25 April 2016
On the 25th April, the world recognises the global efforts to control Malaria. The Malaria endemic exists as a broad band around the equator in areas of the America, parts of Asia and Africa. The World Health Organisation (WHO) estimates that in 2015 there were 214 million cases of malaria and 438,000 deaths, making this a leading cause of death in the developing world.
Malaria is a life-threatening disease that is usually transmitted through the feeding of female Anopheles mosquitoes from infected animals and humans. Once an infected mosquito feeds a human it transmits the parasite – Plasmodium falciparum – that multiply in the host’s liver before infecting and destroying red blood cells. Lysis of red blood cells results in a range of symptoms including fever, headaches and convulsions with high morbidity and mortality rates if uncontrolled although treatment is available. Due to medical facilitates in some areas of the world, effective diagnostics is not possible, and researchers are working hard to improve the prevention of malaria infection, with just one malaria vaccine been close to licensed.
The WHO Global Technical Strategy for Malaria 2016-2030 has set ambitious but achievable targets to reduce malaria cases and death and eliminate malaria in at least 35 countries by 2030.
Aptamers to Malaria Diagnostics
There is now a growing body of research using aptamers as diagnostic agents. Many of the systems recognise a well characterised biomarker of Plasmodium infection – Plasmodium falciparum lactate dehydrogenase (PfLDH). This enzyme serves a key role in the metabolism of the parasite, which relies heavily on anaerobic respiration in order to proliferate. Several aptamer based approaches have targeted PfLDH, by either conjugating the aptamer to an electrochemical impedance platform (Lee et al., 2012) or to gold nanoparticles for a colorimetric test (Jeon et al., 2013). The APTEC platform, designed by Dirkzwager and colleagues also targets PfLDH, but uses the enzyme directly to elicit a colour change.
Aptamers to Malaria Therapeutics
Despite multiple different agents available for treating malaria, there is a constant need for novel, effective therapies to be developed. As antimalarial drug resistances rises, this places an increased pressure for scientists to innovate and several aptamer based therapeutics are of increasing interest. RNA aptamers targeting the cytoadhesion receptor, PfEMP1 have been shown to effectively reduce ‘rosetting’ of infected red blood cells (Barfod et al., 2009) which may help reduce symptoms. Whilst PfEMP1 appears to be the predominant target, alternative strategies are under way. DNA aptamers binding to heme have been shown to increase parasite toxicity by inhibiting natural detoxification pathways (Niles et al., 2009) in a similar fashion to existing heme chelating drugs. Both PfEMP1 and heme targeting aptamers are still in a pre-clinical phase of testing and it is currently unknown when they will enter clinical trials.
Effective diagnosis and treatment of malaria, particularly in resource-deprived areas remains a high priority for health organisations across the globe. Aptamers, both as diagnostic and therapeutic agents may help in combatting Malaria endemic, although further research is required to translate the findings from the bench to the clinic.
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