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  1. Article: Infection-related hemolysis and susceptibility to Gram-negative bacterial co-infection.

    Orf, Katharine / Cunnington, Aubrey J

    Frontiers in microbiology

    2015  Volume 6, Page(s) 666

    Abstract: Increased susceptibility to co-infection with enteric Gram-negative bacteria, particularly non-typhoidal Salmonella, is reported in malaria and Oroya fever (Bartonella bacilliformis infection), and can lead to increased mortality. Accumulating ... ...

    Abstract Increased susceptibility to co-infection with enteric Gram-negative bacteria, particularly non-typhoidal Salmonella, is reported in malaria and Oroya fever (Bartonella bacilliformis infection), and can lead to increased mortality. Accumulating epidemiological evidence indicates a causal association with risk of bacterial co-infection, rather than just co-incidence of common risk factors. Both malaria and Oroya fever are characterized by hemolysis, and observations in humans and animal models suggest that hemolysis causes the susceptibility to bacterial co-infection. Evidence from animal models implicates hemolysis in the impairment of a variety of host defense mechanisms, including macrophage dysfunction, neutrophil dysfunction, and impairment of adaptive immune responses. One mechanism supported by evidence from animal models and human data, is the induction of heme oxygenase-1 in bone marrow, which impairs the ability of developing neutrophils to mount a competent oxidative burst. As a result, dysfunctional neutrophils become a new niche for replication of intracellular bacteria. Here we critically appraise and summarize the key evidence for mechanisms which may contribute to these very specific combinations of co-infections, and propose interventions to ameliorate this risk.
    Language English
    Publishing date 2015-06-30
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2587354-4
    ISSN 1664-302X
    ISSN 1664-302X
    DOI 10.3389/fmicb.2015.00666
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Remdesivir during induction chemotherapy for newly diagnosed paediatric acute lymphoblastic leukaemia with concomitant SARS-CoV-2 infection.

    Orf, Katharine / Rogosic, Srdan / Dexter, Daniel / Ancliff, Phil / Badle, Saket / Brierley, Joe / Cheng, Danny / Dalton, Caroline / Dixon, Garth / Du Pré, Pascale / Grandjean, Louis / Ghorashian, Sara / Mittal, Prabal / O'Connor, David / Pavasovic, Vesna / Rao, Anupama / Samarasinghe, Sujith / Vora, Ajay / Bamford, Alasdair /
    Bartram, Jack

    British journal of haematology

    2020  Volume 190, Issue 5, Page(s) e274–e276

    MeSH term(s) Adenosine Monophosphate/administration & dosage ; Adenosine Monophosphate/analogs & derivatives ; Alanine/administration & dosage ; Alanine/analogs & derivatives ; Betacoronavirus/metabolism ; COVID-19 ; Child, Preschool ; Coronavirus Infections/diagnosis ; Coronavirus Infections/drug therapy ; Coronavirus Infections/etiology ; Humans ; Induction Chemotherapy ; Male ; Pandemics ; Pneumonia, Viral/diagnosis ; Pneumonia, Viral/drug therapy ; Pneumonia, Viral/etiology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/diagnosis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/virology ; SARS-CoV-2
    Chemical Substances remdesivir (3QKI37EEHE) ; Adenosine Monophosphate (415SHH325A) ; Alanine (OF5P57N2ZX)
    Keywords covid19
    Language English
    Publishing date 2020-08-23
    Publishing country England
    Document type Case Reports ; Letter
    ZDB-ID 80077-6
    ISSN 1365-2141 ; 0007-1048
    ISSN (online) 1365-2141
    ISSN 0007-1048
    DOI 10.1111/bjh.17014
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Impairment of neutrophil oxidative burst in children with sickle cell disease is associated with heme oxygenase-1.

    Evans, Ceri / Orf, Katharine / Horvath, Erzsebet / Levin, Michael / De La Fuente, Josu / Chakravorty, Subarna / Cunnington, Aubrey J

    Haematologica

    2015  Volume 100, Issue 12, Page(s) 1508–1516

    Abstract: Sickle cell disease is a risk factor for invasive bacterial infections, and splenic dysfunction is believed to be the main underlying cause. We have previously shown that the liberation of heme in acute hemolysis can induce heme oxygenase-1 during ... ...

    Abstract Sickle cell disease is a risk factor for invasive bacterial infections, and splenic dysfunction is believed to be the main underlying cause. We have previously shown that the liberation of heme in acute hemolysis can induce heme oxygenase-1 during granulopoiesis, impairing the ability of developing neutrophils to mount a bactericidal oxidative burst, and increasing susceptibility to bacterial infection. We hypothesized that this may also occur with the chronic hemolysis of sickle cell disease, potentially contributing to susceptibility to infections. We found that neutrophil oxidative burst activity was significantly lower in treatment-naïve children with sickle cell disease compared to age-, gender- and ethnicity-matched controls, whilst degranulation was similar. The defect in neutrophil oxidative burst was quantitatively related to both systemic heme oxygenase-1 activity (assessed by carboxyhemoglobin concentration) and neutrophil mobilization. A distinct population of heme oxygenase-1-expressing cells was present in the bone marrow of children with sickle cell disease, but not in healthy children, with a surface marker profile consistent with neutrophil progenitors (CD49d(Hi) CD24(Lo) CD15(Int) CD16(Int) CD11b(+/-)). Incubation of promyelocytic HL-60 cells with the heme oxygenase-1 substrate and inducer, hemin, demonstrated that heme oxygenase-1 induction during neutrophilic differentiation could reduce oxidative burst capacity. These findings indicate that impairment of neutrophil oxidative burst activity in sickle cell disease is associated with hemolysis and heme oxygenase-1 expression. Neutrophil dysfunction might contribute to risk of infection in sickle cell disease, and measurement of neutrophil oxidative burst might be used to identify patients at greatest risk of infection, who might benefit from enhanced prophylaxis.
    MeSH term(s) Adolescent ; Anemia, Sickle Cell/enzymology ; Anemia, Sickle Cell/pathology ; Antigens, CD/metabolism ; Child ; Child, Preschool ; Female ; HL-60 Cells ; Heme Oxygenase-1/metabolism ; Humans ; Infant ; Male ; Neutrophils/enzymology ; Neutrophils/pathology ; Respiratory Burst
    Chemical Substances Antigens, CD ; HMOX1 protein, human (EC 1.14.14.18) ; Heme Oxygenase-1 (EC 1.14.14.18)
    Language English
    Publishing date 2015-12
    Publishing country Italy
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2015.128777
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Remdesivir during induction chemotherapy for newly diagnosed paediatric acute lymphoblastic leukaemia with concomitant SARS-CoV-2 infection

    Orf, Katharine / Rogosic, Srdan / Dexter, Daniel / Ancliff, Phil / Badle, Saket / Brierley, Joe / Cheng, Danny / Dalton, Caroline / Dixon, Garth / Du Pré, Pascale / Grandjean, Louis / Ghorashian, Sara / Mittal, Prabal / O039, / Connor, David / Pavasovic, Vesna / Rao, Anupama / Samarasinghe, Sujith / Vora, Ajay /
    Bamford, Alasdair / Bartram, Jack

    Br J Haematol

    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #640126
    Database COVID19

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  5. Article ; Online: Remdesivir during induction chemotherapy for newly diagnosed paediatric acute lymphoblastic leukaemia with concomitant SARS‐CoV‐2 infection

    Orf, Katharine / Rogosic, Srdan / Dexter, Daniel / Ancliff, Phil / Badle, Saket / Brierley, Joe / Cheng, Danny / Dalton, Caroline / Dixon, Garth / Du Pré, Pascale / Grandjean, Louis / Ghorashian, Sara / Mittal, Prabal / O'Connor, David / Pavasovic, Vesna / Rao, Anupama / Samarasinghe, Sujith / Vora, Ajay / Bamford, Alasdair /
    Bartram, Jack

    British Journal of Haematology ; ISSN 0007-1048 1365-2141

    2020  

    Keywords Hematology ; covid19
    Language English
    Publisher Wiley
    Publishing country us
    Document type Article ; Online
    DOI 10.1111/bjh.17014
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Childhood meningitis in the conjugate vaccine era: a prospective cohort study.

    Sadarangani, Manish / Willis, Louise / Kadambari, Seilesh / Gormley, Stuart / Young, Zoe / Beckley, Rebecca / Gantlett, Katherine / Orf, Katharine / Blakey, Sarah / Martin, Natalie G / Kelly, Dominic F / Heath, Paul T / Nadel, Simon / Pollard, Andrew J

    Archives of disease in childhood

    2015  Volume 100, Issue 3, Page(s) 292–294

    Abstract: Bacterial conjugate vaccines have dramatically changed the epidemiology of childhood meningitis; viral causes are increasingly predominant, but the current UK epidemiology is unknown. This prospective study recruited children under 16 years of age ... ...

    Abstract Bacterial conjugate vaccines have dramatically changed the epidemiology of childhood meningitis; viral causes are increasingly predominant, but the current UK epidemiology is unknown. This prospective study recruited children under 16 years of age admitted to 3 UK hospitals with suspected meningitis. 70/388 children had meningitis-13 bacterial, 26 viral and 29 with no pathogen identified. Group B Streptococcus was the most common bacterial pathogen. Infants under 3 months of age with bacterial meningitis were more likely to have a reduced Glasgow Coma Score and respiratory distress than those with viral meningitis or other infections. There were no discriminatory clinical features in older children. Cerebrospinal fluid (CSF) white blood cell count and plasma C-reactive protein at all ages, and CSF protein in infants <3 months of age, distinguished between bacterial meningitis and viral meningitis or other infections. Improved diagnosis of non-bacterial meningitis is urgently needed to reduce antibiotic use and hospital stay.
    MeSH term(s) Child ; Child, Preschool ; Cohort Studies ; Female ; Humans ; Infant ; Male ; Meningitis, Bacterial/diagnosis ; Meningitis, Bacterial/microbiology ; Meningitis, Bacterial/prevention & control ; Meningitis, Viral/diagnosis ; Meningitis, Viral/prevention & control ; Meningitis, Viral/virology ; Prospective Studies ; United Kingdom ; Vaccines, Conjugate/administration & dosage
    Chemical Substances Vaccines, Conjugate
    Language English
    Publishing date 2015-03
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 524-1
    ISSN 1468-2044 ; 0003-9888 ; 1359-2998
    ISSN (online) 1468-2044
    ISSN 0003-9888 ; 1359-2998
    DOI 10.1136/archdischild-2014-306813
    Database MEDical Literature Analysis and Retrieval System OnLINE

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