7 research outputs found
RECRUDESCENCE IN ARTESUNATE-TREATED PATIENTS WITH FALCIPARUM MALARIA IS DEPENDENT ON PARASITE BURDEN NOT ON PARASITE FACTORS
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 µl 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
MEASURING ALLELIC HETEROGENEITY IN PLASMODIUM FALCIPARUM BY A HETERODUPLEX TRACKING ASSAY
We developed a novel Plasmodium falciparum genotyping strategy based on the heteroduplex tracking
assay (HTA) method commonly used to genotype viruses. Because it can detect both sequence and size polymorphisms,
we hypothesized that HTA is more sensitive than current methods. To test this hypothesis, we compared the ability of
HTA and a nested polymerase chain reaction (PCR) to detect genetic diversity in 17 Thai samples. The HTA detected
more MSP1 sequence variants in eight isolates (47%), less sequence variants in three isolates (18%), and an equal
number of sequence variants in six isolates (35%), suggesting that HTA is equal to or more sensitive than the nested
PCR. This study is a proof of concept that HTA is a sensitive allelic discrimination method able to determine genetic
diversity in P. falciparum and warrants its use in studies of antimalarial drug efficacy