PDF(Sci-hub)
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.疟疾是英国最常见的热带病，每年报告1300-1800例，2-11人死亡。2.英国报告的疟疾病例中约有四分之三是由恶性疟原虫引起的，能够侵入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是由间日疟原虫引起的；少数病例是由其他种类的疟原虫引起的：卵疟原虫，疟疾疟原虫或诺氏疟原虫。4.可能发生一种以上寄生虫的混合感染；它们通常涉及恶性疟原虫，伴随着严重疟疾的风险。5.没有典型的疟疾临床特征；甚至发烧也不总是存在。儿童（有时是成人）的疟疾可能会出现误导性症状，如胃肠道特征，喉咙痛或下呼吸道不适。6.必须始终在去过疟疾流行地区的发烧或生病的儿童或成人中寻求疟疾的诊断。有关疟疾的具体国家信息可在http://travelhealthpro.org上找到。英国/。恶性疟原虫感染很少在暴露后六个月以上出现，但其他物种的出现可能在暴露后一年以上出现。7.疟疾的管理取决于对诊断的认识和进行正确的诊断测试：在检查多个血液样本之前，不能排除诊断。其他旅行相关感染，尤其是病毒性出血热,也应该考虑。8.最佳的诊断程序是由专家检查厚薄的血膜，以检测和鉴定疟疾寄生虫。恶性疟原虫和间日疟原虫(取决于产品)疟疾可以使用检测疟原虫抗原的快速诊断测试(RDT)几乎同样准确地诊断。其他疟原虫物种的RDT并不那么可靠。9.大多数治疗恶性疟原虫疟疾的患者应住院至少24小时，因为患者可能会突然恶化，尤其是在治疗过程的早期。在看大量病人的专业单位，如果患者选择和随访的具体方案到位,可以考虑门诊治疗.10.应使用青蒿素联合疗法（1A级）治疗无并发症的恶性疟原虫疟疾。蒿甲醚-lumefantrine（Riamet（®））是首选药物（Grade2C），双氢青蒿素-哌喹（Eurartesim（®））是一种替代药物。如果ACT不可用，可以使用奎宁或atovaquone-proguanil（Malarone（®））。奎宁是非常有效的，但在长期治疗中耐受性差，应与其他药物联合使用。通常口服多西环素。11.严重的恶性疟疾,或由相对较高的寄生虫计数（超过2％的红细胞被寄生）并发的感染应进行静脉治疗，直到患者足够好，可以继续口服治疗。严重疟疾是间日疟原虫或诺氏疟原虫感染的罕见并发症，也需要肠胃外治疗。12.成人和儿童的严重或复杂疟疾的治疗选择是静脉青蒿琥酯(1A级)。静脉注射青蒿琥酯在欧盟是未经许可的，但在许多中心都有。另一种选择是静脉注射奎宁，如果青蒿琥酯不可用，应立即开始（1A级）。静脉注射奎宁治疗的患者需要仔细监测低血糖。13.严重或复杂的疟疾患者应在高度依赖或重症监护环境中进行管理。他们可能需要血液动力学支持和治疗：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,和严重的并发感染，包括革兰氏阴性菌血症/败血症。14.患有严重疟疾的儿童也应使用经验性广谱抗生素治疗，直到可以排除细菌感染（1B级）。15.静脉青蒿琥酯治疗后，约10-15％的患者发生溶血。在用IV青蒿素（2C级）治疗的患者中，应在治疗后约14天检查血红蛋白浓度。16.妊娠期恶性疟疾更可能是复杂的：胎盘中含有高水平的寄生虫，如果寄生虫集中在胎盘中而血液中缺乏，则可能会发生死产或早期分娩，并且诊断可能很困难。17.在妊娠的第二和第三个三个月中，无并发症的恶性疟疾应使用蒿甲醚-lumefantrine（2B级）治疗。妊娠早期无并发症的恶性疟疾通常应使用奎宁和克林霉素治疗，但应寻求专家的建议。妊娠任何三个月的严重疟疾都应与青蒿琥酯优于奎宁（1C级）的任何其他患者一样进行治疗。18.无并发症的疟疾患儿应使用ACT（蒿甲醚-本美特林或双氢青蒿素-哌喹）作为一线治疗（1A级）。奎宁与多西环素或克林霉素，也可以使用适当剂量的atovaquone-丙胍。强力霉素不应给予12岁以下的儿童。19.口服ACT或氯喹均可用于治疗非恶性疟疾。混合感染优选口服ACT，如果感染物种不确定，或来自氯喹耐药性常见地区的间日疟原虫感染（1B级）。20.在治疗间日疟原虫或卵卵圆虫感染后，休眠寄生虫（催眠体）在肝脏中持续存在：目前唯一有效的根除催眠体的药物是伯氨喹（1A）。如果与氯喹同时服用，伯氨喹在预防复发方面更有效（1C级）。21.葡萄糖-6-磷酸脱氢酶缺乏症（G6PD）患者应避免使用伯氨喹或在专家监督下谨慎使用，可能导致严重溶血。22.Primaquine（用于根除间日疟原虫或卵卵圆虫的催眠）在怀孕和母乳喂养时（直到知道儿童的G6PD状态）是禁忌的;在这些感染的初始治疗后，孕妇应每周服用氯喹，直到分娩或停止母乳喂养后才能考虑根除催眠菌。23.疟疾的急性发作并不能防止未来的发作：患有疟疾的个人在今后访问流行地区时应采取有效的防蚊预防措施和化学预防。
