Resisting resistance: is there a solution for malaria?

Abstract

IntroductionCurrently, widely used antimalarial drugs have a limited clinical lifespan due to parasite resistance development. With resistance continuously rising, antimalarial drug discovery requires strategies to decrease the time of delivering a new antimalarial drug while simultaneously increasing the drug"s therapeutic lifespan. Areas coveredLessons learnt from various chemotherapeutic resistance studies in the fields of antibiotic and cancer research offer potentially useful strategies that can be applied to antimalarial drug discovery. In this review we discuss current strategies to circumvent resistance in malaria and alternatives that could be employed. Expert opinionWe have been "beating back" the malaria parasite with novel drugs for the past 49 years but the constant rise in antimalarial drug resistance is forcing the drug discovery community to explore alternative strategies. Avant-garde anti-resistance strategies from alternative fields may assist our endeavors to manage, control and prevent antimalarial drug resistance to progress beyond beating the resistant parasite back, to stopping it dead in its tracks. Here we investigate the 2 development of strategies that are able to either overwhelm or outwit the parasite in its attempts to develop resistance. Article Highlights box In most instances the malaria parasite develops drug resistance at a faster rate than a novel antimalarial drug can be developed. For antimalarial drug discovery to remain sustainable, the clinical lifespan of an antimalarial drug must as least exceed the time taken to develop the drug. Currently, antimalarial drug resistance is being controlled through the development of novel drugs, which are combined with an appropriate drug partner into a combination therapy. Polypharmacology (multitargeting) may be able to speed up the delivery of a novel antimalarial drug while simultaneously increasing the clinical lifespan of the drug. Unexplored targets such as the virulence potential, hijacked host factors and stress factors may deliver drugs that can effectively resist resistance. Other post-resistance strategies such as molecular decoys and chemogenomics may also prove valuable in curbing resistance.

The effect of malaria and anti-malarial drugs on skeletal and cardiac muscles

“…However, there is serious concern that malaria parasites are developing resistance to this treatment. With parasite resistance continuously rising, anti-malarial drug discovery requires strategies to decrease the time of delivering a new anti-malarial drug while simultaneously increasing the efficacy of existing treatments, developing alternative treatments [42], as well putting in place preventative measures, such as bed nets. In addition to causing serious whole body side effects, these drugs also have the ability to directly affect skeletal and cardiac muscles [43, 44].…”

“…Prolonged administration of it can cause heart block and progressive myopathy [42]. It has also been reported as cause of toxicity, mostly in the retina [45, 46].…”

Identification and Validation of Novel Drug Targets for the Treatment of Plasmodium falciparum Malaria: New Insights

“…As stated by Verlinden et al: "History has clearly indicated that new antimalarials must be continually developed in the ensuing event of resistance development to the current antimalarial arsenal." The occurrence of drug resistance in malaria is significantly faster than the development of antimalarials [3]. Thus, a constant supply of novel unrelated antimalarial compounds with orthogonal modes of action is urgently required.…”

“…Despite the effort and funds spent on malaria eradication, it continues to infect approximately 200 million people worldwide every year and kill one in every four infected [2]. While effective in the past, current antimalarials are becoming less and less reliable as the parasite rapidly develops drug resistance [3]. There…”

Biochemical Indices of Cardaic Function of Albino Wistar Rats Exposed to Hippocratea Africana Root Bark Extract

“…Epidemiological studies have shown that elevated concentrations of serum total cholesterol and LDL-cholesterol, triglycerides, fibrinogen and platelet count are independent risk factors for CVD [19]. Verlinde et al, (2016) [20] reports that prolonged administration of chloroquine can cause heart block and progressive myopathy. Ikezoe et al, (2009) [22] reports that chloroquine triggers the disruption of lysosomal enzymes, including amyloid-β accumulation and endoplasmic reticulum (ER) stress.…”