Diseases Commons^™

Dual Engagement Of The Nlrp3 And Aim2 Inflammasomes By Plasmodium-Derived Hemozoin And Dna During Malaria, Parisa Kalantari, Rosane B. Deoliveira, Jennie Chan, Yolanda Corbett, Vijay A. K. Rathinam, Andrea Stutz, Eicke Latz, Ricardo T. Gazzinelli, Douglas T. Golenbock, Katherine A. Fitzgerald

Katherine A. Fitzgerald

Hemozoin (Hz) is the crystalline detoxification product of hemoglobin in Plasmodium-infected erythrocytes. We previously proposed that Hz can carry plasmodial DNA into a subcellular compartment that is accessible to Toll-like receptor 9 (TLR9), inducing an inflammatory signal. Hz also activates the NLRP3 inflammasome in primed cells. We found that Hz appears to colocalize with DNA in infected erythrocytes, even before RBC rupture or phagolysosomal digestion. Using synthetic Hz coated in vitro with plasmodial genomic DNA (gDNA) or CpG oligodeoxynucleotides, we observed that DNA-complexed Hz induced TLR9 translocation, providing a priming and an activation signal for inflammasomes. After phagocytosis, Hz and …

Malaria-Induced Nlrp12/Nlrp3-Dependent Caspase-1 Activation Mediates Inflammation And Hypersensitivity To Bacterial Superinfection, Marco A. Ataide, Warrison A. Andrade, Dario S. Zamboni, Donghai Wang, Maria Do Carmo Souza, Bernardo S. Franklin, Samir Elian, Flaviano S. Martins, Dhelio Pereira, George W. Reed, Katherine A. Fitzgerald, Douglas T. Golenbock, Ricardo T. Gazzinelli

Katherine A. Fitzgerald

Cyclic paroxysm and high fever are hallmarks of malaria and are associated with high levels of pyrogenic cytokines, including IL-1beta. In this report, we describe a signature for the expression of inflammasome-related genes and caspase-1 activation in malaria. Indeed, when we infected mice, Plasmodium infection was sufficient to promote MyD88-mediated caspase-1 activation, dependent on IFN-gamma-priming and the expression of inflammasome components ASC, P2X7R, NLRP3 and/or NLRP12. Pro-IL-1beta expression required a second stimulation with LPS and was also dependent on IFN-gamma-priming and functional TNFR1. As a consequence of Plasmodium-induced caspase-1 activation, mice produced extremely high levels of IL-1beta upon a second …

Evaluating The Effectivesness Of Information Sources Regarding Hiv Among Gold Miners In Quảng Nam, Noah Landesberg

Independent Study Project (ISP) Collection

Young migrant males in strenuous manual labor environments represent a high-­‐risk population for the transmission of HIV/AIDS. In Vietnam, gold miners are representative of this high-­‐risk population. Phước Sơn district, Quảng Nam province is home to much of Vietnam’s mining activity and has a comparatively high rate of HIV. Previous studies have been done on HIV/AIDS prevalence in Quảng Nam as well as related knowledge and practices. This analysis of a 2014 questionnaire examines the effects of varying information sources on HIV/AIDS knowledge. The sample of workers was mostly male and between 25 and 49 years old. Migrants made up …

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 …

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 …

Classification Of Dengue Illness Based On Readily Available Laboratory Data, James Potts, Stephen Thomas, Anon Srikiatkhachorn, Pra-On Supradish, Wenjun Li, Ananda Nisalak, Suchitra Nimmannitya, Timothy Endy, Daniel Libraty, Robert Gibbons, Sharone Green, Alan Rothman, Siripen Kalayanarooj

Alan Rothman

The aim of this study was to examine retrospective dengue-illness classification using only clinical laboratory data, without relying on X-ray, ultrasound, or percent hemoconcentration. We analyzed data from a study of children who presented with acute febrile illness to two hospitals in Thailand. Multivariable logistic regression models were used to distinguish: (1) dengue hemorrhagic fever (DHF) versus dengue fever (DF), (2) DHF versus DF + other febrile illness (OFI), (3) dengue versus OFI, and (4) severe dengue versus non-severe dengue + OFI. Data from the second hospital served as a validation set. There were 1,227 patients in the analysis. The …

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 …

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.

Characterizing The Response Of Multidrug-Resistant Klebsiella Pneumoniae Species To The Application Of A Phage Cocktail, Steven Liu

Symposium

Project Summary: The application of bacteriophages to treat bacterial infections is known as phage therapy, which takes advantage of bacteriophage’s natural ability to infect and lyse bacterial hosts. Phages have been shaped by billions of years of evolution to be highly specialized deliverers of bactericidal agents to the cytoplasm of their target bacteria. Ever since discovery of bacteriophages in 1915, phage therapy was recognized as a potentially powerful tool for eliminating bacterial infections. The effectiveness of phage therapy can be increased by creating a mixture of multiple phages to target a wider variety of bacterial strains. Furthermore, phage therapy has …

Host Species Restriction Of Middle East Respiratory Syndrome Coronavirus Through Its Receptor, Dipeptidyl Peptidase 4, Neeltje Van Doremalen, Kerri L. Miazgowicz, Shauna Milne-Price, Trenton Bushmaker, Shelly Robertson, Dana Scott, Joerg Kinne, Jason S. Mclellan

Dartmouth Scholarship

Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012. Recently, the MERS-CoV receptor dipeptidyl peptidase 4 (DPP4) was identified and the specific interaction of the receptor-binding domain (RBD) of MERS-CoV spike protein and DPP4 was determined by crystallography. Animal studies identified rhesus macaques but not hamsters, ferrets, or mice to be susceptible for MERS-CoV. Here, we investigated the role of DPP4 in this observed species tropism. Cell lines of human and nonhuman primate origin were permissive of MERS-CoV, whereas hamster, ferret, or mouse cell lines were not, despite the presence of DPP4. Expression of human DPP4 in nonsusceptible BHK and …

Cystic Echinococcoses In Mongolia: Molecular Identification, Serology And Risk Factors, Akira Ito, Temuulen Dorjsuren, Anu Davaasuren, Tetsuya Yanagida, Yasuhito Sako, Kazuhiro Nakaya, Minoru Nakao, Oyun-Erdene Bat-Ochir, Tsendjav Ayushkhuu, Narantuya Bazarragchaa, Nyamkhuu Gonchigsengee, Tiaoying Li, Gurbadam Agvaandaram, Abmed Davaajav, Chinchuluun Boldbaatar, Gantigmaa Chuluunbaatar

Harold W. Manter Laboratory: Library Materials

Abstract

Background

Cystic echinococcosis (CE) is a globally distributed cestode zoonosis that causes hepatic cysts. Although Echinococcus granulosus sensu stricto (s.s.) is the major causative agent of CE worldwide, recent molecular epidemiological studies have revealed that E. canadensis is common in countries where camels are present. One such country is Mongolia.

Methodology/Principal Findings

Forty-three human hepatic CE cases that were confirmed histopathologically at the National Center of Pathology (NCP) in Ulaanbaatar (UB) were identified by analysis of mitochondrial cox1 gene as being caused by either E. canadensis (n = 31, 72.1%) or E. granulosus s.s. ( …

Avirulent Strains Of Toxoplasma Gondii Infect Macrophages By Active Invasion From The Phagosome, Yanlin Zhao, Andrew H. Marple, David J. P. Ferguson, David J. Bzik, George S. Yap

Dartmouth Scholarship

Unlike most intracellular pathogens that gain access into host cells through endocytic pathways, Toxoplasma gondii initiates infection at the cell surface by active penetration through a moving junction and subsequent formation of a parasitophorous vacuole. Here, we describe a noncanonical pathway for T. gondii infection of macrophages, in which parasites are initially internalized through phagocytosis, and then actively invade from within a phagosomal compartment to form a parasitophorous vacuole. This phagosome to vacuole invasion (PTVI) pathway may represent an intermediary link between the endocytic and the penetrative routes for host cell entry by intracellular pathogens. The PTVI pathway is preferentially …

Babesiosis: An Under-Recognized Tick Bourne Illness, Michael N. Daniels Do, Katie Mastoris Do, Mark Knouse Md, Stacey Smith Md, Facp

Department of Medicine

No abstract provided.

Supervised Treatment Interruption (Sti) In An Urban Hiv Clinical Practice: A Prospective Analysis, Joseph L. Yozviak Do, Facp, Peter Kouvatos Do, R Eric Doerfler Np, Cch, William C. Woodward Do

Joseph L Yozviak DO, FACP

Background: In acute HIV-1 infection, STI may induce immunologic control of HIV-1 replication. Several prospective trials of STI in chronic HIV-1 infection have been less encouraging. A previously presented retrospective analysis of our patients showed that in those with a significant CD4 increase (>200 cells) on antiretroviral therapy (ART), 2 or more interruptions may significantly lower viral set point. This prospective study describes STI in a cohort of patients.

Methods: 10 patients with either a positive response to therapy interruption retrospectively or those expressing interest in the strategy who met inclusion criteria (VL BLQ on ART, good adherence, robust …

Vaccine-Preventable Diseases In Travelers, Edith Mirzaian, Jeffery A. Goad, Ani Amloian, Fady Makar

Pharmacy Faculty Articles and Research

Travel to the developing world is increasing among those from developed countries, placing them at risk for vaccine preventable and non-vaccine preventable diseases. From 2007-2011, the GeoSentinel Network reported 737 returned travelers with a vaccine preventable disease. While it is essential that clinicians use vaccines when available for a disease of risk, they should also be aware that the vast majority of diseases acquired by travelers are non-vaccine preventable. The vaccine preventable diseases can be divided into routine travel vaccines, special travel vaccines and routine vaccines used for travel. The routine travel vaccines include Hepatitis A and B, typhoid; special …