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Barnes, Kayle

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Barnes

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Kayle

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Barnes, Kayle

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2017 - 20184

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Author's Publications: search.filters.isAuthorOfPublication.f3d615d3-54d5-40b9-8465-8804603de890

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    Field-deployable viral diagnostics using CRISPR-Cas13
    Yozwiak, 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, Lauren
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    Zika virus evolution and spread in the Americas
    (SpringerNature, 2017) Metsky, Hayden C; Matranga, Christian B; Wohl, Shirlee; Schaffner, Stephen; Freije, Catherine; Winnicki, Sarah; West, Kendra L.; Qu, James; Baniecki, Mary; Gladden-Young, Adrianne; Lin, Aaron; Tomkins-Tinch, Christopher; Ye, Simon H; Park, Daniel; Luo, Cynthia; Barnes, Kayle; Shah, Rickey; Chak, Bridget; Barbosa-Lima, Giselle; Delatorre, Edson; Vieira, Yasmine R; Paul, Lauren M; Tan, Amanda L; Barcellona, Carolyn M; Porcelli, Mario C; Vasquez, Chalmers; Cannons, Andrew C; Cone, Marshall R; Hogan, Kelly N; Kopp, Edgar W; Anzinger, Joshua J; Garcia, Kimberly F; Parham, Leda A; Gelvez Ramirez, Rosa Margarita; Miranda Montoya, Maria Consuelo; Rojas, Diana P; Brown, Catherine M; Hennigan, Scott; Sabina, Brandon; Scotland, Sarah; Gangavarapu, Karthik; Grubaugh, Nathan D; Oliveira, Glenn; Robles-Sikisaka, Refugio; Rambaut, Andrew; Gehrke, Lee; Smole, Sandra; Halloran, M Elizabeth; Villar Centeno, Luis Angel; Mattar, Salim; Lorenzana, Ivette; Cerbino-Neto, Jose; Valim, Clarissa; Degrave, Wim; Bozza, Patricia T; Gnirke, Andreas; Andersen, Kristian G; Isern, Sharon; Michael, Scott; Bozza, Fernando A; Souza, Thiago ML; Bosch, Irene; Yozwiak, Nathan L; MacInnis, Bronwyn L; Sabeti, Pardis
    Despite great attention given to the recent Zika virus (ZIKV) epidemic in the Americas, much remains unknown about its epidemiology and evolution, in part due to a lack of genomic data. We applied multiple sequencing approaches to generate 100 ZIKV genomes from clinical and mosquito samples from 10 countries and territories, greatly expanding the observed viral genetic diversity from this outbreak. We analyzed the timing and patterns of introductions into distinct geographic regions, confirming phylogenetic evidence for the origin and rapid expansion of the outbreak in Brazil, and for multiple introductions from Brazil into Honduras, Colombia, Puerto Rico, other Caribbean islands, and the continental US. We find that ZIKV circulated undetected in many regions of the Americas for up to a year before the first locally transmitted cases were confirmed, highlighting the challenge of effective surveillance for this virus. We further characterize genetic variation across the outbreak to identify mutations with possible functional implications for ZIKV biology and pathogenesis.
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    Genomic Footprints of Selective Sweeps from Metabolic Resistance to Pyrethroids in African Malaria Vectors Are Driven by Scale up of Insecticide-Based Vector Control
    (Public Library of Science, 2017) Barnes, Kayle; Weedall, Gareth D.; Ndula, Miranda; Irving, Helen; Mzihalowa, Themba; Hemingway, Janet; Wondji, Charles S.
    Insecticide resistance in mosquito populations threatens recent successes in malaria prevention. Elucidating patterns of genetic structure in malaria vectors to predict the speed and direction of the spread of resistance is essential to get ahead of the ‘resistance curve’ and to avert a public health catastrophe. Here, applying a combination of microsatellite analysis, whole genome sequencing and targeted sequencing of a resistance locus, we elucidated the continent-wide population structure of a major African malaria vector, Anopheles funestus. We identified a major selective sweep in a genomic region controlling cytochrome P450-based metabolic resistance conferring high resistance to pyrethroids. This selective sweep occurred since 2002, likely as a direct consequence of scaled up vector control as revealed by whole genome and fine-scale sequencing of pre- and post-intervention populations. Fine-scaled analysis of the pyrethroid resistance locus revealed that a resistance-associated allele of the cytochrome P450 monooxygenase CYP6P9a has swept through southern Africa to near fixation, in contrast to high polymorphism levels before interventions, conferring high levels of pyrethroid resistance linked to control failure. Population structure analysis revealed a barrier to gene flow between southern Africa and other areas, which may prevent or slow the spread of the southern mechanism of pyrethroid resistance to other regions. By identifying a genetic signature of pyrethroid-based interventions, we have demonstrated the intense selective pressure that control interventions exert on mosquito populations. If this level of selection and spread of resistance continues unabated, our ability to control malaria with current interventions will be compromised.
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    Ebola Virus Persistence in Ocular Tissues and Fluids (EVICT) Study: Reverse Transcription-Polymerase Chain Reaction and Cataract Surgery Outcomes of Ebola Survivors in Sierra Leone☆
    (Elsevier, 2018) Shantha, Jessica G.; Mattia, John G.; Goba, Augustine; Barnes, Kayle; Ebrahim, Faiqa K.; Kraft, Colleen S.; Hayek, Brent R.; Hartnett, Jessica N.; Shaffer, Jeffrey G.; Schieffelin, John S.; Sandi, John D.; Momoh, Mambu; Jalloh, Simbirie; Grant, Donald S.; Dierberg, Kerry; Chang, Joyce; Mishra, Sharmistha; Chan, Adrienne K.; Fowler, Rob; O'Dempsey, Tim; Kaluma, Erick; Hendricks, Taylor; Reiners, Roger; Reiners, Melanie; Gess, Lowell A.; ONeill, Kwame; Kamara, Sarian; Wurie, Alie; Mansaray, Mohamed; Acharya, Nisha R.; Liu, William J.; Bavari, Sina; Palacios, Gustavo; Teshome, Moges; Crozier, Ian; Farmer, Paul E.; Uyeki, Timothy M.; Bausch, Daniel G.; Garry, Robert F.; Vandy, Matthew J.; Yeh, Steven
    Background: Ebola virus disease (EVD) survivors are at risk for uveitis during convalescence. Vision loss has been observed following uveitis due to cataracts. Since Ebola virus (EBOV) may persist in the ocular fluid of EVD survivors for an unknown duration, there are questions about the safety and feasibility of vision restorative cataract surgery in EVD survivors. Methods: We conducted a cross-sectional study of EVD survivors anticipating cataract surgery and patients with active uveitis to evaluate EBOV RNA persistence in ocular fluid, as well as vision outcomes post cataract surgery. Patients with aqueous humor that tested negative for EBOV RNA were eligible to proceed with manual small incision cataract surgery (MSICS). Findings: We screened 137 EVD survivors from June 2016 – August 2017 for enrolment. We enrolled 50 EVD survivors; 46 with visually significant cataract, 1 with a subluxated lens, 2 with active uveitis and 1 with a blind painful eye due to uveitis. The median age was 24.0 years (IQR 17–35) and 35 patients (70%) were female. The median logMAR visual acuity (VA) was 3.0 (Snellen VA Hand motions; Interquartile Range, IQR: 1.2-3.0, Snellen VA 20/320 – Hand motions). All patients tested negative for EBOV RNA by RT-PCR in aqueous humor/vitreous fluid and conjunctiva at a median of 19 months (IQR 18-20) from EVD diagnosis in Phase 1 of ocular fluid sampling and 34 months (IQR 32-36) from EVD diagnosis in Phase 2 of ocular fluid sampling. Thirty-four patients underwent MSICS, with a preoperative median VA improvement from hand motions to 20/30 at three-month postoperative follow-up (P < 0.001). Interpretation EBOV persistence by RT-PCR was not identified in ocular fluid or conjunctivae of fifty EVD survivors with ocular disease. Cataract surgery can be performed safely with vision restorative outcomes in patients who test negative for EBOV RNA in ocular fluid specimens. These findings impact the thousands of West African EVD survivors at-risk for ocular complications who may also require eye surgery during EVD convalescence.
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    Field validation of recombinant antigen immunoassays for diagnosis of Lassa fever
    (Nature Publishing Group UK, 2018) Boisen, Matthew L.; Hartnett, Jessica N.; Shaffer, Jeffrey G.; Goba, Augustine; Momoh, Mambu; Sandi, John Demby; Fullah, Mohamed; Nelson, Diana K. S.; Bush, Duane J.; Rowland, Megan M.; Heinrich, Megan L.; Koval, Anatoliy P.; Cross, Robert W.; Barnes, Kayle; Lachenauer, Anna E.; Lin, Aaron; Nekoui, Mahan; Kotliar, Dylan; Winnicki, Sarah; Siddle, Katherine; Gbakie, Michael; Fonnie, Mbalu; Koroma, Veronica J.; Kanneh, Lansana; Kulakosky, Peter C.; Hastie, Kathryn M.; Wilson, Russell B.; Andersen, Kristian G.; Folarin, Onikepe O.; Happi, Christian T.; Sabeti, Pardis; Geisbert, Thomas W.; Saphire, Erica Ollmann; Khan, S. Humarr; Grant, Donald S.; Schieffelin, John S.; Branco, Luis M.; Garry, Robert F.
    Lassa fever, a hemorrhagic fever caused by Lassa virus (LASV), is endemic in West Africa. It is difficult to distinguish febrile illnesses that are common in West Africa from Lassa fever based solely on a patient’s clinical presentation. The field performance of recombinant antigen-based Lassa fever immunoassays was compared to that of quantitative polymerase chain assays (qPCRs) using samples from subjects meeting the case definition of Lassa fever presenting to Kenema Government Hospital in Sierra Leone. The recombinant Lassa virus (ReLASV) enzyme-linked immunosorbant assay (ELISA) for detection of viral antigen in blood performed with 95% sensitivity and 97% specificity using a diagnostic standard that combined results of the immunoassays and qPCR. The ReLASV rapid diagnostic test (RDT), a lateral flow immunoassay based on paired monoclonal antibodies to the Josiah strain of LASV (lineage IV), performed with 90% sensitivity and 100% specificity. ReLASV immunoassays performed better than the most robust qPCR currently available, which had 82% sensitivity and 95% specificity. The performance characteristics of recombinant antigen-based Lassa virus immunoassays indicate that they can aid in the diagnosis of LASV Infection and inform the clinical management of Lassa fever patients.