Department of Internal Medicine, Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
IRSS/Clinical Research Unit of Nanoro (CRUN), Nanoro, Burkina Faso.
PLoS One. 2020 Nov 30;15(11):e0242507. doi: 10.1371/journal.pone.0242507. eCollection 2020.
Asymptomatic malaria infections may affect red blood cell (RBC) homeostasis. Reports indicate a role for chronic hemolysis and splenomegaly, however, the underlying processes are incompletely understood. New hematology analysers provide parameters for a more comprehensive analysis of RBC hemostasis. Complete blood counts were analysed in subjects from all age groups (n = 1118) living in a malaria hyperendemic area and cytokines and iron biomarkers were also measured. Subjects were divided into age groups (<2 years, 2-4, 5-14 and ≥15 years old) and clinical categories (smear-negative healthy subjects, asymptomatic malaria and clinical malaria). We found that hemoglobin levels were similar in smear-negative healthy children and asymptomatic malaria children but significantly lower in clinical malaria with a maximum difference of 2.2 g/dl in children <2 years decreasing to 0.1 g/dl in those aged ≥15 years. Delta-He, presenting different hemoglobinization of reticulocytes and RBC, levels were lower in asymptomatic and clinial malaria, indicating a recent effect of malaria on erythropoiesis. Reticulocyte counts and reticulocyte production index (RPI), indicating the erythropoietic capacity of the bone marrow, were higher in young children with malaria compared to smear-negative subjects. A negative correlation between reticulocyte counts and Hb levels was found in asymptomatic malaria (ρ = -0.32, p<0.001) unlike in clinical malaria (ρ = -0.008, p = 0.92). Free-Hb levels, indicating hemolysis, were only higher in clinical malaria. Phagocytozing monocytes, indicating erythophagocytosis, were highest in clinical malaria, followed by asymptomatic malaria and smear-negative subjects. Circulating cytokines and iron biomarkers (hepcidin, ferritin) showed similar patterns. Pro/anti-inflammatory (IL-6/IL-10) ratio was higher in clinical than asymptomatic malaria. Cytokine production capacity of ex-vivo whole blood stimulation with LPS was lower in children with asymptomatic malaria compared to smear-negative healthy children. Bone marrow response can compensate the increased red blood cell loss in asymptomatic malaria, unlike in clinical malaria, possibly because of limited level and length of inflammation. Trial registration: Prospective diagnostic study: ClinicalTrials.gov identifier: NCT02669823. Explorative cross-sectional field study: ClinicalTrials.gov identifier: NCT03176719.
无症状疟疾感染可能会影响红细胞（RBC）的内环境稳定。有报告表明，慢性溶血和脾肿大与此相关，但潜在的发病机制尚不完全清楚。新型血液分析仪为更全面地分析 RBC 止血功能提供了参数。对生活在疟疾高度流行地区的所有年龄段的受试者（n=1118）进行了全血细胞分析，并测量了细胞因子和铁生物标志物。将受试者按年龄组（<2 岁、2-4 岁、5-14 岁和≥15 岁）和临床类别（阴性涂片健康受试者、无症状疟疾和临床疟疾）进行分组。我们发现，在阴性涂片健康儿童和无症状疟疾儿童中，血红蛋白水平相似，但在临床疟疾中显著降低，<2 岁的儿童差异最大，为 2.2g/dl，而≥15 岁的儿童差异为 0.1g/dl。Delta-He 反映了网织红细胞和 RBC 的不同血红蛋白化水平，在无症状和临床疟疾中较低，表明疟疾对红细胞生成的近期影响。年轻疟疾患儿的网织红细胞计数和网织红细胞生成指数（RPI）较高，表明骨髓的红细胞生成能力较高，与阴性涂片组相比。在无症状疟疾中，网织红细胞计数与 Hb 水平呈负相关（ρ=-0.32，p<0.001），而在临床疟疾中无相关性（ρ=-0.008，p=0.92）。游离血红蛋白水平（反映溶血）仅在临床疟疾中升高。吞噬网织红细胞的单核细胞（反映红细胞吞噬作用）在临床疟疾中最高，其次是无症状疟疾和阴性涂片组。循环细胞因子和铁生物标志物（hepcidin、ferritin）表现出相似的模式。与无症状疟疾相比，临床疟疾的促炎/抗炎（IL-6/IL-10）比值更高。与阴性涂片健康儿童相比，体外全血刺激 LPS 产生细胞因子的能力在无症状疟疾儿童中较低。骨髓反应可以补偿无症状疟疾中增加的红细胞丢失，与临床疟疾不同，这可能是因为炎症的程度和持续时间有限。试验注册：前瞻性诊断研究：ClinicalTrials.gov 标识符：NCT02669823。探索性横断面现场研究：ClinicalTrials.gov 标识符：NCT03176719。
