Can African Malaria Programmes Get Ahead of Antimalarial Resistance

For years, artemisinin-based combination therapies (ACTs) have been used for the treatment of uncomplicated plasmodium falciparum malaria. That confidence is now being tested. Artemisinin partial resistance, once largely associated with Southeast Asia, has now been documented in multiple African settings, with resistance-associated kelch13 mutations detected across countries including East and Northeast Africa, including Rwanda, Uganda, Tanzania, Ethiopia and Eritrea [1,2]. A 2025 analysis of over 100,000 Plasmodium falciparum samples found that the recent rise of resistance markers in Africa resembles patterns observed in Southeast Asia 10–15 years earlier [3]. The concern is not that ACTs have suddenly stopped working: many infections involving artemisinin-partial-resistant parasites can still be cured when the partner drug remains effective. Rather, slower parasite clearance leaves more parasites exposed to the partner drug, potentially increasing selection for resistance to both components [2,3]. WHO has described antimalarial drug resistance as a growing challenge to malaria progress [4], which raises the question: can programmes adapt before resistance becomes widespread treatment failure?

Why rational use of ACT matters

The immediate response to this changing landscape is not to abandon ACTs, but to protect the medicines that still work. ACTs depend on two complementary components: the artemisinin derivative rapidly reduces the parasite burden, while the longer-acting partner drug clears the remaining parasites. Where artemisinin partial resistance is present, preserving partner-drug efficacy becomes particularly important [5]. This makes rational treatment more than a clinical principle; it is part of resistance management. WHO recommends confirmed diagnosis before antimalarial treatment and warns against practices that contribute to resistance, including artemisinin monotherapy [6]. At the policy level, countries are also considering more adaptive approaches, including multiple first-line therapies that diversify drug pressure and extend the useful life of ACTs [7]. Rwanda offers a recent example of this approach, using regional resistance patterns to tailor ACT choices rather than treating the country as a single resistance landscape [8]. The question is therefore becoming less about finding one replacement for ACTs and more about using the treatments we have intelligently while preparing for what comes next.

How do we preserve the effectiveness of ACTs?

  1. Accurate diagnosis: Protecting ACTs begins with deciding who actually needs them. If every fever is treated as malaria, it increases unnecessary drug exposure and makes it harder to interpret whether treatment is failing because of resistance or because malaria was never the cause of illness. WHO therefore recommends parasitological confirmation with microscopy or a rapid diagnostic test (RDT) for suspected malaria and emphasises quality assurance for both approaches [6]. This is not simply a diagnostic issue. It is a resistance-management issue. Accurate testing supports appropriate treatment, protects patients from unnecessary medicines and strengthens the quality of the data used to understand malaria trends. Yet diagnostic quality cannot be assumed simply because an RDT is available. Product quality, storage, quality control, health-worker training, and clear action on test results matter in a resistance landscape where treatment decisions must be increasingly precise; the reliability of the first decision point matters.
  2. Effective preventive measure: If accurate diagnosis helps ensure that ACTs are used when they are needed, prevention reduces the number of infections that require treatment in the first place. This is an increasingly important part of the resistance conversation. Seasonal malaria chemoprevention (SMC), for example, provides antimalarial medicines to children at high risk during peak seasonal transmission, reducing malaria illness among vulnerable populations, and the current malaria vaccine adds an additional layer of protection. Prevention therefore complements, rather than replaces, resistance management: fewer infections mean fewer episodes requiring antimalarial treatment, while effective prevention protects health before treatment is needed. But effectiveness on paper is not enough. Coverage, timing, acceptability, supply chains, adherence and delivery quality determine whether preventive interventions achieve their intended effect. WHO’s experience with SMC implementation has consequently emphasised adapting delivery to local contexts and strengthening monitoring and evaluation [9]. The resistance challenge strengthens the case for taking these implementation questions seriously.
  3. Health system strengthening: Science may tell us that resistance is emerging, but health systems determine whether that information is detected, interpreted and acted upon in time. Therapeutic efficacy surveillance remains central to monitoring antimalarial effectiveness, yet recent work has highlighted important limitations in high-transmission settings, including the cost and logistical demands of conventional surveillance and the difficulty of distinguishing treatment failure from reinfection [10]. Strong interventions therefore need more than new drugs or better laboratory methods; they need reliable diagnostics, effective prevention, functioning supply chains, trained providers, quality-assured medicines, usable data and mechanisms for adapting implementation when evidence changes. For implementation partners, this means generating evidence not only about whether an intervention can work, but whether it works as intended in real-world settings and reaches the populations most at risk.

Conclusion

The parasite will continue to evolve; our response must evolve with it. Staying ahead of ACT resistance will require more than waiting for treatment failure or developing the next antimalarial. It will require a connected response that:

  • protect the effectiveness of existing ACTs through rational use,
  • diagnose malaria accurately,
  • prevent infections before treatment is needed,
  • strengthen surveillance and continuously improve programme delivery.

For malaria programmes and their implementation partners, the opportunity is to turn evidence into action early enough to preserve the tools that work while building the systems needed for the next phase of malaria control.

We cannot control how the parasite evolves, but we can strengthen the systems that:

  1.  Prevent infections,
  2.  Detect change, and 
  3. Respond before resistance becomes widespread treatment failure.

 

References

  1. Rosenthal, P. J., Asua, V., & Conrad, M. D. (2024). Emergence, transmission dynamics and mechanisms of artemisinin partial resistance in malaria parasites in Africa. Nature Reviews Microbiology, 22(6), 373–384. https://doi.org/10.1038/s41579-024-01008-2
  2. White, N. J., & Chotivanich, K. (2024). Artemisinin-resistant malaria. Clinical Microbiology Reviews, 37(4), e00109-24. https://doi.org/10.1128/cmr.00109-24
  3. Balmer, A. J., White, N. F. D., Ünlü, E. S., Lee, C., Pearson, R. D., Almagro-Garcia, J., & Ariani, C. V. (2025). Understanding the global rise of artemisinin resistance: Insights from over 100,000 Plasmodium falciparum eLife, 14, e105544. https://doi.org/10.7554/eLife.105544
  4. World Health Organization. (2025a). African health leaders and global partners unite to confront rising threat of antimalarial drug resistance. World Health Organization. https://www.who.int/news/item/20-05-2025-african-health-leaders-and-global-partners-unite-to-confront-rising-threat-of-antimalarial-drug-resistance
  5. Zheng, D., Liu, T., Yu, S., Liu, Z., Wang, J., & Wang, Y. (2024). Antimalarial Mechanisms and Resistance Status of Artemisinin and Its Derivatives. Tropical medicine and infectious disease, 9(9), 223. https://doi.org/10.3390/tropicalmed9090223
  6. World Health Organization. (2025b). WHO guidelines for malaria. World Health Organization. https://www.who.int/publications/i/item/guidelines-for-malaria
  7. World Health Organization. (2024). Multiple first-line therapies as part of the response to antimalarial drug resistance. World Health Organization. https://www.who.int/publications/i/item/9789240103603
  8. Muvunyi, C. M., Gashema, P., Mbituyumuremyi, A., Iradukunda, P. G., Siddig, E. E., Niyonzima, J. D., Hakizimana, E., Umulisa, N., Noor, A. M., Semahore, J. M., Tuyishime, A., Harelimana, J. D., Umuhire, J., Butera, Y., & Nsanzimana, S. (2025). Strategies for mitigating emerging artemisinin-based antimalarial drug resistance in Rwanda: A promising approach for managing therapies in malaria-endemic countries. BMJ Global Health, 10(10), e020884. https://doi.org/10.1136/bmjgh-2025-020884
  9. World Health Organization. (2025c). Optimizing seasonal malaria chemoprevention. World Health Organization. https://tdr.who.int/newsroom/news/item/21-04-2025-optimizing-efforts-to-prevent-malaria
  10. White, N. J., & Watson, J. A. (2026). Reconsidering the clinical assessment of resistance to slowly eliminated antimalarial drugs in high-transmission settings. The Lancet Infectious Diseases, 26(5), e240–e247. https://doi.org/10.1016/S1473-3099(25)00435-9