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https://www.readbyqxmd.com/read/28922385/metabolomics-analyses-identify-platelet-activating-factors-and-heme-breakdown-products-as-lassa-fever-biomarkers
#1
Trevor V Gale, Timothy M Horton, Donald S Grant, Robert F Garry
Lassa fever afflicts tens of thousands of people in West Africa annually. The rapid progression of patients from febrile illness to fulminant syndrome and death provides incentive for development of clinical prognostic markers that can guide case management. The small molecule profile of serum from febrile patients triaged to the Viral Hemorrhagic Fever Ward at Kenema Government Hospital in Sierra Leone was assessed using untargeted Ultra High Performance Liquid Chromatography Mass Spectrometry. Physiological dysregulation resulting from Lassa virus (LASV) infection occurs at the small molecule level...
September 18, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28875769/understanding-the-cryptic-nature-of-lassa-fever-in-west-africa
#2
Rory Gibb, Lina M Moses, David W Redding, Kate E Jones
Lassa fever (LF) is increasingly recognized by global health institutions as an important rodent-borne disease with severe impacts on some of West Africa's poorest communities. However, our knowledge of LF ecology, epidemiology and distribution is limited, which presents barriers to both short-term disease forecasting and prediction of long-term impacts of environmental change on Lassa virus (LASV) zoonotic transmission dynamics. Here, we synthesize current knowledge to show that extrapolations from past research have produced an incomplete picture of the incidence and distribution of LF, with negative consequences for policy planning, medical treatment and management interventions...
September 6, 2017: Pathogens and Global Health
https://www.readbyqxmd.com/read/28869611/human-monoclonal-antibody-therapy-protects-nonhuman-primates-against-advanced-lassa-fever
#3
Chad E Mire, Robert W Cross, Joan B Geisbert, Viktoriya Borisevich, Krystle N Agans, Daniel J Deer, Megan L Heinrich, Megan M Rowland, Augustine Goba, Mambu Momoh, Mathew L Boisen, Donald S Grant, Mohamed Fullah, Sheik Humarr Khan, Karla A Fenton, James E Robinson, Luis M Branco, Robert F Garry, Thomas W Geisbert
There are no approved treatments for Lassa fever, which is endemic to the same regions of West Africa that were recently devastated by Ebola. Here we show that a combination of human monoclonal antibodies that cross-react with the glycoproteins of all four clades of Lassa virus is able to rescue 100% of cynomolgus macaques when treatment is initiated at advanced stages of disease, including up to 8 d after challenge.
September 4, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28863471/moving-lassa-fever-research-and-care-into-the-21st-century
#4
William A Fischer, David A Wohl
No abstract text is available yet for this article.
June 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28826838/interferon-%C3%AE-driven-inos-a-molecular-pathway-to-terminal-shock-in-arenavirus-hemorrhagic-fever
#5
Melissa M Remy, Mehmet Sahin, Lukas Flatz, Tommy Regen, Lifen Xu, Mario Kreutzfeldt, Benedict Fallet, Camille Doras, Toni Rieger, Lukas Bestmann, Uwe-Karsten Hanisch, Beat A Kaufmann, Doron Merkler, Daniel D Pinschewer
Arenaviruses such as Lassa virus (LASV) cause hemorrhagic fever. Terminal shock is associated with a systemic cytokine storm, but the mechanisms are ill defined. Here we used HLA-A2-expressing mice infected with a monkey-pathogenic strain of lymphocytic choriomeningitis virus (LCMV-WE), a close relative of LASV, to investigate the pathophysiology of arenavirus hemorrhagic fever (AHF). AHF manifested as pleural effusions, edematous skin swelling, and serum albumin loss, culminating in hypovolemic shock. A characteristic cytokine storm included numerous pro-inflammatory cytokines and nitric oxide (NO) metabolites...
September 13, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28797730/an-lasv-gpc-pseudotyped-virus-based-reporter-system-enables-evaluation-of-vaccines-in-mice-under-non-bsl-4-conditions
#6
Qianqian Li, Qiang Liu, Weijin Huang, Jiajing Wu, Jianhui Nie, Meng Wang, Chenyan Zhao, Li Zhang, Youchun Wang
Lassa virus (LASV) causes a severe hemorrhagic fever endemic throughout western Africa. Because of the ability to cause lethal disease in humans, limited treatment options, and potential as a bioweapon, the need for vaccines to prevent LASV epidemic is urgent. However, LASV vaccine development has been hindered by the lack of appropriate small animal models for efficacy evaluation independent of biosafety level four (BSL-4) facilities. Here we generated an LASV-glycoprotein precursor (GPC)-pseudotyped Human immunodeficiency virus containing firefly luciferase (Fluc) reporter gene as surrogate to develop a bioluminescent-imaging-based BALB/c mouse model for one-round infection under non-BSL-4 conditions, in which the bioluminescent intensity of Fluc was utilized as endpoint when evaluating vaccine efficacy...
August 7, 2017: Vaccine
https://www.readbyqxmd.com/read/28794024/highly-pathogenic-new-world-arenavirus-infection-activates-the-pattern-recognition-receptor-pkr-without-attenuating-virus-replication-in-human-cells
#7
Cheng Huang, Olga A Kolokoltsova, Elizabeth J Mateer, Takaaki Koma, Slobodan Paessler
The arenavirus family consists of several highly pathogenic viruses including the Old World (OW) arenavirus Lassa fever virus (LASV) and the New World (NW) Junín virus (JUNV) and Machupo virus (MACV). Host response to infection by these pathogenic arenaviruses is distinct in many aspects. NW JUNV and MACV infections readily induce an IFN response in human cells, while OW LASV infection usually triggers an undetectable or weak IFN response. JUNV induces IFN response through RIG-I, suggesting that the host non-self RNA sensor readily detects JUNV viral RNAs during infection and activates IFN response...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28780425/enhanced-protection-against-experimental-junin-virus-infection-through-the-use-of-a-modified-favipiravir-loading-dose-strategy
#8
Brian B Gowen, Jonna B Westover, Eric J Sefing, Arnaud J Van Wettere, Kevin W Bailey, Luci Wandersee, Takashi Komeno, Yousuke Furuta
A collection of Old and New World arenaviruses are etiologic agents of viral hemorrhagic fever, a syndrome that features hematologic abnormalities, vascular leak, hypovolemia, and multi-organ failure. Treatment is limited to ribavirin for Lassa fever and immune plasma for Argentine hemorrhagic fever. Improved therapeutic options that are safe, more effective and widely available are needed. Here, we show that modification of favipiravir treatment to include a high-dose loading period achieves complete protection in a guinea pig model of Argentine hemorrhagic fever when treatment was initiated two days following challenge with Junin virus (JUNV)...
September 2017: Antiviral Research
https://www.readbyqxmd.com/read/28748835/prevalence-of-lassa-virus-among-rodents-trapped-in-three-south-south-states-of-nigeria
#9
D E Agbonlahor, A Erah, I M Agba, F E Oviasogie, A F Ehiaghe, M Wankasi, O A Eremwanarue, I J Ehiaghe, E C Ogbu, R I Iyen, S Abbey, M Y Tatfeng, J Uhunmwangho
BACKGROUND & OBJECTIVES: Lassa fever has been endemic in Nigeria since 1969. The rodent Mastomys natalensis has been widely claimed to be the reservoir host of the Lassa virus. This study was designed to investigate the dis- tribution of species of rodents in three states (Edo, Delta and Bayelsa) of Nigeria and to determine the prevalence of Lassa virus amongst trapped rodents in the selected states. METHODS: Rodents were trapped during November 2015 to October 2016 from the three states in South-South re- gion of Nigeria...
April 2017: Journal of Vector Borne Diseases
https://www.readbyqxmd.com/read/28701331/lassa-fever
#10
REVIEW
Catherine Houlihan, Ron Behrens
No abstract text is available yet for this article.
July 12, 2017: BMJ: British Medical Journal
https://www.readbyqxmd.com/read/28690743/-knowledge-and-attitudes-of-community-volunteers-on-lassa-and-ebola-viral-haemorrhagic-fevers-in-the-donga-department-north-benin
#11
Cossi Angelo Attinsounon, Cossi Athanase Hounnankan, Comlan Albert Dovonou, Cossi Adébayo Alassani, Sourakatou Salifou
No abstract text is available yet for this article.
2017: Pan African Medical Journal
https://www.readbyqxmd.com/read/28679759/mutational-analysis-of-lassa-virus-glycoprotein-highlights-regions-required-for-alpha-dystroglycan-utilization
#12
Marissa Acciani, Jacob T Alston, Guohui Zhao, Hayley Reynolds, Afroze M Ali, Brian Xu, Melinda A Brindley
Lassa virus (LASV) is an enveloped RNA virus endemic to West Africa and responsible for severe cases of hemorrhagic fever. Virus entry is mediated by the glycoprotein complex consisting of a stable-signal peptide, a receptor-binding subunit, GP1, and a viral-host membrane fusion subunit, GP2. Several cellular receptors can interact with the GP1 subunit and mediate viral entry, including alpha-dystroglycan (αDG) and lysosome-associated membrane protein 1 (LAMP1). In order to define the regions within GP1 that interact with the cellular receptors, we implemented insertional mutagenesis, carbohydrate shielding, and alanine scanning mutagenesis...
September 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28671959/prevalence-of-lassa-virus-disease-lvd-in-nigerian-children-with-fever-or-fever-and-convulsions-in-an-endemic-area
#13
Odigie C Akhuemokhan, Rosemary O Ewah-Odiase, Nosa Akpede, Jacqueline Ehimuan, Donatus I Adomeh, Ikpomwonsa Odia, Sylvia C Olomu, Meike Pahlmann, Beate Becker-Ziaja, Christian T Happi, Danny A Asogun, Sylvanus A Okogbenin, Peter O Okokhere, Osagie S Dawodu, Irekpono U Omoike, Pardis C Sabeti, Stephan Günther, George O Akpede
BACKGROUND: Convulsions with fever in children are a common neurologic emergency in the tropics, and determining the contribution of endemic viral infections can be challenging. In particular, there is a dearth of data on the prevalence and clinical differentiation of Lassa virus disease (LVD) in febrile children in endemic areas of Nigeria, which has multiple lineages of the virus. The aim of this study was to determine the prevalence and presentation of LVD in febrile children with and without convulsions...
July 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28638939/-consequences-of-autopsies-for-the-living-causes-of-death-in-the-clinical-diagnosis-septic-and-toxic-shock
#14
REVIEW
L Ozretić, A Schwindowski, H-P Dienes, R Büttner, U Drebber, J W U Fries
BACKGROUND: There is reason to believe that the diagnosis of septic and toxic shock, as indicated on the death certificate, cannot be confirmed as the cause of death without autopsy and subsequent histological analysis. The external examination of the corpse can therefore not represent the sole basis for a reliable statement about the infection status of a corpse, e. g. as a prerequisite for embalming. MATERIAL AND METHODS: The validity of autopsy in determining septic and toxic shock as the cause of death is demonstrated in 7 exemplary cases...
June 21, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28584177/structural-drivers-of-vulnerability-to-zoonotic-disease-in-africa
#15
Vupenyu Dzingirai, Salome Bukachi, Melissa Leach, Lindiwe Mangwanya, Ian Scoones, Annie Wilkinson
This paper argues that addressing the underlying structural drivers of disease vulnerability is essential for a 'One Health' approach to tackling zoonotic diseases in Africa. Through three case studies-trypanosomiasis in Zimbabwe, Ebola and Lassa fever in Sierra Leone and Rift Valley fever in Kenya-we show how political interests, commercial investments and conflict and securitization all generate patterns of vulnerability, reshaping the political ecology of disease landscapes, influencing traditional coping mechanisms and affecting health service provision and outbreak responses...
July 19, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28584172/integrative-modelling-for-one-health-pattern-process-and-participation
#16
REVIEW
I Scoones, K Jones, G Lo Iacono, D W Redding, A Wilkinson, J L N Wood
This paper argues for an integrative modelling approach for understanding zoonoses disease dynamics, combining process, pattern and participatory models. Each type of modelling provides important insights, but all are limited. Combining these in a '3P' approach offers the opportunity for a productive conversation between modelling efforts, contributing to a 'One Health' agenda. The aim is not to come up with a composite model, but seek synergies between perspectives, encouraging cross-disciplinary interactions...
July 19, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28584171/local-disease-ecosystem-livelihood-dynamics-reflections-from-comparative-case-studies-in-africa
#17
Melissa Leach, Bernard Bett, M Said, Salome Bukachi, Rosemary Sang, Neil Anderson, Noreen Machila, Joanna Kuleszo, Kathryn Schaten, Vupenyu Dzingirai, Lindiwe Mangwanya, Yaa Ntiamoa-Baidu, Elaine Lawson, Kofi Amponsah-Mensah, Lina M Moses, Annie Wilkinson, Donald S Grant, James Koninga
This article explores the implications for human health of local interactions between disease, ecosystems and livelihoods. Five interdisciplinary case studies addressed zoonotic diseases in African settings: Rift Valley fever (RVF) in Kenya, human African trypanosomiasis in Zambia and Zimbabwe, Lassa fever in Sierra Leone and henipaviruses in Ghana. Each explored how ecological changes and human-ecosystem interactions affect pathogen dynamics and hence the likelihood of zoonotic spillover and transmission, and how socially differentiated peoples' interactions with ecosystems and animals affect their exposure to disease...
July 19, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28572385/structural-basis-for-antibody-mediated-neutralization-of-lassa-virus
#18
Kathryn M Hastie, Michelle A Zandonatti, Lara M Kleinfelter, Megan L Heinrich, Megan M Rowland, Kartik Chandran, Luis M Branco, James E Robinson, Robert F Garry, Erica Ollmann Saphire
The arenavirus Lassa causes severe hemorrhagic fever and a significant disease burden in West Africa every year. The glycoprotein, GPC, is the sole antigen expressed on the viral surface and the critical target for antibody-mediated neutralization. Here we present the crystal structure of the trimeric, prefusion ectodomain of Lassa GP bound to a neutralizing antibody from a human survivor at 3.2-angstrom resolution. The antibody extensively anchors two monomers together at the base of the trimer, and biochemical analysis suggests that it neutralizes by inhibiting conformational changes required for entry...
June 2, 2017: Science
https://www.readbyqxmd.com/read/28555386/molecular-pathogenesis-of-viral-hemorrhagic-fever
#19
REVIEW
Christopher F Basler
The clinical syndrome referred to as viral hemorrhagic fever (VHF) can be caused by several different families of RNA viruses, including select members of the arenaviruses, bunyaviruses, filoviruses, and flaviviruses. VHF is characterized by malaise, fever, vascular permeability, decreased plasma volume, coagulation abnormalities, and varying degrees of hemorrhage. Study of the filovirus Ebola virus has demonstrated a critical role for suppression of innate antiviral defenses in viral pathogenesis. Additionally, antigen-presenting cells are targets of productive infection and immune dysregulation...
May 29, 2017: Seminars in Immunopathology
https://www.readbyqxmd.com/read/28511600/knowledge-attitude-and-practices-toward-lassa-fever-control-and-prevention-among-residents-of-ile-ife-southwest-nigeria
#20
S A Olowookere, C A Adegbenro, A Idowu, A G Omisore, O M Shabi, U R Ikem, G A Ekwere, I F Oderinde
Lassa fever had been reported as a cause of death especially in endemic parts of Nigeria. This study assessed the knowledge, attitude, and practices toward Lassa fever control and prevention among residents of Ile-Ife, southwest Nigeria. Descriptive cross-sectional study was conducted among consenting randomly selected adults using an interviewer administered questionnaire. Data were analyzed using descriptive and inferential statistics. A total of 400 questionnaires with completed data were analyzed (response rate 96%)...
January 2017: International Quarterly of Community Health Education
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