Department of Infectious Diseases, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA.
Vet Parasitol. 2011 Mar 22;176(4):361-7. doi: 10.1016/j.vetpar.2011.01.022. Epub 2011 Jan 19.
The antifilarial effects of tetracycline drugs were first demonstrated when they were found to be highly effective against L(3) and L(4) of Brugia pahangi and Litomosoides sigmodontis in rodent models. Tetracyclines are also now known to have activity against microfilariae and adult Dirofilaria immitis, but assessment of their activity against larval and juvenile heartworms has not been reported previously. This study assessed the effects of doxycycline administered orally at 10mg/kg twice daily for 30-day periods at selected times during the early part of the life cycle of D. immitis in dogs with dual infections of D. immitis and B. pahangi. Twenty beagles were randomly allocated by weight to four groups of five dogs each. On Day 0, each dog was given 50 D. immitis L(3) and 200 B. pahangi L(3) by SC injection. Dogs received doxycycline on Days 0-29 (Group 1); Days 40-69 (Group 2); or Days 65-94 (Group 3). Group 4 served as untreated controls. Blood samples were collected for microfilariae counting and antigen testing. Necropsy for collection of adult heartworms and selected tissues were performed Days 218-222. Heartworms recovered were examined by immunohistology, conventional microscopy/transmission electron microscopy, and molecular biology techniques. No live heartworms were recovered from dogs in Group 1; dogs in Group 2 had 0 to 2 live worms (98.4% efficacy), and dogs in Group 3 had 0-36 live worms (69.6% efficacy). All control dogs had live adult heartworms (25-41). The live worms recovered from dogs in Groups 2 and 3 were less developed and smaller that worms from control dogs. Microfilariae were not detected in any dogs in Groups 1 and 2; one dog in Group 3 had 1 microfilariae/ml at necropsy. All control dogs had microfilariae at necropsy. One dog in Group 1 was antigen positive at one sampling (Day 166). One dog in Group 2 was antigen positive Days 196 and 218-222 and three dogs in Group 3 were antigen positive at one or more samplings All five control dogs were antigen positive at all three sampling times. These findings suggest that doxycycline at 10mg/kg orally twice daily for 30 days has efficacy against migrating tissue-phase larvae and juvenile worms and will delay or restrict microfilarial production.
四环素类药物的抗丝虫作用最初是在它们被发现对啮齿动物模型中的 Brugia pahangi 和 Litomosoides sigmodontis 的 L(3)和 L(4)具有高度疗效时得到证实的。现在已知四环素类药物也对微丝蚴和成年犬心丝虫有效，但以前没有报道过它们对幼虫和幼体犬心丝虫的活性评估。本研究评估了在犬双重感染犬心丝虫和犬心丝虫的早期生活史的选定时间内，每天两次口服 10mg/kg 多西环素 30 天对犬心丝虫的 L(3)和 200 条犬心丝虫的 L(3)进行 SC 注射。20 只比格犬按体重随机分为四组，每组 5 只。第 0 天，每只狗都通过 SC 注射给予 50 条犬心丝虫 L(3)和 200 条犬心丝虫 L(3)。第 0-29 天(D 组 1)；第 40-69 天(D 组 2)；或第 65-94 天(D 组 3)。第 4 组作为未处理的对照组。采集血液样本进行微丝蚴计数和抗原检测。第 218-222 天进行尸检以收集成虫心丝虫和选定组织。从犬中回收的成虫心丝虫通过免疫组织化学、常规显微镜/透射电子显微镜和分子生物学技术进行检查。D 组 1 中的犬未回收活心丝虫；D 组 2 中的犬有 0 至 2 条活虫(98.4%疗效)，D 组 3 中的犬有 0-36 条活虫(69.6%疗效)。所有对照犬均有活成虫心丝虫(25-41)。从 D 组 2 和 3 的犬中回收的活虫发育程度较低，比对照犬中的虫体小。D 组 1 和 2 中的犬均未检测到微丝蚴；D 组 3 中的一只犬在尸检时检测到 1 条微丝蚴/ml。所有对照犬在尸检时均有微丝蚴。D 组 1 中的一只犬在一次采样(第 166 天)时抗原阳性。D 组 2 中的一只犬在第 196 天和第 218-222 天以及 D 组 3 中的三只犬在一次或多次采样时抗原阳性。所有五只对照犬在三次采样的所有三个时间点均呈抗原阳性。这些发现表明，每天口服 10mg/kg 多西环素 30 天对移行组织相幼虫和幼体虫具有疗效，并将延迟或限制微丝蚴的产生。
