Constant Tchandema and Pierre Lutgen
Potassium, the most abundant cation in the human body, regulates intracellular enzyme function and neuromuscular tissue excitability. Serum potassium is normally maintained within thenarrow range of 3.5 to 5.5 mEq/L.
Hypokalemia (plasma potassium concentrations below normal range) has been recognized over recent years to be very frequent in malaria and not only in severe malaria. In a study of 1415 patients in Thailand 44% of the patients infected by Plasmodium falciparum and Plasmodium vivax were hypokalemic (V Thanachartwet et al., Trop Doct 2008, 38, 155-157)
Similar percentages were found in India (H Jasmin et al., J Clin Diagnostic Res, 2012, 6 678-681). And in Nigeria (J Ebele et al., Int J Trop Med, 2010, 5, 46-49). And in Kenya (K Maitland et al., Pediatric Crit Care Med, 2004 Jan 5, 81-85). Potassium deperdition is enhanced by vomiting and diarrhoea.
From the existing literature, it is clear that hypokalemia is now a well documented phenomena in malaria patients and may have been highly underestimated. It also has been noticed in chikungunya (Rampal et al., J Assoc Physicians India, 2012, 56:598) and in dengue ( S Jha et al., Neurol India, 2010 58, 592-594) often leading to hypokalemic paralysis.
During malaria infection the cytosol of infected erythrocytes is poor in potasium and rich in sodium while in the parasite this relation is inversed (H Ginsberg et al., Z Parisitenk, 1986, 72, 185-199). The parasite plasma membrane potential changes with extracellular potassium concentration : it depolarizes at higher concentrations and hyperpolarizes a low concentrations (R Allen et al., J Biol Chem, 2004, 279, 11264-11272). In a medium with high potassium concentration the invasion of erythrocytes by merozoites is inhibited (W Trager et al., J Protozool 1984, 31, 562-7). Dietary potassium also reduces hypertension and acts as antioxidant by reducing ROS production (K Ando et al, Curr Vasc Pharmacol. 2010 8, 59-63)
More disturbing is the fact that artemisinin and its derivatives can potentially cause hypokalemia. They have been known to affect voltage-gated potassium currents, and their administration in patients of hypokalemia has been known to prolong the QT-interval. (Hara et al.J Vet Med Sci 69 697-702, 2007). Artemether significantly increases the potassium concentration in urine (R Akomalofe et al., Afric J of Biotechnology, 2011, 10, 4226-4233). The same diuretic effect has been noticed for artesunate (Indian J Pharmacol 2011, 43, 472-473). In fact the severe diuretic effect of intravenous injection of artesunate is known since 2002 ( A Seguro et al., Am J Trop Med Hyg, 67, 2002, 473-4749). The use of artesunate recommended by WHO for intravenous injections is thus a double-edged weapon : the increased urinary loss of water and electrolytes can worsen renal failure.
Low plasma potassium can of course be corrected by oral or intravenous injection. But there appears to be another treatment which merits more research. Among all the medicinal plants those of the Artemisia family have the highest potassium content. The first to report this were E Brisibe, P de Magalhaes, J Ferreira et al, (Food Chemistry, 2008, 115, 1240-46). Potassium concentrations in Artemisia annua are 10 to 100 times higher than those of other minerals. A study in Morocco measured the potassium content of four medicinal plants. For Artemisia herba alba it is the highest (R Imelouane et al., J Mater Envir Si 2011, 2, 104-11). A more complete study in Pakistan, comparing 10 medicinal plants finds that potassium content in Artemisia annua is the highest (I Hussain et al., World Appl Sci J., 2011, 12, 1464-1468). A Tunesian study finds higher concentrations of potassium in Artemisia herba alba and A campestris than in Rosmarinus or Thymus. An extensive study at the University of Islamabad analyzed the elemental content in 17 indigenous species of Artemisia that are commonly used against ailments in Pakistan. (A. scoparia, A. absinthium, A. indica, A. santolinifolia, A. maritime, A. vulgaris, A. japonica, A. nilagirica, A. herba-alba, A. annua, A. brevifolia, A. moorcroftiana, A. dracunculus, A. roxburghiana and A. dubia. In all potassium concentrations are high in a fairly narrow range around 16 000 ppm and most of them are known to have antimalarial properties (M Ashraf et al., J Med Plant Res 2010, 4, 2256-63).In our own research work with the University of Dakar (T Alassane et al., Afr J Biotech, 2013, 12 4179-86) we had found that the concentrations of potasssium in Artemisia annua from different origins was twice as high as in Camelia sinensis.
Many research efforts on Artemisia probably have missed this point because they work with extracts obtained in organic solvents. Only aqueous infusions and powdered leaves in capsules or tablets will deliver this essential constituant to malaria patients. The well known therapeuticac efficacy of all genotypes from the large Artemisia family against many diseases mght to a large extent be related to their high concentration in potassium. Hypokalemia (plasma potassium concentrations below normal range) have been recognized over recent years to be very frequent in malaria and not only in severe malaria. In a study of 1415 patients in Thailand 44% of the patients infected by Plasmodium falciparum and Plasmodium vivax were hypokalemic (V Thanachartwet et al., Trop Doct 2008, 38, 155-157) Similar percentages were found in India (H Jasmin et al., J Clin Diagnostic Res, 2012, 6 678-681). And in Nigeria (J Ebele et al., Int J Trop Med, 2010, 5, 46-49). And in Kenya (K Maitland et al., Pediatric Crit Care Med, 2004 Jan 5, 81-85). Potassium deperdition is enhanced by vomiting and diarrhoea.