Malaria patients in a Phase 3 clinical trial in West Africa were successfully cured with a single dose of a treatment combining four widely available malaria drugs, according to findings released Wednesday at the Annual Meeting of the American Society of Tropical Medicine and Hygiene (ASTMH).
The breakthrough addresses two major obstacles that have stalled progress against a disease that kills about 600,000 people annually: the rise of drug-resistant malaria and poor adherence to the standard three-day, six-dose regimen, which fuels resistance and allows treatable cases to worsen.
“We found that our single-dose treatment was just as effective as the standard course that typically requires taking six doses over three days, which many patients never complete,” said Ghyslain Mombo-Ngoma, lead author of the study and head of clinical operations at the Medical Research Center of Lambaréné, Gabon.
The one-time therapy, combining sulfadoxine, pyrimethamine, artesunate, and pyronaridine (SPAP), may also work better against resistant parasites because it targets four different weaknesses in the malaria parasite, compared to the two targeted by standard treatments.
Mombo-Ngoma said using multiple drugs simultaneously forces parasites into a “multi-front battle,” a strategy already used to counter drug-resistant tuberculosis and increasingly considered for malaria control.
A single-dose option, he added, also helps curb resistance that emerges when patients fail to finish their full course of treatment, while preventing undertreated infections from progressing to severe, life-threatening disease.
The need for new malaria treatment strategies is urgent. In sub-Saharan Africa, home to 95 percent of global malaria cases and deaths, progress has stalled.
After sharp declines from 2000 to 2015, cases and deaths have crept back up. According to the World Health Organization, 263 million cases and 597,000 deaths were recorded in 2023, up from 216 million cases and 445,000 deaths in 2016. Partial resistance to artemisinin combination therapies (ACTs), the backbone of treatment in Africa, is an emerging threat.
“Another challenge is that ACTs must be taken for three days to clear parasites, and a third or more of patients don’t complete the full course,” Mombo-Ngoma said. Incomplete treatment allows parasites to linger and multiply, increasing the chances of severe illness and giving resistant strains room to evolve.
The trial, conducted from May 2024 to October 2025, enrolled more than 1,000 patients with uncomplicated malaria, about half of them children under 10. Safety was first evaluated in a small group, followed by the larger Phase 3 efficacy trial.
In total, 539 patients received the single-dose therapy combining the SP and AP drug pairs, while 442 patients were treated with a widely used ACT-artemether-lumefantrine, taken over three days.
After 28 days, 93 percent of patients in the single-dose group were parasite-free, compared to 90 percent in the ACT group, showing the treatments were essentially equally effective. No serious drug-related adverse events were reported.
“Another key advantage is that our single-dose cure uses medicines already available to malaria programs across Africa, and they’re relatively affordable,” Mombo-Ngoma noted.
The findings arrive as new anti-malaria compounds show promise in early research, but even in the best-case scenario, experts say it will take several years before they are widely deployed.
“I’m a malaria researcher, but I’m also a doctor treating many malaria patients, and I need new options now,” Mombo-Ngoma said. “If we continue to see success with this single-dose cure, it could serve as a bridge to the next generation of treatments, something we can deploy immediately while we await other solutions.”
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