Late Stage Infection in Sleeping Sickness
Publication Date
March 27, 2012
Journal
PLOS ONE
Authors
Hartwig Wolburg, Stefan Mogk, Sven Acker, Claudia Frey, et al
Volume
7
Issue
3
Pages
e34304
DOI
https://dx.plos.org/10.1371/journal.pone.0034304
Publisher URL
http://journals.plos.org/plosone/article?id=10.1371%2Fjournal.pone.0034304
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/22496723
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3320268
Europe PMC
http://europepmc.org/abstract/MED/22496723
Web of Science
000303894900079
Scopus
84858971155
Mendeley
http://www.mendeley.com/research/late-stage-infection-sleeping-sickness
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Mendeley | Further Information

{"title"=>"Late stage infection in sleeping sickness", "type"=>"journal", "authors"=>[{"first_name"=>"Hartwig", "last_name"=>"Wolburg", "scopus_author_id"=>"7005348251"}, {"first_name"=>"Stefan", "last_name"=>"Mogk", "scopus_author_id"=>"55143913600"}, {"first_name"=>"Sven", "last_name"=>"Acker", "scopus_author_id"=>"55141755000"}, {"first_name"=>"Claudia", "last_name"=>"Frey", "scopus_author_id"=>"55141108400"}, {"first_name"=>"Monika", "last_name"=>"Meinert", "scopus_author_id"=>"55144059800"}, {"first_name"=>"Caroline", "last_name"=>"Schönfeld", "scopus_author_id"=>"9741804600"}, {"first_name"=>"Michael", "last_name"=>"Lazarus", "scopus_author_id"=>"7006094741"}, {"first_name"=>"Yoshihiro", "last_name"=>"Urade", "scopus_author_id"=>"7005116541"}, {"first_name"=>"Bruno Kilunga", "last_name"=>"Kubata", "scopus_author_id"=>"6603292836"}, {"first_name"=>"Michael", "last_name"=>"Duszenko", "scopus_author_id"=>"7003342875"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84858971155", "doi"=>"10.1371/journal.pone.0034304", "issn"=>"19326203", "pui"=>"364514510", "sgr"=>"84858971155", "isbn"=>"19326203", "pmid"=>"22496723"}, "id"=>"0aa0208e-ff7e-38e4-9c01-7b87b6b82191", "abstract"=>"At the turn of the 19(th) century, trypanosomes were identified as the causative agent of sleeping sickness and their presence within the cerebrospinal fluid of late stage sleeping sickness patients was described. However, no definitive proof of how the parasites reach the brain has been presented so far. Analyzing electron micrographs prepared from rodent brains more than 20 days after infection, we present here conclusive evidence that the parasites first enter the brain via the choroid plexus from where they penetrate the epithelial cell layer to reach the ventricular system. Adversely, no trypanosomes were observed within the parenchyma outside blood vessels. We also show that brain infection depends on the formation of long slender trypanosomes and that the cerebrospinal fluid as well as the stroma of the choroid plexus is a hostile environment for the survival of trypanosomes, which enter the pial space including the Virchow-Robin space via the subarachnoid space to escape degradation. Our data suggest that trypanosomes do not intend to colonize the brain but reside near or within the glia limitans, from where they can re-populate blood vessels and disrupt the sleep wake cycles.", "link"=>"http://www.mendeley.com/research/late-stage-infection-sleeping-sickness", "reader_count"=>40, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>8, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>3, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>8, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>14, "Student > Postgraduate"=>1, "Student > Master"=>4, "Student > Bachelor"=>3, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>5, "Medicine and Dentistry"=>6, "Agricultural and Biological Sciences"=>17, "Neuroscience"=>3, "Arts and Humanities"=>2, "Chemistry"=>3, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Neuroscience"=>{"Neuroscience"=>3}, "Chemistry"=>{"Chemistry"=>3}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>17}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>5}, "Unspecified"=>{"Unspecified"=>2}, "Arts and Humanities"=>{"Arts and Humanities"=>2}}, "reader_count_by_country"=>{"Netherlands"=>1, "United Kingdom"=>1, "Chile"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/662846"], "description"=>"<p><b>a,</b> A representative micrograph showing a trypanosome (T) within the lumen (L) of a brain microvessel; no trypanosomes were found beyond the blood-brain barrier within the brain parenchyma (BP). <b>b,</b> Cross-section of the choroid plexus showing a fenestrated blood vessel (fV) and trypanosomes (T) within lumen and stroma (S); E, erythrocyte. Trypanosomes inside the blood vessel contain the VSG coat, while parasites in stroma are naked. <b>c,</b> Trypanosomes (T) in the stroma (S) between fenestrated capillaries (fV) containing the VSG surface coat. Note: in Figs a–c the brain was directly fixed by perfusion with glutaraldhyde prior to isolation. <b>d,</b> A trypanosome (T) inside a plexus cell within a lysosome suggesting phagocytosis of coatless trypanosomes. Trypanosomal and lysosomal membranes are labelled by double arrows. <b>e,</b> Low magnification of a choroid plexus showing the ventricle (V), plexus epithelial cells (PEC) and, in the stroma, a fenestrated capillary (fV) with a trypanosome (T). KC = Kolmer cell. <b>f,</b> Detail of the apical region of a plexus epithelial cell showing two trypanosomes (T) in close proximity of the microvilli of an epithelial cell and a Kolmer cell (KC), respectively.</p>", "links"=>[], "tags"=>["micrographs", "trypanosomes", "choroid", "plexus", "ventricle", "20", "days"], "article_id"=>333311, "categories"=>["Microbiology", "Neuroscience", "Infectious Diseases"], "users"=>["Hartwig Wolburg", "Stefan Mogk", "Sven Acker", "Claudia Frey", "Monika Meinert", "Caroline Schönfeld", "Michael Lazarus", "Yoshihiro Urade", "Bruno Kilunga Kubata", "Michael Duszenko"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0034304.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Electron_micrographs_showing_the_distribution_of_trypanosomes_in_the_choroid_plexus_and_ventricle_system_more_than_20_days_after_a_blood_infection_/333311", "title"=>"Electron micrographs showing the distribution of trypanosomes in the choroid plexus and ventricle system more than 20 days after a blood infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:19:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/662965"], "description"=>"<p><b>a,</b> Scanning electron micrographs of typical stumpy, intermediate and slender form trypanosomes. The size of the pictured trypanosome is 17 µm, 22 µm and 26 µm, respectively. <b>b,</b> Blood samples of 3 infected rats were analyzed for trypanosome titer up to 20 days (♦ [cells/ml]), shown is a representative curve. Additionally, the overall length of the parasites (n = 27) was measured and grouped into stumpy forms (up to 17 µm), intermediate forms (17–23 µm) and slender forms (longer than 23 µm). Intermediate forms (▪ [%]) represent proliferating trypanosomes. Slender forms (▴ [%]) increase continuously at low level during the course of infection and reach up to 40% after 20 days <i>p.i</i>. Distribution of stumpy forms is not explicitly shown but can be calculated as the difference to 100%. <b>c,</b> Comparison of trypanosomes isolated from blood or brain of infected rats. AnTat1.1 has been isolated from rat blood (4 days <i>p.i.</i>, red bars) and rat brain (35 days <i>p.i.</i>, blue bars). The overall length of parasites (n = 96) was measured from the back of the trypanosome to the tip of the flagellum (see inset). We here show that the brain isolate contains a significant amount of trypanosomes longer than 23 µm.</p>", "links"=>[], "tags"=>["trypanosomal", "morphology"], "article_id"=>333443, "categories"=>["Microbiology", "Neuroscience", "Infectious Diseases"], "users"=>["Hartwig Wolburg", "Stefan Mogk", "Sven Acker", "Claudia Frey", "Monika Meinert", "Caroline Schönfeld", "Michael Lazarus", "Yoshihiro Urade", "Bruno Kilunga Kubata", "Michael Duszenko"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0034304.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Changes_of_trypanosomal_morphology_during_the_course_of_infection_/333443", "title"=>"Changes of trypanosomal morphology during the course of infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:19:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/663041"], "description"=>"<p>AnTat1.1 was isolated 11 days <i>p.i.</i> from rat blood, separated from blood cells and adjusted to a cell density of 5*10<sup>4</sup> parasites in 100 µl of the respective solution. Contamination of csf with blood did not exceed 20%, as judged from the erythrocyte count. <i>Rattus norvegicus</i> csf supported survival of the parasites only for some 30 hours (▴) and could not be prolonged by supplementing 33 mM glucose (data not shown). However, in a mixture of csf and HMI-9 medium (1∶1), trypanosomes survived significantly longer (i.e. approx. 45 h, ▪). As HMI-9 medium (<b>♦</b>) contains all nutrients in excess, it supports growth of trypanosomes for approximately 56 h, even if diluted with saline solution (1∶1, X).</p>", "links"=>[], "tags"=>["trypanosome", "times", "cerebrospinal-fluid", "hmi-9"], "article_id"=>333519, "categories"=>["Microbiology", "Neuroscience", "Infectious Diseases"], "users"=>["Hartwig Wolburg", "Stefan Mogk", "Sven Acker", "Claudia Frey", "Monika Meinert", "Caroline Schönfeld", "Michael Lazarus", "Yoshihiro Urade", "Bruno Kilunga Kubata", "Michael Duszenko"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0034304.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Comparison_of_trypanosome_survival_times_in_cerebrospinal_fluid_and_or_HMI_9_medium_/333519", "title"=>"Comparison of trypanosome survival times in cerebrospinal-fluid and/or HMI-9 medium.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:20:16"}
  • {"files"=>["https://ndownloader.figshare.com/files/663175"], "description"=>"<p><b>a,</b> Trypanosomes (T) are in close proximity to pial cells (PC) within the subarachnoid space (SAS); BP brain parenchyma. <b>b,</b> Trypanosomes (T) are located intimately between pial cells (PC) at the intersection between subarachnoid space and <i>pia mater</i>. <b>c,</b> Area of the <i>pia mater</i> containing densly packed trypanosomes between pial cells. A, astroglial endfeet forming the <i>glia limitans</i>; SAS, subarachnoid space. <b>d,</b> Detail of c. Astrocytes (A) forming the <i>glia limitans</i> (lower line of vertical arrows). The upper line of vertical arrows marks the mesothelium. The horizontal arrow labels a tight junction between two pial cells. Trypanosomes (T) are seen between pial cells. <b>e, </b><i>Glia limitans</i> (labelled by two arrows) marks the border between brain parenchyma (BP) and <i>pia mater</i> (PM); A, foot of an astrocyte. In this image trypanosomes (T) are located within the dilated <i>glial limitans</i> (asterisks). <b>f,</b> A trypanosome located between pial cells (PC). The two arrows point to the two flagella proving that the parasites are capable of cell division at this location.</p>", "links"=>[], "tags"=>["micrographs", "trypanosomes", "20", "days"], "article_id"=>333653, "categories"=>["Microbiology", "Neuroscience", "Infectious Diseases"], "users"=>["Hartwig Wolburg", "Stefan Mogk", "Sven Acker", "Claudia Frey", "Monika Meinert", "Caroline Schönfeld", "Michael Lazarus", "Yoshihiro Urade", "Bruno Kilunga Kubata", "Michael Duszenko"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0034304.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Electron_micrographs_showing_the_location_of_trypanosomes_more_than_20_days_after_blood_infection_/333653", "title"=>"Electron micrographs showing the location of trypanosomes more than 20 days after blood infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-02-20 07:20:55"}

PMC Usage Stats | Further Information

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Relative Metric

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