Department of Biomedical Sciences

Optimal targeting of seasonal influenza vaccination toward younger ages isrobust to parameter uncertainty

2013-05-17T23:05:17Z

Optimal targeting of seasonal influenza vaccination toward younger ages isrobust to parameter uncertainty Martial L. Ndeffo Mbah; Jan Medlock; Lauren Ancel Meyers; Alison P. Galvani; Jeffrey P. Townsend Identification of the optimal vaccine allocation for the control of influenza requires consideration of uncertainty arising from numerous unpredictable factors, including viral evolution and diversity within the human population’s immunity as well as variation in vaccine efficacy. The best policy must account for diverse potential outcomes based on these uncertainties. Here we used a mathematical model parametrized with survey-based contact data, demographic, and epidemiological data from seasonal influenza in the United States to determine the optimal vaccine allocation for five outcome measures:infections, hospitalizations, deaths, years of life loss, and contingent valuation. We incorporated uncertainty of epidemiological parameters and derive probability distributions of optimal age- and risk-specific allocation of vaccine. Our analysis demonstrated that previous recommendations of targeting schoolchildren (ages 5–17 years) and young adults (18–44 years) are generally robust in the face of uncertainty.However, when the outcome measure is to minimize deaths, years of life loss, or contingent valuation, uncertainty analysis identified scenarios under which it is optimal to target people at high risk for complications, even when vaccine are in abundance. This is the author's peer-reviewed final manuscript. The version of record is copyrighted by Elsevier and can be found here: http://www.journals.elsevier.com/vaccine/

Using Gross Energy Improves Metabolizable Energy Predictive Equations for Pet Foods Whereas Undigested Protein and Fiber Content Predict Stool Quality

2013-03-12T16:30:42Z

Using Gross Energy Improves Metabolizable Energy Predictive Equations for Pet Foods Whereas Undigested Protein and Fiber Content Predict Stool Quality Hall, Jean A.; Melendez, Lynda D.; Jewell, Dennis E. Because animal studies are labor intensive, predictive equations are used extensively for calculating metabolizable energy (ME) concentrations of dog and cat pet foods. The objective of this retrospective review of digestibility studies, which were conducted over a 7-year period and based upon Association of American Feed Control Officials (AAFCO) feeding protocols, was to compare the accuracy and precision of equations developed from these animal feeding studies to commonly used predictive equations. Feeding studies in dogs and cats (331 and 227 studies, respectively) showed that equations using modified Atwater factors accurately predict ME concentrations in dog and cat pet foods (r² = 0.97 and 0.98, respectively). The National Research Council (NRC) equations also accurately predicted ME concentrations in pet foods (r² = 0.97 for dog and cat foods). For dogs, these equations resulted in an average estimate of ME within 0.16% and 2.24% of the actual ME measured (equations using modified Atwater factors and NRC equations, respectively); for cats these equations resulted in an average estimate of ME within 1.57% and 1.80% of the actual ME measured. However, better predictions of dietary ME in dog and cat pet foods were achieved using equations based on analysis of gross energy (GE) and new factors for moisture, protein, fat and fiber. When this was done there was less than 0.01% difference between the measured ME and the average predicted ME (r² = 0.99 and 1.00 in dogs and cats, respectively) whereas the absolute value of the difference between measured and predicted was reduced by approximately 50% in dogs and 60% in cats. Stool quality, which was measured by stool score, was influenced positively when dietary protein digestibility was high and fiber digestibility was low. In conclusion, using GE improves predictive equations for ME content of dog and cat pet foods. Nondigestible protein and fiber content of diets predicts stool quality. This is the publisher’s final pdf. The published article is copyrighted by Public Library of Science and can be found at: http://www.plos.org/.

Clostridium difficile Spore-Macrophage Interactions: Spore Survival

2013-02-12T17:35:41Z

Clostridium difficile Spore-Macrophage Interactions: Spore Survival Paredes-Sabja, Daniel; Cofre-Araneda, Glenda; Brito-Silva, Christian; Pizarro-Guajardo, Marjorie; Sarker, Mahfuzur R. Background: Clostridium difficile is the main cause of nosocomial infections including antibiotic associated diarrhea, pseudomembranous colitis and toxic megacolon. During the course of Clostridium difficile infections (CDI), C. difficile undergoes sporulation and releases spores to the colonic environment. The elevated relapse rates of CDI suggest that C. difficile spores has a mechanism(s) to efficiently persist in the host colonic environment. Methodology/Principal Findings: In this work, we provide evidence that C. difficile spores are well suited to survive the host's innate immune system. Electron microscopy results show that C. difficile spores are recognized by discrete patchy regions on the surface of macrophage Raw 264.7 cells, and phagocytosis was actin polymerization dependent. Fluorescence microscopy results show that >80% of Raw 264.7 cells had at least one C. difficile spore adhered, and that similar to 60% of C. difficile spores were phagocytosed by Raw 264.7 cells. Strikingly, presence of complement decreased Raw 264.7 cells' ability to phagocytose C. difficile spores. Due to the ability of C. difficile spores to remain dormant inside Raw 264.7 cells, they were able to survive up to 72 h of macrophage infection. Interestingly, transmission electron micrographs showed interactions between the surface proteins of C. difficile spores and the phagosome membrane of Raw 264.7 cells. In addition, infection of Raw 264.7 cells with C. difficile spores for 48 h produced significant Raw 264.7 cell death as demonstrated by trypan blue assay, and nuclei staining by ethidium homodimer-1. Conclusions/Significance: These results demonstrate that despite efficient recognition and phagocytosis of C. difficile spores by Raw 264.7 cells, spores remain dormant and are able to survive and produce cytotoxic effects on Raw 264.7 cells. This is the publisher’s final pdf. The published article is copyrighted by the Public Library of Science and can be found at: http://www.plosone.org/home.action.

Footprint of Positive Selection in Treponema pallidum subsp. pallidum Genome Sequences Suggests Adaptive Microevolution of the Syphilis Pathogen

2012-08-22T14:56:38Z

Footprint of Positive Selection in Treponema pallidum subsp. pallidum Genome Sequences Suggests Adaptive Microevolution of the Syphilis Pathogen Giacani, Lorenzo; Chattopadhyay, Sujay; Centurion-Lara, Arturo; Jeffrey, BrendanM.; Le, Hoavan T.; Molini, Barbara J.; Lukehart, Sheila A.; Sokurenko, Evgeni V.; Rockey, Daniel D. In the rabbit model of syphilis, infection phenotypes associated with the Nichols and Chicago strains of Treponema pallidum (T. pallidum), though similar, are not identical. Between these strains, significant differences are found in expression of, and antibody responses to some candidate virulence factors, suggesting the existence of functional genetic differences between isolates. The Chicago strain genome was therefore sequenced and compared to the Nichols genome, available since 1998. Initial comparative analysis suggested the presence of 44 single nucleotide polymorphisms (SNPs), 103 small (<= 3 nucleotides) indels, and 1 large (1204 bp) insertion in the Chicago genome with respect to the Nichols genome. To confirm the above findings, Sanger sequencing was performed on most loci carrying differences using DNA from Chicago and the Nichols strain used in the original T. pallidum genome project. A majority of the previously identified differences were found to be due to errors in the published Nichols genome, while the accuracy of the Chicago genome was confirmed. However, 20 SNPs were confirmed between the two genomes, and 16 (80.0%) were found in coding regions, with all being of nonsynonymous nature, strongly indicating action of positive selection. Sequencing of 16 genomic loci harboring SNPs in 12 additional T. pallidum strains, (SS14, Bal 3, Bal 7, Bal 9, Sea 81-3, Sea 81-8, Sea 86-1, Sea 87-1, Mexico A, UW231B, UW236B, and UW249C), was used to identify "Chicago-" or "Nichols-specific" differences. All but one of the 16 SNPs were "Nichols-specific", with Chicago having identical sequences at these positions to almost all of the additional strains examined. These mutations could reflect differential adaptation of the Nichols strain to the rabbit host or pathoadaptive mutations acquired during human infection. Our findings indicate that SNPs among T. pallidum strains emerge under positive selection and, therefore, are likely to be functional in nature. This is the publisher’s final pdf. The published article is copyrighted by PLoS and can be found at: http://www.plosone.org/home.action.