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评估青蒿琥酯单药疗法和双氢青蒿素哌喹作为未来疟疾疫苗现场效力试验期间疫苗接种前根治性治疗的潜在抗疟选择。

Evaluating artesunate monotherapy and dihydroartemisinin-piperaquine as potential antimalarial options for prevaccination radical cures during future malaria vaccine field efficacy trials.

作者信息

Ouédraogo Alphonse, Ouattara Daouda, Ouattara San Maurice, Diarra Amidou, Badoum Emilie S, Hema Alimatou, Ouédraogo Amidou Z, Hien Denise, Bougouma Edith C, Nébié Issa, Bocquet Valéry, Vaillant Michel, Tiono Alfred B, Sirima Sodiomon B

机构信息

Groupe de Recherche Action en Santé (GRAS), Ouagadougou, West Africa, Burkina Faso.

Luxembourg Institute of Health (LIH), Luxembourg, Europe, Luxembourg.

出版信息

Malar J. 2024 Dec 18;23(1):377. doi: 10.1186/s12936-024-05198-1.

DOI:10.1186/s12936-024-05198-1

PMID:39695728

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11656655/

Abstract

BACKGROUND

In malaria vaccine clinical trials, immune responses after vaccination may be compromised due to immunosuppression caused by concurrent Plasmodium falciparum infection. This has a direct effect on the protective efficacy of the vaccine being evaluated. Therefore, parasite clearance prior to vaccination is being considered. Drugs with good safety and efficacy profiles and a short posttreatment prophylaxis period should be used. Two antimalarial drugs, artesunate (AS) as monotherapy and dihydroartemisinin-piperaquine (DHAPQ), have been evaluated in order to identify the most suitable option for use in future trials.

METHODS

A cohort of children aged 1.5-12 years living in the Banfora Health District area was recruited. They were randomly assigned to receive supervised curative doses of AS monotherapy for 7 days or DHAPQ for 3 days. A polymerase chain reaction (PCR) was performed 21 days after treatment to confirm clearance of infection, and only those with a negative PCR were included in the study cohort for a 6-month longitudinal follow-up. Cohort children were actively visited fortnightly to collect blood samples for P. falciparum detection via microscopy and PCR. Passive surveillance was also conducted at the local health facility to record incident malaria episodes that occurred between two active visits.

RESULTS

A total of 513 children were treated. Among these patients, 458 (89.3%) were free of P. falciparum malaria infection on day 21: 87.3% (226/259) in the AS group vs 91.3% (232/254) in the DHAPQ group (p = 0.053). The mean time to first malaria infection by microscopy was 154.9 (2.9) days in the DHAPQ arm and 129.0 (3.9) days in the AS arm (p < 0.01). The incidence rates of clinical malaria episodes during the follow-up period were 0.507 (0.369-0.645) and 0.293 (0.190-0.397) in the AS and DHAPQ arms, respectively (p < 0.05).

CONCLUSIONS

These findings suggest that although both drugs are effective in clearing P. falciparum infections, AS is likely to cause no more than minimal interference with the evaluation of vaccine efficacy endpoints and could, therefore, be considered for use.

TRIAL REGISTRATION

NCT04601714.

摘要

背景

在疟疾疫苗临床试验中，由于同时感染恶性疟原虫导致的免疫抑制，接种疫苗后的免疫反应可能会受到损害。这对正在评估的疫苗的保护效力有直接影响。因此，正在考虑在接种疫苗前清除寄生虫。应使用安全性和有效性良好且治疗后预防期短的药物。为了确定最适合在未来试验中使用的药物，对两种抗疟药物青蒿琥酯（AS）单药治疗和双氢青蒿素哌喹（DHAPQ）进行了评估。

方法

招募了居住在班福拉健康区的1.5至12岁儿童队列。他们被随机分配接受7天的AS单药治疗或3天的DHAPQ治疗的监督治疗剂量。治疗21天后进行聚合酶链反应（PCR）以确认感染清除，只有PCR阴性的儿童被纳入研究队列进行为期6个月的纵向随访。每两周对队列儿童进行一次主动访视，采集血样通过显微镜检查和PCR检测恶性疟原虫。还在当地卫生机构进行被动监测，以记录两次主动访视之间发生的疟疾发病情况。

结果

共治疗了513名儿童。在这些患者中，458名（89.3%）在第21天时没有恶性疟原虫感染：AS组为87.3%（226/259），DHAPQ组为91.3%（232/254）（p = 0.053）。通过显微镜检查首次感染疟疾的平均时间在DHAPQ组为154.9（2.9）天，在AS组为129.0（3.9）天（p < 0.01）。随访期间临床疟疾发作的发病率在AS组和DHAPQ组分别为0.507（0.369 - 0.645）和0.293（0.190 - 0.397）（p < 0.05）。