Poster Presentation First Malaria World Congress 2018

Characterisation of artemisinin-induced dormancy using a controlled human malaria infection (#473)

Chris L Peatey 1 , Maria Rebelo 2 , Karryn Gresty 1 , Karen Anderson 1 , Rebecca Pawliw 2 , Fiona Amante 2 , Nanhua Chen 1 , James McCarthy 2 , Qin Cheng 1
  1. Australian Defence Force Malaria and Infectious Disease Institute, Enoggera, QLD, Australia
  2. Clinical Tropical Medicine, QIMR-Berghofer, Brisbane, Queensland, Australia

Artemisinin induced dormancy is a plausible underlying mechanism for frequent failures of mono-therapy reported in the field, and is linked with artemisinin resistance in Plasmodium falciparum.  The biological characterization and recovery dynamics of dormant parasites have been well characterised in vitro but there remains conjecture whether this phenomenon occurs in vivo. A controlled human malaria infection model (CHMI) was employed to determine if P. falciparum parasites display dormancy in vivo and to phenotypically and genotypically characterise the dormant and recovered parasites.

Three healthy volunteers were infected with 3D7 and treated initially with a single oral dose of artesunate (~2mg/kg). Parasitemia declined rapidly following treatment, then remained at a stable low level between days 2-6, followed by recrudescence, a pattern of parasite dynamics that is consistent with dormancy and recovery.  Blood samples taken from each subject prior to treatment and 72 hrs after treatment were used to examine morphology as well as to regrow parasites in standard cultures. These parasites grown out ex vivo were then characterised to determine if dormant parasites were present and would recover.

The ex vivo 3D7 cultures recovered to 5% parasitemia before 20 days post-artesunate. This regrowth was consistent with previous in vitro dormancy recovery phenotypes.  Giemsa stained blood slides taken from subjects, 72hrs post treatment revealed parasites with morphology typical of dormancy (blue cytoplasm and condensed red chromatin). The duration of dormancy and the growth rates of the ex vivo recovered parasites as compared to pre-treatment parasites will be presented. Molecular markers of dormancy and drug resistance were also examined for the recovered parasites. This data suggest that the artemisinin induced dormancy phenomenon exists in vivo and plays a role in recrudescence.