Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-7 (of 7 Records) |
Query Trace: Dunham L[original query] |
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Vital Signs: Health disparities in hemodialysis-associated staphylococcus aureus bloodstream infections - United States, 2017-2020
Rha B , See I , Dunham L , Kutty PK , Moccia L , Apata IW , Ahern J , Jung S , Li R , Nadle J , Petit S , Ray SM , Harrison LH , Bernu C , Lynfield R , Dumyati G , Tracy M , Schaffner W , Ham DC , Magill SS , O'Leary EN , Bell J , Srinivasan A , McDonald LC , Edwards JR , Novosad S . MMWR Morb Mortal Wkly Rep 2023 72 (6) 153-159 INTRODUCTION: Racial and ethnic minorities are disproportionately affected by end-stage kidney disease (ESKD). ESKD patients on dialysis are at increased risk for Staphylococcus aureus bloodstream infections, but racial, ethnic, and socioeconomic disparities associated with this outcome are not well described. METHODS: Surveillance data from the 2020 National Healthcare Safety Network (NHSN) and the 2017-2020 Emerging Infections Program (EIP) were used to describe bloodstream infections among patients on hemodialysis (hemodialysis patients) and were linked to population-based data sources (CDC/Agency for Toxic Substances and Disease Registry [ATSDR] Social Vulnerability Index [SVI], United States Renal Data System [USRDS], and U.S. Census Bureau) to examine associations with race, ethnicity, and social determinants of health. RESULTS: In 2020, 4,840 dialysis facilities reported 14,822 bloodstream infections to NHSN; 34.2% were attributable to S. aureus. Among seven EIP sites, the S. aureus bloodstream infection rate during 2017-2020 was 100 times higher among hemodialysis patients (4,248 of 100,000 person-years) than among adults not on hemodialysis (42 of 100,000 person-years). Unadjusted S. aureus bloodstream infection rates were highest among non-Hispanic Black or African American (Black) and Hispanic or Latino (Hispanic) hemodialysis patients. Vascular access via central venous catheter was strongly associated with S. aureus bloodstream infections (NHSN: adjusted rate ratio [aRR] = 6.2; 95% CI = 5.7-6.7 versus fistula; EIP: aRR = 4.3; 95% CI = 3.9-4.8 versus fistula or graft). Adjusting for EIP site of residence, sex, and vascular access type, S. aureus bloodstream infection risk in EIP was highest in Hispanic patients (aRR = 1.4; 95% CI = 1.2-1.7 versus non-Hispanic White [White] patients), and patients aged 18-49 years (aRR = 1.7; 95% CI = 1.5-1.9 versus patients aged ≥65 years). Areas with higher poverty levels, crowding, and lower education levels accounted for disproportionately higher proportions of hemodialysis-associated S. aureus bloodstream infections. CONCLUSIONS AND IMPLICATIONS FOR PUBLIC HEALTH PRACTICE: Disparities exist in hemodialysis-associated S. aureus infections. Health care providers and public health professionals should prioritize prevention and optimized treatment of ESKD, identify and address barriers to lower-risk vascular access placement, and implement established best practices to prevent bloodstream infections. |
Provider perspectives: Identification and follow-up of infants who are deaf or hard of hearing
Cree RA , Bitsko R , Grimm C , Nash A , Cahill E , Dunham E , Logan N , McKay SL , Martinez DR , Gaffney M . Am J Perinatol 2022 OBJECTIVE: Without timely screening, diagnosis, and intervention, hearing loss can cause significant delays in a child's speech, language, social, and emotional development. In 2019, Texas had nearly twice the average rate of loss to follow-up (LFU) or loss to documentation (LTD; i.e., missing documentation of services received) among infants who did not pass their newborn hearing screening compared to the United States overall (51.1% vs. 27.5%). We aimed to identify factors contributing to LFU/LTD among infants who do not pass their newborn hearing screening in Texas. STUDY DESIGN: Data were collected through semi-structured qualitative interviews with 56 providers along the hearing care continuum, including hospital newborn hearing screening program staff, audiologists, primary care physicians, and early intervention (EI) program staff located in three rural and urban public health regions in Texas. Following recording and transcription of the interviews, we used qualitative data analysis software to analyze themes using a conventional content analysis approach. RESULTS: Frequently cited barriers included problems with family access to care, difficulty contacting patients, problems with communication between providers and referrals, lack of knowledge among providers and parents, and problems using the online reporting system. Providers in rural areas more often mentioned problems with family access to care and contacting families compared to providers in urban areas. CONCLUSION: These findings provide insight into strategies that public health professionals and health care providers can use to work together to help further increase the number of children identified early who may benefit from EI services. |
Review of Institute of Medicine and National Research Council recommendations for One Health Initiative
Rubin C , Myers T , Stokes W , Dunham B , Harris S , Lautner B , Annelli J . Emerg Infect Dis 2013 19 (12) 1913-7 Human health is inextricably linked to the health of animals and the viability of ecosystems; this is a concept commonly known as One Health. Over the last 2 decades, the Institute of Medicine (IOM) and the National Research Council (NRC) have published consensus reports and workshop summaries addressing a variety of threats to animal, human, and ecosystem health. We reviewed a selection of these publications and identified recommendations from NRC and IOM/NRC consensus reports and from opinions expressed in workshop summaries that are relevant to implementation of the One Health paradigm shift. We grouped these recommendations and opinions into thematic categories to determine if sufficient attention has been given to various aspects of One Health. We conclude that although One Health themes have been included throughout numerous IOM and NRC publications, identified gaps remain that may warrant targeted studies related to the One Health approach. |
Immune evasion and recognition of the syphilis spirochete in blood and skin of secondary syphilis patients: two immunologically distinct compartments
Cruz AR , Ramirez LG , Zuluaga AV , Pillay A , Abreu C , Valencia CA , La Vake C , Cervantes JL , Dunham-Ems S , Cartun R , Mavilio D , Radolf JD , Salazar JC . PLoS Negl Trop Dis 2012 6 (7) e1717 BACKGROUND: The clinical syndrome associated with secondary syphilis (SS) reflects the propensity of Treponema pallidum (Tp) to escape immune recognition while simultaneously inducing inflammation. METHODS: To better understand the duality of immune evasion and immune recognition in human syphilis, herein we used a combination of flow cytometry, immunohistochemistry (IHC), and transcriptional profiling to study the immune response in the blood and skin of 27 HIV(-) SS patients in relation to spirochetal burdens. Ex vivo opsonophagocytosis assays using human syphilitic sera (HSS) were performed to model spirochete-monocyte/macrophage interactions in vivo. RESULTS: Despite the presence of low-level spirochetemia, as well as immunophenotypic changes suggestive of monocyte activation, we did not detect systemic cytokine production. SS subjects had substantial decreases in circulating DCs and in IFNgamma-producing and cytotoxic NK-cells, along with an emergent CD56-/CD16+ NK-cell subset in blood. Skin lesions, which had visible Tp by IHC and substantial amounts of Tp-DNA, had large numbers of macrophages (CD68+), a relative increase in CD8+ T-cells over CD4+ T-cells and were enriched for CD56+ NK-cells. Skin lesions contained transcripts for cytokines (IFN-gamma, TNF-alpha), chemokines (CCL2, CXCL10), macrophage and DC activation markers (CD40, CD86), Fc-mediated phagocytosis receptors (FcgammaRI, FcgammaR3), IFN-beta and effector molecules associated with CD8 and NK-cell cytotoxic responses. While HSS promoted uptake of Tp in conjunction with monocyte activation, most spirochetes were not internalized. CONCLUSIONS: Our findings support the importance of macrophage driven opsonophagocytosis and cell mediated immunity in treponemal clearance, while suggesting that the balance between phagocytic uptake and evasion is influenced by the relative burdens of bacteria in blood and skin and the presence of Tp subpopulations with differential capacities for binding opsonic antibodies. They also bring to light the extent of the systemic innate and adaptive immunologic abnormalities that define the secondary stage of the disease, which in the skin of patients trends towards a T-cell cytolytic response. |
Cost-effectiveness of 2009 pandemic influenza A(H1N1) vaccination in the United States
Prosser LA , Lavelle TA , Fiore AE , Bridges CB , Reed C , Jain S , Dunham KM , Meltzer MI . PLoS One 2011 6 (7) e22308 BACKGROUND: Pandemic influenza A(H1N1) (pH1N1) was first identified in North America in April 2009. Vaccination against pH1N1 commenced in the U.S. in October 2009 and continued through January 2010. The objective of this study was to evaluate the cost-effectiveness of pH1N1 vaccination. METHODOLOGY: A computer simulation model was developed to predict costs and health outcomes for a pH1N1 vaccination program using inactivated vaccine compared to no vaccination. Probabilities, costs and quality-of-life weights were derived from emerging primary data on pH1N1 infections in the US, published and unpublished data for seasonal and pH1N1 illnesses, supplemented by expert opinion. The modeled target population included hypothetical cohorts of persons aged 6 months and older stratified by age and risk. The analysis used a one-year time horizon for most endpoints but also includes longer-term costs and consequences of long-term sequelae deaths. A societal perspective was used. Indirect effects (i.e., herd effects) were not included in the primary analysis. The main endpoint was the incremental cost-effectiveness ratio in dollars per quality-adjusted life year (QALY) gained. Sensitivity analyses were conducted. RESULTS: For vaccination initiated prior to the outbreak, pH1N1 vaccination was cost-saving for persons 6 months to 64 years under many assumptions. For those without high risk conditions, incremental cost-effectiveness ratios ranged from $8,000-$52,000/QALY depending on age and risk status. Results were sensitive to the number of vaccine doses needed, costs of vaccination, illness rates, and timing of vaccine delivery. CONCLUSIONS: Vaccination for pH1N1 for children and working-age adults is cost-effective compared to other preventive health interventions under a wide range of scenarios. The economic evidence was consistent with target recommendations that were in place for pH1N1 vaccination. We also found that the delays in vaccine availability had a substantial impact on the cost-effectiveness of vaccination. |
Surface immunolabeling and consensus computational framework to identify candidate rare outer membrane proteins of Treponema pallidum
Cox DL , Luthra A , Dunham-Ems S , Desrosiers DC , Salazar JC , Caimano MJ , Radolf JD . Infect Immun 2010 78 (12) 5178-94 Treponema pallidum reacts poorly with the antibodies present in rabbit and human syphilitic sera, a property attributed to the paucity of proteins in its outer membrane. To better understand the basis for the syphilis spirochete's "stealth pathogenicity", we used a dual-label, 3-step amplified assay in which treponemes encapsulated in gel microdroplets were probed with syphilitic sera in parallel with anti-FlaA antibodies. A small (approx. 5-10%) but reproducible fraction of intact treponemes bound IgG and/or IgM antibodies. Three lines of evidence supported that the surface antigens were likely beta-barrel-forming outer membrane proteins (OMPs): (i) surface-labeling with anti-lipoidal (VDRL) antibodies was not observed, (ii) immunoblot analysis confirmed prior results that T. pallidum glycolipids are not immunoreactive, and (iii) labeling of intact organisms was not appreciably affected by proteinase K (PK) treatment. With this method, we also demonstrate that TprK (TP0897), an extensively studied candidate OMP, and TP0136, a lipoprotein recently reported to be surface-exposed, are both periplasmic. Consistent with the immunolabeling studies, TprK also was found to lack amphiphilicity, a characteristic property of beta-barrel-forming proteins. Using a consensus computational framework that combined subcellular localization and beta-barrel structural prediction tools, we generated ranked groups of candidate rare OMPs, the predicted T. pallidum outer membrane proteome (OMPeome), which we postulate includes the surface-exposed molecules detected by our enhanced gel microdroplet assay. In addition to underscoring the syphilis spirochete's remarkably poor surface antigenicity, our findings help to explain the complex and shifting balance between pathogen and host defenses that characterizes syphilitic infection. |
Cryo-electron tomography elucidates the molecular architecture of Treponema pallidum, the syphilis spirochete
Izard J , Renken C , Hsieh CE , Desrosiers DC , Dunham-Ems S , La Vake C , Gebhardt LL , Limberger RJ , Cox DL , Marko M , Radolf JD . J Bacteriol 2009 191 (24) 7566-80 Cryo-electron tomography (CET) was used to examine the native cellular organization of Treponema pallidum, the syphilis spirochete. T. pallidum cells appeared to form flat waves, did not contain an outer coat, and, except for bulges over the basal bodies and widening in the vicinity of flagellar filaments, displayed a uniform periplasmic space. Although the outer membrane (OM) generally was smooth in contour, OM extrusions and blebs frequently were observed, highlighting the structure's fluidity and lack of attachment to underlying periplasmic constituents. Cytoplasmic filaments converged from their attachment points opposite the basal bodies to form arrays that run roughly parallel to the flagellar filaments along the inner surface of the cytoplasmic membrane (CM). Motile treponemes stably attached to rabbit epithelial cells predominantly via their tips. CET revealed that T. pallidum cell ends have a complex morphology and assume at least four distinct morphotypes. Images of dividing treponemes and organisms shedding cell envelope-derived blebs provided evidence for the spirochete's complex membrane biology. In the regions without flagellar filaments, PG was visualized as a thin layer that divided the periplasmic space into zones of higher and lower electron density adjacent to the CM and OM, respectively. Flagellar filaments were observed overlying the PG layer, while image modeling placed the PG-basal body contact site in the vicinity of the stator-P-collar junction. Bioinformatics and homology modeling indicated that the MotB proteins of T. pallidum, T. denticola, and B. burgdorferi have membrane topologies and PG binding sites highly similar to those of their well characterized E. coli and H. pylori orthologs. Collectively, our results help to clarify fundamental differences in cell envelope ultrastructure between spirochetes and Gram-negatives. They also confirm that PG stabilizes the flagellar motor and enable us to propose that in most spirochetes motility results from rotation of the flagellar filaments against the PG. |
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