Infectious Disease Commons^™

Site-Specific Mutation Of The Sensor Kinase Gras In Staphylococcus Aureus Alters The Adaptive Response To Distinct Cationic Antimicrobial Peptides, Ambrose L. Cheung, Arnold S. Bayer, Michael R. Yeaman, Yan Q. Xiong, Alan J. Waring, Guido Memmi, Niles Donegan

Dartmouth Scholarship

The Staphylococcus aureus two-component regulatory system, GraRS, is involved in resistance to killing by distinct host defense cationic antimicrobial peptides (HD-CAPs). It is believed to regulate downstream target genes such as mprF and dltABCD to modify the S. aureus surface charge. However, the detailed mechanism(s) by which the histidine kinase, GraS, senses specific HD-CAPs is not well defined. Here, we studied a well-characterized clinical methicillin-resistant S. aureus (MRSA) strain (MW2), its isogenic graS deletion mutant (ΔgraS strain), a nonameric extracellular loop mutant (ΔEL strain), and four residue-specific ΔEL mutants (D37A, P39A, P39S, and D35G D37G D41G strains). The ΔgraS and …

Social Network Analysis (Sna) Of Clark County, Nevada Tuberculosis (Tb) Case And Contact Investigation Data To Determine Pediatric Risk Factors For Disease Transmission, Darin Michael Cozatt

UNLV Theses, Dissertations, Professional Papers, and Capstones

Within the spectrum of childhood (infancy, early childhood, middle childhood, and adolescence), TB is a priority disease, and preventive care is recommended by the American Academy of Pediatrics (AAP)/Bright Futures initiative (AAP, 2008). Within the early childhood stage (15 months to 4 years), TB is classified as "HR2" (high risk 2), behind lead poisoning, which is "HR1" (AAP, 2008), the highest risk within this age range. Within the middle childhood stage (5 to 10 years), TB becomes an HR1. TB is preventable, and targeted screening is the best prevention method. The AAP/Bright Futures initiative further specifies the risk based on …

Surface Attachment Induces Pseudomonas Aeruginosa Virulence, Albert Siryaporn, Sherry L. Kuchma, George A. Ou2019toole, Zemer Gitai

Dartmouth Scholarship

Pseudomonas aeruginosa infects every type of host that has been examined by deploying multiple virulence factors. Previous studies of virulence regulation have largely focused on chemical cues, but P. aeruginosa may also respond to mechanical cues. Using a rapid imaging-based virulence assay, we demonstrate that P. aeruginosa activates virulence in response to attachment to a range of chemically distinct surfaces, suggesting that this bacterial species responds to mechanical properties of its substrates. Surface-activated virulence requires quorum sensing, but activating quorum sensing does not induce virulence without surface attachment. The activation of virulence by surfaces also requires the surface-exposed protein PilY1, …

Acidosis Potentiates The Host Proinflammatory Interleukin-1Β Response To Pseudomonas Aeruginosa Infection, I. M. Torres, Y. R. Patankar, Tamer B. Shabaneh, E. Dolben, Deborah Hogan, David Leib, Brent L. Berwin

Dartmouth Scholarship

Infection by Pseudomonas aeruginosa, and bacteria in general, frequently promotes acidification of the local microenvironment, and this is reinforced by pulmonary exertion and exacerbation. However, the consequence of an acidic environment on the host inflammatory response to P. aeruginosa infection is poorly understood. Here we report that the pivotal cellular and host proinflammatory interleukin-1β (IL-1β) response, which enables host clearance of the infection but can produce collateral inflammatory damage, is increased in response to P. aeruginosa infection within an acidic environment. Synergistic mechanisms that promote increased IL-1β release in response to P. aeruginosa infection in an acidic environment are …

Successful Mdr-Tb Treatment Regimens Including Amikacin Are Associated With High Rates Of Hearing Loss, Chawangwa Modongo, Rafal S. Sobota, Boikobo Kesenogile, Ronald Ncube

Dartmouth Scholarship

Aminoglycosides are a critical component of multidrug-resistant tuberculosis (MDR-TB) treatment but data on their efficacy and adverse effects in Botswana is scarce. We determined the effect of amikacin on treatment outcomes and development of hearing loss in MDR-TB patients. Patients started on MDR-TB treatment between 2006 and 2012 were included. Multivariate analysis was used to determine the effect of amikacin on treatment outcomes and development of hearing loss.

Intimate Partner Violence After Disclosure Of Hiv Test Results Among Pregnant Women In Harare, Zimbabwe, Simukai Shamu, Christina Zarowsky, Tamara Shefer, Marleen Temmerman, Naeemah Abrahams

Obstetrics and Gynaecology, East Africa

Background: HIV status disclosure is a central strategy in HIV prevention and treatment but in high prevalence settings women test disproportionately and most often during pregnancy. This study reports intimate partner violence (IPV) following disclosure of HIV test results by pregnant women.

Methods: In this cross sectional study we interviewed 1951 postnatal women who tested positive and negative for HIV about IPV experiences following HIV test disclosure, using an adapted WHO questionnaire. Multivariate regression models assessed factors associated with IPV after disclosure and controlled for factors such as previous IPV and other known behavioural factors associated with IPV.

Results: Over …

Prevalence Of Hepatitis B Virus Infection Among Barbers And Their Knowledge, Attitude And Practices In The District Of Sukkur, Sindh ., Imran Naeem Abbasi, Zafar Fatmi, Muhammad Masood Kadir, Nalini Sathiakumar

Community Health Sciences

Abstract

OBJECTIVES:

Several occupations in developing countries lag behind in ensuring the safety of their workers in occupational settings. Lack of implementation of safety guidelines at workplaces can expose workers to health risks. In Pakistan, barbers are one of the un-regulated occupational groups. Low literacy, increased frequency of direct skin contact and blade/razors use can expose barbers to body fluids including blood of the customers. We conducted this study in order to determine hepatitis B virus (HBV) prevalence among barbers and their knowledge, attitude and practices in a peri-urban district of Sindh.

MATERIAL AND METHODS:

Three hundred eighty-five barbers from …

The Association Of Meningococcal Disease With Influenza In The United States, 1989-2009, Jessica Hartman Jacobs, Cecile Viboud, Eric Tchetgen Tchetgen, Joel Schwartz, Claudia Steiner, Lone Simonsen, Marc Lipsitch

Global Health Faculty Publications

Importance and Objective

Prior influenza infection is a risk factor for invasive meningococcal disease. Quantifying the fraction of meningococcal disease attributable to influenza could improve understanding of viral-bacterial interaction and indicate additional health benefits to influenza immunization.

Design, Setting and Participants

A time series analysis of the association of influenza and meningococcal disease using hospitalizations in 9 states from 1989–2009 included in the State Inpatient Databases from the Agency for Healthcare Research and Quality and the proportion of positive influenza tests by subtype reported to the Centers for Disease Control. The model accounts for the autocorrelation of meningococcal disease and …

Role Of Adaptor Trfa And Clppc In Controlling Levels Of Ssra-Tagged Proteins And Antitoxins In Staphylococcus Aureus, Niles P. Donegan, Jonathan S. Marvin, Ambrose L. Cheung

Dartmouth Scholarship

Staphylococcus aureus responds to changing extracellular environments in part by adjusting its proteome through alterations of transcriptional priorities and selective degradation of the preexisting pool of proteins. In Bacillus subtilis, the proteolytic adaptor protein MecA has been shown to play a role in assisting with the proteolytic degradation of proteins involved in competence and the oxidative stress response. However, the targets of TrfA, the MecA homolog in S. aureus, have not been well characterized. In this work, we investigated how TrfA assists chaperones and proteases to regulate the proteolysis of several classes of proteins in S. aureus. …

Delayed Switch Of Antiretroviral Therapy After Virologic Failure Associated With Elevated Mortality Among Hiv-Infected Adults In Africa, Maya L. Petersen, Linh Tran, Elvin H. Geng, Steven J. Reynolds, Andrew Kambugu, Robin Wood, David Bangsberg, Constantin T. Yiannoutsos, Steven G. Deeks, Jeffrey N. Martin

OHSU-PSU School of Public Health Faculty Publications and Presentations

Objective—Routine monitoring of plasma HIV RNA among HIV-infected patients on antiretroviral therapy (ART) is unavailable in many resource-limited settings. Alternative monitoring approaches correlate poorly with virologic failure and can substantially delay switch to second-line therapy. We evaluated the impact of delayed switch on mortality among patients with virologic failure in Africa.

Design—A cohort.

Methods—We examined patients with confirmed virologic failure on first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from four cohorts with serial HIV RNA monitoring in Uganda and South Africa. Marginal structural models aimed to estimate the effect of delayed switch on mortality in a hypothetical trial in which …

Disrupted Human–Pathogen Co-Evolution: A Model For Disease, Nuri Kodaman, Rafal S. Sobota, Robertino Mera, Barbara G. Schneider, Scott M. Williams

Dartmouth Scholarship

A major goal in infectious disease research is to identify the human and pathogenic genetic variants that explain differences in microbial pathogenesis. However, neither pathogenic strain nor human genetic variation in isolation has proven adequate to explain the heterogeneity of disease pathology. We suggest that disrupted co-evolution between a pathogen and its human host can explain variation in disease outcomes, and that genome-by-genome interactions should therefore be incorporated into genetic models of disease caused by infectious agents. Genetic epidemiological studies that fail to take both the pathogen and host into account can lead to false and misleading conclusions about disease …

Co-Infection With Hpv Types From The Same Species Provides Natural Cross-Protection From Progression To Cervical Cancer, Rafal S. Sobota, Doreen Ramogola-Masire, Scott M. Williams, Nicola M. Zetola

Dartmouth Scholarship

The worldwide administration of bivalent and quadrivalent HPV vaccines has resulted in cross-protection against non-vaccine HPV types. Infection with multiple HPV types may offer similar cross-protection in the natural setting. We hypothesized that infections with two or more HPV types from the same species, and independently, infections with two or more HPV types from different species, associate with protection from high-grade lesions.

Epoxide-Mediated Differential Packaging Of Cif And Other Virulence Factors Into Outer Membrane Vesicles, A. E. Ballok, L. M. Filkins, J.. M. Bomberger, B. A. Stanton, George A. O'Toole

Dartmouth Scholarship

Pseudomonas aeruginosa produces outer membrane vesicles (OMVs) that contain a number of secreted bacterial proteins, including phospholipases, alkaline phosphatase, and the CFTR inhibitory factor (Cif). Previously, Cif, an epoxide hydrolase, was shown to be regulated at the transcriptional level by epoxides, which serve as ligands of the repressor, CifR. Here, we tested whether epoxides have an effect on Cif levels in OMVs. We showed that growth of P. aeruginosa in the presence of specific epoxi

Imaging Luciferase-Expressing Viruses, Michael A. Barry, Shannon May, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Optical imaging of luciferage gene expression has become a powerful tool to track cells and viruses in vivo in small animal models. Luciferase imaging has been used to study the location of infection by replication-defective and replication-competent viruses and to track changes in the distribution of viruses in mouse models. This approach has also been used in oncolytic studies as a non-invasive means to monitor the growth and killing of tumor cells modified with luciferase genes. In this chapter, we describe the techniques used for luciferase imaging as have been applied to track replication-defective and replication-competent adenoviruses in mouse and …

The Mucosal Expression Pattern Of Interferon-Ε In Rhesus Macaques, Andrew Demers, Guobin Kang, Fangrui Ma, Wuxun Lu, Zhe Yuan, Yue Li, Mark Lewis, Edmundo N. Kraiselburd, Luis Montaner, Qingsheng Li

Qingsheng Li Publications

Type I IFNs play an important role in innate and adaptive immunity against viral infections. A novel type I IFN, namely IFN-ε, which can protect against vaginal transmission of HSV2 and Chlamydia muridarum bacterial infection, has been described in mice and humans. Nevertheless, the principle cell type and the expression pattern of IFN-ε in tissues remain uncertain. In addition, the expression of IFN-ε in Indian rhesus macaques (Macaca mulatta) has not been reported. Here, we analyzed IFN-ε expression in multiple mucosal sites of uninfected or SIV-infected Indian rhesus macaques using IHCS. We report for the first time the …

Clinical, Lifestyle, Socioeconomic Determinants And Rate Of Asymptomatic Intracranial Atherosclerosis In Stroke Free Pakistanis., Ayeesha Kamran Kamal, Farzin Majeed, Omrana Pasha, Hasan Rehman, Muhammad Islam, Iqbal Azam Syed, Muhammad Saleem Ilyas, Munawar Hussain, Kamran Masood, Bilal Ahmed, Sumaira Nazir, Zafar Sajjad, Scott E. Kasner

Department of Medicine

Background: Intracranial Atherosclerotic Disease (ICAD) is the most frequent etiology of stroke with high prevalence among Asians. Despite this, early determinants of ICAD have not been described from this region.

Methods: The study is an analytical prospective cross-sectional study of 200 adults from Radiology Departments of two diagnostic centers in Karachi. Eligible participants confirmed the absence of stroke symptoms via the Questionnaire for Verifying Stroke Free Status (QVSFS) and underwent an interview covering medical, socio demographic, lifestyle and anthropometric evaluation using locally validated and standardized definitions. Magnetic Resonance Images (MRI) were centrally reviewed to detect ICAD using the criterion used …

Tackling The Existing Burden Of Infectious Diseases In The Developing World: Existing Gaps And The Way Forward, Zulfiqar Ahmed Bhutta, Rehana A. Salam, Jai K. Das, Zohra S. Lassi

Department of Paediatrics and Child Health

This series evaluates the effectiveness of community-based interventions (CBIs) to prevent and control infectious diseases of poverty (IDoP). Evidence from our reviews suggests that CBIs and school-based delivery platforms are effective in averting risk behaviors and reducing the disease burden. Co-implementation of interventions through existing community-based programs including immunization campaigns, antenatal care and maternal and child health programs have the potential to scale-up interventions for IDoP. Future research should focus on the process of developing and implementing efficient community-based programs through a comprehensive approach, and to gauge the effectiveness of various existing delivery models in order to improve morbidity and …

Metabolomics Analysis Identifies Intestinal Microbiota-Derived Biomarkers Of Colonization Resistance In Clindamycin-Treated Mice, Robin L.P. Jump, Myreen Tomas, Abhishek Deshpande, Curtis J. Donskey

Faculty Scholarship

Background: The intestinal microbiota protect the host against enteric pathogens through a defense mechanism termed colonization resistance. Antibiotics excreted into the intestinal tract may disrupt colonization resistance and alter normal metabolic functions of the microbiota. We used a mouse model to test the hypothesis that alterations in levels of bacterial metabolites in fecal specimens could provide useful biomarkers indicating disrupted or intact colonization resistance after antibiotic treatment. Methods: To assess in vivo colonization resistance, mice were challenged with oral vancomycin-resistant Enterococcus or Clostridium difficile spores at varying time points after treatment with the lincosamide antibiotic clindamycin. For concurrent groups of …

Impact Of Peak/Mid Luteal Estradiol On Pregnancy Outcome After Intracytoplasmic Sperm Injection, Rehana Rehman, Zahir Hussain, Huma Zahir, Rakhshaan Khan

Department of Biological & Biomedical Sciences

Abstract

Objective: To compare peak to mid estradiol ratio with the probability of successful conception after intracytoplasmic

sperm injection.

Method: The quasi-experimental study was conducted in an infertility clinic at Islamabad from June 2010 till August

2011, and comprised couples subjected to intra-cytoplasmic sperm injection. Down-regulation of ovaries was

followed by calculated stimulation, ovulation induction, oocytes retrieval, intra cytoplasmic sperm injection, in vitro

maturation of embryos and finally blastocysts transfer. Serum estradiol was measured by enzyme-linked

immunosorbent assay on ovulation induction day and the day of embryo transfer. Failure of procedure was detected

by beta human chorionic gonadotropin5-25mIU/ml (Group I; …

Bacteria On Shared Mobile Phones Can Lead To Infections, Roberta Basol, Jean Beckel, Judy Gilsdorf-Gracie, Amy Hilleren-Listerud, Terri Mccaffrey, Sherri Reischl, Pamela Rickbeil, Mary Schimnich, Kirsten Skillings, Mary A. Struffert

Articles

It's now a common practice for hospital-owned mobile phones to be shared among healthcare employees from shift to shift. Despite the benefit of increased, timely communication between caregivers, sharing mobile devices can lead to the spread of healthcare-associated infections (HAIs) if they aren't properly disinfected. The Guidelines for Disinfection and Sterilization in Healthcare Facilities describe "non-critical environmental surfaces" as items that are frequently touched by the hand and may pose a risk of secondary infection transmission.