A randomized, controlled trial of artemisinin-piperaquine vs dihydroartemisinin-piperaquine phosphate in treatment of falciparum malaria

Objective:The study aimed to evaluate and compare the efficacy and safety of dihydroartemisininpiperaquine phosphate(Artekin) and artemisinin-piperaquine(Artequick) in the treatment of uncomplicated falciparum malaria.Methods:A total of 103 uncomplicated falciparum malaria patients were enrolled and randomly assigned to two groups:52 cases in the Artequick group,and 51 cases in the Artekin group.The patients in the Artequick group were administered with Artequick,twice in 24 h,whereas the patients in the...     

Efficacy of dihydroartemisinin-mefloquine on acute uncomplicated falciparum malaria

目的　观察双氢青蒿素与甲氟喹联用治疗急性无并发症恶性疟疾的临床疗效。方法　以首日单剂双氢青蒿素 12 0mg顿服 ,次日及第三日甲氟喹 750mg及 50 0mg顿服的 3日疗法 ,治疗无并发症的恶性疟 54例 ,并于治疗后 1、2、3、4、7、14、2 1和 2 8天进行了随访。结果　 54例患者经治疗后全部临床治愈 ,平均疟原虫转阴时间为 30 .7± 3.6小时。平均退热时间为 2 1.2± 2 .8小时 ,54例中 2例在疟原虫血症消失后第 2 1、2 5天复燃 ,复燃率 3.7% ;治愈率 96.3%。除少数病人发生轻微及短暂的恶心呕吐、纳差外 ,余未发现严重不良反应。结论　双氢青蒿素与甲氟喹联用 3日疗法治疗无并发症恶性疟疾具有良好疗效。     

A phase III clinical trial of alpha, beta-arteether injection 150 mg/ml in patients of P falciparum malaria

The aim of study was to evaluate efficacy and safety of alpha, beta-arteether injection 150 mg/ml by performing a phase III, multicentre, open label, and single treatment study in patients with P falciparum malaria. A total of 145 patients with P falciparum malaria were screened to achieve patient pool of 101 subjects based on inclusion and exclusion criteria, from which 100 patients completed the study successfully. Mean cure rate was calculated as primary efficacy parameter, while mean parasite clearance time (hours) and mean fever clearance time (hours) were calculated as secondary efficacy parameters, to evaluate efficacy of alpha, beta-arteether injection 150 mg/ml. Safety evaluation was measured by observing and monitoring adverse events, clinical examination, assessment of vitals and haematology laboratory parameters. Statistical analysis was performed with 5% level of significance. Mean cure rate, mean parasite clearance time (hours) and mean fever clearance time (hours) were 99.01%, 24.72 +/- 0.41 hours and 46.86 +/- 0.97 hours respectively. A total of 6 patients were observed with pain at injection site out of 101 enrolled patients. There were no clinically significant vitals and haematology changes. There were no abnormal posttreatment values observed. The study confirmed that alpha, gamma-arteether injection 150 mg/ml is highly effective in treatment of P falciparum malaria.     

国产双氢青蒿素哌喹片治疗非洲恶性疟疾疗效观察

目的观察国产双氢青蒿素哌喹片治疗恶性疟疾的临床效果。方法在援尼日尔共和国工作期间采用随机分组的方法,将224例恶性疟疾患者分为治疗组和对照组,各112例,治疗组口服双氢青蒿素哌喹片（商品名为科泰复,每片含双氢青蒿素40mg、磷酸哌喹320mg）,首剂2片,8、24和32h分别服2片,一个疗程共8片;对照组用双氢青蒿素片（商品名为科泰新,每片60mg）,每天1片,首剂加倍,7d为1疗程,共8片。观察和记录病例的临床症状和药物的副作用。结果治疗组和对照组的临床治愈率为100％和96．4％,两组差异无统计学意义（P〉0．05）;平均退热时间为（36．16±13．32）和（40．42±15．63）h,两组差异有统计学意义（P〈．05）,治疗组短于对照组;复燃率为3．6％和13．4％。两组差异有统计学意义（P〈0．01）,治疗组低于对照组。结论国产双氢青蒿素哌喹片治疗非洲恶性疟疾效果明显。临床治愈率高,退热时间缩短,复燃率降低,无明显毒副作用,可作为治疗普通型恶性疟疾的首选药物。     

Halofantrine in the treatment of uncomplicated falciparum malaria with a three-dose regimen in Papua New Guinea: a preliminary report

We evaluated the efficacy and safety of halofantrine in 19 patients with acute uncomplicated falciparum malaria. Each patient received oral halofantrine hydrochloride 500 mg every 6 hours for 3 doses (total 1.5 g). In almost all the patients clinical symptoms of malaria and parasitaemia disappeared within 2 and 3 days, respectively, of starting treatment. We observed no recurrence of parasitaemia during 14 days of follow-up. Tolerance to halofantrine was good except for minor and self-limiting gastrointestinal side-effects. Haematological and biochemical indices were not seriously affected. Halofantrine-induced prolongation of Q-T/Q-Tc intervals was the consistent cardiac manifestation in 84% of patients. The Q-T/Q-Tc interval prolongation increased with each dose; it reached a maximum between 18 and 24 hours and thereafter returned to baseline. These preliminary data indicate that, apart from the cardiac side-effects, halofantrine is an effective and safe drug, well tolerated by most of the patients in the study.     

蒿甲醚联合复方双氢青蒿素片治疗维和任务区非重症疟疾的疗效

目的 评价蒿甲醚联合复方双氢青蒿素片对刚果（金）维和任务区非重症疟疾的临床疗效。方法 回顾性分析刚果（金）中国二级医院2018年9月—2019年9月收治的维和任务区56例非重症疟疾患者的临床资料。患者明确诊断后即予“蒿甲醚注射液”肌肉注射治疗,2~3 d后改为口服复方双氢青蒿素片。定期观察患者症状、体温、疟原虫密度和药物不良反应等指标。按WHO抗疟药物临床疗效分类综合评价治疗方案的疗效。结果 56例非重症疟疾患者中,单纯恶性疟41例,混合疟15例。全部患者均获得完全临床原虫治疗成功,无严重不良反应发生。平均退热时间单纯恶性疟患者为（28.5±7.6） h,混合疟患者为（26.4±6.5） h;平均疟原虫清除时间单纯恶性疟患者为（31.5±8.3） h,混合疟患者为（30.4±6.7） h;平均疟原虫清除半衰期单纯恶性疟为（2.54±0.55） h,混合疟患者为（2.42±0.43） h。两组患者退热时间、疟原虫清除时间及清除半衰期差异均无统计学意义（P>0.05）。结论 蒿甲醚联合复方双氢青蒿素片可有效治疗刚果（金）维和任务区非重症疟疾,且安全性良好。     

Comparison Between Different Effects Gained by Courses Of Different Length in Treating Falciparum Malaria with Artesunate Tablet

Ｃｏｍｐａｒｉｓｏｎ　Ｂｅｔｗｅｅｎ　Ｄｉｆｆｅｒｅｎｔ　Ｅｆｆｅｃｔｓ　Ｇａｉｎｅｄ　ｂｙ　Ｃｏｕｒｓｅｓ　Ｏｆ　Ｄｉｆｆｅｒｅｎｔ　Ｌｅｎｇｔｈ　ｉｎ　Ｔｒｅａｔｉｎｇ　Ｆａｌｃｉｐａｒｕｍ　Ｍａｌａｒｉａ　ｗｉｔｈ　Ａｒｔｅｓｕｎａｔｅ　Ｔａｂ...     

Development of the New antimalarial Drug Pyronaridine：A Review

This report outlines the structure scheme and development of a new antimalarial drug pryonaridine,which was synthesized from either 2-aminopyridine or pyridine.A series of in vivo and in vitro experimental studies and the assessment of toxicity revealed pyronaridine to be a promising agent against erybthrocytic stage of malaria parasites.It exhibited low toxicity and had no corss-resistance to chloroquine.Chlinical administration in malaria cases showed high efficacy and mild side-effects.In order to retard the development of resistance of Plasmodium falciparum to pyronaridine,a combination of pyronaridine/sulfadoxine/pyrimethamine was used in the treatment of chloroquine-resistant falciarum malaria in Hainan Province.Further in vivo test was carried out to monitor the sensitivity of Pfalciparum to this combined formula for 5 years(1986-1990)in Diaoluo area where chloquineresistant falciparum malaria was prevalent.Drug resistance was not demonstrated in this field study.     

青蒿素哌喹片联合伯氨喹治疗科摩罗无并发症恶性疟临床疗效观察(英文)

【目的】评价青蒿素哌喹片联合伯氨喹治疗科摩罗恶性疟有效性和安全性,验证青蒿素哌喹片—伯氨喹治疗非洲恶性疟的有效临床剂量。【方法】共观察了无并发症恶性疟患者155例。成人口服青蒿素哌喹片—伯氨喹片1次/d,2片/次,连续2 d,1个疗程共4片(青蒿素320 mg,哌喹1 500 mg,伯氨喹16 mg);6岁以下儿童使用青蒿素哌喹片—伯氨喹颗粒剂。28 d后观察复燃率、平均原虫清除时间、平均退热时间、副作用等。【结果】服药后患者临床症状快速缓解。平均原虫清除时间(PCT)为(51.0±25.9)h,平均退热时间为(20.8±11.4)h。患者对青蒿素哌喹片—伯氨喹有良好的耐受性。只有少数患者出现恶心、呕吐和头晕等不良反应,副作用发生局限且能自愈。患者用药前及开始用药后的第7天观察血常规、生化检查未见明显毒副作用。【结论】青蒿素哌喹片—伯氨喹治疗无并发症恶性疟具有高效、速效、副作用低和疗程短等特点。     

Use of buffy coat thick films in detecting malaria parasites in patients with negative conventional thick films

Objective

To determine the frequency of malaria parasite detection from the buffy coat blood films by using capillary tube in falciparum malaria patients with negative conventional thick films.

Methods

Thirty six uncomplicated falciparum malaria patients confirmed by conventional thick and thin films were included in the study. The patients were treated with artemisinin combination therapy at Hospital for Tropical Diseases, Bangkok, Thailand for 28 day. Fingerpricks for conventional blood films were conducted every 6 hours until negative parasitemia, then daily fingerpricks for parasite checks were conducted until the patients were discharged from hospital. Blood samples were also concurrently collected in 3 heparinized capillary tubes at the same time of fingerpricks for conventional blood films when the prior parasitemia was negative on thin films and parasitemia was lower than 50 parasites/200 white blood cells by thick film. The first negative conventional thick films were compared with buffy coat thick films for parasite identification.

Results

Out of 36 patients with thick films showing negative for asexual forms of parasites, buffy coat films could detect remaining 10 patients (27.8%) with asexual forms of Plasmodium falciparum.

Conclusions

The study shows that buffy coat thick films are useful and can detect malarial parasites in 27.8% of patients whose conventional thick films show negative parasitemia.     

云南省恶性疟治疗研究现状

回顾了近40a来云南省对治疗恶性疟研究的疗效判定标准、抗性判定标准、病例入选标准和排除标准、病例观察方法以及实验室血液和生化指标选择,描述了5个单方和15个联合用药的效果观察结果,认为近年来云南的恶性疟原虫对氯喹的抗性仍然维持较高的水平;萘酚喹的治愈率高但是其临床即时效果不明显;蒿甲醚与本芴醇联用的效果最好;复方蒿甲醚和青蒿琥酯＋萘酚喹两配伍的治愈率、平均退热时间和平均无性体原虫清除时间均相似,是复方中较好的;青蒿素栓可首选与甲氟喹500mg伍用;青蒿琥酯与苯勿醇伍用的治愈率高达100％但是平均退热时间较长（仅次于苯勿醇单用）．对方法学按照目前国际流行的GCP进行了初步评价,针对存在的问题建议即按照GCP的要求建立云南省的恶性疟治疗效果评价标准方案和监查的标准规程（SOP）,建立必要的抗疟药临床实验基地,对常用的药物开展纵向敏感性观察、应用现代成熟的分子生物学方法为效果判断提供准确的数据．     

Halofantrine versus quinine-Fansidar combination in the treatment of post-chloroquine falciparum parasitaemia

The standard first-line treatment for malaria in adults in Papua New Guinea is chloroquine; for severe and treatment-failure malaria standard therapy is a combination of quinine and Fansidar (sulphadoxine-pyrimethamine). These standard treatments are currently under revision. The present study evaluated the effect of halofantrine in treatment-failure falciparum malaria in adults in Port Moresby compared to standard therapy. In the halofantrine group all parasites were cleared by day 5 after starting therapy, in the quinine-Fansidar group by day 7. There was no evidence of recurrence of parasitaemia during the 21-day follow-up in either group. Nausea was associated with halofantrine use in 68% of patients. In the quinine-Fansidar group 79% had muffled deafness, 32% tinnitus and 26% dizziness; 32% of patients withdrew from treatment on day 2 because of intolerance to quinine. Halofantrine in this study population provided an efficacy against treatment-failure falciparum malaria similar to that of quinine-Fansidar, with a more favourable profile of adverse effects.     

Therapeutic efficacy of chloroquine or amodiaquine in combination with sulfadoxine-pyrimethamine for uncomplicated falciparum malaria in Papua New Guinea

Resistance of Plasmodium falciparum to chloroquine is widespread in Papua New Guinea. At a meeting in Port Moresby in October 1997, it was decided to explore a possible change of the current first-line treatment of uncomplicated malaria with chloroquine alone (amodiaquine for children under five years) to chloroquine or amodiaquine in combination with sulfadoxine-pyrimethamine (S-P). To assess the therapeutic efficacy of the new drug combination in Papua New Guinea, a study was carried out in 1998-1999 at five hospital outpatient departments. From the 513 patients enrolled for the study, 95 defaulted from follow-up. Of the remaining 418, 399 (95.5%) had an adequate clinical response (ACR). Out of the 19 patients who did not have an ACR, 3 (0.7% of the total) developed severe signs in the first 24 hours and were treated in hospital; they were regarded as early treatment failures. The remaining 16 did not complete the study on the basis of various exclusion criteria but were not excluded from the analysis. From these results it was concluded that the combination was effective and a decision was taken in May 2000 to introduce the two-drug combination regimens as the standard first-line treatment of uncomplicated malaria, including falciparum malaria, in Papua New Guinea.     

Evaluation of leptin,interleukin–1 beta and tumor necrosis factor alpha in serum of malaria patients as prognostic markers of treatment outcome

ObjectiveTo analyze serum leptin levels in patients with malaria falciparum and compare them with healthy controls and correlate with development and outcome of malaria infection.MethodsSixty cases of malaria falciparum were included in this study as patients. Thirty healthy individuals of comparable age, racial and body mass index were taken as controls. All patients were diagnosed by clinical picture and the presence of malaria parasites in blood film. Estimation of liver function test, kidney function test, complete blood count, fasting blood sugar, fasting serum insulin, pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) and interleukin 1 (IL1), estimation of morning serum leptin and calculation of body mass index (kg/m²) were done in both groups on the day of admission, on discharge and 7 d after discharge.ResultsAt admission, leptin levels were significantly higher in patients group than in control while fasting serum insulin levels were not significantly different between the two groups. There were significant increases as regard to TNFα and IL1 in malaria patients. Significant differences were observed between the control and the patient group for leptin, TNFα and IL1 at the time of admission and discharge. After discharge for 7 d, a significant decline in serum leptin levels, TNFα and IL1 in the patients group was observed as compared with time of admission and time of discharge, a positive correlation between serum leptin levels and TNFα and IL1.ConclusionsLeptin hormone level might play an important role in development and outcome of malaria infection.     

青蒿琥酯与二盐酸奎宁治疗恶性疟的随机比较

青蒿琥酯３天疗程总量４．８ｍｇ／ｋｇ，二盐酸奎宁３天疗程总量１００ｍｇ／ｋｇ，随机分组，分别治疗恶性疟３０例。平均退热时间青蒿琥酯组为１７．６ｈ，奎宁组为２９．２ｈ（Ｐ＜０．０１）；平均原虫转阴时间青蒿琥酯组为５８．８ｈ．奎宁组为７８．８ｈ（Ｐ＜０．０１）；原虫复燃率青蒿琥酯组５６．７％，奎宁组５０％（Ｐ＞０．０５）；清除原虫９５％所需时间青蒿琥酯为１６ｈ，奎宁为２８ｈ。青蒿琥酯组未见任何副反应，奎宁组有明显的中枢神经系统和胃肠道副反应。     

Intramuscular loading dose of quinine for falciparum malaria: pharmacokinetics and toxicity

In a study of intramuscular injection of quinine eight adults with moderately severe falciparum malaria resistant to chloroquine were treated with quinine dihydrochloride, being given a loading dose of 20 mg salt (16.7 mg base)/kg followed by three or four eight hourly maintenance doses of 10 mg salt (8.3 mg base)/kg injected into the anterior thigh. All patients responded to treatment. Fever and parasite clearance times (mean (SD) 60 (23) h and 53 (22) h respectively) were comparable with those obtained with intravenous quinine. The mean peak plasma quinine concentration of 11.0 mg/l (34.4 mu mol/l) [corrected] was reached a median of five hours after administration of the loading dose. In all patients plasma quinine concentrations exceeded the high minimum inhibitory concentration for Plasmodium falciparum malaria prevalent in Thailand within four hours of the start of treatment but did not cause toxicity other than mild cinchonism. When intravenous infusion is not possible an intramuscular quinine loading dose is an effective means of starting treatment in patients with moderately severe falciparum malaria who cannot swallow tablets.     

A recombinant multi-epitope, multi-stage malaria vaccine candidate expressed in Escherichia coli

Ｔｈｅｄｅｖｅｌｏｐｍｅｎｔｏｆａｎｅｆｆｅｃｔｉｖｅｍａｌａｒｉａｖａｃｃｉｎｅｐｒｏｖｉｄｅｓａｃｏｓｔｅｆｆｅｃｔｉｖｅｉｎｔｅｒｖｅｎｔｉｏｎｆｏｒａｄｄｉｔｉｏｎｔｏｃｕｒｒｅｎｔｌｙａｖａｉｌａｂｌｅｍａｌａｒｉａｃｏｎｔｒｏｌｓｔｒａｔｅｇｉｅｓ１　Ｈｏｗｅｖｅｒ,ｓｅｖｅｒａｌｉｍｐｏｒｔａｎｔｆａｃｔｏｒｓ,ｉｎｃｌｕｄｉｎｇｔｈｅｄｅｖｅｌｏｐｍｅｎｔａｌｒｅｇｕｌａｔｉｏｎｏｆａｎｔｉｇｅｎｅｘｐｒｅｓｓｉｏｎｄｕｒｉｎｇｐａｒａｓｉｔｅｒｅｐｌｉｃａｔｉｏｎ,ｎｏｎｒ…     

二十二碳六烯酸抑制大鼠视网膜光感受器细胞凋亡

目的:观察二十二碳六烯酸(DHA)对N-甲基-N-亚硝基脲(MNU)所致视网膜光感受器细胞凋亡的影响,为其临床应用提供理论依据.方法:35只雌性SD大鼠随机分为7组,每组5只.除正常组外,其余各组均于出生后35 d开始灌胃,DHA组和造模组每日分别灌服含有一定量DHA的脱脂牛奶或等体积的脱脂牛奶,持续15 d后行腹腔注射MNU 40 mg/kg.分别于造模后12,24,48 h全麻后处死相应动物,取眼球行光镜观察及用末端脱氧核苷酸转移酶介导dUTP缺口末段标记(TUNEL)法检测各组大鼠视网膜细胞的凋亡.结果:光镜下显示中周部视网膜在造模后24 h开始出现光感受器细胞排列紊乱,少量核固缩,48 h后光感受器细胞已大量溶解,而DHA组光感受器细胞的形态均接近正常,仅见排列紊乱、稀疏.造模组光感受器细胞在造模后12,24,48h的凋亡百分率(AD分别为(5.3±1.1)％、(60.6±4.1)％、(97.1±1.9)％,DHA组在造模后12,24,48 h的AI分别为(4.3±1.4)％、(44.5±7.8)％和(78.7±5.8)％,24 h和48 h后造模组和DHA组间比较均有统计学差异(P＜0.05).结论:二十二碳六烯酸40 mg/(kg·d)可以有效抑制视网膜光感受器细胞的凋亡.     

Comparative clinical study of duodongning and ritalin in treating attention- deficit/hyperactivity disorder) and ritalin in treating attention- deficit/hyperactivity disorder

Objective: To study the effect and side-effects of Duodongning (DDN), a traditional Chinese medicine (TCM) granule in treating attention-deficit/hyperactivity disorder (ADHD).Methods: Double blind method was used to compare DDN with ritalin for ADHD in clinical practice from December 1995 to December 1996. The total number of cases was 70.Results: There were 37 cases in DDN group, with 17 cases (45.9 %) markedly effective, 16 cases (43.2%) effective, the Conners hyperactive index (HI) 2. 01 ± 0. 83 (before treatment), 1.17 ± 0.76 (after 4 weeks ’ treatment); and there were 33 cases in the ritalin group, with 15 cases (45.5%) markedly effective, 14 cases (42.4%) effective, HI2.07±0.91 (before treatment), 1.47±0.79 (after 4 weeks’ treatment). Insignificant difference existed between the effectiveness in these 2 groups (P > 0.05). The chief side-effects were 3 cases (8.1%) of anorexia in DDN group, and 7 cases (21.2%) in ritalin group.Conclusion: The effect of DDN is not significantly different from that of ritalin, and the side-effects in ritalin group were more than those in DDN group.     

复方萘酚喹治疗恶性疟疾的剂量探索

【目的】进一步探索新近研制成功的复方抗疟药复方萘酚喹 (由磷酸萘酚喹、双氢青蒿素和甲氧苄啶组成 )治疗恶性疟的用药剂量。【方法】采用 1d疗程 2次分服 ,设总剂量 4片组和 2片组 ,评价和比较其疗效。两组分别治疗无并发症恶性疟患者各 50例。【结果】 2片组的退热时间与 4片组相似 ,但原虫转阴时间明显慢于 4片组 ,2 8d治愈率 2片组 ( 85.1% )亦显著低于 4组片 ( 97.8% )。且 2片组出现早期 ( 14d)原虫复燃 ,说明其药量不足。【结论】推荐复方萘酚喹治疗恶性疟的临床试验治疗总剂量采用 3～ 4片为宜