This study sought to measure medium-sized extracellular vesicles (mEVs) in plasma, when patients have low Plasmodium falciparum early in infection. We aimed to define the relationship between plasma mEVs and: (i) parasitaemia, (ii) period from onset of malaria symptoms until seeking medical care (patient delay, PD), (iii) age and (iv) gender. In this cross-sectional study, n = 434 patients were analysed and Nanosight Tracking Analysis (NTA) used to quantify mEVs (vesicles of 150-500 nm diameter, isolated at 15,000 × g, β-tubulin-positive and staining for annexin V, but weak or negative for CD81). Overall plasma mEV levels (1.69 × 1010 mEVs mL-1) were 2.3-fold higher than for uninfected controls (0.51 × 1010 mEVs mL-1). Divided into four age groups, we found a bimodal distribution with 2.5- and 2.1-fold higher mEVs in infected children (<11 years old [yo]) (median:2.11 × 1010 mEVs mL-1) and the elderly (>45 yo) (median:1.92 × 1010 mEVs mL-1), respectively, compared to uninfected controls; parasite density varied similarly with age groups. There was a positive association between mEVs and parasite density (r = 0.587, p < 0.0001) and mEVs were strongly associated with PD (r = 0.919, p < 0.0001), but gender had no effect on plasma mEV levels (p = 0.667). Parasite density was also exponentially related to patient delay. Gender (p = 0.667) had no effect on plasma mEV levels. During periods of low parasitaemia (PD = 72h), mEVs were 0.93-fold greater than in uninfected controls. As 75% (49/65) of patients had low parasitaemia levels (20-500 parasites µL-1), close to the detection limits of microscopy of Giemsa-stained thick blood films (5-150 parasites µL-1), mEV quantification by NTA could potentially have early diagnostic value, and raises the potential of Pf markers in mEVs as early diagnostic targets.

中文翻译：

---

低寄生虫血症的加纳疟疾患者的血浆mEV水平高于健康对照者，这增加了mEV中寄生虫标志物作为诊断目标的可能性。

这项研究旨在在患者感染初期恶性疟原虫含量较低的情况下测量血浆中大小的细胞外囊泡（mEVs）。我们旨在定义血浆mEV与以下之间的关系：（i）寄生虫血症，（ii）从疟疾症状发作到寻求医疗护理（患者延误，PD），（iii）年龄和（iv）性别的时期。在这项横断面研究中，对434例患者进行了分析，并使用Nanosight跟踪分析（NTA）定量了mEV（直径为150-500 nm的囊泡，以15,000×g分离，β-微管蛋白阳性，膜联蛋白V染色，但对CD81不利或不利）。血浆总mEV水平（1.69×1010 mEVs mL-1）比未感染对照（0.51×1010 mEVs mL-1）高2.3倍。分为四个年龄段，我们发现受感染儿童的mEV分别高出2.5和2.1倍（< 与未感染的对照组相比，分别为11岁（中位数：2.11×1010 mEVs mL-1）和老年人（> 45岁）（中位数：1.92×1010 mEVs mL-1）；寄生虫密度随年龄组的变化相似。mEVs与寄生虫密度之间呈正相关（r = 0.587，p <0.0001），mEVs与PD密切相关（r = 0.919，p <0.0001），但性别对血浆mEV水平没有影响（p = 0.667） 。寄生虫密度也与患者的延迟成指数关系。性别（p = 0.667）对血浆mEV水平没有影响。在低寄生虫血症期间（PD = 72h），mEV比未感染的对照组高0.93倍。由于75％（49/65）的患者具有较低的寄生虫血症水平（20-500寄生虫µL-1），接近吉姆萨染色的厚血膜（5-150寄生虫µL-1）的显微镜检出限，