Understanding Intra-Species and Inter-Species Prion Conversion and Zoonotic Potential Using Protein Misfolding Cyclic Amplification

Prion diseases are fatal neurodegenerative disorders that affect humans and animals, and can also be transmitted from animals to humans. A fundamental event in prion disease pathogenesis is the conversion of normal host prion protein (PrPC) to a disease-associated misfolded form (PrPSc). Whether or not an animal prion disease can infect humans cannot be determined a priori. There is a consensus that classical bovine spongiform encephalopathy (C-type BSE) in cattle transmits to humans, and that classical sheep scrapie is of little or no risk to human health. However, the zoonotic potential of more recently identified animal prion diseases, such as atypical scrapie, H-type and L-type BSE and chronic wasting disease (CWD) in cervids, remains an open question. Important components of the zoonotic barrier are (i) physiological differences between humans and the animal in question, (ii) amino acid sequence differences of the animal and human PrPC, and (iii) the animal prion strain, enciphered in the conformation of PrPSc. Historically, the direct inoculation of experimental animals has provided essential information on the transmissibility and compatibility of prion strains. More recently, cell-free molecular conversion assays have been used to examine the molecular compatibility on prion replication and zoonotic potential. One such assay is Protein Misfolding Cyclic Amplification (PMCA), in which a small amount of infected tissue homogenate, containing PrPSc, is added as a seed to an excess of normal tissue homogenate containing PrPC, and prion conversion is accelerated by cycles of incubation and ultrasonication. PMCA has been used to measure the molecular feasibility of prion transmission in a range of scenarios using genotypically homologous and heterologous combinations of PrPSc seed and PrPC substrate. Furthermore, this method can be used to speculate on the molecular profile of PrPSc that might arise from a zoonotic transmission. We discuss the experimental approaches that have been used to model both the intra- and inter-species molecular compatibility of prions, and the factors affecting PrPc to PrPSc conversion and zoonotic potential. We conclude that cell-free prion protein conversion assays, especially PMCA, are useful, rapid and low-cost approaches for elucidating the mechanisms of prion propagation and assessing the risk of animal prions to humans

Variant CJD: Reflections a Quarter of a Century on

Twenty-five years has now passed since variant Creutzfeldt-Jakob disease (vCJD) was first described in the United Kingdom (UK). Early epidemiological, neuropathological and biochemical investigations suggested that vCJD represented a new zoonotic form of human prion disease resulting from dietary exposure to the bovine spongiform encephalopathy (BSE) agent. This hypothesis has since been confirmed though a large body of experimental evidence, predominantly using animal models of the disease. Today, the clinical, pathological and biochemical phenotype of vCJD is well characterized and demonstrates a unique and remarkably consistent pattern between individual cases when compared to other human prion diseases. While the numbers of vCJD cases remain reassuringly low, with 178 primary vCJD cases reported in the UK and a further 54 reported worldwide, concerns remain over the possible appearance of new vCJD cases in other genetic cohorts and the numbers of asymptomatic individuals in the population harboring vCJD infectivity. This review will provide a historical perspective on vCJD, examining the origins of this acquired prion disease and its association with BSE. We will investigate the epidemiology of the disease along with the unique clinicopathological and biochemical phenotype associated with vCJD cases. Additionally, this review will examine the impact vCJD has had on public health in the UK and the ongoing concerns raised by this rare group of disorders

The State of Accreditation Readiness in Georgia: A Case Study

Background: Georgia’s public health districts first began exploring the idea of national public health accreditation in 2008 when Cobb & Douglas Public Health included accreditation in their strategic plan. In May 2015, Cobb & Douglas Public Health was the first Georgia public health district to achieve national accreditation status. This article discusses the current state of accreditation readiness in Georgia and explores strengths and barriers to accreditation. Methods: This study utilized a case study approach in order to examine PHAB accreditation efforts in Georgia within a real life context. Data came from three sources: nine Accreditation Readiness Assessments, a PHAB Pre-Application Technical Assistance Survey, and state-wide Accreditation Readiness Survey. Results: The Accreditation Readiness Assessments resulted in several lessons learned about common strengths and barriers to accreditation. Strengths included a dedicated staff and supportive Boards of Health. Barriers included accreditation fees and a lack of personnel time. The PHAB Pre-application TA Survey revealed that the majority of those surveyed would recommend TA to other agencies pursuing PHAB accreditation (91%). The Accreditation Readiness Survey revealed that 14 of 18 GA public health districts are either PHAB accredited (1 district), actively pursuing PHAB accreditation (2 districts), or planning to apply (11 districts). This includes 116 of the 159 Georgia counties (73%). Conclusions: The results of this case study show that 72% of Georgia’s public health districts are engaged in accreditationrelated activities. This includes activities such as accreditation readiness assessment, community health assessment, QI council and plan development, strategic planning, and policy review

The State of Accreditation Readiness in Georgia: A Case Study

Background: Georgia’s public health districts first began exploring the idea of national public health accreditation in 2008 when Cobb & Douglas Public Health included accreditation in their strategic plan. In May 2015, Cobb & Douglas Public Health was the first Georgia public health district to achieve national accreditation status. This article discusses the current state of accreditation readiness in Georgia and explores strengths and barriers to accreditation. Methods: This study utilized a case study approach in order to examine PHAB accreditation efforts in Georgia within a reallife context. Data came from three sources: nine Accreditation Readiness Assessments, a PHAB Pre-Application Technical Assistance Survey, and state-wide Accreditation Readiness Survey. Results: The Accreditation Readiness Assessments resulted in several lessons learned about common strengths and barriers to accreditation. Strengths included a dedicated staff and supportive Boards of Health. Barriers included accreditation fees and a lack of personnel time. The PHAB Pre-application TA Survey revealed that the majority of those surveyed would recommend TA to other agencies pursuing PHAB accreditation (91%). The Accreditation Readiness Survey revealed that 14 of 18 GA public health districts are either PHAB accredited (1 district), actively pursuing PHAB accreditation (2 districts), or planning to apply (11 districts). This includes 116 of the 159 Georgia counties (73%). Conclusions: The results of this case study show that 72% of Georgia’s public health districts are engaged in accreditationrelated activities. This includes activities such as accreditation readiness assessment, community health assessment, QI council and plan development, strategic planning, and policy review

Assessing a Quality Improvement Project in a Georgia County Health Department

The study and evaluation of quality improvement among Georgia’s public health systems continues to be a major priority for the Georgia Public Health Practice Based Research Network (GAPH-PBRN). This article focuses on the application and evaluation of a Quality Improvement project in a Georgia County Health Department. The QI team sought to reduce the waiting time in the teen clinic; thereby, increasing the Quality Improvement culture one project at a time in this Health Department. The project revealed that Quality Improvement is a continuous process that requires change and adaptation by employees. This initial Quality Improvement project was the first step in helping to establish Quality Improvement culture in the County Health Department

Health Districts as Quality Improvement Collaboratives and Multi-Jurisdictional Entities

Research Objective: The Georgia Public Health PBRN assessed the utility of the Multi-county Health District as a structured Quality Improvement Collaborative (QIC), and as multi jurisdictional entities for purposes of meeting standards for accreditation by the Public Health Accreditation Board. Data Sets and Sources: Data were collected from online surveys followed up with phone interviews or paper surveys to maximize participation. A newly developed clinical care QIC instrument (Schouten et al, 2010) was modified to collect data with a revised focus on QICs for public health. We retained QI culture constructs in the instrument while shifting the focus from healthcare to public health essential services related to accreditation standards. Study Design: Data was collected from a purposeful sample of local public health key informants in Georgia who were identified by the District Directors’ office as local key informants. Invitations Key informants included county and district staff and county board of health members. Analysis: Psychometric testing of the QIC assessment instrument included tests for validity and reliability. Census-based and self-reported demographic characteristics were used to compare responses. Principal Findings: Strong consensus emerged across various constituencies that Districts were critical for local public health to provide essential services. Key opinion leaders from both the rural and non-rural counties agreed that the Districts were important. Conclusion: Regionalization using Georgia Districts has major potential for supporting QI and meeting quality assurance standards associated with accreditation. Implications for Field of PHSSR: Accreditation has the potential to substantially clarify and enhance the role of public health in the 21st century. But local public health agencies, based on small municipality or county populations, are unlikely to possess and sustain capacity to meet the challenges of comprehensive essential services. Regionalization of local public health capacity is a critical emerging issue with the launching of public health accreditation

Clarifying and Expanding Concepts of Cross-Jurisdictional Sharing: Early Lessons Learned from Conducting QI with Georgia’s Health Districts

Research Objective: Assess the legal and organization cultural foundations for Cross-Jurisdictional Sharing (CJS) in support of local public health accreditation and QI in Georgia. Data Sets and Sources: Archival data (primarily state statutes), secondary data from previous qualitative comparative research on Deep South public health organization, secondary data from previous surveys, and oral interviews and written communication. Study Design: Primarily Qualitative design combining ethnographic and participatory research methods. Analysis: Qualitative Content analysis based on predetermined and emergent themes. Principal Findings: Georgia’s Health Districts have emerged as major CJS entities that support delivery of essential services and local public health (LPH) QI and LPH accreditation readiness, driven primarily by local organizational leadership and culture that is facilitated through enabling statutes in contrast to more top-down state-mandating statutes, regulations and directives. Conclusion: Georgia’s use of districts as multi-county public health entities serves as a primary structure for providing local public health services and has become a critical structure to address the looming demands for QI and accreditation, even though the statutes clearly establish the county as the primary local public health entity. Implications for the Field of PHSSR: This CJS structure to facilitate public health QI and accreditation in Georgia illustrates how agency cultures can emerge from local demands for economies of scale, more than formal policies generated at state level. This is a model that could be very important for advancing CJS in other regions of the country