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Malaria control in the 21st Century

Progress, stalled gains, and the path forward

Over the last twenty years, international efforts have helped to advance malaria control worldwide, reducing global malaria deaths by 29% from 2002 to 2024.1 A parasitic illness spread through the bites of infected mosquitoes, malaria has been a persistent public health threat throughout the course of human history. While it is serious and potentially life-threatening in general populations, it is particularly deadly in paediatric and pregnant populations.

Today, more tools than ever before are being leveraged to combat the spread of malaria and reduce its impact. However, in the face of climate change, drug resistance and other challenges, this progress has stalled. Taking a high-level look at the advances and obstacles faced by antimalaria efforts in the 21st century provides critical context for future progress.

The last 20 years of antimalaria efforts

Since the World Health Organisation (WHO) began recommending an artemesinin-based combination therapy (ACT) as the standard first-line treatment for malaria in 2006, these therapies have gone largely unchanged, even as drug-resistance grows. This means the reduction in malaria mortality is largely not due to advances in treatment. In part, it has been the result of concerted efforts to supply impacted areas with the treatments and tools they need to fight malaria, such as insecticide-treated mosquito nets. Additionally, a great deal of progress can be attributed to important advances in diagnosis and prevention of malaria.

The advent of accessible, high-quality rapid diagnostic tests (RDTs), which can detect malaria in minutes, has made a significant impact. Fast, accurate diagnosis is critical to disease surveillance and to timely, targeted interventions that minimise the development of antimalarial resistance. Previously, the standard for diagnosis was microscopy, which requires skilled interpretation and quality equipment that may not be readily available in resource-limited regions.2 Such requirements are particularly challenging for low- and middle-income countries in which malaria is endemic. Conversely, RDTs, introduced in the mid-2000s, only require the application of blood to a test strip for the assay to detect the target antigen, with results in 15 to 30 minutes.3 They offer an alternative that empowers community health workers to diagnose malaria outside of laboratory settings, and to respond quickly and appropriately.

In the 2010s, the practice of seasonal malaria chemoprevention was introduced to areas where malaria is endemic. This strategy involves periodically administering a curative dose of antimalarial medicine to all children at high risk for infection during the peak season for transmission, whether or not they are actually infected. By maintaining high levels of antimalarials in the bloodstream throughout the period of greatest risk, children are cleared of existing infections and protected against new ones. To support this approach, the WHO recommends that first- and second- line malaria treatments within a country should not be used for its chemoprevention efforts, to avoid exacerbating drug resistance, and instead suggests amodiaquine plus sulfadoxine–pyrimethamine as an effective and relatively inexpensive option.4

New developments in vaccination have also contributed to prevention. While researchers have long sought an effective vaccine against malaria, they found little success until very recently. To date, the WHO has recommended two vaccines: RTS,S/AS01 (endorsed in 2021) and R21/Matrix-M (endorsed in 2023).5 Both have been shown to reduce malaria cases by more than 50% during the first year after vaccination, providing protection across the time period when children are typically most vulnerable to illness and death.6 Although these vaccines fall short of the 90% efficacy rate goal set by the WHO, they nevertheless represent a meaningful step forward in protecting at-risk populations against serious illness.

Current challenges in fighting malaria

Despite these advances, progress has stagnated. Efforts are falling short of the goals that the WHO set for malaria control, with more than three times the target number of yearly global malaria deaths reported in 2024.7 The reasons for this are numerous and complex.

Climate change is a major contributor to rising malaria case numbers and associated deaths. With warmer temperatures, and shifting rainfall and humidity levels, environments hospitable to mosquitoes are expanding. Milder conditions allow mosquitoes to flourish year-round in some regions where malaria transmission was previously only a seasonal threat. Additionally, extreme weather events are becoming more frequent with climate change, often damaging homes and the infrastructure that helps to control malaria transmission, such as accessible healthcare and protective housing. One model predicts that, between these ecological and infrastructure-disrupting effects, climate change could account for 123 million additional cases of malaria in Africa by 2050.8 

Other infrastructural challenges also hinder malaria control. Inequitable access to healthcare and limited funding in low- and middle-income countries makes it difficult for patients to get appropriate, timely treatments.9 Disruptions, such as the COVID-19 pandemic or regional conflict, can also make access to care difficult.7

Perhaps the most pressing challenge for drug developers is the growth of drug resistance, in which Plasmodium parasites that cause malaria have proven adept at evolving defenses against new drugs. Currently, ACT is the recommended first-line treatment and remains generally effective. However, artemisinin-resistant strains have emerged, meaning these therapies will not be effective indefinitely, leaving few reliable treatment options once resistance becomes more widespread.10 

Future needs in antimalaria tools

Many of the needed solutions for improving malaria control are structural, such as improved funding for necessary supplies and more accessible healthcare options. Nevertheless, there are several much-needed tools drug developers can provide.

Chief among these is the development of new, non-artemesinin-based antimalarial drugs, which use mechanisms different from the current first-line therapy. With drug resistance on the rise, introducing new options will be critical to successfully treating infections. At present, at least one new non-artemisinin drug, KAF156 (Ganaplacide), has shown efficacy in large clinical trials, offering hope for an alternative treatment.11 However, if only one such drug is available, the emergence of resistance to it would leave malaria treatments highly vulnerable once more. 

Since history has shown a pattern of resistance, it will be important to take steps to prevent it from developing in any new drugs. A single-dose cure would be especially powerful in ensuring a new drug’s longevity, as resistance often develops as a result of multi-day regimens with delays in parasite clearance. Other strategies to slow resistance include alternating between drugs on a yearly basis, or assigning different first-line treatments to neighbouring regions.

Improved vaccines would also be highly meaningful. In addition to increasing efficacy towards the 90% goal set by the WHO, new vaccines should prioritise fewer doses. The two established vaccines both require multiple doses over the course of a year. While this protection is vital, it can be challenging for patients in many malaria-endemic countries to adhere to a multi-dose schedule, in part due to healthcare access inequities. Vaccines that require fewer doses would make it significantly easier for patients to receive full protection.

Continuing to push for progress

Malaria and its spread are impacted by many factors, from global shifts to local challenges. Although combatting this disease will take a concerted effort from numerous governments, health organisations, researchers and individuals around the world, the last 20 years have shown that progress is possible. With time and the right tools, malaria control may someday be within reach.

References

1 Malaria. https://www.theglobalfund.org/en/malaria/. Accessed 9 Apr. 2026.

2 Aidoo, Michael, and Sandra Incardona. “Ten Years of Universal Testing: How the Rapid Diagnostic Test Became a Game Changer for Malaria Case Management and Improved Disease Reporting.” The American Journal of Tropical Medicine and Hygiene, vol. 106, no. 1, Jan. 2022, pp. 29–32. PubMed Central, https://doi.org/10.4269/ajtmh.21-0643.

3 Ojeniyi, Fiyinfoluwa Demilade, et al. “Performance and Challenges of Malaria Rapid Diagnostic Tests in Endemic Regions of Africa.” Scientific Reports, vol. 15, no. 1, Dec. 2025, p. 43663. www.nature.com, https://doi.org/10.1038/s41598-025-97259-x.

4 Seasonal Malaria Chemoprevention with Sulfadoxine–Pyrimethamine plus Amodiaquine in Children: A Field Guide. https://www.who.int/publications/i/item/9789240073692. Accessed 9 Apr. 2026.

5 Feehan, Jack, et al. “Recent Perspectives in Clinical Development of Malaria Vaccines.” Nature Communications, vol. 16, no. 1, Apr. 2025, p. 3565. www.nature.com, https://doi.org/10.1038/s41467-025-58963-4.

6 Malaria Vaccines (RTS,S and R21). https://www.who.int/news-room/questions-and-answers/item/q-a-on-rts-s-malaria-vaccine. Accessed 9 Apr. 2026.

7 New Tools Saved a Million Lives from Malaria Last Year but Progress under Threat as Drug Resistance Rises. https://www.who.int/news/item/04-12-2025-new-tools-saved-a-million-lives-from-malaria-last-year-but-progress-under-threat-as-drug-resistance-rises. Accessed 9 Apr. 2026.

8 Symons, Tasmin L., et al. “Projected Impacts of Climate Change on Malaria in Africa.” Nature, vol. 651, no. 8105, Mar. 2026, pp. 390–96. www.nature.com, https://doi.org/10.1038/s41586-025-10015-z.

9 Domingos, Edmilson Serra. “Rethinking Malaria Elimination: A Perspective on Challenges and Solutions in Angola.” Malaria Journal, vol. 24, July 2025, p. 214. PubMed Central, https://doi.org/10.1186/s12936-025-05398-3.

10 White, N. J., and K. Chotivanich. “Artemisinin-Resistant Malaria.” Clinical Microbiology Reviews, vol. 37, no. 4, pp. e00109-24. PubMed Central, https://doi.org/10.1128/cmr.00109-24. Accessed 9 Apr. 2026.

11 Novartis, with Study Success, to Seek Approval of New Kind of Malaria Drug | BioPharma Dive. https://www.biopharmadive.com/news/novartis-malaria-GanLum-ganaplacide-study-results/805258/. Accessed 9 Apr. 2026.

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