Infectious Disease Commons^™

Divergent Antibody Subclass And Specificity Profiles But Not Protective Hla-B Alleles Are Associated With Variable Antibody Effector Function Among Hiv-1 Controllers, Jennifer I. Lai, Anna F. Licht, Anne-Sophie Dugast, Todd Suscovich, Ickwon Choi, Chris Bailey-Kellogg, Galit Alter, Margaret E. Ackerman

Dartmouth Scholarship

Understanding the coordination between humoral and cellular immune responses may be the key to developing protective vaccines, and because genetic studies of long-term HIV-1 nonprogressors have associated specific HLA-B alleles with spontaneous control of viral replication, this subject group presents an opportunity to investigate relationships between arms of the adaptive immune system. Given evidence suggesting that cellular immunity may play a role in viral suppression, we sought to determine whether and how the humoral immune response might vary among controllers. Significantly, Fc-mediated antibody effector functions have likewise been associated with durable viral control. In this study, we compared the effector …

Global Mortality Estimates For The 2009 Influenza Pandemic From The Glamor Project: A Modeling Study, Lone Simonsen, Peter Spreeuwenberg, Roger Lustig, Robert J. Taylor, Douglas M. Fleming, Madelon Kroneman, Maria D. Van Kerkhove, Anthony D. Mounts, W. John Paget

Global Health Faculty Publications

Background

Assessing the mortality impact of the 2009 influenza A H1N1 virus (H1N1pdm09) is essential for optimizing public health responses to future pandemics. The World Health Organization reported 18,631 laboratory-confirmed pandemic deaths, but the total pandemic mortality burden was substantially higher. We estimated the 2009 pandemic mortality burden through statistical modeling of mortality data from multiple countries.

Methods and Findings

We obtained weekly virology and underlying cause-of-death mortality time series for 2005–2009 for 20 countries covering ~35% of the world population. We applied a multivariate linear regression model to estimate pandemic respiratory mortality in each collaborating country. We then used …

Salmonella Cholecystitis: Atypical Presentation Of A Typical Condition, Rehan Ali, Shakeel Ahmed, Maqbool Qadir, Huba Atiq, Muhammad Hamid

Department of Emergency Medicine

Salmonella cholecystitis is a rare but important complication of Salmonella typhi infection. We are reporting an 11 years old female child who presented with complaints of high-grade fever, jaundice and right sided abdominal pain (Charcot's triad). Her examination showed tender hepatomegaly. Initial blood results revealed high white cell counts with left shift, deranged liver function tests. Abdominal ultrasonography revealed distended gallbladder with minimal layer of sludge seen within its lumen along with streak of pericholecystic fluid. Blood culture grew Salmonella typhi. She was successfully treated with intravenous ceftriaxone.

Healthcare-Associated Infections-Is Targeting Zero A Global Reality?, Mary Lou Manning Phd, Crnp, Cic, Faan, Denise Murphy Rn, Mph, Cic, Faan

Population Health Matters (Formerly Health Policy Newsletter)

No abstract provided.

Snapin, Positive Regulator Of Stimulation- Induced Ca(2+) Release Through Ryr, Is Necessary For Hiv-1 Replication In T Cells., Shigemi M Kinoshita, Amane Kogure, Shizuka Taguchi, Garry P Nolan

Department of Microbiology and Immunology Faculty Papers

To identify critical host factors necessary for human immunodeficiency virus 1 (HIV-1) replication, large libraries of short-peptide-aptamers were expressed retrovirally. The target of one inhibitor peptide, Pep80, identified in this screen was determined to be Snapin, a protein associated with the soluble N-ethyl maleimide sensitive factor adaptor protein receptor (SNARE) complex that is critical for calcium-dependent exocytosis during neurotransmission. Pep80 inhibited Ca(2+) release from intracellular stores and blocked downstream signaling by direct interruption of the association between Snapin and an intracellular calcium release channel, the ryanodine receptor (RyR). NFAT signaling was preferentially abolished by Pep80. Expression of Snapin overcame Pep80-mediated …

Defining The Vulnerable Period For Re-Establishment Of Clostridium Difficile Colonization After Treatment Of C. Difficile Infection With Oral Vancomycin Or Metronidazole, Venkata C.K. Sunkesula, Sirisha Kundrapu, Robin L. Jump, Curtis J. Donskey

Faculty Scholarship

Background:Clostridium difficile is an anaerobic, spore-forming bacterium that is the most common cause of healthcare-associated diarrhea in developed countries. A significant proportion of patients receiving oral vancomycin or metronidazole for treatment of Clostridium difficile infection (CDI) develop recurrences. However, the period of vulnerability to re-establishment of colonization by C. difficile after therapy is not well defined.Principal Findings:In a prospective study of CDI patients, we demonstrated that most vancomycin-treated patients maintained inhibitory concentrations of vancomycin in stool for 4 to 5 days after therapy, whereas metronidazole was only detectable during therapy. From the time of elimination of the antibiotics to 14 …

Photo Quiz: Young Girl With Cough, Headache, And Visual Loss., Aisha Ilyas, Naima Fasih, Kauser Jabeen, Ehsan Bari, Syed Faisal Mahmood

Department of Medicine

No abstract provided.

Pseudomonas Aeruginosa Exotoxin Y-Mediated Tau Hyperphosphorylation Impairs Microtubule Assembly In Pulmonary Microvascular Endothelial Cells, Ron Balczon, Nutan Prasain, Cristhiaan Ochoa, Jason Prater, Bing Zhu, Mikhail Alexeyev, Sarah Sayner, Dara W. Frank, Troy Stevens

University Faculty and Staff Publications

Pseudomonas aeruginosa uses a type III secretion system to introduce the adenylyl and guanylyl cyclase exotoxin Y (ExoY) into the cytoplasm of endothelial cells. ExoY induces Tau hyperphosphorylation and insolubility, microtubule breakdown, barrier disruption and edema, although the mechanism(s) responsible for microtubule breakdown remain poorly understood. Here we investigated both microtubule behavior and centrosome activity to test the hypothesis that ExoY disrupts microtubule dynamics. Fluorescence microscopy determined that infected pulmonary microvascular endothelial cells contained fewer microtubules than control cells, and further studies demonstrated that the microtubule-associated protein Tau was hyperphosphorylated following infection and dissociated from microtubules. Disassembly/reassembly studies determined that …

Potential Health Impacts Of Heavy Metals On Hiv-Infected Population In Usa, Xiaohui Xu, Hui Hu, Amy B. Dailey, Greg Kearney, Evelyn O. Talbott, Robert L. Cook

Health Sciences Faculty Publications

Purpose: Noninfectious comorbidities such as cardiovascular diseases have become increasingly prevalent and occur earlier in life in persons with HIV infection. Despite the emerging body of literature linking environmental exposures to chronic disease outcomes in the general population, the impacts of environmental exposures have received little attention in HIV-infected population. The aim of this study is to investigate whether individuals living with HIV have elevated prevalence of heavy metals compared to non-HIV infected individuals in United States.

Methods: We used the National Health and Nutrition Examination Survey (NHANES) 2003-2010 to compare exposures to heavy metals including cadmium, lead, and total …

Multicenter Study Of High-Dose Daptomycin For Treatment Of Enterococcal Infections, Anthony M. Casapao, Ravina Kullar, Susan L. Davis, Donald P. Levine, Jing J. Zhao, Brian A. Potoski, Debra A. Goff, Christopher W. Crank, John Segreti, George Sakoulas, Sara E. Cosgrove, Michael J. Rybak

Internal Medicine Faculty Publications

Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggests that daptomycin > 6mg/kg/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (> 6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two-hundred and forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by 49 (20%) Enterococcus faecalis and 21 (9%) Enterococcus spp., overall 204 (83%) were VRE. Enterococcal infections included bacteremia (173, 71%), intra-abdominal (35, …

Ultrasound Based Evaluation Of Hepatic Steatosis And Fibrosis In Hepatitis C Non-Responders, Saba Sohail, Sina Aziz, Talat Mirza

Department of Radiology

Objective: To determine the accuracy of ultrasound in the diagnosis and grading of steatosis and fibrosis in Hepatitis C (HCV) patients not responding to ribavarin-interferon therapy.
Study design: A cross-sectional, analytical study.
Place and duration of study: Radiology Department, Civil Hospital, Karachi, from March 2008 to August 2010.
Methodology: Patients with positive HCV RNA despite 24 weeks ribavarin-interferon therapy (non-responders) were subjected to ultrasound and biopsy prior to institution of pegylated interferon therapy for detection and grading of steatosis and fibrosis. Using histopathology as the gold standard, sensitivity, specificity, negative and positive predictive values for ultrasound were determined.
Results: The …

Pouring Salt On A Wound: Pseudomonas Aeruginosa Virulence Factors Alter Na+ And Cl− Flux In The Lung, Alicia E. Ballok, George A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa is a ubiquitous opportunistic pathogen with multiple niches in the human body, including the lung. P. aeruginosa infections are particularly damaging or fatal for patients with ventilator-associated pneumonia, chronic obstructive pulmonary disease, and cystic fibrosis (CF). To establish an infection, P. aeruginosa relies on a suite of virulence factors, including lipopolysaccharide, phospholipases, exoproteases, phenazines, outer membrane vesicles, type III secreted effectors, flagella, and pili. These factors not only damage the epithelial cell lining but also induce changes in cell physiology and function such as cell shape, membrane permeability, and protein synthesis. While such virulence factors are important in …

Acute Glomerulonephritis In A Child With Chlamydia Pneumoniae Infection: A Case Report., Giovanna Vitaliti, Raffaele Falsaperla, Leandra Giunta, Giuseppina Spataro, Venerando Rapisarda, Mario Velardita, Giuseppe Nunnari, Piero Pavone

Division of Infectious Diseases and Environmental Medicine Faculty Papers

Background. Infectious diseases seem to be an important and independent risk factor for renal failure, but the underlying mechanism of renal involvement during some kinds of infectious diseases is still unclear, even if the literature data report immunomediated and/or autoimmune mechanisms to explain the pathogenic relationship between the two diseases. In paediatric patients, Chlamydia pneumoniae is a rare cause of renal complications and it may manifest in several ways, mainly involving the respiratory system, even if also renal and glomerulalr complications, have been described. Case Diagnosis/Treatment. Herein we report a case of a 3-year-old child who developed an acute glomerulonephritis …

Effectiveness Of Pentavalent And Monovalent Rotavirus Vaccines In Concurrent Use Among Us Children <5 Years Of Age, 2009-2011, Daniel C. Payne, Julie A. Boom, Mary Allen Staat, Kathryn M. Edwards, Peter G. Szilagyi, Eileen J. Klein, Rangaraj Selvarangan, Parvin H. Azimi, Christopher J. Harrison, Mary Moffatt, Samantha H. Johnston, Leila C. Sahni, Carol J, Baker, Marcia A. Rench, Stephanie Donauer, Monica Mcneal, James Chappell, Geoffrey A. Weinberg, Azadeh Tasslimi, Jacqueline E. Tate, Mary Wikswo, Aaron T. Curns, Iddrisu Sulemana, Slavica Mijatovic-Rustempasic, Mathew D. Esona, Michael D. Bowen, Jon R. Gentsch, Umesh D. Parashar

Manuscripts, Articles, Book Chapters and Other Papers

Background We assessed vaccine effectiveness (VE) for RotaTeq (RV5; 3 doses) and Rotarix (RV1; 2 doses) at reducing rotavirus acute gastroenteritis (AGE) inpatient and emergency department (ED) visits in US children.

Methods We enrolled children vaccine, age, ethnicity, genotype, and clinical setting.

Results RV5-specific analyses included 359 rotavirus cases and 1811 rotavirus-negative AGE controls. RV1-specific analyses included 60 rotavirus cases and 155 rotavirus-negative AGE controls. RV5 and RV1 were 84% (95% confidence interval [CI], 78%-88%) and 70% (95% CI, 39%-86%) effective, respectively, against rotavirus-associated ED visits and hospitalizations combined. By clinical setting, RV5 VE against ED and inpatient rotavirus-associated visits …

To Bear Witness: A Journey Of Healing And Solidarity, Updated, Revised, And Expanded Edition, Kevin M. Cahill, M.D.

International Affairs

For more than fifty years, Dr. Cahill has been helping to heal the world, as a leading specialist in tropical medicine and as a driving force in humanitarian assistance and relief efforts around the globe. In this revised and expanded edition, he chronicles extraordinary achievements of compassion and commitment. Bringing together a rich selection of writings, he crafts a fascinating memoir of a life devoted to others. The book includes front-line reports from places under siege—Lebanon, Somalia, Sudan, Nicaragua, Gaza, and Ireland; there are also visionary essays from the origins of the AIDS epidemic and landmine crises, and no less …

Crash Course In United States Pharmacopeia Standard 797 (Usp 797): Investigation Of Positive Sterility Cultures From A Hospital Pharmacy Preparation, Terry Burger Mba, Bsn, Rn, Ne-Bc, Cic, Deborah Fry Mt (Ascp), Mba, Cic, Gary Tallarita Mt (Ascp), Cindy L. Mitman Pharm D

Department of Medicine

No abstract provided.

A Comparison Of Who Guidelines Issued In 1997 And 2009 For Dengue Fever - Single Centre Experience., Munawar Khursheed, Uzma R. Khan, Kiran Ejaz, Jabeen Fayyaz, Irum Qamar, J. Razzak

Department of Emergency Medicine

Objective: To compare the original (1997) and revised (2009) versions of World Health Organization guidelines for dengue patients
Methods: Adult patients with a positive dengue Immunoglobulin M serology, and a diagnosis of dengue were included in the study at Aga Khan University Hospital during a three-year period from January 2005 to December 2007. Data related to these dengue patients was collected from their medical records. Guidelines were then applied by the research assistant and correlation among these guidelines was computed. SPSS 19 was used for statistical analysis.
Results: A total of 612 patients were found with a diagnosis of dengue, …

B Cell Response And Hemagglutinin Stalk-Reactive Antibody Production In Different Age Cohorts Following 2009 H1n1 Influenza Virus Vaccination, Mark Y. Sangster, Jane Baer, Felix W. Santiago, Theresa T. Fitzgerald, Natalia A. Ilyushina

Dartmouth Scholarship

The 2009 pandemic H1N1 (pH1N1) influenza virus carried a swine-origin hemagglutinin (HA) that was closely related to the HAs of pre-1947 H1N1 viruses but highly divergent from the HAs of recently circulating H1N1 strains. Consequently, prior ex- posure to pH1N1-like viruses was mostly limited to individuals over the age of about 60 years. We related age and associated dif- ferences in immune history to the B cell response to an inactivated monovalent pH1N1 vaccine given intramuscularly to subjects in three age cohorts: 18 to 32 years, 60 to 69 years, and >70 years. The day 0 pH1N1-specific hemagglutination inhibition (HAI) …

Evaluation Of Clinical Outcomes Of Prophylactic Versus Preemptive Cytomegalovirus Strategy In Liver Transplant Recipients, Ifeanyi Onor, Sarah Todd, Erika Meredith, Sebastian Perez, Aneesh Mehta, G Lyon, Stuart Knechtle, Steven Hanish

Faculty and Staff Publications

Cytomegalovirus (CMV) is a major cause of morbidity and mortality following solid organ transplantation (SOT). Two strategies, prophylactic, and preemptive have emerged for the prevention of CMV infection and disease after SOT. This retrospective chart review of two liver transplant cohorts: prophylactic and preemptive, compares the clinical impact of transitioning from prophylactic to preemptive strategy. The primary outcome is the incidence of CMV viremia at 3-and 6-months post-transplant. Secondary outcomes include: incidence of CMV tissue-invasive disease, acute cellular rejection, leukopenia and neutropenia, opportunistic infection rates, hospital readmission rates, and mortality at 3-and 6-months post-transplant. A total of 109 patients were …

Closing The Gap: Revising Sterility Testing Policies And Procedures Based On The United States Pharmacopeia (Usp) 797 Guidelines And A Near Miss, Cindy L. Mitman Pharm D, Terry Burger Mba, Bsn, Rn, Ne-Bc, Cic, Deborah Fry Mt (Ascp), Mba, Cic, Gary Tallarita Mt (Ascp)

Department of Medicine

No abstract provided.

Anr And Its Activation By Plch Activity In Pseudomonas Aeruginosa Host Colonization And Virulence, Angelyca A. Jackson, Maegan J. Gross, Emily F. Daniels, Thomas H. Hampton, John H. Hammond, Isabelle Vallet-Gely, Simon L. Dove, Bruce A. Stanton, Deborah A. Hogan

Dartmouth Scholarship

Pseudomonas aeruginosa hemolytic phospholipase C (PlcH) degrades phosphatidylcholine (PC), an abundant lipid in cell membranes and lung surfactant. A ΔplcHR mutant, known to be defective in virulence in animal models, was less able to colonize epithelial cell monolayers and was defective in biofilm formation on plastic when grown in lung surfactant. Microarray analyses found that strains defective in PlcH production had lower levels of Anr-regulated transcripts than the wild type. PC degradation stimulated the Anr regulon in an Anr-dependent manner under conditions where Anr activity was submaximal because of the presence of oxygen. Two PC catabolites, choline and glycine …

History And Hope: The International Humanitarian Reader, Kevin M. Cahill, M.D.

Institute of International Humanitarian Affairs

History and Hope: The International Humanitarian Reader provides a better understanding—both within and outside academia—of the multifaceted demands posed by humanitarian assistance programs. The Reader is a compilation of the most important chapters in the twelve-volume International Humanitarian Affairs book series published by Fordham University Press. Each selected chapter has been edited and updated. In addition, the series editor, Kevin M. Cahill, M.D., has written, among other chapters, an introductory essay explaining the academic evolution of the discipline of humanitarian assistance. It focuses on the “Fordham Experience”: its Institute of International Humanitarian Affairs (IIHA) has developed practical programs for training …

Beliefs About Complementary And Alternative Medicine In Hiv-Infected Black Women Using The Theory Of Planned Behavior, Stephanie G. Lino

Loma Linda University Electronic Theses, Dissertations & Projects

Background. Black women make up 12% of the female population in the U.S, yet they account for 66% of new HIV infections. In 2002, AIDS was the most cited reason for death among Black women age 25-34. While prevention remains, a major effort targeting treatment efficacy and modalities for this sub-group need to be better understood.

Purpose. The purpose of this study is to assess whether HIV-positive Black women’s attitudes, subjective norms and perceived behavioral control are related to intention of dietary supplements and spiritual practices use in their HIV treatment.

Method. In phase one, Grounded Theory methods (N= …

Listeria Monocytogenes Cholecystitis: A Possible New Syndrome., Jackrapong Bruminhent, Timothy K Lynch, Jonathan Gefen, Jerome Santoro

Division of Internal Medicine Faculty Papers & Presentations

: The U.S. Food and Drug Administration recently added potentially fatal Listeria monocytogenes infection to the list of opportunistic infections that can occur in patients who receive tumor necrosis factor inhibitor therapy. In this study, the first reported case of L monocytogenes cholecystitis associated with etanercept use is described. It also appears that tumor necrosis factor inhibitor therapy likely increases the risk for Listeria cholecystitis. Clinicians need to be aware of this association when selecting antimicrobial therapy for these patients.

Antibody Quality And Protection From Lethal Ebola Virus Challenge In Nonhuman Primates Immunized With Rabies Virus Based Bivalent Vaccine., Joseph E Blaney, Andrea Marzi, Mallory Willet, Amy B Papaneri, Christoph Wirblich, Friederike Feldmann, Michael Holbrook, Peter Jahrling, Heinz Feldmann, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

We have previously described the generation of a novel Ebola virus (EBOV) vaccine platform based on (a) replication-competent rabies virus (RABV), (b) replication-deficient RABV, or (c) chemically inactivated RABV expressing EBOV glycoprotein (GP). Mouse studies demonstrated safety, immunogenicity, and protective efficacy of these live or inactivated RABV/EBOV vaccines. Here, we evaluated these vaccines in nonhuman primates. Our results indicate that all three vaccines do induce potent immune responses against both RABV and EBOV, while the protection of immunized animals against EBOV was largely dependent on the quality of humoral immune response against EBOV GP. We also determined if the induced …

Effects Of Clostridium Difficile On The Human Immune Response, Mike Mcgovern

Honors Projects in Science and Technology

Clostridium difficile is a bacterium that is rapidly becoming a large issue in the medical community due to its tendency to infect hospital patients and its resistance to antibiotics. By studying the way in which the pathogen interacts with the human immune system, it is possible to better understand how the body naturally fights off the disease. This knowledge can allow medical professionals to develop treatments that can help curtail the infection before serious symptoms occur. Working under a grant program alongside Professors Kirsten Hokeness and Chris Reid, I was able to research the effects that exposure to the C. …

Perception Of Disease Risk And Vulnerability As A Function Of Proximity To National Park Boundaries In East Africa, Irene Bridget Feretti

Honors Theses and Capstones

Studies suggest households closest to parks and protected areas (PAs) are more likely to sustain park-related losses, but the relationship between human sickness and PAs has not been fully explored. Existing literature primarily focuses on human-wildlife conflicts (i.e. crop raiding) and the potential for zoonotic disease spillover and emergence at the human-livestock-wildlife interface at PA boundaries. Understanding local perceptions of disease risk and vulnerability is essential for assessing human health relative to conservation areas. This understanding will promote better-informed consideration of human health impacts in decision making for conservation. Data from surveys taken at 301 households around Kibale National Park …

Infective Endocarditis In The U.S., 1998–2009: A Nationwide Study, David H. Bor, Steffie Woolhandler, Rachel Nardin, David Brusch, David U. Himmelstein

Publications and Research

Background
Previous studies based on local case series estimated the annual incidence of endocarditis in the U.S. at about 4 per 100,000 population. Small-scale studies elsewhere have reported similar incidence rates. However, no nationally-representative population-based studies have verified these estimates.

Methods and Findings
Using the 1998–2009 Nationwide Inpatient Sample, which provides diagnoses from about 8 million U.S. hospitalizations annually, we examined endocarditis hospitalizations, bacteriology, co-morbidities, outcomes and costs. Hospital admissions for endocarditis rose from 25,511 in 1998 to 38, 976 in 2009 (12.7 per 100,000 population in 2009). The age-adjusted endocarditis admission rate increased 2.4% annually. The proportion of patients …

First Steps Phase I Initiative: Improving Immunizations For Children And Adolescents, Kimberley S. Fox Mpa, Carolyn E. Gray Mph

Population Health & Health Policy

This evalution report, authored by research staff at the USM Muskie School, assesses the change in immunization rates in participating pediatric and family practices that serve a high volume of children insured by MaineCare (Maine's Medicaid system). The authors also summarize lessons learned in implementing changes in practices and challenges in using the immunization measures at the practice-level to inform quality improvement.

Lps And Pan-Induced Podocyte Injury In An In Vitro Model Of Minimal Change Disease: Changes In Tlr Profile., Tarak Srivastava, Mukut Sharma, Kok-Hooi Yew, Ram Sharma, R Scott Duncan, Moin A. Saleem, Ellen T. Mccarthy, Alexander Kats, Patricia A. Cudmore, Uri S. Alon, Christopher J. Harrison

Manuscripts, Articles, Book Chapters and Other Papers

Minimal change disease (MCD), the most common idiopathic nephrotic syndrome in children, is characterized by proteinuria and loss of glomerular visceral epithelial cell (podocyte) ultrastructure. Lipopolysaccharide (LPS) and puromycin aminonucleoside (PAN) are used to study podocyte injury in models of MCD in vivo and in vitro. We hypothesized that LPS and PAN influence components of the innate immune system in podocytes such as the Toll-Like Receptor (TLRs), TLR adapter molecules, and associated cytokines. Our results show that cultured human podocytes constitutively express TLRs 1-6 and TLR-10, but not TLRs 7-9. LPS (25 μg/ml) or PAN (60 μg/ml) caused comparable derangement …