Malaria burden and artemisinin resistance in the mobile and migrant population on the Thai-Myanmar border, 1999-2011: an observational study.
Malaria burden and artemisinin resistance in the mobile and migrant population on the Thai-Myanmar border, 1999-2011: an observational study.
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DOI：
10.1371/journal.pmed.1001398
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发表时间：
2013
期刊：
影响因子：
15.8
通讯作者：
Nosten F
中科院分区：
文献类型：
--
作者：
Carrara VI;Lwin KM;Phyo AP;Ashley E;Wiladphaingern J;Sriprawat K;Rijken M;Boel M;McGready R;Proux S;Chu C;Singhasivanon P;White N;Nosten F
Francois Nosten及其同事评估了1999年至2011年期间缅甸与泰国边境一侧流动人口中的疟疾流行率和发病率，并评估了对青蒿素的耐药性。Shoklo疟疾研究中心25年来一直在泰缅边境开展工作，提供疟疾的早期诊断和治疗。恶性疟原虫的传播已经下降，但对青蒿琥酯的抗药性已经出现。我们通过EDT扩大了疟疾活动，并在12年期间评估了影响。1999年10月1日至2011年9月30日期间，Shoklo疟疾研究股将跨境（缅甸方面）保健设施的数量从两个增加到11个，并记录了疟疾咨询的次数。疟疾发病率的变化从一组孕妇中估计，流行率从横断面调查中估计。监测抗疟药物在体内和体外的疗效。在此期间，发现的疟疾病例数最初有所增加，但随后迅速下降。在5岁以下儿童中，因疟疾就诊的百分比从78% (95% CI 76-80)（1,048/1,344次就诊）降至7% (95% CI 6.2-7.1)（767/11,542次就诊），p<0.001。恶性疟原虫/P。间日疟原虫从1.4 （95% CI 1.3-1.4）下降到0.7 （95% CI 0.7 - 0.8）。病死率较低（39/75,126;0.05% [95% CI 0.04-0.07]）。疟疾发病率从每名孕妇每年1.1例下降到0.1例。恶性疟原虫的累积比例从24.3% (95% CI 21.0 ~ 28.0)（143/588例孕妇）显著下降到3.4% (95% CI 2.8 ~ 4.3)（76/ 2207例孕妇），p<0.001。甲氟喹-青蒿琥酯的体内疗效稳步下降，2011年急剧下降（第42天pcr调整治愈率为42% [95% CI 20-62]）。在第3天仍呈疟疾滑行阳性的患者比例从2000年的0%上升到2011年的28% (95% CI 13-45)（8/29例患者）。尽管恶性疟原虫出现了对青蒿琥酯的耐药性，但EDT与以青蒿素为基础的联合治疗的策略与生活在泰缅边境的移民人口疟疾的减少有关。尽管受观测性质的限制，这项研究提供了关于战略上至关重要的地理区域的疟疾负担的有用数据。迫切需要替代固定联合治疗，以取代失败的甲氟喹和青蒿琥酯一线方案。根据最新数字，世界卫生组织估计，每年有2亿多疟疾病例，死亡人数超过75万人。几种疟原虫引起疟疾（最严重的是恶性疟原虫），并通过受感染的夜间飞行的蚊子叮咬传播给人。通过使用杀虫剂控制蚊子和睡在经杀虫剂处理过的蚊帐内，可以预防疟疾的传播。然而，在东南亚，这些措施的效果有限。用抗疟疾药物，特别是以青蒿素为基础的联合疗法治疗感染者，是减少疟疾造成的死亡和残疾的一项关键战略。然而，由于东南亚出现了对青蒿琥酯（青蒿素的一种常见成分）具有耐药性的恶性疟原虫分离株，目前进展受到威胁。这一事态发展令人关切，因为对青蒿素家族药物（青蒿琥酯是其中一员）的耐药性可能在世界许多地方引发疟疾死灰复燃，并损害在治疗严重疟疾方面取得的进展。在泰国和缅甸边境附近地区已证实恶性疟原虫对青蒿素产生耐药性。在这一边境地区控制疟疾尤其具有挑战性，因为缅甸境内有一个疟疾库（其疾病负担高于泰国），人口流动频繁，边界两侧在适当控制措施方面存在差异。在这项研究中，作者评估了1999年10月1日至2011年9月30日期间缅甸边境一侧流动人口的疟疾流行率和发病率，以评估增加获得早期诊断和青蒿素联合疗法治疗的机会是否与疟疾负担的下降有关。Shoklo疟疾研究股25年来一直在泰缅边境开展工作，提供疟疾的早期诊断和治疗，并在过去几年中将其服务从边境缅甸一侧的两个保健设施（卫生站）扩大到11个。为了评估自扩大服务以来疟疾负担的任何变化，研究人员记录了经确诊为疟疾的所有卫生保健机构诊所和卫生站的咨询人数，并跟踪了边境缅甸一侧人口中疟疾流行率的变化（通过在村庄进行横断面调查）。研究人员还评估了生活在边境两侧的一组孕妇的疟疾发病率，并监测了这段时间内抗疟疾药物的疗效。研究人员发现，尽管边境泰国一侧的流动人口保持不变，但边境地区诊所和卫生站覆盖的村庄的人口增加了四倍。在这段时间里，研究人员发现确诊的疟疾病例（恶性疟原虫）数量最初有所增加，从2000年的5000多例上升到2006年的13764例，然后下降到2011年的3500多例。一个引人注目的发现是年轻成年男性的感染优势（50,316/90,321;55.7%）。令人鼓舞的是，五岁以下儿童因疟疾就诊的百分比从78%下降到7%，疟疾发病率从每名孕妇每年1.1例下降到0.1例。此外，因严重疾病住院的患者比例保持稳定，疟疾死亡人数仍然极低，总病死率为0.05%。研究人员还发现，恶性疟原虫与间日疟原虫感染的比例从1.4下降到0.7，恶性疟原虫的患病率从24.3%下降到3.4%。然而，令人担忧的是，在少数接受药效试验的患者中，青蒿琥酯的药效稳步下降，在治疗第3天仍感染疟疾的患者比例从2000年的0%上升到2011年的28%。这些发现表明，尽管恶性疟原虫出现了对青蒿琥酯的耐药性，而且青蒿琥酯类联合疗法的疗效有所下降，但早期诊断和以联合疗法治疗疟疾的策略与泰缅边境人口疟疾发病率的下降有关。此外，这些发现表明，基于早期发现和治疗病例的积极战略，结合媒介控制和信息，可能是消除疟疾的前进方向。虽然2011年仅有少数患者参与药效试验，但本研究表明，迫切需要替代固定联合治疗方案，以取代甲氟喹和青蒿琥酯一线方案的失败。请通过本摘要的在线版本（http://dx.doi.org/10.1371/journal.pmed.1001398）访问这些网站。有关Shoklo疟疾研究中心的更多信息，请查阅。世界卫生组织网站上有关于抗疟药物疗效和耐药性的更多信息。比尔和梅琳达·盖茨基金会网站讲述了疟疾耐药性的故事
Francois Nosten and colleagues evaluate malaria prevalence and incidence in the mobile population on the Myanmar side of the border with Thailand between 1999 and 2011, and also assess resistance to artemisinin. The Shoklo Malaria Research Unit has been working on the Thai–Myanmar border for 25 y providing early diagnosis and treatment (EDT) of malaria. Transmission of Plasmodium falciparum has declined, but resistance to artesunate has emerged. We expanded malaria activities through EDT and evaluated the impact over a 12-y period. Between 1 October 1999 and 30 September 2011, the Shoklo Malaria Research Unit increased the number of cross-border (Myanmar side) health facilities from two to 11 and recorded the number of malaria consultations. Changes in malaria incidence were estimated from a cohort of pregnant women, and prevalence from cross-sectional surveys. In vivo and in vitro antimalarial drug efficacy were monitored. Over this period, the number of malaria cases detected increased initially, but then declined rapidly. In children under 5 y, the percentage of consultations due to malaria declined from 78% (95% CI 76–80) (1,048/1,344 consultations) to 7% (95% CI 6.2–7.1) (767/11,542 consultations), p<0.001. The ratio of P. falciparum/P. vivax declined from 1.4 (95% CI 1.3–1.4) to 0.7 (95% CI 0.7–0.8). The case fatality rate was low (39/75,126; 0.05% [95% CI 0.04–0.07]). The incidence of malaria declined from 1.1 to 0.1 episodes per pregnant women-year. The cumulative proportion of P. falciparum decreased significantly from 24.3% (95% CI 21.0–28.0) (143/588 pregnant women) to 3.4% (95% CI 2.8–4.3) (76/2,207 pregnant women), p<0.001. The in vivo efficacy of mefloquine-artesunate declined steadily, with a sharp drop in 2011 (day-42 PCR-adjusted cure rate 42% [95% CI 20–62]). The proportion of patients still slide positive for malaria at day 3 rose from 0% in 2000 to reach 28% (95% CI 13–45) (8/29 patients) in 2011. Despite the emergence of resistance to artesunate in P. falciparum, the strategy of EDT with artemisinin-based combination treatments has been associated with a reduction in malaria in the migrant population living on the Thai–Myanmar border. Although limited by its observational nature, this study provides useful data on malaria burden in a strategically crucial geographical area. Alternative fixed combination treatments are needed urgently to replace the failing first-line regimen of mefloquine and artesunate. Please see later in the article for the Editors' Summary According to latest figures, the World Health Organization estimates that there are over 200 million cases of malaria each year, with over three-quarters of a million deaths. Several Plasmodium parasites cause malaria (the most serious being Plasmodium falciparum) and are transmitted to people through the bites of infected night-flying mosquitoes. Malaria transmission can be prevented by using insecticides to control the mosquitoes and by sleeping under insecticide-treated bed nets. However, in Southeast Asia the effectiveness of these measures is limited. Treating infected people with antimalarial drugs, particularly with artemisinin-based combination treatments (ACTs), is a key strategy in reducing the deaths and disability caused by malaria. However, progress is now threatened by the emergence in Southeast Asia of P. falciparum isolates that are resistant to artesunate (a common component of ACT). This development is concerning, as resistance to the artemisinin family of drugs, of which artesunate is a member, could trigger a resurgence in malaria in many parts of the world and compromise the progress made in the treatment of severe malaria. P. falciparum resistance to artemisinin has been confirmed in the area around the border between Thailand and Myanmar. Malaria control in this border area is particularly challenging, as there is a reservoir of malaria in Myanmar (where the disease burden is higher than in Thailand), frequent population movement, and differences in adequate control measures on the two sides of the border. In this study the authors evaluated malaria prevalence and incidence in the mobile population on the Myanmar side of the border between 1 October 1999 and 30 September 2011 to assess whether increasing access to early diagnosis and treatment with ACT was associated with a decline in the malaria burden. The Shoklo Malaria Research Unit (SMRU) has been working on the Thai–Myanmar border for 25 years providing early diagnosis and treatment of malaria and has extended its services from two to 11 health care facilities (health posts) on the Myanmar side of the border over the past few years. In order to evaluate any changes in the malaria burden since the expansion of services, the researchers recorded the number of consultations in all SMRU clinics and health posts with confirmed malaria diagnosis and tracked changes in the prevalence of malaria in the population on the Myanmar side of the border (via cross-sectional surveys in villages). The researchers also assessed the incidence of malaria in a cohort of pregnant women living on both sides of the border and monitored antimalarial drug efficacy over this time period. The researchers found that although the mobile population on the Thai side of the border remained constant, the population in villages covered by the clinics and health posts in the border area increased four-fold. Over the time period, the researchers found that the number of confirmed malaria cases (P. falciparum) increased initially, rising from just over 5,000 in 2000 to a peak of 13,764 in 2006, and then declined to just over 3,500 in 2011. A striking finding was the predominance of infections in young adult males (50,316/90,321; 55.7%). Encouragingly, the percentage of consultations due to malaria in children under five years fell from 78% to 7%, and the incidence of malaria declined from 1.1 to 0.1 episodes per pregnant woman-year. In addition, the proportion of patients admitted to hospital with severe disease was stable, and the number of deaths from malaria remained extremely low, with an overall case fatality rate of 0.05%. The researchers also found that the ratio of P. falciparum to P. vivax infections declined from 1.4 to 0.7, and the prevalence of P. falciparum decreased from 24.3% to 3.4%. However, worryingly, in the small number of patients undertaking drug efficacy tests, the drug efficacy of artesunate declined steadily, with the proportion of patients still infected with malaria at day 3 of treatment increasing from 0% in 2000 to 28% in 2011. These findings indicate that despite the emergence of resistance to artesunate in P. falciparum, and the decline in the efficacy of ACT, the strategy of early diagnosis and treatment with ACTs has been associated with a reduction in malaria in the population living on the Thai–Myanmar border. Furthermore, these findings suggest that an aggressive strategy based on early detection and treatment of cases, combined with vector control and information, could be the way forward to eliminate malaria. Although there were only a small number of patients involved in drug efficacy tests in 2011, this study shows that alternative fixed combination treatments are needed urgently to replace the failing first-line regimen of mefloquine and artesunate. Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001398. More information about the Shoklo Malaria Research Unit is available The World Health Organization website has more information about antimalarial drug efficacy and drug resistance The Bill & Melinda Gates Foundation website tells the malaria resistance story
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影响因子：
168.9
作者：
Dondorp, Arjen M.;Fanello, Caterina I.;White, Nicholas J.
通讯作者：
White, Nicholas J.
疟疾风险的全球分布和人口：过去，现在和未来。
影响因子：
56.3
作者：
Hay, SI;Guerra, CA;Tatem, AJ;Noor, AM;Snow, RW
通讯作者：
Snow, RW
影响因子：
11.8
作者：
Phyo, Aung Pyae;Lwin, Khin Maung;Nosten, Francois
通讯作者：
Nosten, Francois
DOI：
10.1016/0035-9203(93)90262-o
发表时间：
1993-11-01
影响因子：
2.2
作者：
DOLAN, G;TERKUILE, FO;NOSTEN, F
通讯作者：
NOSTEN, F
影响因子：
168.9
作者：
Phyo, Aung Pyae;Nkhoma, Standwell;Stepniewska, Kasia;Ashley, Elizabeth A.;Nair, Shalini;McGready, Rose;Moo, Carit Ler;Al-Saai, Salma;Dondorp, Arjen M.;Lwin, Khin Maung;Singhasivanon, Pratap;Day, Nicholas P. J.;White, Nicholas J.;Anderson, Tim J. C.;Nosten, Francois
通讯作者：
Nosten, Francois