跨中缅边境疟疾感染危险因素和间日疟根治难题研究

Control of malaria importation and radical treatment of Plasmodium vivax are two difficulties in malaria-eliminating settings. China has declared to the world to eliminate malaria by 2020. Control of communicatble diseases cross along border is one of cooperation areas agreed in the fifth health minister summit of the Association of South east Asian Nations, and one of the priorities “one Belt and one Road” economic development and diplomatism with neighbouring countries. To make sure malaria elimination according to scheduled time by national malaria elimination action plan, the research intend to identify risk factors for malaria infection on the border, to find epidemiological characteristics of malaria cross China-Myanmar border, hotspots and hot populations through using case-control technicals. Meanwhile, the issues of efficacy, safety, tolerance and compliance can be solved through randomized clinical trial of artemisinin-naphthoquine combination for three days plus primaquine for two days versus chloroquine-primaquine for eight days to treat vivax malaria. The outcomes will provide scientific evidences and technical supports for reduction of malaria importation, timely finding and clearing malaria importation, eradication of malaria infection sources, and interruption of malaria transmission on the border of China. In the other hand, these outcomes would be useful for keeping the status of malaria elimination and control of other communication diseases cross the common border in future.

输入性疟疾控制和间日疟的根治是消除疟疾研究的两大难题。到2020年全国消除疟疾是中国政府对世界的承诺，同时跨境传染病防控是第五届中国-东盟卫生部长会确定的合作领域，是建设“一带一路”和周边外交优先方向。为保证云南省按国家规划时间消除疟疾，本研究计划通过使用病例对照研究技术，研究跨境疟疾感染危险因素，找出跨中缅边境疟疾的流行病学特征、疟疾感染热点及热点人群；同时开展复方青蒿素萘酚喹加伯喹(ANQ-PQ)三日疗法与氯伯喹（CQ-PQ）八日疗法根治间日疟病人临床随机对比试验，解决间日疟根治的效果、安全性、耐受性和依从性等问题。从而为减少输入性疟疾,及时有效地发现和清除输入性疟疾，根除疟疾传染源和阻断疟疾传播提供科学依据和技术支撑。此外，本研究结果也有助于指导将来疟疾消除的维持，和其它传染病的跨边境控制。

输入性疟疾防控和间日疟根治是消除疟疾两大技术难题。为揭示跨中缅边境疟疾感染热点地区和危险因素，同时，研究寻找更安全有效间日疟治疗方案，开展了跨中缅边境疟疾流行病学和复方青蒿素萘酚喹加低剂量伯喹(ANQ-PQ)与氯喹加伯胺喹疟疾治疗方案临床治疗和根治间日疟随机对比临床试验。研究结果鉴定出缅甸克钦邦第二特区拉咱、掸邦第二特区（当地称“佤邦”）萨尔温江河谷和掸邦东部第四特区南板县是中缅边境三个疟疾流行热点地区。疟疾感染危险因素病例对照研究完成疟疾病例组223例和对照（非疟疾病人）组446例问卷调查,多因素Logistic回归分析鉴定出疟疾发病前1个月内曾在缅甸过夜比值比(OR)=11.2531(95%CI：5.3233- 23.7884),在缅甸居住在农村坝区或山脚OR=2.7292(1.4489-5.1409),居住地海拔<500米OR=5.6754(95%CI：3.0083-10.7073)，居住地周围100米内有溪流OR=9.9826 (95%CI：4.9600-20.0914)，无疟疾传播知识OR=2.1678 (95%CI：1.4167-3.3173)，为疟疾感染危险因素。临床试验ANQ-PQ组完成172例，CQ-PQ组完成196例（国内80例，国外116例）365天间日疟根治效果追踪随访。临床治疗结果为ANQ-PQ组平均退热时间27.07±8.04小时比CQ-PQ组35.33±12.35小时显著缩短(F=1.6643, <0.0001)；ANQ-PQ组平均疟原虫转阴时间27.91±9.61小时也较CQ-PQ组39.11± 17.43小时显著缩短(F=1.2868,<0.001), 显示ANQ-PQ临床治疗效果更好。1年内ANQ-PQ组根治率88.37%(95%CI：82.61- 92.75%)，CQ-PQ组根治率87.76%(95%CI：82.33-91.99%),两组无显著差异(X2=0.0002, P=0.9832)。流行病学的研究结果及时提供给云南边境消除疟疾使用。现全云南已经实现三年以上无本土感染疟疾病例的消除疟疾目标。临床试验结果说明ANQ-PQ三日方案治疗间日疟临床效果、安全性和依从性更好，根治间日疟效果与CQ-PQ八日或十四日方案相近，可通过扩大应用试验进一步验证后，把ANQ-PQ三日方案作为间日疟根治方案之一。