A study recently published in Nature Medicine1 reports of the emergence of de novo laboratory markers for artemisinin resistance in Rwanda. While concerning, the study has also shown that the artemisinin-based combination therapies (ACTs), which are the first-line treatment for acute uncomplicated P. falciparum malaria, nevertheless continue to cure the disease in Africa.
In Rwanda, the two ACTs investigated in the study, artemether-lumefantrine and dihydroartemisinin-piperaquine, continue to show cure rates of >95%.
The study findings, based on parasites collected from 2013–2015, have also been clinically confirmed in a 2018 study2 by the Rwandan National Malaria Control Programme and President’s Malaria Initiative. Markers for artemisinin resistance were also identified in this subsequent study and were associated with delayed parasite clearance. However, such findings do not necessarily imply resistance to ACTs if the partner drug is still working.
The 2018 study found artemisinin resistance markers and a delay in parasite clearance time, though in keeping with the study published in Nature Medicine, artemether-lumefantrine nevertheless provided high cure rates (94%-97% across sites). No early clinical treatment failure was noted.
Surveillance of antimalarial drug resistance needs to be intensified
The studies indicate that these malaria parasites identified in Rwanda with laboratory markers for artemisinin resistance are not the result of resistance spreading from the Mekong sub-region of Asia, where today it is widespread, but have arisen independently.
The report serves as an important reminder of the need to intensify surveillance for laboratory markers of antimalarial drug resistance and for any decline in the efficacy of malaria treatments in the field. It will also be important to focus on strategies that can reduce the development and spread of artemisinin and partner drug resistance in Africa, as well as be prepared with next-generation antimalarial medicines for the time when it becomes more widespread.
MMV is working with partners to develop next-generation antimalarials
“Although ACTs remain effective in the treatment of malaria and can continue to be used in line with guidelines, the identification of early indicators of artemisinin resistance in Africa is cause for concern,” said Dr David Reddy, CEO of MMV. “It comes on the back of the COVID-19 pandemic, which has demonstrated the crucial nature of R&D and the consequences of not being able to simply reach onto the shelf for an already developed medicine. With our partners, MMV is working to avoid this reality for malaria patients by developing next-generation medicines to ensure they can continue to be treated if and when the current medicines fail.”
“The study findings support the need to fast-track antimalarial drug efficacy research and will inform which strategies should be adopted to eliminate mutant parasites today as well as provide guidance to governments, drug development partners and other stakeholders regarding future needs,” said Dr Aline Uwimana of the Rwanda Biomedical Center and Principal Investigator for the studies. “In addition, these findings will be shared among countries and partners to support effective partnerships and surveillance within the region.”
Key measures to address emerging artemisinin resistance include:
1. Continued surveillance of genetic markers of antimalarial drug resistance in endemic countries
2. Continued surveillance of both clinical and laboratory indicators of drug efficacy in endemic countries
3. Action to be taken today to maximize the longevity of the ACTs, such as education around the importance of differential diagnosis of fever and of completing antimalarial treatments with high-quality medicines
4. Intensified efforts to develop the next generation of malaria medicines as back up for eventual appearance of resistance.
MMV and partners have a number of novel drug candidates moving forward in development to help address this need. The resistance profile of these drug candidates is one of the key criteria for their further development. MMV is also supporting efforts to increase access to the most effective treatments in malaria-endemic countries, as well as to chemoprevention to reduce the risk of infection for those at greatest risk of severe malaria.
The data in the Nature Medicine article was generated by WHO’s surveillance systems and more details on artemisinin resistance can be found in the WHO’s Q&A on the topic.
1 Uwimana A et al. Emergence and clonal expansion of in vitro artemisinin-resistant Plasmodium falciparum kelch13 R561H mutant parasites in Rwanda. Nat Med. 2020 Aug 3.
2 Uwimana A et al. Efficacy of artemether lumefantrine for the treatment of uncomplicated Plasmodium falciparum infection in Rwanda, 2018. ASTMH 2019 poster, LB-5134.