title: In vitro activity of immunosuppressive drugs against Plasmodium falciparum.
abstract: BACKGROUND
  Solid organ transplant recipients are particularly vulnerable for infectious diseases due to prolonged immunosuppressive treatment. Residents of endemic regions and travellers may be exposed to malaria and may, therefore, require prolonged antimalarial chemoprophylaxis. The hypothesis of this study was that certain immunosuppressive drugs may exert clinically relevant anti-malarial activity. It was therefore designed to assess the intrinsic anti-malarial activity of everolimus, mycophenolic acid, and rapamycin against Plasmodium falciparum in an in vitro model.
  
  
  METHODS
  Three laboratory adapted clones of P. falciparum and two isolates were used to assess the potential of mycophenolic acid, rapamycin and everolimus to inhibit in vitro growth of P. falciparum. The standard histidine rich protein 2 assay was employed and inhibitory drug concentrations (IC) were computed by non-linear regression analysis.
  
  
  RESULTS
  All drugs were associated with complete inhibition of P. falciparum growth in in vitro assays. Mycophenolic acid demonstrated IC(50) and IC(90) values of 5.4 μmol/L and 15.3 μmol/L. Rapamycin inhibited P. falciparum growth at 7.2 μmol/L (IC(50)) and 12.5 μmol/L (IC(90)), respectively. Finally, everolimus displayed IC(50) and IC(90) values of 6.2 μmol/L and 11.5 μmol/L. There was no difference in in vitro activity against chloroquine sensitive or chloroquine resistant parasites.
  
  
  CONCLUSIONS
  All immunosuppressive drugs evaluated in this in vitro study demonstrated activity against P. falciparum. Inhibitory concentrations of mycophenolic acid are within clinically achievable plasma concentrations when used in solid organ transplant recipients. Further in vivo evaluation of mycophenolic acid either alone or in combination regimens may prove promising for the concomitant prevention of P. falciparum in solid organ transplant recipients living or travelling in malaria endemic regions.
authors.forename: Luzia
authors.initials: L
authors.lastname: Veletzky
authors.forename: Khalid
authors.initials: K
authors.lastname: Rehman
authors.forename: Tilman
authors.initials: T
authors.lastname: Lingscheid
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Poeppl
authors.forename: Felix
authors.initials: F
authors.lastname: Loetsch
authors.forename: Heinz
authors.initials: H
authors.lastname: Burgmann
authors.affiliation: Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria. michael.ramharter@medizin.uni-tuebingen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Ramharter
mesh_terms: D000962:Antimalarials / Q000494:pharmacology*; D058492:Drug Repositioning; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D009173:Mycophenolic Acid / Q000494:pharmacology; D021261:Parasitic Sensitivity Tests; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D020123:Sirolimus / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000962:Antimalarials; D007166:Immunosuppressive Agents; D000068338:Everolimus; D009173:Mycophenolic Acid; D020123:Sirolimus