Malaria

Q&A on artemisinin resistance

December 2017

1. What is artemisinin?

Isolated from the plant Artemisia annua, or sweet wormwood, artemisinin and its derivatives are powerful medicines known for their ability to swiftly reduce the number of Plasmodium parasites in the blood of patients with malaria. Artemisinin-based combination therapies (ACTs) are recommended by WHO as the first-line treatment for uncomplicated P. falciparum malaria.

Expanding access to ACTs in malaria-endemic countries has been integral to the remarkable recent success in reducing the global malaria burden. The number of ACT treatment courses procured from manufacturers increased globally from 187 million in 2010 to 409 million in 2016.

ACTs combine artemisinin derivatives with a partner drug. The role of the artemisinin compound is to reduce the main parasite load during the first 3 days of treatment, while the role of the partner drug is to eliminate the remaining parasites. In patients who are infected with artemisinin-resistant strains of malaria, the artemisinin compound is less effective in clearing all parasites within this 3-day period. However, patients are still cured as part of a longer treatment regimen, provided that they are treated with an ACT containing a partner drug that is effective in that geographical area. WHO currently recommends 5 different ACTs.

2. What is the state of artemisinin resistance around the world?

As of December 2017, artemisinin resistance has been confirmed in 5 countries of the Greater Mekong Subregion (GMS): Cambodia, the Lao People’s Democratic Republic, Myanmar, Thailand and Viet Nam. In the large majority of sites, patients with artemisinin-resistant parasites still recover after treatment. However, along the Cambodia-Thailand border, P. falciparum has become resistant to almost all available antimalarial medicines. There is a real risk that multidrug resistance will soon emerge in other parts of the subregion as well.

Artemisinin resistance has occurred as a consequence of several factors: poor treatment practices, inadequate patient adherence to prescribed antimalarial regimens, and the widespread availability of oral artemisinin-based monotherapies and substandard forms of the drug.

The geographic scope of the problem could widen quickly and have important public health consequences: the spread or independent emergence of artemisinin resistance in other parts of the world could pose a health security risk as no alternative antimalarial medicine is available at present with the same level of efficacy and tolerability as ACTs.

In late 2013, researchers identified a molecular marker: mutations in the Kelch 13 (K13) propeller domain were shown to be associated with delayed parasite clearance in vitro and in vivo. The molecular marker could allow for a more precise mapping and monitoring of the geographical distribution of resistance. It could also enable a retrospective mapping of possible resistance in a large number of settings.

WHO is working with researchers, national malaria programmes and other partners – within and outside of the GMS – to map the presence of artemisinin resistance. Meanwhile, therapeutic efficacy studies remain a central tool for monitoring the efficacy of nationally recommended antimalarial treatments in all countries.

3. How is WHO supporting countries in their efforts to tackle artemisinin resistance?

In collaboration with national malaria programmes and partners, WHO led the development of the Strategy for malaria elimination in the Greater Mekong Subregion (2015–2030). Urging immediate action, the strategy calls for the elimination of all species of human malaria across the GMS by 2030, with priority action targeted to areas where multidrug-resistant malaria parasites have been identified.

With technical guidance from WHO, all GMS countries have developed national malaria elimination plans. As countries implement these plans, WHO is providing ongoing technical support through its 6 GMS country offices, regional offices in New Delhi and Manila, and the Organization’s Geneva headquarters.

Antimalarial drug efficacy is assessed through therapeutic efficacy studies (TES). Such studies at regular intervals at the same sites allow for the early detection of declines in drug efficacy, providing evidence for guiding national malaria treatment policies. To improve the response to multidrug resistance in the GMS, countries, with the support of WHO and partners, continually collect and analyse quality data at sentinel sites across the subregion.

In 2017, WHO launched the Mekong Malaria Elimination (MME) programme. The MME subregional team in Phnom Penh, Cambodia, supports the GMS malaria elimination strategy by facilitating coordination and dialogue among partners, communicating with external stakeholders, and coordinating cross-border initiatives.

Urgent action now will deliver significant savings in the long run, improving the sustainability and public health impact of malaria interventions around the world.

4. Who is funding these efforts?

The fight to eliminate malaria in the GMS is supported through generous contributions from a number of donors, including: the Australian Department of Foreign Affairs and Trade, the Bill & Melinda Gates Foundation, the Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund), the UK Department for International Development and the US Agency for International Development.

In response to the emergence of artemisinin resistance in the GMS, the Global Fund launched the Regional Artemisinin-resistance Initiative (RAI) in 2013. Funding provided through this initiative has enabled countries to purchase and distribute commodities such as long-lasting insecticidal nets (LLINs), rapid diagnostic tests and quality-assured drugs.

Earlier this year, the Global Fund announced an expansion of the RAI, committing an additional US$ 242 million for the period 2018 to 2020. WHO is working with GMS countries and the Global Fund to optimize the use of this funding in the subregion.

4. What more needs to be done to address this threat?

Scaling up prevention and control interventions and implementing all of WHO’s recommendations require considerable financial resources, long-term political commitment, and strong cross-border cooperation. Governments of endemic countries also need to take targeted regulatory measures to remove oral artemisinin-based monotherapies from markets, along with antimalarials that do not meet international quality standards.

Endemic countries outside this region – and in particular in the WHO African Region, where malaria took an estimated 407 000 lives in 2016 – also need to identify additional resources to fully implement WHO recommendations to prevent the emergence of artemisinin resistance. One of the most urgent challenges is to strengthen pharmaceutical market regulation, and remove oral artemisinin-based monotherapies from markets around the world once and for all.

This Q&A was originally issued in April 2013 and was last updated in December 2017.



Note

To learn more about which countries still allow the marketing of oral artemisinin-based monotherapies, and which companies still produce and market these products, please visit: