Assessing Chloroquine Resistance of Plasmodium Vivax in Malaria Endemic Area
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 73
- 试验地点
- 1
- 主要终点
- Number of patients with P. vivax CQ resistant parasite
研究概览
简要总结
The investigators propose to leverage the unique infrastructures and expertise of National Centre for Parasitology Entomology and Malaria Control and the Pasteur Institute in Cambodia and combine modern fieldwork, including a mobile laboratory fully equipped for molecular biology and culture experiments, with state-of-the-art genomic analyses to investigate how Plasmodium vivax parasites respond to antimalarial drugs. The investigators will focus on resistance to CQ, the choice treatment for vivax malaria in most endemic countries, for which treatment failures have been reported in Cambodia. The study will address some of the key biological mechanisms limiting the efficiency of drug therapy in P. vivax, including the identification of genetic polymorphisms underlying drug resistance in Cambodian P. vivax. The findings will provide a first unbiased perspective on the mechanisms of drug resistance in P. vivax and have the strong potential to significantly improve malaria control in Southeast Asia.
详细描述
In order to assess the resistance phenotype of P. vivax to CQ, the methodology will involve the following steps:
- Inclusion of P.vivax mono-infected patients from villages in treatment failure-reported area (Ban Lung district, Rattanakiri)
- Pv diagnostic confirmation (microscopy and qPCR)
- Transfer of patients to Ban Lung hospital for a 7-days clinical follow-up
- Blood collection followed by CQ administration
- Parasite clearance and whole blood CQ concentration follow-up during 7 days.
- Parasitemia follow-up during 2 months with patients staying in Ban Lung during the entire study to make sure no re-infection occurs (Ban Lung is a no-transmission area).
- Ex vivo drug susceptibility assay of P. vivax isolates and after any recrudescence/relapse, if any.
- Genotyping analysis of parasites at Day 0 and after any recrudescence/relapse, if any.
Research design
The study will be carried out in Ban Lung district (Rattanakir province, Cambodia) between April 2014 and December 2014. This research site (Rattanakiri) is chosen on the basis of relatively high reports of treatment failures to CQ. In Ban Lung district villages, all P. vivax mono-infected adult patients seeking treatment at community level (VMW and Health centers) will be offered to participate to the study
The sample size calculation was based on addressing the primary objective of identifying a true resistance phenotype to CQ. Therefore a minimum of 50 patients is required and ideally, around 100 patients will increase the probability of detecting resistant parasites.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •(i) Being aged 15 years or more with competency to give informed consent, (ii) Being positive for P. vivax and mono-infected
排除标准
- •(i) Being aged 14 years or less (ii) Individuals with illness that affected competency to give informed consent, (iii) Pregnant or lactating women (iv) Having taken antimalarial drugs in the past month
研究组 & 干预措施
Chloroquine
Patients treat with chloroquine sulfate (NIVAQUINE) 10 mg/kg/day - 3 days
干预措施: Chloroquine sulfate (Drug)
DHA-PP
Patient treat with DHA 40 mg and PP 320 mg, (Duo-Cotecxin®) The approximate total adult dose is 2-4 mg/kg for DHA and 20mg/kg for PP
干预措施: DHA-PP (Drug)
结局指标
主要结局
Number of patients with P. vivax CQ resistant parasite
时间窗: 6 months
Based on parasite clearance time (slow versus fast clearers) and treatments failure (according to the CQ blood concentration)
次要结局
- Number of isolates characterized by whole genome sequencing and multiple Single Nucleotide Polymorphisms Bar Code(1 year)
研究者
Didier Menard
Malaria Molecular Epidemiology Unit
Institut Pasteur, Cambodia