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Lassa fever

Vincent Madelain, Jérémie Guedj, France Mentré, Thi Huyen Tram Nguyen, Frédéric Jacquot, Lisa Oestereich, Takumi Kadota, Koichi Yamada, Anne-Marie Taburet, Xavier de Lamballerie, Hervé Raoul
Favipiravir is a RNA polymerase inhibitor that showed a strong antiviral efficacy in vitro and in small animal models of several viruses responsible for hemorrhagic fever (HF) including Ebola virus. The aim of this work was to characterize the complex pharmacokinetics of favipiravir in non-human primates (NHP) in order to guide future efficacy studies of favipiravir in large animal models.Four different studies were conducted in 30 uninfected cynomolgus macaques of Chinese (n=17) or Mauritian (n=13) origin treated with intravenous favipiravir for 7 to 14 days with maintenance doses of 60 to 180 mg/kg BID...
October 10, 2016: Antimicrobial Agents and Chemotherapy
Aileen E O'Hearn, Matthew A Voorhees, David P Fetterer, Nadia Wauquier, Moinya R Coomber, James Bangura, Joseph N Fair, Jean-Paul Gonzalez, Randal J Schoepp
BACKGROUND: Sub-Saharan Africa is home to a variety of pathogens, but disease surveillance and the healthcare infrastructure necessary for proper management and control are severely limited. Lassa virus, the cause of Lassa fever, a severe hemorrhagic fever in humans is endemic in West Africa. In Sierra Leone at the Kenema Government Hospital Lassa Diagnostic Laboratory, up to 70 % of acute patient samples suspected of Lassa fever test negative for Lassa virus infection. This large amount of acute undiagnosed febrile illness can be attributed in part to an array of hemorrhagic fever and arthropod-borne viruses causing disease that goes undetected and untreated...
October 3, 2016: Virology Journal
Svenja Wolff, Tilman Schultze, Sarah Katharina Fehling, Jan Philipp Mengel, Gerrit Kann, Timo Wolf, Markus Eickmann, Stephan Becker, Torsten Hain, Thomas Strecker
Lassa virus (LASV) is a zoonotic, hemorrhagic fever-causing virus endemic in West Africa, for which no approved vaccines or specific treatment options exist. Here, we report the genome sequence of LASV isolated from the first case of acquired Lassa fever disease outside of Africa.
2016: Genome Announcements
Samson E Isa, Attah Okwute, Kelly O Iraoyah, Shehu Y Nathan, Gomerep S Simji, Mark O Okolo, Joseph Anejo-Okopi, Daria Spicola, Daisy E Isa
BACKGROUND: Secondary transmission of Lassa fever (LF) occurs in the community and in health-care facilities, and is associated with high fatality in Nigeria. We investigated the role of oral ribavirin postexposure prophylaxis (orPEP) in preventing LF among the primary contacts of confirmed cases from December 2015 to March 2016. MATERIALS AND METHODS: Epidemiological and clinical data of LF contacts were prospectively collected. However, information regarding ribavirin adverse effects (AEs) were collected retrospectively through a telephone interview...
July 2016: Nigerian Medical Journal: Journal of the Nigeria Medical Association
Junjie Shao, Xiaoying Liu, Hinh Ly, Yuying Liang
: Arenaviruses can cause lethal hemorrhagic fevers in humans with limited preventative and therapeutic measures. The arenaviral glycoprotein stable signal peptide (SSP) is unique among signal peptides in that it is an integral component of the mature glycoprotein complex (GPC) and plays important roles not only in the GPC expression and processing but also in the membrane fusion process during viral entry. Using the Pichinde virus (PICV) reverse genetics system, we analyzed the effects of alanine substitutions at many conserved residues within SSP on viral replication in cell culture and in a guinea-pig infection model...
September 14, 2016: Journal of Virology
Giovanni Lo Iacono, Andrew A Cunningham, Elisabeth Fichet-Calvet, Robert F Garry, Donald S Grant, Melissa Leach, Lina M Moses, Gordon Nichols, John S Schieffelin, Jeffrey G Shaffer, Colleen T Webb, James L N Wood
A considerable amount of disease is transmitted from animals to humans and many of these zoonoses are neglected tropical diseases. As outbreaks of SARS, avian influenza and Ebola have demonstrated, however, zoonotic diseases are serious threats to global public health and are not just problems confined to remote regions. There are two fundamental, and poorly studied, stages of zoonotic disease emergence: 'spillover', i.e. transmission of pathogens from animals to humans, and 'stuttering transmission', i.e. when limited human-to-human infections occur, leading to self-limiting chains of transmission...
September 2016: PLoS Neglected Tropical Diseases
Masaharu Iwasaki, Cherie T Ng, Beatrice Cubitt, Juan C de la Torre
: Several arenaviruses, chiefly Lassa virus (LASV), cause hemorrhagic fever disease in humans and pose serious public health concerns in their endemic regions. Moreover, mounting evidence indicates that the worldwide-distributed, prototypic arenavirus, lymphocytic choriomeningitis virus (LCMV), is a neglected human pathogen of clinical significance. We have documented that a recombinant LCMV containing the glycoprotein gene (GPC) of LASV within the backbone of the immunosuppressive Clone 13 (Cl-13) variant of Armstrong strain of LCMV (rCl-13/LASV-GPC) exhibited Cl-13 like growth properties in cultured cells but in contrast to Cl-13, rCl-13/LASV-GPC was unable to establish persistence in immune competent adult mice, which prevented its use for some in vivo experiments...
August 31, 2016: Journal of Virology
Wei Wang, Zheng Zhou, Leike Zhang, Shaobo Wang, Gengfu Xiao
Mammarenaviruses, including lethal pathogens such as Lassa virus and Junín virus, can cause severe hemorrhagic fever in humans. Entry is a key step for virus infection, which starts with binding of the envelope glycoprotein (GP) to receptors on target cells and subsequent fusion of the virus with target cell membranes. The GP precursor is synthesized as a polypeptide, and maturation occurs by two cleavage events, yielding a tripartite GP complex (GPC) formed by a stable signal peptide (SSP), GP1 and GP2. The unique retained SSP interacts with GP2 and plays essential roles in virion maturation and infectivity...
August 4, 2016: Virologica Sinica
Robert W Cross, Chad E Mire, Luis M Branco, Joan B Geisbert, Megan M Rowland, Megan L Heinrich, Augustine Goba, Mambu Momoh, Donald S Grant, Mohamed Fullah, Sheik Humarr Khan, James E Robinson, Thomas W Geisbert, Robert F Garry
Lassa fever is a significant health threat to West African human populations with hundreds of thousands of annual cases. There are no approved medical countermeasures currently available. Compassionate use of the antiviral drug ribavirin or transfusion of convalescent serum has resulted in mixed success depending on when administered or the donor source, respectively. We previously identified several recombinant human monoclonal antibodies targeting the glycoprotein of Lassa virus with strong neutralization profiles in vitro...
September 2016: Antiviral Research
Kuan-Wei Huang, Kai-Cheng Hsu, Lee-Ya Chu, Jinn-Moon Yang, Hanna S Yuan, Yu-Yuan Hsiao
The DEDDh family of exonucleases plays essential roles in DNA and RNA metabolism in all kingdoms of life. Several viral and human DEDDh exonucleases can serve as antiviral drug targets due to their critical roles in virus replication. Here using RNase T and CRN-4 as the model systems, we identify potential inhibitors for DEDDh exonucleases. We further show that two of the inhibitors, ATA and PV6R, indeed inhibit the exonuclease activity of the viral protein NP exonuclease of Lassa fever virus in vitro. Moreover, we determine the crystal structure of CRN-4 in complex with MES that reveals a unique inhibition mechanism by inducing the general base His179 to shift out of the active site...
September 8, 2016: Journal of Medicinal Chemistry
Matthew L Boisen, Robert W Cross, Jessica N Hartnett, Augustine Goba, Mambu Momoh, Mohamed Fullah, Michael Gbakie, Sidiki Safa, Mbalu Fonnie, Francis Baimba, Veronica J Koroma, Joan B Geisbert, Stephanie McCormick, Diana K S Nelson, Molly M Millett, Darin Oottamasathien, Abby B Jones, Ha Pham, Bethany L Brown, Jeffrey G Shaffer, John S Schieffelin, Brima Kargbo, Momoh Gbetuwa, Sahr M Gevao, Russell B Wilson, Kelly R Pitts, Thomas W Geisbert, Luis M Branco, Sheik H Khan, Donald S Grant, Robert F Garry
BACKGROUND:  The 2013-2016 West African Ebola virus disease (EVD) epidemic is the largest recorded. Triage on the basis of clinical signs had limited success, and the time to diagnosis by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) could exceed 5 days. Here we describe the development and field validation of the ReEBOV Antigen Rapid Test (ReEBOV RDT) to aid triage of individuals with suspected EVD. METHODS:  Samples from patients with suspected EVD were submitted to Kenema Government Hospital, Sierra Leone, for Lassa fever and EVD screening throughout 2014...
October 15, 2016: Journal of Infectious Diseases
Augustine Goba, S Humarr Khan, Mbalu Fonnie, Mohamed Fullah, Alex Moigboi, Alice Kovoma, Vandi Sinnah, Nancy Yoko, Hawa Rogers, Siddiki Safai, Mambu Momoh, Veronica Koroma, Fatima K Kamara, Edwin Konowu, Mohamed Yillah, Issa French, Ibraham Mustapha, Franklyn Kanneh, Momoh Foday, Helena McCarthy, Tiangay Kallon, Mustupha Kallon, Jenneh Naiebu, Josephine Sellu, Abdul A Jalloh, Michael Gbakie, Lansana Kanneh, James L B Massaly, David Kargbo, Brima Kargbo, Mohamed Vandi, Momoh Gbetuwa, Sahr M Gevao, John D Sandi, Simbirie C Jalloh, Donald S Grant, Sylvia O Blyden, Ian Crozier, John S Schieffelin, Susan L McLellan, Shevin T Jacob, Matt L Boisen, Jessica N Hartnett, Robert W Cross, Luis M Branco, Kristian G Andersen, Nathan L Yozwiak, Stephen K Gire, Ridhi Tariyal, Daniel J Park, Allyson M Haislip, Christopher M Bishop, Lilia I Melnik, William R Gallaher, William C Wimley, Jing He, Jeffrey G Shaffer, Brian M Sullivan, Sonia Grillo, Scott Oman, Courtney E Garry, Donna R Edwards, Stephanie J McCormick, Deborah H Elliott, Julie A Rouelle, Chandrika B Kannadka, Ashley A Reyna, Benjamin T Bradley, Haini Yu, Rachael E Yenni, Kathryn M Hastie, Joan B Geisbert, Peter C Kulakosky, Russell B Wilson, Michael B A Oldstone, Kelly R Pitts, Lee A Henderson, James E Robinson, Thomas W Geisbert, Erica Ollmann Saphire, Christian T Happi, Danny A Asogun, Pardis C Sabeti, Robert F Garry
BACKGROUND:  Kenema Government Hospital (KGH) has developed an advanced clinical and laboratory research capacity to manage the threat of Lassa fever, a viral hemorrhagic fever (VHF). The 2013-2016 Ebola virus (EBOV) disease (EVD) outbreak is the first to have occurred in an area close to a facility with established clinical and laboratory capacity for study of VHFs. METHODS:  Because of its proximity to the epicenter of the EVD outbreak, which began in Guinea in March 2014, the KGH Lassa fever Team mobilized to establish EBOV surveillance and diagnostic capabilities...
July 11, 2016: Journal of Infectious Diseases
Kehinde Charles Mofolorunsho
No abstract text is available yet for this article.
2016: Pan African Medical Journal
Amanda L Coyle
No abstract text is available yet for this article.
July 2016: Nursing
(no author information available yet)
No abstract text is available yet for this article.
May 27, 2016: Relevé épidémiologique Hebdomadaire
Sundaresh Shankar, Landon R Whitby, Hedi E Casquilho-Gray, Joanne York, Dale L Boger, Jack H Nunberg
UNLABELLED: Arenavirus species are responsible for severe life-threatening hemorrhagic fevers in western Africa and South America. Without effective antiviral therapies or vaccines, these viruses pose serious public health and biodefense concerns. Chemically distinct small-molecule inhibitors of arenavirus entry have recently been identified and shown to act on the arenavirus envelope glycoprotein (GPC) to prevent membrane fusion. In the tripartite GPC complex, pH-dependent membrane fusion is triggered through a poorly understood interaction between the stable signal peptide (SSP) and the transmembrane fusion subunit GP2, and our genetic studies have suggested that these small-molecule inhibitors act at this interface to antagonize fusion activation...
August 1, 2016: Journal of Virology
Lisa Oestereich, Anja Lüdtke, Paula Ruibal, Elisa Pallasch, Romy Kerber, Toni Rieger, Stephanie Wurr, Sabrina Bockholt, José V Pérez-Girón, Susanne Krasemann, Stephan Günther, César Muñoz-Fontela
Lassa fever (LASF) is a highly severe viral syndrome endemic to West African countries. Despite the annual high morbidity and mortality caused by LASF, very little is known about the pathophysiology of the disease. Basic research on LASF has been precluded due to the lack of relevant small animal models that reproduce the human disease. Immunocompetent laboratory mice are resistant to infection with Lassa virus (LASV) and, to date, only immunodeficient mice, or mice expressing human HLA, have shown some degree of susceptibility to experimental infection...
May 2016: PLoS Pathogens
James E Robinson, Kathryn M Hastie, Robert W Cross, Rachael E Yenni, Deborah H Elliott, Julie A Rouelle, Chandrika B Kannadka, Ashley A Smira, Courtney E Garry, Benjamin T Bradley, Haini Yu, Jeffrey G Shaffer, Matt L Boisen, Jessica N Hartnett, Michelle A Zandonatti, Megan M Rowland, Megan L Heinrich, Luis Martínez-Sobrido, Benson Cheng, Juan C de la Torre, Kristian G Andersen, Augustine Goba, Mambu Momoh, Mohamed Fullah, Michael Gbakie, Lansana Kanneh, Veronica J Koroma, Richard Fonnie, Simbirie C Jalloh, Brima Kargbo, Mohamed A Vandi, Momoh Gbetuwa, Odia Ikponmwosa, Danny A Asogun, Peter O Okokhere, Onikepe A Follarin, John S Schieffelin, Kelly R Pitts, Joan B Geisbert, Peter C Kulakoski, Russell B Wilson, Christian T Happi, Pardis C Sabeti, Sahr M Gevao, S Humarr Khan, Donald S Grant, Thomas W Geisbert, Erica Ollmann Saphire, Luis M Branco, Robert F Garry
Lassa fever is a severe multisystem disease that often has haemorrhagic manifestations. The epitopes of the Lassa virus (LASV) surface glycoproteins recognized by naturally infected human hosts have not been identified or characterized. Here we have cloned 113 human monoclonal antibodies (mAbs) specific for LASV glycoproteins from memory B cells of Lassa fever survivors from West Africa. One-half bind the GP2 fusion subunit, one-fourth recognize the GP1 receptor-binding subunit and the remaining fourth are specific for the assembled glycoprotein complex, requiring both GP1 and GP2 subunits for recognition...
2016: Nature Communications
Joel Oppliger, Giulia Torriani, Antonio Herrador, Stefan Kunz
UNLABELLED: The pathogenic Old World arenavirus Lassa virus (LASV) causes a severe hemorrhagic fever with a high rate of mortality in humans. Several LASV receptors, including dystroglycan (DG), TAM receptor tyrosine kinases, and C-type lectins, have been identified, suggesting complex receptor use. Upon receptor binding, LASV enters the host cell via an unknown clathrin- and dynamin-independent pathway that delivers the virus to late endosomes, where fusion occurs. Here we investigated the mechanisms underlying LASV endocytosis in human cells in the context of productive arenavirus infection, using recombinant lymphocytic choriomeningitis virus (rLCMV) expressing the LASV glycoprotein (rLCMV-LASVGP)...
July 15, 2016: Journal of Virology
Ayodeji Olayemi, Daniel Cadar, N'Faly Magassouba, Adeoba Obadare, Fode Kourouma, Akinlabi Oyeyiola, Samuel Fasogbon, Joseph Igbokwe, Toni Rieger, Sabrina Bockholt, Hanna Jérôme, Jonas Schmidt-Chanasit, Mutien Garigliany, Stephan Lorenzen, Felix Igbahenah, Jean-Nicolas Fichet, Daniel Ortsega, Sunday Omilabu, Stephan Günther, Elisabeth Fichet-Calvet
Lassa virus (LASV) causes a deadly haemorrhagic fever in humans, killing several thousand people in West Africa annually. For 40 years, the Natal multimammate rat, Mastomys natalensis, has been assumed to be the sole host of LASV. We found evidence that LASV is also hosted by other rodent species: the African wood mouse Hylomyscus pamfi in Nigeria, and the Guinea multimammate mouse Mastomys erythroleucus in both Nigeria and Guinea. Virus strains from these animals were isolated in the BSL-4 laboratory and fully sequenced...
2016: Scientific Reports
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