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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
In vitro activity of immunosuppressive drugs against Plasmodium falciparum
Malaria Journal, Volume 13, No. 1, Article 476, Year 2014
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Description
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 IC50 and IC90 values of 5.4 μmol/L and 15.3 μmol/L. Rapamycin inhibited P. falciparum growth at 7.2 μmol/L (IC50) and 12.5 μmol/L (IC90), respectively. Finally, everolimus displayed IC50 and IC90 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. © 2014 Veletzky et al.
Authors & Co-Authors
Veletzky, Luzia
Austria, Vienna
Medizinische Universität Wien
Rehman, Khalid
Austria, Vienna
Medizinische Universität Wien
Poeppl, Wolfgang
Austria, Vienna
Medizinische Universität Wien
Lötsch, Felix
Austria, Vienna
Medizinische Universität Wien
Burgmann, H.
Austria, Vienna
Medizinische Universität Wien
Ramharter, Michael
Austria, Vienna
Medizinische Universität Wien
Germany, Tubingen
Eberhard Karls Universität Tübingen
Statistics
Citations: 9
Authors: 6
Affiliations: 3
Identifiers
Doi:
10.1186/1475-2875-13-476
ISSN:
14752875
Research Areas
Infectious Diseases
Study Approach
Quantitative