Harnessing the Potential of miRNAs in Malaria Diagnostic and Prevention

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.

Transfer RNA-Derived Small RNAs in the Pathogenesis of Parasitic Protozoa

“…The lack of Dicer and Argonaute (AGO) homologs, which are responsible for miRNA cleavage, suggests that P. falciparum may utilize an alternative pathway for post-transcriptional regulation [ 45 ]. Despite this, recent findings are suggestive of Plasmodium having the capability to manipulate host miRNA production as seen from differential miRNA profiling of plasma samples from patients with severe and uncomplicated malaria respectively [ 61 , 62 ].…”

microRNAs: An opportunity to overcome significant challenges in malaria detection and control

“…MicroRNAs (miRNAs) are 18–24 nucleotide-long, non-coding RNAs that are rapidly released into the blood circulation upon infection and organ damage ( Gupta and Wassmer, 2021 ). They regulate gene expression endogenously at the post-transcriptional level, either through translation repression or mRNA degradation ( Gupta and Wassmer, 2021 ).…”

“…MicroRNAs (miRNAs) are 18–24 nucleotide-long, non-coding RNAs that are rapidly released into the blood circulation upon infection and organ damage ( Gupta and Wassmer, 2021 ). They regulate gene expression endogenously at the post-transcriptional level, either through translation repression or mRNA degradation ( Gupta and Wassmer, 2021 ). Secreted miRNAs are extremely stable in biologic fluids, which makes them highly promising non-invasive biomarkers to detect an infection and early-stage tissue or organ damage ( Zhou et al., 2016 ; Tribolet et al., 2020 ; Gupta and Wassmer, 2021 ).…”

“…They regulate gene expression endogenously at the post-transcriptional level, either through translation repression or mRNA degradation ( Gupta and Wassmer, 2021 ). Secreted miRNAs are extremely stable in biologic fluids, which makes them highly promising non-invasive biomarkers to detect an infection and early-stage tissue or organ damage ( Zhou et al., 2016 ; Tribolet et al., 2020 ; Gupta and Wassmer, 2021 ). While miRNA-based biomarkers of various infectious diseases ( Tribolet et al., 2020 ) and organ injuries ( Zhou et al., 2016 ) have been identified, very little has been done in the context of malaria.…”

“…Our published analyses of samples from well-characterised Mozambican children and Indian adults have shown the association of miR-3158-3p with severe falciparum malaria, highlighting for the first time a promising candidate biomarker for diagnosis across geographical regions and age groups ( Gupta et al., 2021a , 2021b ). Interestingly, several specific miRNAs (miR-14, 92a, 124, 275, 305, 309, and 989) have also been identified in Pf -infected Anopheles mosquitoes ( Gupta and Wassmer, 2021 ). Thus, there is potential to incorporate parasite-stage-specific miRNAs into new diagnostic and prognostic tools to detect both carrier mosquitoes and infected patients ( Gupta and Wassmer, 2021 ), thereby overcoming the emerging challenges associated with the loss of pfhrp2 .…”