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Article ; Online: Utility of Human

Creager, Hannah M / Kieran, Troy J / Zeng, Hui / Sun, Xiangjie / Pulit-Penaloza, Joanna A / Holmes, Katie E / Johnson, Anders F / Tumpey, Terrence M / Maines, Taronna R / Beauchemin, Catherine A A / Belser, Jessica A

Journal of virology

2023 Volume 97, Issue 1, Page(s) e0153622

Abstract: As influenza A viruses (IAV) continue to cross species barriers and cause human infection, the establishment of risk assessment rubrics has improved pandemic preparedness efforts. ...

Abstract	As influenza A viruses (IAV) continue to cross species barriers and cause human infection, the establishment of risk assessment rubrics has improved pandemic preparedness efforts.
MeSH term(s)	Animals ; Humans ; Ferrets ; Influenza A virus/pathogenicity ; Influenza, Human ; Orthomyxoviridae Infections/pathology ; Risk Assessment/methods ; Swine ; Virus Replication ; Cell Line ; In Vitro Techniques
Language	English
Publishing date	2023-01-05
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/jvi.01536-22
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Article ; Online: Real-time genomic epidemiologic investigation of a multispecies plasmid-associated hospital outbreak of NDM-5-producing Enterobacterales infections.

Raabe, Nathan J / Valek, Abby L / Griffith, Marissa P / Mills, Emma / Waggle, Kady / Srinivasa, Vatsala Rangachar / Ayres, Ashley M / Bradford, Claire / Creager, Hannah M / Pless, Lora L / Sundermann, Alexander J / Van Tyne, Daria / Snyder, Graham M / Harrison, Lee H

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

2024 Volume 142, Page(s) 106971

Abstract: Objectives: New Delhi metallo-β-lactamase (NDM) is an emergent mechanism of carbapenem resistance associated with high mortality and limited treatment options. Because the bla: Methods: Initial outbreak detection of NDM-producing Enterobacterales ... ...

Abstract	Objectives: New Delhi metallo-β-lactamase (NDM) is an emergent mechanism of carbapenem resistance associated with high mortality and limited treatment options. Because the bla Methods: Initial outbreak detection of NDM-producing Enterobacterales identified at an acute care hospital occurred via traditional IP&C methods and was supplemented by real-time WGS surveillance performed weekly. To resolve NDM-encoding plasmids, we performed long-read sequencing and constructed hybrid assemblies. WGS data for suspected outbreaks was shared with the IP&C team for assessment and intervention. Results: We observed a multispecies outbreak of NDM-5-producing Enterobacterales isolated from 15 patients between February 2021 and February 2023. The 19 clinical and surveillance isolates sequenced included 7 bacterial species encoding the same NDM-5 plasmid. WGS surveillance and epidemiologic investigation characterized 10 horizontal plasmid transfer events and 6 bacterial transmission events between patients in varying hospital units. Conclusions: Our investigation revealed a complex, multispecies outbreak of NDM involving multiple plasmid transfer and bacterial transmission events. We highlight the utility of combining traditional IP&C and prospective genomic methods in identifying and containing plasmid-associated outbreaks.
MeSH term(s)	Humans ; Prospective Studies ; Plasmids/genetics ; beta-Lactamases/genetics ; Hospitals ; Genomics ; Klebsiella pneumoniae ; Gammaproteobacteria ; Disease Outbreaks ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Microbial Sensitivity Tests
Chemical Substances	beta-Lactamases (EC 3.5.2.6) ; Anti-Bacterial Agents
Language	English
Publishing date	2024-02-17
Publishing country	Canada
Document type	Journal Article
ZDB-ID	1331197-9
ISSN	1878-3511 ; 1201-9712
ISSN (online)	1878-3511
ISSN	1201-9712
DOI	10.1016/j.ijid.2024.02.014
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Article ; Online: Inherent Heterogeneity of Influenza A Virus Stability following Aerosolization.

Belser, Jessica A / Pulit-Penaloza, Joanna A / Brock, Nicole / Creager, Hannah M / Gustin, Kortney M / Tumpey, Terrence M / Maines, Taronna R

Applied and environmental microbiology

2022 Volume 88, Issue 4, Page(s) e0227121

Abstract: Efficient human-to-human transmission represents a necessary adaptation for a zoonotic influenza A virus (IAV) to cause a pandemic. As such, many emerging IAVs are characterized for transmissibility phenotypes in mammalian models, with an emphasis on ... ...

Abstract	Efficient human-to-human transmission represents a necessary adaptation for a zoonotic influenza A virus (IAV) to cause a pandemic. As such, many emerging IAVs are characterized for transmissibility phenotypes in mammalian models, with an emphasis on elucidating viral determinants of transmission and the role host immune responses contribute to mammalian adaptation. Investigations of virus infectivity and stability in aerosols concurrent with transmission assessments have increased in recent years, enhancing our understanding of this dynamic process. Here, we employed a diverse panel of 17 human and zoonotic IAVs, inclusive of seasonally circulating H1N1 and H3N2 viruses, as well as avian and swine viruses associated with human infection, to evaluate differences in spray factor (a value that assesses efficiency of the aerosolization process), stability, and infectivity following aerosolization. While most seasonal influenza viruses did not exhibit substantial variability within these parameters, there was more heterogeneity among zoonotic influenza viruses, which possess a diverse range of transmission phenotypes. Aging of aerosols at different relative humidities identified strain-specific levels of stability with different profiles identified between zoonotic H3, H5, and H7 subtype viruses associated with human infection. As studies continue to elucidate the complex components governing virus transmissibility, notably aerosol matrices and environmental parameters, considering the relative role of subtype- and strain-specific factors to modulate these parameters will improve our understanding of the pandemic potential of zoonotic influenza A viruses.
MeSH term(s)	Animals ; Humans ; Influenza A Virus, H1N1 Subtype/genetics ; Influenza A Virus, H3N2 Subtype/genetics ; Influenza A virus/genetics ; Influenza, Human ; Mammals ; Orthomyxoviridae Infections ; Swine
Language	English
Publishing date	2022-01-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	223011-2
ISSN	1098-5336 ; 0099-2240
ISSN (online)	1098-5336
ISSN	0099-2240
DOI	10.1128/aem.02271-21
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Article: Implementation of a Rapid Multiplex Polymerase Chain Reaction Pneumonia Panel and Subsequent Antibiotic De-escalation.

Miller, Molly M / Van Schooneveld, Trevor C / Stohs, Erica J / Marcelin, Jasmine R / Alexander, Bryan T / Watkins, Andrew B / Creager, Hannah M / Bergman, Scott J

Open forum infectious diseases

2023 Volume 10, Issue 8, Page(s) ofad382

Abstract: Background: Net effects of implementation of a multiplex polymerase chain reaction (PCR) pneumonia panel (PNP) on antimicrobial stewardship are thus far unknown. This retrospective study evaluated the real-world impact of the PNP on time to antibiotic ... ...

Abstract	Background: Net effects of implementation of a multiplex polymerase chain reaction (PCR) pneumonia panel (PNP) on antimicrobial stewardship are thus far unknown. This retrospective study evaluated the real-world impact of the PNP on time to antibiotic de-escalation in critically ill patients treated for pneumonia at an academic medical center. Methods: This retrospective, quasi-experimental study included adult intensive care unit (ICU) patients with respiratory culture results from 1 May to 15 August 2019 (pre-PNP group) and adult ICU patients with PNP results from 1 May to 15 August 2020 (PNP group) at Nebraska Medical Center. Patients were excluded for the following reasons: any preceding positive coronavirus disease 2019 PCR test, lack of antibiotic receipt, or non-respiratory tract infection indications for antibiotics. The primary outcome was time to discontinuation of anti-methicillin-resistant Results: Sixty-six patients in the pre-PNP group and 58 in the PNP group were included. There were significant differences in patient characteristics between groups. The median time to anti-MRSA agent discontinuation was 49.1 hours in the pre-PNP and 41.8 hours in the PNP group ( Conclusions: This early look at implementation of a multiplex PNP did not demonstrate a statistically significant difference in antibiotic use but lays the groundwork to further evaluate a significant real-world impact on antibiotic de-escalation in ICU patients treated for pneumonia.
Language	English
Publishing date	2023-07-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofad382
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Article ; Online: Infection of Cultured Mammalian Cells with Aerosolized Influenza Virus.

Creager, Hannah M / Tumpey, Terrence M / Maines, Taronna R / Belser, Jessica A

Methods in molecular biology (Clifton, N.J.)

2018 Volume 1836, Page(s) 387–399

Abstract: Inoculation of animals via inhaled aerosols has long been used to study the infectivity and pathogenesis of both influenza virus and other respiratory pathogens in a context that mimics natural infection. In contrast, traditional in vitro studies of ... ...

Abstract	Inoculation of animals via inhaled aerosols has long been used to study the infectivity and pathogenesis of both influenza virus and other respiratory pathogens in a context that mimics natural infection. In contrast, traditional in vitro studies of cellular tropism have been limited to the use of liquid inocula. We have recently shown that cultured cells can become successfully infected after exposure to aerosolized influenza virus. In this chapter, we describe the methodology employed, including the operation of aerosolization instrumentation and calculation of infectious dose, both in experimental planning and after exposure occurs.
MeSH term(s)	Aerosols ; Animals ; Cell Culture Techniques ; Cell Line ; Cells, Cultured ; Humans ; Influenza, Human/transmission ; Influenza, Human/virology ; Orthomyxoviridae/physiology ; Orthomyxoviridae Infections/transmission ; Orthomyxoviridae Infections/virology
Chemical Substances	Aerosols
Language	English
Publishing date	2018-08-22
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-8678-1_19
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Article: Genomic Epidemiologic Investigation of a Multispecies Hospital Outbreak of NDM-5-Producing Enterobacterales Infections.

Raabe, Nathan J / Valek, Abby L / Griffith, Marissa P / Mills, Emma / Waggle, Kady / Srinivasa, Vatsala Rangachar / Ayres, Ashley M / Bradford, Claire / Creager, Hannah / Pless, Lora L / Sundermann, Alexander J / Van Tyne, Daria / Snyder, Graham M / Harrison, Lee H

medRxiv : the preprint server for health sciences

2023

Abstract: Background: New Delhi metallo-β-lactamase (NDM) represents an emergent mechanism of carbapenem resistance associated with high mortality and limited antimicrobial treatment options. Because the : Methods: Initial outbreak detection of NDM-producing ... ...

Abstract	Background: New Delhi metallo-β-lactamase (NDM) represents an emergent mechanism of carbapenem resistance associated with high mortality and limited antimicrobial treatment options. Because the Methods: Initial outbreak detection of NDM-producing Enterobacterales identified at an acute care hospital occurred via traditional IP&C methods and was supplemented by real-time WGS surveillance, which was performed weekly using the Illumina platform. To resolve NDM-encoding plasmids, we performed long-read Oxford Nanopore sequencing and constructed hybrid assemblies using Illumina and Nanopore sequencing data. Reports of relatedness between NDM-producing organisms and reactive WGS for suspected outbreaks were shared with the IP&C team for assessment and intervention. Findings: We observed a multispecies outbreak of NDM-5-producing Enterobacterales isolated from 15 patients between February 2021 and February 2023. The 19 clinical and surveillance isolates sequenced included seven bacterial species and each encoded the same NDM-5 plasmid, which showed high homology to NDM plasmids previously observed in Asia. WGS surveillance and epidemiologic investigation characterized ten horizontal plasmid transfer events and six bacterial transmission events between patients housed in varying hospital units. Transmission prevention focused on enhanced observation and adherence to basic infection prevention measures. Interpretation: Our investigation revealed a complex, multispecies outbreak of NDM that involved multiple plasmid transfer and bacterial transmission events, increasing the complexity of outbreak identification and transmission prevention. Our investigation highlights the utility of combining traditional IP&C and prospective genomic methods in identifying and containing plasmid-associated outbreaks. Funding: This work was funded in part by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIH) (R01AI127472) (R21AI1783691).
Language	English
Publishing date	2023-09-01
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.08.31.23294545
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Article ; Online: Infection and Replication of Influenza Virus at the Ocular Surface.

Creager, Hannah M / Kumar, Amrita / Zeng, Hui / Maines, Taronna R / Tumpey, Terrence M / Belser, Jessica A

Journal of virology

2018 Volume 92, Issue 7

Abstract: Although influenza viruses typically cause respiratory tract disease, some viruses, particularly those with an H7 hemagglutinin, have been isolated from the eyes of conjunctivitis cases. Previous work has shown that isolates of multiple subtypes from ... ...

Abstract	Although influenza viruses typically cause respiratory tract disease, some viruses, particularly those with an H7 hemagglutinin, have been isolated from the eyes of conjunctivitis cases. Previous work has shown that isolates of multiple subtypes from both ocular and respiratory infections are capable of replication in human
MeSH term(s)	Animals ; Conjunctivitis, Viral/metabolism ; Conjunctivitis, Viral/pathology ; Conjunctivitis, Viral/virology ; Cornea/metabolism ; Cornea/pathology ; Cornea/virology ; Dogs ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Epithelial Cells/virology ; Humans ; Influenza A Virus, H3N2 Subtype/physiology ; Influenza, Human/metabolism ; Influenza, Human/pathology ; Madin Darby Canine Kidney Cells ; Viral Tropism/physiology ; Virus Replication/physiology
Language	English
Publishing date	2018-03-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80174-4
ISSN	1098-5514 ; 0022-538X
ISSN (online)	1098-5514
ISSN	0022-538X
DOI	10.1128/JVI.02192-17
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Article ; Online: Pathogenesis, Transmissibility, and Tropism of a Highly Pathogenic Avian Influenza A(H7N7) Virus Associated With Human Conjunctivitis in Italy, 2013.

Belser, Jessica A / Creager, Hannah M / Zeng, Hui / Maines, Taronna R / Tumpey, Terrence M

The Journal of infectious diseases

2017 Volume 216, Issue suppl_4, Page(s) S508–S511

Abstract: H7 subtype influenza viruses represent a persistent public health threat because of their continued detection in poultry and ability to cause human infection. An outbreak of highly pathogenic avian influenza H7N7 virus in Italy during 2013 resulted in 3 ... ...

Abstract	H7 subtype influenza viruses represent a persistent public health threat because of their continued detection in poultry and ability to cause human infection. An outbreak of highly pathogenic avian influenza H7N7 virus in Italy during 2013 resulted in 3 cases of human conjunctivitis. We determined the pathogenicity and transmissibility of influenza A/Italy/3/2013 virus in mouse and ferret models and examined the replication kinetics of this virus in several human epithelial cell types. The moderate virulence observed in mammalian models and the capacity for transmission in a direct contact model underscore the need for continued study of H7 subtype viruses.
MeSH term(s)	Animals ; Cells, Cultured ; Conjunctivitis, Viral/diagnosis ; Disease Models, Animal ; Endothelium, Corneal/cytology ; Endothelium, Corneal/virology ; Female ; Ferrets/virology ; Humans ; Influenza A Virus, H7N7 Subtype/isolation & purification ; Influenza A Virus, H7N7 Subtype/physiology ; Influenza in Birds/diagnosis ; Influenza in Birds/transmission ; Influenza, Human/diagnosis ; Italy/epidemiology ; Male ; Mice ; Mice, Inbred BALB C ; Nasal Mucosa/cytology ; Nasal Mucosa/virology ; Poultry/virology ; Viral Tropism ; Virus Replication
Language	English
Publishing date	2017-09-21
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiw559
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Article ; Online: Author Correction: Aerosol and surface contamination of SARS-CoV-2 observed in quarantine and isolation care.

Santarpia, Joshua L / Rivera, Danielle N / Herrera, Vicki L / Morwitzer, M Jane / Creager, Hannah M / Santarpia, George W / Crown, Kevin K / Brett-Major, David M / Schnaubelt, Elizabeth R / Broadhurst, M Jana / Lawler, James V / Reid, St Patrick / Lowe, John J

Scientific reports

2020 Volume 10, Issue 1, Page(s) 13892

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...

Abstract	An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Keywords	covid19
Language	English
Publishing date	2020-08-12
Publishing country	England
Document type	Journal Article ; Published Erratum
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-70939-6
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Article ; Online: Oseltamivir inhibits influenza virus replication and transmission following ocular-only aerosol inoculation of ferrets.

Belser, Jessica A / Maines, Taronna R / Creager, Hannah M / Katz, Jacqueline M / Tumpey, Terrence M

Virology

2015 Volume 484, Page(s) 305–312

Abstract: Ocular exposure to influenza virus represents an alternate route of virus entry capable of establishing a respiratory infection in mammals, but the effectiveness of currently available antiviral treatments to limit virus replication within ocular tissue ... ...

Abstract	Ocular exposure to influenza virus represents an alternate route of virus entry capable of establishing a respiratory infection in mammals, but the effectiveness of currently available antiviral treatments to limit virus replication within ocular tissue or inhibit virus spread from ocular sites to the respiratory tract is poorly understood. Using an inoculation method that delivers an aerosol inoculum exclusively to the ocular surface, we demonstrate that oral oseltamivir administration following ocular-only aerosol inoculation with multiple avian and human influenza viruses protected ferrets from a fatal and systemic infection, reduced clinical signs and symptoms of illness, and decreased virus transmissibility to susceptible contacts when a respiratory infection was initiated. The presence of oseltamivir further inhibited influenza virus replication in primary human corneal epithelial cells. These findings provide critical experimental evidence supporting the use of neuraminidase inhibitors during outbreaks of influenza virus resulting in ocular disease or following ocular exposure.
MeSH term(s)	Administration, Oral ; Animals ; Antiviral Agents/administration & dosage ; Disease Models, Animal ; Ferrets ; Male ; Orthomyxoviridae/physiology ; Orthomyxoviridae Infections/drug therapy ; Orthomyxoviridae Infections/virology ; Oseltamivir/administration & dosage ; Survival Analysis ; Virus Replication/drug effects
Chemical Substances	Antiviral Agents ; Oseltamivir (20O93L6F9H)
Language	English
Publishing date	2015-07-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	200425-2
ISSN	1096-0341 ; 0042-6822
ISSN (online)	1096-0341
ISSN	0042-6822
DOI	10.1016/j.virol.2015.06.020
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