Treating malaria

ACTs

Over the past decade, a new group of antimalarials – the artemisinin compounds, especially artesunate, artemether and dihydroartemisinin – have been deployed on an increasingly large scale. These produce a rapid therapeutic response, are active against multi-drug resistant P. falciparum malaria, are well tolerated by patients and reduce gametocyte carriage. To date, no parasite resistance to these compounds has been detected.  Studies in Southeast Asia have shown that combinations of artemisinin compounds with certain other antimalarials produce high cure rates in just 3 days of treatment.^{19, 20} Furthermore, there is some evidence that use of such combinations can greatly retard development of resistance to the partner drug.

Combining antimalarials - the advantages

Artemisinin derivatives have a short elimination half-life (2-3 hours). The main drawback of the short half-life is that it can produce substantial recrudescence when artemisinin derivatives are used alone for less than 5 days. For this reason, artemisinins are often used in free combination with other antimalarials.

A fixed combination of two antimalarials offers additional important advantages over the free combination of such drugs. Firstly, it facilitates compliance, and secondly, by preventing the patients from taking either drug alone, it helps to prevent the development of resistant Plasmodium strains. Coartemether is such a fixed combination antimalarial.

Artemisinin derivatives           

Artemisinin is a sesquiterpene lactone containing a bridged endoperoxide. It has:

• two main lipophilic derivatives, artemether and arteether
• a lesser, hydrophilic derivative, artesunate
• a major active metabolite in vivo, dihydroartemisinin.

The artemisinin derivatives (artesunate, artemether or arteether) are very fast acting and potent antimalarials that offer an important alternative to current treatments.

Background

At present, the production of ACTs stems from a surge in demand for a class of drugs that heavily relies on a natural plant ingredient – Aretemisia Annua – which has been used for treating fevers in traditional Chinese medicine for some 2000 years. In 1970, Chinese scientists isolated the active component, artemisinin, and developed it for the treatment of malaria.

The entire supply chain – from raw materials, to active ingredients to finished product, is being scaled up significantly in the context of a yet unstable and rapidly expanding market. International cooperation is needed to align demand and supply, until a stable market is established. One way of improving availability is to scale up cultivation of Artemisia annua and extraction. The plant has so far been grown mainly in China and Vietnam. It is now cultivated in some parts of Africa, where, in some areas, the yields of artemisinin have been high. Thus, African farmers in some areas could contribute significantly to supplying the world market. The World Health Organization (WHO) is currently working with partners to stimulate local production and extraction of artemisinin from Artemisia annua in Kenya and Tanzania.²¹