Oral Artemisinin-Based Monotherapies

Oral Artemisinin-Based Monotherapies

Oral artemisinin-based monotherapies refer to antimalarial treatments that contain only artemisinin or one of its derivatives as the active ingredient, administered orally. While these treatments were once widely used, they are now strongly discouraged by the World Health Organization (WHO) and many national health authorities due to concerns about drug resistance and reduced efficacy.

Artemisinin and its derivatives, such as artesunate, artemether, and dihydroartemisinin, are powerful antimalarial compounds that rapidly reduce the parasite load in the blood. When used alone, they can provide quick relief from malaria symptoms. However, several critical issues arise with their use as monotherapies:

Short half-life: Artemisinin compounds have a very short half-life in the body, typically less than one hour. This means they are quickly eliminated from the bloodstream, potentially leaving some parasites unexposed to the drug for a sufficient duration to ensure complete elimination.

Recrudescence: Due to the short duration of action, there is a high risk of recrudescence (return of symptoms) if the entire parasite population is not eliminated. This can occur even after initial symptomatic improvement.

Drug resistance: The use of artemisinin monotherapies significantly increases the risk of parasites developing resistance to these crucial drugs. This is particularly concerning given the central role of artemisinins in current malaria treatment strategies.

Incomplete treatment: Patients may discontinue treatment prematurely once symptoms improve, further contributing to the risk of recrudescence and resistance development.

Given these concerns, the WHO has taken a strong stance against the use of oral artemisinin-based monotherapies since 2006. Instead, the organization recommends artemisinin-based combination therapies (ACTs) as the first-line treatment for uncomplicated Plasmodium falciparum malaria.

ACTs combine an artemisinin derivative with a partner drug that has a different mechanism of action and a longer half-life. This combination approach offers several advantages:

Improved efficacy: The partner drug continues to act against parasites after the artemisinin component has been eliminated, ensuring more complete parasite clearance.

Reduced risk of resistance: The use of two drugs with different mechanisms of action makes it less likely for parasites to develop resistance to both components simultaneously.

Shorter treatment duration: ACTs typically require a 3-day treatment course, which is more likely to be completed by patients than longer regimens.

Lower recrudescence rates: The combination of drugs leads to more effective parasite clearance, reducing the likelihood of symptom recurrence.

Despite the clear recommendations against their use, oral artemisinin-based monotherapies remain available in some markets, particularly in areas with less regulated pharmaceutical sectors. This continued availability poses a significant threat to malaria control efforts and the long-term efficacy of artemisinin-based treatments.

Efforts to phase out oral artemisinin monotherapies have included:

Regulatory actions: Many countries have banned the import, manufacture, and sale of these products.

Education campaigns: Healthcare providers and the public are educated about the risks of monotherapies and the benefits of ACTs.

Market withdrawal: Pharmaceutical companies have been encouraged to voluntarily withdraw monotherapy products from the market.

Improved access to ACTs: Initiatives to increase the availability and affordability of ACTs have been implemented to discourage the use of monotherapies.