EVALUATION OF ANTIMALARIAL COMPOUNDS IN MOSQUITO TEST SYSTEMS
EVALUATION OF ANTIMALARIAL COMPOUNDS IN MOSQUITO TEST SYSTEMS
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DOI：
10.1016/0035-9203(71)90014-9
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发表时间：
1971-01-01
影响因子：
2.2
通讯作者：
GERBERG, EJ
中科院分区：
文献类型：
--
作者：
GERBERG, EJ
描述了一种筛选技术来测试化合物针对疟原虫的杀孢子活性。据报道，该方法快速（14 天即可出结果）、便宜（仅需要几毫克药物）且可靠。该测试将仅选择那些抑制孢子发生的化合物。雌性埃及伊蚊和鸡疟原虫雏鸡、史氏按蚊与P.食蟹猴或P。恶性疟原虫志愿者被用作实验模型。笼中装有 40 只三天龄的白鹭。让埃及蚊子吃含有已知对照药物氯胍、浓度为0.1%至0.00001%的候选化合物或未处理的蔗糖对照的10%蔗糖溶液2天，然后禁食2天。然后让蚊子以受感染的小鸡为食，然后更换蔗糖药物混合物。 9天后，除去一些蚊子，检查肠道中的卵囊和唾液腺中的子孢子。当使用灵长类动物或人类疟疾感染时，A.用受感染的宿主喂养史蒂芬西，然后在第 14 天之前提供含或不含药物的蔗糖溶液，除了短期内补充正常血粉外。第 14 天取出代表性蚊子样本，进行解剖并检查是否存在卵囊和子孢子。子孢子的存在与否被认为是主要标准。在3年的时间内测试了超过80000种化合物，一年内5%的化合物表现出一定的抗疟活性。 TheA.斯蒂芬西/P.食蟹猴系统和A.斯蒂芬西/P.恶性疟原虫的敏感性似乎相同，并且均优于埃及伊蚊/疟原虫。只给出标准抗疟药的结果；活性裂殖剂，例如氯喹、奎宁和美帕林几乎没有活性，而两种标准预防药物氯胍和乙胺嘧啶在浓度为 0.01% 时可完全抑制卵囊，而乙胺嘧啶在浓度为 00001% 时可完全抑制蚊子中子孢子的发育。 H.G.理查兹。
A screening technique is described to test compounds for sporontocidal activity against plasmodia. The method is reported as rapid (results in 14 days), cheap (only a few mg of drug are required), and reliable. The test will select only those compounds that inhibit sporogony. FemaleAedes aegyptimosquitoes andPlasmodium gallinaceumin chicks,Anopheles stephensiwith eitherP. cynomolgiin rhesus monkeys orP. falciparumin volunteers, were used as experimental models. Cages of 40 three-day-oldAe. aegyptimosquitoes were allowed to feed for 2 days on a 10% sucrose solution containing a known control drug, proguanil, a candidate compound at 0.1% to 0.00001% concentration, or an untreated sucrose control, then starved for 2 days. The mosquitoes were then allowed to feed on an infected chick after which the sucrose-drug mixture was replaced. After 9 days some mosquitoes were removed, the gut examined for oöcysts and the salivary glands for sporozoites.When primate or human malaria infections were used,A. stephensiwere fed on an infected host, then sucrose solutions with or without drug were available until day 14, except for short time periods when supplementary normal blood meals were given. Representative mosquito samples were removed on day 14, dissected and examined for the presence of oôcysts and sporozoites. The presence or absence of sporozoites was considered as the main criterion.More than 80000 compounds were tested over a 3-year period and in one year 5% of the compounds showed some antimalarial activity. TheA. stephensi/P. cynomolgisystem andA. stephensi/P. falciparumappear equal in sensitivity and both are superior toAe aegypti/P. gallinaceum.Only the results of standard antimalarials are given; active schizontocides, such as chloroquine, quinine and mepacrine had little or no activity, whereas two standard prophylactic drugs, proguanil and pyrimethamine, gave complete suppression of oöcysts at a concentration of 0.01 %, and pyrimethamine completely suppressed sporozoite development in the mosquito at a level of 00001%.W. H. G. Richards.