Person:
Gire, Stephen K

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Gire

First Name

Stephen K

Name

Gire, Stephen K
Author's Publications: search.filters.isAuthorOfPublication.6cb6d794-94b4-45ac-aa3d-9ebef19df6dd

Search Results

Now showing 1 - 7 of 7
  • Thumbnail Image
    Publication
    Lassa Fever in Post-Conflict Sierra Leone
    (Public Library of Science, 2014) Shaffer, Jeffrey G.; Grant, Donald S.; Schieffelin, John S.; Boisen, Matt L.; Goba, Augustine; Hartnett, Jessica N.; Levy, Danielle C.; Yenni, Rachael E.; Moses, Lina M.; Fullah, Mohammed; Momoh, Mambo; Fonnie, Mbalu; Fonnie, Richard; Kanneh, Lansana; Koroma, Veronica J.; Kargbo, Kandeh; Ottomassathien, Darin; Muncy, Ivana J.; Jones, Abigail B.; Illick, Megan M.; Kulakosky, Peter C.; Haislip, Allyson M.; Bishop, Christopher M.; Elliot, Deborah H.; Brown, Bethany L.; Zhu, Hu; Hastie, Kathryn M.; Andersen, Kristian G; Gire, Stephen K; Tabrizi, Shervin; Tariyal, Ridhi; Stremlau, Mathew; Matschiner, Alex; Sampey, Darryl B.; Spence, Jennifer S.; Cross, Robert W.; Geisbert, Joan B.; Folarin, Onikepe A.; Happi, Christian T.; Pitts, Kelly R.; Geske, F. Jon; Geisbert, Thomas W.; Saphire, Erica Ollmann; Robinson, James E.; Wilson, Russell B.; Sabeti, Pardis; Henderson, Lee A.; Khan, S. Humarr; Bausch, Daniel G.; Branco, Luis M.; Garry, Robert F.
    Background: Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease. Methodology/Principal Findings Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. Conclusions/Significance: Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF.
  • Thumbnail Image
    Publication
    Enhanced methods for unbiased deep sequencing of Lassa and Ebola RNA viruses from clinical and biological samples
    (BioMed Central, 2014) Matranga, Christian B; Andersen, Kristian G; Winnicki, Sarah; Busby, Michele; Gladden, Adrianne D; Tewhey, Ryan; Stremlau, Matthew; Berlin, Aaron; Gire, Stephen K; England, Eleina; Moses, Lina M; Mikkelsen, Tarjei S; Odia, Ikponmwonsa; Ehiane, Philomena E; Folarin, Onikepe; Goba, Augustine; Kahn, S Humarr; Grant, Donald S; Honko, Anna; Hensley, Lisa; Happi, Christian; Garry, Robert F; Malboeuf, Christine M; Birren, Bruce W; Gnirke, Andreas; Levin, Joshua Z; Sabeti, Pardis
    We have developed a robust RNA sequencing method for generating complete de novo assemblies with intra-host variant calls of Lassa and Ebola virus genomes in clinical and biological samples. Our method uses targeted RNase H-based digestion to remove contaminating poly(rA) carrier and ribosomal RNA. This depletion step improves both the quality of data and quantity of informative reads in unbiased total RNA sequencing libraries. We have also developed a hybrid-selection protocol to further enrich the viral content of sequencing libraries. These protocols have enabled rapid deep sequencing of both Lassa and Ebola virus and are broadly applicable to other viral genomics studies. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0519-7) contains supplementary material, which is available to authorized users.
  • Thumbnail Image
    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, Pardis
    In 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.
  • Thumbnail Image
    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.)
  • No Thumbnail Available
    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, Andrew
    The 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.
  • Thumbnail Image
    Publication
    High Depth, Whole-Genome Sequencing of Cholera Isolates from Haiti and the Dominican Republic
    (BioMed Central, 2012) Sealfon, Rachel; Gire, Stephen K; Ellis, Crystal Nicole; Calderwood, Stephen; Qadri, Firdausi; Hensley, Lisa; Kellis, Manolis; Ryan, Edward; Larocque, Regina; Harris, Jason; Sabeti, Pardis
    Background: Whole-genome sequencing is an important tool for understanding microbial evolution and identifying the emergence of functionally important variants over the course of epidemics. In October 2010, a severe cholera epidemic began in Haiti, with additional cases identified in the neighboring Dominican Republic. We used whole- genome approaches to sequence four Vibrio cholerae isolates from Haiti and the Dominican Republic and three additional V. cholerae isolates to a high depth of coverage (>2000x); four of the seven isolates were previously sequenced. Results: Using these sequence data, we examined the effect of depth of coverage and sequencing platform on genome assembly and identification of sequence variants. We found that 50x coverage is sufficient to construct a whole-genome assembly and to accurately call most variants from 100 base pair paired-end sequencing reads. Phylogenetic analysis between the newly sequenced and thirty-three previously sequenced V. cholerae isolates indicates that the Haitian and Dominican Republic isolates are closest to strains from South Asia. The Haitian and Dominican Republic isolates form a tight cluster, with only four variants unique to individual isolates. These variants are located in the CTX region, the SXT region, and the core genome. Of the 126 mutations identified that separate the Haiti-Dominican Republic cluster from the V. cholerae reference strain (N16961), 73 are non-synonymous changes, and a number of these changes cluster in specific genes and pathways. Conclusions: Sequence variant analyses of V. cholerae isolates, including multiple isolates from the Haitian outbreak, identify coverage-specific and technology-specific effects on variant detection, and provide insight into genomic change and functional evolution during an epidemic.
  • Thumbnail Image
    Publication
    Molecular Diagnostics for Lassa Fever at Irrua Specialist Teaching Hospital, Nigeria: Lessons Learnt from Two Years of Laboratory Operation
    (Public Library of Science, 2012) Asogun, Danny A.; Adomeh, Donatus I.; Ehimuan, Jacqueline; Odia, Ikponmwonsa; Hass, Meike; Gabriel, Martin; Ölschläger, Stephan; Becker-Ziaja, Beate; Folarin, Onikepe; Phelan, Eric; Ehiane, Philomena E.; Ifeh, Veritas E.; Uyigue, Eghosasere A.; Oladapo, Yemisi T.; Muoebonam, Ekene B.; Osunde, Osagie; Dongo, Andrew; Okokhere, Peter O.; Okogbenin, Sylvanus A.; Momoh, Mojeed; Alikah, Sylvester O.; Akhuemokhan, Odigie C.; Imomeh, Peter; Odike, Maxy A. C.; Gire, Stephen K; Andersen, Kristian G; Sabeti, Pardis; Happi, Christian; Akpede, George O.; Günther, Stephan
    Background: Lassa fever is a viral hemorrhagic fever endemic in West Africa. However, none of the hospitals in the endemic areas of Nigeria has the capacity to perform Lassa virus diagnostics. Case identification and management solely relies on non-specific clinical criteria. The Irrua Specialist Teaching Hospital (ISTH) in the central senatorial district of Edo State struggled with this challenge for many years. Methodology/Principal Findings A laboratory for molecular diagnosis of Lassa fever, complying with basic standards of diagnostic PCR facilities, was established at ISTH in 2008. During 2009 through 2010, samples of 1,650 suspected cases were processed, of which 198 (12%) tested positive by Lassa virus RT-PCR. No remarkable demographic differences were observed between PCR-positive and negative patients. The case fatality rate for Lassa fever was 31%. Nearly two thirds of confirmed cases attended the emergency departments of ISTH. The time window for therapeutic intervention was extremely short, as 50% of the fatal cases died within 2 days of hospitalization—often before ribavirin treatment could be commenced. Fatal Lassa fever cases were older (p = 0.005), had lower body temperature (p<0.0001), and had higher creatinine (p<0.0001) and blood urea levels (p<0.0001) than survivors. Lassa fever incidence in the hospital followed a seasonal pattern with a peak between November and March. Lassa virus sequences obtained from the patients originating from Edo State formed—within lineage II—a separate clade that could be further subdivided into three clusters. Conclusions/Significance: Lassa fever case management was improved at a tertiary health institution in Nigeria through establishment of a laboratory for routine diagnostics of Lassa virus. Data collected in two years of operation demonstrate that Lassa fever is a serious public health problem in Edo State and reveal new insights into the disease in hospitalized patients.