Poster Presentation First Malaria World Congress 2018

Chloroquine uptake and efflux studies in clinical Plasmodium falciparum and P. vivax field isolates reveal important differences between species (#336)

Grennady Wirjanata 1 , Leo Leonardo 2 , Irene Handayuni 1 , Pak Prayoga 2 , Dwi Apriyanti 3 , Ruland Wandosa 2 , Basbak Gobay 2 , Enny Kenangalem 2 , Jeanne R Poespoprodjo 2 4 , Rintis Noviyanti 3 , Niranjan K Namelikonda 5 , Roman Manetsch 5 , Dennis E Kyle 6 , Qin Cheng 7 , Ric N Price 1 8 , Jutta Marfurt 1
  1. Global and Tropical Health Division, Menzies School of Health Research, Charles Darwin University, Darwin, NT 0811, Australia
  2. Papuan Health and Community Development Foundation (PHCDF), Timika, Papua, Indonesia
  3. Eijkman Institute for Molecular Biology, Jakarta, Indonesia
  4. Department of Paediatrics, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia
  5. Department of Chemistry and Chemical Biology and Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA
  6. Center for Tropical & Emerging Global Diseases, University of Georgia, Athens, GA, USA
  7. Drug Resistance and Diagnosis, Australian Army Malaria Institute, Enoggera, QLD, Australia
  8. Centre for Tropical Medicine and Global Health, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK

Chloroquine (CQ) resistance is associated with decreased accumulation of CQ in the parasite digestive vacuole of P. falciparum, but its mechanism in P. vivax is unknown.

CQ uptake and efflux was quantified in ring and trophozoite stages of P. falciparum and P. vivax field isolates, and the effect of CQ resistance reversal agents (CQRRA) on CQ uptake and efflux was assessed in both species.

CQ resistance in P. falciparum was associated with reduced CQ accumulation, but not an increase in CQ efflux. In contrast, CQ accumulation occurred faster and CQ efflux slower in P. vivax, although CQ uptake was not associated with CQ susceptibility in P. vivax. CQ uptake was modified by CQRRAs in P. falciparum, but not in P. vivax. The results add to a growing body of evidence that the mechanism of CQ resistance and possibly the mode of CQ action are different between these two species.