Breakthroughs Blog

We have made significant global progress against malaria over the last few decades, with three countries officially eliminating the disease just last year, joining the ranks of nearly 50 countries worldwide that have now achieved malaria-free status. Yet, malaria remains a formidable global challenge, with an estimated 282 million cases and 610,000 deaths in 2024, roughly 9 million more cases than in 2023. Climate change, conflict and instability, and funding disruptions all contribute to this persistent threat.  The rise of drug and insecticide resistance, a decades-old obstacle, has drawn renewed attention as it threatens to erode years of momentum. New tools addressing resistance, including novel drug combinations and vector control tools, offer hope for regaining lost ground. The long history of antimalarial drug resistance and new innovations to curb its riseAntimalarial drug resistance dates back nearly 75 years. Resistance to chloroquine, once of the most widely used antimalarial drugs, was first detected in the 1950s and spread unchecked for decades, contributing to a global rise in malaria-related mortality. Varying degrees of resistance also emerged to the therapies introduced to replace chloroquine. By the time artemisinin-based therapies were widely introduced in the 1990s, the World Health Organization took proactive steps to protect their efficacy by recommending they be used only in combination with other drugs.Artemisinin-based combination therapies (ACTs) have since become the global standard treatment. However, partial resistance to artemisinin-based drugs has now been confirmed or suspected in at least eight African countries, and several of the drugs used in combination with artemisinin are also showing declining efficacy. Emerging therapies in late-stage development could help address these growing challenges.In fall 2025, Novartis announced positive Phase 3 results for a novel, non-artemisinin combination malaria therapy developed with the Medicines for Malaria Venture. Delivered as a once-daily packet of oral granules taken over three days, the therapy was found to be highly effective against multiple forms of the malaria parasite and was also able to kill drug-resistant strains. If approved, it would represent the first major innovation in malaria treatment since ACTs.Another promising approach in late-stage development is triple ACTs, which combine artemisinin-based drugs with two additional drugs to fend off the emergence of resistance. In fall 2025, the Mahidol Oxford Tropical Medicine Research Unit, with funding from the Global Health Innovative Technology Fund, launched the first Phase 3 trial of a fixed-dose triple ACT in Rwanda. Taken once daily for three days, the therapy is designed to be affordable, easy-to-administer, and suitable across age groups, supporting adherence and reducing the risk of incomplete treatment, a key driver of resistance.  Historical lessons and new frontiers in vector control tools to tackle insecticide resistance Beyond parasite resistance, widespread insecticide resistance in mosquito vectors—dating back to the 1950s—has reduced the impact of existing vector control tools. The widespread uptake of insecticide-treated bednets helped drastically reduce malaria cases in Africa over recent decades, but most nets deployed since 2000 relied on pyrethroid insecticides. Resistance to pyrethroids is now widespread.In response, the World Health Organization recommended the first next-generation insecticide-treated nets in 2017. Since then, global partners, including the Innovative Vector Control Consortium, PATH, and the Gates Foundation, have collaborated to deploy more than 56 million of these new-generation nets, which have been shown to significantly improve malaria control outcomes.Additional innovations in the pipeline could complement these next-generation bednets. One promising group of tools is endectocides, or medicines taken by humans that kill mosquitoes when they bite. Ivermectin, an antiparasitic drug long used in mass drug administration campaigns for neglected tropical diseases, is the most studied endectocide to date. A 2025 study led by the Kenya Medical Research Institute, the Barcelona Institute for Global Health, and the Manhiça Health Research Center found that mass administration of ivermectin reduced new malaria infections by 26 percent when implemented alongside standard vector control measures. Unlike bednets or indoor residual spraying, which are limited to certain places or times of day, endectocides can protect people from malaria wherever they are.Early-stage research is also exploring gene drive technology, which genetically modifies mosquito populations to reduce their ability to transmit malaria. Target Malaria is investigating several gene drive approaches, including one of its most promising strategies: modifying male mosquitoes to carry a gene that causes some females to become sterile. Another approach involves genetically modifying males to produce predominantly male offspring, which can decrease mosquito numbers over time and reduce parasite transmission, since only female mosquitoes bite and transmit malaria. While still early in development, these tools could one day offer a transformative way to control mosquito populations.Drug and insecticide resistance represent some of the most urgent threats to the global fight against malaria, but they are not insurmountable. History shows that sustained innovation can blunt the impact of emerging resistance and help restore progress. Increased investment in new tools, alongside global coordination to ensure rapid and equitable deployment, will be essential to accelerating progress against malaria in the years ahead.