Altered Subpopulations of Red Blood Cells and Post-treatment Anemia in Malaria

Abstract

In acute malaria, the bulk of erythrocyte loss occurs after therapy, with a nadir of hemoglobin generally observed 3–7 days after treatment. The fine mechanisms leading to this early post-treatment anemia are still elusive. We explored pathological changes in RBC subpopulations by quantifying biochemical and mechanical alterations during severe malaria treated with artemisinin derivatives, a drug family that induce “pitting” in the spleen. In this study, the hemoglobin concentration dropped by 1.93 G/dl during therapy. During the same period, iRBC accounting for 6.12% of all RBC before therapy (BT) were replaced by pitted-RBC, accounting for 5.33% of RBC after therapy (AT). RBC loss was thus of 15.9%, of which only a minor part was due to the loss of iRBC or pitted-RBC. When comparing RBC BT and AT to normal controls, lipidomics revealed an increase in the cholesterol/phosphatidylethanolamine ratio (0.17 versus 0.24, p < 0.001) and cholesterol/phosphatidylinositol ratio (0.36 versus 0.67, p = 0.001). Using ektacytometry, we observed a reduced deformability of circulating RBC, similar BT and AT, compared to health control donors. The mean Elongation Index at 1.69Pa was 0.24 BT and 0.23 AT vs. 0.28 in controls (p < 0.0001). At 30Pa EI was 0.56 BT and 0.56 AT vs. 0.60 in controls (p < 0.001). The retention rate (rr) of RBC subpopulations in spleen-mimetic microsphere layers was higher for iRBC (rr = 20% p = 0.0033) and pitted-RBC (rr = 19%, p = 0.0031) than for healthy RBC (0.12%). Somewhat surprisingly, the post-treatment anemia in malaria results from the elimination of RBC that were never infected.

Chewing the fat: How lipidomics is changing our understanding of human health and disease in 2022

“…Malaria, tuberculosis, and Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) remain within the 10 top causes of death in low‐ to middle‐income countries 306 . These diseases have been subject to clinical lipidomics experiments to further disease understanding and manifestation 310–314 …”

“…Bibliometric analyses of clinical lipidomics publications in 2022 using Scopus search terms “lipidomics” AND “clinic*” on 15 th December 2022 …”

“…Bibliometric analyses of clinical lipidomics publications in 2022 according to separation techniques, detectors, and RPLC columns used. 51,60,61,68,77,[155][156][157]166,[212][213][214][215][310][311][312][313][314][322][323][324][325][326][327][328][329][330][331][332][333][334][335] All legends are in order of largest to smallest percentage. *Note: All techniques that represent ≥1.0% of total publications have been reported.…”

“…306 These diseases have been subject to clinical lipidomics experiments to further disease understanding and manifestation. [310][311][312][313][314] Tuberculosis (TB) is a highly contagious airborne disease, dating back more than 9,000 years, 315 caused by the bacteria Mycobacterium tuberculosis. In 2020, the WHO reported an estimated 10 million new tuberculosis cases and 1.5 million TB-related deaths globally with twothirds of the cases spread across eight countries: India, China, Indonesia, Philippines, Pakistan, Nigeria, Bangladesh, and South Africa.…”

“…Bibliometric analyses of clinical lipidomics publications in 2022 using Scopus search terms "lipidomics" AND "clinic*" on 15 th December 2022. 51,60,61,68,77,[155][156][157]166,[212][213][214][215][310][311][312][313][314][322][323][324][325][326][327][328][329][330][331][332][333][334][335] . *Note: All biological sample types with more than 1.0% of total publications have been reported individually with all remainder combined under "Other".…”