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Book ; Online: Scanning electron diffraction tomography of strain

Tovey, Robert / Johnstone, Duncan N. / Collins, Sean M. / Lionheart, William R. B. / Midgley, Paul A. / Benning, Martin / Schönlieb, Carola-Bibiane

2020

Abstract: Strain engineering is used to obtain desirable materials properties in a range of modern technologies. Direct nanoscale measurement of the three-dimensional strain tensor field within these materials has however been limited by a lack of suitable ... ...

Abstract	Strain engineering is used to obtain desirable materials properties in a range of modern technologies. Direct nanoscale measurement of the three-dimensional strain tensor field within these materials has however been limited by a lack of suitable experimental techniques and data analysis tools. Scanning electron diffraction has emerged as a powerful tool for obtaining two-dimensional maps of strain components perpendicular to the incident electron beam direction. Extension of this method to recover the full three-dimensional strain tensor field has been restricted though by the absence of a formal framework for tensor tomography using such data. Here, we show that it is possible to reconstruct the full non-symmetric strain tensor field as the solution to an ill-posed tensor tomography inverse problem. We then demonstrate the properties of this tomography problem both analytically and computationally, highlighting why incorporating precession to perform scanning precession electron diffraction may be important. We establish a general framework for non-symmetric tensor tomography and demonstrate computationally its applicability for achieving strain tomography with scanning precession electron diffraction data.
Keywords	Mathematics - Numerical Analysis ; Condensed Matter - Materials Science
Subject code	669
Publishing date	2020-08-03
Publishing country	us
Document type	Book ; Online
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Article ; Online: Renal peroxiredoxin 6 interacts with anion exchanger 1 and plays a novel role in pH homeostasis.

Sorrell, Sara L / Golder, Zoe J / Johnstone, Duncan B / Frankl, Fiona E Karet

Kidney international

2016 Volume 89, Issue 1, Page(s) 105–112

Abstract: Peroxiredoxin 6 (PRDX6) is one of the six members of the PRDX family, which have peroxidase and antioxidant activity. PRDX6 is unique, containing only one conserved cysteine residue (C47) rather than the two found in other PRDXs. A yeast two-hybrid ... ...

Abstract	Peroxiredoxin 6 (PRDX6) is one of the six members of the PRDX family, which have peroxidase and antioxidant activity. PRDX6 is unique, containing only one conserved cysteine residue (C47) rather than the two found in other PRDXs. A yeast two-hybrid screen found PRDX6 to be a potential binding partner of the C-terminal tail of anion exchanger 1 (AE1), a Cl(-)/HCO(3)(-) exchanger basolaterally expressed in renal α-intercalated cells. PRDX6 immunostaining in human kidney was both cytoplasmic and peripheral and colocalized with AE1. Analysis of native protein showed that it was largely monomeric, whereas expressed tagged protein was more dimeric. Two methionine oxidation sites were identified. In vitro and ex vivo pull-downs and immunoprecipitation assays confirmed interaction with AE1, but mutation of the conserved cysteine resulted in loss of interaction. Prdx6 knockout mice had a baseline acidosis with a major respiratory component and greater AE1 expression than wild-type animals. After an oral acid challenge, PRDX6 expression increased in wild-type mice, with preservation of AE1. However, AE1 expression was significantly decreased in knockout animals. Kidneys from acidified mice showed widespread proximal tubular vacuolation in wild-type but not knockout animals. Knockdown of PRDX6 by siRNA in mammalian cells reduced both total and cell membrane AE1 levels. Thus, PRDX6-AE1 interaction contributes to the maintenance of AE1 during cellular stress such as during metabolic acidosis.
MeSH term(s)	Acidosis/metabolism ; Animals ; Anion Exchange Protein 1, Erythrocyte/chemistry ; Anion Exchange Protein 1, Erythrocyte/metabolism ; Homeostasis ; Humans ; Hydrogen-Ion Concentration ; Immunohistochemistry ; Immunoprecipitation ; Kidney/metabolism ; Kidney/pathology ; Mice ; Mice, Knockout ; Peroxiredoxin VI/chemistry ; Peroxiredoxin VI/genetics ; Peroxiredoxin VI/metabolism
Chemical Substances	Anion Exchange Protein 1, Erythrocyte ; Peroxiredoxin VI (EC 1.11.1.15)
Language	English
Publishing date	2016-01-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1038/ki.2015.277
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Article ; Online: Alterations in nuclear structure promote lupus autoimmunity in a mouse model.

Singh, Namrata / Johnstone, Duncan B / Martin, Kayla A / Tempera, Italo / Kaplan, Mariana J / Denny, Michael F

Disease models & mechanisms

2016 Volume 9, Issue 8, Page(s) 885–897

Abstract: ... the Pelger-Huet anomaly, and had prominent mis-splicing of mRNA encoding the nuclear membrane protein lamin B receptor ...

Abstract	Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the development of autoantibodies that recognize components of the cell nucleus. The vast majority of lupus research has focused on either the contributions of immune cell dysfunction or the genetics of the disease. Because granulocytes isolated from human SLE patients had alterations in neutrophil nuclear morphology that resembled the Pelger-Huet anomaly, and had prominent mis-splicing of mRNA encoding the nuclear membrane protein lamin B receptor (LBR), consistent with their Pelger-Huet-like nuclear morphology, we used a novel mouse model system to test the hypothesis that a disruption in the structure of the nucleus itself also contributes to the development of lupus autoimmunity. The lupus-prone mouse strain New Zealand White (NZW) was crossed with c57Bl/6 mice harboring a heterozygous autosomal dominant mutation in Lbr (B6.Lbr(ic/+)), and the (NZW×B6.Lbr(ic))F1 offspring were evaluated for induction of lupus autoimmunity. Only female (NZW×B6.Lbr(ic))F1 mice developed lupus autoimmunity, which included splenomegaly, kidney damage and autoantibodies. Kidney damage was accompanied by immune complex deposition, and perivascular and tubule infiltration of mononuclear cells. The titers of anti-chromatin antibodies exceeded those of aged female MRL-Fas(lpr) mice, and were predominantly of the IgG2 subclasses. The anti-nuclear antibody staining profile of female (NZW×B6.Lbr(ic))F1 sera was complex, and consisted of an anti-nuclear membrane reactivity that colocalized with the A-type lamina, in combination with a homogeneous pattern that was related to the recognition of histones with covalent modifications that are associated with gene activation. An anti-neutrophil IgM recognizing calreticulin, but not myeloperoxidase (MPO) or proteinase 3 (PR3), was also identified. Thus, alterations in nuclear structure contribute to lupus autoimmunity when expressed in the context of a lupus-prone genetic background, suggesting a mechanism for the development of lupus autoimmunity in genetically predisposed individuals that is induced by the disruption of nuclear architecture.
MeSH term(s)	Animals ; Autoantibodies/blood ; Autoantibodies/immunology ; Autoantigens/blood ; Autoantigens/immunology ; Autoimmunity ; Calreticulin/metabolism ; Cell Nucleus/pathology ; Cell Separation ; Crosses, Genetic ; Disease Models, Animal ; Female ; Granulocytes/metabolism ; Granulocytes/pathology ; Histones/metabolism ; Humans ; Immunoglobulin M/immunology ; Kidney/pathology ; Lamin Type A/metabolism ; Lupus Erythematosus, Systemic/blood ; Lupus Erythematosus, Systemic/immunology ; Lupus Erythematosus, Systemic/pathology ; Male ; Mice, Inbred C57BL ; Myeloblastin/metabolism ; Peroxidase/metabolism ; RNA Splicing/genetics ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Receptors, Cytoplasmic and Nuclear/genetics ; Receptors, Cytoplasmic and Nuclear/metabolism ; Splenomegaly/pathology ; Transcriptional Activation ; Lamin B Receptor
Chemical Substances	Autoantibodies ; Autoantigens ; Calreticulin ; Histones ; Immunoglobulin M ; Lamin Type A ; RNA, Messenger ; Receptors, Cytoplasmic and Nuclear ; Peroxidase (EC 1.11.1.7) ; Myeloblastin (EC 3.4.21.76)
Language	English
Publishing date	2016-06-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2451104-3
ISSN	1754-8411 ; 1754-8403
ISSN (online)	1754-8411
ISSN	1754-8403
DOI	10.1242/dmm.024851
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Article ; Online: Background strain and the differential susceptibility of podocyte-specific deletion of Myh9 on murine models of experimental glomerulosclerosis and HIV nephropathy.

Johnstone, Duncan B / Ikizler, Omer / Zhang, Jidong / Holzman, Lawrence B

PloS one

2013 Volume 8, Issue 7, Page(s) e67839

Abstract: We previously reported that podocyte-specific deletion of Myh9 (conventional myosin heavy chain 2A) in C57BL/6 mice does not cause spontaneous kidney disease but instead results in a predisposition to glomerulosclerosis in response to a second model of ... ...

Abstract	We previously reported that podocyte-specific deletion of Myh9 (conventional myosin heavy chain 2A) in C57BL/6 mice does not cause spontaneous kidney disease but instead results in a predisposition to glomerulosclerosis in response to a second model of glomerular injury. In contrast, other investigators reported that podocyte-specific deletion of Myh9 (PodΔMyh9) resulted in spontaneous glomerulosclerosis in mice on a mixed background, suggesting that the glomerulosclerosis is dependent on background strain. In order to elucidate the cause of this strain dependent effect Podocin::Cre and Myh9(flox) alleles were backcrossed to mouse strain FVB/N, which is highly susceptible to glomerulosclerosis, with the aim of intercrossing susceptible FVB/N and resistant C57BL/6 mice in subsequent congenic analyses. However, after backcrossing mice to FVB/N and aging mice to 28 weeks, we found no evidence of glomerular disease in PodΔMyh9 mice vs control littermates (urine MAC ratio all p>0.05). We also tested C57BL/6 PodΔMyh9 mice for a predisposition to injury from models other than Adriamycin including HIV nephropathy (HIVAN), puromycin nephropathy, and sheep nephrotoxic serum. In the Tg26 model of HIVAN, we found that podocyte-specific deletion of Myh9 resulted in a modest hypersensitivity in adults compared to Tg26+ control littermates (urine MAC ratio, p<0.05 or less). In contrast, we found that PodΔMyh9 mice were not predisposed to injury in response to other injury models including puromycin nephropathy and sheep nephrotoxic serum. While the mechanism of injury in these models is not fully understood, we conclude that PodΔMyh9 results in a variable susceptibility to glomerulosclerosis in response to different models of glomerular injury. In addition, based on the lack of a spontaneous phenotype of glomerulosclerosis in both C57BL/6 and FVB/N mice, we propose that Myh9 is not absolutely required in adult podocytes.
MeSH term(s)	AIDS-Associated Nephropathy/genetics ; AIDS-Associated Nephropathy/pathology ; Animals ; Disease Models, Animal ; Female ; Gene Deletion ; Genetic Predisposition to Disease/genetics ; Glomerulosclerosis, Focal Segmental/genetics ; Glomerulosclerosis, Focal Segmental/pathology ; HIV-1/physiology ; Male ; Mice ; Mice, Congenic ; Mice, Inbred C57BL ; Mice, Inbred Strains/genetics ; Mice, Transgenic ; Myosin Heavy Chains ; Nonmuscle Myosin Type IIA/genetics ; Organ Specificity/genetics ; Podocytes/metabolism
Chemical Substances	Myh9 protein, mouse ; Nonmuscle Myosin Type IIA (EC 3.6.1.-) ; Myosin Heavy Chains (EC 3.6.4.1)
Language	English
Publishing date	2013-07-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0067839
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Article: Clinical impact of research on the podocyte slit diaphragm.

Johnstone, Duncan B / Holzman, Lawrence B

Nature clinical practice. Nephrology

2006 Volume 2, Issue 5, Page(s) 271–282

Abstract: This Review summarizes recent research on the podocyte slit diaphragm. A growing number of molecules that function at the slit diaphragm have been identified in patients with inherited and sporadic nephrotic syndromes. Genetic deletion of nearly all of ... ...

Abstract	This Review summarizes recent research on the podocyte slit diaphragm. A growing number of molecules that function at the slit diaphragm have been identified in patients with inherited and sporadic nephrotic syndromes. Genetic deletion of nearly all of these molecules results in proteinuria and effacement of foot processes. Nephrin, Neph1 and podocin seem to form a multifunctional receptor complex at the slit diaphragm. Most of the other components of the slit diaphragm interact directly with this complex, in many cases coupling slit diaphragm components to the podocyte's actin cytoskeleton. These molecular findings are being applied to patients with glomerular disease. Over the next decade, these data might help to improve disease classification and prediction of which patients will respond to immunosuppressive treatment.
MeSH term(s)	Gene Expression ; Glomerular Filtration Rate/physiology ; Humans ; Intercellular Junctions/physiology ; Intracellular Signaling Peptides and Proteins ; Membrane Proteins/genetics ; Membrane Proteins/physiology ; Nephrotic Syndrome/diagnosis ; Nephrotic Syndrome/genetics ; Nephrotic Syndrome/physiopathology ; Nephrotic Syndrome/therapy ; Podocytes/physiology ; Signal Transduction/physiology
Chemical Substances	Intracellular Signaling Peptides and Proteins ; KIRREL1 protein, human ; Membrane Proteins ; NPHS2 protein ; nephrin
Language	English
Publishing date	2006-08-16
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2228557-X
ISSN	1745-8331 ; 1745-8323
ISSN (online)	1745-8331
ISSN	1745-8323
DOI	10.1038/ncpneph0180
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Article ; Online: Background strain and the differential susceptibility of podocyte-specific deletion of Myh9 on murine models of experimental glomerulosclerosis and HIV nephropathy.

Duncan B Johnstone / Omer Ikizler / Jidong Zhang / Lawrence B Holzman

PLoS ONE, Vol 8, Iss 7, p e

2013 Volume 67839

Abstract	We previously reported that podocyte-specific deletion of Myh9 (conventional myosin heavy chain 2A) in C57BL/6 mice does not cause spontaneous kidney disease but instead results in a predisposition to glomerulosclerosis in response to a second model of glomerular injury. In contrast, other investigators reported that podocyte-specific deletion of Myh9 (PodΔMyh9) resulted in spontaneous glomerulosclerosis in mice on a mixed background, suggesting that the glomerulosclerosis is dependent on background strain. In order to elucidate the cause of this strain dependent effect Podocin::Cre and Myh9(flox) alleles were backcrossed to mouse strain FVB/N, which is highly susceptible to glomerulosclerosis, with the aim of intercrossing susceptible FVB/N and resistant C57BL/6 mice in subsequent congenic analyses. However, after backcrossing mice to FVB/N and aging mice to 28 weeks, we found no evidence of glomerular disease in PodΔMyh9 mice vs control littermates (urine MAC ratio all p>0.05). We also tested C57BL/6 PodΔMyh9 mice for a predisposition to injury from models other than Adriamycin including HIV nephropathy (HIVAN), puromycin nephropathy, and sheep nephrotoxic serum. In the Tg26 model of HIVAN, we found that podocyte-specific deletion of Myh9 resulted in a modest hypersensitivity in adults compared to Tg26+ control littermates (urine MAC ratio, p<0.05 or less). In contrast, we found that PodΔMyh9 mice were not predisposed to injury in response to other injury models including puromycin nephropathy and sheep nephrotoxic serum. While the mechanism of injury in these models is not fully understood, we conclude that PodΔMyh9 results in a variable susceptibility to glomerulosclerosis in response to different models of glomerular injury. In addition, based on the lack of a spontaneous phenotype of glomerulosclerosis in both C57BL/6 and FVB/N mice, we propose that Myh9 is not absolutely required in adult podocytes.
Keywords	Medicine ; R ; Science ; Q
Subject code	572
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
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Article ; Online: Recalibrated estimates of non-bacteremic and bacteremic pneumococcal community acquired pneumonia in hospitalized Canadian adults from 2010 to 2017 with addition of an extended spectrum serotype-specific urine antigen detection assay.

Vaccine

2022 Volume 40, Issue 18, Page(s) 2635–2646

Abstract: Objective(s): In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in ... ...

Abstract	Objective(s): In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017. Methods: S. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16-49, 50-64, and 65 + ) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)]. Results: 11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50-64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP. Conclusion(s): Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD.
MeSH term(s)	Adult ; Canada/epidemiology ; Child ; Community-Acquired Infections/diagnosis ; Community-Acquired Infections/epidemiology ; Humans ; Pneumococcal Infections/prevention & control ; Pneumococcal Vaccines ; Pneumonia ; Pneumonia, Pneumococcal/diagnosis ; Pneumonia, Pneumococcal/epidemiology ; Pneumonia, Pneumococcal/prevention & control ; Serogroup ; Streptococcus pneumoniae ; Vaccines, Conjugate
Chemical Substances	Pneumococcal Vaccines ; Vaccines, Conjugate
Language	English
Publishing date	2022-03-18
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2022.02.081
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Article ; Online: Liquid-phase sintering of lead halide perovskites and metal-organic framework glasses.

Hou, Jingwei / Chen, Peng / Shukla, Atul / Krajnc, Andraž / Wang, Tiesheng / Li, Xuemei / Doasa, Rana / Tizei, Luiz H G / Chan, Bun / Johnstone, Duncan N / Lin, Rijia / Schülli, Tobias U / Martens, Isaac / Appadoo, Dominique / Ari, Mark S' / Wang, Zhiliang / Wei, Tong / Lo, Shih-Chun / Lu, Mingyuan /

Li, Shichun / Namdas, Ebinazar B / Mali, Gregor / Cheetham, Anthony K / Collins, Sean M / Chen, Vicki / Wang, Lianzhou / Bennett, Thomas D

Science (New York, N.Y.)

2021 Volume 374, Issue 6567, Page(s) 621–625

Abstract: Lead halide perovskite (LHP) semiconductors show exceptional optoelectronic properties. Barriers for their applications, however, lie in their polymorphism, instability to polar solvents, phase segregation, and susceptibility to the leaching of lead ions. ...

Abstract	Lead halide perovskite (LHP) semiconductors show exceptional optoelectronic properties. Barriers for their applications, however, lie in their polymorphism, instability to polar solvents, phase segregation, and susceptibility to the leaching of lead ions. We report a family of scalable composites fabricated through liquid-phase sintering of LHPs and metal-organic framework glasses. The glass acts as a matrix for LHPs, effectively stabilizing nonequilibrium perovskite phases through interfacial interactions. These interactions also passivate LHP surface defects and impart bright, narrow-band photoluminescence with a wide gamut for creating white light-emitting diodes (LEDs). The processable composites show high stability against immersion in water and organic solvents as well as exposure to heat, light, air, and ambient humidity. These properties, together with their lead self-sequestration capability, can enable breakthrough applications for LHPs.
Language	English
Publishing date	2021-10-28
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.abf4460
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Article ; Online: Alterations in nuclear structure promote lupus autoimmunity in a mouse model

Namrata Singh / Duncan B. Johnstone / Kayla A. Martin / Italo Tempera / Mariana J. Kaplan / Michael F. Denny

Disease Models & Mechanisms, Vol 9, Iss 8, Pp 885-

2016 Volume 897

Abstract: ... anomaly, and had prominent mis-splicing of mRNA encoding the nuclear membrane protein lamin B receptor ...

Abstract	Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the development of autoantibodies that recognize components of the cell nucleus. The vast majority of lupus research has focused on either the contributions of immune cell dysfunction or the genetics of the disease. Because granulocytes isolated from human SLE patients had alterations in neutrophil nuclear morphology that resembled the Pelger–Huet anomaly, and had prominent mis-splicing of mRNA encoding the nuclear membrane protein lamin B receptor (LBR), consistent with their Pelger–Huet-like nuclear morphology, we used a novel mouse model system to test the hypothesis that a disruption in the structure of the nucleus itself also contributes to the development of lupus autoimmunity. The lupus-prone mouse strain New Zealand White (NZW) was crossed with c57Bl/6 mice harboring a heterozygous autosomal dominant mutation in Lbr (B6.Lbric/+), and the (NZW×B6.Lbric)F1 offspring were evaluated for induction of lupus autoimmunity. Only female (NZW×B6.Lbric)F1 mice developed lupus autoimmunity, which included splenomegaly, kidney damage and autoantibodies. Kidney damage was accompanied by immune complex deposition, and perivascular and tubule infiltration of mononuclear cells. The titers of anti-chromatin antibodies exceeded those of aged female MRL-Faslpr mice, and were predominantly of the IgG2 subclasses. The anti-nuclear antibody staining profile of female (NZW×B6.Lbric)F1 sera was complex, and consisted of an anti-nuclear membrane reactivity that colocalized with the A-type lamina, in combination with a homogeneous pattern that was related to the recognition of histones with covalent modifications that are associated with gene activation. An anti-neutrophil IgM recognizing calreticulin, but not myeloperoxidase (MPO) or proteinase 3 (PR3), was also identified. Thus, alterations in nuclear structure contribute to lupus autoimmunity when expressed in the context of a lupus-prone genetic background, suggesting a mechanism for the development ...
Keywords	Nucleus ; Chromatin ; Histone modifications ; Calreticulin ; Lamina ; Autoantibody ; Medicine ; R ; Pathology ; RB1-214
Subject code	570
Language	English
Publishing date	2016-08-01T00:00:00Z
Publisher	The Company of Biologists
Document type	Article ; Online
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Article: Recalibrated estimates of non-bacteremic and bacteremic pneumococcal community acquired pneumonia in hospitalized Canadian adults from 2010 to 2017 with addition of an extended spectrum serotype-specific urine antigen detection assay

Vaccine. 2022 Feb. 24,

2022

Abstract: In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized ... ...

Abstract	In the context of age- and risk-based pneumococcal vaccine recommendations in Canada, this study presents updated data from active surveillance of pneumococcal community acquired pneumonia (pCAP) and invasive pneumococcal disease (IPD) in hospitalized adults from 2010 to 2017. S. pneumoniae was detected using culture (blood and sputum), and urine antigen detection (UAD). Serotyping was performed with Quellung, PCR, or using the PCV13- and PPV23 (non-PCV13)-specific UADs. Laboratory results, demographic, and outcome data were categorized by age (16–49, 50–64, and 65 +) and by disease [non-bacteremic pCAP, bacteremic pCAP, and IPD(non-CAP)]. 11,129 CAP cases and 216 cases of IPD (non-CAP) were identified. Laboratory testing for S. pneumoniae was performed in 8912 CAP cases, identifying 1264 (14.2%) as pCAP. Of pCAP cases, 811 (64.1%) were non-bacteremic and 455 (35.9%) were bacteremic. Adults 65 + years represented 54.5% of non-bacteremic pCAP, 41.4% of bacteremic pCAP, and 48.6% of IPD cases. Adults 50–64 years contributed 30.3%, 33.1%, and 29.9%, respectively. In pCAP, PCV13 serotypes declined between 2010 and 2014 due to declines in serotypes 7F and 19A, then plateaued from 2015 to 2017 with persistence of serotype 3. In later study years, non-bacteremic pCAP was predominant, and PPV23 (non-PCV13) serotypes increased from 2015 to 2017, with serotypes 22F, 11A, and 9 N being most frequently identified. Compared to non-pCAP, pCAP cases were more likely to be admitted to intensive care units and require mechanical ventilation. These outcomes and mortality were more common in bacteremic pCAP and IPD, versus non-bacteremic pCAP. Along with IPD, pCAP surveillance (bacteremic and non-bacteremic) is important as their trends may differ over time. With insufficient herd protection from PCV13 childhood immunization, or use of PPV23 in adults, this study supports direct adult immunization with PCV13 or higher valency conjugate vaccines to reduce the residual burden of pCAP and IPD.
Keywords	Streptococcus pneumoniae ; adults ; antigen detection ; blood ; childhood ; herds ; immunization ; monitoring ; mortality ; pneumonia ; serotypes ; urine ; vaccines ; Canada
Language	English
Dates of publication	2022-0224
Publishing place	Elsevier Ltd
Document type	Article
Note	Pre-press version
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2022.02.081
Database	NAL-Catalogue (AGRICOLA)

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In stock of ZB MED Cologne/Königswinter

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Full text online

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Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito