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https://www.readbyqxmd.com/read/28095824/community-based-health-care-is-an-essential-component-of-a-resilient-health-system-evidence-from-ebola-outbreak-in-liberia
#1
Kendra Siekmans, Salim Sohani, Tamba Boima, Florence Koffa, Luay Basil, Saïd Laaziz
BACKGROUND: Trained community health workers (CHW) enhance access to essential primary health care services in contexts where the health system lacks capacity to adequately deliver them. In Liberia, the Ebola outbreak further disrupted health system function. The objective of this study is to examine the value of a community-based health system in ensuring continued treatment of child illnesses during the outbreak and the role that CHWs had in Ebola prevention activities. METHODS: A descriptive observational study design used mixed methods to collect data from CHWs (structured survey, n = 60; focus group discussions, n = 16), government health facility workers and project staff...
January 17, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28095476/a-systematic-review-of-ebola-treatment-trials-to-assess-the-extent-to-which-they-adhere-to-ethical-guidelines
#2
Thomas Richardson, Andrew McDonald Johnston, Heather Draper
BACKGROUND: Objective: To determine to what extent each trial met criteria specified in three research frameworks for ethical trial conduct. Design: Systematic review and narrative analysis. METHODS AND FINDINGS: Data sources: MEDBASE and EMBASE databases were searched using a specific search strategy. The Cochrane database for systematic reviews, the PROSPERO database and trial registries were examined. A grey literature search and citation search were also carried out...
2017: PloS One
https://www.readbyqxmd.com/read/27959624/will-there-be-a-cure-for-ebola
#3
Anthony P Cardile, Travis K Warren, Karen A Martins, Ronald B Reisler, Sina Bavari
Despite the unprecedented Ebola virus outbreak response in West Africa, no Ebola medical countermeasures have been approved by the US Food and Drug Administration. However, multiple valuable lessons have been learned about the conduct of clinical research in a resource-poor, high risk-pathogen setting. Numerous therapeutics were explored or developed during the outbreak, including repurposed drugs, nucleoside and nucleotide analogues (BCX4430, brincidofovir, favipiravir, and GS-5734), nucleic acid-based drugs (TKM-Ebola and AVI-7537), and immunotherapeutics (convalescent plasma and ZMapp)...
January 6, 2017: Annual Review of Pharmacology and Toxicology
https://www.readbyqxmd.com/read/27942512/treating-the-host-response-to-emerging-virus-diseases-lessons-learned-from-sepsis-pneumonia-influenza-and-ebola
#4
REVIEW
David S Fedson
There is an ongoing threat of epidemic or pandemic diseases that could be caused by influenza, Ebola or other emerging viruses. It will be difficult and costly to develop new drugs that target each of these viruses. Statins and angiotensin receptor blockers (ARBs) have been effective in treating patients with sepsis, pneumonia and influenza, and a statin/ARB combination appeared to dramatically reduce mortality during the recent Ebola outbreak. These drugs target (among other things) the endothelial dysfunction found in all of these diseases...
November 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27914852/a-call-to-strengthen-the-global-strategy-against-schistosomiasis-and-soil-transmitted-helminthiasis-the-time-is-now
#5
REVIEW
Nathan C Lo, David G Addiss, Peter J Hotez, Charles H King, J Russell Stothard, Darin S Evans, Daniel G Colley, William Lin, Jean T Coulibaly, Amaya L Bustinduy, Giovanna Raso, Eran Bendavid, Isaac I Bogoch, Alan Fenwick, Lorenzo Savioli, David Molyneux, Jürg Utzinger, Jason R Andrews
In 2001, the World Health Assembly (WHA) passed the landmark WHA 54.19 resolution for global scale-up of mass administration of anthelmintic drugs for morbidity control of schistosomiasis and soil-transmitted helminthiasis, which affect more than 1·5 billion of the world's poorest people. Since then, more than a decade of research and experience has yielded crucial knowledge on the control and elimination of these helminthiases. However, the global strategy has remained largely unchanged since the original 2001 WHA resolution and associated WHO guidelines on preventive chemotherapy...
November 30, 2016: Lancet Infectious Diseases
https://www.readbyqxmd.com/read/27902714/evaluation-of-the-activity-of-lamivudine-and-zidovudine-against-ebola-virus
#6
Yu Cong, Julie Dyall, Brit J Hart, Lisa Evans DeWald, Joshua C Johnson, Elena Postnikova, Huanying Zhou, Robin Gross, Oscar Rojas, Isis Alexander, Nicole Josleyn, Tengfei Zhang, Julia Michelotti, Krisztina Janosko, Pamela J Glass, Mike Flint, Laura K McMullan, Christina F Spiropoulou, Tim Mierzwa, Rajarshi Guha, Paul Shinn, Sam Michael, Carleen Klumpp-Thomas, Crystal McKnight, Craig Thomas, Ann E Eakin, Kathleen G O'Loughlin, Carol E Green, Paul Catz, Jon C Mirsalis, Anna N Honko, Gene G Olinger, Richard S Bennett, Michael R Holbrook, Lisa E Hensley, Peter B Jahrling
In the fall of 2014, an international news agency reported that patients suffering from Ebola virus disease (EVD) in Liberia were treated successfully with lamivudine, an antiviral drug used to treat human immunodeficiency virus-1 and hepatitis B virus infections. According to the report, 13 out of 15 patients treated with lamivudine survived and were declared free from Ebola virus disease. In this study, the anti-Ebola virus (EBOV) activity of lamivudine and another antiretroviral, zidovudine, were evaluated in a diverse set of cell lines against two variants of wild-type EBOV...
2016: PloS One
https://www.readbyqxmd.com/read/27898018/combating-ebola-with-repurposed-therapeutics-using-the-cando-platform
#7
Gaurav Chopra, Sashank Kaushik, Peter L Elkin, Ram Samudrala
Ebola virus disease (EVD) is extremely virulent with an estimated mortality rate of up to 90%. However, the state-of-the-art treatment for EVD is limited to quarantine and supportive care. The 2014 Ebola epidemic in West Africa, the largest in history, is believed to have caused more than 11,000 fatalities. The countries worst affected are also among the poorest in the world. Given the complexities, time, and resources required for a novel drug development, finding efficient drug discovery pathways is going to be crucial in the fight against future outbreaks...
November 25, 2016: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/27893999/ebola-virus-disease-an-update-on-current-prevention-and-management-strategies
#8
REVIEW
M A Trad, W Naughton, A Yeung, L Mazlin, M O'sullivan, N Gilroy, D A Fisher, R L Stuart
Ebola virus disease (EVD) is characterised by systemic viral replication, immuno-suppression, abnormal inflammatory responses, large volume fluid and electrolyte losses, and high mortality in under-resourced settings. There are various therapeutic strategies targeting EVD including vaccines utilizing different antigen delivery methods, antibody-based therapies and antiviral drugs. These therapies remain experimental, but received attention following their use particularly in cases treated outside West Africa during the 2014-15 outbreak, in which 20 (80%) out of 25 patients survived...
January 2017: Journal of Clinical Virology: the Official Publication of the Pan American Society for Clinical Virology
https://www.readbyqxmd.com/read/27890675/synergistic-drug-combination-effectively-blocks-ebola-virus-infection
#9
Wei Sun, Shihua He, Carles Martínez-Romero, Jennifer Kouznetsova, Gregory Tawa, Miao Xu, Paul Shinn, Ethan G Fisher, Yan Long, Omid Motabar, Shu Yang, Philip E Sanderson, Peter R Williamson, Adolfo García-Sastre, Xiangguo Qiu, Wei Zheng
Although a group of FDA-approved drugs were previously identified with activity against Ebola virus (EBOV), most of them are not clinically useful because their human blood concentrations are not high enough to inhibit EBOV infection. We screened 795 unique three-drug combinations in an EBOV entry assay. Two sets of three-drug combinations, toremifene-mefloquine-posaconazole and toremifene-clarithromycin-posaconazole, were identified that effectively blocked EBOV entry and were further validated for inhibition of live EBOV infection...
January 2017: Antiviral Research
https://www.readbyqxmd.com/read/27888126/understanding-the-complex-evolution-of-rapidly-mutating-viruses-with-deep-sequencing-beyond-the-analysis-of-viral-diversity
#10
REVIEW
Preston Leung, Auda A Eltahla, Andrew R Lloyd, Rowena A Bull, Fabio Luciani
With the advent of affordable deep sequencing technologies, detection of low frequency variants within genetically diverse viral populations can now be achieved with unprecedented depth and efficiency. The high-resolution data provided by next generation sequencing technologies is currently recognised as the gold standard in estimation of viral diversity. In the analysis of rapidly mutating viruses, longitudinal deep sequencing datasets from viral genomes during individual infection episodes, as well as at the epidemiological level during outbreaks, now allow for more sophisticated analyses such as statistical estimates of the impact of complex mutation patterns on the evolution of the viral populations both within and between hosts...
November 22, 2016: Virus Research
https://www.readbyqxmd.com/read/27880800/minimal-in-vivo-efficacy-of-iminosugars-in-a-lethal-ebola-virus-guinea-pig-model
#11
Joanna L Miller, Simon G Spiro, Stuart D Dowall, Irene Taylor, Antony Rule, Dominic S Alonzi, Andrew C Sayce, Edward Wright, Emma M Bentley, Ruth Thom, Graham Hall, Raymond A Dwek, Roger Hewson, Nicole Zitzmann
The antiviral properties of iminosugars have been reported previously in vitro and in small animal models against Ebola virus (EBOV); however, their effects have not been tested in larger animal models such as guinea pigs. We tested the iminosugars N-butyl-deoxynojirimycin (NB-DNJ) and N-(9-methoxynonyl)-1deoxynojirimycin (MON-DNJ) for safety in uninfected animals, and for antiviral efficacy in animals infected with a lethal dose of guinea pig adapted EBOV. 1850 mg/kg/day NB-DNJ and 120 mg/kg/day MON-DNJ administered intravenously, three times daily, caused no adverse effects and were well tolerated...
2016: PloS One
https://www.readbyqxmd.com/read/27879115/preface
#12
Avner Friedman, Mirosław Lachowicz, Urszula Ledzewicz, Monika Joanna Piotrowska, Zuzanna Szymanska
This volume was inspired by the topics presented at the international conference "Micro and Macro Systems in Life Sciences" which was held on Jun 8-12, 2015 in Będlewo, Poland. System biology is an approach which tries to understand how micro systems, at the molecular and cellular levels, affect macro systems such as organs, tissue and populations. Thus it is not surprising that a major theme of this volume evolves around cancer and its treatment. Articles on this topic include models for tumor induced angiogenesis, without and with delays, metastatic niche of the bone marrow, drug resistance and metronomic chemotherapy, and virotherapy of glioma...
February 1, 2017: Mathematical Biosciences and Engineering: MBE
https://www.readbyqxmd.com/read/27872619/ebola-vp40-in-exosomes-can-cause-immune-cell-dysfunction
#13
Michelle L Pleet, Allison Mathiesen, Catherine DeMarino, Yao A Akpamagbo, Robert A Barclay, Angela Schwab, Sergey Iordanskiy, Gavin C Sampey, Benjamin Lepene, Sergei Nekhai, M J Aman, Fatah Kashanchi
Ebola virus (EBOV) is an enveloped, ssRNA virus from the family Filoviridae capable of causing severe hemorrhagic fever with up to 80-90% mortality rates. The most recent outbreak of EBOV in West Africa starting in 2014 resulted in over 11,300 deaths; however, long-lasting persistence and recurrence in survivors has been documented, potentially leading to further transmission of the virus. We have previously shown that exosomes from cells infected with HIV-1, HTLV-1 and Rift Valley Fever virus are able to transfer viral proteins and non-coding RNAs to naïve recipient cells, resulting in an altered cellular activity...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27864075/the-natural-compound-silvestrol-is-a-potent-inhibitor-of-ebola-virus-replication
#14
Nadine Biedenkopf, Kerstin Lange-Grünweller, Falk W Schulte, Aileen Weißer, Christin Müller, Dirk Becker, Stephan Becker, Roland K Hartmann, Arnold Grünweller
The DEAD-box RNA helicase eIF4A, which is part of the heterotrimeric translation initiation complex in eukaryotes, is an important novel drug target in cancer research because its helicase activity is required to unwind extended and highly structured 5'-UTRs of several proto-oncogenes. Silvestrol, a natural compound isolated from the plant Aglaia foveolata, is a highly efficient, non-toxic and specific inhibitor of eIF4A. Importantly, 5'-capped viral mRNAs often contain structured 5'-UTRs as well, which may suggest a dependence on eIF4A for their translation by the host protein synthesis machinery...
January 2017: Antiviral Research
https://www.readbyqxmd.com/read/27849485/psychological-impact-of-deploying-in-support-of-the-u-s-response-to-ebola-a-systematic-review-and-meta-analysis-of-past-outbreaks
#15
Kartavya J Vyas, Eileen M Delaney, Jennifer A Webb-Murphy, Scott L Johnston
OBJECTIVE: To examine the potential psychological impact of deploying in support of the U.S. response to Ebola in west Africa by systematic review and meta-analysis. METHODS: Peer-reviewed articles published between January 2000 and December 2014 were identified using PubMed, PsycINFO, and Web of Science. Thirty-two studies involving 26,869 persons were included in the systematic review; 13 studies involving 7,785 persons were included in the meta-analysis. Pooled standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated...
November 2016: Military Medicine
https://www.readbyqxmd.com/read/27799354/comprehensive-characterization-of-cellular-immune-responses-following-ebola-virus-infection
#16
Christine Dahlke, Sebastian Lunemann, Rahel Kasonta, Benno Kreuels, Stefan Schmiedel, My L Ly, Sarah K Fehling, Thomas Strecker, Stephan Becker, Marcus Altfeld, Abdourahmane Sow, Ansgar W Lohse, César Muñoz-Fontela, Marylyn M Addo
The West-African Ebola virus disease (EVD) outbreak was the largest EVD outbreak in history. However, data on lymphocyte dynamics and antigen-specificity of T-cells in Ebola survivors are scarce and our understanding of EVD-pathophysiology is limited.The care for an EVD-survivor, who cleared the infection without experimental drugs allowed for the detailed examination of lymphocyte dynamics. We demonstrate persistence of T-cell activation well beyond viral clearance and detect Ebola-specific T-cells. Our study provides significant insights into lymphocyte specificity during the re-convalescent phase of EVD and may inform novel strategies to treat EVD...
October 31, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27792169/integrated-computational-approach-for-virtual-hit-identification-against-ebola-viral-proteins-vp35-and-vp40
#17
Muhammad Usman Mirza, Nazia Ikram
The Ebola virus (EBOV) has been recognised for nearly 40 years, with the most recent EBOV outbreak being in West Africa, where it created a humanitarian crisis. Mortalities reported up to 30 March 2016 totalled 11,307. However, up until now, EBOV drugs have been far from achieving regulatory (FDA) approval. It is therefore essential to identify parent compounds that have the potential to be developed into effective drugs. Studies on Ebola viral proteins have shown that some can elicit an immunological response in mice, and these are now considered essential components of a vaccine designed to protect against Ebola haemorrhagic fever...
October 26, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27771389/lassa-and-ebola-virus-inhibitors-identified-using-minigenome-and-recombinant-virus-reporter-systems
#18
Stephen R Welch, Lisa Wiggleton Guerrero, Ayan K Chakrabarti, Laura K McMullan, Mike Flint, Gregory R Bluemling, George R Painter, Stuart T Nichol, Christina F Spiropoulou, César G Albariño
Lassa virus (LASV) and Ebola virus (EBOV) infections are important global health issues resulting in significant morbidity and mortality. While several promising drug and vaccine trials for EBOV are ongoing, options for LASV infection are currently limited to ribavirin treatment. A major factor impeding the development of antiviral compounds to treat these infections is the need to manipulate the virus under BSL-4 containment, limiting research to a few institutes worldwide. Here we describe the development of a novel LASV minigenome assay based on the ambisense LASV S segment genome, with authentic terminal untranslated regions flanking a ZsGreen (ZsG) fluorescent reporter protein and a Gaussia princeps luciferase (gLuc) reporter gene...
October 19, 2016: Antiviral Research
https://www.readbyqxmd.com/read/27764560/ebola-vaccines-in-clinical-trial-the-promising-candidates
#19
Yuxiao Wang, Jingxin Li, Yuemei Hu, Qi Liang, Mingwei Wei, Fengcai Zhu
Ebola virus disease (EVD) has become a great threat to humans across the world in recent years. The 2014 Ebola epidemic in West Africa caused numerous deaths and attracted worldwide attentions. Since no specific drugs and treatments against EVD was available, vaccination was considered as the most promising and effective method of controlling this epidemic. So far, 7 vaccine candidates had been developed and evaluated through clinical trials. Among them, the recombinant vesicular stomatitis virus-based vaccine (rVSV-EBOV) is the most promising candidate, which demonstrated a significant protection against EVD in phase III clinical trial...
October 20, 2016: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/27754861/deciphering-assumptions-about-stepped-wedge-designs-the-case-of-ebola-vaccine-research
#20
Adélaïde Doussau, Christine Grady
Ethical concerns about randomising persons to a no-treatment arm in the context of Ebola epidemic led to consideration of alternative designs. The stepped wedge (SW) design, in which participants or clusters are randomised to receive an intervention at different time points, gained popularity. Common arguments in favour of using this design are (1) when an intervention is likely to do more good than harm, (2) all participants should receive the experimental intervention at some time point during the study and (3) the design might be preferable for practical reasons...
October 17, 2016: Journal of Medical Ethics
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