Browsing by Subject "infection"
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Item Antifungal Susceptibilities Among Different Serotypes Of Cryptococcus Gattii And Cryptococcus Neoformans(2009-01) Thompson, George R.; Wiederhold, Nathan P.; Fothergill, Annette W.; Vallor, Ana C.; Wickes, Brian L.; Patterson, Thomas F.; Wiederhold, Nathan P.We measured antifungal activity against 128 cryptococcal isolates (86 of C. neoformans and 42 of C. gattii) to determine if differences in serotype susceptibility exist. Contrary to previous results, we found no serotype susceptibility differences. Isavuconazole, posaconazole, and voriconazole demonstrated excellent potency against each isolate and serotype, including isolates with reduced fluconazole susceptibilities.Item Efficacy Of Posaconazole As Treatment And Prophylaxis Against Fusarium Solani(2010-03) Wiederhold, Nathan P.; Najvar, Laura K.; Bocanegra, Rosie; Graybill, John R.; Patterson, Thomas F.; Wiederhold, Nathan P.Invasive fusariosis is a highly aggressive fungal infection associated with high mortality in heavily immunocompromised patients. Although posaconazole is efficacious as salvage therapy against infections caused by Fusarium species, concerns remain regarding this agent in the setting of reduced potency. To evaluate the efficacy of posaconazole as treatment or prophylaxis against invasive fusariosis caused by Fusarium solani, we utilized a neutropenic murine model of disseminated disease. ICR mice were administered escalating doses of posaconazole (6.25, 12.5, 25, or 50 mg/kg of body weight twice daily [BID]) by oral gavage beginning 2 days prior to inoculation in the prophylaxis studies or beginning 12 h after inoculation as treatment. Therapy was continued until day 9 postinoculation, and animals were monitored off therapy until day 15 for survival. Fungal burden was assessed as CFU in the kidneys. A clear dose-response relationship was observed, as the highest dose of posaconazole (50 mg/kg) was the most effective in prolonging survival and reducing tissue fungal burden both as prophylaxis and as treatment. This dose response was associated with high posaconazole serum concentrations as measured by bioassay. However, the extent of efficacy was also dependent on the infecting inoculum, as greater increases in survival and reductions in fungal burden were observed with the lower inocula tested. In this model high dosages of posaconazole were effective as treatment and prophylaxis against disseminated fusariosis caused by F. solani.Item Flagella and Pili-Mediated Near-Surface Single-Cell Motility Mechanisms in P. aeruginosa(2011-04) Conrad, Jacinta C.; Gibiansky, Maxsim L.; Jin, Fan; Gordon, Vernita D.; Motto, Dominick A.Bacterial biofilms are structured multicellular communities that are responsible for a broad range of infections. Knowing how free-swimming bacteria adapt their motility mechanisms near a surface is crucial for understanding the transition from the planktonic to the biofilm phenotype. By translating microscopy movies into searchable databases of bacterial behavior and developing image-based search engines, we were able to identify fundamental appendage-specific mechanisms for the surface motility of Pseudomonas aeruginosa. Type IV pili mediate two surface motility mechanisms: horizontally oriented crawling, by which the bacterium moves lengthwise with high directional persistence, and vertically oriented walking, by which the bacterium moves with low directional persistence and high instantaneous velocity, allowing it to rapidly explore microenvironments. The flagellum mediates two additional motility mechanisms: near-surface swimming and surface-anchored spinning, which often precedes detachment from a surface. Flagella and pili interact cooperatively in a launch sequence whereby bacteria change orientation from horizontal to vertical and then detach. Vertical orientation facilitates detachment from surfaces and thereby influences biofilm morphology.Item Letter to H.B. Stenzel from W.H. Wright on 1944-06-07(1944-06-07) Wright, W.H.Item Long-Term Control Of Viral Replication In A Group O, Human Immunodeficiency Virus Type 1-Infected Individual(2014-06) Buckheit, R. W.; Sexauer, S. B.; Sedaghat, A. R.; Wilke, C. O.; Laeyendecker, O.; Basseth, C. R.; Blankson, J. N.; Wilke, Claus O.Item Optimal H1N1 Vaccination Strategies Based on Self-Interest Versus Group Interest(2011-02) Shim, Eunha; Meyers, Lauren Ancel; Galvani, Alison P.; Meyers, Lauren AnceInfluenza vaccination is vital for reducing H1N1 infection-mediated morbidity and mortality. To reduce transmission and achieve herd immunity during the initial 2009-2010 pandemic season, the US Centers for Disease Control and Prevention (CDC) recommended that initial priority for H1N1 vaccines be given to individuals under age 25, as these individuals are more likely to spread influenza than older adults. However, due to significant delay in vaccine delivery for the H1N1 influenza pandemic, a large fraction of population was exposed to the H1N1 virus and thereby obtained immunity prior to the wide availability of vaccines. This exposure affects the spread of the disease and needs to be considered when prioritizing vaccine distribution. Methods: To determine optimal H1N1 vaccine distributions based on individual self-interest versus population interest, we constructed a game theoretical age-structured model of influenza transmission and considered the impact of delayed vaccination. Results: Our results indicate that if individuals decide to vaccinate according to self-interest, the resulting optimal vaccination strategy would prioritize adults of age 25 to 49 followed by either preschool-age children before the pandemic peak or older adults (age 50-64) at the pandemic peak. In contrast, the vaccine allocation strategy that is optimal for the population as a whole would prioritize individuals of ages 5 to 64 to curb a growing pandemic regardless of the timing of the vaccination program. Conclusions: Our results indicate that for a delayed vaccine distribution, the priorities that are optimal at a population level do not align with those that are optimal according to individual self-interest. Moreover, the discordance between the optimal vaccine distributions based on individual self-interest and those based on population interest is even more pronounced when vaccine availability is delayed. To determine optimal vaccine allocation for pandemic influenza, public health agencies need to consider both the changes in infection risks among age groups and expected patterns of adherence.