Safety and effectiveness of mass drug administration to accelerate elimination of artemisinin-resistant falciparum malaria: A pilot trial in four villages of Eastern Myanmar.
Safety and effectiveness of mass drug administration to accelerate elimination of artemisinin-resistant falciparum malaria: A pilot trial in four villages of Eastern Myanmar.
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DOI：
10.12688/wellcomeopenres.12240.1
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发表时间：
2017
影响因子：
--
通讯作者：
Nosten FH
中科院分区：
文献类型：
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作者：
Landier J;Kajeechiwa L;Thwin MM;Parker DM;Chaumeau V;Wiladphaingern J;Imwong M;Miotto O;Patumrat K;Duanguppama J;Cerqueira D;Malleret B;Rénia L;Nosten S;von Seidlein L;Ling C;Proux S;Corbel V;Simpson JA;Dondorp AM;White NJ;Nosten FH
背景：青蒿素及其伙伴耐药性恶性疟疾正在大湄公河次区域（GMS）蔓延。在药物仍保持足够疗效的同时消除大湄公河次区域的恶性疟疾，可以防止抗疟药耐药性在全球蔓延。快速消除疟疾需要针对无症状寄生虫携带者的储存库。 该试点试验旨在评估大规模药物管理（MDA）在缅甸东部四个村庄减少疟疾的可接受性、安全性、可行性和有效性。 方法：选择疟疾患病率≥30%的村庄。提供了长效杀虫蚊帐（LLIN）和疟疾早期诊断和治疗（EDT）。两个村庄立即收到了 MDA，另外两个村庄在 MDA 之前接受了为期九个月的跟踪。 MDA 包括为期 3 天的双氢青蒿素哌喹疗程和单次低剂量伯氨喹疗程，每月服用一次，持续三个月。通过访谈和咨询来监测不良事件（AE）。为期 24 个月，每季度通过超灵敏 PCR 评估疟疾患病率。监测有症状的疟疾发病率、昆虫学指数和抗疟疾耐药标记。 结果：MDA 耐受性良好。 5.6%（212/3931）的访谈中没有报告严重的 AE，有轻度至中度的 AE。在较小的村庄中，参加三门 MDA 课程的比例分别为 61% 和 57%，而在较大的村庄中，这一比例为 28% 和 29%。干预村的基线患病率高于对照村（18.7%（95%CI=16.1-21.6）对比6.8%（5.2-8.7），p<0.0001），而开始MDA后三个月，干预村的患病率较低（0.4%（0.04-1.3）对比2.7%（1.7-4.1），p=0.0014）。九个月后，差异不再显着（2.0%（1.0-3.5）与 0.9%（0.04-1.8），p=0.10）。干预组和对照组之间 M0-M9 症状性恶性疟发病率相似。 MDA前后比较显示，无症状恶性疟原虫携带和按蚊载体阳性率显着下降，而青蒿素抗性分子标记的流行率保持稳定。 结论：该 MDA 安全可行，并且在社区参与充分的情况下，除了 EDT 和 LLIN 之外，还可以加速消除恶性疟原虫。
Background: Artemisinin and partner drug-resistant falciparum malaria is expanding over the Greater Mekong Sub-region (GMS). Eliminating falciparum malaria in the GMS while drugs still retain enough efficacy could prevent global spread of antimalarial resistance. Eliminating malaria rapidly requires targeting the reservoir of asymptomatic parasite carriers. This pilot trial aimed to evaluate the acceptability, safety, feasibility and effectiveness of mass-drug administration (MDA) in reducing malaria in four villages in Eastern Myanmar. Methods: Villages with ≥30% malaria prevalence were selected. Long-lasting insecticidal bednets (LLINs) and access to malaria early diagnosis and treatment (EDT) were provided. Two villages received MDA immediately and two were followed for nine months pre-MDA. MDA consisted of a 3-day supervised course of dihydroartemisinin-piperaquine and single low-dose primaquine administered monthly for three months. Adverse events (AE) were monitored by interviews and consultations. Malaria prevalence was assessed by ultrasensitive PCR quarterly for 24 months. Symptomatic malaria incidence,entomological indices, and antimalarial resistance markers were monitored. Results: MDA was well tolerated. There were no serious AE and mild to moderate AE were reported in 5.6%(212/3931) interviews. In the smaller villages, participation to three MDA courses was 61% and 57%, compared to 28% and 29% in the larger villages. Baseline prevalence was higher in intervention than in control villages (18.7% (95%CI=16.1-21.6) versus 6.8%(5.2-8.7), p<0.0001) whereas three months after starting MDA, prevalence was lower in intervention villages (0.4%(0.04-1.3) versus 2.7%(1.7-4.1), p=0.0014). After nine months the difference was no longer significant (2.0%(1.0-3.5) versus 0.9%(0.04-1.8), p=0.10). M0-M9 symptomatic falciparum incidence was similar between intervention and control. Before/after MDA comparisons showed that asymptomatic P. falciparum carriage and anopheline vector positivity decreased significantly whereas prevalence of the artemisinin-resistance molecular marker remained stable. Conclusions: This MDA was safe and feasible, and, could accelerate elimination of P. falciparum in addition to EDT and LLINs when community participation was sufficient.