Quantification of the infectious dose of Leishmania major transmitted to the skin by single sand flies
Quantification of the infectious dose of Leishmania major transmitted to the skin by single sand flies
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DOI：
10.1073/pnas.0802331105
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发表时间：
2008-07-22
影响因子：
11.1
通讯作者：
Sacks, David
中科院分区：
文献类型：
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作者：
Kimblin, Nicola;Peters, Nathan;Sacks, David
利什曼病是通过吸血媒介沙蝇的叮咬在哺乳动物宿主之间传播的。寄生虫传播到哺乳动物宿主的剂量从未直接确定。我们开发了一种基于实时PCR的方法，以确定接种到活小鼠的耳朵中的利什曼原虫寄生虫的数量，在喂养过程中由个别感染的苍蝇（Phlebotomus duboscqi）。在检测到利什曼原虫的58只耳中，传播的寄生虫数量在很大范围内变化，并表现出明显的双峰分布。大多数受感染的小鼠接种了低剂量的1，000和高达100，000个细胞。高剂量传播与> 30，000个寄生虫的重中肠感染、不完全的血液喂养以及在苍蝇中传播高百分比的寄生虫负荷有关。为了测试接种量对感染结果的影响，我们比较了C57 BL/6小鼠耳部的代表性高剂量（5，000）和低剂量（100）皮内针头感染。为了模拟自然传播，我们使用了白蛉衍生的L。并将注射部位预先暴露于未受感染的苍蝇的叮咬。在接受高剂量接种物的小鼠的耳朵中迅速形成大的病变。低剂量仅导致轻微病理，但在慢性期寄生虫滴度较高，并使宿主成为一个有效的长期感染宿主，使其回到媒介白蛉。
Leishmaniasis is transmitted between mammalian hosts by the bites of bloodsucking vector sand flies. The dose of parasites transmitted to the mammalian host has never been directly determined. We developed a real-time PCR-based method to determine the number of Leishmania major parasites inoculated into the ears of living mice during feeding by individual infected flies (Phlebotomus duboscqi). The number of parasites transmitted varied over a wide range in the 58 ears in which Leishmania were detected and demonstrated a clear bimodal distribution. Most of the infected mice were inoculated with a low dose of 1,000 and up to 100,000 cells. High-dose transmission was associated with a heavy midgut infection of >30,000 parasites, incomplete blood feeding, and transmission of a high percentage of the parasite load in the fly. To test the impact of inoculum size on infection outcome, we compared representative high- (5,000) and low- (100) dose intradermal needle infections in the ears of C57BL/6 mice. To mimic natural transmission, we used sand fly-derived metacyclic forms of L. major and preexposed the injection site to the bites of uninfected flies. Large lesions developed rapidly in the ears of mice receiving the high-dose inoculum. The low dose resulted in only minor pathology but a higher parasite titer in the chronic phase, and it established the host as an efficient long-term reservoir of infection back to vector sand flies.