دورية أكاديمية
Total parasite biomass but not peripheral parasitaemia is associated with endothelial and haematological perturbations in Plasmodium vivax patients.
| العنوان: | Total parasite biomass but not peripheral parasitaemia is associated with endothelial and haematological perturbations in Plasmodium vivax patients. |
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| المؤلفون: | Silva-Filho JL; Laboratory of Tropical Diseases - Prof. Luiz Jacintho da Silva, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.; Wellcome Centre for Integrative Parasitology, Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, United Kingdom., Dos-Santos JC; Laboratory of Tropical Diseases - Prof. Luiz Jacintho da Silva, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.; Post-Graduation in Medical Pathophysiology, School of Medical Sciences, University of Campinas, Campinas, Brazil., Judice C; Laboratory of Tropical Diseases - Prof. Luiz Jacintho da Silva, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil., Beraldi D; Wellcome Centre for Integrative Parasitology, Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, United Kingdom., Venugopal K; Wellcome Centre for Integrative Parasitology, Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, United Kingdom., Lima D; School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil., Nakaya HI; School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.; Hospital Israelita Albert Einstein, São Paulo, Brazil., De Paula EV; Department of Clinical Pathology, School of Medical Sciences, University of Campinas, Campinas, Brazil., Lopes SC; Department of Clinical Pathology, School of Medical Sciences, University of Campinas, Campinas, Brazil.; Institute Leônidas & Maria Deane, Fiocruz, Manaus, Brazil.; Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, Brazil., Lacerda MV; Institute Leônidas & Maria Deane, Fiocruz, Manaus, Brazil.; Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, Brazil., Marti M; Wellcome Centre for Integrative Parasitology, Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, United Kingdom., Costa FT; Laboratory of Tropical Diseases - Prof. Luiz Jacintho da Silva, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil. |
| المصدر: | ELife [Elife] 2021 Sep 29; Vol. 10. Date of Electronic Publication: 2021 Sep 29. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012- |
| مواضيع طبية MeSH: | Malaria, Vivax/*parasitology , Parasitemia/*parasitology , Plasmodium vivax/*physiology, Adult ; Biomass ; Female ; Humans ; Malaria, Vivax/pathology ; Malaria, Vivax/physiopathology ; Male ; Middle Aged ; Young Adult |
| مستخلص: | Plasmodium vivax is the major cause of human malaria in the Americas. How P. vivax infection can lead to poor clinical outcomes, despite low peripheral parasitaemia, remains a matter of intense debate. Estimation of total P. vivax biomass based on circulating markers indicates existence of a predominant parasite population outside of circulation. In this study, we investigate associations between both peripheral and total parasite biomass and host response in vivax malaria. We analysed parasite and host signatures in a cohort of uncomplicated vivax malaria patients from Manaus, Brazil, combining clinical and parasite parameters, multiplexed analysis of host responses, and ex vivo assays. Patterns of clinical features, parasite burden, and host signatures measured in plasma across the patient cohort were highly heterogenous. Further data deconvolution revealed two patient clusters, here termed Vivax low and Vivax high . These patient subgroups were defined based on differences in total parasite biomass but not peripheral parasitaemia. Overall Vivax low patients clustered with healthy donors and Vivax high patients showed more profound alterations in haematological parameters, endothelial cell (EC) activation, and glycocalyx breakdown and levels of cytokines regulating different haematopoiesis pathways compared to Vivax low . Vivax high patients presented more severe thrombocytopenia and lymphopenia, along with enrichment of neutrophils in the peripheral blood and increased neutrophil-to-lymphocyte ratio (NLCR). When patients' signatures were combined, high association of total parasite biomass with a subset of markers of EC activation, thrombocytopenia, and lymphopenia severity was observed. Finally, machine learning models defined a combination of host parameters measured in the circulation that could predict the extent of parasite infection outside of circulation. Altogether, our data show that total parasite biomass is a better predictor of perturbations in host homeostasis in P. vivax patients than peripheral parasitaemia. This supports the emerging paradigm of a P. vivax tissue reservoir, particularly in the haematopoietic niche of bone marrow and spleen. Competing Interests: JS, JD, CJ, DB, KV, DL, HN, ED, SL, ML, MM, FC No competing interests declared (© 2021, Silva-Filho et al.) |
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| معلومات مُعتمدة: | 104111 United Kingdom WT_ Wellcome Trust; United Kingdom WT_ Wellcome Trust |
| فهرسة مساهمة: | Keywords: Plasmodium vivax; endothelial activation; haematopoiesis; human; infectious disease; malaria parasite; microbiology; tissue infection; total biomass |
| تواريخ الأحداث: | Date Created: 20210929 Date Completed: 20211124 Latest Revision: 20220218 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC8536259 |
| DOI: | 10.7554/eLife.71351 |
| PMID: | 34585667 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2050-084X |
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| DOI: | 10.7554/eLife.71351 |