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MORU. Photographer: Lorenz von Seidlein
Mutations indicating artemisinin-resistance have been found in more than 10% of malaria infected individuals in Ethiopia, Eritrea, Rwanda, Uganda, and Tanzania, note the group of researchers from 10 countries in Africa, Asia, the Americas and Asia. This could signal the end of the remarkable effectiveness of artemisinin combination therapies (ACTs) to fight malaria in Africa over the last two decades
“Now is the time to act before millions of people die due to increasingly ineffective antimalarial treatments,” said Prof Olugbenga Mokuolu, Department of Paediatrics and Child Health, College of Health Sciences, University of Ilorin, Nigeria.
“We ask funders, specifically the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) and the US government’s President’s Malaria Initiative, to be visionary and to step up funding for malaria control and elimination programs to contain the spread of artemisinin resistance in Africa – as they have done effectively in Southeast Asia since 2014,” said Ntuli Kapologwe, Director of Preventive Services, Ministry of Health, Tanzania.
In Eritrea, PfK13 mutations – the markers of artemisinin resistance - jumped from 8% of cases in 2016 to 21%. Between 2017 and 2022, the prevalence of the PfK13 R622I mutation increased across three regions of Ethiopia, and by 2022, similar mutations had spread across Uganda, reaching a prevalence of more than 20% in many districts.
In Rwanda, where artemisinin resistance was first detected in Africa, the PfK13 R561H mutation prevalence had reached 20% in Masaka and 10% in Rukara by 2018. In Kagera, a Tanzanian region bordering Uganda and Rwanda with a 7.7% prevalence of R561H in 2021, Karagwe district has a prevalence of artemisinin-resistant mutations of 22%.
“Recent experience from Southeast Asia suggests that the trend will only worsen,” said co-author Prof Sir Nick White, based at the Mahidol Oxford Tropical Medicine Research Unit (MORU), in Bangkok.
Prof White warned that we have been here before: Between 1980 and 2004, the continued use of an increasingly ineffective antimalarial, chloroquine, resulted in malaria-related deaths rising more than three-fold per year in Africa from an estimated 493,000 deaths/year in 1980 to 1.6m in 2004.
“We must act now so we don’t repeat the catastrophic mistakes we made with chloroquine when it was used for too many years after it was no longer effective,” said co-author, Dr Mehul Dhorda, who is also based at MORU, in Bangkok.
“WHO recognized the threat posed by the emergence of artemisinin resistance in Africa and published a strategy in 2022 that lists potential options to counter artemisinin resistance, but a clear plan and directions are now needed. The key new interventions need to be identified and agreed in collaborations with experts and country representatives, so that countries can adapt and implement them urgently,” said senior author Prof Lorenz von Seidlein, MORU.
The researchers detailed these urgent policy changes and actions – many previously trialled in SE Asia - to counter artemisinin-resistant malaria in East Africa:
Drug therapy
“Combining an artemisinin derivative drug with two partner drugs in triple artemisinin combination therapies (TACTs) is the simplest, most affordable, readily implementable, and sustainable approach to counter artemisinin resistance,” said Dr Dhorda.
- Change from ACTs to TACTs now.
- Add single low-dose primaquine to antimalarial regimens for P. falciparum.
- Accelerate the development, evaluation and roll-out of additional TACTs and new classes of antimalarials.
Vector control
Malaria mosquitoes have become resistant to many insecticides.
- Newer classes of insecticides and combinations of insecticides must be rolled out to provide better protection than the original pyrethroid only treated bednets.
- Expand the coverage of bednets with the appropriate insecticide combinations.
- Expand indoor residual spraying (IRS) where appropriate.
- Improve the quality of insecticide impregnated bednets in terms of bio-efficiency, size, and durability.
- Validate and implement effective the existing vector control tools and explore innovative approaches against indoor and outdoor biting mosquitoes.
Community Health Workers (CHWs)
“Support for CHWs was the key factor for the success of the malaria elimination programme in the Greater Mekong sub-region (GMS) of SE Asia.” says physician and social scientist Dr Bipin Adhikari, a co-author on the paper. “Creating a network of CHWs in affected African regions may well be essential for success. This will ensure access to early diagnosis and treatment of uncomplicated malaria episodes and pre-referral management of patients with severe malaria with rectal artesunate suppositories.”
Vaccines
“Finally, after decades of waiting we have now not only one but now two malaria vaccines approved and ready to roll out in many African countries. We must use these vaccines to push malaria back and ultimately eliminate it!” says Prof Lorenz von Seidlein.
- Include malaria vaccines in childhood vaccination programs.
- Implement vaccination campaigns of entire populations.
Monitoring
“ The constant monitoring of treatment failures is a critical component of successful containment of artemisinin resistance,” says co-author Dr Chanaki Amaratunga.
- Extend and validate surveillance for resistance to the available antimalarial drugs.
- Conduct appropriate therapeutic and preventive efficacy evaluation studies.
- Monitor the efficacy of seasonal malaria chemoprevention (SMC) and perennial malaria chemoprevention (PMC) in East Africa.
Funder
The Wellcome Trust (UK)
Article details
Artemisinin-resistant malaria in Africa demands urgent action. Dhorda M, Kaneko A, Komatsu R, Achyut KC, Mshamu S, Gesase S, Kapologwe N, Assefa A, Opigo J, Adoke Y, Ebong C, Karema C, Uwimana A, Ndikumana Mangara J-L, Amaratunga C, Peto TJ, Tripura R, Callery JJ, Adhikari B, Mukaka M, Cheah PY, Mutesa L, Day NPJ, Barnes KI, Dondorp A, Rosenthal PJ, White NJ, von Seidlein L. Science. Under strict embargo to 14:00 EDT (USA) / 19:00 BST (UK) 18 July 2024.