Person: Yozwiak, Nathan
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Yozwiak
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Nathan
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Yozwiak, Nathan
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Publication Discovery of Novel Rhabdoviruses in the Blood of Healthy Individuals from West Africa(Public Library of Science, 2015) Stremlau, Matthew H.; Andersen, Kristian G.; Folarin, Onikepe A.; Grove, Jessica N.; Odia, Ikponmwonsa; Ehiane, Philomena E.; Omoniwa, Omowunmi; Omoregie, Omigie; Jiang, Pan-Pan; Yozwiak, Nathan; Matranga, Christian B.; Yang, Xiao; Gire, Stephen K.; Winnicki, Sarah; Tariyal, Ridhi; Schaffner, Stephen F.; Okokhere, Peter O.; Okogbenin, Sylvanus; Akpede, George O.; Asogun, Danny A.; Agbonlahor, Dennis E.; Walker, Peter J.; Tesh, Robert B.; Levin, Joshua Z.; Garry, Robert F.; Sabeti, Pardis; Happi, Christian T.Next-generation sequencing (NGS) has the potential to transform the discovery of viruses causing unexplained acute febrile illness (UAFI) because it does not depend on culturing the pathogen or a priori knowledge of the pathogen’s nucleic acid sequence. More generally, it has the potential to elucidate the complete human virome, including viruses that cause no overt symptoms of disease, but may have unrecognized immunological or developmental consequences. We have used NGS to identify RNA viruses in the blood of 195 patients with UAFI and compared them with those found in 328 apparently healthy (i.e., no overt signs of illness) control individuals, all from communities in southeastern Nigeria. Among UAFI patients, we identified the presence of nucleic acids from several well-characterized pathogenic viruses, such as HIV-1, hepatitis, and Lassa virus. In our cohort of healthy individuals, however, we detected the nucleic acids of two novel rhabdoviruses. These viruses, which we call Ekpoma virus-1 (EKV-1) and Ekpoma virus-2 (EKV-2), are highly divergent, with little identity to each other or other known viruses. The most closely related rhabdoviruses are members of the genus Tibrovirus and Bas-Congo virus (BASV), which was recently identified in an individual with symptoms resembling hemorrhagic fever. Furthermore, by conducting a serosurvey of our study cohort, we find evidence for remarkably high exposure rates to the identified rhabdoviruses. The recent discoveries of novel rhabdoviruses by multiple research groups suggest that human infection with rhabdoviruses might be common. While the prevalence and clinical significance of these viruses are currently unknown, these viruses could have previously unrecognized impacts on human health; further research to understand the immunological and developmental impact of these viruses should be explored. More generally, the identification of similar novel viruses in individuals with and without overt symptoms of disease highlights the need for a broader understanding of the human virome as efforts for viral detection and discovery advance.Publication Field-deployable viral diagnostics using CRISPR-Cas13Yozwiak, Nathan; Michael, Scott; Isern, Sharon; Nogueira, Mauricio; Barnes, Kayle; Freije, Catherine; Sabeti, Pardis; Abudayyeh, Omar; Gehrke, Lee; Myhrvold, Cameron; Bosch, Irene; Durbin, Ann; Gootenberg, Jonathan; Kellner, Max; Zhang, Feng; Metsky, Hayden; Tan, Amanda; Parham, Leda; Garcia, Kimberly; Lorenzana, Ivette; Chak, Bridget; Mondini, Adriano; Macinnis, Bronwyn; Paul, LaurenPublication Nomenclature- and Database-Compatible Names for the Two Ebola Virus Variants that Emerged in Guinea and the Democratic Republic of the Congo in 2014(MDPI, 2014) Kuhn, Jens H.; Andersen, Kristian G; Baize, Sylvain; Bào, Yīmíng; Bavari, Sina; Berthet, Nicolas; Blinkova, Olga; Brister, J. Rodney; Clawson, Anna N.; Fair, Joseph; Gabriel, Martin; Garry, Robert F.; Gire, Stephen K.; Goba, Augustine; Gonzalez, Jean-Paul; Günther, Stephan; Happi, Christian T.; Jahrling, Peter B.; Kapetshi, Jimmy; Kobinger, Gary; Kugelman, Jeffrey R.; Leroy, Eric M.; Maganga, Gael Darren; Mbala, Placide K.; Moses, Lina M.; Muyembe-Tamfum, Jean-Jacques; N’Faly, Magassouba; Nichol, Stuart T.; Omilabu, Sunday A.; Palacios, Gustavo; Park, Daniel J.; Paweska, Janusz T.; Radoshitzky, Sheli R.; Rossi, Cynthia A.; Sabeti, Pardis; Schieffelin, John S.; Schoepp, Randal J.; Sealfon, Rachel; Swanepoel, Robert; Towner, Jonathan S.; Wada, Jiro; Wauquier, Nadia; Yozwiak, Nathan; Formenty, PierreIn 2014, Ebola virus (EBOV) was identified as the etiological agent of a large and still expanding outbreak of Ebola virus disease (EVD) in West Africa and a much more confined EVD outbreak in Middle Africa. Epidemiological and evolutionary analyses confirmed that all cases of both outbreaks are connected to a single introduction each of EBOV into human populations and that both outbreaks are not directly connected. Coding-complete genomic sequence analyses of isolates revealed that the two outbreaks were caused by two novel EBOV variants, and initial clinical observations suggest that neither of them should be considered strains. Here we present consensus decisions on naming for both variants (West Africa: “Makona”, Middle Africa: “Lomela”) and provide database-compatible full, shortened, and abbreviated names that are in line with recently established filovirus sub-species nomenclatures.Publication Genomic surveillance elucidates Ebola virus origin and transmission during the 2014 outbreak(American Association for the Advancement of Science (AAAS), 2014) Gire, Stephen K; Goba, A.; Andersen, Kristian G; Sealfon, R. S. G.; Park, D. J.; Kanneh, L.; Jalloh, S.; Momoh, M.; Fullah, M.; Dudas, G.; Wohl, Shirlee; Moses, L. M.; Yozwiak, Nathan; Winnicki, Sarah; Matranga, C. B.; Malboeuf, C. M.; Qu, J.; Gladden, Adrianne; Schaffner, Stephen; Yang, X.; Jiang, P.-P.; Nekoui, M.; Colubri, Andres; Coomber, M. R.; Fonnie, M.; Moigboi, A.; Gbakie, M.; Kamara, F. K.; Tucker, V.; Konuwa, E.; Saffa, S.; Sellu, J.; Jalloh, A. A.; Kovoma, A.; Koninga, J.; Mustapha, I.; Kargbo, K.; Foday, M.; Yillah, M.; Kanneh, F.; Robert, W.; Massally, J. L. B.; Chapman, S. B.; Bochicchio, J.; Murphy, C.; Nusbaum, C.; Young, S.; Birren, B. W.; Grant, D. S.; Scheiffelin, J. S.; Lander, Eric; Happi, Christian; Gevao, S. M.; Gnirke, A.; Rambaut, A.; Garry, R. F.; Khan, S. H.; Sabeti, PardisIn its largest outbreak, Ebola virus disease is spreading through Guinea, Liberia, Sierra Leone, and Nigeria. We sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone to ~2000× coverage. We observed a rapid accumulation of interhost and intrahost genetic variation, allowing us to characterize patterns of viral transmission over the initial weeks of the epidemic. This West African variant likely diverged from central African lineages around 2004, crossed from Guinea to Sierra Leone in May 2014, and has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources. Because many of the mutations alter protein sequences and other biologically meaningful targets, they should be monitored for impact on diagnostics, vaccines, and therapies critical to outbreak response.Publication Ebola Virus Epidemiology and Evolution in Nigeria(Oxford University Press, 2016) Folarin, Onikepe A.; Ehichioya, Deborah; Schaffner, Stephen; Winnicki, Sarah; Wohl, Shirlee; Eromon, Philomena; West, Kendra L.; Gladden-Young, Adrianne; Oyejide, Nicholas E.; Matranga, Christian B.; Deme, Awa Bineta; James, Ayorinde; Tomkins-Tinch, Christopher; Onyewurunwa, Kenneth; Ladner, Jason T.; Palacios, Gustavo; Nosamiefan, Iguosadolo; Andersen, Kristian G.; Omilabu, Sunday; Park, Daniel J.; Yozwiak, Nathan; Nasidi, Abdusallam; Garry, Robert F.; Tomori, Oyewale; Sabeti, Pardis; Happi, Christian T.Containment limited the 2014 Nigerian Ebola virus (EBOV) disease outbreak to 20 reported cases and 8 fatalities. We present here clinical data and contact information for at least 19 case patients, and full-length EBOV genome sequences for 12 of the 20. The detailed contact data permits nearly complete reconstruction of the transmission tree for the outbreak. The EBOV genomic data are consistent with that tree. It confirms that there was a single source for the Nigerian infections, shows that the Nigerian EBOV lineage nests within a lineage previously seen in Liberia but is genetically distinct from it, and supports the conclusion that transmission from Nigeria to elsewhere did not occur.Publication Clinical Illness and Outcomes in Patients with Ebola in Sierra Leone(New England Journal of Medicine (NEJM/MMS), 2014) Schieffelin, John S.; Shaffer, Jeffrey G.; Goba, Augustine; Gbakie, Michael; Gire, Stephen K; Colubri, Andres; Sealfon, Rachel; Kanneh, Lansana; Moigboi, Alex; Momoh, Mambu; Fullah, Mohammed; Moses, Lina M.; Brown, Bethany L.; Andersen, Kristian G; Winnicki, Sarah; Schaffner, Stephen; Park, Daniel John; Yozwiak, Nathan; Jiang, Pan-Pan; Kargbo, David; Jalloh, Simbirie; Fonnie, Mbalu; Sinnah, Vandi; French, Issa; Kovoma, Alice; Kamara, Fatima K.; Tucker, Veronica; Konuwa, Edwin; Sellu, Josephine; Mustapha, Ibrahim; Foday, Momoh; Yillah, Mohamed; Kanneh, Franklyn; Saffa, Sidiki; Massally, James L.B.; Boisen, Matt L.; Branco, Luis M.; Vandi, Mohamed A.; Grant, Donald S.; Happi, Christian; Gevao, Sahr M.; Fletcher, Thomas E.; Fowler, Robert A.; Bausch, Daniel G.; Sabeti, Pardis; Khan, S. Humarr; Garry, Robert F.Background;Limited clinical and laboratory data are available on patients with Ebola virus disease (EVD). The Kenema Government Hospital in Sierra Leone, which had an existing infrastructure for research regarding viral hemorrhagic fever, has received and cared for patients with EVD since the beginning of the outbreak in Sierra Leone in May 2014. Methods;We reviewed available epidemiologic, clinical, and laboratory records of patients in whom EVD was diagnosed between May 25 and June 18, 2014. We used quantitative reverse-transcriptase–polymerase-chain-reaction assays to assess the load of Ebola virus (EBOV, Zaire species) in a subgroup of patients. Results;Of 106 patients in whom EVD was diagnosed, 87 had a known outcome, and 44 had detailed clinical information available. The incubation period was estimated to be 6 to 12 days, and the case fatality rate was 74%. Common findings at presentation included fever (in 89% of the patients), headache (in 80%), weakness (in 66%), dizziness(in 60%), diarrhea (in 51%), abdominal pain (in 40%), and vomiting (in 34%). Clinical and laboratory factors at presentation that were associated with a fatal outcome included fever, weakness, dizziness, diarrhea, and elevated levels of blood urea nitrogen, aspartate aminotransferase, and creatinine. Exploratory analyses indicated that patients under the age of 21 years had a lower case fatality rate than those over the age of 45 years (57% vs. 94%, P=0.03), and patients presenting with fewer than 100,000 EBOV copies per milliliter had a lower case fatality rate than those with 10 million EBOV copies per milliliter or more (33% vs. 94%, P=0.003). Bleeding occurred in only 1 patient.Conclusions; The incubation period and case fatality rate among patients with EVD in Sierra Leone are similar to those observed elsewhere in the 2014 outbreak and in previous outbreaks. Although bleeding was an infrequent finding, diarrhea and other gastrointestinal manifestations were common. (Funded by the National Institutes of Health and others.)Publication Virus genomes reveal factors that spread and sustained the Ebola epidemic(Springer Science and Business Media LLC, 2017-04) Dudas, Gytis; Carvalho, Luiz Max; Bedford, Trevor; Tatem, Andrew J.; Baele, Guy; Faria, Nuno R.; Park, Daniel John; Ladner, Jason T.; Arias, Armando; Asogun, Danny; Bielejec, Filip; Caddy, Sarah L.; Cotten, Matthew; D’Ambrozio, Jonathan; Dellicour, Simon; Di Caro, Antonino; Diclaro, Joseph W.; Duraffour, Sophie; Elmore, Michael J.; Fakoli, Lawrence S.; Faye, Ousmane; Gilbert, Merle L.; Gevao, Sahr M.; Gire, Stephen K; Gladden-Young, Adrianne; Gnirke, Andreas; Goba, Augustine; Grant, Donald S.; Haagmans, Bart L.; Hiscox, Julian A.; Jah, Umaru; Kugelman, Jeffrey R.; Liu, Di; Lu, Jia; Malboeuf, Christine M.; Mate, Suzanne; Matthews, David A.; Matranga, Christian B.; Meredith, Luke W.; Qu, James; Quick, Joshua; Pas, Suzan D.; Phan, My V. T.; Pollakis, Georgios; Reusken, Chantal B.; Sanchez-Lockhart, Mariano; Schaffner, Stephen; Schieffelin, John S.; Sealfon, Rachel; Simon-Loriere, Etienne; Smits, Saskia L.; Stoecker, Kilian; Thorne, Lucy; Tobin, Ekaete Alice; Vandi, Mohamed A.; Watson, Simon J.; West, Kendra L.; Whitmer, Shannon; Wiley, Michael R.; Winnicki, Sarah; Wohl, Shirlee; Wölfel, Roman; Yozwiak, Nathan; Andersen, Kristian G; Blyden, Sylvia O.; Bolay, Fatorma; Carroll, Miles W.; Dahn, Bernice; Diallo, Boubacar; Formenty, Pierre; Fraser, Christophe; Gao, George F.; Garry, Robert F.; Goodfellow, Ian; Günther, Stephan; Happi, Christian; Holmes, Edward C.; Kargbo, Brima; Keïta, Sakoba; Kellam, Paul; Koopmans, Marion P. G.; Kuhn, Jens H.; Loman, Nicholas J.; Magassouba, N’Faly; Naidoo, Dhamari; Nichol, Stuart T.; Nyenswah, Tolbert; Palacios, Gustavo; Pybus, Oliver G.; Sabeti, Pardis; Sall, Amadou; Ströher, Ute; Wurie, Isatta; Suchard, Marc A.; Lemey, Philippe; Rambaut, AndrewThe 2013–2016 epidemic of Ebola virus disease was of unprecedented magnitude, duration and impact. Analysing 1610 Ebola virus genomes, representing over 5% of known cases, we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic ‘gravity’ model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already set the seeds for an international epidemic, rendering these measures ineffective in curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing they were susceptible to significant outbreaks but at lower risk of introductions. Finally, we reveal this large epidemic to be a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help inform interventions in future epidemics.