's "Is Research Working for You?" survey.</p> <p>Findings</p> <p>Based on responses from 25 organizations that collectively provide services to approximately 32,000 clients per year with 290 full-time equivalent staff, we found organizational capacity to acquire, assess, adapt, and apply research evidence to be low. CBO strengths include supporting a culture that rewards flexibility and quality improvement, exchanging information within their organization, and ensuring that their decision-making processes have a place for research. However, CBO Executive Directors indicated that they lacked the skills, time, resources, incentives, and links with experts to acquire research, assess its quality and reliability, and summarize it in a user-friendly way.</p> <p>Conclusion</p> <p>Given the limited capacity to find and use research evidence, we recommend a capacity-building strategy for HIV/AIDS CBOs that focuses on providing the tools, resources, and skills needed to more consistently acquire, assess, adapt, and apply research evidence. Such a strategy may be appropriate in other sectors and jurisdictions as well given that CBO Executive Directors in the HIV/AIDS sector in Ontario report low capacity despite being in the enviable position of having stable government infrastructure in place to support them, benefiting from long-standing investment in capacity building, and being part of an active provincial network. CBOs in other sectors and jurisdictions that have fewer supports may have comparable or lower capacity. Future research should examine a larger sample of CBO Executive Directors from a range of sectors and jurisdictions.</p

Assessing positive mental health in people with chronic physical health problems: correlations with socio-demographic variables and physical health status

Background: A holistic perspective on health implies giving careful consideration to the relationship between physical and mental health. In this regard the present study sought to determine the level of Positive Mental Health (PMH) among people with chronic physical health problems, and to examine the relationship between the observed levels of PMH and both physical health status and socio-demographic variables. Methods: The study was based on the Multifactor Model of Positive Mental Health (Lluch, 1999), which comprises six factors: Personal Satisfaction (F1), Prosocial Attitude (F2), Self-control (F3), Autonomy (F4), Problem-solving and Self-actualization (F5), and Interpersonal Relationship Skills (F6). The sample comprised 259 adults with chronic physical health problems who were recruited through a primary care center in the province of Barcelona (Spain). Positive mental health was assessed by means of the Positive Mental Health Questionnaire (Lluch, 1999). Results: Levels of PMH differed, either on the global scale or on specific factors, in relation to the following variables: age: global PMH scores decreased with age (r=-0.129; p=0.038); b) gender: men scored higher on F1 (t=2.203; p=0.028) and F4 (t=3.182; p=0.002), while women scored higher on F2 (t -3.086; p=0.002) and F6 (t=-2.744; p=0.007); c) number of health conditions: the fewer the number of health problems the higher the PMH score on F5 (r=-0.146; p=0.019); d) daily medication: polymedication patients had lower PMH scores, both globally and on various factors; e) use of analgesics: occasional use of painkillers was associated with higher PMH scores on F1 (t=-2.811; p=0.006). There were no significant differences in global PMH scores according to the type of chronic health condition. The only significant difference in the analysis by factors was that patients with hypertension obtained lower PMH scores on the factor Autonomy (t=2.165; p=0.032). Conclusions: Most people with chronic physical health problems have medium or high levels of PMH. The variables that adversely affect PMH are old age, polypharmacy and frequent consumption of analgesics. The type of health problem does not influence the levels of PMH. Much more extensive studies with samples without chronic pathology are now required in order to be able to draw more robust conclusions

Referrals for positive tuberculin tests in new health care workers and students: a retrospective cohort study

<p>Abstract</p> <p>Background</p> <p>Documentation of test results for latent tuberculosis (TB) infection is important for health care workers and students before they begin work. A negative result provides a baseline for comparison with future tests. A positive result affords a potential opportunity for treatment of latent infection when appropriate. We sought to evaluate the yield of the referral process for positive baseline tuberculin tests, among persons beginning health care work or studies.</p> <p>Methods</p> <p>Retrospective cohort study. We reviewed the charts of all new health care students and workers referred to the Montreal Chest Institute in 2006 for positive baseline tuberculin skin tests (≥10 mm). Health care workers and students evaluated for reasons other than positive baseline test results were excluded.</p> <p>Results</p> <p>630 health care students and workers were evaluated. 546 (87%) were foreign-born, and 443 (70%) reported previous Bacille Calmette-Guérin (BCG) vaccination. 420 (67%) were discharged after their first evaluation without further treatment. 210 (33%) were recommended treatment for latent TB infection, of whom 165 (79%) began it; of these, 115 (70%) completed adequate treatment with isoniazid or rifampin. Treatment discontinuation or interruption occurred in a third of treated subjects, and most often reflected loss to follow-up, or abdominal discomfort. No worker or student had active TB.</p> <p>Conclusions</p> <p>Only a small proportion of health care workers and students with positive baseline tuberculin tests were eligible for, and completed treatment for latent TB infection. We discuss recommendations for improving the referral process, so as to better target workers and students who require specialist evaluation and treatment for latent TB infection. Treatment adherence also needs improvement.</p

The persisting burden of invasive pneumococcal disease in HIV patients: an observational cohort study

<p>Abstract</p> <p>Background</p> <p>The increasing use of highly active antiretroviral therapy (HAART) and pneumococcal immunization along with shifting community exposures may have altered the burden of <it>Streptococcus pneumoniae </it>disease in HIV-infected persons. We describe the burden and risk factors for pneumococcal disease in the modern era of HIV care and evaluate the use of a 23-valent pneumococcal polysaccharide vaccine (PPV-23).</p> <p>Methods</p> <p>The incidence of invasive pneumococcal disease (IPD) between January 1^st, 2000 and January 1^st, 2010 in a regional HIV population in Southern Alberta, Canada was determined by linking comprehensive laboratory and hospital surveillance data. Clinical and epidemiologic data including risk factors for <it>S. pneumoniae</it>, history of pneumococcal immunization, serotypes of infections, and length of any hospitalizations for pneumococcal disease were evaluated with multivariate analysis. CD4 count and viral load at immunization were evaluated with a nested case-control analysis.</p> <p>Results</p> <p>In 1946 HIV-patients with 11,099 person-years of follow up, there were 68 distinct episodes of pneumococcal disease occurring in 50 patients. Increased risk was seen if female, age >60, Aboriginal ethnicity, lower education, injection drug use, smoking, nadir CD4 <200/μL, chronic obstructive pulmonary disease, and hepatitis C. Overall, the incidence of IPD was 342/100,000 person-years and was reduced to 187/100,000 within three years of PPV-23 immunization (P < 0.01). Although 78% of patients received PPV-23, 74% of IPD episodes were caused by PPV-23 serotypes. In a case-control analysis, HIV viral load at immunization was significantly predictive of PPV-23 failure, while CD4 count was not. 80% of IPD cases required hospitalization: median length of stay was 7 days (range: 1-71); four patients died.</p> <p>Conclusions</p> <p>Despite universal access to intensive measures to prevent pneumococcal disease including the widespread use of HAART and PPV-23 immunization, the incidence of IPD remains high in HIV patients with its associated morbidity and mortality.</p