BACKGROUND Trials to assess the efficacy of the radical cure of Plasmodium vivax malaria with 8-aminoquinolines require that most post-treatment relapses are identified, but there is no consensus on the optimal duration of follow-up in either symptomatic or asymptomatic vivax malaria. The efficacy of a 14-day course of primaquine on the cumulative incidence of recurrent asymptomatic P. vivax infections detected by ultrasensitive quantitative PCR (uPCR) as a primary endpoint was assessed. METHODS A randomized, placebo-controlled, single-blind trial was conducted in four villages of the Lao PDR during 2016-2018 nested in a larger project evaluating mass drug administrations (MDA) with dihydroartemisinin-piperaquine (DP) and a single low-dose primaquine to clear Plasmodium falciparum infections. In the nested sub-study, eligible participants with mono- or mixed P. vivax infections detected by uPCR were randomized to receive either 14 days of primaquine (0.5 mg/kg/day) or placebo during the last round of MDA (round 3) through directly observed therapy. Participants were checked monthly for 12 months for parasitaemia using uPCR. The primary outcome was cumulative incidence of participants with at least one recurrent episode of P. vivax infection. RESULTS 20 G6PD-normal participants were randomized in each arm. 5 (29%) of 20 participants in the placebo arm experienced asymptomatic, recurrent P. vivax infections, resulting in a cumulative incidence at month 12 of 29%. None of the 20 participants in the intervention arm had recurrent infections (p = 0.047 Fisher's exact test). Participants with recurrent P. vivax infections were found to be parasitaemic for between one and five sequential monthly tests. The median time to recurrence of P. vivax parasitaemia was 178 days (range 62-243 days). CONCLUSIONS A 14-day course of primaquine in addition to a DP-MDA was safe, well-tolerated, and prevented recurrent asymptomatic P. vivax infections. Long follow-up for up to 12 months is required to capture all recurrences following the treatment of asymptomatic vivax infection. To eliminate all malarias in settings where P. vivax is endemic, a full-course of an 8-aminoquinolines should be added to MDA to eliminate all malarias. Trial registration This study was registered with ClinicalTrials.gov under NCT02802813 on 16th June 2016. https://clinicaltrials.gov/ct2/show/NCT02802813.

中文翻译：

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使用超灵敏定量 PCR 评估伯氨喹对间日疟原虫感染无症状复发的影响：老挝人民民主共和国的一项随机对照试验。


背景 评估用 8-氨基喹啉彻底治愈间日疟原虫疟疾的功效的试验需要确定大多数治疗后复发，但对于有症状或无症状间日疟疾的最佳随访时间尚未达成共识。作为主要终点，评估了 14 天伯氨喹疗程对通过超灵敏定量 PCR (uPCR) 检测到的复发性无症状间日疟原虫感染累积发生率的功效。方法 2016 年至 2018 年期间，在老挝人民民主共和国的四个村庄进行了一项随机、安慰剂对照、单盲试验，该试验嵌套在一个更大的项目中，评估双氢青蒿素哌喹 (DP) 和单一低剂量的大规模药物管理 (MDA)伯氨喹可清除恶性疟原虫感染。在嵌套子研究中，通过 uPCR 检测到单一或混合间日疟原虫感染的合格参与者被随机分配，在最后一轮 MDA（第 3 轮）期间接受 14 天的伯氨喹（0.5 毫克/公斤/天）或安慰剂通过直接观察治疗。连续 12 个月，每月使用 uPCR 对参与者进行寄生虫血症检查。主要结果是至少一次复发性间日疟原虫感染的参与者的累积发生率。结果 每组 20 名 G6PD 正常参与者被随机分配。安慰剂组的 20 名参与者中有 5 名 (29%) 经历过无症状、复发性间日疟原虫感染，导致第 12 个月的累积发病率为 29%。干预组的 20 名参与者均未出现复发性感染（p = 0.047 Fisher 精确检验）。患有复发性间日疟原虫感染的参与者在每月一到五次的连续测试中被发现患有寄生虫病。 P 复发的中位时间。 间日疟原虫血症为 178 天（范围 62-243 天）。结论 14 天的伯氨喹联合 DP-MDA 疗程是安全的、耐受性良好的，并且可以预防复发性无症状间日疟原虫感染。需要长达 12 个月的长期随访才能捕获无症状间日感染治疗后的所有复发情况。为了消除间日疟原虫流行地区的所有疟疾，应将全程 8-氨基喹啉添加到 MDA 中以消除所有疟疾。试验注册 本研究于 2016 年 6 月 16 日在 ClinicalTrials.gov 注册，编号为 NCT02802813。https://clinicaltrials.gov/ct2/show/NCT02802813。