Azathioprine favourably influences the course of malaria. Academic Article uri icon


  • BACKGROUND: Azathioprine triggers suicidal erythrocyte death or eryptosis, characterized by cell shrinkage and exposure of phosphatidylserine at the erythrocyte surface. Eryptosis may accelerate the clearance of Plasmodium-infected erythrocytes. The present study thus explored whether azathioprine influences eryptosis of Plasmodium-infected erythrocytes, development of parasitaemia and thus the course of malaria. METHODS: Human erythrocytes were infected in vitro with Plasmodium falciparum (P. falciparum) (strain BinH) in the absence and presence of azathioprine (0.001 - 10 microM), parasitaemia determined utilizing Syto16, phosphatidylserine exposure estimated from annexin V-binding and cell volume from forward scatter in FACS analysis. Mice were infected with Plasmodium berghei (P. berghei) ANKA by injecting parasitized murine erythrocytes (1 x 106) intraperitoneally. Where indicated azathioprine (5 mg/kg b.w.) was administered subcutaneously from the eighth day of infection. RESULTS: In vitro infection of human erythrocytes with P. falciparum increased annexin V-binding and initially decreased forward scatter, effects significantly augmented by azathioprine. At higher concentrations azathioprine significantly decreased intraerythrocytic DNA/RNA content (>or= 1 microM) and in vitro parasitaemia (>or= 1 microM). Administration of azathioprine significantly decreased the parasitaemia of circulating erythrocytes and increased the survival of P. berghei-infected mice (from 0% to 77% 22 days after infection). CONCLUSION: Azathioprine inhibits intraerythrocytic growth of P. falciparum, enhances suicidal death of infected erythrocytes, decreases parasitaemia and fosters host survival during malaria.

published proceedings

  • Malar J

author list (cited authors)

  • Bobbala, D., Koka, S., Geiger, C., Fller, M., Huber, S. M., & Lang, F.

citation count

  • 13

complete list of authors

  • Bobbala, Diwakar||Koka, Saisudha||Geiger, Corinna||Föller, Michael||Huber, Stephan M||Lang, Florian

publication date

  • May 2009