Landier Jordi, Kajeechiwa Ladda, Thwin May Myo, Parker Daniel M, Chaumeau Victor, Wiladphaingern Jacher, Imwong Mallika, Miotto Olivo, Patumrat Krittaya, Duanguppama Jureeporn, Cerqueira Dominique, Malleret Benoit, Rénia Laurent, Nosten Suphak, von Seidlein Lorenz, Ling Clare, Proux Stéphane, Corbel Vincent, Simpson Julie A, Dondorp Arjen M, White Nicholas J, Nosten François H
Shoklo Malaria Research Unit, Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Mae Sot, Thailand.
Maladies Infectieuses et Vecteurs Ecologie, Génétique, Evolution et Contrôle (IRD 224-CNRS 4280 UM1-UM2), Institut de Recherche pour le Développement, Montpellier, France.
Wellcome Open Res. 2017 Sep 6;2:81. doi: 10.12688/wellcomeopenres.12240.1. eCollection 2017.
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. 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. 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 carriage and anopheline vector positivity decreased significantly whereas prevalence of the artemisinin-resistance molecular marker remained stable. This MDA was safe and feasible, and, could accelerate elimination of in addition to EDT and LLINs when community participation was sufficient.
青蒿素及联合用药耐药的恶性疟正在大湄公河次区域（GMS）蔓延。在药物仍具有足够疗效时消除GMS地区的恶性疟，可防止抗疟药耐药性在全球传播。迅速消除疟疾需要针对无症状寄生虫携带者这一传染源。这项试点试验旨在评估群体服药（MDA）在减少缅甸东部四个村庄疟疾方面的可接受性、安全性、可行性和有效性。选择疟疾患病率≥30%的村庄。提供长效驱虫蚊帐（LLINs）以及疟疾早期诊断和治疗（EDT）服务。两个村庄立即接受MDA，另外两个村庄在MDA前随访9个月。MDA包括一个为期3天的双氢青蒿素哌喹监督疗程，以及每月一次单剂量低剂量伯氨喹，共三个月。通过访谈和咨询监测不良事件（AE）。每季度通过超灵敏PCR评估疟疾患病率，为期24个月。监测有症状疟疾发病率、昆虫学指标和抗疟药耐药标志物。MDA耐受性良好。在5.6%（212/3931）的访谈中未报告严重AE，报告了轻度至中度AE。在较小的村庄，参加三个MDA疗程的比例分别为61%和57%，而在较大的村庄分别为28%和29%。干预村庄的基线患病率高于对照村庄（18.7%（95%CI=16.1-21.6）对6.8%（5.2-8.7），p<0.0001），而开始MDA三个月后，干预村庄的患病率较低（0.4%（0.04-1.3）对2.7%（1.7-4.1），p=0.0014）。九个月后差异不再显著（2.0%（1.0-3.5）对0.9%（（0.04-1.8），p=0.10）。干预组和对照组之间M0-M9有症状恶性疟发病率相似。MDA前后比较显示，无症状携带率和按蚊媒介阳性率显著下降，而青蒿素耐药分子标志物的患病率保持稳定。当社区参与度足够时，这种MDA除了EDT和LLINs外，是安全可行的，并且可以加速消除疟疾。
