蒿甲醚和伯氨喹治疗多国维和部队疟疾病人82例临床分析

疟疾是一种世界性流行传染病，据统计每年约有100～300万人死于该病，以非洲地区据多。作为中国政府派出的首支维和医疗分队共43人，于2003年4月～2003年12月参加了联合国在非洲刚果(金)的维和行动，主要为数千人的多国维和部队提供医疗保障。期间采用国产抗疟药蒿甲醚治疗了82例疟疾，其中25例重症疟疾加用磷酸伯氨喹治疗，疗效显著。结果报告如下。     

蒿甲醚片治疗恶性疟疾的临床观察

为了解蒿甲醚片治疗恶性疟疾的临床效果，最大限度地降低恶性疟疾的凶险发作及治疗过程中的不良反应，结合赴利比里亚维和治疗疟疾的工作实际，对其治疗效果进行了临床观察，现将结果报告如下。     

蒿甲醚胶囊治疗非洲黑色人种恶性疟疾的临床疗效

全世界每年有3～5亿的疟疾患者，其中90％发生在非洲。长期以来。在非洲广泛应用并被认为是抗疟特效药的盐酸间苯二酚奎宁（Quinimax），其用量越来越大。而另一种抗疟药青蒿素（Arteminin）对各种疟原虫红内期无性体具有强力杀灭作用，能有效缓解症状和杀灭疟原虫，但青蒿素在尼日尔的市场占有率非常低。为提高对该药的认识，我们在尼日尔共和国马拉迪住院中心工作3年期间，应用国产蒿甲醚胶囊和法国生产的盐酸间苯二酚奎宁注射液治疗非洲黑色人种恶性疟疾，进行临床疗效比较，现报道如下。     

蒿甲醚治疗老年恶性疟疾48例临床报告

青蒿素衍生物蒿甲醚对各型疟疾都有良好疗效。笔者在马达加斯加昂布翁贝地区援外医疗期间,主要使用该药救治了数千名疟疾患者,其中的48例60岁以上老年住院患者,多伴有高血压、糖尿病、冠心病等基础疾病。这些患者病情复杂多变,但用蒿甲醚联合其他药物救治,疗效较为满意,现报告如下。临床资料一、一般资料 48例恶性疟疾均为2000年7月～2002年10月在马达加斯加昂布翁贝医院住院的老年患者,     

复方蒿甲醚和本芴醇胶丸治疗恶性疟疗效对比

１９９６年６—１１月在海南省三亚市对复方蒿甲醚与本芴醇胶丸治疗恶性疟的疗效进行了比较,实验采用随机、对比的方法。病人入院后实行２８天封闭观察。实验共收治１００例病人,其中复方蒿甲醚组（Ａ）５１例,本芴醇胶丸组（Ｂ）４９例。Ａ、Ｂ两组的平均退热时数分别为１７．１±８．６、２９．４±２４．９小时;平均原虫转阴时间分别为２９．７±８．９、５４．７±１７．４小时;Ａ、Ｂ两组的治愈率分别为９８．０％、９５．９％。结果表明,复方蒿甲醚和本芴醇胶丸对恶性疟均有良好的治疗作用,但复方蒿甲醚在杀虫速度和控制症状方面明显优于本芴醇胶丸。     

Authentication of artemether, artesunate and dihydroartemisinin antimalarial tablets using a simple colorimetric method

The recent and widespread appearance of counterfeit antimalarial tablets in South-east Asia prompted the search for simple field assays to identify genuine drugs. In a recently described colorimetric assay for artesunate, Fast red TR salt reacted with an alkali-decomposition product of artesunate to produce a distinct yellow colour. However, that assay is specific for artesunate and it cannot be used to test for artemether. Because of potential concerns over artemether tablet counterfeiting, the colorimetric assay was modified to detect artemether, dihydroartemisinin and artesunate tablets. Other common antimalarials (artemisinin, chloroquine diphosphate, mefloquine HCl, sulphadoxine and pyrimethamine), as well as aspirin and acetaminophen, were negative in the assay, indicating its specificity for artemether, dihydroartemisinin and artesunate. The colorimetric method can be used to obtain a rapid visual assessment of tablet authenticity. The method can also be used to quantify the drug content of tablets, when used in conjunction with a spectrophotometer.     

双氢青蒿素哌喹复方片治疗缅甸恶性疟的临床观察

目的观察双氢青蒿素哌喹复方片对缅甸无并发症恶性疟的疗效。方法 2007-2008年,分别在缅甸佤邦和克钦邦两个区,选择6～60岁无并发症、原虫无性体密度为500～200 000个/μl的单纯恶性疟病例,使用双氢青蒿素哌喹复方片治疗,成人总剂量8片(每片含双氢青蒿素40 mg,磷酸哌喹320 mg),儿童剂量按年龄递减,疗程3 d。观察患者的退热时间、原虫转阴时间、无性体清除情况和不良反应等。结果共完成治疗134例患者,平均退热时间为(25.5±2.8)h,平均原虫转阴时间为(39.5±7.8)h,无性体7 d清除率100%,治后28 d有4例复燃;16例在服药后出现中枢神经系统及胃肠道反应,如头痛、恶心、呕吐和腹泻等轻微症状,停药后即自行消失。结论双氢青蒿素哌喹复方片在缅甸治疗无并发症恶性疟效果良好。     

Efficacy and safety of CGP 56697 (artemether and benflumetol) compared with chloroquine to treat acute falciparum malaria in Tanzanian children aged 1–5 years

A randomized, open trial involving 260 Tanzanian children, aged 1–5 years, with acute Plasmodium falciparum malaria was conducted to evaluate the efficacy of the combination antimalarial CGP 56697 (artemether and benflumetol), and to compare it with chloroquine, the standard drug used for malaria treatment in the Kilombero area. Children who had received rescue medication within the first 48 h or had a negative slide at the same time were excluded. Seven-day parasitological cure rates were 94% (95% CI 88–97.5) for CGP 56697 and 35.4% (95% CI 25.9–45.8) for chloroquine. Using the same definition, the 14-day parasitological cure rates were 86.4% (95% CI 78.5–92.2) for CGP 56697 and 10.3% (95% CI 5.1–18.1) for chloroquine. Gametocytes were more effectively suppressed by CGP 56697 than by chloroquine. There were no major adverse events with either drug. CGP 56697 is highly efficacious against P. falciparum in this area of Tanzania. The study contributes to the discussion on treatment strategies, particularly whether chloroquine may still fulfil its role as first-line drug in an area of high malaria transmission and very high levels of chloroquine resistance.     

双氢青蒿素、青蒿琥酯和蒿甲醚连续给药及伍用治疗小鼠血吸虫病效果观察

目的观察双氢青蒿素、青蒿琥酯和蒿甲醚连续给药或伍用治疗小鼠血吸虫病的效果,为日本血吸虫病病原学治疗提供药物配伍实验依据。方法采用腹部贴片感染法,每鼠感染日本血吸虫尾蚴40±1条,分别于感染后6~8 d(童虫期)和34~36 d(成虫期),以300 mg/kg双氢青蒿素、青蒿琥酯和蒿甲醚连续给药及3种药物等剂量配伍给药,在感染后50 d解剖小鼠,收集成虫,计算减虫率和减雌率。结果在感染后6~8 d,双氢青蒿素、青蒿琥酯、蒿甲醚连续3 d单独给药和3种药物等剂量配伍给药,小鼠减虫率为79.5%~86.0%;减雌率为79.4%~86.7%,差异均无统计学意义(P均>0.05);在感染后34~36 d给药,减虫率为73.8%~75.8%,减雌率为88.7%~93.1%,差异无统计学意义(P均>0.05)。结论双氢青蒿素、青蒿琥酯和蒿甲醚连续给药及伍用治疗小鼠血吸虫病效果无显著差异。     

Intramuscular artemether vs intravenous quinine: an open,randomized trial in Malawian children with cerebral malaria

objectives To compare artemether (by intramuscular injection) and quinine (by intravenous infusion) as treatments for cerebral malaria in African children.methods An open, randomized trial conducted at the Queen Elizabeth Central Hospital in Blantyre, Malawi. This trial was part of a multicentre study designed to determine if treatment with artemether would significantly lower mortality rates compared with quinine. Data from 83 artemether recipients and 81 quinine recipients are reported here.results Overall mortality rates and coma resolution times were not significantly different in the two treatment groups. Parasite and fever clearance times were significantly more rapid in the artemether recipients. Analyses which took into account the possible confounding variables did not significantly alter the findings of these unadjusted analyses.conclusion These results do not suggest that treatment with artemether would confer a survival advantage in children with life-threatening malaria. The power and precision of the estimated treatment effects of artemether would be enhanced by a meta-analysis of all relevant clinical trials.     

Artemether treatment of recrudescent Plasmodium falciparum malaria in children

Summary Intramuscular artemether given for five days was evaluated prospectively in 32 patients with acute recrudescent Plasmodium falciparum malaria. All patients had experienced one or more treatment failures with one or more courses of the following drugs: chloroquine, amodiaquine, sulphadoxine-pyrimethamine and erythromycin given alone or in combination. There was a prompt response to treatment with fever and parasite clearance times of 10.7 (3.6) h (range 6–24) and 32.3 (8.3) h (range 24–48) respectively. Parasite reduction at 24 h was 93.2 (7.8)% (range 75–100). The cure rate on day 14 was 100%. The drug was well tolerated. These results suggest that artemether is rapidly effective in acute recrudescent Plasmodium falciparum malaria and is without deleterious side effects.     

Pharmacokinetic study of artemether-lumefantrine given once daily for the treatment of uncomplicated multidrug-resistant falciparum malaria

BACKGROUND: Adherence to antimalarial drug regimens is improved by simple dosing. If the fixed antimalarial drug combination artemether-lumefantrine (AL) could be given once daily, this should improve adherence and thus effectiveness and lower the risk of selecting for resistance. METHODS: In an open randomized study, 43 patients with uncomplicated falciparum malaria were given equivalent doses of AL with 200 ml flavoured milk either as the conventional twice-daily regimen or as a single daily dose for 3 days. The primary end point was a comparison of the areas under the plasma lumefantrine concentration-time curves (AUC). Secondary end points were the day 42 polymerase chain reaction (PCR)-adjusted cure rates and the tolerability profiles. RESULTS: Lumefantrine pharmacokinetic profiles were obtained for 36 patients. The AUC((0-->infinity)) of the once-daily regimen was 30% lower than that in the conventional regimen (P = 0.011) with a median (range) value of 306 (114-5781) microg/ml h, compared with 432 (308-992) microg/ml h. There was no significant difference in the peak plasma concentrations reached. PCR-adjusted cure rate estimates at day 42 of follow-up were 94% (95% CI: 84-100) in the six-dose arm and 85% (70-100) in the three-dose arm (P = 0.3). CONCLUSION: Artemether-lumefantrine efficacy is reduced by once-daily dosing, because absorption of lumefantrine is dose limited. At currently recommended doses, this antimalarial should be given twice daily in a 3-day regimen, with food containing fat.     

驻西非3例华人特殊疟疾病例诊疗体会

疟疾是对全球健康影响最大的传染病,西非是疟疾的高流行地区。本文通过报道我国援塞拉利昂军事医学专家组在塞拉利昂诊治的3例疟疾患者的经验和体会,以期为临床医生在诊治类似疾病时提供参考、借鉴。     

Use of antenatal care services and intermittent preventive treatment for malaria among pregnant women in Blantyre District, Malawi

Malaria in pregnancy contributes to low birth weight and increased infant mortality. As part of WHO's Roll Back Malaria initiative, African heads of state pledged that by 2005, 60% of pregnant women will receive malaria chemoprophylaxis or intermittent preventive treatment (IPT). We performed a cluster sample survey to study the use of sulfadoxine-pyrimethamine (SP) for IPT among recently pregnant women in February 2000 in Blantyre District, Malawi. Among 391 women in the sample, 98.6% had attended antenatal clinic at least once and 90.2% knew that SP/IPT was recommended during pregnancy. Overall, only 36.8% received the full recommended two-dose regimen of SP/IPT. Using data from 187 women with antenatal clinic cards, we found that residence location, housing type and gender/age/education of the head of household were not associated with failure to receive SP/IPT. Adjusting for education, multigravid women were more likely not to receive the recommended SP/IPT regimen (RR 1.2, 95% CI 1.02-1.5, P=0.03). A substantial effort to improve the delivery and use of SP/IPT in Malawi will be necessary, but the Roll Back Malaria 2005 goal appears achievable.     

Open label randomized comparison of dihydroartemisinin–piperaquine and artesunate–amodiaquine for the treatment of uncomplicated Plasmodium falciparum malaria in central Vietnam

Objective  Artesunate–amodiaquine (AAQ) is efficacious for the treatment of uncomplicated Plasmodium falciparum malaria in Africa, but little is known about its efficacy in Southeast Asia. We compared the efficacy of dihydroartemisinin–piperaquine (DHP) and AAQ against falciparum malaria in central Vietnam.
Methods  Open, randomized clinical trial of 116 patients (36 children aged 6–14 years, 80 adults aged 15–60 years) were randomly allocated a 3-day course of either DHP (∼2.3 mg/kg dihydroartemisinin plus ∼18.5 mg/kg of piperaquine per day) or AAQ (∼4.4 mg/kg of artesunate plus ∼10.6 mg/kg of amodiaquine per day). The follow-up period was 42 days.
Results  The two drug combinations were well tolerated by all age groups with no obvious drug associated adverse events. Of the patients who completed 42 days of follow-up, 49 were on DHP (15 children, 34 adults) and 49 were on AAQ (14 children, 35 adults). The 42 day cure rates adjusted for reinfection identified by PCR genotyping for the two groups were similar [100% (49/49) and 98% (48/49) for DHP and AAQ, respectively]. With fewer reinfections, DHP appears to possess greater post-treatment prophylactic activity than AAQ.
Conclusion  AAQ, an inexpensive artemisinin-based combination, could be an additional option to DHP for the treatment of multidrug-resistant falciparum malaria in Vietnam.