The emergence of drug-resistant malarial parasites has been a growing challenge to medical science to safeguard public health in the malaria-endemic regions of the globe. With time, the parasite develops newer resistance mechanisms to defunct the drug's action one after another. Genetic mutation is the prime weapon parasites rely upon to initiate the resistance mechanism in a case-specific manner, following various strategies such as structural changes in the target protein, metabolic alterations, and tweaking the drug-transported channels. In order to combat these resistances, different approaches have evolved among these developing inhibitors against critical parasite enzymes and metabolic pathways, combinatorial/hybrid drug therapies, exploring new drug targets and analogues of existing drugs, use of resistance-reversal agents, drug-repurposing, gene blocking/altering using RNA interference and CRISPR/Cas systems are prominent. However, the effectiveness of these approaches needs to be earnestly monitored for better management of the disease, which demands the development of a reliable diagnosis technique. Several methodologies have been investigated in search of a suitable diagnosis technique, such as in vivo, in vitro, ex vivo drug efficacy studies, and molecular techniques. A parallel effort to transform the efficient method into an inexpensive and portable diagnosis tool for rapid screening of drug resistance malaria among masses in the societal landscape is advocated. This review gives an insight into the historical perspectives of drug-resistant malaria and the recent developments in malaria diagnosis and antimalarial drug discovery. Efforts have been made to update recent strategies formulated to combat and diagnose drug-resistant malaria. Finally, a concluding remark with a future perspective on the subject has been forwarded.
Keywords: CRISPR/Cas; Plasmodium parasites; biosensors; genetic mutation; hybrid drug therapy; inhibitors.