Glycocalyx Breakdown Is Associated With Severe Disease and Fatal Outcome in Plasmodium falciparum Malaria
Year: 2019
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Interactions between the endothelium and infected erythrocytes play a major role in the pathogenesis of falciparum malaria, with microvascular dysfunction and parasite sequestration associated with worsening outcomes. The glycocalyx is a carbohydrate-rich layer that lines the endothelium, with multiple roles in vascular homeostasis. The role of the glycocalyx in falciparum malaria and the association with disease severity has not been investigated. METHODS: We prospectively enrolled Indonesian inpatients (aged ≥18 years) with severe (SM) or moderately severe (MSM) falciparum malaria, as defined by World Health Organization criteria, and healthy controls (HCs). On enrollment, blood and urine samples were collected concurrently with measurements of vascular nitric oxide (NO) bioavailability. Urine was assayed for glycocalyx breakdown products (glycosaminoglycans) using a dimethylmethylene blue (GAG-DMMB) and liquid chromatography-tandem mass spectrometry (GAG-MS) assay. RESULTS: A total of 129 patients (SM = 43, MSM = 57, HC=29) were recruited. GAG-DMMB and GAG-MS (g/mol creatinine) were increased in SM (mean, 95% confidence interval: 3.98, 2.44-5.53 and 6.82, 5.19-8.44) compared to MSM patients (1.78, 1.27-2.29 and 4.87, 4.27-5.46) and HCs (0.22, 0.06-0.37 and 1.24, 0.89-1.59; P < 0.001). In SM patients, GAG-DMMB and GAG-MS were increased in those with a fatal outcome (n = 3; median, interquartile range: 6.72, 3.80-27.87 and 12.15, 7.88-17.20) compared to survivors (n = 39; 3.10, 0.46-4.5 and 4.64, 2.02-15.20; P = 0.03). Glycocalyx degradation was significantly associated with parasite biomass in both MSM (r = 0.48, GAG-DMMB and r = 0.43, GAG-MS; P < 0.001) and SM patients (r = 0.47, P = 0.002 and r = 0.33, P = 0.04) and inversely associated with endothelial NO bioavailability. CONCLUSIONS: Increased endothelial glycocalyx breakdown is associated with severe disease and a fatal outcome in adults with falciparum malaria.
Source: Clinical Infectious Diseases
DOI: 10.1093/cid/ciz038
Language: English
Topic: Malaria Research and Control
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $4,763
Funders: Wellcome Trust, International Center for Responsible Gaming, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, National Medical Research Council, National Heart, Lung, and Blood Institute, National Institute of Allergy and Infectious Diseases
Awards: Nitric Oxide and Microvascular Dysfunction in Severe Malaria, G1617459808, Research & Training to reduce morbidity & mortality from malaria in Papua ( Indonesia)& Papua New Guinea, Pathophysiology and treatment of malaria in our region, G3164689820, G3544314491, Improving Health Outcomes in the Tropical North: A Multidisciplinary Collaboration, G4727761779, G4951795592, Improving the treatment of Plasmodium vivax, G5403359577, G5650507700, Tropical diseases: Translating discoveries into better health, Arginine, Nitric Oxide, and Severe Malaria, Improving the treatment of Plasmodium vivax
OpenAlex ID: W2913809202