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Immunosuppression, ACTs and malaria resistance

July 16, 2013 - 06:39 -- Pierre Lutgen

A paradigm change

It was always believed that resistance is provoked by antimalarial drugs; they cause plasmodium to evolve and become tougher. Consequently it was important to kill the last parasite to avoid recrudescence. But Andrew Read (Conference Evolution, Utah, June 21-25 2013) finds that in a weakened immune system parasites multiply to extremely high densities. This pool of parasites contains a larger number of mutants, upping the chances of some having greater virulence potential.

It is common knowledge that anything which leads to a depressed immune system (diarrhea, repeated malaria episodes, pregnancy, HIV, malnutrition, immune suppressing drugs…) will lead to a higher plasmodium load in the infected person.

The easiest way, although incomplete, to assess immunosuppression is the CD4 count. Several recent papers (JK Kirinyet et al., Intern.J. Adv Res. 2013, 1:3, 140-149, SN Shah et al., HIV infection and Antimalarial Treatment, 2006, 194, 1519-28) have shown that in patients with low CD4 count it was impossible to lower the high plasmodium load to zero with antimalarial treatment, even with the strongest drug known: dihydroartemisinin (YM Tatfeng et al., J Vect Borne Dis , 44. June 2007, 111-115). After a malaria attack the CD4 count remains low for several months in persons which had a low CD4 baseline at the moment of the infection.

Boosting the immune system becomes eventually more important in the fight against malaria than reducing the parasite count with a strong antimalarial drug.

Artemisinin and its chemical derivatives, as well as amodiaquine and mefloquine are immunodepressive. As ACTs they may give spectacular results in the short run, but be detrimental in the long run for malaria eradication. PCR at day 28 is a vain effort if it is not done in parallel with a CD4 count.

Artemisia annua tea however contains many substances stimulating the immune system, like polyphenols, scopoletin, polysaccharides or essential oils. These have a prophylactic effect against malaria as shown by PE Ogwang in Uganda (Trop J Pharm Res 2012, 13:3, 445-53). And Fr van der Kooy even found that Artemisia afra not containing any artemisinin had the strongest anti-HIV activity ( A Lubbe et al., J Ethnopharmacology, 2012, 141:3, 854-859).