A crisis in malaria treatment is coming — we must act faster to contain it

For malaria treatment, drug resistance is an evolutionary certainty. The question we face is not if resistance will emerge, but when it will become clinically significant. That’s why we must act now, and not wait until our current therapies fail. Malaria remains one of the deadliest threats to young children worldwide. For two decades, artemisinin-based combination therapies, or ACTs, have been the world’s most powerful weapon against this threat, and during this time, deaths and suffering have decreased. But now malaria is rebounding. The reasons include crises and conflict, fragile health systems, climate change and insufficient funding. On top of that, in parts of Africa, we’re seeing the warning signs of future drug failure — and the global response is not fast enough. In the 1990s, the failure of chloroquine led to a catastrophic spike in malaria deaths: nearly 2 million annually by the early 2000s. By the time effective alternatives were widely deployed millions of lives had been lost. We cannot afford to let history repeat itself. The warning signs are flashing red In 2000, the first cases of partial resistance to ACTs were reported in Southeast Asia — the historical epicenter of antimalarial drug resistance. Relying on one drug to treat malaria is a risk. In Southeast Asia, the challenge was the presence of artemisinin partial resistance, leading to the partner drugs being under pressure. It was, in part, thanks to the use of other ACT combinations that the overall class of ACTs was protected. It's important to understand that ACTs won’t fail until the partner drugs fail — this is what we must keep an eye on. Thanks to a coordinated response, this was brought under control in Southeast Asia. However, partial resistance has now been confirmed in several African countries, including Rwanda, Uganda, and Tanzania. At the 78th World Health Assembly this year African member states raised the alarm, calling for a united response. Recent reports of artemisinin partial resistance in Africa have been supported by modelling studies, which suggest that these mutations will be deeply embedded in the parasite population in the short-term future. This means that from 2030, without replacements for artemisinin, the combination partners will come under increasing pressure. If the partner drugs start to show resistance — and there are already warning signs — we could end up in a position where none of the ACTs work. Without new treatments, this would be catastrophic. To stop resistance in its tracks, it’s important to understand the problem. We need to enhance our surveillance mechanisms. The challenge is that funding cuts are eroding our early warning system — the real-world studies that track how well malaria treatments work. Without them, we are flying blind into an approaching storm. What needs to happen — now To effectively tackle malaria drug resistance, we need to implement a coordinated, multilayered approach — immediate intervention, balanced with long-term innovation. These four steps are key: 1. Diversifying treatment options Right now, patients in Africa rely mainly on one combination therapy — but there are five others available and approved by the World Health Organization. By offering multiple first-line therapies rather than just one, to make it harder for parasites to develop resistance, and expanding access to alternatives, we can reduce the burden on a single drug and delay the development of resistance. Cost remains a barrier however. The newer ACTs need to approach cost parity with the older ACTs to ensure widespread adoption, and MMV, the organization I lead, is working on this. 2. Adding an extra line of defence: Triple ACTs Triple ACTs, or TACTs, combine artemisinin with two partner drugs, making it harder for resistance to develop and spread. This approach has shown strong promise in clinical studies, particularly in those areas where resistance to partner drugs is emerging. Trials have demonstrated that TACTs are not only more efficacious against artemisinin-partially resistant malaria, but also delay reinfection. The clinical studies show that TACT combinations can extend the lifespan of existing therapies while new medicines are being developed. The first coformulated TACT is being trialled in a Phase 3 study with potential approval in 2027. 3. Stopping malaria transmission at its source One of the biggest lessons from COVID-19 was the importance of cutting transmission quickly. For malaria, we already have a tool to do this: a single low dose of primaquine, or sLDPQ, approved by WHO more than a decade ago to block the spread of the parasite. The challenge was that no child-friendly version existed — despite children being infected most often. That gap has finally been filled. The next step is simple but crucial: ensure primaquine tablets are packaged together with ACT treatments so they reach every patient. Evidence shows it works in all settings, especially where drug resistance threatens progress. Sometimes, the solutions are straightforward — we just need to make them standard practice. 4. Progressing the pipeline of new tools A new generation of treatments is in development that are not based on artemisinin. The most advanced is ganaplacide-lumefantrine, which is completing Phase 3 trials led by Novartis in collaboration with Medicines for Malaria Venture. Other combinations are in earlier stages of development. These new therapies could reshape the treatment landscape in the face of antimalarial resistance. Innovation can’t wait — we need to act now Antimalarial drug resistance is a ticking clock, and the cost of inaction is measured in lives lost. We know what works: When public funding aligns with academic expertise and industry innovation, lifesaving medicines can be developed. Product development partnerships have demonstrated this time and again — delivering tools that have saved millions of lives. But to stay ahead of the parasite, we must invest now in next-generation medicines. The COVID-19 pandemic demonstrated that accelerated development is possible when the stakes are high and the global community is aligned. For malaria, we have the know-how, the partnerships, and the scientific momentum and progress is being made, guided by WHO’s antimalarial drug resistance strategy. What’s needed now is sustained funding, coordinated action, and global solidarity to act swiftly. Resistance won’t wait. Neither should we.