Chloroquine-susceptible and -resistant Plasmodium falciparum strains survive high chloroquine concentrations by becoming dormant but are eliminated by prolonged exposure

Johan Ursing*, Rasmus Johns, Berit Aydin-Schmidt, Carla Calçada, Poul Erik Kofoed, Najia Karim Ghanchi, Maria Isabel Veiga, Lars Rombo

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

BACKGROUND: Plasmodium falciparum strains that are resistant to standard-dose chloroquine can be treated by higher chloroquine concentrations maintained for a longer time in vivo. OBJECTIVES: To determine the relative importance of chloroquine concentrations versus exposure time for elimination of chloroquine-susceptible and -resistant P. falciparum in vitro. METHODS: Chloroquine-susceptible (3D7) and -resistant (FCR3) strains were exposed in vitro to 1, 2, 4, 8, 16 or 32 times their respective 90% inhibitory chloroquine concentrations for 3, 5, 7 or 14 days and then followed until recrudescence, or not, by 42 days after the end of exposure. RESULTS: Exposure to chloroquine appeared to eliminate susceptible and resistant parasites, leaving small pyknotic apparently dead parasites. Chloroquine-susceptible and -resistant parasites recrudesced after 3 and 5 days of chloroquine exposure. Recrudescence occurred in one out of four 7 day exposure series but not after 14 days exposure. The median time to recrudescence was 13 to 28 days with a range of 8 to 41 days after the end of exposure. Time to recrudescence after the end of exposure increased with duration of exposure for susceptible and resistant strains (P < 0.001). Time to recrudescence did not correlate with concentrations greater than 1× IC90. CONCLUSIONS: Chloroquine-susceptible and -resistant P. falciparum probably become dormant. Elimination of dormant parasites is primarily dependent upon the duration of chloroquine exposure. Exposure to effective drug concentrations for 7 days eliminates most parasites in vitro. The results support in vivo data indicating that elimination of chloroquine-resistant P. falciparum correlates with Day 7 chloroquine concentrations.

Original languageEnglish
JournalThe Journal of antimicrobial chemotherapy
Volume77
Issue number4
Pages (from-to)1005-1011
ISSN0305-7453
DOIs
Publication statusPublished - 31. Mar 2022

Bibliographical note

Publisher Copyright:
© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.

Keywords

  • Antimalarials/pharmacology
  • Chloroquine/pharmacology
  • Drug Resistance
  • Humans
  • Malaria, Falciparum/drug therapy
  • Plasmodium falciparum

Fingerprint

Dive into the research topics of 'Chloroquine-susceptible and -resistant Plasmodium falciparum strains survive high chloroquine concentrations by becoming dormant but are eliminated by prolonged exposure'. Together they form a unique fingerprint.

Cite this