1921
Volume 75, Issue 6
  • ISSN: 0002-9637
  • E-ISSN: 1476-1645

Abstract

Nowadays, chloroquine-resistant malaria appears in almost all endemic regions. Ferroquine is a derivative of chloroquine and shows good activity and in animal models, but the development of cross-resistance is of concern. We tested susceptibilities of field isolates from Gabon to ferroquine, chloroquine, and artesunate. As expected, chloroquine resistance was present in all parasite isolates (median 50% inhibitory concentration = 113 nmol/L). Ferroquine (1.94 nmol/L) and artesunate (0.96 nmol/L) were highly active, and no significant correlation between any of the three drugs was observed. In contrast to our findings, previous studies showed an association between chloroquine and ferroquine activities. We could reproduce this association by using different initial parasitemias, but analysis of covariance revealed that initial parasitemia and not parasite strain was the critical determinant for the correlation between chloroquine and ferroquine activities. We conclude that ferroquine is highly active in chloroquine-resistant parasites, and we anticipate no enhanced selection for resistance against ferroquine in chloroquine-resistant parasites.

Loading

Article metrics loading...

The graphs shown below represent data from March 2017
/content/journals/10.4269/ajtmh.2006.75.1178
2006-12-01
2019-11-21
Loading full text...

Full text loading...

/deliver/fulltext/14761645/75/6/0751178.html?itemId=/content/journals/10.4269/ajtmh.2006.75.1178&mimeType=html&fmt=ahah

References

  1. Snow RW, Trape JF, Marsh K, 2001. The past, present and future of childhood malaria mortality in Africa. Trends Parasitol 17 : 593–597. [Google Scholar]
  2. Mordmüller B, Graninger W, Kremsner PG, 1998. Malaria therapy in the era of chloroquine resistence. Wien Klin Wochenschr 110 : 321–325. [Google Scholar]
  3. Payne D, 1987. Spread of chloroquine resistance in Plasmodium falciparum. Parasitol Today 3 : 241–246. [Google Scholar]
  4. Paschke R, Paetz C, Mueller T, Schmoll HJ, Mueller H, Sorkau E, Sinn E, 2003. Biomolecules linked to transition metal complexes—new chances for chemotherapy. Curr Med Chem 10 : 2033–2044. [Google Scholar]
  5. Domarle O, Blampain G, Agnaniet H, Nzadiyabi T, Lebibi J, Brocard J, Maciejewski L, Biot C, Georges AJ, Millet P, 1998. In vitro antimalarial activity of a new organometallic analog, ferrocene-chloroquine. Antimicrob Agents Chemother 42 : 540–544. [Google Scholar]
  6. Biot C, Glorian G, Maciejewski LA, Brocard JS, 1997. Synthesis and antimalarial activity in vitro and in vivo of a new ferrocene-chloroquine analogue. J Med Chem 40 : 3715–3718. [Google Scholar]
  7. Atteke C, Ndong JM, Aubouy A, Maciejewski L, Brocard J, Lebibi J, Deloron P, 2003. In vitro susceptibility to a new antimalarial organometallic analogue, ferroquine, of Plasmodium falciparum isolates from the Haut-Ogooue region of Gabon. J Antimicrob Chemother 51 : 1021–1024. [Google Scholar]
  8. Pradines B, Fusai T, Daries W, Laloge V, Rogier C, Millet P, Panconi E, Kombila M, Parzy D, 2001. Ferrocene-chloroquine analogues as antimalarial agents: in vitro activity of ferrochloroquine against 103 Gabonese isolates of Plasmodium falciparum. J Antimicrob Chemother 48 : 179–184. [Google Scholar]
  9. Pradines B, Tall A, Rogier C, Spiegel A, Mosnier J, Marrama L, Fusai T, Millet P, Panconi E, Trape JF, Parzy D, 2002. In vitro activities of ferrochloroquine against 55 Senegalese isolates of Plasmodium falciparum in comparison with those of standard antimalarial drugs. Trop Med Int Health 7 : 265–270. [Google Scholar]
  10. Noedl H, Wernsdorfer WH, Miller RS, Wongsrichanalai C, 2002. Histidine-rich protein II: A novel approach to malaria drug sensitivity testing. Antimicrob Agents Chemother 46 : 1658–1664. [Google Scholar]
  11. Wernsdorfer WH, Payne D, 1991. The dynamics of drug resistance in Plasmodium falciparum. Pharmacol Ther 50 : 95–121. [Google Scholar]
  12. Borrmann S, Binder RK, Adegnika AA, Missinou MA, Issifou S, Ramharter M, Wernsdorfer WH, Kremsner PG, 2002. Reassessment of the resistance of Plasmodium falciparum to chloroquine in Gabon: Implications for the validity of tests in vitro vs. in vivo. Trans R Soc Trop Med Hyg 96 : 660–663. [Google Scholar]
  13. Ramharter M, Wernsdorfer WH, Kremsner PG, 2004. In vitro activity of quinolines against Plasmodium falciparum in Gabon. Acta Trop 90 : 55–60. [Google Scholar]
  14. Gluzman IY, Schlesinger PH, Krogstad DJ, 1987. Inoculum effect with chloroquine and Plasmodium falciparum. Antimicrob Agents Chemother 31 : 32–36. [Google Scholar]
  15. Kremsner PG, Krishna S, 2004. Antimalarial combinations. Lancet 364 : 285–294. [Google Scholar]
  16. World Health Organization, 2005. Malaria Control Today. Geneva: World Health Organization.
  17. Mordmüller B, Kremsner PG, 2006. Malarial parasites vs. anti-malarials: Never-ending rumble in the jungle. Curr Mol Med 6 : 247–251. [Google Scholar]
http://instance.metastore.ingenta.com/content/journals/10.4269/ajtmh.2006.75.1178
Loading
/content/journals/10.4269/ajtmh.2006.75.1178
Loading

Data & Media loading...

  • Received : 12 Oct 2005
  • Accepted : 30 Jun 2006

Most Cited This Month

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error