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Proc Natl Acad Sci U S A 2008 Jul 22;105(29):10125-30

Quantification of the infectious dose of Leishmania major transmitted to the skin by single sand flies.

Kimblin N, Peters N, Debrabant A, Secundino N, Egen J, Lawyer P, Fay MP, Kamhawi S, Sacks D

Sacks, D, NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA US FDA, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA

Abstract

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 <600 parasites. One in four received a higher 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.


Category: Journal Article
PubMed ID: #18626016
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-04 Entry Last Modified: 2012-08-29
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