The study was conducted by a team of researchers from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, working with French and Cambodian colleagues in Cambodia. They set out to test whether parasites could be identified as coming from patients with slow-clearing or fast-clearing infections using a novel in vitro ring-stage survival assay (RSA), investigate the in vitro response to dihydroartemisinin (DHA, the active metabolite of artemisinins), and assess whether an ex vivo RSA could detect artemisinin-resistant P. falciparum infections.
Their findings demonstrated a significant difference between the in vitro survival rate of culture-adapted parasites from slow-clearing and fast-clearing infections when assays were performed on very young (0-3 hours old) ring stage parasites. Crucially, the assays deliver an assessment within 72 hours, providing a viable laboratory platform for the molecular characterisation of artemisinin resistance. The ex vivo RSA showed that survival rates significantly correlated with in vivo parasite clearance half-lives. The assays can be easily implemented in endemic countries where surveillance for artemisinin resistance is needed.
Commenting on the findings, Carol Hopkins Sibley from the WorldWide Antimalarial Resistance Network (WWARN) says, “These assays will allow the rapid validation of candidate molecular markers by directly testing the correlation of proposed markers with the output from their survival assay. The in vitro test will also provide a platform for understanding the mechanism of the reduced artemisinin response. With these simple methods in place, rapid tracking of the geographical and temporal changes in artemisinin resistance will be feasible in many sites. This far more comprehensive information will allow policy makers to design effective responses to the threat of artemisinin failure, and prolong the useful therapeutic life of ACTs.”
Publications
Witkowski et al. Novel phenotypic assays for the detection of artemisinin-resistant Plasmodium falciparum malaria in Cambodia: in-vitro and ex-vivo drug-response studies. Lancet Infect Dis. 2013 Dec;13(12):1043-9. doi: 10.1016/S1473-3099(13)70252-4. Epub 2013 Sep 11.
Carol Hopkins Sibley’s commentary was published in The Lancet Infectious Diseases:
Sibley. Tracking artemisinin resistance in Plasmodium falciparum. Lancet Infect Dis. 2013 Dec;13(12):999-1000. doi: 10.1016/S1473-3099(13)70260-3. Epub 2013 Sep 11.
