Sequestration and Red Cell Deformability as Determinants of Hyperlactatemia in Falciparum Malaria
| Autor: | Arjen M. Dondorp, Richard J. Maude, Katherine Plewes, Kesinee Chotivanich, Charles J. Woodrow, Nicholas J. White, Prakaykaew Charunwatthana, Mahtab Uddin Hasan, Benjamas Intharabut, Hugh W F Kingston, Amir Hossain, Nicholas P. J. Day, Abdullah Abu Sayeed, Haruhiko Ishioka, Aniruddha Ghose, M. Abul Faiz |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
Male 0301 basic medicine Plasmodium falciparum malaria hyperlactatemia Young Adult Major Articles and Brief Reports 03 medical and health sciences chemistry.chemical_compound Erythrocyte Deformability parasite biomass parasitic diseases medicine Humans Immunology and Allergy Erythrocyte deformability Parasites Malaria Falciparum Bangladesh biology Red Cell red blood cell deformability Middle Aged biology.organism_classification medicine.disease 3. Good health 030104 developmental biology Infectious Diseases chemistry Artesunate Anaerobic glycolysis Lactic acidosis Immunology Lactates Female Hyperlactatemia Malaria |
| Zdroj: | The Journal of Infectious Diseases |
| ISSN: | 1537-6613 0022-1899 |
| Popis: | Despite the recent gains in malaria control, falciparum malaria still causes an estimated 198 million cases globally and kills 0.58 million patients each year [1]. Once severe disease develops, the case-fatality rate is around 8% in children and 15% in adults despite optimal antimalarial treatment with artesunate [2]. A better understanding of the underlying pathophysiology is critical for developing adjunctive treatments to lower morality. Lactic acidosis is a common complication of severe malaria, which has a strong predictive value for death in both pediatric and adult patients [3, 4]. Lactate accounts for approximately one fourth of the strong acids [5] present in severe malaria. The high lactate to pyruvate ratios in severe malaria indicate that anaerobic glycolysis most likely results from microcirculatory hypoperfusion [6]. Impairment of tissue microcirculatory flow is caused by the sequestration of cytoadherent red blood cells (RBCs) containing mature forms of the malaria parasite [7–9]. Rosetting, autoagglutination, and endothelial cell dysfunction may further compromise microcirculatory flow [10, 11]. Reduced uninfected RBC deformability (RCD) is thought to be an additional contributing factor [10, 12]. Other causes include circulatory shock and severe anemia, compromising oxygen delivery. The relative contributions of these factors to lactic acidosis have not been well established. In this prospective study of adults hospitalized with falciparum malaria, we measured the plasma P. falciparum histidine-rich protein 2 (HRP2) concentration as a proxy measure for the total and sequestered parasite biomass [13], RCD, and other established contributors to lactic acidosis and assessed their relative associations with plasma lactate concentrations. |
| Databáze: | OpenAIRE |
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