Aptamers as innovative tools for malaria diagnosis and treatment: advances and future perspectives

Abstract

Malaria, caused by Plasmodium spp. parasites (P. vivax, P. falciparum, P. ovale, P. malariae, and P. knowlesi), remains a significant global health challenge, with 263 million cases and 567 000 deaths reported in 2023. Diagnosis in endemic regions relies on clinical symptoms, microscopy, and rapid diagnostic tests. Although widely used, microscopy suffers from variability in sensitivity due to operator expertise and low parasitemia. Rapid diagnostic tests, which are favored for their simplicity and speed, show high sensitivity for P. vivax but reduced accuracy (80%) for P. falciparum, which is attributed to deletions in histidine-rich protein 2/3 proteins caused by Pfhrp2/3 gene mutations. Innovative diagnostic and therapeutic technologies, such as aptamers, are gaining attention. Aptamers are single-stranded oligonucleotides that bind specifically to target molecules with high affinity. They have shown promise in disease diagnosis, therapeutics, and environmental monitoring. In malaria, aptamers are being explored as highly sensitive and specific diagnostic tools capable of detecting Plasmodium proteins across all infection stages. Additionally, they offer potential for novel therapeutic strategies, enhancing disease control and treatment options. These advancements highlight the use of aptamers as versatile and innovative approaches for addressing malaria and other infectious diseases. A comprehensive literature search was conducted in the PubMed, ScienceDirect, and SCOPUS databases via the keywords "Aptamers" AND "Malaria" AND "Aptamers" AND "Plasmodium." Additionally, patent searches were carried out in the LENS, WIPO, and LATIPAT databases via the same search terms. In total, 88 relevant articles were selected for this review, providing a comprehensive and evidence-based foundation to discuss emerging aptamer technologies for malaria diagnosis and treatment. The proteins commonly employed in rapid malaria diagnostic tests, such as histidine-rich protein 2, P. lactate dehydrogenase, and prostaglandin dehydrogenase, are highlighted. However, the identification of new targets, such as HMIGB1 and DRX1 (1-deoxy-d-xylulose-5-phosphate reductoisomerase), and the detection of whole cells have also been emphasized.

Keywords: HRP2; HRP3; LDH; SELEX; aptamers; diagnosis; malaria; red blood; treatment.

Figure 1

Comparison between traditional methods for malaria diagnosis and potential applications of aptamers for the diagnosis and treatment of the disease. (A) Conventional tools for malaria diagnosis. (B) Aptamers for diagnosis and treatment. (C) Comparison of key aspects between traditional methods and aptamers for the diagnosis of malaria

Figure 2

Overview of aptamers in the diagnosis and treatment of malaria. (A) Summary of the SELEX strategy for the development of aptamers. (B) Adaptation of the aptamers in different diagnostic formats. (C) Potential use of the aptamers for malaria control