Immunology and Infectious Disease Commons^™

Mutations In The Plasmodium Falciparum Chloroquine Resistance Transporter, Pfcrt, Enlarge The Parasite's Food Vacuole And Alter Drug Sensitivities, Serena Pulcini, Henry M. Staines, Andrew H. Lee, Sarah H. Shafik, Guillaume Bouyer, Catherine M. Moore, Daniel A. Daley, Matthew J. Hoke, Lindsey M. Altenhofen, Heather J. Painter, Jainbing Mu, David J.P. Ferguson, Manuel Llinás, Rowena E. Martin, David A. Fidock, Roland A. Cooper, Sanjeev Krishna

Biological Sciences Faculty Publications

Mutations in the Plasmodium falciparum chloroquine resistance transporter, PfCRT, are the major determinant of chloroquine resistance in this lethal human malaria parasite. Here, we describe P. falciparum lines subjected to selection by amantadine or blasticidin that carry PfCRT mutations (C101F or L272F), causing the development of enlarged food vacuoles. These parasites also have increased sensitivity to chloroquine and some other quinoline antimalarials, but exhibit no or minimal change in sensitivity to artemisinins, when compared with parental strains. A transgenic parasite line expressing the L272F variant of PfCRT confirmed this increased chloroquine sensitivity and enlarged food vacuole phenotype. Furthermore, the introduction …

Saccharomyces Boulardii And Bismuth Subsalicylate As Low-Cost Interventions To Reduce The Duration And Severity Of Cholera, Johnathan Sheele, Jessica Cartowski, Angela Dart, Arjun Poddar, Shikha Gupta, Ajay Gupta

Computer Science Faculty Publications

We conducted a randomised single-blinded clinical trial of 100 cholera patients in Port-au-Prince, Haiti to determine if the probiotic Saccharomyces cerevisiae var. boulardii and the anti-diarrhoeal drug bismuth subsalicylate (BS) were able to reduce the duration and severity of cholera. Subjects received either: S. boulardii 250 mg, S. boulardii 250 mg capsule plus BS 524 mg tablet, BS 524 mg, or two placebo capsules every 6 hours alongside standard treatment for cholera. The length of hospitalisation plus the number and volume of emesis, stool and urine were recorded every 6 hours until the study subject was discharged (n=83), left against …

Survey Of The Ectoparasites Of The Invasive Small Indian Mongoose (Herpestes Auropunctatus [Carnivora: Herpestidae]) On St. John, U.S. Virgin Islands, Kelsey L. Townsend, Karen E. Powers

Virginia Journal of Science

In March 2012, live trapping surveys were conducted for invasive small Indian mongoose (Herpestes auropunctatus) on St. John, U.S. Virgin Islands. Forty mongoose were sampled (31%, 9&) for ectoparasites, and cat fleas (Ctenocephalides felis) were discovered on 17 individuals. There was no difference in the number of ectoparasites per mongoose across age classifications (r = 0.109, P = 0.579). However, males had more cat fleas than females, even when mass was taken into account (males are generally heavier). Future behavioral studies may explain these sex differences. Although management suggestions from this research are limited, these …

Discretized Agent-Based Model Of Infectious Disease Spread That Uses Contact Probability, Tyrell L. Gardner

Computational Modeling & Simulation Engineering Theses & Dissertations

This study uses contact probability in an agent-based model to simulate the spread of an infectious disease. In order to perform the study, the agent-based model must first be discretized into events. Each agent in the model is given its own infectious disease state machine taken from the Susceptible-Exposed-Infected-Recovered (SEIR) model. The agents move between squares in a grid environment where each square represents a group. Groups have a contact probability as an attribute that is used to predict whether an agent comes in close contact with another agent. The transitions between the states in the SEIR model are easily …

Transcriptome Of The Female Synganglion Of The Black-Legged Tick Ixodes Scapularis (Acari: Ixodidae) With Comparison Between Illumina And 454 Systems, Noble Egekwu, Daniel E. Sonenshine, Brooke W. Bissinger, R. Michael Roe

Biological Sciences Faculty Publications

Illumina and 454 pyrosequencing were used to characterize genes from the synganglion of female Ixodes scapularis. GO term searching success for biological processes was similar for samples sequenced by both methods. However, for molecular processes, it was more successful for the Illumina samples than for 454 samples. Functional assignments of transcripts predicting neuropeptides, neuropeptide receptors, neurotransmitter receptors and other genes of interest was done, supported by strong e-values (<-6), and high consensus sequence alignments. Transcripts predicting 15 putative neuropeptide prepropeptides ((allatostatin, allatotropin, bursicon α, corticotropin releasing factor (CRF), CRF-binding protein, eclosion hormone, FMRFamide, glycoprotein A, insulin-like peptide, ion transport peptide, myoinhibitory peptide, inotocin ( = neurophysin-oxytocin), Neuropeptide F, sulfakinin and SIFamide)) and transcripts predicting receptors for 14 neuropeptides (allatostatin, calcitonin, cardioacceleratory peptide, corazonin, CRF, eclosion hormone, gonadotropin-releasing hormone/AKH-like, insulin-like peptide, neuropeptide F, proctolin, pyrokinin, SIFamide, sulfakinin and tachykinin) are reported. Similar to Dermacentor variabilis, we found transcripts matching pro-protein convertase, essential for converting neuropeptide hormones to their mature form. Additionally, transcripts predicting 6 neurotransmitter/neuromodulator receptors (acetylcholine, GABA, dopamine, glutamate, octopamine and …

Role Of Peripheral Immune Response In Microglia Activation And Regulation Of Brain Chemokine And Proinflammatory Cytokine Responses Induced During Vsv Encephalitis, Christina D. Steel, Kimberly Breving, Susan Tavakoli, Woong-Ki Kim, Larry D. Sanford, Richard P. Ciavarra

Biological Sciences Faculty Publications

We report herein that neuroinvasion by vesicular stomatitis virus (VSV) activates microglia and induces a peripheral dendritic cell (DC)-dependent inflammatory response in the central nervous system (CNS). VSV neuroinvasion rapidly induces multiple brain chemokine and proinflammatory cytokine mRNAs that display bimodal kinetics. Peripheral DC ablation or T cell depletion suppresses the second wave of this response demonstrating that infiltrating T cells are primarily responsible for the bimodal characteristics of this response. The robust infiltrate associated with VSV encephalitis likely depends on sustained production of brain CCL19 and CCR7 expression on infiltrating inflammatory cells. © 2013 Elsevier B.V. All rights reserved.

Ehrlichia And Spotted Fever Group Rickettsiae Surveillance In Amblyomma Americanum In Virginia Through Use Of A Novel Six-Plex Real-Time Pcr Assay, David N. Gaines, Darwin J. Operario, Suzanne Stroup, Ellen Stromdahl, Chelsea Wright, Holly Gaff, James Broyhill, Joshua Smith, Douglas E. Norris, Tyler Henning, Agape Lucas, Eric Houpt

Biological Sciences Faculty Publications

The population of the lone star tick Amblyomma americanum has expanded in North America over the last several decades. It is known to be an aggressive and nondiscriminatory biter and is by far the most common human-biting tick encountered in Virginia. Few studies of human pathogen prevalence in ticks have been conducted in our state since the mid-twentieth century. We developed a six-plex real-time PCR assay to detect three Ehrlichia species (E. chaffeensis, E. ewingii, and Panola Mountain Ehrlichia) and three spotted fever group Rickettsiae (SFGR; R. amblyommii, R. parkeri, and R. rickettsii …

Single-Tube Real-Time Pcr Assay For Differentiation Of Ixodes Affinis And Ixodes Scapularis, Chelsea L. Wright, Wayne L. Hynes, Breanna T. White, Mindy N. Marshall, Holly D. Gaff, David T. Gauthier

Biological Sciences Faculty Publications

Ixodes affinis Neumann (1899) and Ixodes scapularis Say (1821) are tick vectors of the etiologic agent of Lyme disease, Borrelia burgdorferi sensu stricto. Ixodes affinis and I. scapularis are morphologically very similar, and as they are sympatric in the mid- and south-Atlantic U.S. coastal states, their accurate identification is crucial to studies of disease and vector ecology in this area. This work describes a rapid, single-tube SYBR® Green-based real-time PCR assay for differentiation of I. affinis and I. scapularis at all life stages. The assay employs 2 pairs of species specific primers directed against the internal transcribed spacer 2 (ITS2) …

Prevalence Of Ehrlichia Chaffeensis And Ehrlichia Ewingii In Amblyomma Americanum And Dermacentor Variabilis Collected From Southeastern Virginia, 2010-2011, Chelsea L. Wright, Holly D. Gaff, Wayne L. Hynes

Biological Sciences Faculty Publications

Amblyomma americanum is the most commonly-encountered tick species in southeastern Virginia, representing approximately 95% of the human-biting tick population in this area. Here we investigated the prevalence of Ehrlichia chaffeensis and Ehrlichia ewingii in questing Amblyomma americanum and Dermacentor variabilis ticks collected from multiple sites in southeastern Virginia from 2010–2011. Although both Ehrlichia species were detected in Amblyomma americanum, no evidence of either pathogen was found in Dermacentor variabilis. Prevalence of E. chaffeensis varied by location, ranging from 0 – 5.08% among Amblyomma americanum populations. Ehrlichia ewingii prevalence was slightly higher, ranging from 0 – 8.20% among A. …

Ticks And Spotted Fever Group Rickettsiae Of Southeastern Virginia, Robyn M. Nadolny, Chelsea L. Wright, Daniel E. Sonenshine, Wayne L. Hynes, Holly D. Gaff

Biological Sciences Faculty Publications

The incidence of tick-borne rickettsial disease in the southeastern United States has been rising steadily through the past decade, and the range expansions of tick species and tick-borne infectious agents, new and old, has resulted in an unprecedented mix of vectors and pathogens. The results of an ongoing 4-year surveillance project describe the relative abundance of questing tick populations in southeastern Virginia. Since 2009, more than 66,000 questing ticks of 7 species have been collected from vegetation in a variety of habitats, with Amblyomma americanum constituting over 95% of ticks collected. Other species represented included Ixodes scapularis, Dermacentor variabilis …

Comparison Of Phenology And Pathogen Prevalence, Including Infection With The Ehrlichia Muris-Like (Eml) Agent, Of Ixodes Scapularis Removed From Soldiers In The Midwestern And Northeastern United States Over A 15 Year Period (1997-2012), Ellen Stromdahl, Sarah Hamer, Sarah Jenkins, Lynne Sloan, Phillip Williamson, Erik Foster, Robyn Nadolny, Chad Elkins, Mary Vince, Bobbi Pritt

Biological Sciences Faculty Publications

Background: Since 1997, human-biting ticks submitted to the Department of Defense Human Tick Test Kit Program (HTTKP) of the US Army Public Health Command have been tested for pathogens by PCR. We noted differences in the phenology and infection prevalence among Ixodes scapularis ticks submitted from military installations in different geographic regions. The aim of this study was to characterize these observed differences, comparing the phenology and pathogen infection rates of I. scapularis submitted from soldiers at two sites in the upper Midwest ( Camp Ripley, MN, and Ft. McCoy, WI) and one site in the northeastern US (Ft. Indiantown …

Fine Tuning A Well-Oiled Machine: Influence Of Nk1.1 And Nkg2d On Nkt Cell Development And Function, Sunil K. Joshi, Mark L. Lang

Bioelectrics Publications

Natural killer T cells (NKT) represent a group of CD1d-restricted T-lineage cells that provide a functional interface between innate and adaptive immune responses in infectious disease, cancer, allergy and autoimmunity. There have been remarkable advances in understanding the molecular events that underpin NKT development in the thymus and in the complex array of functions in the periphery. Most functional studies have focused on activation of T cell antigen receptors expressed by NKT cells and their responses to CD1d presentation of glycolipid and related antigens. Receiving less attention has been several molecules that are hallmarks of Natural Killer (NK) cells, but …

The Role Of P38 Mapk In The Aetiopathogenesis Of Psoriasis And Psoriatic Arthritis, Athanasios Mavropoulos, Eirini I. Rigopoulou, Christos Liaskos, Dimitrios P. Bogdanos, Lazaros I. Sakkas

Biological Sciences Faculty Publications

The pathogenetic mechanisms responsible for the induction of immune-mediated disorders, such as psoriasis, remain not well characterized. Molecular signaling pathways are not well described in psoriasis, as well as psoriatic arthritis, which is seen in up to 40% of patients with psoriasis. Signaling pathway defects have long been hypothesized to participate in the pathology of psoriasis, yet their implication in the altered psoriatic gene expression still remains unclear. Emerging data suggest a potential pathogenic role for mitogen activated protein kinases p38 (p38 MAPK) extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) in the development of psoriasis. The data …

Correlates Of Consistent Condom Use Among Female Entertainment Workers In Shanghai, China: A Repeated Measures Analysis, Xiushi Yang, Guomei Xia

Sociology & Criminal Justice Faculty Publications

Female entertainment workers (FEWs) in China are at increased risk of HIV and other sexually transmitted infections, but correlates of their risky sexual behaviour remain poorly understood. Using data from a series of four surveys, this paper employs repeated measures analysis to identify individual and social correlates of consistent condom use among FEWs in Shanghai. Results reveal that both individual cognitive and social influence factors are statistically significant in their bivariate relationships to consistent condom use with a stable or non-stable partner; only prevention motivation and perceived self-efficacy in condom use remain significant in the multiple regressions. When individual and …

In Vitro Propagation Of Candidatus Rickettsia Andeanae Isolated From Amblyomma Maculatum, Alison Luce-Fedrow, Chelsea Wright, Holly D. Gaff, Daniel E. Sonenshine, Wayne L. Hynes, Allen L. Richards

Biological Sciences Faculty Publications

Candidatus Rickettsia andeanae was identified during an investigation of a febrile outbreak in northwestern Peru (2002). DNA sequencing from two ticks (Amblyomma maculatum, Ixodes boliviensis) collected during the investigation revealed a novel Rickettsia agent with similarity to the spotted fever group rickettsiae. Since then, Candidatus R. similar to andeanae has been detected in A. maculatum ticks collected in the southeastern and southcentral United States, Argentina, and Peru. To date, Candidatus R. andeanae has not been successfully cultivated in the laboratory. We present evidence for the continuous cultivation in three cell lines of Candidatus R. similar to …

The Fecal Viral Flora Of Wild Rodents, Tung G. Phan, Beatrix Kapusinszky, Chunlin Wang, Robert K. Rose, Howard L. Lipton, Eric L. Delwart

Biological Sciences Faculty Publications

The frequent interactions of rodents with humans make them a common source of zoonotic infections. To obtain an initial unbiased measure of the viral diversity in the enteric tract of wild rodents we sequenced partially purified, randomly amplified viral RNA and DNA in the feces of 105 wild rodents (mouse, vole, and rat) collected in California and Virginia. We identified in decreasing frequency sequences related to the mammalian viruses families Circoviridae, Picobirnaviridae, Picornaviridae, Astroviridae, Parvoviridae, Papillomaviridae, Adenoviridae, and Coronaviridae. Seventeen small circular DNA genomes containing one or two replicase genes distantly related to the Circoviridae representing several potentially …

Rickettsia Parkeri In Gulf Coast Ticks, Southeastern Virginia, Usa, Chelsea L. Wright, Robyn M. Nadolny, Ju Jiang, Allen L. Richards, Daniel E. Sonenshine, Holly D. Gaff, Wayne L. Hynes

Biological Sciences Faculty Publications

We report evidence that Amblyomma maculatum tick populations are well established in southeastern Virginia. We found that 43.1% of the adult Gulf Coast ticks collected in the summer of 2010 carried Rickettsia parkeri, suggesting that persons living in or visiting southeastern Virginia are at risk for infection with this pathogen.

Estimating The Impact Of Human Papillomavirus (Hpv) Vaccination On Hpv Prevalence And Cervical Cancer Incidence In Mali, Leree Tracy, Holly Gaff, Colleen Burgess, Samba Sow, Patti E. Gravitt, J. Kathleen Tracy

Biological Sciences Faculty Publications

Human papillomavirus vaccines have potential to reduce cervical cancer incidence and mortality; however, cultural and economic barriers may hinder success in developing countries. We assessed impact of a single vaccine campaign in Mali with use of mathematical modeling. Our model shows that decreases in the prevalence of Human papillomavirus infection are proportional to achieved vaccination coverage.

Efficacy Of The Pentavalent Rotavirus Vaccine, Rotateq (Rv5), Between Doses Of A 3-Dose Series And With Less Than 3 Doses (Incomplete Regimen), Penelope D. Dennehy, Timo Vesikari, David O. Matson, Robbin F. Itzler, Michael J. Dallas, Michelle G. Goveia, Mark J. Dinubile, Penny M. Heaton, Max Ciarlet

Community & Environmental Health Faculty Publications

Post-hoc analyses of the Rotavirus Efficacy and Safety Trial (RES T) were conducted to determine whether the pentavalent rotavirus vaccine (RV5) confers early protection against rotavirus gastroenteritis (RVGE) before completion of the 3-dose regimen. To evaluate the efficacy of RV5 between doses in reducing the rates of RVGE-related hospitalizations and emergency department (ED) visits in infants who ultimately received all 3 doses of RV5/placebo, events occurring from 2 weeks after the first and second doses to receipt of the subsequent dose (Analysis A) and events occurring from 2 weeks after the first and second doses to 2 weeks after the …

Mathematical Model To Assess The Relative Effectiveness Of Rift Valley Fever Countermeasures, Holly Gaff, Colleen Burgess, Jacqueline Jackson, Tianchan Niu, Yiannis Papelis, David Hartley

Biological Sciences Faculty Publications

Mathematical modeling of infectious diseases is increasingly used to explicate the mechanics of disease propagation, impact of controls, and sensitivity of countermeasures. The authors demonstrate use of a Rift Valley Fever (RVF) model to study efficacy of countermeasures to disease transmission parameters. RVF is a viral infectious disease that propagates through infected mosquitoes and primarily affects animals but also humans. Vaccines exist to protect against the disease but there is lack of data comparing efficacy of vaccination with alternative countermeasures such as managing mosquito population or destroying infected livestock. This paper presents a compartmentalized multispecies deterministic ordinary differential equation model …

Estimating The Reproductive Numbers For The 2008-2009 Cholera Outbreaks In Zimbabwe, Zindoga Mukandavire, Shu Liao, Jin Wang, Holly Gaff, David L. Smith, J. Glenn Morris Jr.

Biological Sciences Faculty Publications

Cholera remains an important global cause of morbidity and mortality, capable of causing periodic epidemic disease. Beginning in August 2008, a major cholera epidemic occurred in Zimbabwe, with 98,585 reported cases and 4,287 deaths. The dynamics of such outbreaks, particularly in nonestuarine regions, are not well understood. We explored the utility of mathematical models in understanding transmission dynamics of cholera and in assessing the magnitude of interventions necessary to control epidemic disease. Weekly data on reported cholera cases were obtained from the Zimbabwe Ministry of Health and Child Welfare (MoHCW) for the period from November 13, 2008 to July 31, …

Distinct Macrophage Subpopulations Regulate Viral Encephalitis But Not Viral Clearance In The Cns, Christina D. Steel, Woong-Ki Kim, Larry Sanford, Laurie Wellman, Sandra Burnett, Nico Van Rooijen, Rochard P. Ciavarra

Biological Sciences Faculty Publications

Intranasal application of vesicular stomatitis virus (VSV) induces acute encephalitis characterized by a pronounced myeloid and T cell infiltrate. The role of distinct phagocytic populations on VSV encephalitis was therefore examined in this study. Ablation of peripheral macrophages did not impair VSV encephalitis or viral clearance from the brain, whereas, depletion of splenic marginal dendritic cells impaired this response and enhanced morbidity/mortality. Selective depletion of brain perivascular macrophages also suppressed this response without altering viral clearance. Thus, two anatomically distinct phagocytic populations regulate VSV encephalitis in a non-redundant fashion although neither population is essential for viral clearance in the CNS. …

Cd1d-Dependent B-Cell Help By Nk-Like T Cells Leads To Enhanced And Sustained Production Of Bacillus Anthracis Lethal Toxin-Neutralizing Antibodies, T. Scott Devera, Lindsay M. Aye, Gillian A. Lang, Sunil K. Joshi, Jimmy D. Ballard, Mark L. Lang

Bioelectrics Publications

The current Bacillus anthracis vaccine consists largely of protective antigen (PA), the protein of anthrax toxin that mediates entry of edema factor (EF) or lethal factor (LF) into cells. PA induces protective antibody (Ab)-mediated immunity against Bacillus anthracis but has limited efficacy and duration. We previously demonstrated that activation of CD1d-restricted natural killer-like T cells (NKT) with a CD1d-binding glycolipid led to enhanced Ab titers specific for foreign antigen (Ag). We therefore tested the hypothesis that activation of NKT cells with the CD1d ligand (alpha-galactosylceramide [alpha-GC]) at the time of immunization improves PA-specific Ab responses. We observed that alpha-GC enhanced …

Ecological Interactions Between Spiders And The Purple Pitcher Plant, Sarracenia Purpurea, Marc Aaron Milne

Biological Sciences Theses & Dissertations

Spiders and harvestmen are commonly captured by or reside upon the carnivorous purple pitcher plant, Sarracenia purpurea. Although spiders and harvestmen are often known to be prey of S. purpurea, other ecological interactions between these arthropods and the plant are poorly understood. Studies were undertaken at three pitcher plant populations, two in Virginia and one in North Carolina, to assess the ecological relationships between spiders and harvestmen and S. purpurea. Multiple plots containing pitcher plants (treatment) and plots lacking pitcher plants (control) were created at these locations. Spiders and harvestmen were collected through five different techniques. Spatial, …

Robustness Of The Healthcare Utilization Results From The Rotavirus Efficacy And Safety Trial (Rest) Evaluating The Human-Bovine (Wc3) Reassortant Pentavalent Rotavirus Vaccine (Rv5), Robbin Itzler, Gary Koch, David O. Matson, Leif Gothefors, Pierre Van Damme, Mark J. Dinubile, Penny M. Heaton

Community & Environmental Health Faculty Publications

Background: The Rotavirus Efficacy and Safety Trial was a placebo-controlled Phase III study that evaluated the safety and efficacy of a three-dose pentavalent rotavirus vaccine (RV5) including its effect on healthcare utilization for rotavirus gastroenteritis (RVGE). The per-protocol (PP) analyses, which counted events occurring 14 days after dose 3 among infants without protocol violations, have already been published. This paper evaluates the consistency of the healthcare utilization results based on the modified intention to treat (MITT) analyses with the PP analyses. The MITT analyses include all infants receiving at least one dose of vaccine or placebo and follow-up begins after …

Chloroquine Susceptibility And Reversibility In A Plasmodium Falciparum Genetic Cross, Jigar J. Patel, Drew Thacker, John C. Tan, Perri Pleeter, Lisa Checkley, Joseph M. Gonzales, Bingbing Deng, Paul D. Roepe, Roland A. Cooper, Michael T. Ferdig

Biological Sciences Faculty Publications

Mutations in the Plasmodium falciparum chloroquine (CQ) resistance transporter (PfCRT) are major determinants of verapamil (VP)-reversible CQ resistance (CQR). In the presence of mutant PfCRT, additional genes contribute to the wide range of CQ susceptibilities observed. It is not known if these genes influence mechanisms of chemosensitization by CQR reversal agents. Using quantitative trait locus (QTL) mapping of progeny clones from the HB3 x Dd2 cross, we show that the P. falciparum multidrug resistance gene 1 (pfmdr1) interacts with the South-East Asia-derived mutant pfcrt haplotype to modulate CQR levels. A novel chromosome 7 locus is predicted to contribute …

A Review Of The Lethal Spiny Lobster Virus Pav1 - Ten Years After Its Discovery, Donald C. Behringer, Mark J. Butler Iv, Jeffrey D. Shields

Biological Sciences Faculty Publications

In 1999, we discovered that juvenile Caribbean spiny lobsters (Panulirus argus) in the Florida Keys were infected with PaV1 (Panulirus argus virus 1), the first naturally occurring pathogenic virus reported from lobsters. The virus profoundly affects their biology and ecology. PaV1 is probably wide-spread in the Caribbean with confirmed infections from the United States (Florida), St Croix, Mexico, and Belize; and anecdotal reports from the Bahamas and Cuba. Mean prevalence in the Florida Keys has been stable since 1999 (5 - 8%), but has risen from 2.7% to 10.9% in Mexico (Puerto Morelos), the only other country where …

Lipid Targets Of The Antimalarial Trioxanes In Plasmodium Falciparum, Carmony Leah Hartwig

Biological Sciences Theses & Dissertations

Malaria is among the most debilitating diseases of man. The protozoan parasite, Plasmodium falciparum, causes over a million annual fatalities. The antimalarial trioxanes, exemplified by artemisinin, are among the few pharmaceuticals for which clinical resistance has not become widespread. Artemisinin is a naturally occurring sesquiterpene lactone, containing a unique endoperoxide pharmacophore. Despite extensive study, the precise antimalarial mechanism of action of trioxanes remains elusive. Heme iron-mediated cleavage of the endoperoxide within the parasite digestive vacuole is hypothesized to generate cytotoxic metabolites capable of alkylating heme and damaging cellular macromolecules. The hypothesis of this research is that the endoperoxide pharmacophore …

Comparison Of Immune Correlates, Age Related Changes And Proteomic Profiling Of Healthy Individuals Receiving Influenza Vaccines, Gaurav Basu

Theses and Dissertations in Biomedical Sciences

The burden of influenza related infections is substantial, both in terms of illness, lives lost and economic impact on society. The degree of impact of influenza related infections is much higher in the elderly population where it is a leading cause of catastrophic disability; greatly affecting the quality of life of elderly persons above 65 years of age. Vaccination is the mainstay for control and prevention of influenza infections. There are two vaccine formulations that are licensed for use at present. The inactivated influenza vaccines (TIIV) which have been used for 60 years in all age groups and the new …

Do Hospitalists Or Physicians With Greater Inpatient Hiv Experience Improve Hiv Care In The Era Of Highly Active Antiretroviral Therapy? Results From A Multicenter Trial Of Academic Hospitalists, John A. Schneider, Qi Zhang, Andrew Auerbach, David Gonzales, Peter Kaboli, Jeffrey Schnipper, Tosha B. Wetterneck, David L. Pitrak, David O. Meltzer

Community & Environmental Health Faculty Publications

Background. Little is known about the effect of provider type and experience on outcomes, resource use, and processes of care of hospitalized patients with human immunodeficiency virus (HIV) infection. Hospitalists are caring for this population with increasing frequency.

Methods. Data from a natural experiment in which patients were assigned to physicians on the basis of call cycle was used to study the effects of provider type—that is, hospitalist versus non hospitalist—and HIV-specific inpatient experience on resource use, outcomes, and selected measures of processes of care at 6 academic institutions. Administrative data, inpatient interviews, 30-day follow-up interviews, and the National Death …