New assay identifies slow-clearing, artemisinin-resistant P. falciparum malaria
New in vitro and ex vivo ring-stage survival assays can identify slow-clearing Plasmodium falciparum parasites in patients with malaria and determine whether they are artemisinin-resistant, according to finding in a report published in The Lancet Infectious Diseases.
P. falciparum is the most deadly malaria parasite, killing up to 1.2 million people each year. Previously, slow- and fast-clearing parasites were only differentiated by continuously counting the number of parasites in the blood during a 3-day monitoring period after treatment.
“We were clearly able to see the difference in the clinical response to artemisinin between people infected with parasites that were drug-resistant or drug-susceptible in vitro,” study researcher Didier Menard, PhD, of the Institut Pasteur du Cambodge in Phnom Penh, Cambodia, said in a press release. “Our observations confirm that artemisinin resistance is associated with the very early stages of parasite development in the blood.”
Researchers from the Cambodian National Malaria Center, the Institut Pasteur and the NIH tested an in vitro ring-stage survival assay to distinguish between fast- and slow-clearing parasites and the ex vivo ring-stage survival assay to detect artemisinin-resistant parasites.
Results from the ex vivo assay indicated that parasite survival rate was associated with clearance half-time. Researchers also were able to identify novel slow-clearing malaria infections in Preah Vihear and Ratanakiri, Cambodia.
These two assays can help to understand artemisinin resistance and eventually develop new antimalaria drugs while monitoring the spread of P. falciparum, according to the press release.
Using parasites from Pursat, Cambodia, the researchers also tested the in vitro response of early ring, late ring and trophozoites parasite blood stages to dihydroartemisinin — the artemisinin active metabolite. They found that more slow-clearing parasites from early rings (0 to 3 hours after invasion) survived dihydroartemisinin than fast-clearing parasites.
“In the race against time to stop the spread of artemisinin-resistant malaria, new diagnostic tools are urgently needed to identify and track resistant parasites,” Menard said in the press release. “These simple in vitro and ex vivo ring-stage survival assays can clearly identify artemisinin-resistant, slow-clearing Plasmodium falciparum parasites in people with malaria and can deliver results much faster than the current clinical approach used to monitor response to drugs in patients.”