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The Diagnostic Utility Of Induced Sputum Microscopy And Culture In Childhood Pneumonia., David R Murdoch, Susan C Morpeth, Laura L Hammitt, Amanda J Driscoll, Nora L Watson, Daniel E Park, +Several Additional Authors Jun 2017

The Diagnostic Utility Of Induced Sputum Microscopy And Culture In Childhood Pneumonia., David R Murdoch, Susan C Morpeth, Laura L Hammitt, Amanda J Driscoll, Nora L Watson, Daniel E Park, +Several Additional Authors

Epidemiology Faculty Publications

Background.

Sputum microscopy and culture are commonly used for diagnosing the cause of pneumonia in adults but are rarely performed in children due to difficulties in obtaining specimens. Induced sputum is occasionally used to investigate lower respiratory infections in children but has not been widely used in pneumonia etiology studies. Methods.

We evaluated the diagnostic utility of induced sputum microscopy and culture in patients enrolled in the Pneumonia Etiology Research for Child Health (PERCH) study, a large study of community-acquired pneumonia in children aged 1–59 months. Comparisons were made between induced sputum samples from hospitalized children with radiographically confirmed pneumonia …


Emerging Antimicrobial Resistance In Early And Late-Onset Neonatal Sepsis, Lamiaa Mohnsen, Nermin Ramy, Dalia Saied, Dina Akmal, Niveen Salama, Mona Abdel Haleim, Hany Aly Jun 2017

Emerging Antimicrobial Resistance In Early And Late-Onset Neonatal Sepsis, Lamiaa Mohnsen, Nermin Ramy, Dalia Saied, Dina Akmal, Niveen Salama, Mona Abdel Haleim, Hany Aly

Pediatrics Faculty Publications

Background

Compared to developed countries, the use of antimicrobials in Egypt is less regulated and is available over the counter without the need for prescriptions. The impact of such policy on antimicrobial resistance has not been studied. This study aimed to determine the prevalence of early and late onset sepsis, and the frequency of antimicrobial resistance in a major referral neonatal intensive care unit (NICU).

Methods

The study included all neonates admitted to the NICU over a 12-month period. Prospectively collected clinical and laboratory data were retrieved, including blood cultures and endotracheal aspirate cultures if performed.

Results

A total of …


Rnaseq Analysis Of The Drosophila Response To The Entomopathogenic Nematode Steinernema., Shruti Yadav, Sean Daugherty, Amol Carl Shetty, Ioannis Eleftherianos Jun 2017

Rnaseq Analysis Of The Drosophila Response To The Entomopathogenic Nematode Steinernema., Shruti Yadav, Sean Daugherty, Amol Carl Shetty, Ioannis Eleftherianos

Computational Biology Institute

Drosophila melanogaster is an outstanding model to study the molecular and functional basis of host-pathogen interactions. Currently, our knowledge of microbial infections in D. melanogaster is well understood; however, the response of flies to nematode infections is still in its infancy. Here, we have used the potent parasitic nematode Steinernema carpocapsae, which lives in mutualism with its endosymbiotic bacteria Xenorhabdus nematophila, to examine the transcriptomic basis of the interaction between D. melanogaster and entomopathogenic nematodes. We have employed next-generation RNA sequencing (RNAseq) to investigate the transcriptomic profile of D. melanogaster larvae in response to infection by S. carpocapsae symbiotic (carrying …


Subsets Of Inflammatory Cytokine Gene Polymorphisms Are Associated With Risk Of Carcinogenic Liver Fluke Opisthorchis Viverrini-Associated Advanced Periductal Fibrosis And Cholangiocarcinoma., Arpa Surapaitoon, Sutas Suttiprapa, Eimorn Mairiang, Narong Khuntikeo, Chawalit Pairojkul, Jeffrey Bethony, Paul J Brindley, Banchob Sripa Jun 2017

Subsets Of Inflammatory Cytokine Gene Polymorphisms Are Associated With Risk Of Carcinogenic Liver Fluke Opisthorchis Viverrini-Associated Advanced Periductal Fibrosis And Cholangiocarcinoma., Arpa Surapaitoon, Sutas Suttiprapa, Eimorn Mairiang, Narong Khuntikeo, Chawalit Pairojkul, Jeffrey Bethony, Paul J Brindley, Banchob Sripa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Opisthorchis viverrini infection induces chronic inflammation, and a minor proportion of infected individuals develop advanced periductal fibrosis (APF) and cholangiocarcinoma (CCA). Inflammatory cytokines and/or their gene polymorphisms may link to these biliary pathologies. We therefore investigated associations among cytokine gene polymorphisms and cytokine production in 510 Thai cases infected with O. viverrini who presented with APF+ or APF−, as established by abdominal ultrasonography as well as in patients diagnosed with CCA. Levels of pro-inflammatory and anti-inflammatory cytokines were determined in culture supernatants after stimulation of peripheral blood mononuclear cells (PBMCs) with O. viverrini excretory-secretory (ES) products. Pro-inflammatory cytokines, IL-1β, IL-6, …


Emergence Of Livestock-Associated Methicillin-Resistant Staphylococcus Aureus Bloodstream Infections In Denmark., Jesper Larsen, Andreas Petersen, Anders R Larsen, Raphael N Sieber, Marc Stegger, Anders Koch, Frank M Aarestrup, Lance B Price, Robert L Skov May 2017

Emergence Of Livestock-Associated Methicillin-Resistant Staphylococcus Aureus Bloodstream Infections In Denmark., Jesper Larsen, Andreas Petersen, Anders R Larsen, Raphael N Sieber, Marc Stegger, Anders Koch, Frank M Aarestrup, Lance B Price, Robert L Skov

Environmental and Occupational Health Faculty Publications

Background

Livestock-associated methicillin-resistant Staphylococcus aureus clonal complex 398 (LA-MRSA CC398) is causing an increasing number of skin and soft tissue infections (SSTIs) in Denmark and other European countries with industrial pig production. Yet, its impact on MRSA bloodstream infections (BSIs) has not been well studied.

Methods

We investigated the clinical epidemiology of all human cases of LA-MRSA CC398 BSI during 2010–2015. Cases of LA-MRSA CC398 BSI were compared to cases of BSI caused by other types of MRSA and cases of SSTI caused by LA-MRSA CC398. Whole-genome sequence analysis was used to assess the phylogenetic relationship among LA-MRSA CC398 isolates …


Financing Of International Collective Action For Epidemic And Pandemic Preparedness., Gavin Yamey, Marco Schäferhoff, Ole Kristian Aars, Barry Bloom, Dennis Carroll, Mukesh Chawla, Victor Dzau, Ricardo Echalar, Indermit Singh Gill, Tore Godal, Sanjeev Gupta, Dean Jamison, Patrick Kelley, Frederik Kristensen, Ceci Mundaca-Shah, Ben Oppenheim, Julie Pavlin, Rodrigo Salvado, Peter Sands, Rocio Schmunis, Agnes Soucat, Lawrence H Summers, Anas El Turabi, Ron Waldman, Ed Whiting May 2017

Financing Of International Collective Action For Epidemic And Pandemic Preparedness., Gavin Yamey, Marco Schäferhoff, Ole Kristian Aars, Barry Bloom, Dennis Carroll, Mukesh Chawla, Victor Dzau, Ricardo Echalar, Indermit Singh Gill, Tore Godal, Sanjeev Gupta, Dean Jamison, Patrick Kelley, Frederik Kristensen, Ceci Mundaca-Shah, Ben Oppenheim, Julie Pavlin, Rodrigo Salvado, Peter Sands, Rocio Schmunis, Agnes Soucat, Lawrence H Summers, Anas El Turabi, Ron Waldman, Ed Whiting

Global Health Faculty Publications

The global pandemic response has typically followed cycles of panic followed by neglect. We are now, once again, in a phase of neglect, leaving the world highly vulnerable to massive loss of life and economic shocks from natural or human-made epidemics and pandemics. Quantifying the size of the losses caused by large-scale outbreaks is challenging because the epidemiological and economic research in this field is still at an early stage. Research on the 1918 influenza H1N1 pandemic and recent epidemics and pandemics has shown a range of estimated losses (panel).1; 2; 3; 4; …


Whole Genome Analysis Of A Schistosomiasis-Transmitting Freshwater Snail., Coen M Adema, Ladeana W Hillier, Catherine S Jones, Eric S Loker, Matty Knight, Patrick Minx, +Several Additional Authors May 2017

Whole Genome Analysis Of A Schistosomiasis-Transmitting Freshwater Snail., Coen M Adema, Ladeana W Hillier, Catherine S Jones, Eric S Loker, Matty Knight, Patrick Minx, +Several Additional Authors

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify …


Cohort Profile: Seek, Test, Treat And Retain United States Criminal Justice Cohort., Redonna Chandler, Michael S Gordon, Bridget Kruszka, Lauren N Strand, Frederick L Altice, Irene Kuo, +Several Additional Authors May 2017

Cohort Profile: Seek, Test, Treat And Retain United States Criminal Justice Cohort., Redonna Chandler, Michael S Gordon, Bridget Kruszka, Lauren N Strand, Frederick L Altice, Irene Kuo, +Several Additional Authors

Epidemiology Faculty Publications

BACKGROUND: The STTR treatment cascade provides a framework for research aimed at improving the delivery of services, care and outcomes of PLWH. The development of effective approaches to increase HIV diagnoses and engage PLWH in subsequent steps of the treatment cascade could lead to earlier and sustained ART treatment resulting in viral suppression. There is an unmet need for research applying the treatment cascade to improve outcomes for those with criminal justice involvement.

METHODS: The Seek, Test, Treat, and Retain (STTR) criminal justice (CJ) cohort combines data from 11 studies across the HIV treatment cascade that focused on persons involved …


Pediatric Intrafalcine Empyema From A Sinogenic Origin: A Case Report., Kyle Mueller, John Myseros May 2017

Pediatric Intrafalcine Empyema From A Sinogenic Origin: A Case Report., Kyle Mueller, John Myseros

Neurological Surgery Faculty Publications

Sinusitis and otitis are common within the pediatric population. If left untreated, these can extend intracranially and lead to the development of infections in the various intracranial compartments resulting in a high rate of morbidity and mortality. We report the first case of an intrafalcine empyema, absent subdural purulence, in a patient with the likely spread from a sinogenic origin. This case illustrates the novelty of this as a pathological entity as well as the surgical considerations for intrafalcine purulence in the absence of expected subdural collections.


Safety And Immunogenicity Of The Na-Gst-1 Hookworm Vaccine In Brazilian And American Adults., David J Diemert, Janaína Freire, Vanderson Valente, Carlos Geraldo Fraga, Frederico Talles, Shannon Grahek, Doreen Campbell, Amar Jariwala, Maria Victoria Periago, Martin Enk, Maria Flávia Gazzinelli, Maria Elena Bottazzi, Robert Hamilton, Jill Brelsford, Anna Yakovleva, Guangzhao Li, Jin Peng, Rodrigo Correa-Oliveira, Peter Hotez, Jeffrey Bethony May 2017

Safety And Immunogenicity Of The Na-Gst-1 Hookworm Vaccine In Brazilian And American Adults., David J Diemert, Janaína Freire, Vanderson Valente, Carlos Geraldo Fraga, Frederico Talles, Shannon Grahek, Doreen Campbell, Amar Jariwala, Maria Victoria Periago, Martin Enk, Maria Flávia Gazzinelli, Maria Elena Bottazzi, Robert Hamilton, Jill Brelsford, Anna Yakovleva, Guangzhao Li, Jin Peng, Rodrigo Correa-Oliveira, Peter Hotez, Jeffrey Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Necator americanus Glutathione-S-Transferase-1 (Na-GST-1) plays a role in the digestion of host hemoglobin by adult N. americanus hookworms. Vaccination of laboratory animals with recombinant Na-GST-1 is associated with significant protection from challenge infection. Recombinant Na-GST-1 was expressed in Pichia pastoris and adsorbed to aluminum hydroxide adjuvant (Alhydrogel) according to current Good Manufacturing Practice. Two Phase 1 trials were conducted in 142 healthy adult volunteers in the United States and Brazil, first in hookworm-naïve individuals and then in residents of a N. americanus endemic area in Brazil. Volunteers received one of three doses of recombinant …


Mll3/Mll4 Are Required For Cbp/P300 Binding On Enhancers And Super-Enhancer Formation In Brown Adipogenesis., Binbin Lai, Ji-Eun Lee, Younghoon Jang, Lifeng Wang, Weiqun Peng, Kai Ge Apr 2017

Mll3/Mll4 Are Required For Cbp/P300 Binding On Enhancers And Super-Enhancer Formation In Brown Adipogenesis., Binbin Lai, Ji-Eun Lee, Younghoon Jang, Lifeng Wang, Weiqun Peng, Kai Ge

Anatomy and Regenerative Biology Faculty Publications

Histone H3K4me1/2 methyltransferases MLL3/MLL4 and H3K27 acetyltransferases CBP/p300 are major enhancer epigenomic writers. To understand how these epigenomic writers orchestrate enhancer landscapes in cell differentiation, we have profiled genomic binding of MLL4, CBP, lineage-determining transcription factors (EBF2, C/EBPβ, C/EBPα, PPARγ), coactivator MED1, RNA polymerase II, as well as epigenome (H3K4me1/2/3, H3K9me2, H3K27me3, H3K36me3, H3K27ac), transcriptome and chromatin opening during adipogenesis of immortalized preadipocytes derived from mouse brown adipose tissue (BAT). We show that MLL4 and CBP drive the dynamic enhancer epigenome, which correlates with the dynamic transcriptome. MLL3/MLL4 are required for CBP/p300 binding on enhancers activated during adipogenesis. Further, MLL4 …


Pulmonary Microrna Profiles Identify Involvement Of Creb1 And Sec14l3 In Bronchial Epithelial Changes In Allergic Asthma., Sabine Bartel, Nikola Schulz, Francesca Alessandrini, Andrea C Schamberger, Philipp Pagel, Fabian J Theis, Katrin Milger, Elfriede Noessner, Stephen M Stick, Anthony Kicic, Oliver Eickelberg, Robert J Freishtat, Susanne Krauss-Etschmann Apr 2017

Pulmonary Microrna Profiles Identify Involvement Of Creb1 And Sec14l3 In Bronchial Epithelial Changes In Allergic Asthma., Sabine Bartel, Nikola Schulz, Francesca Alessandrini, Andrea C Schamberger, Philipp Pagel, Fabian J Theis, Katrin Milger, Elfriede Noessner, Stephen M Stick, Anthony Kicic, Oliver Eickelberg, Robert J Freishtat, Susanne Krauss-Etschmann

Medicine Faculty Publications

Asthma is highly prevalent, but current therapies cannot influence the chronic course of the disease. It is thus important to understand underlying early molecular events. In this study, we aimed to use microRNAs (miRNAs) - which are critical regulators of signaling cascades - to identify so far uncharacterized asthma pathogenesis pathways. Therefore, deregulation of miRNAs was assessed in whole lungs from mice with ovalbumin (OVA)-induced allergic airway inflammation (AAI). In silico predicted target genes were confirmed in reporter assays and in house-dust-mite (HDM) induced AAI and primary human bronchial epithelial cells (NHBE) cultured at the air-liquid interface. We identified and …


Internal Medicine Resident Perspectives Regarding Broad-Spectrum Antibiotic Usage., Ann M Laake, Gayle Bernabe, James Peterson, Angelike P Liappis Apr 2017

Internal Medicine Resident Perspectives Regarding Broad-Spectrum Antibiotic Usage., Ann M Laake, Gayle Bernabe, James Peterson, Angelike P Liappis

Medicine Faculty Publications

Focus groups held with internal medicine residents discussed their perspectives regarding broad-spectrum antibiotic (BSA) usage. Residents knew of BSA-associated adverse events, but they did not associate such events with increased patient morbidity and mortality, and they were more likely to use BSA in situations with diagnostic uncertainty and sick patients.


Development Of An Interleukin-4-Inducing Principle From Schistosoma Mansoni Eggs (Ipse)-Specific Pcr Assay As A Quantitative Predictor Of Schistosomiasis-Associated Morbidity, Dannah Farah, Evaristis Mbanefo, Michael H. Hsieh Apr 2017

Development Of An Interleukin-4-Inducing Principle From Schistosoma Mansoni Eggs (Ipse)-Specific Pcr Assay As A Quantitative Predictor Of Schistosomiasis-Associated Morbidity, Dannah Farah, Evaristis Mbanefo, Michael H. Hsieh

GW Research Days 2016 - 2020

Schistosomiasis is a neglected tropical disease affecting between 200-500 million people worldwide. The two species causing most human cases of schistosomiasis are Schistosoma mansoni and Schistosoma haematobium. The gold standard for diagnosis is parasitological detection of parasite eggs in stool using the Kato-Katz method. Counting eggs shed in stool is labor-intensive and inaccurate. Interleukin-4- inducing principle from Schistosoma mansoni eggs (IPSE) is the most abundant secreted protein from schistosome eggs. We hypothesized that the mRNA transcripts of the IPSE protein may be found in the liver tissue and stool of experimentally infected animals, and that these transcripts can be specifically …


A Comparison Of Influenza & Tdap Vaccination Rates By Characteristics Of Child-Bearing-Aged Women, Francis Connor, Dnp, Msn, Mph, Fnp-Bc Apr 2017

A Comparison Of Influenza & Tdap Vaccination Rates By Characteristics Of Child-Bearing-Aged Women, Francis Connor, Dnp, Msn, Mph, Fnp-Bc

Doctor of Nursing Practice Projects

Background

The Advisory Committee on Immunization Practices recommend childbearing-aged women receive an annual influenza vaccine, one dose of Tdap instead of TD after 18 years of age, and one dose of Tdap during the 3rd trimester of each pregnancy. Despite these recommendations, influenza and Tdap vaccination rates remain lower than current goals.

Objectives

The purpose was to assess influenza and Tdap vaccination rates among women of childbearing age by pregnancy status, age group, and race/ethnicity.

Methods

The retrospective secondary data analysis included a nationally representative sample of women aged 18 to 44 years from the 2014 Behavioral Risk Factors …


Maternal Characteristics And Obstetrical Complications Impact Neonatal Outcomes In Indonesia: A Prospective Study., Trisari Anggondowati, Ayman A E El-Mohandes, S Nurul Qomariyah, Michele Kiely, Judith J Ryon, Reginald F Gipson, Benjamin Zinner, Anhari Achadi, Linda L Wright Mar 2017

Maternal Characteristics And Obstetrical Complications Impact Neonatal Outcomes In Indonesia: A Prospective Study., Trisari Anggondowati, Ayman A E El-Mohandes, S Nurul Qomariyah, Michele Kiely, Judith J Ryon, Reginald F Gipson, Benjamin Zinner, Anhari Achadi, Linda L Wright

Medicine Faculty Publications

BACKGROUND: We investigated associations between maternal characteristics, access to care, and obstetrical complications including near miss status on admission or during hospitalization on perinatal outcomes among Indonesian singletons.

METHODS: We prospectively collected data on inborn singletons at two hospitals in East Java. Data included socio-demographics, reproductive, obstetric and neonatal variables. Reduced multivariable models were constructed. Outcomes of interest included low and very low birthweight (LBW/VLBW), asphyxia and death.

RESULTS: Referral from a care facility was associated with a reduced risk of LBW and VLBW [AOR = 0.28, 95% CI = 0.11-0.69, AOR = 0.18, 95% CI = 0.04-0.75, respectively], stillbirth …


Broadly Neutralizing Antibodies As Treatment: Effects On Virus And Immune System., Jinal N Bhiman, Rebecca M Lynch Mar 2017

Broadly Neutralizing Antibodies As Treatment: Effects On Virus And Immune System., Jinal N Bhiman, Rebecca M Lynch

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Purpose of Review

The purpose of this study is to summarize recent advances in the use of broadly neutralizing antibodies (bNAbs) as therapeutics in human clinical trials and in non-human primate (NHP) models. We seek to highlight lessons from these studies with an emphasis on consequences to the virus and immune system.

Recent Findings

In the past 10 years, advances in HIV-1 trimer structure and B cell isolation methods have precipitated the identification of “new-generation” anti-HIV antibodies with broad and potent neutralization. In the past 2 years, the concept of using these bNAbs as therapeutic tools has moved from NHP …


Dynamic Transcriptomes Identify Biogenic Amines And Insect-Like Hormonal Regulation For Mediating Reproduction In Schistosoma Japonicum., Jipeng Wang, Ying Yu, Haimo Shen, Tao Qing, Yuanting Zheng, Qing Li, Xiaojin Mo, Shuqi Wang, Nana Li, Riyi Chai, Bin Xu, Mu Liu, Paul J Brindley, Donald P Mcmanus, Zheng Feng, Leming Shi, Wei Hu Mar 2017

Dynamic Transcriptomes Identify Biogenic Amines And Insect-Like Hormonal Regulation For Mediating Reproduction In Schistosoma Japonicum., Jipeng Wang, Ying Yu, Haimo Shen, Tao Qing, Yuanting Zheng, Qing Li, Xiaojin Mo, Shuqi Wang, Nana Li, Riyi Chai, Bin Xu, Mu Liu, Paul J Brindley, Donald P Mcmanus, Zheng Feng, Leming Shi, Wei Hu

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Eggs produced by the mature female parasite are responsible for the pathogenesis and transmission of schistosomiasis. Female schistosomes rely on a unique male-induced strategy to accomplish reproductive development, a process that is incompletely understood. Here we map detailed transcriptomic profiles of male and female Schistosoma japonicum across eight time points throughout the sexual developmental process from pairing to maturation. The dynamic gene expression pattern data reveal clear sex-related characteristics, indicative of an unambiguous functional division between males and females during their interplay. Cluster analysis, in situ hybridization and RNAi assays indicate that males likely use biogenic amine neurotransmitters through the …


Impact Of A National Guideline On Antibiotic Selection For Hospitalized Pneumonia., Derek J Williams, Matthew Hall, Jeffrey S Gerber, Mark I Neuman, Adam L Hersh, Thomas V Brogan, Kavita Parikh, Sanjay Mahant, Anne J Blaschke, Samir S Shah, Carlos G Grijalva Mar 2017

Impact Of A National Guideline On Antibiotic Selection For Hospitalized Pneumonia., Derek J Williams, Matthew Hall, Jeffrey S Gerber, Mark I Neuman, Adam L Hersh, Thomas V Brogan, Kavita Parikh, Sanjay Mahant, Anne J Blaschke, Samir S Shah, Carlos G Grijalva

Pediatrics Faculty Publications

BACKGROUND: We evaluated the impact of the 2011 Pediatric Infectious Diseases Society/Infectious Diseases Society of America pneumonia guideline and hospital-level implementation efforts on antibiotic prescribing for children hospitalized with pneumonia.

METHODS: We assessed inpatient antibiotic prescribing for pneumonia at 28 children's hospitals between August 2009 and March 2015. Each hospital was also surveyed regarding local implementation efforts targeting antibiotic prescribing and organizational readiness to adopt guideline recommendations. To estimate guideline impact, we used segmented linear regression to compare the proportion of children receiving penicillins in March 2015 with the expected proportion at this same time point had the guideline not …


A Murine Model To Study Epilepsy And Sudep Induced By Malaria Infection., Paddy Ssentongo, Anna E Robuccio, Godfrey Thuku, Derek G Sim, Ali Nabi, Fatemeh Bahari, Balaji Shanmugasundaram, Myles W Billard, Andrew Geronimo, Kurt W Short, Patrick J Drew, Jennifer Baccon, Steven L Weinstein, Frank G Gilliam, José A Stoute, Vernon M Chinchilli, Andrew F Read, Bruce J Gluckman, Steven J Schiff Mar 2017

A Murine Model To Study Epilepsy And Sudep Induced By Malaria Infection., Paddy Ssentongo, Anna E Robuccio, Godfrey Thuku, Derek G Sim, Ali Nabi, Fatemeh Bahari, Balaji Shanmugasundaram, Myles W Billard, Andrew Geronimo, Kurt W Short, Patrick J Drew, Jennifer Baccon, Steven L Weinstein, Frank G Gilliam, José A Stoute, Vernon M Chinchilli, Andrew F Read, Bruce J Gluckman, Steven J Schiff

Neurology Faculty Publications

One of the largest single sources of epilepsy in the world is produced as a neurological sequela in survivors of cerebral malaria. Nevertheless, the pathophysiological mechanisms of such epileptogenesis remain unknown and no adjunctive therapy during cerebral malaria has been shown to reduce the rate of subsequent epilepsy. There is no existing animal model of postmalarial epilepsy. In this technical report we demonstrate the first such animal models. These models were created from multiple mouse and parasite strain combinations, so that the epilepsy observed retained universality with respect to genetic background. We also discovered spontaneous sudden unexpected death in epilepsy …


The Role Of Estradiol Metabolism In Urogenital Schistosomiasis-Induced Bladder Cancer, Nuno Vale, Maria Gouveia, Gabriel Rinaldi, Julio Santos, Lucio Lara Santos, Paul J. Brindley, Jose Correia Da Costa Mar 2017

The Role Of Estradiol Metabolism In Urogenital Schistosomiasis-Induced Bladder Cancer, Nuno Vale, Maria Gouveia, Gabriel Rinaldi, Julio Santos, Lucio Lara Santos, Paul J. Brindley, Jose Correia Da Costa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Urogenital schistosomiasis is a neglected tropical disease that can lead to bladder cancer. How urogenital schistosomiasis induces carcinogenesis remains unclear, although there is evidence that the human blood fluke Schistosoma haematobium, the infectious agent of urogenital schistosomiasis, releases estradiol-like metabolites. These kind of compounds have been implicated in other cancers. Aiming for enhanced understanding of the pathogenesis of the urogenital schistosomiasisinduced bladder cancer, here we review, interpret, and discuss findings of estradiol-like metabolites detected in both the parasite and in the human urine during urogenital schistosomiasis. Moreover, we predict pathways and enzymes that are involved in the production of these …


Population-Based Pertussis Incidence And Risk Factors In Infants Less Than 6 Months In Nepal., Michelle M Hughes, Janet A Englund, Jane Kuypers, James M Tielsch, Subarna K Khatry, Laxman Shrestha, Steven C Leclerq, Mark Steinhoff, Joanne Katz Mar 2017

Population-Based Pertussis Incidence And Risk Factors In Infants Less Than 6 Months In Nepal., Michelle M Hughes, Janet A Englund, Jane Kuypers, James M Tielsch, Subarna K Khatry, Laxman Shrestha, Steven C Leclerq, Mark Steinhoff, Joanne Katz

Global Health Faculty Publications

Background.

Pertussis is estimated to cause 2 percent of childhood deaths globally and is a growing public health problem in developed countries despite high vaccination coverage. Infants are at greatest risk of morbidity and mortality. Maternal vaccination during pregnancy may be effective to prevent pertussis in young infants, but population-based estimates of disease burden in infants are lacking, particularly in low-income countries. The objective of this study was to estimate the incidence of pertussis in infants less than 6 months of age in Sarlahi District, Nepal.

Methods.

Nested within a population-based randomized controlled trial of influenza vaccination during pregnancy, infants …


Effect Of Immediate Initiation Of Antiretroviral Therapy On Risk Of Severe Bacterial Infections In Hiv-Positive People With Cd4 Cell Counts Of More Than 500 Cells Per Μl: Secondary Outcome Results From A Randomised Controlled Trial., Jemma O'Connor, Michael J Vjecha, Andrew N Phillips, Brian Angus, David Cooper, Fred Gordin, +Several Additional Authors Mar 2017

Effect Of Immediate Initiation Of Antiretroviral Therapy On Risk Of Severe Bacterial Infections In Hiv-Positive People With Cd4 Cell Counts Of More Than 500 Cells Per Μl: Secondary Outcome Results From A Randomised Controlled Trial., Jemma O'Connor, Michael J Vjecha, Andrew N Phillips, Brian Angus, David Cooper, Fred Gordin, +Several Additional Authors

Medicine Faculty Publications

BACKGROUND: The effects of antiretroviral therapy on risk of severe bacterial infections in people with high CD4 cell counts have not been well described. In this study, we aimed to quantify the effects of immediate versus deferred ART on the risk of severe bacterial infection in people with high CD4 cell counts in a preplanned analysis of the START trial.

METHODS: The START trial was a randomised controlled trial in ART-naive HIV-positive patients with CD4 cell count of more than 500 cells per μL assigned to immediate ART or deferral until their CD4 cell counts were lower than 350 cells …


Elevated Prevalence Of Helicobacter Species And Virulence Factors In Opisthorchiasis And Associated Hepatobiliary Disease., Raksawan Deenonpoe, Eimorn Mairiang, Pisaln Mairiang, Chawalit Pairojkul, Yaovalux Chamgramol, Gabriel Rinaldi, Alex Loukas, Paul J. Brindley, Banchob Sripa Feb 2017

Elevated Prevalence Of Helicobacter Species And Virulence Factors In Opisthorchiasis And Associated Hepatobiliary Disease., Raksawan Deenonpoe, Eimorn Mairiang, Pisaln Mairiang, Chawalit Pairojkul, Yaovalux Chamgramol, Gabriel Rinaldi, Alex Loukas, Paul J. Brindley, Banchob Sripa

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Recent reports suggest that Opisthorchis viverrini serves as a reservoir of Helicobacter and implicate Helicobacter in pathogenesis of opisthorchiasis-associated cholangiocarcinoma (CCA). Here, 553 age-sex matched cases and controls, 293 and 260 positive and negative for liver fluke O. viverrini eggs, of residents in Northeastern Thailand were investigated for associations among infection with liver fluke, Helicobacter and hepatobiliary fibrosis. The prevalence of H. pylori infection was higher in O. viverrini-infected than uninfected participants. H. pylori bacterial load correlated positively with intensity of O. viverrini infection, and participants with opisthorchiasis exhibited higher frequency of virulent cagA-positive H. pylori than those free of …


Advances In Neglected Tropical Disease Vaccines: Developing Relative Potency And Functional Assays For The Na-Gst-1/Alhydrogel Hookworm Vaccine., Jill B. Brelsford, Jordan L Plieskatt, Anna Yakovleva, Amar Jariwala, Brian P Keegan, Jin Peng, Pengjun Xia, Guangzhao Li, Doreen Campbell, Maria Victoria Periago, Rodrigo Correa-Oliveira, Maria Elena Bottazzi, Peter J. Hotez, David Diemert, Jeffrey M. Bethony Feb 2017

Advances In Neglected Tropical Disease Vaccines: Developing Relative Potency And Functional Assays For The Na-Gst-1/Alhydrogel Hookworm Vaccine., Jill B. Brelsford, Jordan L Plieskatt, Anna Yakovleva, Amar Jariwala, Brian P Keegan, Jin Peng, Pengjun Xia, Guangzhao Li, Doreen Campbell, Maria Victoria Periago, Rodrigo Correa-Oliveira, Maria Elena Bottazzi, Peter J. Hotez, David Diemert, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Publications

A new generation of vaccines for the neglected tropical diseases (NTDs) have now advanced into clinical development, with the Na-GST-1/Alhydrogel Hookworm Vaccine already being tested in Phase 1 studies in healthy adults. The current manuscript focuses on the often overlooked critical aspects of NTD vaccine product development, more specifically, vaccine stability testing programs. A key measure of vaccine stability testing is "relative potency" or the immunogenicity of the vaccine during storage. As with most NTD vaccines, the Na-GST-1/Alhydrogel Hookworm Vaccine was not developed by attenuation or inactivation of the pathogen (Necator americanus), so conventional methods for measuring relative potency are …


Parasite Infection, Carcinogenesis And Human Malignancy., Hoang Van Tong, Paul J. Brindley, Christian G Meyer, Thirumalaisamy P Velavan Feb 2017

Parasite Infection, Carcinogenesis And Human Malignancy., Hoang Van Tong, Paul J. Brindley, Christian G Meyer, Thirumalaisamy P Velavan

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Cancer may be induced by many environmental and physiological conditions. Infections with viruses, bacteria and parasites have been recognized for years to be associated with human carcinogenicity. Here we review current concepts of carcinogenicity and its associations with parasitic infections. The helminth diseases schistosomiasis, opisthorchiasis, and clonorchiasis are highly carcinogenic while the protozoan Trypanosoma cruzi, the causing agent of Chagas disease, has a dual role in the development of cancer, including both carcinogenic and anticancer properties. Although malaria per se does not appear to be causative in carcinogenesis, it is strongly associated with the occurrence of endemic Burkitt lymphoma in …


Bridging The Divide White Paper: Pregnant Women And Substance Use: Overview Of Research & Policy In The United States, Darla Bishop, Liz Borkowski, Megan Couillard, Amy Allina, Susanna Baruch, Susan Wood Feb 2017

Bridging The Divide White Paper: Pregnant Women And Substance Use: Overview Of Research & Policy In The United States, Darla Bishop, Liz Borkowski, Megan Couillard, Amy Allina, Susanna Baruch, Susan Wood

Jacobs Institute of Women's Health

This paper examines the current literature and policy implications of substance use and substance use disorders among pregnant and parenting women. While this is not meant to serve as an exhaustive literature review on this topic, it seeks to describe: current research on health effects of substance use and substance use disorders on pregnant women1 and their children; policies and programs that help ensure that pregnant women who use substances have access to the highest quality healthcare, including prenatal care; the current barriers to accessing treatment for substance use disorders for pregnant women, including those who are incarcerated; and the …


A Comparison Of The Quality Of Informed Consent For Clinical Trials Of An Experimental Hookworm Vaccine Conducted In Developed And Developing Countries., David J. Diemert, Lucas Lobato, Ashley Styczynski, Maria Zumer, Amanda Soares, Maria Flávia Gazzinelli Jan 2017

A Comparison Of The Quality Of Informed Consent For Clinical Trials Of An Experimental Hookworm Vaccine Conducted In Developed And Developing Countries., David J. Diemert, Lucas Lobato, Ashley Styczynski, Maria Zumer, Amanda Soares, Maria Flávia Gazzinelli

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Informed consent is one of the principal ethical requirements of conducting clinical research, regardless of the study setting. Breaches in the quality of the informed consent process are frequently described in reference to clinical trials conducted in developing countries, due to low levels of formal education, a lack of familiarity with biomedical research, and limited access to health services in these countries. However, few studies have directly compared the quality of the informed consent process in developed and developing countries using the same tool and in similar clinical trials. This study was conducted to compare the quality of the informed …


Identification Of Candidate Infection Genes From The Model Entomopathogenic Nematode Heterorhabditis Bacteriophora., Jonathan Vadnal, Ramesh Ratnappan, Melissa Keaney, Eric Kenney, Ioannis Eleftherianos, Damien O'Halloran, John M. Hawdon Jan 2017

Identification Of Candidate Infection Genes From The Model Entomopathogenic Nematode Heterorhabditis Bacteriophora., Jonathan Vadnal, Ramesh Ratnappan, Melissa Keaney, Eric Kenney, Ioannis Eleftherianos, Damien O'Halloran, John M. Hawdon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Despite important progress in the field of innate immunity, our understanding of host immune responses to parasitic nematode infections lags behind that of responses to microbes. A limiting factor has been the obligate requirement for a vertebrate host which has hindered investigation of the parasitic nematode infective process. The nematode parasite Heterorhabditis bacteriophora offers great potential as a model to genetically dissect the process of infection. With its mutualistic Photorhabdus luminescens bacteria, H. bacteriophora invades multiple species of insects, which it kills and exploits as a food source for the development of several nematode generations. The ability to culture …


Using Diagnostic Tests To Inform Better Care, Save Lives And Fight Antibiotic Resistance: A Factsheet For Healthcare Professionals, Antibiotic Resistance Action Center (Arac) Jan 2017

Using Diagnostic Tests To Inform Better Care, Save Lives And Fight Antibiotic Resistance: A Factsheet For Healthcare Professionals, Antibiotic Resistance Action Center (Arac)

Antibiotic Resistance Action Center (ARAC)

No abstract provided.