Dried Whole Plant Artemisia annua as an Antimalarial Therapy

Mostafa A Elfawal,Stephen M Rich,Melissa J Towler,Pamela J Weathers,Douglas Golenbock,Nicholas G Reich,Georges Snounou

doi:10.1371/journal.pone.0052746

Abstract

Drugs are primary weapons for reducing malaria in human populations. However emergence of resistant parasites has repeatedly curtailed the lifespan of each drug that is developed and deployed. Currently the most effective anti-malarial is artemisinin, which is extracted from the leaves of Artemisia annua. Due to poor pharmacokinetic properties and prudent efforts to curtail resistance to monotherapies, artemisinin is prescribed only in combination with other anti-malarials composing an Artemisinin Combination Therapy (ACT). Low yield in the plant, and the added cost of secondary anti-malarials in the ACT, make artemisinin costly for the developing world. As an alternative, we compared the efficacy of oral delivery of the dried leaves of whole plant (WP) A. annua to a comparable dose of pure artemisinin in a rodent malaria model (Plasmodium chabaudi). We found that a single dose of WP (containing 24 mg/kg artemisinin) reduces parasitemia more effectively than a comparable dose of purified drug. This increased efficacy may result from a documented 40-fold increase in the bioavailability of artemisinin in the blood of mice fed the whole plant, in comparison to those administered synthetic drug. Synergistic benefits may derive from the presence of other anti-malarial compounds in A. annua. If shown to be clinically efficacious, well-tolerated, and compatible with the public health imperative of forestalling evolution of drug resistance, inexpensive, locally grown and processed A. annua might prove to be an effective addition to the global effort to reduce malaria morbidity and mortality.

Highlights

Malaria is among the most prevalent infectious diseases in the developing world, imposing a vast burden of mortality and perpetuating cycles of poverty
We found conclusive evidence that orally ingested, powdered dried leaves of whole plant A. annua kills malaria parasites more effectively than a comparable dose of pure drug
The suppression of parasitemia was significant in the three treatment groups after a single dose treatment, low dose WPLO resulted in faster recrudescence than either WPHI or ANHI (Figure 3), suggesting that multiple treatments at this dose would be necessary for a curative effect

Summary

Introduction

Malaria is among the most prevalent infectious diseases in the developing world, imposing a vast burden of mortality and perpetuating cycles of poverty. In 2009, the World Health Organization (WHO) estimated that 225 million cases of malaria occurred, with .780,000 deaths [1]. In spite of recent advances in our understanding of this parasite, efforts to prevent transmission have remained largely unchanged for over a century. Though malaria vaccines hold future promise, vector control and chemotherapy remain the primary weapons for reducing the burden of disease in individuals and populations. Artemisinin, in the form of Artemisinin-based Combination Therapy (ACT), is currently the best treatment option against those malaria parasites that have evolved resistance to drugs such as chloroquine [2]. Artemisinin (AN) and its derivatives have been shown to affect a number of viruses, a variety of human cancer cell lines [3,4], several neglected tropical parasitic diseases including schistosomiasis [5], leishmaniasis [6,7], New- and Old-World trypanosomiases [8], and some livestock diseases [9]

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Results

Conclusion