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《2016年英国疟疾治疗指南》

UK malaria treatment guidelines 2016.

作者信息

Lalloo David G, Shingadia Delane, Bell David J, Beeching Nicholas J, Whitty Christopher J M, Chiodini Peter L

机构信息

Department of Clinical Sciences, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool L3 5QA, UK.

Department of Infectious Diseases, Great Ormond Street Hospital, Great Ormond Street, London WC1N 3JH, UK.

出版信息

J Infect. 2016 Jun;72(6):635-649. doi: 10.1016/j.jinf.2016.02.001. Epub 2016 Feb 12.

Abstract

1.Malaria is the tropical disease most commonly imported into the UK, with 1300-1800 cases reported each year, and 2-11 deaths. 2. Approximately three quarters of reported malaria cases in the UK are caused by Plasmodium falciparum, which is capable of invading a high proportion of red blood cells and rapidly leading to severe or life-threatening multi-organ disease. 3. Most non-falciparum malaria cases are caused by Plasmodium vivax; a few cases are caused by the other species of plasmodium: Plasmodium ovale, Plasmodium malariae or Plasmodium knowlesi. 4. Mixed infections with more than one species of parasite can occur; they commonly involve P. falciparum with the attendant risks of severe malaria. 5. There are no typical clinical features of malaria; even fever is not invariably present. Malaria in children (and sometimes in adults) may present with misleading symptoms such as gastrointestinal features, sore throat or lower respiratory complaints. 6. A diagnosis of malaria must always be sought in a feverish or sick child or adult who has visited malaria-endemic areas. Specific country information on malaria can be found at http://travelhealthpro.org.uk/. P. falciparum infection rarely presents more than six months after exposure but presentation of other species can occur more than a year after exposure. 7. Management of malaria depends on awareness of the diagnosis and on performing the correct diagnostic tests: the diagnosis cannot be excluded until more than one blood specimen has been examined. Other travel related infections, especially viral haemorrhagic fevers, should also be considered. 8. The optimum diagnostic procedure is examination of thick and thin blood films by an expert to detect and speciate the malarial parasites. P. falciparum and P. vivax (depending upon the product) malaria can be diagnosed almost as accurately using rapid diagnostic tests (RDTs) which detect plasmodial antigens. RDTs for other Plasmodium species are not as reliable. 9. Most patients treated for P. falciparum malaria should be admitted to hospital for at least 24 h as patients can deteriorate suddenly, especially early in the course of treatment. In specialised units seeing large numbers of patients, outpatient treatment may be considered if specific protocols for patient selection and follow up are in place. 10. Uncomplicated P. falciparum malaria should be treated with an artemisinin combination therapy (Grade 1A). Artemether-lumefantrine (Riamet(®)) is the drug of choice (Grade 2C) and dihydroartemisinin-piperaquine (Eurartesim(®)) is an alternative. Quinine or atovaquone-proguanil (Malarone(®)) can be used if an ACT is not available. Quinine is highly effective but poorly-tolerated in prolonged treatment and should be used in combination with an additional drug, usually oral doxycycline. 11. Severe falciparum malaria, or infections complicated by a relatively high parasite count (more than 2% of red blood cells parasitized) should be treated with intravenous therapy until the patient is well enough to continue with oral treatment. Severe malaria is a rare complication of P. vivax or P. knowlesi infection and also requires parenteral therapy. 12. The treatment of choice for severe or complicated malaria in adults and children is intravenous artesunate (Grade 1A). Intravenous artesunate is unlicensed in the EU but is available in many centres. The alternative is intravenous quinine, which should be started immediately if artesunate is not available (Grade 1A). Patients treated with intravenous quinine require careful monitoring for hypoglycemia. 13. Patients with severe or complicated malaria should be managed in a high-dependency or intensive care environment. They may require haemodynamic support and management of: acute respiratory distress syndrome, disseminated intravascular coagulation, acute kidney injury, seizures, and severe intercurrent infections including Gram-negative bacteraemia/septicaemia. 14. Children with severe malaria should also be treated with empirical broad spectrum antibiotics until bacterial infection can be excluded (Grade 1B). 15. Haemolysis occurs in approximately 10-15% patients following intravenous artesunate treatment. Haemoglobin concentrations should be checked approximately 14 days following treatment in those treated with IV artemisinins (Grade 2C). 16. Falciparum malaria in pregnancy is more likely to be complicated: the placenta contains high levels of parasites, stillbirth or early delivery may occur and diagnosis can be difficult if parasites are concentrated in the placenta and scanty in the blood. 17. Uncomplicated falciparum malaria in the second and third trimester of pregnancy should be treated with artemether-lumefantrine (Grade 2B). Uncomplicated falciparum malaria in the first trimester of pregnancy should usually be treated with quinine and clindamycin but specialist advice should be sought. Severe malaria in any trimester of pregnancy should be treated as for any other patient with artesunate preferred over quinine (Grade 1C). 18. Children with uncomplicated malaria should be treated with an ACT (artemether-lumefantrine or dihydroartemisinin-piperaquine) as first line treatment (Grade 1A). Quinine with doxycycline or clindamycin, or atovaquone-proguanil at appropriate doses for weight can also be used. Doxycycline should not be given to children under 12 years. 19. Either an oral ACT or chloroquine can be used for the treatment of non-falciparum malaria. An oral ACT is preferred for a mixed infection, if there is uncertainty about the infecting species, or for P. vivax infection from areas where chloroquine resistance is common (Grade 1B). 20. Dormant parasites (hypnozoites) persist in the liver after treatment of P. vivax or P. ovale infection: the only currently effective drug for eradication of hypnozoites is primaquine (1A). Primaquine is more effective at preventing relapse if taken at the same time as chloroquine (Grade 1C). 21. Primaquine should be avoided or given with caution under expert supervision in patients with Glucose-6-phosphate dehydrogenase deficiency (G6PD), in whom it may cause severe haemolysis. 22. Primaquine (for eradication of P. vivax or P. ovale hypnozoites) is contraindicated in pregnancy and when breastfeeding (until the G6PD status of child is known); after initial treatment for these infections a pregnant woman should take weekly chloroquine prophylaxis until after delivery or cessation of breastfeeding when hypnozoite eradication can be considered. 23. An acute attack of malaria does not confer protection from future attacks: individuals who have had malaria should take effective anti-mosquito precautions and chemoprophylaxis during future visits to endemic areas.

摘要
  1. 疟疾是最常输入英国的热带疾病,每年报告1300 - 1800例病例,并有2 - 11人死亡。2. 在英国报告的疟疾病例中,约四分之三由恶性疟原虫引起,该疟原虫能够侵袭高比例的红细胞,并迅速导致严重或危及生命的多器官疾病。3. 大多数非恶性疟疾病例由间日疟原虫引起;少数病例由其他疟原虫种类引起:卵形疟原虫、三日疟原虫或诺氏疟原虫。4. 可发生一种以上寄生虫的混合感染;常见的是恶性疟原虫与严重疟疾相关风险的混合感染。5. 疟疾没有典型的临床特征;甚至发热也并非总是出现。儿童(有时成人)疟疾可能表现出误导性症状,如胃肠道症状、喉咙痛或下呼吸道症状。6. 对于去过疟疾流行地区的发热或患病儿童或成人,必须始终考虑疟疾诊断。有关疟疾的具体国家信息可在http://travelhealthpro.org.uk/查询。恶性疟原虫感染在接触后很少在六个月以上出现,但其他种类的感染可在接触后一年以上出现。7. 疟疾的管理取决于对诊断的认识以及进行正确的诊断测试:在检查多个血液标本之前不能排除诊断。还应考虑其他与旅行相关的感染,特别是病毒性出血热。8. 最佳诊断程序是由专家检查厚血膜和薄血膜以检测和鉴定疟原虫。使用检测疟原虫抗原的快速诊断测试(RDT)几乎可以同样准确地诊断恶性疟原虫和间日疟原虫(取决于产品)。用于其他疟原虫种类的RDT不太可靠。9. 大多数接受恶性疟原虫疟疾治疗的患者应住院至少24小时,因为患者可能突然恶化,尤其是在治疗过程的早期。在诊治大量患者的专科单位,如果有患者选择和随访的特定方案,可考虑门诊治疗。10. 非重症恶性疟原虫疟疾应采用青蒿素联合疗法治疗(1A级)。蒿甲醚 - 本芴醇(Riamet(®))是首选药物(2C级),双氢青蒿素 - 哌喹(Eurartesim(®))是替代药物。如果没有青蒿素联合疗法,可使用奎宁或阿托伐醌 - 氯胍(Malarone(®))。奎宁非常有效,但长期治疗耐受性差,应与另一种药物联合使用,通常是口服强力霉素。11. 重症恶性疟原虫疟疾或伴有相对高寄生虫计数(超过2%的红细胞被寄生)的感染应采用静脉治疗,直到患者病情好转足以继续口服治疗。重症疟疾是间日疟原虫或诺氏疟原虫感染的罕见并发症,也需要胃肠外治疗。12. 成人和儿童重症或复杂性疟疾的治疗选择是静脉注射青蒿琥酯(1A级)。静脉注射青蒿琥酯在欧盟未获许可,但在许多中心均可获得。替代药物是静脉注射奎宁,如果没有青蒿琥酯,应立即开始使用(1A级)。接受静脉注射奎宁治疗的患者需要密切监测低血糖。13. 重症或复杂性疟疾患者应在高依赖性或重症监护环境中进行管理。他们可能需要血流动力学支持以及对以下情况的管理:急性呼吸窘迫综合征、弥散性血管内凝血、急性肾损伤、癫痫发作以及包括革兰氏阴性菌血症/败血症在内的严重并发感染。14. 重症疟疾儿童也应接受经验性广谱抗生素治疗,直到排除细菌感染(1B级)。15. 静脉注射青蒿琥酯治疗后,约10 - 15%的患者会发生溶血。接受静脉注射青蒿素治疗的患者应在治疗后约14天检查血红蛋白浓度(2C级)。16. 妊娠期恶性疟原虫疟疾更易出现并发症:胎盘含有高水平的寄生虫,可能发生死产或早产,如果寄生虫集中在胎盘而血液中含量稀少,诊断可能会很困难。17. 妊娠中期和晚期的非重症恶性疟原虫疟疾应采用蒿甲醚 - 本芴醇治疗(2B级)。妊娠早期的非重症恶性疟原虫疟疾通常应采用奎宁和克林霉素治疗,但应寻求专科建议。妊娠任何阶段的重症疟疾应与其他患者一样治疗,首选青蒿琥酯而非奎宁(1C级)。18. 非重症疟疾儿童应采用青蒿素联合疗法(蒿甲醚 - 本芴醇或双氢青蒿素 - 哌喹)作为一线治疗(1A级)。奎宁与强力霉素或克林霉素,或按适当体重剂量服用阿托伐醌 - 氯胍也可使用。强力霉素不应给予12岁以下儿童。19. 口服青蒿素联合疗法或氯喹均可用于治疗非恶性疟疾病例。如果存在混合感染、感染种类不确定或来自氯喹耐药常见地区的间日疟原虫感染,口服青蒿素联合疗法是首选(1B级)。20. 间日疟原虫或卵形疟原虫感染治疗后,休眠寄生虫(潜隐子)会持续存在于肝脏中:目前唯一有效根除潜隐子的药物是伯氨喹(1A级)。与氯喹同时服用时,伯氨喹预防复发更有效(1C级)。21. 葡萄糖 - 6 - 磷酸脱氢酶缺乏(G6PD)患者应避免使用伯氨喹或在专家监督下谨慎使用,因为它可能导致严重溶血。22. 伯氨喹(用于根除间日疟原虫或卵形疟原虫潜隐子)在妊娠和哺乳期(直到知道儿童的G6PD状态)禁用;这些感染初始治疗后,孕妇应每周服用氯喹预防,直到分娩后或停止母乳喂养,此时可考虑根除潜隐子。23. 疟疾急性发作不能预防未来发作:患过疟疾的个体在未来前往流行地区时应采取有效的防蚊措施和化学预防措施。

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