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https://www.readbyqxmd.com/read/28532397/a-systematic-review-of-factors-that-shape-implementation-of-mass-drug-administration-for-lymphatic-filariasis-in-sub-saharan-africa
#1
Adam Silumbwe, Joseph Mumba Zulu, Hikabasa Halwindi, Choolwe Jacobs, Jessy Zgambo, Rosalia Dambe, Mumbi Chola, Gershom Chongwe, Charles Michelo
BACKGROUND: Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF) elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA) region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities...
May 22, 2017: BMC Public Health
https://www.readbyqxmd.com/read/28523851/identification-of-multiple-druggable-secondary-sites-by-fragment-screening-against-dc-sign
#2
Jonas Aretz, Hannes Baukmann, Elena Shanina, Jonas Hanske, Robert Wawrzinek, Viktor A Zapol'skii, Peter H Seeberger, Dieter E Kaufmann, Christoph Rademacher
DC-SIGN is a cell-surface receptor for several pathogenic threats, such as HIV, Ebola virus, or Mycobacterium tuberculosis. Multiple attempts to develop inhibitors of the underlying carbohydrate-protein interactions have been undertaken in the past fifteen years. Still, drug-like DC-SIGN ligands are sparse, which is most likely due to its hydrophilic, solvent-exposed carbohydrate-binding site. Herein, we report on a parallel fragment screening against DC-SIGN applying SPR and a reporter displacement assay, which complements previous screenings using (19) F NMR spectroscopy and chemical fragment microarrays...
May 19, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28520909/large-scale-data-driven-integrative-framework-for-extracting-essential-targets-and-processes-from-disease-associated-gene-data-sets
#3
Gaston K Mazandu, Emile R Chimusa, Kayleigh Rutherford, Elsa-Gayle Zekeng, Zoe Z Gebremariam, Maryam Y Onifade, Nicola J Mulder
Populations worldwide currently face several public health challenges, including growing prevalence of infections and the emergence of new pathogenic organisms. The cost and risk associated with drug development make the development of new drugs for several diseases, especially orphan or rare diseases, unappealing to the pharmaceutical industry. Proof of drug safety and efficacy is required before market approval, and rigorous testing makes the drug development process slow, expensive and frequently result in failure...
May 18, 2017: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28516937/ebola-outbreak-in-the-congo-tuberculosis-drug-resistance-in-russia-and-gm-mustard-seeds-in-india
#4
(no author information available yet)
No abstract text is available yet for this article.
May 17, 2017: Nature
https://www.readbyqxmd.com/read/28482272/screening-of-commercial-cyclic-peptide-conjugated-to-hiv-1-tat-peptide-as-inhibitor-of-n-terminal-heptad-repeat-glycoprotein-2-ectodomain-ebola-virus-through-in-silico-analysis
#5
Usman Sumo Friend Tambunan, Ahmad Husein Alkaff, Mochammad Arfin Fardiansyah Nasution, Arli Aditya Parikesit, Djati Kerami
Ebola Hemorrhagic Fever (EHF) is a disease caused by viruses from genus Ebolavirus. Zaire ebolavirus (EBOV) is the deadliest species which has 76% case fatality rate. Up until now, there is no U.S. Food and Drug Administration (FDA) approved drugs to treat EHF. Antiviral drug based on EBOV N-terminal heptad repeat glycoprotein-2 (NHR GP2) Ectodomain inhibitor is one kind of treatment that has not well developed. NHR GP2 Ectodomain has an important role in the process of EBOV entry into the cell through endocytosis mechanism...
April 21, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28462833/recent-progress-on-the-treatment-of-ebola-virus-disease-with-favipiravir-and-other-related-strategies
#6
Tao Zhang, Min Zhai, Jianbo Ji, Jian Zhang, Ye Tian, Xinyong Liu
Ebola virus is one of the most threatening pathogens with the mortality rate as high as 90% in the world. There are no licensed therapeutic drugs or preventive vaccines for Ebola hemorrhagic fever up to date. Favipiravir, a novel antiviral drug which was mainly used for the treatment of influenza, now has been demonstrated to have a curative effect in treating Ebola virus infection. In this review, we present an overview of recent progress on the treatment of Ebola virus disease with Favipiravir and describe its possible mechanism...
June 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28457226/commentary-restarting-ntd-programme-activities-after-the-ebola-outbreak-in-liberia
#7
Brent C Thomas, Karsor Kollie, Benjamin Koudou, Charles Mackenzie
It is widely known that the recent Ebola Virus Disease (EVD) in West Africa caused a serious disruption to the national health system, with many of ongoing disease focused programmes, such as mass drug administration (MDA) for onchocerciasis (ONC), lymphatic filariasis (LF) and schistosomiasis (SCH), being suspended or scaled-down. As these MDA programmes attempt to restart post-EVD it is important to understand the challenges that may be encountered. This commentary addresses the opinions of the major health sectors involved, as well as those of community members, regarding logistic needs and challenges faced as these important public health programmes consider restarting...
May 1, 2017: Infectious Diseases of Poverty
https://www.readbyqxmd.com/read/28430779/a-coevolution-analysis-for-identifying-protein-protein-interactions-by-fourier-transform
#8
Changchuan Yin, Stephen S-T Yau
Protein-protein interactions (PPIs) play key roles in life processes, such as signal transduction, transcription regulations, and immune response, etc. Identification of PPIs enables better understanding of the functional networks within a cell. Common experimental methods for identifying PPIs are time consuming and expensive. However, recent developments in computational approaches for inferring PPIs from protein sequences based on coevolution theory avoid these problems. In the coevolution theory model, interacted proteins may show coevolutionary mutations and have similar phylogenetic trees...
2017: PloS One
https://www.readbyqxmd.com/read/28404864/longitudinal-peripheral-blood-transcriptional-analysis-of-a-patient-with-severe-ebola-virus-disease
#9
John C Kash, Kathie-Anne Walters, Jason Kindrachuk, David Baxter, Kelsey Scherler, Krisztina B Janosko, Rick D Adams, Andrew S Herbert, Rebekah M James, Spencer W Stonier, Matthew J Memoli, John M Dye, Richard T Davey, Daniel S Chertow, Jeffery K Taubenberger
The 2013-2015 outbreak of Ebola virus disease in Guinea, Liberia, and Sierra Leone was unprecedented in the number of documented cases, but there have been few published reports on immune responses in clinical cases and their relationships with the course of illness and severity of Ebola virus disease. Symptoms of Ebola virus disease can include severe headache, myalgia, asthenia, fever, fatigue, diarrhea, vomiting, abdominal pain, and hemorrhage. Although experimental treatments are in development, there are no current U...
April 12, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28403145/the-phosphatidylinositol-3-phosphate-5-kinase-inhibitor-apilimod-blocks-filoviral-entry-and-infection
#10
Elizabeth A Nelson, Julie Dyall, Thomas Hoenen, Alyson B Barnes, Huanying Zhou, Janie Y Liang, Julia Michelotti, William H Dewey, Lisa Evans DeWald, Richard S Bennett, Patrick J Morris, Rajarshi Guha, Carleen Klumpp-Thomas, Crystal McKnight, Yu-Chi Chen, Xin Xu, Amy Wang, Emma Hughes, Scott Martin, Craig Thomas, Peter B Jahrling, Lisa E Hensley, Gene G Olinger, Judith M White
Phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) is a lipid kinase involved in endosome maturation that emerged from a haploid genetic screen as being required for Ebola virus (EBOV) infection. Here we analyzed the effects of apilimod, a PIKfyve inhibitor that was reported to be well tolerated in humans in phase 2 clinical trials, for its effects on entry and infection of EBOV and Marburg virus (MARV). We first found that apilimod blocks infections by EBOV and MARV in Huh 7, Vero E6 and primary human macrophage cells, with notable potency in the macrophages (IC50, 10 nM)...
April 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28402862/cooperativity-enables-non-neutralizing-antibodies-to-neutralize-ebolavirus
#11
Katie A Howell, Jennifer M Brannan, Christopher Bryan, Andrew McNeal, Edgar Davidson, Hannah L Turner, Hong Vu, Sergey Shulenin, Shihua He, Ana Kuehne, Andrew S Herbert, Xiangguo Qiu, Benjamin J Doranz, Frederick W Holtsberg, Andrew B Ward, John M Dye, M Javad Aman
Drug combinations are synergistic when their combined efficacy exceeds the sum of the individual actions, but they rarely include ineffective drugs that become effective only in combination. We identified several "enabling pairs" of neutralizing and non-neutralizing anti-ebolavirus monoclonal antibodies, whose combination exhibited new functional profiles, including transforming a non-neutralizing antibody to a neutralizer. Sub-neutralizing concentrations of antibodies 2G4 or m8C4 enabled non-neutralizing antibody FVM09 (IC50 >1 μM) to exhibit potent neutralization (IC50 1-10 nM)...
April 11, 2017: Cell Reports
https://www.readbyqxmd.com/read/28377530/topoisomerase-ii-inhibitors-induce-dna-damage-dependent-interferon-responses-circumventing-ebola-virus-immune-evasion
#12
Priya Luthra, Sebastian Aguirre, Benjamin C Yen, Colette A Pietzsch, Maria T Sanchez-Aparicio, Bersabeh Tigabu, Lorraine K Morlock, Adolfo García-Sastre, Daisy W Leung, Noelle S Williams, Ana Fernandez-Sesma, Alexander Bukreyev, Christopher F Basler
Ebola virus (EBOV) protein VP35 inhibits production of interferon alpha/beta (IFN) by blocking RIG-I-like receptor signaling pathways, thereby promoting virus replication and pathogenesis. A high-throughput screening assay, developed to identify compounds that either inhibit or bypass VP35 IFN-antagonist function, identified five DNA intercalators as reproducible hits from a library of bioactive compounds. Four, including doxorubicin and daunorubicin, are anthracycline antibiotics that inhibit topoisomerase II and are used clinically as chemotherapeutic drugs...
April 4, 2017: MBio
https://www.readbyqxmd.com/read/28376850/depressive-symptoms-among-survivors-of-ebola-virus-disease-in-conakry-guinea-preliminary-results-of-the-postebogui-cohort
#13
Mamady Mory Keita, Bernard Taverne, Sékou Sy Savané, Laura March, Morifodé Doukoure, Mamadou Saliou Sow, Abdoulaye Touré, Jean François Etard, Moumié Barry, Eric Delaporte
BACKGROUND: The 2013-2016 West African Ebola outbreak infected 28,616 people and caused 11,310 deaths by 11 May 2016, across six countries. The outbreak has also resulted in the largest number of EVD survivors in history-over 17,000. Guinea was declared Ebola-free on 1 June 2016. Reports from the outbreak documented 3814 cases resulting in 2544 deaths and 1270 survivors. EVD survivors face various neuropsychological and psycho-affective alterations that have not been fully identified yet...
April 4, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28358050/antibody-dependent-cellular-cytotoxicity-inducing-antibodies-significantly-affect-the-post-exposure-treatment-of-ebola-virus-infection
#14
Qiang Liu, Changfa Fan, Qianqian Li, Shuya Zhou, Weijin Huang, Lan Wang, Chunyun Sun, Meng Wang, Xi Wu, Jian Ma, Baowen Li, Liangzhi Xie, Youchun Wang
Passive immunotherapy with monoclonal antibodies (mAbs) is an efficacious treatment for Ebola virus (EBOV) infections in animal models and humans. Understanding what constitutes a protective response is critical for the development of novel therapeutic strategies. We generated an EBOV-glycoprotein-pseudotyped Human immunodeficiency virus to develop sensitive neutralizing and antibody-dependent cellular cytotoxicity (ADCC) assays as well as a bioluminescent-imaging-based mouse infection model that does not require biosafety level 4 containment...
March 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28357917/the-ongoing-evolution-of-antibody-based-treatments-for-ebola-virus-infection
#15
REVIEW
Emelissa J Mendoza, Trina Racine, Gary P Kobinger
The 2014-2016 Ebola virus outbreak in West Africa was the deadliest in history, prompting the evaluation of various drug candidates, including antibody-based therapeutics for the treatment of Ebola hemorrhagic fever (EHF). Prior to 2014, only convalescent blood products from EHF survivors had been administered to newly infected individuals as a form of treatment. However, during the recent outbreak, monoclonal antibody cocktails such as ZMapp, ZMAb and MB-003 were either tested in a human clinical safety and efficacy trial or provided to some based on compassionate grounds...
March 2017: Immunotherapy
https://www.readbyqxmd.com/read/28351976/comparing-nonpharmaceutical-interventions-for-containing-emerging-epidemics
#16
Corey M Peak, Lauren M Childs, Yonatan H Grad, Caroline O Buckee
Strategies for containing an emerging infectious disease outbreak must be nonpharmaceutical when drugs or vaccines for the pathogen do not yet exist or are unavailable. The success of these nonpharmaceutical strategies will depend on not only the effectiveness of isolation measures but also the epidemiological characteristics of the infection. However, there is currently no systematic framework to assess the relationship between different containment strategies and the natural history and epidemiological dynamics of the pathogen...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28299152/ebola-viral-disease-in-west-africa-a-threat-to-global-health-economy-and-political-stability
#17
Semeeh Akinwale Omoleke, Ibrahim Mohammed, Yauba Saidu
The West African sub-continent is currently experiencing its first, and ironically, the largest and longest Ebola viral diseases (EVD) outbreak ever documented in modern medical history. The current outbreak is significant in several ways, including longevity, magnitude of morbidity and mortality, occurrence outside the traditional niches, rapid spread and potential of becoming a global health tragedy. The authors provided explicit insights into the current and historical background, drivers of the epidemic, societal impacts, status of vaccines and drugs development and proffered recommendations to halt and prevent future occurrences...
August 17, 2016: Journal of Public Health in Africa
https://www.readbyqxmd.com/read/28277549/the-final-oral-ebola-vaccine-trial-on-captive-chimpanzees
#18
Peter D Walsh, Drishya Kurup, Dana L Hasselschwert, Christoph Wirblich, Jason E Goetzmann, Matthias J Schnell
Could new oral vaccine technologies protect endangered wildlife against a rising tide of infectious disease? We used captive chimpanzees to test oral delivery of a rabies virus (RABV) vectored vaccine against Ebola virus (EBOV), a major threat to wild chimpanzees and gorillas. EBOV GP and RABV GP-specific antibody titers increased exponentially during the trial, with rates of increase for six orally vaccinated chimpanzees very similar to four intramuscularly vaccinated controls. Chimpanzee sera also showed robust neutralizing activity against RABV and pseudo-typed EBOV...
March 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28240606/anticancer-kinase-inhibitors-impair-intracellular-viral-trafficking-and-exert-broad-spectrum-antiviral-effects
#19
Elena Bekerman, Gregory Neveu, Ana Shulla, Jennifer Brannan, Szu-Yuan Pu, Stanley Wang, Fei Xiao, Rina Barouch-Bentov, Russell R Bakken, Roberto Mateo, Jennifer Govero, Claude M Nagamine, Michael S Diamond, Steven De Jonghe, Piet Herdewijn, John M Dye, Glenn Randall, Shirit Einav
Global health is threatened by emerging viral infections, which largely lack effective vaccines or therapies. Targeting host pathways that are exploited by multiple viruses could offer broad-spectrum solutions. We previously reported that AAK1 and GAK, kinase regulators of the host adaptor proteins AP1 and AP2, are essential for hepatitis C virus (HCV) infection, but the underlying mechanism and relevance to other viruses or in vivo infections remained unknown. Here, we have discovered that AP1 and AP2 cotraffic with HCV particles in live cells...
April 3, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28231247/favipiravir-pharmacokinetics-in-ebola-infected-patients-of-the-jiki-trial-reveals-concentrations-lower-than-targeted
#20
Thi Huyen Tram Nguyen, Jérémie Guedj, Xavier Anglaret, Cédric Laouénan, Vincent Madelain, Anne-Marie Taburet, Sylvain Baize, Daouda Sissoko, Boris Pastorino, Anne Rodallec, Géraldine Piorkowski, Sara Carazo, Mamoudou N Conde, Jean-Luc Gala, Joseph Akoi Bore, Caroline Carbonnelle, Frédéric Jacquot, Hervé Raoul, Denis Malvy, Xavier de Lamballerie, France Mentré
BACKGROUND: In 2014-2015, we assessed favipiravir tolerance and efficacy in patients with Ebola virus (EBOV) disease (EVD) in Guinea (JIKI trial). Because the drug had never been used before for this indication and that high concentrations of the drugs were needed to achieve antiviral efficacy against EBOV, a pharmacokinetic model had been used to propose relevant dosing regimen. Here we report the favipiravir plasma concentrations that were achieved in participants in the JIKI trial and put them in perspective with the model-based targeted concentrations...
February 2017: PLoS Neglected Tropical Diseases
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