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Non-radioisotopic glucose turnover in children with falciparum malaria and enteric fever

Singh B, Choo KE, Ibrahim J, Johnston W, Davis TM

Trans R Soc Trop Med Hyg, 1998 12 23;92(5):532-7.
PMID: 9861371

To determine whether glucose turnover is increased in acute falciparum malaria compared to enteric fever in children, steady-state 6,6-D2-glucose turnover was measured in 9 Malaysian children with uncomplicated malaria (6 males and 3 females; median age 10 years, body weight 22 kg) and in 12 with uncomplicated enteric fever (8 males and 4 females; median age 10 years, body weight 24 kg) in acute illness, after quinine (5 malaria patients) and in convalescence. Baseline plasma glucose concentrations in malaria and enteric fever were similar (all values are medians [ranges in brackets]) 5.6 [3.2-11.3] vs. 5.5 [4.2-8.0] mmol/L), as were serum insulin levels (5.6 [0.4-26.5] vs. 6.8 [1.1-22.5] milliunits/L; P > 0.4). Glucose turnover in the malaria patients was higher than in patients with enteric fever (6.27 [2.71-6.87] vs. 5.20 [4.50-6.08] mg/kg.min; P = 0.02) and in convalescence (4.74 [3.35-6.79] mg/kg.min; P = 0.05 vs. acute malaria study), and fell after quinine together with a rise in serum insulin (P = 0.03). Basal plasma lactate concentrations were higher in enteric fever than in malaria (3.4 [1.8-6.4] vs. 0.8 [0.3-3.8] mmol/L; P < 0.0001) and correlated inversely with glucose turnover in this group (rs = -0.60; n = 12; P = 0.02). These data suggest that glucose turnover is 20% greater in malaria than in enteric fever. This might reflect increased non-insulin-mediated glucose uptake in falciparum malaria and/or impaired gluconeogenesis in enteric fever, and may have implications for metabolic complications and their clinical management in both infections.

Matched MeSH terms: Malaria, Falciparum/metabolism*
Fulltext A Novel Malaria Pf/Pv Ab Rapid Diagnostic Test Using a Differential Diagnostic Marker Identified by Network Biology

Cho SJ, Lee J, Lee HJ, Jo HY, Sinniah M, Kim HY, et al.

Int J Biol Sci, 2016;12(7):824-35.
PMID: 27313496 DOI: 10.7150/ijbs.14408

Rapid diagnostic tests (RDTs) can detect anti-malaria antibodies in human blood. As they can detect parasite infection at the low parasite density, they are useful in endemic areas where light infection and/or re-infection of parasites are common. Thus, malaria antibody tests can be used for screening bloods in blood banks to prevent transfusion-transmitted malaria (TTM), an emerging problem in malaria endemic areas. However, only a few malaria antibody tests are available in the microwell-based assay format and these are not suitable for field application. A novel malaria antibody (Ab)-based RDT using a differential diagnostic marker for falciparum and vivax malaria was developed as a suitable high-throughput assay that is sensitive and practical for blood screening. The marker, merozoite surface protein 1 (MSP1) was discovered by generation of a Plasmodium-specific network and the hierarchical organization of modularity in the network. Clinical evaluation revealed that the novel Malaria Pf/Pv Ab RDT shows improved sensitivity (98%) and specificity (99.7%) compared with the performance of a commercial kit, SD BioLine Malaria P.f/P.v (95.1% sensitivity and 99.1% specificity). The novel Malaria Pf/Pv Ab RDT has potential for use as a cost-effective blood-screening tool for malaria and in turn, reduces TTM risk in endemic areas.

Matched MeSH terms: Malaria, Falciparum/metabolism
Fulltext Longitudinal changes in iron homeostasis in human experimental and clinical malaria

Woolley SD, Grigg MJ, Marquart L, Gower JSE, Piera K, Nair AS, et al.

EBioMedicine, 2024 Jul;105:105189.
PMID: 38851058 DOI: 10.1016/j.ebiom.2024.105189

BACKGROUND: The interaction between iron status and malaria is incompletely understood. We evaluated longitudinal changes in iron homeostasis in volunteers enrolled in malaria volunteer infection studies (VIS) and in Malaysian patients with falciparum and vivax malaria.
METHODS: We retrieved data and samples from 55 participants (19 female) enrolled in malaria VIS, and 171 patients (45 female) with malaria and 30 healthy controls (13 female) enrolled in clinical studies in Malaysia. Ferritin, hepcidin, erythropoietin, and soluble transferrin receptor (sTfR) were measured by ELISA.
FINDINGS: In the VIS, participants' parasitaemia was correlated with baseline mean corpuscular volume (MCV), but not iron status (ferritin, hepcidin or sTfR). Ferritin, hepcidin and sTfR all increased during the VIS. Ferritin and hepcidin normalised by day 28, while sTfR remained elevated. In VIS participants, baseline ferritin was associated with post-treatment increases in liver transaminase levels. In Malaysian patients with malaria, hepcidin and ferritin were elevated on admission compared to healthy controls, while sTfR increased following admission. By day 28, hepcidin had normalised; however, ferritin and sTfR both remained elevated.
INTERPRETATION: Our findings demonstrate that parasitaemia is associated with an individual's MCV rather than iron status. The persistent elevation in sTfR 4 weeks post-infection in both malaria VIS and clinical malaria may reflect a causal link between malaria and iron deficiency.
FUNDING: National Health and Medical Research Council (Program Grant 1037304, Project Grants 1045156 and 1156809; Investigator Grants 2016792 to BEB, 2016396 to JCM, 2017436 to MJG); US National Institute of Health (R01-AI116472-03); Malaysian Ministry of Health (BP00500420).

Matched MeSH terms: Malaria, Falciparum/metabolism
Fulltext Intravascular haemolysis in severe Plasmodium knowlesi malaria: association with endothelial activation, microvascular dysfunction, and acute kidney injury

Barber BE, Grigg MJ, Piera KA, William T, Cooper DJ, Plewes K, et al.

Emerg Microbes Infect, 2018 Jun 06;7(1):106.
PMID: 29872039 DOI: 10.1038/s41426-018-0105-2

Plasmodium knowlesi occurs throughout Southeast Asia, and is the most common cause of human malaria in Malaysia. Severe disease in humans is characterised by high parasite biomass, reduced red blood cell deformability, endothelial activation and microvascular dysfunction. However, the roles of intravascular haemolysis and nitric oxide (NO)-dependent endothelial dysfunction, important features of severe falciparum malaria, have not been evaluated, nor their role in acute kidney injury (AKI). In hospitalised Malaysian adults with severe (n = 48) and non-severe (n = 154) knowlesi malaria, and in healthy controls (n = 50), we measured cell-free haemoglobin (CFHb) and assessed associations with the endothelial Weibel-Palade body (WPB) constituents, angiopoietin-2 and osteoprotegerin, endothelial and microvascular function, and other markers of disease severity. CFHb was increased in knowlesi malaria in proportion to disease severity, and to a greater extent than previously reported in severe falciparum malaria patients from the same study cohort. In knowlesi malaria, CFHb was associated with parasitaemia, and independently associated with angiopoietin-2 and osteoprotegerin. As with angiopoietin-2, osteoprotegerin was increased in proportion to disease severity, and independently associated with severity markers including creatinine, lactate, interleukin-6, endothelial cell adhesion molecules ICAM-1 and E-selectin, and impaired microvascular reactivity. Osteoprotegerin was also independently associated with NO-dependent endothelial dysfunction. AKI was found in 88% of those with severe knowlesi malaria. Angiopoietin-2 and osteoprotegerin were both independent risk factors for acute kidney injury. Our findings suggest that haemolysis-mediated endothelial activation and release of WPB constituents is likely a key contributor to end-organ dysfunction, including AKI, in severe knowlesi malaria.

Matched MeSH terms: Malaria, Falciparum/metabolism