The Transmission of Artemisinin Resistant Parasites Before and After Conventional Artemisinin-combination Therapy: a Longitudinal Study
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 160
- 试验地点
- 4
- 主要终点
- Mean within person percent change (presented as percent reduction) in mosquito infection rate in infectious individuals from baseline.
研究概览
简要总结
A prospective study will be carried out in an area where parasites with reduced sensitivity to malaria drugs (artemisinins) have recently emerged. The study will recruit participants from patients who attend the clinic with uncomplicated malaria and asymptomatically infected individuals. Participants are treated with conventional artemisinin-combination therapies (ACT) as part of standard clinical care. From this population, we will select P. falciparum gametocyte carriers.
Before, during and after ACT treatment, the transmission potential of artemisinin resistant and wild type infections will be assessed by microscopy, molecular methods, parasite culture and mosquito feeding assays. Parasite clearance will be determined in the first days (d0-3) after treatment.
The study population will consist of passively recruited patients with uncomplicated P. falciparum malaria and asymptomatically infected individuals who are microscopy positive for gametocytes. Participants will be treated with conventional therapies for uncomplicated malaria without randomization: artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHA-PPQ). All doses are supervised. Parasite clearance is assessed ex vivo by ring-stage survival assays and by daily slides during the first days of treatment.
Gametocyte carriage and gametocyte commitment/production will be determined for resistant and wild type infections before, during and after treatment. In addition, venous blood will be collected at three timepoints to assess transmission to mosquitoes before (d0), during (d2) and after treatment (d7). The total duration of participation will be 7 days, the primary endpoint will be the reduction in mosquito infection rates at d2 (artemether-lumefantrine) or d7 (dihydroartemisinin-piperaquine) compared to pre-treatment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •age ≥2 years
- •blood smear positive for P. falciparum gametocytes
- •mono-infection with P. falciparum confirmed by positive blood smear;
- •parasitaemia of >100 P. falciparum asexual forms/µL;
- •ability to swallow oral medication;
- •ability and willingness to comply with the study protocol for the duration of the study and to comply with the study visit schedule;
- •informed consent from parent or guardian;
- •haemoglobin ≥ 7.0 g/dl for children below 10 years of age or ≥8.0g/dL for older individuals
排除标准
- •presence of general danger signs;
- •mixed or mono-infection with another Plasmodium species detected by microscopy;
- •presence of severe malnutrition defined as a very low weight for height (below -3z scores of the median WHO growth standards), by visible severe wasting, or by the presence of nutritional oedema.
- •presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhoea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS);
- •history of hypersensitivity reactions or contraindications to any of the medicine(s) being tested
研究组 & 干预措施
dihydroartemisinin-piperaquine
dihydroartemisinin-piperaquine according to manufacturer instructions
干预措施: Dihydroartemisinin-Piperaquine (Drug)
artemether-lumefantrine
artemether-lumefantrine according to manufacturer instructions
干预措施: Artemether-lumefantrine (Drug)
结局指标
主要结局
Mean within person percent change (presented as percent reduction) in mosquito infection rate in infectious individuals from baseline.
时间窗: day 2 vs day 0 (AL arm) and day 7 vs day 0 (DP arm)
Mean within person percent change (presented as percent reduction) in mosquito infection rate in infectious individuals from baseline (day 0, pre-treatment) to day 2 post treatment in the AL and day 7 post-treatment in the DHA-PPQ arm. Infectivity is assessed by mosquito membrane feeding assays; percent reduction is calculated separately for ΔPfK13 vs wild type infections.
次要结局
- Mean within person percent change (presented as percent reduction) in mosquito infection rate from baseline(days 0, 2, 7)
- Mean oocyst intensity (in all/all infected mosquitoes)(days 0, 2, 7)
- Male and female gametocyte sex ratio (proportion male)(days 0, 1, 2, 3, 7)
- Gametocyte circulation time(days 0, 1, 2, 3, 7)
- Gametocyte area under the curve(days 0, 1, 2, 3, 7)
- Asexual parasite prevalence(days 0, 1, 2, 3, 7)
- Asexual parasite density(days 0, 1, 2, 3, 7)
- Total parasite prevalence(days 0, 1, 2, 3, 7)
- Total parasite density(days 0, 1, 2, 3, 7)
- The density of ΔPfK13 vs wild type genotypes(days 0, 1, 2, 3, 7)
- The density of ΔPfK13 vs wild type genotypes in oocysts and sporozoites in mosquitoes that become infected before and after initiation of treatment(days 0, 2, 7)
- Mean within person percent change (presented as percent reduction) in mosquito infection rate from baseline after gametocyte enrichment(days 0, 2, 7)
- Asexual parasite prevalence(Hours 0, 8, 16, Days 1, 2, 3, 7, 14)
- Asexual parasite density(Hours 0, 8, 16, Days 1, 2, 3, 7, 14)
- Total parasite prevalence(Hours 0, 8, 16, Days 1, 2, 3, 7, 14)
- Total parasite density(Hours 0, 8, 16, Days 1, 2, 3, 7, 14)