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  1. Article ; Online: Aspergillus sensitisation detection using point-of-care lateral flow assay in moderate to severe asthma.

    Wang, Ran / Eades, Chris / Palmer, Maisie / Platt, Gareth / Fowler, Stephen J / Kosmidis, Chris

    Medical mycology

    2023  Volume 61, Issue 8

    Abstract: Allergic fungal airway diseases are associated with asthma exacerbations and poor control. However, the early identification of allergic Aspergillus airway diseases can be challenging, especially in resource-poor countries. We aimed to evaluate the ... ...

    Abstract Allergic fungal airway diseases are associated with asthma exacerbations and poor control. However, the early identification of allergic Aspergillus airway diseases can be challenging, especially in resource-poor countries. We aimed to evaluate the clinical utility of the point-of-care Aspergillus IgG-IgM lateral flow assay in diagnosing Aspergillus airway diseases in patients with moderate-severe asthma. Patients with moderate-severe asthma, severe asthma with fungal sensitisation (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) were recruited. Clinical information was extracted from clinical records. Blood samples were collected for serological tests. Serum samples were evaluated using Aspergillus immunochromatographic test (ICT). A total of 65 patients were recruited into the study, of whom 23.1% had clinical diagnosis of ABPA, 18.5% had SAFS and 58.5% had moderate-to-severe asthma who did not fit ABPA or SAFS criteria. The ICT test gave a sensitivity of 69 [95% confidence interval: 51-88]% and a specificity of 77 [60-88]% in predicting a positive Aspergillus IgG test. The sensitivity and specificity for a positive Aspergillus IgE were 77 [59-88]% and 86 [71-94]%, respectively. The majority (sensitivity: 87 [62-96]%) of patients with ABPA had positive ICT results, with a specificity of 70%. The negative predictive value was high (95 [82-99]%) with a low negative likelihood ratio (< 0.2), making it potentially useful in ruling out ABPA. The ICT assay may be valuable in ruling out ABPA in resource-limited countries where serological investigations are less feasible. The ICT assay may be particularly useful in ruling out ABPA and warrants further validation.
    MeSH term(s) Animals ; Point-of-Care Systems ; Aspergillus ; Asthma/complications ; Asthma/veterinary ; Aspergillosis, Allergic Bronchopulmonary/complications ; Aspergillosis, Allergic Bronchopulmonary/veterinary ; Antibodies, Fungal ; Immunoglobulin G ; Aspergillus fumigatus
    Chemical Substances Antibodies, Fungal ; Immunoglobulin G
    Language English
    Publishing date 2023-07-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 1421796-x
    ISSN 1460-2709 ; 1369-3786
    ISSN (online) 1460-2709
    ISSN 1369-3786
    DOI 10.1093/mmy/myad076
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Detection of carbapenemases, AmpC and ESBL genes in Acinetobacter isolates from ICUs by DNA microarray.

    Uddin, Fakhur / McHugh, Timothy D / Roulston, Kerry / Platt, Gareth / Khan, Taseer Ahmed / Sohail, Muhammad

    Journal of microbiological methods

    2018  Volume 155, Page(s) 19–23

    Abstract: The accumulation of multiple inherent and acquired resistance mechanisms in Acinetobacter spp. results in emergence of "pandrug resistant" strains which is one of the major concerns in healthcare sectors worldwide. Surveillance of the carbapenemase/ ... ...

    Abstract The accumulation of multiple inherent and acquired resistance mechanisms in Acinetobacter spp. results in emergence of "pandrug resistant" strains which is one of the major concerns in healthcare sectors worldwide. Surveillance of the carbapenemase/ extended-spectrum β-lactamases (ESBLs) genes in A. baumannii by phenotypic methods is challenging especially in developing countries, like Pakistan. In this context, a novel microarray (CT 103XL Check-MDR) assay was used for simultaneous detection of genes encoding clinically important carbapenemases and ESBLs. The results were compared with the phenotypic methods including MHT, Rapidec Carba NP, EDTA+DDST and Rosco (KPC/MBL). The results of the microarray were also confirmed by PCR. All of the strains of A. baumannii (47) were resistant to imipenem and meropenem. Microarray and PCR results showed presence of OXA-23 in all the isolates of A. baumannii while 36.17% also harbored PER. Rosco kit test showed 100% sensitivity to detect carbapenemases but exhibited low specificity to classify them. Rapidec Carba NP test has 100% sensitivity and specificity to detect the carbapenemases when compared with microarray. Sensitivity and specificity of microarray assay were 100% for bla-genes in comparison to PCR. This reveals that Check-MDR CT103 XL assay is an accurate method for the identification of ESBLs and carbapenemase genes in A. baumannii in comparison to the other methods.
    MeSH term(s) Acinetobacter/drug effects ; Acinetobacter/genetics ; Acinetobacter/isolation & purification ; Acinetobacter baumannii/drug effects ; Acinetobacter baumannii/genetics ; Acinetobacter baumannii/isolation & purification ; Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/genetics ; Bacterial Proteins/isolation & purification ; DNA, Bacterial ; Genes, Bacterial/genetics ; Humans ; Imipenem/pharmacology ; Meropenem/pharmacology ; Microbial Sensitivity Tests ; Molecular Typing/methods ; Oligonucleotide Array Sequence Analysis/methods ; Pakistan ; Phenotype ; Sensitivity and Specificity ; beta-Lactamases/genetics ; beta-Lactamases/isolation & purification
    Chemical Substances Anti-Bacterial Agents ; Bacterial Proteins ; DNA, Bacterial ; Imipenem (71OTZ9ZE0A) ; beta-lactamase OXA-23 (EC 3.5.2.-) ; AmpC beta-lactamases (EC 3.5.2.6) ; beta-Lactamases (EC 3.5.2.6) ; carbapenemase (EC 3.5.2.6) ; Meropenem (FV9J3JU8B1)
    Language English
    Publishing date 2018-11-10
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 604916-3
    ISSN 1872-8359 ; 0167-7012
    ISSN (online) 1872-8359
    ISSN 0167-7012
    DOI 10.1016/j.mimet.2018.11.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Prospective observational study of SARS-CoV-2 infection, transmission and immunity in a cohort of households in Liverpool City Region, UK (COVID-LIV): a study protocol.

    Setiabudi, Wega / Hungerford, Daniel / Subramaniam, Krishanthi / Vaselli, Natasha Marcella / Shaw, Victoria E / Wilton, Moon / Vivancos, Roberto / Aston, Stephen / Platt, Gareth / Moitt, Tracy / Jones, Ashley P / Gabbay, Mark / Buchan, Iain / Carrol, Enitan D / Iturriza-Gomara, Miren / Solomon, Tom / Greenhalf, William / Naisbitt, Dean J / Adams, Emily R /
    Cunliffe, Nigel A / Turtle, Lance / French, Neil

    BMJ open

    2021  Volume 11, Issue 3, Page(s) e048317

    Abstract: Introduction: The emergence and rapid spread of COVID-19 have caused widespread and catastrophic public health and economic impact, requiring governments to restrict societal activity to reduce the spread of the disease. The role of household ... ...

    Abstract Introduction: The emergence and rapid spread of COVID-19 have caused widespread and catastrophic public health and economic impact, requiring governments to restrict societal activity to reduce the spread of the disease. The role of household transmission in the population spread of SARS-CoV-2, and of host immunity in limiting transmission, is poorly understood. This paper describes a protocol for a prospective observational study of a cohort of households in Liverpool City Region, UK, which addresses the transmission of SARS-CoV-2 between household members and how immunological response to the infection changes over time.
    Methods and analysis: Households in the Liverpool City Region, in which members have not previously tested positive for SARS-CoV-2 with a nucleic acid amplification test, are followed up for an initial period of 12 weeks. Participants are asked to provide weekly self-throat and nasal swabs and record their activity and presence of symptoms. Incidence of infection and household secondary attack rates of COVID-19 are measured. Transmission of SARS-CoV-2 will be investigated against a range of demographic and behavioural variables. Blood and faecal samples are collected at several time points to evaluate immune responses to SARS-CoV-2 infection and prevalence and risk factors for faecal shedding of SARS-CoV-2, respectively.
    Ethics and dissemination: The study has received approval from the National Health Service Research Ethics Committee; REC Reference: 20/HRA/2297, IRAS Number: 283 464. Results will be disseminated through scientific conferences and peer-reviewed open access publications. A report of the findings will also be shared with participants. The study will quantify the scale and determinants of household transmission of SARS-CoV-2. Additionally, immunological responses before and during the different stages of infection will be analysed, adding to the understanding of the range of immunological response by infection severity.
    MeSH term(s) COVID-19/epidemiology ; COVID-19/immunology ; COVID-19/transmission ; Humans ; Observational Studies as Topic ; Prospective Studies ; Research Design ; State Medicine ; United Kingdom/epidemiology
    Language English
    Publishing date 2021-03-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2020-048317
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Characterization of the interaction between human respiratory syncytial virus and the cell cycle in continuous cell culture and primary human airway epithelial cells.

    Wu, Weining / Munday, Diane C / Howell, Gareth / Platt, Gareth / Barr, John N / Hiscox, Julian A

    Journal of virology

    2011  Volume 85, Issue 19, Page(s) 10300–10309

    Abstract: Viruses can modify conditions inside cells to make them more favorable for replication and progeny virus production. One way of doing this is through manipulation of the cell cycle, a process that describes the ordered growth and division of cells. ... ...

    Abstract Viruses can modify conditions inside cells to make them more favorable for replication and progeny virus production. One way of doing this is through manipulation of the cell cycle, a process that describes the ordered growth and division of cells. Analysis of model cell lines, such as A549 cells and primary airway epithelial cells, infected with human respiratory syncytial virus (HRSV) has shown alteration of the cell cycle during infection, although the signaling events were not clearly understood. In this study, targeted transcriptomic analysis of HRSV-infected primary airway epithelial cells revealed alterations in the abundances of many mRNAs encoding cell cycle-regulatory molecules, including decreases in the D-type cyclins and corresponding cyclin-dependent kinases (CDK4 and CDK6 [CDK4/6]). These alterations were reflected in changes in protein abundance and/or relocalization in HRSV-infected cells; taken together, they were predicted to result in G(0)/G(1) phase arrest. In contrast, there was no change in the abundances of D-type cyclins in A549 cells infected with HRSV. However, the abundance of the G(1)/S phase progression inhibitor p21(WAF1/CIP1) was increased over that in mock-treated cells, and this, again, was predicted to result in G(0)/G(1) phase arrest. The G(0)/G(1) phase arrest in both HRSV-infected primary cells and A549 cells was confirmed using dual-label flow cytometry that accurately measured the different stages of the cell cycle. Comparison of progeny virus production in primary and A549 cells enriched in G(0)/G(1) using a specific CDK4/6 kinase inhibitor with asynchronously replicating cells indicated that this phase of the cell cycle was more efficient for virus production.
    MeSH term(s) Cell Cycle ; Cell Cycle Proteins/biosynthesis ; Cells, Cultured ; Epithelial Cells/virology ; Flow Cytometry ; Gene Expression Profiling ; Host-Pathogen Interactions ; Humans ; Respiratory Syncytial Virus, Human/pathogenicity ; Signal Transduction
    Chemical Substances Cell Cycle Proteins
    Keywords covid19
    Language English
    Publishing date 2011-07-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.05164-11
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Comparison of Established Diagnostic Methodologies and a Novel Bacterial smpB Real-Time PCR Assay for Specific Detection of Haemophilus influenzae Isolates Associated with Respiratory Tract Infections.

    Reddington, Kate / Schwenk, Stefan / Tuite, Nina / Platt, Gareth / Davar, Danesh / Coughlan, Helena / Personne, Yoann / Gant, Vanya / Enne, Virve I / Zumla, Alimuddin / Barry, Thomas

    Journal of clinical microbiology

    2015  Volume 53, Issue 9, Page(s) 2854–2860

    Abstract: Haemophilus influenzae is a significant causative agent of respiratory tract infections (RTI) worldwide. The development of a rapid H. influenzae diagnostic assay that would allow for the implementation of infection control measures and also improve ... ...

    Abstract Haemophilus influenzae is a significant causative agent of respiratory tract infections (RTI) worldwide. The development of a rapid H. influenzae diagnostic assay that would allow for the implementation of infection control measures and also improve antimicrobial stewardship for patients is required. A number of nucleic acid diagnostics approaches that detect H. influenzae in RTIs have been described in the literature; however, there are reported specificity and sensitivity limitations for these assays. In this study, a novel real-time PCR diagnostic assay targeting the smpB gene was designed to detect all serogroups of H. influenzae. The assay was validated using a panel of well-characterized Haemophilus spp. Subsequently, 44 Haemophilus clinical isolates were collected, and 36 isolates were identified as H. influenzae using a gold standard methodology that combined the results of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and a fucK diagnostic assay. Using the novel smpB diagnostic assay, 100% concordance was observed with the gold standard, demonstrating a sensitivity of 100% (95% confidence interval [CI], 90.26% to 100.00%) and a specificity of 100% (95% CI, 63.06% to 100.00%) when used on clinical isolates. To demonstrate the clinical utility of the diagnostic assay presented, a panel of lower RTI samples (n = 98) were blindly tested with the gold standard and smpB diagnostic assays. The results generated were concordant for 94/98 samples tested, demonstrating a sensitivity of 90.91% (95% CI, 78.33% to 97.47%) and a specificity of 100% (95% CI, 93.40% to 100.00%) for the novel smpB assay when used directly on respiratory specimens.
    MeSH term(s) Bacteriological Techniques/methods ; Haemophilus Infections/diagnosis ; Haemophilus influenzae/chemistry ; Haemophilus influenzae/genetics ; Haemophilus influenzae/isolation & purification ; Humans ; Molecular Diagnostic Techniques/methods ; Real-Time Polymerase Chain Reaction/methods ; Respiratory Tract Infections/diagnosis ; Sensitivity and Specificity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods
    Language English
    Publishing date 2015-06-24
    Publishing country United States
    Document type Comparative Study ; Evaluation Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 390499-4
    ISSN 1098-660X ; 0095-1137
    ISSN (online) 1098-660X
    ISSN 0095-1137
    DOI 10.1128/JCM.00777-15
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Direct Whole-Genome Sequencing of Sputum Accurately Identifies Drug-Resistant Mycobacterium tuberculosis Faster than MGIT Culture Sequencing.

    Doyle, Ronan M / Burgess, Carrie / Williams, Rachel / Gorton, Rebecca / Booth, Helen / Brown, James / Bryant, Josephine M / Chan, Jackie / Creer, Dean / Holdstock, Jolyon / Kunst, Heinke / Lozewicz, Stefan / Platt, Gareth / Romero, Erika Yara / Speight, Graham / Tiberi, Simon / Abubakar, Ibrahim / Lipman, Marc / McHugh, Timothy D /
    Breuer, Judith

    Journal of clinical microbiology

    2018  Volume 56, Issue 8

    Abstract: The current methods available to diagnose antimicrobial- ... ...

    Abstract The current methods available to diagnose antimicrobial-resistant
    MeSH term(s) Antitubercular Agents/pharmacology ; Drug Resistance, Bacterial/drug effects ; Drug Resistance, Bacterial/genetics ; Early Diagnosis ; Genome, Bacterial/genetics ; Humans ; Microbial Sensitivity Tests ; Molecular Diagnostic Techniques/methods ; Molecular Diagnostic Techniques/standards ; Mycobacterium tuberculosis/drug effects ; Mycobacterium tuberculosis/genetics ; Mycobacterium tuberculosis/isolation & purification ; Sputum/chemistry ; Sputum/microbiology ; Tuberculosis/diagnosis ; Tuberculosis/microbiology ; Tuberculosis, Multidrug-Resistant/diagnosis ; Tuberculosis, Multidrug-Resistant/microbiology ; Whole Genome Sequencing
    Chemical Substances Antitubercular Agents
    Language English
    Publishing date 2018-07-26
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 390499-4
    ISSN 1098-660X ; 0095-1137
    ISSN (online) 1098-660X
    ISSN 0095-1137
    DOI 10.1128/JCM.00666-18
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Immunogenicity of standard and extended dosing intervals of BNT162b2 mRNA vaccine

    Payne, Rebecca P. / Longet, Stephanie / Austin, James A. / Skelly, Donal T. / Dejnirattisai, Wanwisa / Adele, Sandra / Meardon, Naomi / Faustini, Sian / Al-Taei, Saly / Moore, Shona C. / Tipton, Tom / Hering, Luisa M. / Angyal, Adrienn / Brown, Rebecca / Nicols, Alexander R. / Gillson, Natalie / Dobson, Susan L. / Amini, Ali / Supasa, Piyada /
    Cross, Andrew / Bridges-Webb, Alice / Reyes, Laura Silva / Linder, Aline / Sandhar, Gurjinder / Kilby, Jonathan A. / Tyerman, Jessica K. / Altmann, Thomas / Hornsby, Hailey / Whitham, Rachel / Phillips, Eloise / Malone, Tom / Hargreaves, Alexander / Shields, Adrian / Saei, Ayoub / Foulkes, Sarah / Stafford, Lizzie / Johnson, Sile / Wootton, Daniel G. / Conlon, Christopher P. / Jeffery, Katie / Matthews, Philippa C. / Frater, John / Deeks, Alexandra S. / Pollard, Andrew J. / Brown, Anthony / Rowland-Jones, Sarah L. / Mongkolsapaya, Juthathip / Barnes, Eleanor / Hopkins, Susan / Hall, Victoria / Dold, Christina / Duncan, Christopher J.A. / Richter, Alex / Carroll, Miles / Screaton, Gavin / de Silva, Thushan I. / Turtle, Lance / Klenerman, Paul / Dunachie, Susanna / Abuelgasim, Hibatullah / Adland, Emily / Adlou, Syed / Akther, Hossain Delowar / Alhussni, Ahmed / Ali, Mohammad / Ansari, M. Azim / Arancibia-Cárcamo, Carolina V. / Bayley, Martin / Brown, Helen / Chalk, Jeremy / Chand, Meera / Chawla, Anu / Chinnakannan, Senthil / Cutteridge, Jospeh / de Lara, Catherine / Denly, Lucy / Diffey, Ben / Dimitriadis, Stavros / Drake, Thomas M. / Donnison, Timothy / Dupont, Maeva / Eyre, David / Fairman, Alex / Gardiner, Siobhan / Gilbert-Jarmillo, Javier / Goulder, Philip / Hackstein, Carl-Philipp / Hambleton, Sophie / Haniffa, Muzlifah / Haworth, Jenny / Holmes, Jennifer / Horner, Emily / Jämsén, Anni / Jones, Chris / Kasanyinga, Mwila / Kelly, Sinead / Kirk, Rosemary / Knight, Michael L. / Lawrie, Allan / Lee, Lian / Lett, Lauren / Lillie, Katy / Lim, Nicholas / Mehta, Hema / Mentzer, Alexander J. / O’Donnell, Denise / Ogbe, Ane / Pace, Matthew / Payne, Brendan A.I. / Platt, Gareth / Poolan, Sonia / Provine, Nicholas / Ramamurthy, Narayan / Robinson, Nichola / Romaniuk, Leigh / Rongkard, Patpong / Sampson, Oliver L. / Simmons, Beatrice / Spegarova, Jarmila S. / Stephenson, Emily / Subramaniam, Kris / Thaventhiran, James / Thomas, Sarah / Travis, Simon / Tucker, Stephanie / Turton, Helena / Watson, Adam / Watson, Lisa / Weeks, Esme / Wilson, Robert / Wood, Steven / Wright, Rachel / Xiao, Huiyuan / Zawia, Amira A.T.

    Cell. 2021 Nov. 11, v. 184, no. 23

    2021  

    Abstract: Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United ... ...

    Institution on behalf of the PITCH Consortium
    Abstract Extension of the interval between vaccine doses for the BNT162b2 mRNA vaccine was introduced in the United Kingdom to accelerate population coverage with a single dose. At this time, trial data were lacking, and we addressed this in a study of United Kingdom healthcare workers. The first vaccine dose induced protection from infection from the circulating alpha (B.1.1.7) variant over several weeks. In a substudy of 589 individuals, we show that this single dose induces severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) neutralizing antibody (NAb) responses and a sustained B and T cell response to the spike protein. NAb levels were higher after the extended dosing interval (6–14 weeks) compared with the conventional 3- to 4-week regimen, accompanied by enrichment of CD4⁺ T cells expressing interleukin-2 (IL-2). Prior SARS-CoV-2 infection amplified and accelerated the response. These data on dynamic cellular and humoral responses indicate that extension of the dosing interval is an effective immunogenic protocol.
    Keywords Severe acute respiratory syndrome coronavirus 2 ; health services ; immunogenicity ; interleukin-2 ; vaccines ; United Kingdom
    Language English
    Dates of publication 2021-1111
    Size p. 5699-5714.e11.
    Publishing place Elsevier Inc.
    Document type Article
    ZDB-ID 187009-9
    ISSN 1097-4172 ; 0092-8674
    ISSN (online) 1097-4172
    ISSN 0092-8674
    DOI 10.1016/j.cell.2021.10.011
    Database NAL-Catalogue (AGRICOLA)

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