Aspirin and artemisinin, beware?

The interference of analgesics with ACTs (Coartem, Corsucam…) has barely been studied in clinical trials.
Aspirin (acetylsalicylic acid) is sold over the counter in Africa and appears to be the first line treatment when children or adults have fever. Chronic salicylate poisoning by overdosis is common. Many children brought to a hospital in Africa have a high load of salicylic acid in their blood. Paracetamol is also of common use.
Platelets kill intraerytrocytic malarial parasites and mediate survival to infection (B J Mc Morran et al Science, 2009, 323:797). Experiments in mice showed that animals genetically deficient in platelets were significantly more susceptible to death from Plasmodium chabaudi infection than were isogenic non–platelet-deficient mice. Similarly, aspirin-treated mice were more susceptible to death from P. chabaudi infection than were placebo-treated animals. This effect has been confirmed by a very recent paper (CN Morrell et al., Blood, 2014, Feb28).

Thrombocytopenia, low platelet count, is common in malaria. (Shuaib Ansari et al.,J Ayub Med Coll Abootabad 2009;21-2). The same author refers to 5 other studies describing the same effect. It is more frequent than anaemia and can be used as a predictor of severity of malaria. This is an important finding, because blood platelets are parasitocidal (McMorran BJ et al., Science, 22012 338, 1348-51). They bind to parasitized cells and kill the Plasmodium falciparum parasite within.
An extensive study was undertaken in India (P Sentikumaar et al., Europ J Exp Biology, 2013, 3, 199-195) to compare certain serological parameters. Hb content, total blood cell count, WBC differential count, platelet count etc between normal persons and malaria affected patients. Mainly the platelets count and serum potassium levels in malaria infected blood were significantly different. A very recent paper from Thailand (M Kotepui et al., Malaria Journal 2014, 13:218) studied the effect of malaria on haematological parameters for a large sample size. The most common complication is thrombocytopenia (platelet counts <150 000/microliter).
Aspirin, like other platelet antagonists abrogate the antiparasitic activity of human platelets. Salicylic acid decreases the size of platelets (LF Fajardo Am J Clin Path 1975, 63-4, 554-8). The Finnish Medical Society guideline on thrombocytopenia states: “Many drugs cause thrombocytopenia relatively frequently… Non-steroidal anti-inflammatory drugs, especially acetylsalicylic acid frequently impair platelet function and bring about a bleeding tendency. This tendency is disproportionately strong among thrombocytopenic patients.”
Paracetamol vs placebo in treatment of non-severe malaria was studied in Guinea Bissau. It showed that time to parasite clearance is significantly longer in children treated with paracetamol and recrudescence was higher ( P E Kofoed et al, Malaria Journal, 2011, 10:148).
This confirms a previous study from Gabon. TNF which has an important antiparasitic role in malaria was reduced in the paracetamol group (CH Brandts et al., Lancet 1997, 350, 704-9). Paracetamol by itself may lead to thrombocytopenia (JR Thornton et al., British Medical Association 1990, ISSN 0017-5749). The cost of paracetamol for poor families is substantial. No evidence shows that it is beneficial in malaria.
No papers could be found studying the effect of artemisinin or derivatives on platelet count or inflammation. Platelets control many inflammatory processes. Only the study made at the University of Louvain (P de Magalhaes et al., Food Chemistry, 2012) has shown that the Artemisia annua from Luxembourg, poor in artemisinin, reduces IL-6 and IL-8). A thesis from the Western Cape University (Y Kriel) on Artemisia afra confirms these anti-inflammatory findings and shows that sesquiterpene lactones inhibit platelet aggregation. This effect of Artemisia decoctions could also be related to the presence of scopoletin which is known to inhibit platelet aggregation in the use of the Noni fruit.

The hematological effects of a few other herbs have been studied. The methanolic extract of Anthacleista grandiflora (Odeghe Othuke B et al., Internet J of Applied Science and Technology 2:5,2012, 58-65) significantly increased the number of platelets and white blood cells in malaria infected mice. The aqueous extract of Euphorbia hirta also has a platelet increasing effect in thrombocytopenic rats ( JC Apostolet al., IJPFR 2012 2, 1-11). And reduces clotting time and mean bleeding time. Aqueous extracts of Carica Papaya ( Swati Patil et al., J Pharmacognosy and Phytochem, 1, 5, 2013, 57-60) and Ocimum gratissimum (OE Ofem et al., 2,-1, 2012, 38-42) also increase the platelet count.
All these studies are fairly recent and open a new research field in the fight against malaria

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