Responding to antimalarial drug resistance
Resistance to antimalarial medicines is a threat to global efforts to control and eliminate malaria. Improved access to effective malaria treatments has been a key contributing factor to the significant reduction in the malaria burden in recent years. Protecting the efficacy of the recommended malaria treatments is a top priority for malaria endemic countries and the global malaria community.
Therapeutic efficacy studies results and treatment policy change
Therapeutic efficacy studies (TES) are the main reference from which national malaria control programmes determine their national treatment policy. To ensure the efficacy of treatments implemented through national policies, WHO recommends that:
- National malaria control programme should adopt antimalarial medicines with a parasitological cure rate of more than 95%. Medicines should then be monitored at least once every 24 months at established sentinel sites;
- Regions for which there is evidence of resistance should consider adding more sentinel sites to facilitate early detection of new resistance foci.
A change in the national malaria treatment policy should be initiated if the total treatment failure rate is equal to 10% or greater, as assessed through monitoring of therapeutic efficacy.
Changing the treatment policy for Plasmodium falciparum
Nearly all malaria endemic countries recommend artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated P. falciparum. Therapeutic efficacy results help determine:
- the proportion of patients with confirmed presence of parasites in the blood on day 3 (currently the main indicator to identify suspected artemisinin resistance in P. falciparum);
- the proportion of treatment failure by day 28 or 42.
Recommended steps for making treatment policy decisions in response to TES findings
Changing the treatment policy for Plasmodium vivax
Most countries endemic for vivax malaria recommend chloroquine or ACT for the treatment of uncomplicated P. vivax. Most also include primaquine to eliminate latent liver stage infections and prevent relapse (a method known as radical cure), as it improves the activity of chloroquine against chloroquine-resistant blood stage parasites.
A change in treatment policy to an ACT is recommended if efficacy studies for chloroquine find a total treatment failure rate equal to 10% or greater. To date P. vivax resistance to an ACT has not been detected.
Preventing and containing antimalarial drug resistance
Several factors influence the emergence and spread of drug resistant malaria parasites, including the number of parasites exposed to a drug, the drug concentration to which the parasites are exposed, and the simultaneous presence of other antimalarials in the blood to which the parasite is not resistant.
In areas where the recommended antimalarial treatments remain fully efficacious, correct medicine use must be promoted, with special attention to expanding diagnostic testing, quality-assured treatment, and good patient adherence to the prescribed treatment. Further extending basic malaria interventions, including vector control, will reduce the number of parasites exposed to a drug and the risk of resistance.
Use of oral artemisinin-based monotherapy (oAMT) is considered a contributing factor to the development and spread of resistance to artemisinins. WHO has urged regulatory authorities in malaria-endemic countries to take measures to halt the production and marketing of oAMT, and promote access to quality-assured ACTs for the treatment of falciparum malaria.
Countries where resistance to artemisinins or to ACT partner drugs is reported need to intensify malaria control in order to reduce the burden of the disease, and delay or prevent the spread of resistance. Prevention and containment activities need to build on, expand and accelerate ongoing national efforts to control and eliminate malaria. In areas of low transmission where antimalarial drug resistance is present, countries should target rapid elimination of falciparum malaria to limit the risk of spread and minimize the impact of resistance in the region.
Elimination of multidrug resistant malaria: the special case of the Greater Mekong Subregion
The Greater Mekong Subregion has long been the epicentre of antimalarial drug resistance. P. falciparum resistance to artemisinin is present in 5 countries of the subregion: Cambodia, the Lao People’s Democratic Republic, Myanmar, Thailand and Viet Nam.
While containment efforts to stop the spread of resistant parasites were underway, it was discovered that artemisinin resistance had emerged independently in multiple areas and that resistance to ACT partner drugs had also emerged, threatening the progress achieved in the region to date.
In 2014, WHO conducted a study on the feasibility of P. falciparum elimination in the subregion. This study concluded that elimination is technically and operationally feasible at a reasonable cost. These developments, together with the impressive reduction in the malaria burden in the subregion in the last decade, lead to a shift in strategy focusing on malaria elimination. A Strategy for malaria elimination in the Greater Mekong Subregion (2015-2030) has been developed and is targeting malaria elimination in the GMS by 2030.
- Eliminating malaria in the Greater Mekong Subregion: United to end a deadly disease (2016)
- Malaria elimination strategy for the Greater Mekong Subregion (2015)