Recrudescence in Artesunate-Treated Patients With Falciparum Malaria Is Dependent on Parasite Burden Not on Parasite Factors

Abstract

Artemisinin derivatives are first-line antimalarial drugs in Thailand. No firm evidence of clinically relevant artemisinin resistance exists. When used as monotherapy, artesunate has been associated with a high treatment failure (recrudescence) rate, which could be due to low-level artemisinin resistance. To understand the causes of recrudescence, we retrospectively studied a cohort of 104 malaria patients treated with artesunate monotherapy, 32 of whom recrudesced. There was no difference in in vitro artesunate sensitivities between 6 nonrecrudescent isolates and 16 paired admission and recrudescent isolates. Paired admission and recrudescent isolates from 10 patients were genotyped; only 3 had pfmdr1 mutations. Patients with admission parasitemias >10,000 per l had a 9-fold higher likelihood of recrudescence (adjusted odds ratio) compared with patients with lower parasitemias. This study suggests (1) recrudescence after treatment with artesunate is not the result of inherent parasite resistance, and (2) admission parasitemia may be useful in choosing therapeutic options.

No Evidence of Delayed Parasite Clearance after Oral Artesunate Treatment of Uncomplicated Falciparum Malaria in Mali

“…The two most powerful predictors of parasite clearance time were age (proxy for acquired immunity in this population) and asexual parasitemia at the time of enrollment. [15][16][17][18] Based on previous studies, [16][17][18][19] the following variables were also included in the initial models as potential confounders of parasite clearance: sex, mixed parasite infection, and hemoglobin, gametocyte density, gametocyte carriage, and fever at the time of enrollment. All statistical analyses were done with Stata version 11.0 (StataCorp., College Station, TX).…”

Resistance to Antimalarials in Southeast Asia and Genetic Polymorphisms in pfmdr1

“…Samples were genotyped for msp1, msp2, and glurp by the methods described by Snounou et al (15). PCR amplification and direct sequencing were used to determine the sequences at a single pfcrt polymorphic site (position 76) and five pfmdr1 polymorphic sites (positions 86, 184, 1034, 1042, and 1246), as described previously (8). The sequences at all loci could be determined for 61 isolates plus laboratory strains W2 and PH6.…”

Malaria Parasites Can Develop Stable Resistance to Artemisinin but Lack Mutations in Candidate Genes atp6 (Encoding the Sarcoplasmic and Endoplasmic Reticulum Ca 2+ ATPase), tctp , mdr1 , and cg10

“…When used as monotherapy, artemisinin derivatives are associated with low to moderate levels of recrudescence in vivo following single treatment (17), possibly due to their extremely short elimination half-lives. However, reports of high treatment failure and confirmed in vivo or in vitro resistance to these drugs have not yet been documented.…”