Plasma mEV levels in Ghanain malaria patients with low parasitaemia are higher than those of healthy controls, raising the potential for parasite markers in mEVs as diagnostic targets
Date
2019-12-18
Journal Title
Journal ISSN
Volume Title
Publisher
Journal of Extracellular Vesicles
Abstract
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
Description
Research Article
Keywords
Malaria, extracellular vesicles, parasitaemia, medium-sized extracellular vesicles (mEVs