Abstract

Despite encouraging progress over the past decade, malaria remains a major global health challenge. Its severe form accounts for the majority of malaria-related deaths, and early diagnosis is key for a positive outcome. However, this is hindered by the non-specific symptoms caused by malaria, which often overlap with those of other viral, bacterial and parasitic infections. In addition, current tools are unable to detect the nature and degree of vital organ dysfunction associated with severe malaria, as complications develop silently until the effective treatment window is closed. It is therefore crucial to identify cheap and reliable early biomarkers of this wide-spectrum disease. microRNAs (miRNAs), a class of small non-coding RNAs, are rapidly released into the blood circulation upon physiological changes, including infection and organ damage. The present review details our current knowledge of miRNAs as biomarkers of specific organ dysfunction in patients with malaria, and both promising candidates identified by pre-clinical models and important knowledge gaps are highlighted for future evaluation in humans. miRNAs associated with infected vectors are also described, with a view to expandind this rapidly growing field of research to malaria transmission and surveillance.

Highlights

  • Despite encouraging control progress over the past decade, malaria remains a major global health challenge. 409,000 malaria-associated deaths were reported in 2019, and 94% of these occurred in Africa (WHO, 2020)

  • Severe falciparum malaria is characterized by multi-organ dysfunctions, which are triggered by the sequestration of infected erythrocytes within the microvasculature of the host, combined with an exaggerated production of inflammatory mediators (White et al, 2013; Milner et al, 2014)

  • Severe malaria (SM) cases have been reported in patients infected with P. knowlesi (Pk) (Cox-Singh et al, 2010), P. ovale (Po) (Kotepui et al, 2020a), and P. malariae (Pm) (Kotepui et al, 2020b), these remain anecdotal

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Summary

Introduction

Despite encouraging control progress over the past decade, malaria remains a major global health challenge. 409,000 malaria-associated deaths were reported in 2019, and 94% of these occurred in Africa (WHO, 2020). Specific profiles of miRNAs associated with different phases of the malaria life cycle have the potential to help control and elimination efforts by allowing the identification of (i) carrier mosquitoes, (ii) infected patients, symptomatic or not, and (iii) potential tailored treatment for the former category.

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