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

Antwi-Baffour, Samuel; Malibha-Pinchbeck, Memory; Stratton, Dan; Jorfi, Samireh; Lange, Sigrun; Inal, Jameel

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 (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.

Citation

Antwi-Baffour, S., Malibha-Pinchbeck, M., Stratton, D., Jorfi, S., Lange, S., & Inal, J. (2020). 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. Journal of Extracellular Vesicles, 9(1), Article 1697124. https://doi.org/10.1080/20013078.2019.1697124

• Journal Article Type: Article
• Acceptance Date: Nov 18, 2019
• Online Publication Date: Dec 18, 2019
• Publication Date: 2020-09
• Deposit Date: Jan 6, 2020
• Publicly Available Date: Jan 6, 2020
• Journal: Journal of Extracellular Vesicles
• Print ISSN: 2001-3078
• Publisher: Taylor & Francis Open Access
• Peer Reviewed: Peer Reviewed
• Volume: 9
• Issue: 1
• Article Number: 1697124
• DOI: https://doi.org/10.1080/20013078.2019.1697124
• Keywords: Malaria; extracellular vesicles; parasitaemia
• Public URL: https://hull-repository.worktribe.com/output/3329050
• Additional Information: Peer Review Statement: The publishing and review policy for this title is described in its Aims & Scope.; Aim & Scope: http://www.tandfonline.com/action/journalInformation?show=aimsScope&journalCode=zjev20; Received: 2018-10-11; Revised: 2019-11-06; Accepted: 2019-11-11; Published: 2019-12-18
• Contract Date: Jan 6, 2020