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  1. AU="Mita-Mendoza, Neida K"
  2. AU="Anderson, Richard C E"
  3. AU="Garcia, Paula"
  4. AU="Soumya Nayak"

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  1. Artikel ; Online: A geopositioned and evidence-graded pan-species compendium of Mayaro virus occurrence.

    Celone, Michael / Potter, Alexander M / Han, Barbara A / Beeman, Sean P / Okech, Bernard / Forshey, Brett / Dunford, James / Rutherford, George / Mita-Mendoza, Neida K / Estallo, Elizabet Lilia / Khouri, Ricardo / de Siqueira, Isadora Cristina / Petersen, Kyle / Maves, Ryan C / Anyamba, Assaf / Pollett, Simon

    Scientific data

    2023  Band 10, Heft 1, Seite(n) 460

    Abstract: Mayaro Virus (MAYV) is an emerging health threat in the Americas that can cause febrile illness as well as debilitating arthralgia or arthritis. To better understand the geographic distribution of MAYV risk, we developed a georeferenced database of MAYV ... ...

    Abstract Mayaro Virus (MAYV) is an emerging health threat in the Americas that can cause febrile illness as well as debilitating arthralgia or arthritis. To better understand the geographic distribution of MAYV risk, we developed a georeferenced database of MAYV occurrence based on peer-reviewed literature and unpublished reports. Here we present this compendium, which includes both point and polygon locations linked to occurrence data documented from its discovery in 1954 until 2022. We describe all methods used to develop the database including data collection, georeferencing, management and quality-control. We also describe a customized grading system used to assess the quality of each study included in our review. The result is a comprehensive, evidence-graded database of confirmed MAYV occurrence in humans, non-human animals, and arthropods to-date, containing 262 geo-positioned occurrences in total. This database - which can be updated over time - may be useful for local spill-over risk assessment, epidemiological modelling to understand key transmission dynamics and drivers of MAYV spread, as well as identification of major surveillance gaps.
    Mesh-Begriff(e) Animals ; Alphavirus ; Americas ; Arthropods ; Databases, Factual ; Humans
    Sprache Englisch
    Erscheinungsdatum 2023-07-14
    Erscheinungsland England
    Dokumenttyp Dataset ; Journal Article
    ZDB-ID 2775191-0
    ISSN 2052-4463 ; 2052-4463
    ISSN (online) 2052-4463
    ISSN 2052-4463
    DOI 10.1038/s41597-023-02302-z
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Dimethyl fumarate reduces TNF and Plasmodium falciparum induced brain endothelium activation in vitro.

    Mita-Mendoza, Neida K / Magallon-Tejada, Ariel / Parmar, Priyanka / Furtado, Raquel / Aldrich, Margaret / Saidi, Alex / Taylor, Terrie / Smith, Joe / Seydel, Karl / Daily, Johanna P

    Malaria journal

    2020  Band 19, Heft 1, Seite(n) 376

    Abstract: Background: Cerebral malaria (CM) is associated with morbidity and mortality despite the use of potent anti-malarial agents. Brain endothelial cell activation and dysfunction from oxidative and inflammatory host responses and products released by ... ...

    Abstract Background: Cerebral malaria (CM) is associated with morbidity and mortality despite the use of potent anti-malarial agents. Brain endothelial cell activation and dysfunction from oxidative and inflammatory host responses and products released by Plasmodium falciparum-infected erythrocytes (IE), are likely the major contributors to the encephalopathy, seizures, and brain swelling that are associated with CM. The development of adjunctive therapy to reduce the pathological consequences of host response pathways could improve outcomes. A potentially protective role of the nuclear factor E2-related factor 2 (NRF2) pathway, which serves as a therapeutic target in brain microvascular diseases and central nervous system (CNS) inflammatory diseases such as multiple sclerosis was tested to protect endothelial cells in an in vitro culture system subjected to tumour necrosis factor (TNF) or infected red blood cell exposure. NRF2 is a transcription factor that mediates anti-oxidant and anti-inflammatory responses.
    Methods: To accurately reflect clinically relevant parasite biology a unique panel of parasite isolates derived from patients with stringently defined CM was developed. The effect of TNF and these parasite lines on primary human brain microvascular endothelial cell (HBMVEC) activation in an in vitro co-culture model was tested. HBMVEC activation was measured by cellular release of IL6 and nuclear translocation of NFκB. The transcriptional and functional effects of dimethyl fumarate (DMF), an FDA approved drug which induces the NRF2 pathway, on host and parasite induced HBMVEC activation was characterized. In addition, the effect of DMF on parasite binding to TNF stimulated HBMVEC in a semi-static binding assay was examined.
    Results: Transcriptional profiling demonstrates that DMF upregulates the NRF2-Mediated Oxidative Stress Response, ErbB4 Signaling Pathway, Peroxisome Proliferator-activated Receptor (PPAR) Signaling and downregulates iNOS Signaling and the Neuroinflammation Signaling Pathway on TNF activated HBMVEC. The parasite lines derived from eight paediatric CM patients demonstrated increased binding to TNF activated HBMVEC and varied in their binding and activation of HBMVEC. Overall DMF reduced both TNF and CM derived parasite activation of HBMVEC.
    Conclusions: These findings provide evidence that targeting the NRF2 pathway in TNF and parasite activated HBMVEC mediates multiple protective pathways and may represent a novel adjunctive therapy to improve infection outcomes in CM.
    Mesh-Begriff(e) Anti-Inflammatory Agents/pharmacology ; Antioxidants/metabolism ; Brain/drug effects ; Brain/parasitology ; Child ; Child, Preschool ; Dimethyl Fumarate/pharmacology ; Endothelial Cells/drug effects ; Endothelial Cells/parasitology ; Humans ; Infant ; Malaria, Cerebral/prevention & control ; Malaria, Falciparum/prevention & control ; Plasmodium falciparum/drug effects ; Plasmodium falciparum/physiology ; Tumor Necrosis Factor-alpha/metabolism
    Chemische Substanzen Anti-Inflammatory Agents ; Antioxidants ; Tumor Necrosis Factor-alpha ; Dimethyl Fumarate (FO2303MNI2)
    Sprache Englisch
    Erscheinungsdatum 2020-10-21
    Erscheinungsland England
    Dokumenttyp Journal Article
    ISSN 1475-2875
    ISSN (online) 1475-2875
    DOI 10.1186/s12936-020-03447-7
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  3. Artikel ; Online: High guanidinium permeability reveals dehydration-dependent ion selectivity in the plasmodial surface anion channel.

    Bokhari, Abdullah A B / Mita-Mendoza, Neida K / Fuller, Alexandra / Pillai, Ajay D / Desai, Sanjay A

    BioMed research international

    2014  Band 2014, Seite(n) 741024

    Abstract: Malaria parasites grow within vertebrate erythrocytes and increase host cell permeability to access nutrients from plasma. This increase is mediated by the plasmodial surface anion channel (PSAC), an unusual ion channel linked to the conserved clag gene ... ...

    Abstract Malaria parasites grow within vertebrate erythrocytes and increase host cell permeability to access nutrients from plasma. This increase is mediated by the plasmodial surface anion channel (PSAC), an unusual ion channel linked to the conserved clag gene family. Although PSAC recognizes and transports a broad range of uncharged and charged solutes, it must efficiently exclude the small Na(+) ion to maintain infected cell osmotic stability. Here, we examine possible mechanisms for this remarkable solute selectivity. We identify guanidinium as an organic cation with high permeability into human erythrocytes infected with Plasmodium falciparum, but negligible uptake by uninfected cells. Transport characteristics and pharmacology indicate that this uptake is specifically mediated by PSAC. The rank order of organic and inorganic cation permeabilities suggests cation dehydration as the rate-limiting step in transport through the channel. The high guanidinium permeability of infected cells also allows rapid and stringent synchronization of parasite cultures, as required for molecular and cellular studies of this pathogen. These studies provide important insights into how nutrients and ions are transported via PSAC, an established target for antimalarial drug development.
    Mesh-Begriff(e) Cell Membrane Permeability/physiology ; Dehydration ; Erythrocyte Membrane/metabolism ; Erythrocytes/metabolism ; Erythrocytes/parasitology ; Guanidine/chemistry ; Guanidine/metabolism ; Humans ; Ion Channels/chemistry ; Ion Channels/metabolism ; Malaria, Falciparum/metabolism ; Malaria, Falciparum/parasitology ; Plasmodium falciparum
    Chemische Substanzen Ion Channels ; surface anion channel protein, Plasmodium falciparum ; Guanidine (JU58VJ6Y3B)
    Sprache Englisch
    Erscheinungsdatum 2014-08-27
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Intramural
    ZDB-ID 2698540-8
    ISSN 2314-6141 ; 2314-6133
    ISSN (online) 2314-6141
    ISSN 2314-6133
    DOI 10.1155/2014/741024
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  4. Artikel ; Online: Chagas Disease in Southern Coastal Ecuador: Coinfections with Arboviruses and a Comparison of Serological Assays for Chagas Disease Diagnosis.

    Mita-Mendoza, Neida K / McMahon, Elizabeth / Kenneson, Aileen / Barbachano-Guerrero, Arturo / Beltran-Ayala, Efrain / Cueva, Cinthya / King, Christine A / Lupone, Christina D / Castro-Sesquen, Yagahira E / Gilman, Robert H / Endy, Timothy P / Stewart-Ibarra, Anna M

    The American journal of tropical medicine and hygiene

    2018  Band 99, Heft 6, Seite(n) 1530–1533

    Abstract: Occurrence of Chagas disease and arbovirus coinfections is unknown, despite the vast co-endemic areas throughout the Americas. This study examined the proportion of individuals positive ... ...

    Abstract Occurrence of Chagas disease and arbovirus coinfections is unknown, despite the vast co-endemic areas throughout the Americas. This study examined the proportion of individuals positive for
    Mesh-Begriff(e) Adult ; Aged ; Antigens, Viral/blood ; Chagas Disease/diagnosis ; Chagas Disease/epidemiology ; Chagas Disease/parasitology ; Chikungunya Fever/diagnosis ; Chikungunya Fever/epidemiology ; Chikungunya Fever/parasitology ; Chikungunya virus/genetics ; Chikungunya virus/immunology ; Chikungunya virus/isolation & purification ; Coinfection ; Dengue/diagnosis ; Dengue/epidemiology ; Dengue/parasitology ; Dengue Virus/genetics ; Dengue Virus/immunology ; Dengue Virus/isolation & purification ; Ecuador/epidemiology ; Enzyme-Linked Immunosorbent Assay/standards ; Female ; Humans ; Male ; Middle Aged ; RNA, Viral/blood ; Reverse Transcriptase Polymerase Chain Reaction/standards ; Trypanosoma cruzi/immunology ; Trypanosoma cruzi/isolation & purification ; Zika Virus/genetics ; Zika Virus/immunology ; Zika Virus/isolation & purification ; Zika Virus Infection/diagnosis ; Zika Virus Infection/epidemiology ; Zika Virus Infection/parasitology
    Chemische Substanzen Antigens, Viral ; RNA, Viral
    Sprache Englisch
    Erscheinungsdatum 2018-10-18
    Erscheinungsland United States
    Dokumenttyp Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2942-7
    ISSN 1476-1645 ; 0002-9637
    ISSN (online) 1476-1645
    ISSN 0002-9637
    DOI 10.4269/ajtmh.18-0441
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  5. Artikel ; Online: Activated Neutrophils Are Associated with Pediatric Cerebral Malaria Vasculopathy in Malawian Children.

    Feintuch, Catherine Manix / Saidi, Alex / Seydel, Karl / Chen, Grace / Goldman-Yassen, Adam / Mita-Mendoza, Neida K / Kim, Ryung S / Frenette, Paul S / Taylor, Terrie / Daily, Johanna P

    mBio

    2016  Band 7, Heft 1, Seite(n) e01300–15

    Abstract: Unlabelled: Most patients with cerebral malaria (CM) sustain cerebral microvascular sequestration of Plasmodium falciparum-infected red blood cells (iRBCs). Although many young children are infected with P. falciparum, CM remains a rare outcome; thus, ... ...

    Abstract Unlabelled: Most patients with cerebral malaria (CM) sustain cerebral microvascular sequestration of Plasmodium falciparum-infected red blood cells (iRBCs). Although many young children are infected with P. falciparum, CM remains a rare outcome; thus, we hypothesized that specific host conditions facilitate iRBC cerebral sequestration. To identify these host factors, we compared the peripheral whole-blood transcriptomes of Malawian children with iRBC cerebral sequestration, identified as malarial-retinopathy-positive CM (Ret+CM), to the transcriptomes of children with CM and no cerebral iRBC sequestration, defined as malarial-retinopathy-negative CM (Ret-CM). Ret+CM was associated with upregulation of 103 gene set pathways, including cytokine, blood coagulation, and extracellular matrix (ECM) pathways (P < 0.01; false-discovery rate [FDR] of <0.05). Neutrophil transcripts were the most highly upregulated individual transcripts in Ret+CM patients. Activated neutrophils can modulate diverse host processes, including the ECM, inflammation, and platelet biology to potentially facilitate parasite sequestration. Therefore, we compared plasma neutrophil proteins and neutrophil chemotaxis between Ret+CM and Ret-CM patients. Plasma levels of human neutrophil elastase, myeloperoxidase, and proteinase 3, but not lactoferrin or lipocalin, were elevated in Ret+CM patients, and neutrophil chemotaxis was impaired, possibly related to increased plasma heme. Neutrophils were rarely seen in CM brain microvasculature autopsy samples, and no neutrophil extracellular traps were found, suggesting that a putative neutrophil effect on endothelial cell biology results from neutrophil soluble factors rather than direct neutrophil cellular tissue effects. Meanwhile, children with Ret-CM had lower levels of inflammation, higher levels of alpha interferon, and upregulation of Toll-like receptor pathways and other host transcriptional pathways, which may represent responses that do not favor cerebral iRBC sequestration.
    Importance: There were approximately 198 million cases of malaria worldwide in 2013, with an estimated 584,000 deaths occurring mostly in sub-Saharan African children. CM is a severe and rare form of Plasmodium falciparum infection and is associated with high rates of mortality and neurological morbidity, despite antimalarial treatment. A greater understanding of the pathophysiology of CM would allow the development of adjunctive therapies to improve clinical outcomes. A hallmark of CM is cerebral microvasculature sequestration of P. falciparum-infected red blood cells (iRBCs), which results in vasculopathy in some patients. Our data provide a global analysis of the host pathways associated with CM and newly identify an association of activated neutrophils with brain iRBC sequestration. Products of activated neutrophils could alter endothelial cell receptors and coagulation to facilitate iRBC adherence. Future studies can now examine the role of neutrophils in CM pathogenesis to improve health outcomes.
    Mesh-Begriff(e) Brain/blood supply ; Brain/immunology ; Brain/pathology ; Cell Adhesion ; Child ; Child, Preschool ; Endothelial Cells/cytology ; Erythrocytes/parasitology ; Female ; Gene Expression Profiling ; Humans ; Inflammation ; Leukocyte Elastase/blood ; Malaria, Cerebral/genetics ; Malaria, Cerebral/immunology ; Malaria, Cerebral/parasitology ; Malaria, Cerebral/pathology ; Malawi ; Male ; Metabolic Networks and Pathways/genetics ; Myeloblastin/blood ; Neutrophil Activation ; Neutrophils/physiology ; Peroxidase/blood ; Plasmodium falciparum/physiology
    Chemische Substanzen Peroxidase (EC 1.11.1.7) ; Leukocyte Elastase (EC 3.4.21.37) ; Myeloblastin (EC 3.4.21.76)
    Sprache Englisch
    Erscheinungsdatum 2016-02-16
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mBio.01300-15
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  6. Artikel ; Online: Soluble mediators produced by the crosstalk between microvascular endothelial cells and dengue-infected primary dermal fibroblasts inhibit dengue virus replication and increase leukocyte transmigration.

    Bustos-Arriaga, José / Mita-Mendoza, Neida K / Lopez-Gonzalez, Moises / García-Cordero, Julio / Juárez-Delgado, Francisco J / Gromowski, Gregory D / Méndez-Cruz, René A / Fairhurst, Rick M / Whitehead, Stephen S / Cedillo-Barrón, Leticia

    Immunologic research

    2016  Band 64, Heft 2, Seite(n) 392–403

    Abstract: When dengue virus (DENV)-infected mosquitoes use their proboscis to probe into human skin during blood feeding, both saliva and virus are released. During this process, cells from the epidermis and dermis layers of the skin, along with small blood ... ...

    Abstract When dengue virus (DENV)-infected mosquitoes use their proboscis to probe into human skin during blood feeding, both saliva and virus are released. During this process, cells from the epidermis and dermis layers of the skin, along with small blood vessels, may get exposed to or infected with DENV. In these microenvironments of the skin, the presence of DENV initiates a complex interplay among the DENV-infected and non-infected neighboring cells at the initial bite site. Previous studies suggested that DENV-infected human dermal fibroblasts (HDFs) participate in the immune response against DENV by secreting soluble mediators of innate immunity. In the present study, we investigated whether DENV-infected HDFs activate human dermal microvascular endothelial cells (HDMECs) in co-cultures. Our results suggest that co-cultures of DENV-infected HDFs and HDMECs elicit soluble mediators that are sufficient to reduce viral replication, activate HDMECs, and induce leukocyte migration through HDMEC monolayers. These effects were partly dependent on HDF donor and DENV serotype, which may provide novel insights into the natural variation in host susceptibility to DENV disease.
    Mesh-Begriff(e) Adult ; Biomarkers ; Cell Communication ; Cells, Cultured ; Child, Preschool ; Coculture Techniques ; Cytokines/blood ; Cytokines/metabolism ; Dengue/blood ; Dengue/metabolism ; Dengue/virology ; Dengue Virus/physiology ; Endothelial Cells/metabolism ; Endothelium, Vascular/cytology ; Endothelium, Vascular/metabolism ; Epidermis/cytology ; Epidermis/virology ; Female ; Fibroblasts/metabolism ; Fibroblasts/virology ; Human Umbilical Vein Endothelial Cells ; Humans ; Immunity, Innate ; Inflammation Mediators/blood ; Inflammation Mediators/metabolism ; Intercellular Signaling Peptides and Proteins/blood ; Intercellular Signaling Peptides and Proteins/metabolism ; Leukocytes/physiology ; Male ; Skin/cytology ; Skin/metabolism ; Transendothelial and Transepithelial Migration ; Virus Replication
    Chemische Substanzen Biomarkers ; Cytokines ; Inflammation Mediators ; Intercellular Signaling Peptides and Proteins
    Sprache Englisch
    Erscheinungsdatum 2016-04
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 632857-x
    ISSN 1559-0755 ; 0257-277X
    ISSN (online) 1559-0755
    ISSN 0257-277X
    DOI 10.1007/s12026-015-8675-8
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  7. Artikel ; Online: Effects of age, hemoglobin type and parasite strain on IgG recognition of Plasmodium falciparum-infected erythrocytes in Malian children.

    Zeituni, Amir E / Miura, Kazutoyo / Diakite, Mahamadou / Doumbia, Saibou / Moretz, Samuel E / Diouf, Ababacar / Tullo, Gregory / Lopera-Mesa, Tatiana M / Bess, Cameron D / Mita-Mendoza, Neida K / Anderson, Jennifer M / Fairhurst, Rick M / Long, Carole A

    PloS one

    2013  Band 8, Heft 10, Seite(n) e76734

    Abstract: Background: Naturally-acquired antibody responses to antigens on the surface of Plasmodium falciparum-infected red blood cells (iRBCs) have been implicated in antimalarial immunity. To profile the development of this immunity, we have been studying a ... ...

    Abstract Background: Naturally-acquired antibody responses to antigens on the surface of Plasmodium falciparum-infected red blood cells (iRBCs) have been implicated in antimalarial immunity. To profile the development of this immunity, we have been studying a cohort of Malian children living in an area with intense seasonal malaria transmission.
    Methodology/principal findings: We collected plasma from a sub-cohort of 176 Malian children aged 3-11 years, before (May) and after (December) the 2009 transmission season. To measure the effect of hemoglobin (Hb) type on antibody responses, we enrolled age-matched HbAA, HbAS and HbAC children. To quantify antibody recognition of iRBCs, we designed a high-throughput flow cytometry assay to rapidly test numerous plasma samples against multiple parasite strains. We evaluated antibody reactivity of each plasma sample to 3 laboratory-adapted parasite lines (FCR3, D10, PC26) and 4 short-term-cultured parasite isolates (2 Malian and 2 Cambodian). 97% of children recognized ≥1 parasite strain and the proportion of IgG responders increased significantly during the transmission season for most parasite strains. Both strain-specific and strain-transcending IgG responses were detected, and varied by age, Hb type and parasite strain. In addition, the breadth of IgG responses to parasite strains increased with age in HbAA, but not in HbAS or HbAC, children.
    Conclusions/significance: Our assay detects both strain-specific and strain-transcending IgG responses to iRBCs. The magnitude and breadth of these responses varied not only by age, but also by Hb type and parasite strain used. These findings indicate that studies of acquired humoral immunity should account for Hb type and test large numbers of diverse parasite strains.
    Mesh-Begriff(e) Age Factors ; Antibodies, Protozoan/immunology ; Antigens, Protozoan/immunology ; Child ; Child, Preschool ; Cohort Studies ; Erythrocytes/metabolism ; Erythrocytes/parasitology ; Hemoglobins/classification ; Hemoglobins/genetics ; Humans ; Immunoglobulin G/immunology ; Incidence ; Malaria, Falciparum/epidemiology ; Malaria, Falciparum/genetics ; Malaria, Falciparum/immunology ; Malaria, Falciparum/parasitology ; Mali/epidemiology ; Plasmodium falciparum/immunology ; Seasons
    Chemische Substanzen Antibodies, Protozoan ; Antigens, Protozoan ; Hemoglobins ; Immunoglobulin G
    Sprache Englisch
    Erscheinungsdatum 2013-10-04
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0076734
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  8. Artikel ; Online: A potential role for plasma uric acid in the endothelial pathology of Plasmodium falciparum malaria.

    Mita-Mendoza, Neida K / van de Hoef, Diana L / Lopera-Mesa, Tatiana M / Doumbia, Saibou / Konate, Drissa / Doumbouya, Mory / Gu, Wenjuan / Anderson, Jennifer M / Santos-Argumedo, Leopoldo / Rodriguez, Ana / Fay, Michael P / Diakite, Mahamadou / Long, Carole A / Fairhurst, Rick M

    PloS one

    2013  Band 8, Heft 1, Seite(n) e54481

    Abstract: Background: Inflammatory cytokinemia and systemic activation of the microvascular endothelium are central to the pathogenesis of Plasmodium falciparum malaria. Recently, 'parasite-derived' uric acid (UA) was shown to activate human immune cells in vitro, ...

    Abstract Background: Inflammatory cytokinemia and systemic activation of the microvascular endothelium are central to the pathogenesis of Plasmodium falciparum malaria. Recently, 'parasite-derived' uric acid (UA) was shown to activate human immune cells in vitro, and plasma UA levels were associated with inflammatory cytokine levels and disease severity in Malian children with malaria. Since UA is associated with endothelial inflammation in non-malaria diseases, we hypothesized that elevated UA levels contribute to the endothelial pathology of P. falciparum malaria.
    Methodology/principal findings: We measured levels of UA and soluble forms of intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-Selectin), thrombomodulin (sTM), tissue factor (sTF) and vascular endothelial growth factor (VEGF) in the plasma of Malian children aged 0.5-17 years with uncomplicated malaria (UM, n = 487) and non-cerebral severe malaria (NCSM, n = 68). In 69 of these children, we measured these same factors once when they experienced a malaria episode and twice when they were healthy (i.e., before and after the malaria transmission season). We found that levels of UA, sICAM-1, sVCAM-1, sE-Selectin and sTM increase during a malaria episode and return to basal levels at the end of the transmission season (p<0.0001). Plasma levels of UA and these four endothelial biomarkers correlate with parasite density and disease severity. In children with UM, UA levels correlate with parasite density (r = 0.092, p = 0.043), sICAM-1 (r = 0.255, p<0.0001) and sTM (r = 0.175, p = 0.0001) levels. After adjusting for parasite density, UA levels predict sTM levels.
    Conclusions/significance: Elevated UA levels may contribute to malaria pathogenesis by damaging endothelium and promoting a procoagulant state. The correlation between UA levels and parasite densities suggests that parasitized erythrocytes are one possible source of excess UA. UA-induced shedding of endothelial TM may represent a novel mechanism of malaria pathogenesis, in which activated thrombin induces fibrin deposition and platelet aggregation in microvessels. This protocol is registered at clinicaltrials.gov (NCT00669084).
    Mesh-Begriff(e) E-Selectin/blood ; Endothelium/metabolism ; Endothelium/parasitology ; Endothelium/pathology ; Erythrocytes/parasitology ; Erythrocytes/pathology ; Fibrin/metabolism ; Humans ; Inflammation/metabolism ; Inflammation/parasitology ; Inflammation/physiopathology ; Intercellular Adhesion Molecule-1/blood ; Malaria, Falciparum/blood ; Malaria, Falciparum/parasitology ; Malaria, Falciparum/pathology ; Microvessels/metabolism ; Microvessels/pathology ; Plasmodium falciparum/metabolism ; Plasmodium falciparum/pathogenicity ; Platelet Aggregation/physiology ; Thrombomodulin/blood ; Uric Acid/blood ; Vascular Cell Adhesion Molecule-1/blood
    Chemische Substanzen E-Selectin ; THBD protein, human ; Thrombomodulin ; Vascular Cell Adhesion Molecule-1 ; Intercellular Adhesion Molecule-1 (126547-89-5) ; Uric Acid (268B43MJ25) ; Fibrin (9001-31-4)
    Sprache Englisch
    Erscheinungsdatum 2013-01-22
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Intramural
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0054481
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  9. Artikel ; Online: Plasma uric acid levels correlate with inflammation and disease severity in Malian children with Plasmodium falciparum malaria.

    Lopera-Mesa, Tatiana M / Mita-Mendoza, Neida K / van de Hoef, Diana L / Doumbia, Saibou / Konaté, Drissa / Doumbouya, Mory / Gu, Wenjuan / Traoré, Karim / Diakité, Seidina A S / Remaley, Alan T / Anderson, Jennifer M / Rodriguez, Ana / Fay, Michael P / Long, Carole A / Diakité, Mahamadou / Fairhurst, Rick M

    PloS one

    2012  Band 7, Heft 10, Seite(n) e46424

    Abstract: Background: Plasmodium falciparum elicits host inflammatory responses that cause the symptoms and severe manifestations of malaria. One proposed mechanism involves formation of immunostimulatory uric acid (UA) precipitates, which are released from ... ...

    Abstract Background: Plasmodium falciparum elicits host inflammatory responses that cause the symptoms and severe manifestations of malaria. One proposed mechanism involves formation of immunostimulatory uric acid (UA) precipitates, which are released from sequestered schizonts into microvessels. Another involves hypoxanthine and xanthine, which accumulate in parasitized red blood cells (RBCs) and may be converted by plasma xanthine oxidase to UA at schizont rupture. These two forms of 'parasite-derived' UA stimulate immune cells to produce inflammatory cytokines in vitro.
    Methods and findings: We measured plasma levels of soluble UA and inflammatory cytokines and chemokines (IL-6, IL-10, sTNFRII, MCP-1, IL-8, TNFα, IP-10, IFNγ, GM-CSF, IL-1β) in 470 Malian children presenting with uncomplicated malaria (UM), non-cerebral severe malaria (NCSM) or cerebral malaria (CM). UA levels were elevated in children with NCSM (median 5.74 mg/dl, 1.21-fold increase, 95% CI 1.09-1.35, n = 23, p = 0.0007) and CM (median 5.69 mg/dl, 1.19-fold increase, 95% CI 0.97-1.41, n = 9, p = 0.0890) compared to those with UM (median 4.60 mg/dl, n = 438). In children with UM, parasite density and plasma creatinine levels correlated with UA levels. These UA levels correlated with the levels of seven cytokines [IL-6 (r = 0.259, p<0.00001), IL-10 (r = 0.242, p<0.00001), sTNFRII (r = 0.221, p<0.00001), MCP-1 (r = 0.220, p<0.00001), IL-8 (r = 0.147, p = 0.002), TNFα (r = 0.132, p = 0.006) and IP-10 (r = 0.120, p = 0.012)]. In 39 children, UA levels were 1.49-fold (95% CI 1.34-1.65; p<0.0001) higher during their malaria episode [geometric mean titer (GMT) 4.67 mg/dl] than when they were previously healthy and aparasitemic (GMT 3.14 mg/dl).
    Conclusions: Elevated UA levels may contribute to the pathogenesis of P. falciparum malaria by activating immune cells to produce inflammatory cytokines. While this study cannot identify the cause of elevated UA levels, their association with parasite density and creatinine levels suggest that parasite-derived UA and renal function may be involved. Defining pathogenic roles for parasite-derived UA precipitates, which we have not directly studied here, requires further investigation.
    Trial registration: ClinicalTrials.gov NCT00669084.
    Mesh-Begriff(e) Adolescent ; Child ; Child, Preschool ; Creatinine/blood ; Cytokines/blood ; Humans ; Inflammation/blood ; Inflammation Mediators/blood ; Malaria, Falciparum/blood ; Malaria, Falciparum/physiopathology ; Mali ; Severity of Illness Index ; Uric Acid/blood
    Chemische Substanzen Cytokines ; Inflammation Mediators ; Uric Acid (268B43MJ25) ; Creatinine (AYI8EX34EU)
    Sprache Englisch
    Erscheinungsdatum 2012-10-05
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 2267670-3
    ISSN 1932-6203 ; 1932-6203
    ISSN (online) 1932-6203
    ISSN 1932-6203
    DOI 10.1371/journal.pone.0046424
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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