Abstract
The number of available and effective antimalarial drugs is quickly dwindling. This is mainly because a number of drug resistance-associated mutations in malaria parasite genes, such as crt, mdr1, dhfr/dhps, and others, have led to widespread resistance to all known classes of antimalarial compounds. Unfortunately, malaria parasites have started to exhibit some level of resistance in Southeast Asia even to the most recently introduced class of drugs, artemisinins. While there is much need, the antimalarial drug development pipeline remains woefully thin, with little chemical diversity, and there is currently no alternative to the precious artemisinins. It is difficult to predict where the next generation of antimalarial drugs will come from; however, there are six major approaches: (i) re-optimizing the use of existing antimalarials by either replacement/rotation or combination approach; (ii) repurposing drugs that are currently used to treat other infections or diseases; (iii) chemically modifying existing antimalarial compounds; (iv) exploring natural sources; (v) large-scale screening of diverse chemical libraries; and (vi) through parasite genome-based (“targeted”) discoveries. When any newly discovered effective antimalarial treatment is used by the populus, we must maintain constant vigilance for both parasite-specific and human-related factors that are likely to hamper its success. This article is neither comprehensive nor conclusive. Our purpose is to provide an overview of antimalarial drug resistance, associated parasite genetic factors (1. Introduction; 2. Emergence of artemisinin resistance in P. falciparum), and the antimalarial drug development pipeline (3. Overview of the global pipeline of antimalarial drugs), and highlight some examples of the aforementioned approaches to future antimalarial treatment. These approaches can be categorized into “short term” (4. Feasible options for now) and “long term” (5. Next generation of antimalarial treatment— Approaches and candidates). However, these two categories are interrelated, and the approaches in both should be implemented in parallel with focus on developing a successful, long-lasting antimalarial chemotherapy.
Highlights
More than 40% of the world’s population, much of it socioeconomically and politically challenged, live in areas where malaria, alone or together with HIV/AIDS and tuberculosis, is a significant health risk [1,2]
Among the non-artemisinin and/or non-quinoline combinations and single compounds are: Azithromycin-CQ, fosmidomycin-clindamycin, methylene blue-amodiaquine, SAR 97276, and tinidazole. It is clear from the size of the antimalarial drug development pipeline that the pipeline has not reached critical mass, which is of concern when we consider the recent emergence of artemisinin resistance, and the apparent decrease in time to resistance to each new drug/drug combination
Resistance-conferring alleles have remained at a high frequency 8 years and 2 decades, respectively, after the replacement of SP. It appears that the outcome of the drug replacement/rotation approach is not universal but malaria-endemic region dependent; a number of diverse ecological and epidemiological factors are likely to play a role in determining the outcome of this approach
Summary
More than 40% of the world’s population, much of it socioeconomically and politically challenged, live in areas where malaria, alone or together with HIV/AIDS and tuberculosis, is a significant health risk [1,2]. If children survive multiple infections, such exposure leads to a natural immunity that limits the severity of the disease later in life. This immunity wanes in the absence of continued exposure to malaria infections. Outside of Africa, P. vivax is the most widespread species, occurring largely in Asia, including the Middle East and the Western Pacific, and in Central and South America [12]. This parasite species causes a relatively less lethal form of the disease compared with P. falciparum [12,13]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.