Treatment of Malaria
For various reasons malaria continues to be a growing problem in Africa. The key factor is the widespread resistance of Plasmodium falciparum to conventional anti-malarial drugs, such as chloroquine, mefloquine, sulfadoxine-pyrimethamine (SP) and amodiaquine. Overall, it is estimated that malaria costs Africa more than $12 billion annually, even though it could be controlled for a fraction of this amount.
WHO recommends that all countries experiencing resistance to conventional therapies should use combination therapies, preferably those containing artemisinin derivatives for P. falciparum malaria, called ACTs (Artemisinin Combination Therapies), which now appears to be the only known reliable treatment for malaria. However, lately resistance to ACT has been observed in Thailand-Cambodia border areas. Interestingly, previous incidences of parasite resistance for other anti-malarial substances have also been noted around the same region.
International funding available for malaria prevention, including mosquito-control strategies, and for treatment is estimated at $1.1 billion in 2008, but resource needs are estimated to be much higher exceeding $5 billion per year. International efforts to address malaria have intensified in recent years and the U.N. Millennium Development Goals include targets to reduce the impact of malaria by 2020.
Notwithstanding the malaria control strategies reported to have been widely applied such as, free distribution of mosquito nets in malaria endemic areas and increased level of funding in public and private sector directed at new drugs and vaccines, the world is still awaiting an inexpensive and effective treatment for malaria.
Present Day – World-wide strategy for mass production of safe and reliable cure and Prevention of Malaria
Artemisinin containing Artemisia is primarily available in China, Vietnam and to some extent in East Africa. Besides the limited availability of the plant itself, the artemisinin content is also low, rarely above 0.8% on large scale basis.
Since the isolation and characterization of artemisinin in China, the pharmaceutical initiatives have been based on using only the pure artemisinin or its derivatives, either as a mono-therapy, or as ACT, i.e., Artemisinin combined with other previously developed synthetic anti-malarials.
Thus, apart from development of anti-malarial vaccines on going for the past 25 years, research round the world has been focused on chemical and bio-synthesizing of the artemisinin compound, and to improve the specie to produce higher than average of 1.5% to 2.5 % or higher artemisinin content, which has been successful to a large extent. However, its impact has not yet been accessed.
Although it is recognized that the stereo-specificity of the artemisinin molecule makes total synthesis very difficult and may very well not be adaptable to industrial productions at acceptable price levels, the initiative is still being pursued aggressively. In contrast, the phytochemical investigation of Artemisia has revealed an abnormally wide range of endoperoxides and hydroperoxides similar to artemisinin, many of which have not even been tested for their anti-malarial activity.
It is possible that the pharmaceutical initiatives are focused on products that can be patented. In the meanwhile promising non-patentable solutions are set aside while malaria continues to be the scourge of Sub-Saharan Africa.
The future of artemisinin
Despite much research, artemisinin remains the only known natural product to contain a 1,2,4 -trioxane ring, and Artemisia continues to be its only known source. Although micro propagation of Artemisia can be easily accomplished, it is highly unlikely that this method will yield commercially viable artemisinin.
It appears that wild or field-cultivated Artemisia will be the only viable option for artemisinin in the foreseeable future. Therefore the requirement for increasing acreage under cultivation is of vital importance just as the need for improving the quality of the plant, as well as research for alternate solutions.
A Not-so-unique Approach to Development of Treatment for Malaria
Several issues are related to pure artemisinin or its derivatives as a mono-therapy or as ACT, such as:
- short shelf life
- special storage requirements
- lower intestinal absorption
- dietary considerations unlikely to be met in majority of malaria endemic areas
- unsuitability for high risk populations: children under 5 years and pregnant woman
Besides the above adverse conditions, the primary shortcoming is due to ignoring potential therapeutic value of other endo-peroxides and hydro-peroxides contained in Artemisia in favour of selective extraction of artemisinin.
Following from the above assessment, a further three fundamental criterions were included:
- The treatment should be FULLY EFFECTIVE with rapid resolution of symptoms for the entire population range including those at high levels of risk
- The treatment should be AFFORDABLE & ACCESSIBLE worldwide to all under risk.
- The treatment should have NO SIDE EFFECTS.
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