湖南省1例输入性重症恶性疟的调查与分析

目的 调查分析新冠病毒感染疫情期间湖南省某例因恶性疟原虫感染引起的重症疟疾病例的流行病学特征和临床症状,为输入性疟疾的科学防治提供依据。方法 收集患者的基本信息、流行病学和临床资料等,采集患者服用抗疟药前的末梢血,血涂片法进行疟原虫的病原学检查与虫种形态学鉴定,使用实时荧光定量PCR技术检测原虫基因。结果 患者有非洲境外务工史,新冠病毒感染疫情隔离期间出现发热、神志恍惚等症状,多次新冠病毒核酸检测为阴性。予以抗疟疾及抗感染等对症支持治疗后病情好转,返乡后复发,高度怀疑脑型疟疾,入院使用注射抗疟药病情缓解。病原学检查显示原虫形态上符合恶性疟原虫的特征,PCR检测结果呈阳性,与形态学结果一致。结论 该病例为一起典型的输入性重症恶性疟感染,症状复杂多变,容易误诊为新冠病毒感染,为我国消除疟疾后输入性的防控具有启发意义。     

间日疟病例远期复发1例报道

间日疟患者经抗疟药正规治疗后,停止发作,症状消失,外周血中已检不出疟原虫,在无新感染的情况下,肝内迟发性子孢子经过一段休眠后复苏,进行裂体增殖,使外周血红内期疟原虫大量繁殖,达到发热阈值后再次出现疟疾发作,称为复发.间日疟既有近期复发又有远期复发.     

阿托喹酮+盐酸氯胍(MALARONE)在疟疾治疗中的应用

疟疾抗药的持续流行要求人们加紧研制新型的抗疟药.阿托喹酮是一种广谱抗原虫制剂,它通过阻止寄生虫的电位传递来阻止其裂殖繁殖,而且该药的外观易于接受.早期研究表明,单独使用阿托喹酮治疗疟疾,初期可有效控制疟原虫,但随后出现的疟原虫复发率还比较高.     

小鼠疟原虫感染红内期免疫机制研究进展

疟原虫感染小鼠的免疫应答机制复杂多样,包括特异性免疫和非特异性免疫。特异性免疫主要分为肝内期、红内期、红外期3个阶段,本文主要对小鼠感染疟原虫后红内期免疫应答研究进行总结,有助于后续对疟原虫致病以及自愈机制的认识,并可为开发新的疟疾治疗疫苗、药物或者方法提供新的研究思路和理论依据。     

卫生部发布《抗疟药使用原则和用药方案(修订稿)》

近年来,全球抗疟治疗和疟原虫对抗疟药敏感性的研究取得了较大进展。参照世界卫生组织发布的有关抗疟药使用指南,结合我国疟疾防治工作的实际需要,经征求有关部门、各省（自治区、直辖市）卫生行政部门意见,卫生部组织专家对2007年3月27日印发的《疟疾防治技术方案（试行）》中的附件《抗疟药使用原则和用药方案》进行了修订。原《抗疟药使用原则和用药方案》同时废止。     

IFN—γ，TNF—α介导约氏疟原虫配子体感染力作用的探讨

目的：确定的氏疟原虫感染早期配子体感染力与一些细胞因子的相关性。方法：应用直接蚊吸血实验。观察了约氏疟原虫感染早期小鼠血液中配子体在蚊体内的发育情况,检测来自感染小鼠血清和蚊血食后其胃内血液中IFN－γ,TNF－α的含量,同时观察蚊血食8小时后胃内动合子的形成。结果：在感染后第3天,小鼠血清中IFN－γ显升高,而TNF－α未发现有意义的变化。蚊吸食这样的血液,其胃部囊合子形成数目却达到峰值。蚊胃内吸食的血液中两种细胞因子的含量和蚊体内动合子的形成与上述结果相一致。结论：在约氏疟原虫感染早期发生的自然传播阻断过程中,IFN－γ不是直接灭活配子体感染力的效应分子。     

恶性疟疾发病机制及其防治进展

疟疾仍是目前威胁人类健康的三大传染病之一.近年来,随着我国疟疾防控工作的进展,减少输入性疟疾的发生、降低恶性疟疾的误诊漏诊及死亡率已成为当前疟疾防治的重点.恶性疟疾的发病既涉及宿主因素,又与恶性疟原虫基因表达、抗原变异等相关,对于恶性疟疾的早期诊断、抗疟药、综合治疗等正在不断研究总结.此文主要就恶性疟疾的致病机制、诊断、治疗及疫苗制备等相关进展作一综述.     

青蒿素治疗抗氯疟喹疾36例效果观察

自1960年南美哥伦比亚发现恶性疟原虫对“王牌”抗疟药氯喹产生抗药性以后,抗氯喹疟疾在中南美和东南亚的恶性疟流行区相继出现和扩散。1973～1975年,我国云南孟定、畹町地区和海南岛乐东、崖县某些地区,也证实有抗氯喹株恶性疟原虫。抗氯奎疟疾的发生和流行。更为严重地危害人民健康,影响生产建设和战备工作,阻碍了消灭疟疾进程。因此,寻求无抗药性的高效、速效抗疟药和防治抗氯喹疟疾的药物,是当前疟疾研究工作中的重要课题,也是实现消灭疟疾急待解决的问题。     

输血性疟疾一例报告

<正> 高××,男,37岁,系新乡县小吉镇人,平素健康,无疟疾史和外出史,住户周围近十年来无疟疾病例报告。1992年5月29日因外伤住院,诊断为开放性腹部损伤,因失血过多、休克,立即进行手术、输血等抢救治疗。当天手术中共输入全血2400ml,又于5月30日、6月1日和3日分别输入900ml、600ml、300ml全血,除6月3日的300ml为医院库存外,其余3900ml均由20名外地流入人员供血。术后经抗感染等常规治疗,病情基本稳定,体温恢复正常后4天,于6月7日突然体温升至37.8℃,8日正常,9日达38.5℃。体检伤口愈合良好,无感染征兆。因隔日发热,怀疑疟疾,血检疟原虫阴性。6月11日出现寒战、高烧(T41.5℃),再次血检,疟原虫阳性,12日开始采用氯、伯8日疗法正规治疗后,近40天未出现上述症状,并追踪血检疟原虫3次,均为阴性。患者平素健康,无疟疾史和外出史,输血后9天出现典型的疟疾症状,血检疟原虫阳性,抗疟药治愈。我们认为,本例疟疾为血源性感染无异。     

疟疾病人免疫球蛋白浓度和抗体滴度测定

在间日疟流行区,收集8～9月份60例间日疟病人血清作免疫球蛋白浓度和荧光抗体测定。结果在发病初期人群已具有不同程度的免疫力,药物治疗后15～25天,IgG和IgM浓度,抗体滴度均急剧下降。此后,IgM和IgG浓度持续上升,出现比第一次更高的峰。后者提示患者仍在不断地接受新的疟原虫抗原刺激。而在发病后15～25天,IgG、IgM、IgA浓度和抗体均处于低水平时期,这为治疗后残存的疟原虫再燃或疟原虫重复感染提供了机会。并进一步证明疟疾的发病前或发病初期,荧光抗体检查会出现阴性结果。     

Cell mediated and humoral immunity in experimental Plasmodium berghei infection.

Adoptive passive transfer of immunity to Plasmodium berghei infection has been investigated in an inbred strain of Swiss mice. The mice were made hyperimmune by repeated passage of 10(3) parasites and subsequent therapy with an antimalarial drug. Immune sera and cells obtained from thymus, spleen and peritoneal exudate were transferred to normal animals which were subsequently challenged with standard doses of P. berghei. It was observed that: (a) immune serum in high doses (0.5 ml/mouse) enhanced parasitaemia; when used in smaller doses (0.1 ml/mouse), it afforded a considerable degree of protection; (b) viable immune lymphocytes obtained from thymus and lymph node afforded protection; (c) the mixed population of cells obtained from spleens of immunized mice, as well as peritoneal exudate, protected mice against challenge inoculum; (d) glutaraldehyde-treated spleen cells and material obtained after freezing and thawing the same number of spleen cells, macrophages and lymph node also afforded protection. These findings confirm that, under these experimental conditions, immunity against P. berghei is mediated through (i) specific antibody which is dose-dependent, (ii) cell-mediated immunity and (iii) effective response to processed antigen.     

Antimalarial activity from three ascidians: an exploration of different marine invertebrate phyla

Recent research suggests that marine organisms may produce compounds with activity against malaria parasites. Of a total of 27 aqueous extracts from different marine species, collected on the northwest Cuban coast, 20 were considered as showing no significant activity against Plasmodium falciparum F32, with minimum inhibitory concentrations (MIC) >500 microg/ml, while seven extracts (MIC < or =500 microg/ml) were selected for further investigation by determining their selectivity indices and in vivo antimalarial activity. Three species of tunicates were chosen, as more than 50% reduction of P. berghei parasitaemia was produced after administration of 250 or 500 mg/kg of their crude extracts into infected mice. The aqueous extracts of Microcosmus goanus, Ascidia sydneiensis and Phallusia nigra were partitioned between water and n-butanol; the organic phases inhibited P. falciparum growth by 50% at concentrations of 17.5 microg/ml, 20.9 microg/ml and 29.4 microg/ml respectively. In general, these results are similar to those of most ethnobotanical surveys. Further chemical studies are being undertaken in order to isolate new antimalarial compounds from these Caribbean tunicates.     

Synthesis and antimalarial activity of carbamate and amide derivatives of 4-anilinoquinoline

A series of 4-anilinoquinolines bearing an amino side chain linked to the aromatic ring with a carbamate or an amide bond were synthesized and evaluated for their antimalarial activity and their cytotoxicity upon MRC-5 cells. Among the 17 compounds, a majority was found to be active in the low nanomolar range against both chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro with relative low cytotoxicity. Two compounds were then tested on mice infected by Plasmodium berghei and were found to exhibit reasonable in vivo activity.     

Synthesis and evaluation of sulfonylurea derivatives as novel antimalarials

We have synthesized a series of sulfonylureas and have tested their antimalarial activities, including inhibition of in vitro development of a chloroquine-resistant strain of Plasmodium falciparum, in vitro hemoglobin hydrolysis, hemozoin formation, and development of Plasmodium berghei in murine malaria. The most active antimalarial compound was (E)-1-[4'-(3-(2,4-difluorophenyl)acryloyl)phenyl]-3-tosylurea (22) with an IC(50) of 1.2microM against cultured P. falciparum parasites. Biological results suggest a fairly potent antimalarial activity for this derivative, but also imply that its activity may arise from an unknown mechanism. Indeed, these compounds may act against malaria parasites through multiple mechanisms.     

The effect of combinations of qinghaosu (artemisinin) with standard antimalarial drugs in the suppressive treatment of malaria in mice

Artemisinin is a novel antimalarial drug isolated in China from the wormwood plant Artemisia annua L. Studies with rodent malaria were carried out to detect antagonism and synergism with a variety of antimalarial drugs. Isobolograms of drug interaction were plotted at the ED90 level. With a normally susceptible strain of Plasmodium berghei, marked potentiative synergism was found with mefloquine, tetracycline and spiramycin. There was some synergism also with primaquine. Combinations of artemisinin with dapsone, sulfadiazine, sulfadoxine, pyrimethamine, pyrimethamine/sulfadoxine and cycloguanil showed antagonism. A high degree of potentiation was shown between artemisinin and primaquine with a primaquine-resistant strain, whilst the combination with mefloquine showed enhanced potentiation with a mefloquine-resistant strain. Combinations of artemisinin with mefloquine, primaquine, tetracycline or clindamycin showed marked potentiation with an artemisinin-resistant strain. The mechanisms underlying the drug interactions observed are discussed.     

The effect of 10 alpha-trifluoromethylhydroartemisinin on Plasmodium berghei infection and its toxicity in experimental animals

The antimalarial activity of 10 alpha-trifluoromethylhydroartemisinin (TFMHA) was compared to that of dihydroartemisinin (DHA) in the Plamodium berghei mouse model. Treatment with TFMHA in mice infected with a P. berghei chloroquine-sensitive strain at 25 mg/kg for 3, 5, and 7 d, or DHA at the same dose for 7 d showed the parasite was eliminated from the host within 2.6 d. The radical cure and survival rates of these mice up to 60 d after infection were 90-100%. In mice infected with the P. berghei chloroquine-resistant strain, TFMHA used at 25 mg/kg/day for 3, 5, or 7 d reduced parasitaemia within 2 d. The radical cure and survival rates of these animals up to 60 d after infection were 30, 60, and 90% for the 3 treatment durations respectively. In contrast, DHA only had an inhibitory effect on the growth of the parasite within the first few days of treatment and could not eliminate the parasite even after 7 d of treatment. There was a 100% relapse and all mice died within 28 d after infection. The acute toxicity of TFMHA as determined by the median lethal dose (LD50) in mice treated orally was 820 mg/kg. In rabbits, TFMHA given orally at 20 mg/kg once daily for 28 successive days had no effect on the bodyweight, haematological, biochemical, histopathological and electrocardiogram parameters. The results showed that TFMHA is an effective antimalarial drug with a low level of toxicity.     

Development and decline of antiplasmodial indirect fluorescent antibodies in mice infected with Plasmodium berghei (NK65) and treated with drugs

Malaria parasites in mice present a simplified rodent model for the immunological study of malaria. Experiments have been performed to determine the pattern and persistence of malaria antibody as detected by the indirect fluorescent antibody (IFA) test utilizing specific antimouse IgM and IgG conjugates. The antibody levels in mice inoculated with Plasmodium berghei and treated with antimalarial drugs were traced after complete elimination of the parasites from the host. Within 1-2 weeks after inoculation, both specific IgM and IgG reached peak levels, which thereafter declined rapidly. The results suggest that a high IFA titre may be taken as an indication of recent parasitaemia when the parasites are absent from the host. The protective role of the specific immunoglobulin was not found in the cured animals at the time when the animals showed a high IFA titer. It seems that the detected IFA may not reflect protective immunity against reinfection with malaria parasites.     

Chronic malarial infection of mice: A comparison of single and multiple infections with Plasmodium berghei following P. yoelii.

Chronic malarial infection was induced in two groups of BALB/c mice by injection of Plasmodium yoelii followed by either one or repeated injections of P. berghei. Both groups showed a continuing but fluctuating splenomegaly, and a considerably increased reticulocyte count which also varied regularly, over a period of six months. During this time many mice had a very low grade parasitaemia demonstrable by subinoculation of blood into uninfected recipients. Mice infected with P. yoelii alone did not show any of these changes. One year after the first malarial attack all the infected mice had higher fluorescent antibody titres to P. yoelii than to P. berghei, titres against which were very low. Infected mice showed an increase in plasma cell proliferation in the red pulp of the spleen. There was a significant difference between mice which had received multiple injections of P. berghei and the other infected animals; the former had many germinal centres in the spleen, while the other infected groups did not.     

Increased severity of malaria infection in rats fed supplementary amino acids

Infection with Plasmodium berghei malaria is severely inhibited in rats fed on a low protein diet. A range of amino acid supplements was added to a 4.2% casein diet to determine whether the relationship between level of infection and protein content could be attributed to the dietary amounts of the essential amino acids. Significant increases in levels of infection were achieved by supplementation with specific combinations of amino acids. Threonine was most effective in increasing the degree of parasitaemia but its effect was further enhanced when it was combined with dietary excess of certain other amino acids, notably valine, isoleucine and methionine.     

Plasmodium berghei merozoite surface protein-9: immunogenicity and protective efficacy using a homologous challenge model

Merozoite surface protein-9 (MSP-9) from Plasmodium is considered a promising vaccine candidate due to its location and possible role in erythrocyte invasion. We report the identification and characterization of Plasmodium berghei MSP-9 (PbMSP-9) and its properties as an immunogen using a recombinant PbMSP-9 fragment to immunize BALB/c mice. PbMSP-9 was found to harbor erythrocyte binding and serine protease activity. PbMSP-9 formulation in alum was highly immunogenic in BALB/c mice. To evaluate the protective efficacy, immunized mice were submitted to homologous challenge with P. berghei NK65 blood-stage parasites. Protection against the parasite challenge was observed in BALB/c mice immunized with the PbMSP-9 formulation. These results suggest for the first time that MSP-9 based immunogens may constitute part of an effective malaria vaccine.