二氢青蒿素哌喹治疗印度尼西亚巴布亚和苏门答腊无并发症间日疟原虫和恶性疟原虫疟疾的疗效和安全性。
Efficacy and safety of dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum and Plasmodium vivax malaria in Papua and Sumatra, Indonesia.
机构信息
Malaria and Vector Resistance Unit, Eijkman Institute for Molecular Biology, Jakarta, Indonesia.
Jambi Provincial Health Department, Jambi City, Jambi, Indonesia.
出版信息
Malar J. 2022 Mar 19;21(1):95. doi: 10.1186/s12936-022-04101-0.
BACKGROUND
Dihydroartemisinin-piperaquine (DHA-PPQ) has been adopted as first-line therapy for uncomplicated falciparum malaria in Indonesia since 2010. The efficacy of DHA-PPQ was evaluated in 2 sentinel sites in Keerom District, Papua and Merangin District, Jambi, Sumatra from April 2017 to April 2018.
METHODS
Clinical and parasitological parameters were monitored over a 42-day period following the World Health Organization standard in vivo protocol and subjects meeting the inclusion criteria were treated with DHA-PPQ once daily for 3 days, administered orally.
RESULTS
In Papua, 6339 subjects were screened through active and passive cases detection. Of the 114 falciparum and 81 vivax cases enrolled, 102 falciparum and 80 vivax cases completed the 42 day follow up, and 12 falciparum and 1 vivax cases were either lost to follow up or withdrawn. Kaplan-Meier analysis of microscopy readings of 102 falciparum cases revealed 93.1% (95% CI 86.4-97.2) as Adequate Clinical and Parasitological Response (ACPR). No delay in parasite clearance nor severe adverse reaction was observed. Recurrent parasites of Plasmodium falciparum were detected in 7 cases and categorized as late treatment failures (LTF) at days 21, 35, and 42 and one of which was reinfected by Plasmodium vivax at day 42. Two cases were confirmed as recrudescent infection and 4 were re-infection. The PCR-corrected DHA-PPQ efficacy for P. falciparum was 97.9% (95% CI 92.7-99.7). Of the 80 cases of P. vivax that were followed up, 71 cases were completely cured and classified as ACPR (88.8%, 95% CI 79.7-94.7) and 9 cases showed recurrent infection at days 35 and 42, and classified as LTF. In Sumatra, of the 751 subjects screened, 35 vivax subjects enrolled, 34 completed the 42 day follow up. Thirty-three cases were completely cured and classified as ACPR (97.1%, 95% CI 84.7-99.9) and 1 recurrent infection was observed and classified as LTF. No delay in parasite clearance nor severe adverse reaction was observed. Analysis of the Pfk13 gene in P. falciparum cases from Papua revealed no mutations associated with artemisinin resistance in the 20 SNPs previously reported. Analysis of the Pfpm2 gene at day 0 and day of recurrence in recrudescent cases revealed the same single copy number, whereas 3 of the 4 re-infection cases carried 2-3 Pfpm2 gene copy numbers.
CONCLUSION
Treatment of falciparum and vivax malaria cases with DHA-PPQ showed a high efficacy and safety.
背景
自 2010 年以来，二氢青蒿素-哌喹（DHA-PPQ）已被印度尼西亚采用为治疗无并发症恶性疟的一线药物。2017 年 4 月至 2018 年 4 月，在巴布亚的基尔罗姆区和苏门答腊的 Merangin 区的 2 个哨点对 DHA-PPQ 的疗效进行了评估。
方法
按照世界卫生组织标准体内方案进行 42 天的临床和寄生虫学监测，符合纳入标准的患者每天口服 DHA-PPQ 一次，连续 3 天进行治疗。
结果
在巴布亚，通过主动和被动病例检测共筛查了 6339 例。在纳入的 114 例疟原虫和 81 例间日疟病例中，102 例疟原虫和 80 例间日疟病例完成了 42 天的随访，12 例疟原虫和 1 例间日疟病例失访或退出。102 例疟原虫病例的显微镜读数的 Kaplan-Meier 分析显示，93.1%（95%CI 86.4-97.2）为适当的临床和寄生虫学反应（ACPR）。未观察到寄生虫清除延迟或严重不良反应。在 7 例患者中检测到恶性疟原虫的复发性寄生虫，在第 21、35 和 42 天被归类为迟发性治疗失败（LTF），其中 1 例在第 42 天被间日疟原虫重新感染。2 例被确诊为复发性感染，4 例为再感染。PCR 校正的 DHA-PPQ 对恶性疟原虫的疗效为 97.9%（95%CI 92.7-99.7）。在 80 例随访的间日疟病例中，71 例完全治愈，被归类为 ACPR（88.8%，95%CI 79.7-94.7），9 例在第 35 和 42 天出现复发性感染，被归类为 LTF。在苏门答腊，在筛查的 751 例患者中，有 35 例间日疟患者入组，34 例完成了 42 天的随访。33 例完全治愈，被归类为 ACPR（97.1%，95%CI 84.7-99.9），1 例出现复发性感染，被归类为 LTF。未观察到寄生虫清除延迟或严重不良反应。对来自巴布亚的恶性疟原虫病例的 Pfk13 基因进行分析，未发现与之前报道的 20 个 SNP 相关的青蒿素耐药相关突变。在复发性病例的 Pfpm2 基因分析中，发现第 0 天和复发日的基因拷贝数相同，而 4 例再感染病例中有 3 例携带 2-3 个 Pfpm2 基因拷贝数。
结论
DHA-PPQ 治疗恶性疟和间日疟病例具有较高的疗效和安全性。
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