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In vitro activity of antifungal drugs against Plasmodium falciparum field isolates

In vitro Aktivität von antimykotischen Medikamenten gegen Plasmodium falciparum Isolate

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Zusammenfassung

Die zunehmende Resistenz des Malariaerregers Plasmodium falciparum gegenüber den gängigen Medikamenten erfordert anhaltende Anstrengungen, neue Wirkstoffe zu finden. Deshalb untersuchten wir die in vitro Aktivität der antimykotischen Substanzen Clotrimazol, Fluconazol, Ketokonazol, Itraconazol, Flucytosin, Amphotericin B und Caspofungin gegen klinische Isolate von P. falciparum am Albert Schweizer-Krankenhaus in Lambaréné, Gabun. Für Fluconazol, Itraconazol und Caspofungin wurde hier erstmalig die in vitro Aktivität gegen Malariaparasiten festgestellt. Unsere Messergebnisse für Clotrimazol, Fluconazol, Itraconazol und Caspofungin ergaben mediane 50 % effektive Konzentrationen von 3,1 µg/mL, 1,9 µg/mL, 1,1 µg/mL and 1,1 µg/mL. Ketokonazol, Voriconazol, Flucytosin und Amphotericin B zeigten in unserer Studie nur wenig in vitro Aktivität gegen P. falciparum.

Summary

The increasing resistance of the malaria parasite Plasmodium falciparum to currently available drugs necessitates a continuous effort to develop new antimalarial agents. We therefore aimed to assess the in vitro activity of the antifungal drugs clotrimazole, fluconazole, ketoconazole, itraconazole, voriconazole, flucytosine, amphotericin B, and caspofungin against field isolates of P. falciparum from Lambaréné, Gabon. Using the histidin-rich protein 2 (HRP-2) assay we determined the drug susceptibility (EC50, EC90) of 16 field isolates obtained from outpatients attending the Albert Schweitzer Hospital in Lambaréné, Gabon. For fluconazole, itraconazole and caspofungin the in vitro growth inhibition of these drugs is reported for the first time. Our data indicate that clotrimazole, fluconazole, itraconazole and caspofungin show median EC50 values of 3.1µg/mL, 1.9µg/mL, 1.1µg/mL and 1.1µg/mL respectively. Ketoconazole, voriconazole, flucytosine and amphotercin B showed no relevant growth inhibition within the range of drug concentrations used in this study.

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References

  • Bélard S, Kurth F, Winkler S, Graninger W, Ramharter M. Treatment of malaria in Austria: hazardous for patients or physicians? Wien Klin Wochenschr 2009;121(17–18):598

    Article  PubMed  Google Scholar 

  • Kremsner PG, Krishna S. Antimalarial combinations. Lancet 2004;364(9430):285–94

    Article  PubMed  CAS  Google Scholar 

  • Saliba KJ, Kirk K. Clotrimazole inhibits the growth of Plasmodium falciparum in vitro. Trans R Soc Trop Med Hyg 1998;92(6):666–7

    Article  PubMed  CAS  Google Scholar 

  • Tiffert T. Potent antimalarial activity of clotrimazole in in vitro cultures of Plasmodium falciparum. Proc Natl Acad Sci USA 2000;97(1):331–6

    Article  PubMed  CAS  Google Scholar 

  • Bhattacharya A, Mishra LC, Bhasin VK. In vitro activity of artemisinin in combination with clotrimazole or heat-treated amphotericin B against Plasmodium falciparum. Am J Trop Med Hyg 2008;78(5):721–8

    PubMed  CAS  Google Scholar 

  • Gemma S, Kukreja G, Campiani G, Butini S, Bernetti M, Joshi BP, et al. Development of piperazine-tethered heterodimers as potent antimalarials against chloroquine-resistant P. falciparum strains. Synthesis and molecular modeling. Bioorg Med Chem Lett 2007;17(13):3535–9

    Article  PubMed  CAS  Google Scholar 

  • Tripathi R, Awasthi A, Dutta GP. Mefloquine resistance reversal action of ketoconazole – a cytochrome P450 inhibitor, against mefloquine-resistant malaria. Parasitology 2005;130(Pt 5):475–9

    Article  PubMed  CAS  Google Scholar 

  • Lefèvre G, Carpenter P, Souppart C, Schmidli H, McClean M, Stypinski D. Pharmacokinetics and electrocardiographic pharmacodynamics of artemether-lumefantrine (Riamet) with concomitant administration of ketoconazole in healthy subjects. Br J Clin Pharmacol 2002;54(5):485–92

    Article  PubMed  Google Scholar 

  • Pfaller MA, Krogstad DJ. Imidazole and polyene activity against chloroquine-resistant Plasmodium falciparum. J Infect Dis 1981;144(4):372–5

    Article  PubMed  CAS  Google Scholar 

  • Pfaller MA, Segal JJ, Krogstad DJ. Activity of ketoconazole and its deacyl derivative against Plasmodium falciparum and Candida isolates. Antimicrob Agents Chemother 1982;22(5):917–9

    PubMed  CAS  Google Scholar 

  • Mishra LC, Bhattacharya A, Bhasin VK. Antiplasmodial interactions between artemisinin and triclosan or ketoconazole combinations against blood stages of Plasmodium falciparum in vitro. Am J Trop Med Hyg 2007;76(3):497–501

    PubMed  CAS  Google Scholar 

  • Hatabu T, Takada T, Taguchi N, Suzuki M, Sato K, Kano S. Potent plasmodicidal activity of a heat-induced reformulation of deoxycholate-amphotericin B (Fungizone) against Plasmodium falciparum. Antimicrob Agents Chemother 2005;49(2):493–6

    Article  PubMed  CAS  Google Scholar 

  • Wiehart UIM, Rautenbach M, Hoppe HC. Selective lysis of erythrocytes infected with the trophozoite stage of Plasmodium falciparum by polyene macrolide antibiotics. Biochem Pharmacol 2006;71(6):779–90

    Article  PubMed  CAS  Google Scholar 

  • Fromtling RA. Overview of medically important antifungal azole derivatives. Clin Microbiol Rev 1988;1(2):187–217

    PubMed  CAS  Google Scholar 

  • Ramharter M, Oyakhirome S, Klein Klouwenberg P, Adégnika AA, Agnandji ST, Missinou MA, et al. Artesunate-clindamycin versus quinine-clindamycin in the treatment of Plasmodium falciparum malaria: a randomized controlled trial. Clin Infect Dis 2005;40(12):1777–84

    Article  PubMed  CAS  Google Scholar 

  • Ramharter M, Kurth F, Schreier AC, Nemeth J, Glasenapp IV, Bélard S, et al. Fixed-dose pyronaridine-artesunate combination for treatment of uncomplicated falciparum malaria in pediatric patients in Gabon. J Infect Dis 2008;198(6):911–9

    Article  PubMed  CAS  Google Scholar 

  • Ramharter M, Kurth FM, Bélard S, Bouyou-Akotet MK, Mamfoumbi MM, Agnandji ST, et al. Pharmacokinetics of two paediatric artesunate mefloquine drug formulations in the treatment of uncomplicated falciparum malaria in Gabon. J Antimicrob Chemother 2007;60(5):1091–6

    Article  PubMed  CAS  Google Scholar 

  • Ramharter M, Adegnika AA, Agnandji ST, Matsiegui PB, Grobusch MP, Winkler S, et al. History and perspectives of medical research at the Albert Schweitzer Hospital in Lambaréné, Gabon. Wien Klin Wochenschr 2007;119(19–20 Suppl. 3):8–12

    Article  PubMed  Google Scholar 

  • Ramharter M, Burkhardt D, Nemeth J, Adegnika AA, Kremsner PG. In vitro activity of artemisone compared with artesunate against Plasmodium falciparum. Am J Trop Med Hyg 2006;75(4):637–9

    PubMed  CAS  Google Scholar 

  • Kurth F, Pongratz P, Bélard S, Mordmüller B, Kremsner PG, Ramharter M. In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays. Malar J 2009;8:79

    Article  PubMed  Google Scholar 

  • Ramharter M, Wernsdorfer WH, Kremsner PG. In vitro activity of quinolines against Plasmodium falciparum in Gabon. Acta Trop 2004;90(1):55–60

    Article  PubMed  CAS  Google Scholar 

  • Winkler S, Brandts C, Wernsdorfer WH, Graninger W, Bienzle U, Kremsner PG. Drug sensitivity of Plasmodium falciparum in Gabon. Activity correlations between various antimalarials. Trop Med Parasitol 1994;45(3):214–8

    PubMed  CAS  Google Scholar 

  • Oyakhirome S, Issifou S, Pongratz P, Barondi F, Ramharter M, Kun JF, et al. Randomized controlled trial of fosmidomycin-clindamycin versus sulfadoxine-pyrimethamine in the treatment of Plasmodium falciparum malaria. Antimicrob Agents Chemother 2007;51(5):1869–71

    Article  PubMed  CAS  Google Scholar 

  • Planche T, Krishna S, Kombila M, Engel K, Faucher JF, Ngou-Milama E, et al. Comparison of methods for the rapid laboratory assessment of children with malaria. Am J Trop Med Hyg [Comparative Study] 2001;65(5):599–602

    CAS  Google Scholar 

  • Noedl H, Wernsdorfer WH, Miller RS, Wongsrichanalai C. Histidine-rich protein II: a novel approach to malaria drug sensitivity testing. Antimicrob Agents Chemother 2002;46(6):1658–64

    Article  PubMed  CAS  Google Scholar 

  • Ritz C, Streibig JC. Bioassay Analysis using R. J Stat Softw 2005;12(5):1–18

    Google Scholar 

  • Team RDC. R: A Language and Environment for Statistical Computing. R Foundation for statistical computing, Vienna, Austria 2010:1–18

  • Chong CR, Sullivan DJ. Inhibition of heme crystal growth by antimalarials and other compounds: implications for drug discovery. Biochem Pharmacol 2003;66(11):2201–12

    Article  PubMed  CAS  Google Scholar 

  • Osisanya JO, Gould S, Warhurst DC. Elimination of yeast contamination from malaria cultures using 5-fluorocytosine. Ann Trop Med Parasitol 1980;74(5):559

    PubMed  CAS  Google Scholar 

  • Mäser P, Grether-Bühler Y, Kaminsky R, Brun R. An anti-contamination cocktail for the in vitro isolation and cultivation of parasitic protozoa. Parasitol Res 2002;88(2):172–4

    Article  PubMed  Google Scholar 

  • Roth EF, McKitrick JC, Herz F. The use of 5-fluorocytosine and ketoconazole in the culture of the erythrocytic stages of Plasmodium falciparum and some tumor cell lines. Experientia 1989;45(5):478–80

    Article  PubMed  CAS  Google Scholar 

  • Fluconazole – drug information. Pfizer 2010;25:1–33

  • SPORANOX – drug information. JANSSEN-CILAG 2008;25:1–14

    Google Scholar 

Download references

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Authors and Affiliations

  1. Medical Research Unit, Albert Schweitzer Hospital, Lambaréné, Gabon

    Peter Pongratz, Florian Kurth, Ghyslain Mombo Ngoma, Arti Basra & Michael Ramharter

  2. Institute for Tropical Medicine, University of Tübingen, Tübingen, Germany

    Peter Pongratz, Florian Kurth, Ghyslain Mombo Ngoma, Arti Basra & Michael Ramharter

  3. Department of Medicine IV with Infectious Diseases and Tropical Medicine, Kaiser Franz Josef Hospital, Vienna, Austria

    Peter Pongratz

  4. Department of Neonatology and Paediatric Intensive Care, University Hospital Carl Gustav Carus, Dresden, Germany

    Florian Kurth

  5. Département de Parasitologie-Mycologie, Faculté de Médecine, Université des Sciences de la Santé, Libreville, Gabon

    Ghyslain Mombo Ngoma

  6. Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna, Austria

    Michael Ramharter

Authors
  1. Peter Pongratz
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  2. Florian Kurth
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  3. Ghyslain Mombo Ngoma
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  4. Arti Basra
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  5. Michael Ramharter
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Correspondence to Michael Ramharter.

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Pongratz, P., Kurth, F., Ngoma, G. et al. In vitro activity of antifungal drugs against Plasmodium falciparum field isolates. Wien Klin Wochenschr 123 (Suppl 1), 26–30 (2011). https://doi.org/10.1007/s00508-011-0021-0

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  • DOI: https://doi.org/10.1007/s00508-011-0021-0

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