Resistance to artemisinin in Plasmodium falciparum malaria increases the likelihood of spontaneous resistance to piperaquine, significantly reducing the effectiveness of artemisinin combination therapies, according to Dr. Chanaki Amaratunga and associates.
For the study, P. falciparum malaria patients were enrolled from three Cambodian provinces. In Pursat, where artemisinin resistance is common, 37 of 81 patients had parasite recrudescence; in Preah Vihear, where resistance is emerging, 10 of 63 patients had recrudescence; and in Ratanakiri, where resistance is rare, only 1 of 60 patients had recrudescence.
P. falciparum parasites that were recrudescent were about three times more likely to have kelch13 mutations than were nonrecrudescent parasites. Prevalence of kelch13 mutations were highest in Pursat at 77% during 2012-2013. Recrudescent parasites also had higher piperaquine IC50 values, lower mefloquine IC50 values, and did not have multiple pfmdr1 copies.
Patients with recrudescent parasites were more likely to have detectable piperaquine plasma levels at baseline, compared with patients with nonrecrudescent parasites, but did not differ significantly otherwise.
“Improvements in the treatment of P. falciparum malaria with real-time drug resistance data, identification and treatment of asymptomatic parasite carriers through community treatment campaigns, and prevention of gametocyte transmission to mosquitoes with single low-dose primaquine, are now needed more than ever if malaria elimination is to succeed in Southeast Asia,” the investigators concluded.
Find the full study in the Lancet Infectious Diseases (doi: 10.1016/S1473-3099[15]00487-9).