疟疾疫苗的研究进展

综述了减毒活疫苗、子孢子疫苗和核酸疫苗的研究进展.     

家鸽疟原虫一新种，蛛形疟原虫的记述（孢子虫纲：疟原虫科）

本文描述了广州地区家鸽之间流行的一新种疟原虫。因该虫形成蜘蛛形（Ｓｐｉｄｅｒｆｏｒｍ）滋养体阶段，故命名为蛛形疟原虫（Ｐｌａｓｍｏｄｉｕｍａｒａｃｈｎｉｄｉ，ｓｐ．ｎｏｖ．）。红细胞内发育成熟裂殖体最终产生６～１２个裂殖子及其包含丰富细胞质和长形配子体，无疑是隶属于齐粤虫亚属（Ｃｉｏ－ｖａｎｎｏｌａｉａ）。它的主要特征容易与近似种，即Ｇｕｉｎｄｙｅｔａｌ（１９６５）[３]在埃及戴胜鸟（Ｈｏｏｐｏｅ）记载的甘汉氏疟原虫（Ｐ．ｇａｒｎｈａｍｉ）相鉴别     

顶复门寄生虫顶质体的研究进展

从顶质体的发现、起源、形态学、基因组以及生物学功能等方面介绍了顶复门寄生虫顶质体的一些研究进展，说明了顶质体对于顶复门寄生虫的存活具有十分重要的作用，它参与了脂肪酸、血红素以及类异戊二烯的生物学合成。提示，顶质体所具有的新陈代谢功能也使其成为研制抗寄生虫药的潜在靶位点。     

实验猴间日疟原虫感染的血清学调查

为了解实验猴间日疟原虫感染的基本情况,为猕猴属动物或其他非人类灵长类实验动物间日疟原虫病的防治提供参考。通过酶联免疫吸附试验(ELISA)的检测方法,对采自云南昆明某灵长类研究中心的3种实验猴(恒河猴、豚尾猴、食蟹猴)的血清样品进行间日疟原虫抗原检测。结果,3种实验猴的间日疟原虫血清阳性率平均为1. 62%,其中,豚尾猴的血清阳性率最高为5. 62%,其次恒河猴的血清阳性率为0. 94%,食蟹猴的血清阳性率为0%,3种实验猴的血清阳性率有显著差异(P=0. 004 <0. 05);从性别分析,公猴(2. 89%)和母猴(0. 94%)的血清阳性率之间无显著差异(P=0. 101> 0. 05);从年龄分析,青年猴(≤4岁)血清阳性率为3. 07%,成年猴(> 4岁)血清阳性率为0%,也存在显著性差异(P=0. 007 <0. 05)。从回归分析结果来看,品种因素是引起实验猴感染间日疟原虫的主要风险因子(P=0. 004 <0. 05)。结果表明,该灵长类研究中心的实验猴存在间日疟原虫感染,带虫猴会成为潜在的内部感染源。饲养人员需要加强对实验猴的饲养管理及间日疟原虫的防治工作,提高实验猴质量。     

Inhibitory Activity of Marine Sponge-Derived Natural Products against Parasitic Protozoa

In this study, thirteen sponge-derived terpenoids, including five linear furanoterpenes: furospinulosin-1 (1), furospinulosin-2 (2), furospongin-1 (3), furospongin-4 (4), and demethylfurospongin-4 (5); four linear meroterpenes: 2-(hexaprenylmethyl)-2-methylchromenol (6), 4-hydroxy-3-octaprenylbenzoic acid (7), 4-hydroxy-3-tetraprenyl-phenylacetic acid (8), and heptaprenyl-p-quinol (9); a linear triterpene, squalene (10); two spongian-type diterpenes dorisenone D (11) and 11β-acetoxyspongi-12-en-16-one (12); a scalarane-type sesterterpene; 12-epi-deoxoscalarin (13), as well as an indole alkaloid, tryptophol (14) were screened for their in vitro activity against four parasitic protozoa; Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and Plasmodium falciparum. Cytotoxic potential of the compounds on mammalian cells was also assessed. All compounds were active against T. brucei rhodesiense, with compound 8 being the most potent (IC₅₀ 0.60 μg/mL), whereas 9 and 12 were the most active compounds against T. cruzi, with IC₅₀ values around 4 μg/mL. Compound 12 showed the strongest leishmanicidal activity (IC₅₀ 0.75 μg/mL), which was comparable to that of miltefosine (IC₅₀ 0.20 μg/mL). The best antiplasmodial effect was exerted by compound 11 (IC₅₀ 0.43 μg/mL), followed by compounds 7, 10, and 12 with IC₅₀ values around 1 μg/mL. Compounds 9, 11 and 12 exhibited, besides their antiprotozoal activity, also some cytotoxicity, whereas all other compounds had low or no cytotoxicity towards the mammalian cell line. This is the first report of antiprotozoal activity of marine metabolites 1–14, and points out the potential of marine sponges in discovery of new antiprotozoal lead compounds.     

Isolation and identification of a South China strain of Plasmodium inui from Macaca fascicularis

Southeast Asian macaques are hosts of a number of Plasmodium infections, some of which are transmittable to humans. During examination of blood films of five wild-caught long-tailed macaques Macaca fascicularis from South China, malaria infection was detected in one of the monkeys. In order to isolate this parasite for identification and characterization, we experimentally passed this parasite through both Assamese (M. assamensis) and rhesus (M. mulatta) monkeys by intravenous injection of infected blood. This parasite morphologically resembled Plasmodium inui, and had a typical 72 h quartan periodicity. This parasite was infective to Anopheles dirus mosquitoes, and salivary gland sporozoites appeared 13 days post feeding. Feeding by 20 infected An. dirus mosquitoes on another Assamese monkey produced infection with a prepatent period of 8 days. Molecular analysis of the small subunit rRNA genes and the mitochondrial genome confirmed this parasite as an isolate of P. inui. In spleen-intact macaques, the infection had a protracted duration with parasites being detected during the rearing of the infected monkeys for over two years. In summary, this study identified a P. inui isolate and successfully passed this parasite through Assamese monkeys by both intravenous inoculation and mosquito transmission.     

恶性疟原虫裂殖子新型蛋白质(PF3D7_0811600)的表达纯化及其多克隆抗体的制备

利用大肠杆菌原核表达并纯化恶性疟原虫3D7株裂殖子新型蛋白质PF3D7_0811600,免疫家兔制备特异性多克隆抗体,通过对虫体天然蛋白的识别,分析PF3D7_0811600在虫体内的表达。采用PCR技术从恶性疟原虫3D7株总DNA中获得PF3D7_0811600基因的目的片段,连接到p MD18-T克隆载体,得到的克隆质粒经EcoRⅠ和XhoⅠ双酶切后,构建重组原核表达质粒p ET-PF3D7_0811600和p GEX-PF3D7_0811600,通过优化表达条件,分别在大肠杆菌中得到高效表达,并用亲和层析柱纯化目的蛋白质。用纯化的His标签重组蛋白质免疫家兔,用Western Blot方法检测制备的特异性多克隆抗体。结果表明:成功纯化并获得重组蛋白质,用间接ELISA方法检测多抗效价达到1∶16 000,用Western Blot检测结果表明制备的多克隆抗体具有良好的特异性,能够识别虫体天然蛋白。恶性疟原虫3D7株裂殖子新型蛋白质PF3D7_0811600在虫体晚期表达,说明该蛋白在虫体发育的晚期发挥重要作用,猜测其可能与裂殖子入侵宿主红细胞有关。     

氟乙酰胺对约氏疟原虫红内期超微结构的影响

近亲繁殖的ＮＩＫ小鼠接种约氏疟原虫,４ｄ后,选出疟原虫感染率达２０％￣４０％的小鼠口服氟乙酰胺。透射电镜观察械内期超微结构的变化。给药后１ｄ,少数滋养体的复合膜由原来的２层变成多层,线粒体膜肿胀明显,有些裂殖体的膜出现崩溃中断现象;给药后２ｄ,复合膜肿胀加剧,有的已崩溃、断裂,内质网扩张,其上核糖体脱落;给药后３ｄ,滋养体损伤严重,复合膜结构大部分消失,细胞器已难找见,自体吞噬泡增多,核质致密;给药后４ｄ,滋养体数量明显减少,仅余大小不等的空泡。     

抗疟疾药物研究进展

疟疾是由疟原虫引起的严重危害人类健康和生命安全的重要寄生虫病。近年针对产生耐药性的疟原虫虫株,亟需开发新型的抗疟药物。疟原虫入侵宿主需要蛋白质相互作用、蛋白酶裂解和肌动蛋白-肌球蛋白等关键分子的参与和协调,上述参与入侵过程的蛋白质为抗疟药物开发供了潜在靶点。论文对抗疟原虫入侵关键分子的药物做一概述。