PDF(Pubmed)
Abstract：
BACKGROUND: Artemether-lumefantrine is widely used for uncomplicated Plasmodium falciparum malaria; sulfadoxine-pyrimethamine plus amodiaquine is used for seasonal malaria chemoprevention. We aimed to determine the efficacy of artemether-lumefantrine with and without primaquine and sulfadoxine-pyrimethamine plus amodiaquine with and without tafenoquine for reducing gametocyte carriage and transmission to mosquitoes.
METHODS: In this phase 2, single-blind, randomised clinical trial conducted in Ouelessebougou, Mali, asymptomatic individuals aged 10-50 years with P falciparum gametocytaemia were recruited from the community and randomly assigned (1:1:1:1) to receive either artemether-lumefantrine, artemether-lumefantrine with a single dose of 0·25 mg/kg primaquine, sulfadoxine-pyrimethamine plus amodiaquine, or sulfadoxine-pyrimethamine plus amodiaquine with a single dose of 1·66 mg/kg tafenoquine. All trial staff other than the pharmacist were masked to group allocation. Participants were not masked to group allocation. Randomisation was done with a computer-generated randomisation list and concealed with sealed, opaque envelopes. The primary outcome was the median within-person percent change in mosquito infection rate in infectious individuals from baseline to day 2 (artemether-lumefantrine groups) or day 7 (sulfadoxine-pyrimethamine plus amodiaquine groups) after treatment, assessed by direct membrane feeding assay. All participants who received any trial drug were included in the safety analysis. This study is registered with ClinicalTrials.gov, NCT05081089.
RESULTS: Between Oct 13 and Dec 16, 2021, 1290 individuals were screened and 80 were enrolled and randomly assigned to one of the four treatment groups (20 per group). The median age of participants was 13 (IQR 11-20); 37 (46%) of 80 participants were female and 43 (54%) were male. In individuals who were infectious before treatment, the median percentage reduction in mosquito infection rate 2 days after treatment was 100·0% (IQR 100·0-100·0; n=19; p=0·0011) with artemether-lumefantrine and 100·0% (100·0-100·0; n=19; p=0·0001) with artemether-lumefantrine with primaquine. Only two individuals who were infectious at baseline infected mosquitoes on day 2 after artemether-lumefantrine and none at day 5. By contrast, the median percentage reduction in mosquito infection rate 7 days after treatment was 63·6% (IQR 0·0-100·0; n=20; p=0·013) with sulfadoxine-pyrimethamine plus amodiaquine and 100% (100·0-100·0; n=19; p<0·0001) with sulfadoxine-pyrimethamine plus amodiaquine with tafenoquine. No grade 3-4 or serious adverse events occurred.
CONCLUSIONS: These data support the effectiveness of artemether-lumefantrine alone for preventing nearly all mosquito infections. By contrast, there was considerable post-treatment transmission after sulfadoxine-pyrimethamine plus amodiaquine; therefore, the addition of a transmission-blocking drug might be beneficial in maximising its community impact.
BACKGROUND: Bill & Melinda Gates Foundation.
METHODS: In this phase 2, single-blind, randomised clinical trial conducted in Ouelessebougou, Mali, asymptomatic individuals aged 10-50 years with P falciparum gametocytaemia were recruited from the community and randomly assigned (1:1:1:1) to receive either artemether-lumefantrine, artemether-lumefantrine with a single dose of 0·25 mg/kg primaquine, sulfadoxine-pyrimethamine plus amodiaquine, or sulfadoxine-pyrimethamine plus amodiaquine with a single dose of 1·66 mg/kg tafenoquine. All trial staff other than the pharmacist were masked to group allocation. Participants were not masked to group allocation. Randomisation was done with a computer-generated randomisation list and concealed with sealed, opaque envelopes. The primary outcome was the median within-person percent change in mosquito infection rate in infectious individuals from baseline to day 2 (artemether-lumefantrine groups) or day 7 (sulfadoxine-pyrimethamine plus amodiaquine groups) after treatment, assessed by direct membrane feeding assay. All participants who received any trial drug were included in the safety analysis. This study is registered with ClinicalTrials.gov, NCT05081089.
RESULTS: Between Oct 13 and Dec 16, 2021, 1290 individuals were screened and 80 were enrolled and randomly assigned to one of the four treatment groups (20 per group). The median age of participants was 13 (IQR 11-20); 37 (46%) of 80 participants were female and 43 (54%) were male. In individuals who were infectious before treatment, the median percentage reduction in mosquito infection rate 2 days after treatment was 100·0% (IQR 100·0-100·0; n=19; p=0·0011) with artemether-lumefantrine and 100·0% (100·0-100·0; n=19; p=0·0001) with artemether-lumefantrine with primaquine. Only two individuals who were infectious at baseline infected mosquitoes on day 2 after artemether-lumefantrine and none at day 5. By contrast, the median percentage reduction in mosquito infection rate 7 days after treatment was 63·6% (IQR 0·0-100·0; n=20; p=0·013) with sulfadoxine-pyrimethamine plus amodiaquine and 100% (100·0-100·0; n=19; p<0·0001) with sulfadoxine-pyrimethamine plus amodiaquine with tafenoquine. No grade 3-4 or serious adverse events occurred.
CONCLUSIONS: These data support the effectiveness of artemether-lumefantrine alone for preventing nearly all mosquito infections. By contrast, there was considerable post-treatment transmission after sulfadoxine-pyrimethamine plus amodiaquine; therefore, the addition of a transmission-blocking drug might be beneficial in maximising its community impact.
BACKGROUND: Bill & Melinda Gates Foundation.
摘要：
背景：蒿甲醚-本美特林广泛用于治疗简单的恶性疟原虫疟疾；磺胺多辛-乙胺嘧啶加阿莫地喹用于季节性疟疾化学预防。我们旨在确定在有或没有伯氨喹和磺胺多辛-乙胺嘧啶加阿莫地喹的情况下，有或没有他非诺喹的情况下，蒿甲醚-本美曲碱对减少配子细胞携带和传播至蚊子的功效。
方法：在此阶段2，单盲，在Ouelessebougou进行的随机临床试验，马里,从社区招募了年龄在10-50岁之间的恶性疟原虫配子细胞血症无症状个体，并随机分配（1：1：1：1）接受蒿甲醚-氟美素，单剂量为0·25mg/kg伯氨喹的蒿甲醚-氟美醇，磺胺多辛-乙胺嘧啶加阿米地喹，或磺胺多辛-乙胺嘧啶加阿莫地喹，单剂量为1·66mg/kg他非诺喹。除药剂师以外的所有试验人员都被掩盖了小组分配。参与者没有掩盖小组分配。使用计算机生成的随机化列表进行随机化，并以密封的方式隐藏，不透明的信封。主要结局是治疗后从基线到第2天（蒿甲醚-本特林组）或第7天（磺胺多辛-乙胺嘧啶+阿莫地喹组）感染个体蚊子感染率的人内变化百分比，通过直接膜喂养试验进行评估。所有接受任何试验药物的参与者都被纳入安全性分析。这项研究在ClinicalTrials.gov注册，NCT05081089。
结果：在2021年10月13日至12月16日之间，筛选了1290名个体，其中80人被纳入并随机分配到四个治疗组之一（每组20人）。参与者的平均年龄为13岁（IQR11-20）；80名参与者中有37名（46％）是女性，43名（54％）是男性。在治疗前具有传染性的个体中，使用蒿甲醚-本美曲碱治疗后2天蚊子感染率的平均下降百分比为100·0%(IQR100·0-100·0;n=19;p=0·0011),使用蒿甲醚-本美曲碱和伯氨喹治疗后,蚊子感染率的平均下降百分比为100·0%(100·0-100·0;n=19;p=0·0001).在蒿甲醚-氟美素之后的第2天，只有两个在基线时具有传染性的个体感染了蚊子，而在第5天没有感染蚊子。相比之下,治疗后第7天,使用磺胺多辛-乙胺嘧啶+阿米地喹的蚊子感染率降低的中位数百分比为63·6%(IQR0·0-100·0;n=20;p=0·013),使用磺胺多辛-乙胺嘧啶+阿米地喹+他非诺喹的蚊子感染率降低的中位数百分比为100%(100·0-100·0·0;n=19;p<0·0001无3-4级或严重不良事件发生。
结论：这些数据支持单独使用蒿甲醚-本美特林预防几乎所有蚊子感染的有效性。相比之下,磺胺多辛-乙胺嘧啶加阿莫地喹后有相当多的治疗后传播；因此，增加一种阻断传播的药物可能有利于最大限度地提高其对社区的影响。
背景：比尔和梅琳达·盖茨基金会。
方法：在此阶段2，单盲，在Ouelessebougou进行的随机临床试验，马里,从社区招募了年龄在10-50岁之间的恶性疟原虫配子细胞血症无症状个体，并随机分配（1：1：1：1）接受蒿甲醚-氟美素，单剂量为0·25mg/kg伯氨喹的蒿甲醚-氟美醇，磺胺多辛-乙胺嘧啶加阿米地喹，或磺胺多辛-乙胺嘧啶加阿莫地喹，单剂量为1·66mg/kg他非诺喹。除药剂师以外的所有试验人员都被掩盖了小组分配。参与者没有掩盖小组分配。使用计算机生成的随机化列表进行随机化，并以密封的方式隐藏，不透明的信封。主要结局是治疗后从基线到第2天（蒿甲醚-本特林组）或第7天（磺胺多辛-乙胺嘧啶+阿莫地喹组）感染个体蚊子感染率的人内变化百分比，通过直接膜喂养试验进行评估。所有接受任何试验药物的参与者都被纳入安全性分析。这项研究在ClinicalTrials.gov注册，NCT05081089。
结果：在2021年10月13日至12月16日之间，筛选了1290名个体，其中80人被纳入并随机分配到四个治疗组之一（每组20人）。参与者的平均年龄为13岁（IQR11-20）；80名参与者中有37名（46％）是女性，43名（54％）是男性。在治疗前具有传染性的个体中，使用蒿甲醚-本美曲碱治疗后2天蚊子感染率的平均下降百分比为100·0%(IQR100·0-100·0;n=19;p=0·0011),使用蒿甲醚-本美曲碱和伯氨喹治疗后,蚊子感染率的平均下降百分比为100·0%(100·0-100·0;n=19;p=0·0001).在蒿甲醚-氟美素之后的第2天，只有两个在基线时具有传染性的个体感染了蚊子，而在第5天没有感染蚊子。相比之下,治疗后第7天,使用磺胺多辛-乙胺嘧啶+阿米地喹的蚊子感染率降低的中位数百分比为63·6%(IQR0·0-100·0;n=20;p=0·013),使用磺胺多辛-乙胺嘧啶+阿米地喹+他非诺喹的蚊子感染率降低的中位数百分比为100%(100·0-100·0·0;n=19;p<0·0001无3-4级或严重不良事件发生。
结论：这些数据支持单独使用蒿甲醚-本美特林预防几乎所有蚊子感染的有效性。相比之下,磺胺多辛-乙胺嘧啶加阿莫地喹后有相当多的治疗后传播；因此，增加一种阻断传播的药物可能有利于最大限度地提高其对社区的影响。
背景：比尔和梅琳达·盖茨基金会。
