Trace the evolution of antimalarial drugs from quinine to 8-aminoquinolines, and discuss the challenges of radical cure.

Antimalarial therapy moved from the cinchona-derived alkaloid quinine to laboratory-synthesised compounds in the 1920s, when the 8-aminoquinolines were developed in Germany. This shift solved the problem of relapse but created a new one — safety — which still limits radical cure today.

From quinine to the 8-aminoquinolines

• Quinine, a plant-derived blood-stage drug, was the long-standing standard; it cleared fever but left the parasite reservoir in the liver untouched.
• The 1920s brought plasmochin (pamaquine), the first synthetic 8-aminoquinoline, developed through systematic screening in infected birds — a landmark in rational drug discovery [1].
• Pamaquine proved too toxic for routine use; wartime antimalarial research refined the molecule into primaquine, its safer successor [1].
• Primaquine remains the long-standing licensed drug that kills hypnozoites — the dormant liver forms of P. vivax and P. ovale — making true radical cure possible [2].

Challenges of radical cure

• Haemolysis risk: 8-aminoquinolines can precipitate acute haemolytic anaemia in persons with G6PD deficiency, an inherited enzyme disorder [1][2].
• Testing gap: WHO advises G6PD testing before prescribing primaquine, and has issued an operational guide for G6PD rapid diagnostic tests [3]. Yet frontline workers who carry a malaria RDT rarely carry a G6PD RDT.
• Adherence: the 14-day regimen outlasts the fever, so unsupervised patients stop early; an incomplete course leaves hypnozoites alive and relapse follows [2].
• Surveillance: India's reported cases fell from 11,69,261 (2015) to 2,27,564 (2023) under the National Framework for Malaria Elimination (2016–30) [4], and India exited WHO's HBHI group in 2024 after a 93% fall in incidence [5] — but cases treated outside the public system escape follow-up for radical cure.

Thus a century of chemistry has delivered the cure; delivery systems must now catch up. Pairing G6PD rapid tests with malaria RDTs, supporting shorter regimens and strengthening private-sector notification would make radical cure both safe and complete, securing India's 2030 elimination goal and SDG 3.