Geogenomic segregation and temporal trends of human pathogenic Escherichia coli o157:H7, Washington, USA, 2005-2014

The often-noted and persistent increased incidence of Escherichia coli O157:H7 infections in rural areas is not well understood. We used a cohort of E. coli O157:H7 cases reported in Washington, USA, during 2005–2014, along with phylogenomic characterization of the infecting isolates, to identify geographic segregation of and temporal trends in specific phylogenetic lineages of E. coli O157:H7. Kernel estimation and generalized additive models demonstrated that pathogen lineages were spatially segregated during the period of analysis and identified a focus of segregation spanning multiple, predominantly rural, counties for each of the main clinical lineages, Ib, IIa, and IIb. These results suggest the existence of local reservoirs from which humans are infected. We also noted a secular increase in the proportion of lineage IIa and IIb isolates. Spatial segregation by phylogenetic lineage offers the potential to identify local reservoirs and intervene to prevent continued transmission

Azole Drugs Are Imported By Facilitated Diffusion in Candida albicans and Other Pathogenic Fungi

Despite the wealth of knowledge regarding the mechanisms of action and the mechanisms of resistance to azole antifungals, very little is known about how the azoles are imported into pathogenic fungal cells. Here the in-vitro accumulation and import of Fluconazole (FLC) was examined in the pathogenic fungus, Candida albicans. In energized cells, FLC accumulation correlates inversely with expression of ATP-dependent efflux pumps. In de-energized cells, all strains accumulate FLC, suggesting that FLC import is not ATP-dependent. The kinetics of import in de-energized cells displays saturation kinetics with a Km of 0.64 uM and Vmax of 0.0056 pmol/min/108 cells, demonstrating that FLC import proceeds via facilitated diffusion through a transporter rather than passive diffusion. Other azoles inhibit FLC import on a mole/mole basis, suggesting that all azoles utilize the same facilitated diffusion mechanism. An analysis of related compounds indicates that competition for azole import depends on an aromatic ring and an imidazole or triazole ring together in one molecule. Import of FLC by facilitated diffusion is observed in other fungi, including Cryptococcus neoformans, Saccharomyces cerevisiae, and Candida krusei, indicating that the mechanism of transport is conserved among fungal species. FLC import was shown to vary among Candida albicans resistant clinical isolates, suggesting that altered facilitated diffusion may be a previously uncharacterized mechanism of resistance to azole drugs

Fruit and Vegetable Intake and Food Store Access: A Cross-Sectional Survey Study in Ypsilanti, Michigan

Given declines in supermarkets in Washtenaw County, Michigan (MI), we aim to characterize the relationship between food store access and fruit and vegetable intake in Ypsilanti, MI. A cross-sectional, convenience sample survey was conducted in March 2011 at the Ypsilanti District Library (n=83). Self-reported food store access, perceived food environment, and fruit and vegetable intake were assessed. Linear and logistic regressions were performed between store access, fruit and vegetable intake, and meeting dietary recommendations. Perception was evaluated for effect modification. Adjusting for demographics, each food store within one mile of participants’ homes increased odds of meeting recommended intake by 105% (OR 2.05, 95% CI: 1.02, 4.10). However, contrary to previous literature, each additional minute to the food store was associated with consumption of 0.37 (95% confidence interval [CI]: 0.10, 0.64) more servings of fruits and vegetables per day. Perception was not a statistically significant effect modifier, but data suggest differences for those with divergent perceptions. Food environment is associated with fruit and vegetable intake in Ypsilanti, MI. Inconsistent findings suggest that programs should focus on enhancing the food environment within the context of perceptions and preferences

Enhancing public health surveillance: integrating genomic and epidemiologic data to inform public health action and One Health progress

Thesis (Ph.D.)--University of Washington, 2023Pathogen genomic data can provide highly useful information for public health practice, particularly when combined and analyzed with epidemiologic data in real time. Likewise, a One Health approach pushes our current health surveillance systems beyond their siloed views to consider balancing and optimizing health outcomes across human, animal, and environmental domains. Implementation of genomic epidemiology in public health practice alongside a One Health approach holds promise for early and more specific outbreak detection, improved understanding of health risks, increased hypothesis generation for research, and proactive public health action to prevent health threats.This dissertation focuses on genomic data integration and use within public health practice, highlighting the systems changes required for successful implementation, demonstrating population-level genomic-epidemiologic analyses for the purpose of public health action, and discussing expansion of these concepts to encompass a One Health approach. In the chapters that follow, I first describe implementation of a comprehensive system for large-scale genomic data capture and linkage to epidemiological data and an evaluation of this system. This study identifies key areas of success for this system as well as areas for improvement to enable real-time genomic-epidemiologic analyses. Next, I apply genomic-epidemiologic methods, demonstrating the utility of genomic data produced at the population-level to add information for public health action over the course of the SARS-CoV-2 pandemic. Given the available data, computing infrastructure, workforce, and tools, I outline which genomic-epidemiologic methods are most applicable for ongoing or routine data analysis given the system’s current state, as well as recommendations for improved data capture to support additional methods. Finally, I outline requirements for operationalizing One Health data integration through the development of a framework and possible approaches to One Health genomic data storage and co-analysis. This framework is developed to support data integration across One Health domains, expanding our joint ability to prevent and control disease. Together, this work envisions a more holistic approach to infectious disease surveillance, considering data generated from pathogens, hosts of all species, and the environment to better prepare our public health system to face emerging and endemic health threats

Utility of Whole-Genome Sequencing to Ascertain Locally Acquired Cases of Coccidioidomycosis, Washington, USA

Coccidioidomycosis is an emerging fungal infection in Washington, USA, and the epidemiology of the disease in this state is poorly understood. We used whole-genome sequencing to differentiate locally acquired cases in Washington on the basis of the previously identified phylogeographic population structure of Coccidioides spp. Clinical isolates from coccidioidomycosis cases involving possible Washington soil exposure were included. Of 17 human infections with epidemiologic evidence of possible local acquisition, 4 were likely locally acquired infections and 13 were likely acquired outside Washington. Isolates from locally acquired cases clustered within the previously established Washington clade of C. immitis. Genetic differences among these strains suggest multiple environmental reservoirs of C. immitis in the state

Contribution and Interaction of Shiga Toxin Genes to Escherichia coli O157:H7 Virulence

Escherichia coli O157:H7 is the predominant cause of diarrhea-associated hemolytic uremic syndrome (HUS) worldwide. Its cardinal virulence traits are Shiga toxins, which are encoded by stx genes, the most common of which are stx1a, stx2a, and stx2c. The toxins these genes encode differ in their in vitro and experimental phenotypes, but the human population-level impact of these differences is poorly understood. Using Shiga toxin-encoding bacteriophage insertion typing and real-time polymerase chain reaction, we genotyped isolates from 936 E. coli O157:H7 cases and verified HUS status via chart review. We compared the HUS risk between isolates with stx2a and those with stx2a and another gene and estimated additive interaction of the stx genes. Adjusted for age and symptoms, the HUS incidence of E. coli O157:H7 containing stx2a alone was 4.4% greater (95% confidence interval (CI) −0.3%, 9.1%) than when it occurred with stx1a. When stx1a and stx2a occur together, the risk of HUS was 27.1% lower (95% CI −87.8%, −2.3%) than would be expected if interaction were not present. At the population level, temporal or geographic shifts toward these genotypes should be monitored, and stx genotype may be an important consideration in clinically predicting HUS among E. coli O157:H7 cases

Baylisascaris procyonis Roundworm Infection in Child with Autism Spectrum Disorder, Washington, USA, 2022

We describe a case of Baylisascaris procyonis roundworm infection in a child in Washington, USA, with autism spectrum disorder. Environmental assessment confirmed nearby raccoon habitation and B. procyonis eggs. B. procyonis infections should be considered a potential cause of human eosinophilic meningitis, particularly among young children and persons with developmental delays

Chronic Mastitis in Egypt and Morocco: Differentiating between Idiopathic Granulomatous Mastitis and IgG4â Related Disease

Idiopathic granulomatous mastitis (IGM) is a benign, frequently severe chronic inflammatory lesion of the breast. Its etiology remains unknown and reported cases vary in their presentation and histologic findings with an optimal treatment algorithm yet to be described owing mainly to the disease’s heterogeneity. IgG4â related disease (IgG4â RD) is a newly recognized systemic fibroinflammatory condition characterized by a dense lymphoplasmacytic infiltrate with many IgG4â positive plasma cells, storiform fibrosis, and obliterative phlebitis. Immunosuppressive therapy is considered to be an effective firstâ line therapy for IgG4â RD. We sought to clarify and classify chronic mastitis according to the histologic findings of IgG4â RD mastitis with respect to IGM and to develop a robust diagnostic framework to help select patients for optimal treatment strategies. Using the largest collection to date (43 cases from Egypt and Morocco), we show that despite sharing many features, IGM and IgG4â RD mastitis are separate diseases. To diagnostically separate the diseases, we created a classification schemaâ termed the Michigan Classificationâ based upon our large series of cases, the consensus statement on IgG4â RD, and the histologic description of IGM in the literature. Using our classification, we discerned 17 cases of IgG4â RD and 8 cases of IGM among the 43 chronic mastitis cases, with 18 indeterminate cases. Thus, our Michigan Classification can form the basis of rational stratification of chronic mastitis patients between these two clinically and histopathologically heterogeneous diseases.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134069/1/tbj12628_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134069/2/tbj12628.pd