吡喹酮对曼氏裂头蚴感染小鼠治疗效果的进一步观察

目的进一步观察吡喹酮对曼氏裂头蚴感染小鼠的疗效。方法将72只小鼠分为8组（每组9只）,每只小鼠经口感染5条裂头蚴,感染后1周1-3组分别应用2 000、2 800、3 600mg/kg吡喹酮治疗1个疗程（每日3次,疗程3d）后1周剖杀,4-6组治疗2个疗程后1周剖杀,7、8组为对照组。另选40只小鼠分为4组（每组10只）,每只经口感染5条裂头蚴,感染后14周1～3组应用2 000mg/kg吡喹酮治疗后1、3、5周剖杀;4组为对照组。各组小鼠剖杀后收集裂头蚴数并计算各组的平均检出虫数和减虫率,光镜下观察虫体形态变化。结果小鼠感染裂头蚴后1周,应用2 000、2 800、3 600mg/kg吡喹酮治疗1个疗程后的减虫率分别为70.6%、77.3%及84%（P〉0.05）,治疗2个疗程后的减虫率分别为57.1%、54.6%及54.6%（P〉0.05）。小鼠感染裂头蚴后14周,应用2 000mg/kg吡喹酮治疗后1、3及5周的减虫率分别只有28%、20%及20%（P〉0.05）;虽然治疗后裂头蚴虫体有断裂现象,体壁上出现突起、溃烂及溶解等,但虫体头部无明显破坏。结论增加剂量与疗程不能提高吡喹酮对裂头蚴感染小鼠的疗效;吡喹酮对裂头蚴病的治疗效果可能与感染后的治疗时间有关。     

广西少数民族地区口服伯喹发生227例溶血反应分析

广西境内有16个民族聚居地区,其中壮族占全区人口33.88％。本文根据1975～1991年16个县(市)资料统计,共发现227例溶血反应病例,均经及时处理治愈,无死亡病例。所服伯氨喹啉(伯喹)系上海天平制药厂(沪卫药准字第0284号)产品,每片含量7.5mg(基质),成人每日口服伯喹22.5mg(基质),儿童按年龄递减,其疗程不等,服药天数为1、2、3、4、5和8d。据227例溶血反应发生时间来看,口服伯喹后第1～6d出现     

三种不同疗法治疗间日疟的效果观察

在我国黄淮平原的新沂县间日疟流行区,应用咯萘啶1.6g 伍用伯喹120mg4d 分服,治疗236例间日疟现症患者,并与241例用氯喹1.5g、伯喹120mg 4d 分服及228例用氯喹1.5g、伯喹180mg 8d 分服治疗的患者进行比较,结果咯伯4d 疗法治疗后10个月内复发率8.5％(包括无症状原虫复燃病例,下同)氯伯4d 疗法的复发率为12.4％,而氯伯8d 疗法复发率3.5％,较前两种疗法显著为低。用间接荧光抗体(IFA)观察,在治疗10个月后转阴率咯伯四日组76.3％,氯伯四日组为73.9％及氯伯八日组为73.3％,无显著差别。     

1例热带型间日疟治疗分析

患者 ,男 ,1 9岁 ,四川省凉山州德昌县人。1 997年 5月由缅甸打工返回。6月初出现头痛、畏寒、隔日发热等疟疾症状 ,当地诊断为间日疟 ,给予氯喹 1 2 0 0 mg3d分服 ,伯喹 1 80 mg8d治疗 ,症状一度减轻。 2月后 ,再次出现疟疾症状 ,遂以氯喹 1 5 0 0 mg 3d分服 ,伯喹 90 mg4 d治疗 ,症状再次得到缓解。 1个月后即 9月底又发病 ,并到本所门诊进行诊治 ,血检确诊为间日疟 ,镜下可见各期原虫 ,易见双虫感染 ,红细胞受染率达 30 /万。鉴于病人感染程度较重 ,且前两次常规治疗效果不甚理想 ,病人也自感服药后末见任何药物反应 ,病人体重 90 kg,于…     

葡萄糖酸锑钠长疗程治疗1例利什曼原虫与人类免疫缺陷病毒合并感染患者的追踪观察

目的报道使用葡萄糖酸锑钠长疗程治疗1例利什曼原虫与人类免疫缺陷病毒(HIV)合并感染患者的疗效及预后。方法收集患者的临床资料,追踪观察患者的疗效及预后。结果患者1990年在四川省九寨沟县(内脏利什曼病流行区)工作。1992年末出现发热、肝脾肿大,被多家医院诊断为"肝硬化",对症治疗无效,脾脏持续肿大,并出现严重贫血、消瘦。1994年经骨髓穿刺涂片镜检发现利什曼原虫,诊断为内脏利什曼病,给予葡萄糖酸锑钠(五价锑600 mg/d×6 d,静脉滴注)治疗,病情缓解。2010年8月,患者发现左上腹有包块,伴腹胀,再次行骨髓穿刺涂片镜检,发现利什曼原虫,再次给予葡萄糖酸锑钠(五价锑600 mg/d×6 d,静脉滴注)治疗,病情缓解。住院期间初筛HIV抗体阳性,经蛋白质印迹(Western blotting)检测确认为HIV感染,CD4~+T淋巴细胞仅为42个/μl,诊断为艾滋病(AIDS)。2011年7月,患者开始接受抗HIV常规治疗[拉米夫定(3TC)300 mg/d+齐多夫定(AZT)600 mg/d+依非韦伦(EFV)600 mg/d],治疗2个月后出现严重贫血,将AZT更换为替诺福韦(TDF)300 mg/d,长期服用3TC+TDF+EFV。2012年7月25日患者因"腹胀2年"入住本院,入院时呈重度贫血貌,肝脏位于右锁骨中线肋缘下2 cm;脾脏下缘位于脐下7 cm,右缘位于前正中线右侧2 cm。骨髓涂片镜检查见利什曼原虫。继续给予抗HIV治疗(3TC+TDF+EFV),同时给予葡萄糖酸锑钠静脉滴注治疗内脏利什曼原虫感染[第1个疗程:先后给予葡萄糖酸锑钠(五价锑600 mg/d×4 d,1 200 mg/d×4 d)治疗,肝脾开始缩小后,改为隔天静脉滴注葡萄糖酸锑钠(五价锑600 mg/次×22次)]。在第1个疗程结束后1个月和3个月,分别给予1个疗程葡萄糖酸锑钠治疗(五价锑600 mg/次×18次)。3个疗程共计给予五价锑42 g治疗。2017年4月(抗利什曼原虫治疗结束后50个月)复诊,骨髓涂片检查未见利什曼原虫,CD4~+T淋巴细胞为249个/μl,HIV-RNA低于检测下限。结论对内脏利什曼原虫合并HIV感染的患者给予葡萄糖酸锑钠长疗程及抗HIV治疗,内脏利什曼感染获得治愈,患者预后较好。     

曼氏裂头蚴实验感染小鼠吡喹酮治疗后血清IgG水平的变化

目的观察曼氏裂头蚴实验感染小鼠吡喹酮治疗后血清IgG抗体水平的变化。方法将40只雄性昆明小鼠随机分为4组(每组10只),1~3组分别经口接种1、5、1条裂头蚴,1组和2组于感染后3周应用吡喹酮灌胃治疗(总剂量2 800 mg/kg体重,3次/d,疗程3 d),3组和4组分别为阳性和空白对照组。每周尾静脉采血,ELISA检测血清裂头蚴IgG抗体。治疗后18周剖杀,收集裂头蚴并计算减虫率。结果感染后3周,1条和5条裂头蚴感染小鼠的血清IgG抗体阳性率均为100%;两组小鼠治疗后1周血清IgG抗体水平快速升高,治疗后2周达峰值,然后开始下降,治疗后18周两组小鼠的血清IgG抗体阳性率分别为70%和100%,与治疗后5周相比无明显下降;减虫率分别为20%和0。检出的虫体平均长26.1 cm,比接种时虫体(平均长5 cm)均显著增长,其中36.21%(21/58)的虫体形成囊包。结论吡喹酮(2 800 mg/kg体重)对裂头蚴无明显杀虫作用,裂头蚴感染小鼠应用吡喹酮治疗后血清抗裂头蚴IgG水平无明显下降。     

CTD方案治疗难治或复发多发性骨髓瘤

目的应用环磷酰胺、沙立度胺及地塞米松(CTD)方案治疗难治或复发多发性骨髓瘤(MM)。方法20例难治或复发MM患者接受沙立度胺,100~200mg/d,口服持续应用;环磷酰胺,200~300mg.m-2.d-1,1~4d,静脉注射;地塞米松,20~40mg/d,1~4d,口服。4周为1个疗程。3个疗程后,若出现疗效或病情稳定则再连续应用3个疗程;若病情进展,则停止治疗。结果3个疗程后,13例(65%)患者显示治疗反应,其中9例患者获部分缓解,4例患者获微小缓解。而5例患者病情稳定,2例进展。对病情未进展的18例患者继续治疗3个疗程后再次评价,则部分缓解13例(65%),获微小缓解5例。结论CTD是一个具有较好治疗前景的方案。     

脑疟佳对恶性疟原虫配子体作用的研究

60例恶性疟原虫配子体携带者,其中25例接受脑疟佳治疗,22例用伯喹和13例用氯喹治疗。给药后配子体平均消失时间分别为3.4,4.1和27.4d。脑疟佳的杀配子体效果和伯喹相似,而明显优于氯喹(P<0.01)。另8例病人,给药后观察配子体对媒介按蚊的感染活力,5例给单剂75mg 脑疟佳,给药后12h,4例完全阻断配子体对按蚊的感染,而50mg 组的3例基本无效。     

不同剂量磷酸咯萘啶、磺胺多辛、伯喹伍用治疗抗氯喹恶性疟的观察

在云南西南部抗氯喹恶性疟流行区,用磷酸咯萘啶(咯)1000mg、磺胺多辛(磺)1000mg和伯喹(伯)45mg治疗恶性疟62例;咯1250mg、磺1250mg与伯56.25mg治疗20例;咯1200mg、磺1500mg与伯67.5mg治疗34例,进行比较观察,三组即时疗效相似,三组治疗后28d内的复燃率分别为15.5％、5.9％及8.7％;治疗后7d内的配子体清除率分别为66.7％、100％及100％,三组间有高度显著性差异。结果提示三药伍用治疗抗氯喹恶性疟时,咯萘啶总量不宜少于1200mg;伯喹不宜少于56.25mg。     

咯萘啶合并伯喹根治间日疟的疗效

鉴于氯伯八日疗法疗程长、副反应大,我们从1976年起,试用咯萘啶合并伯喹三日疗法,根治间日疟530例。甲组咯萘啶总量32mg/kg(成人量1.6g),三日分服,各为0.8、0.4、0.4g,每天同时服伯喹30mg,共90mg,乙组咯萘啶总量1.2g,每天0.4g,同服伯喹30mg。氯伯八日疗法对照126例,氯喹总量1.2g,第一日O.6g、二、三日各0.3g,每天服伯喹22.5mg,八天共180mg。本疗法优点:(1)疗程短;每天服药一次,共服三天;(2)杀虫速度快、控制症状快;无性期原虫48小时、有性期原虫72小时全部阴转,投药后即控制症状,无发作第二次者(“药杀热”除外);(3)根治率97.74％,与氯伯八日疗法相当,高于氯伯三日疗法;(4)伯喹用药量少,为氯伯八日疗法中伯喹的半量,副反应少。     

Tafenoquine for the treatment of recurrent Plasmodium vivax malaria

Tafenoquine was used to treat Plasmodium vivax malaria cases who had previously failed treatment with chloroquine and primaquine. Chloroquine was followed by a loading dose of tafenoquine (200 mg base/day for 3 days) and 200 mg a week was given for 8 weeks. One of 27 treated patients relapsed after 6 months of observation. A standard course of chloroquine administered with 8 weeks of tafenoquine may be more effective than chloroquine with primaquine (22.5 mg/day for 14 days) in preventing additional P. vivax relapses. Larger studies are required to optimize the combination, but our findings suggest that an extended use of tafenoquine may be required to prevent relapses of primaquine-tolerant strains of P. vivax malaria.     

Chloroquine sensitivity of Plasmodium vivax in Thailand

Chloroquine has been the standard treatment for Plasmodium vivax malaria for more than 40 years in most regions of the world. Recently, however, chloroquine-resistant P. vivax has been reported from Oceania, several parts of Asia, and South America. In order to assess the situation in Thailand, 886 patients with vivax malaria who were admitted to the Bangkok Hospital for Tropical Diseases from 1992 to 1997 were followed prospectively. Most of the patients had been infected on the western border of Thailand and were experiencing their first malarial infection when admitted. All received oral chloroquine (approximately 25 mg base/kg body weight, administered over 3 days) and then were randomized to receive primaquine (15 mg daily for 14 days) or no further treatment. All the patients were initially responsive to chloroquine, clearing their parasitaemias within 7 days, and there were no significant differences in the clinical or parasitological responses between those treated with primaquine and those given no further treatment. Plasmodium vivax parasitaemias re-appeared within 28 days of chloroquine treatment in just four patients. In each of these four cases, re-treatment with the same regimen of chloroquine resulted in eradication of the parasitaemia, with no further appearance of parasitaemia during the next, 28-day, follow-up period. These data indicate that virtually all acute (i.e. blood-stage) P. vivax infections acquired in Thailand can still be successfully treated with chloroquine.     

Double-blind, randomized, placebo-controlled assessment of chloroquine/primaquine prophylaxis for malaria in nonimmune Colombian soldiers.

To improve upon the efficacy of primaquine prophylaxis for malaria (94%, Plasmodium falciparum malaria; 85%, Plasmodium vivax malaria), we administered chloroquine (300 mg weekly) in combination with primaquine (30 mg daily) to nonimmune Colombian soldiers during 16 weeks of patrol in a region of endemicity and for a further 1 week in base camp. The occurrence of symptomatic parasitemia was determined during those 17 weeks and during a further 3 weeks in base camp. The protective efficacy for the chloroquine/primaquine treatment group of 100 subjects, compared with that for the placebo treatment group of 51 subjects, was 88% (95% confidence interval [CI], 76-94) against all types of malaria, 89% (95% CI, 61-97) against P. falciparum malaria, and 88% (95% CI, 58-93) against P. vivax malaria. Two chloroquine/primaquine recipients had severe gastrointestinal distress. Comparison of these data with data from a previous study indicates that the addition of chloroquine did not increase the prophylactic efficacy of primaquine.     

Short report: a consideration of primaquine dose adjustment for radical cure of Plasmodium vivax malaria

Relapse of Plasmodium vivax malaria following standard primaquine dosing has been reported from many areas, and more recently from sub-Saharan Africa. In this report we describe eight episodes (in five patients) of treatment failure in non-immune Israeli travelers returning from Ethiopia. Retrospective calculation of the primaquine dose per kilogram of body weight for 23 treatment courses showed a lower total dose per kilogram in heavier patients. The mean calculated dose (95% CI) in the eight failed treatments was 2.5 +/- 0.3 mg/kg compared with 4.4 +/- 0.5 mg/kg in the 15 successful treatment courses. Weight-adjusted dosing regimens may prevent inadvertent subtherapeutic drug failure, and thus apparent primaquine failure. In these cases, no relapses were observed in those who received > 3.5 mg/kg. Consideration should be given to adjusting the dose of primaquine according to body weight. For those infected by strains from Ethiopia a dose > 3.5 mg/kg is preferable.     

Use of a rhesus Plasmodium cynomolgi model to screen for anti-hypnozoite activity of pharmaceutical substances

There remains a need for new drugs to prevent relapse of Plasmodium vivax or P. ovale infection. The relapsing primate malaria P. cynomolgi has been used for decades to assess drugs for anti-hypnozoite activity. After sporozoite inoculation and blood-stage cure of initial parasitemia with chloroquine, rhesus macaques were treated on subsequent relapses with chloroquine in conjunction with test regimens of approved drugs. Tested drugs were selected for known liver or blood-stage activity and were tested alone or in conjunction with low-dose primaquine. Tinidazole and pyrazinamide prevented relapse when used in conjunction with chloroquine and low-dose primaquine. Triamterene and tinidazole administered without primaquine achieved radical cure in some animals. All other tested drugs or combinations failed to prevent relapse. The rhesus macaque-P. cynomolgi model remains a useful tool for screening drugs with anti-hypnozoite activity. Tinidazole and pyrazinamide require further investigation as agents to enable dose reduction of primaquine.     

Assessment of therapeutic efficacy of chloroquine for vivax malaria in Thailand

Chloroquine-resistant Plasmodium vivax has been reported in some Asian countries. In 2003, 161 patients infected with vivax malaria were treated according to the Thai National Drug Policy, with oral chloroquine (approximately 25 mg base/kg body weight, administered over 3 days) followed by primaquine on day 28 (15 mg daily for 14 days). All the patients were initially cured after chloroquine treatment, clearing their parasitemias within 7 days. Only one patient presented with parasitemia at 28 days. These data indicate that chloroquine is still effective for the treatment of patients with vivax malaria in Thailand.     

A clinical trial of mefloquine in the treatment of Plasmodium vivax malaria

A clinical field trial was conducted to determine if mefloquine is effective in the treatment of malaria due to Plasmodium vivax. Forty patients with P. vivax malaria were treated with either mefloquine, chloroquine or chloroquine plus primaquine and followed for 28 days. All patients responded rapidly and were cured. There were no significant side effects.     

Efficacy of three chloroquine-primaquine regimens for treatment of Plasmodium vivax malaria in Colombia.

Plasmodium vivax malaria is an important cause of morbidity in Central and South America. In Colombia, this is the most prevalent malaria infection, representing 75% of the reported cases. To define the efficacy of the chloroquine and primaquine regimen to eliminate hypnozoites and prevent relapses, we conducted a random controlled clinical trial of three primaquine regimens in an open-label study. We evaluated the anti-relapse efficacy of total primaquine doses of 45, 105, and 210 mg administered at a dosage of 15 mg/day in 210 adults with P. vivax infection from the northwestern region of Colombia. Cure rates for blood-stage P. vivax malaria by day 28 of follow-up were 100% in all groups. Post-treatment reappearance of parasitemia during the six months of follow-up was 45%, 36.6% and 17.6%, respectively, for each group. When compared with other groups, administration of 210 mg was a significant protection factor for reappearance of parasitemia in a malaria-endemic area.     

Therapeutic efficacy of artesunate in Plasmodium vivax malaria in Thailand

Our previous study showed that in vitro susceptibility of Plasmodium vivax to chloroquine has significantly decreased in Thailand within the past two decades. Thus, the evaluation of alternative antimalarials for treatment of vivax malaria is needed. The aim of this study was to examine parasitological and clinical efficacy of an artemisinin derivative (artesunate) for the treatment of vivax malaria in patients who were admitted to the Bangkok Hospital for Tropical Diseases. We randomly allocated patients aged 12-56 years to receive 3.3mg/kg (adult dose 200 mg) on the first day, and for the next four days each patient was given 1.65 mg/kg orally (adult dose 100 mg), total dose = 600 mg. After the five-day course of artesunate, primaquine was given: a single oral dose of 15mg for 14 days. A total number of 42 patients received treatment. All participants were followed up for 28 days. In all the cases, both parasitemia and fever were resolved rapidly; the mean fever clearance time and parasite clearance time, 14.6 and 36.7 hours, respectively, showed that therapeutic response to artesunate was better than that of chloroquine. The 14-day cure rate was 100%, but reappearance of parasitemia was seen in two patients on days 21 and 25 following treatment, respectively. These two cases of failure rate should be considered as true relapse rather than recrudescence, since the relapse interval in Southeast Asian vivax malaria according to recent findings seems to be 3 weeks after start of treatment, if primaquine is not given or an inadequate amount is given. In conclusion, artesunate might be useful in treatment of vivax malaria, causing a good blood schizontocidal effect. However, to prevent emerging resistance it should never be used alone.     

Sensitivity of Plasmodium vivax to chloroquine in Sa Kaeo Province,Thailand

Following a recent, abrupt local increase in the incidence of vivax malaria, a study was conducted in order to evaluate the efficacy of chloroquine for the treatment of 26 adult patients with acute vivax malaria in Sa Kaeo Province, Thailand. The chloroquine sensitivity of Plasmodium vivax has been assessed in parallel, using a growth inhibition method. Blood samples for the in vitro tests were taken prior to the administration of the standard treatment with chloroquine--in total 25 mg base/kg over 3 days--and primaquine 0.25 mg base/kg once daily for 14 days. The efficacy has been assessed according to the WHO standard in vivo test. The cure rate was 100%. No recrudescence was observed during the follow-up period of 28 days. The mean fever clearance time (FCT) was 40 h, the mean parasite clearance time (PCT) was 49 h. Mean IC(50) and IC(90) of the parasites were 28 and 171 nM, respectively. These results show that local P. vivax is still sensitive to chloroquine. The epidemic outbreak was therefore obviously not due to the presence of chloroquine-resistant P. vivax.