Infectious Disease Commons^™

Β-Thujaplicin: A Soil Antifungal, Dennis J. Baumgardner

Journal of Patient-Centered Research and Reviews

Background: β-thujaplicin (β-Th), also known as hinokitiol, naturally occurs in cedar mulch, is found in personal care products and has in vitro antitumor activities. It is antibacterial and antifungal, but has not been tested on soil. Scedosporium apiospermum (Sce) is an emerging “extremophile” fungal pathogen found in built outdoor environments.

Purpose: Pilot β-Th as “natural” soil antimicrobial or for isolation of extremophiles, and to explore β-Th resistance as selective advantage to Sce in mulched landscape.

Methods: A variety of outdoor and indoor environments were used for 2 sets of 24 paired soil samples. Soil/H20 slurry (0.1 ml) was spread on …

Nested Partially-Latent, Class Models For Dependent Binary Data, Estimating Disease Etiology, Zhenke Wu, Maria Deloria-Knoll, Scott L. Zeger

Johns Hopkins University, Dept. of Biostatistics Working Papers

The Pneumonia Etiology Research for Child Health (PERCH) study seeks to use modern measurement technology to infer the causes of pneumonia for which gold-standard evidence is unavailable. The paper describes a latent variable model designed to infer from case-control data the etiology distribution for the population of cases, and for an individual case given his or her measurements. We assume each observation is drawn from a mixture model for which each component represents one cause or disease class. The model addresses a major limitation of the traditional latent class approach by taking account of residual dependence among multivariate binary outcome …

A Virtual Clinic Improves Pneumococcal Vaccination For Asplenic Veterans At High Risk For Pneumococcal Disease, Robin L.P. Jump, Brigid Wilson, Rebecca Carter, Susan Phillips, Federico Perez

Faculty Scholarship

We developed a "virtual clinic" to improve pneumococcal vaccination among asplenic adults. Using an electronic medical record, we identified patients, assessed their vaccination status, entered orders, and notified patients and providers. Within 180 days, 38 of 76 patients (50%) received a pneumococcal vaccination. Avirtual clinic may optimize vaccinations among high-risk patients.

Extrapolating Evidence About Preventing Recurrent Cellulitis For An Individual Patient Concern, Christina L. Benkert D.O., Amrit K. Basi, Kristina L. Bahrou M.D., Catherine R. Cherri M.D., Suraiya K. Azom M.D., Nicholus H. Yee M.D.

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Thomas KS, Crook AM, Nunn AJ, et al. Penicillin to prevent recurrent leg cellulitis, N Engl J Med. 2013, May 2;368(18):1695-1703. doi: 10.1056/NEJMoa1206300

Parasite Manipulation Of The Invariant Chain And The Peptide Editor H2-Dm Affects Major Histocompatibility Complex Class Ii Antigen Presentation During Toxoplasma Gondii Infection, Louis-Philippe Leroux, Manami Nishi, Sandy El-Hage, Barbara A. Fox, David I Bzik, Florence Dzierszinsk

Dartmouth Scholarship

Toxoplasma gondii is an obligate intracellular protozoan parasite. This apicomplexan is the causative agent of toxoplasmosis, a leading cause of central nervous system disease in AIDS. It has long been known that T. gondii interferes with major histocompatibility complex class II (MHC-II) antigen presentation to attenuate CD4(+) T cell responses and establish persisting infections. Transcriptional downregulation of MHC-II genes by T. gondii was previously established, but the precise mechanisms inhibiting MHC-II function are currently unknown. Here, we show that, in addition to transcriptional regulation of MHC-II, the parasite modulates the expression of key components of the MHC-II antigen presentation pathway, …

Preparation And Characterization Of Anti-Hiv Nanodrug Targeted To Microfold Cell Of Gut-Associated Lymphoid Tissue, Upal Roy, Hong Ding, Sudheesh Pilakka-Kanthikeel, Andrea D. Raymond, Venkata Atluri, Adriana Yndart, Elena M. Kaftanovskaya, Elena Batrakova, Marisela Agudelo, Madhavan Nair

Health & Biomedical Sciences Faculty Publications

The human immunodeficiency virus 1 (HIV-1) still remains one of the leading life-threatening diseases in the world. The introduction of highly active antiretroviral therapy has significantly reduced disease morbidity and mortality. However, most of the drugs have variable penetrance into viral reservoir sites, including gut-associated lymphoid tissue (GALT). Being the largest lymphoid organ, GALT plays a key role in early HIV infection and host–pathogen interaction. Many different treatment options have been proposed to eradicate the virus from GALT. However, it becomes difficult to deliver traditional drugs to the GALT because of its complex physiology. In this regard, we developed a …

Role Of Mrp Transporters In Regulating Antimicrobial Drug Inefficacy And Oxidative Stress-Induced Pathogenesis During Hiv-1 And Tb Infections, Upal Roy, Paul Barber, Yuk-Ching Tse-Dinh, Elena V. Batrakova, Debasis Mondal, Madhavan Nair

Health & Biomedical Sciences Faculty Publications

Multi-Drug Resistance Proteins (MRPs) are members of the ATP binding cassette (ABC) drug-efflux transporter superfamily. MRPs are known to regulate the efficacy of a broad range of anti-retroviral drugs (ARV) used in highly active antiretroviral therapy (HAART) and antibacterial agents used in Tuberculus Bacilli (TB) therapy. Due to their role in efflux of glutathione (GSH) conjugated drugs, MRPs can also regulate cellular oxidative stress, which may contribute to both HIV and/or TB pathogenesis. This review focuses on the characteristics, functional expression, and modulation of known members of the MRP family in HIV infected cells exposed to ARV drugs and discusses …

Characterizing Ebola Transmission Patterns Based On Internet News Reports., J. C. Cleaton, Cecile Viboud, Lone Simonsen, A. M. Hurtado, G. Chowell

Global Health Faculty Publications

BACKGROUND:  Detailed information on patient exposure, contact patterns, and discharge status, is rarely available in real time from traditional surveillance systems in the context of an emerging infectious disease outbreak. Here we validate the systematic collection of Internet news reports to characterize epidemiological patterns of Ebola virus disease (EVD) infections during the West African 2014-2015 outbreak.

METHODS:  Based on 58 news reports, we analyzed a total of 79 EVD clusters (286 cases) of size ranging from 1 to 33 cases between January 2014 and February 2015 in Guinea, Sierra Leone and Liberia.

RESULTS AND CONCLUSIONS:  The great majority of reported …

Mortality In Sepsis And Its Relationship With Gender., Nosheen Nasir, Bushra Jamil, Shahla Siddiqui, Fauzia A. Khan, Rabia Hussain

Department of Medicine

BACKGROUND AND OBJECTIVE:

Sepsis remains a leading cause of death across the world, carrying a mortality rate of 20-50%. Women have been reported to be less likely to suffer from sepsis and to have a lower risk of mortality from sepsis compared to men. The objective of this study was to determine the relationship between gender and mortality in sepsis, and compare cytokine profiles of male and female patients.

METHODS:

This was a prospective case series on 97 patients admitted with sepsis. Clinical and microbiological data was gathered, blood samples were collected for cytokine (IL-10, IL-6 and TNFα) levels and …

Optimizing Antibiotic Stewardship In Nursing Homes: A Narrative Review And Recommendations For Improvement, Robin Jump

Faculty Scholarship

The emerging crisis in antibiotic resistance and concern that we now sit on the precipice of a post-antibiotic era have given rise to advocacy at the highest levels for widespread adoption of programmes that promote judicious use of antibiotics. These antibiotic stewardship programmes, which seek to optimize antibiotic choice when clinically indicated and discourage antibiotic use when clinically unnecessary, are being implemented in an increasing number of acute care facilities, but their adoption has been slower in nursing homes. The antibiotic prescribing process in nursing homes is fundamentally different from that observed in hospital and clinic settings, with formidable challenges …

A Self-Lysis Pathway That Enhances The Virulence Of A Pathogenic Bacterium, Kirsty A. Mcfarland, Emily L. Dolben, Michele Leroux, Tracy K. Kambara, Kathryn Ramsey, Robin Kirkpatrick, Joseph Mougous, Deborah Hogan, Simon Dove

Dartmouth Scholarship

In mammalian cells, programmed cell death (PCD) plays important roles in development, in the removal of damaged cells, and in fighting bacterial infections. Although widespread among multicellular organisms, there are relatively few documented instances of PCD in bacteria. Here we describe a potential PCD pathway in Pseudomonas aeruginosa that enhances the ability of the bacterium to cause disease in a lung infection model. Activation of the system can occur in a subset of cells in response to DNA damage through cleavage of an essential transcription regulator we call AlpR. Cleavage of AlpR triggers a cell lysis program through de-repression of …

Inhaled Nitric Oxide As An Adjunctive Treatment For Cerebral Malaria In Children: A Phase Ii Randomized Open-Label Clinical Trial, Juliet Mwanga-Amumpaire, Ryan W. Carroll, Elisabeth Baudin, Elisabeth Kemigisha, Dorah Nampijjah, Kenneth Mworozi, Data Santorino, Dan Nyehangane, Daniel I. Nathan, Pierre De Beaudrap, Jean-Francois Etard, Martin Feelish, Bernadette O. Fernandez, Annie Berssenbrugge, David Bangsberg, Kenneth D. Bloch, Yap Boum Ii, Warren M. Zapol

OHSU-PSU School of Public Health Faculty Publications and Presentations

Background. Children with cerebral malaria (CM) have high rates of mortality and neurologic sequelae. Nitric oxide (NO) metabolite levels in plasma and urine are reduced in CM.

Methods. This randomized trial assessed the efficacy of inhaled NO versus nitrogen (N2) as an adjunctive treatment for CM patients receiving intravenous artesunate.We hypothesized that patients treated with NO would have a greater increase of the malaria biomarker, plasma angiopoietin-1 (Ang-1) after 48 hours of treatment.

Results. Ninety-two children with CM were randomized to receive either inhaled 80 part per million NO or N₂ for 48 or more hours. Plasma Ang-1 levels …

Clinical Characteristics And Risk Factors Of Candidemia In Tertiary Care Hospital, Iffat Khanum, Syed Faisal Mahmood, Farheen Ali, Hafsa Waqar, Safia Awan

Department of Medicine

Introduction: During the past two decades, the incidence of candidemia has doubled and Candida spp. currently ranks in top blood stream pathogen in developed countries. Given the need to ensure appropriate and timely antifungal therapy, there is need to identify these patients as early as possible and therefore a risk stratification for candidemia is imperative. We aim to identify the risk factors of candidemia in patients admitted at our tertiary care center.

Methods: A retrospective case control study were conducted on adult patients (15 years. or more) admitted to Aga Khan University Hospital between 2009 and 2013 who developed candidemia …

Links Between Anr And Quorum Sensing In Pseudomonas Aeruginosa Biofilms, John H. Hammond, Emily F. Dolben, T. Jarrod Smith, Sabin Bhuju, Deborah Hogan

Dartmouth Scholarship

In Pseudomonas aeruginosa, the transcription factor Anr controls the cellular response to low oxygen or anoxia. Anr activity is high in oxygen-limited environments, including biofilms and populations associated with chronic infections, and Anr is necessary for persistence in a model of pulmonary infection. In this study, we characterized the Anr regulon in biofilm-grown cells at 1% oxygen in the laboratory strain PAO1 and in a quorum sensing (QS)-deficient clinical isolate, J215. As expected, transcripts related to denitrification, arginine fermentation, high-affinity cytochrome oxidases, and CupA fimbriae were lower in the Δanr derivatives. In addition, we observed that transcripts associated with quorum …

Are Staphylococcus Intermedius Infections In Humans Cases Of Mistaken Identity? A Case Series And Literature Review, Roberto Viau, Andrea M. Hujer, Kristine M. Hujer, Robert A. Bonomo, Robin L.P. Jump

Faculty Scholarship

Staphylococcus intermedius and Staphylococcus pseudintermedius are difficult to distinguish using conventional microbiological methods. Molecular diagnostic tools change our understanding of the epidemiology of these 2 organisms. In this study, we present (1) a detailed review of the current literature on molecular diagnostics and (2) a case series in which misidentification was proven in 1 case. We conclude that S pseudintermedius is a more common human pathogen than previously recognized.

Isolation Of Mycobacterium Avium From Potable Water In Homes And Institutions Of Patients With Hiv Infection In Finland And The United States, Matti Ristola, Robert D. Arbeit, C. Fordham Von Reyn, C. Robert Horsburgh

Dartmouth Scholarship

Symptomatic disease by nontuberculous mycobacteria has been linked to potable water from institutional and domestic potable water systems. Potable water samples were collected from homes and institutions of patients with AIDS. Colonization of potable water with nontuberculous mycobacteria was demonstrated in 230 (15%) of 1489 samples collected from domestic and institutional water systems of patients with HIV infection in the United States and Finland. Mycobacterium avium was the most common species and colonization was favored at temperatures of 40–50°C in recirculating hot water systems. Such systems are a plausible source of human infection and disease.

Draft Genome Sequences Of Six Different Staphylococcus Epidermidis Clones, Isolated Individually From Preterm Neonates Presenting With Sepsis At Edinburgh's Royal Infirmary, Paul Walsh, M. Bekaert, J. Carroll, T. Manning, B. Kelly, A. O'Driscoll, X. Lu, C. Smith, P. Dickinson, K. Templeton, P. Ghazal, Roy D. Sleator

Department of Biological Sciences Publications

Herein, we report the draft genome sequences of six individual Staphylococcus epidermidis clones, cultivated from blood taken from different preterm neonatal sepsis patients at the Royal Infirmary, Edinburgh, Scotland, United Kingdom.

The Medical Response To The Black Death, Joseph A. Legan

Senior Honors Projects, 2010-2019

This paper discusses the medical response to the Black Death in both Europe and the Middle East. The Black Death was caused by a series of bacterial strands collectively known as Yersinia pestis. The Plague originated in the Mongolian Steppes. It was spread westward by the east-west trading system. Once it arrived in the Crimea in 1346, Italian merchants helped spread it throughout the Mediterranean. Medicine in Europe and the Middle East were centered on Galen’s theory of humors. There were many religious explanations for the Plague, but the main medical explanation was the spread of bad air, or …

Rush To Judgment: The Sti-Treatment Trials And Hiv In Sub-Saharan Africa, Eileen Stillwaggon, Larry Sawers

Economics Faculty Publications

Introduction: The extraordinarily high incidence of HIV in sub-Saharan Africa led to the search for cofactor infections that could explain the high rates of transmission in the region. Genital inflammation and lesions caused by sexually transmitted infections (STIs) were a probable mechanism, and numerous observational studies indicated several STI cofactors. Nine out of the ten randomized controlled trials (RCTs), however, failed to demonstrate that treating STIs could lower HIV incidence. We evaluate all 10 trials to determine if their design permits the conclusion, widely believed, that STI treatment is ineffective in reducing HIV incidence.

Discussion: Examination of the …

Nonreplicating, Cyst-Defective Type Ii Toxoplasma Gondii Vaccine Strains Stimulate Protective Immunity Against Acute And Chronic Infection, Barbara Andrea Fox, David J. Bzik

Dartmouth Scholarship

Live attenuated vaccine strains, such as type I nonreplicating uracil auxotroph mutants, are highly effective in eliciting lifelong immunity to virulent acute infection by Toxoplasma gondii. However, it is currently unknown whether vaccine-elicited immunity can provide protection against acute infection and also prevent chronic infection. To address this problem, we developed nonreverting, nonreplicating, live attenuated uracil auxotroph vaccine strains in the type II Δku80 genetic background by targeting the deletion of the orotidine 5′-monophosphate decarboxylase (OMPDC) and uridine phosphorylase (UP) genes. Deletion of OMPDC induced a severe uracil auxotrophy with loss of replication, loss of …