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P. vivax antimalarial drug resistance likely overestimated, researchers say
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Based on data collected during a study in Cambodia, researchers said antimalarial drug resistance in Plasmodium vivax parasites is likely overestimated and presents less of a problem than the relapse of dormant parasites.
Writing in The Journal of Infectious Diseases, Jean Popovici, PhD, researcher in the Malaria Molecular Epidemiology Unit at the Pasteur Institute in Cambodia, and colleagues noted that P. vivax malaria is the most widespread human malaria parasite in the world and is often reported to be resistant to chloroquine (CQ), including in Cambodia, where high rates of CQ treatment failure have been reported and where artemisinin combination therapy is now recommended as first-line treatment for uncomplicated cases. They said that scientists’ understanding of vivax malaria is largely derived from studies about P. falciparum.
According to Popovici and colleagues, “rigorous clinical assessment of drug efficacy in vivax malaria is complicated by our inability to reliably classify patient outcomes and, specifically, to distinguish recrudescence (real treatment failure) from reinfections (from new infectious mosquito bites) or relapses (reactivation of dormant parasites from the liver) in patients experiencing recurrence.”
“Here, we describe a clinical drug efficacy study designed to control, as best as possible, for reinfections and relapses, and to rigorously assess CQ clinical efficacy,” they wrote.
To better assess CQ efficacy for P. vivax malaria, Popovici and colleagues enrolled 40 patients with P. vivax malaria in a prospective, open-label drug efficacy study, treating them with 30 mg/kg of CQ and following them for 2 months. They performed frequent clinical examinations and collected capillary blood samples for microscopy, molecule parasite detection and genotyping, and drug concentration measurements. Half of the patients were relocated to transmission-free areas to prevent reinfections.
By day 3, P. vivax parasites were eliminated in all 40 patients after standard CQ treatment. When Popovici and colleagues performed genomic analyses, an equal susceptibility to CQ was identified among all clones in polyclonal infections. There was a similar rate of recurrent infections (n=24) between the relocated and nonrelocated groups, indicating that recurrent infections were not solely caused by reinfections. According to the study, recurrent infections were associated with low CQ therapeutic blood concentration levels, but a second course of CQ treatment cleared them. Whole-genome sequencing showed that two-thirds of the recurrent parasites resulted from heterologous relapses.
Popovici and colleagues did not observe any evidence of CQ resistance and suggested that P. vivax antimalarial drug resistance is likely overestimated. They recommended a revision to the current guidelines for clinical drug studies in P. vivax malaria.
“Our findings suggest that the assumption of chloroquine resistance in Cambodia may have been premature and chloroquine might remain an effective therapeutic option in uncomplicated vivax malaria in several areas,” Popovici and colleagues wrote. – by Marley Ghizzone
Disclosures: The authors report no relevant financial disclosures.
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