Plasmodium malariae is an overlooked malaria parasite with emerging challenges

Plasmodium malariae (P.m.) represents the least studied of the five human-malaria-causing Plasmodium species, despite its widespread global distribution. Control of P.m. is challenging due to the parasite's unique biological features, unavailability of P.m.-specific diagnostic methods, chronic low-grade parasitemia, and suboptimal clinical features. Emerging evidence suggests increasing antimalarial drug resistance and reduced susceptibility to first-line antimalarials. Its capacity for chronic infection, diagnostic challenges, and emerging drug resistance threaten malaria elimination efforts. Thus, it represents a significant yet underappreciated contributor to global malaria burden. Enhanced molecular diagnostics, targeted therapeutic strategies, and improved surveillance systems are urgently needed to address this neglected pathogen and prevent its resurgence when other malaria species are under control. Here, we synthesize current knowledge on P.m. biology, public health impact, immune paradigm, and clinical manifestations. We discuss the research gaps, outstanding questions, and novel approaches to study P.m. biology.