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A Single Mutation in K13 Predominates in Southern China and Is Associated With Delayed Clearance of Plasmodium falciparum Following Artemisinin Treatment.

ABSTRACT: Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and poses a threat to malaria control and elimination. Mutations in a P. falciparum gene encoding a kelch protein on chromosome 13 have been associated with delayed parasite clearance following artemisinin treatment elsewhere in the region, but not yet in China.Therapeutic efficacy studies of artesunate and dihydroartemisinin-piperaquine were conducted from 2009 to 2012 in the Yunnan Province of China near the border with Myanmar. K13 mutations were genotyped by capillary sequencing of DNA extracted from dried blood spots collected in these clinical trials and in routine surveillance. Associations between K13 mutations and delayed parasite clearance were tested using regression models.Parasite clearance half-lives were prolonged after artemisinin treatment, with 44% of infections having half-lives >5 hours (n = 109). Fourteen mutations in K13 were observed, with an overall prevalence of 47.7% (n = 329). A single mutation, F446I, predominated, with a prevalence of 36.5%. Infections with F446I were significantly associated with parasitemia on day 3 following artemisinin treatment and with longer clearance half-lives.Plasmodium falciparum infections in southern China displayed markedly delayed clearance following artemisinin treatment. F446I was the predominant K13 mutation and was associated with delayed parasite clearance.

SUBMITTER: Huang F

PROVIDER: S-EPMC4621243 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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A Single Mutation in K13 Predominates in Southern China and Is Associated With Delayed Clearance of Plasmodium falciparum Following Artemisinin Treatment.

Huang Fang F Takala-Harrison Shannon S Jacob Christopher G CG Liu Hui H Sun Xiaodong X Yang Henglin H Nyunt Myaing M MM Adams Matthew M Zhou Shuisen S Xia Zhigui Z Ringwald Pascal P Bustos Maria Dorina MD Tang Linhua L Plowe Christopher V CV

The Journal of infectious diseases 20150424 10

<h4>Background</h4>Artemisinin resistance in Plasmodium falciparum has emerged in Southeast Asia and poses a threat to malaria control and elimination. Mutations in a P. falciparum gene encoding a kelch protein on chromosome 13 have been associated with delayed parasite clearance following artemisinin treatment elsewhere in the region, but not yet in China.<h4>Methods</h4>Therapeutic efficacy studies of artesunate and dihydroartemisinin-piperaquine were conducted from 2009 to 2012 in the Yunnan ...[more]

PMID: 25910630

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Project description:Artemisinin-based combination therapy (ACT) is widely recommended as first-line therapy for uncomplicated Plasmodium falciparum malaria worldwide. Artemisinin resistance has now been reported in Southeast Asia with a clinical phenotype manifested by slow parasite clearance. Although there are no reliable reports of artemisinin resistance in Africa, there is a need to better understand the dynamics of parasite clearance in African children treated with ACT in order to better detect the emergence of artemisinin resistance.Data from a cohort of Ugandan children four to five years old, enrolled in a longitudinal, randomized, clinical trial comparing two leading ACT, artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DP), were analysed. For all episodes of uncomplicated P. falciparum malaria over a 14-month period, daily blood smears were performed for three days following the initiation of therapy. Associations between pre-treatment variables of interest and persistent parasitaemia were estimated using multivariate, generalized, estimating equations with adjustment for repeated measures in the same patient.A total of 202 children were included, resulting in 416 episodes of malaria treated with AL and 354 episodes treated with DP. The prevalence of parasitaemia on days 1, 2, and 3 following initiation of therapy was 67.6, 5.6 and 0% in those treated with AL, and 52.2, 5.7 and 0.3% in those treated with DP. Independent risk factors for persistent parasitaemia on day 1 included treatment with AL vs DP (RR?=?1.34, 95% CI 1.20-1.50, p?<?0.001), having a temperature ?38.0°C vs?<?37.0°C (RR?=?1.19, 95% CI 1.05-1.35, p?=?0.007) and having a parasite density >20,000/?L vs <4,000/?L (RR?=?3.37, 95% CI 2.44-4.49, p?<?0.001). Independent risk factors for having persistent parasitaemia on day 2 included elevated temperature, higher parasite density, and being HIV infected.Among Ugandan children, parasite clearance following treatment with AL or DP was excellent with only one of 752 patients tested having a positive blood slide three days after initiation of therapy. The type of ACT given, pre-treatment temperature, pre-treatment parasite density and HIV status were associated with differences in persistent parasitaemia, one or two days following therapy.Current Controlled Trials Identifier NCT00527800.

Dataset Information

A Single Mutation in K13 Predominates in Southern China and Is Associated With Delayed Clearance of Plasmodium falciparum Following Artemisinin Treatment.

Publications

A Single Mutation in K13 Predominates in Southern China and Is Associated With Delayed Clearance of Plasmodium falciparum Following Artemisinin Treatment.

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