Volume 13 Supplement 1

Challenges in malaria research: Core science and innovation

Open Access

Can we stop malaria parasites in the skin?

  • Ross Douglas1,
  • Miriam Ester1,
  • Janina Hellmann1 and
  • Friedrich Frischknecht1
Malaria Journal201413(Suppl 1):O7

https://doi.org/10.1186/1475-2875-13-S1-O7

Published: 22 September 2014

Background

Since the discovery of malaria transmission by mosquitoes, it was assumed that the parasites are injected directly into the blood stream. However, indirect experiments [1] and direct microscopic observations using mice as hosts and fluorescent rodent malaria species showed that the parasites are instead injected into the skin. These Plasmodium sporozoites then migrate rapidly through the dermis and enter blood or lymph vessels [2]. Stopping sporozoite motility also halts infection [3]. We aim at understanding the mechanisms that drive sporozoite motility and identify drug-like compounds that stop parasite locomotion. To this end, we have adapted and developed new methods including a screening pipeline to test small molecules that could interfere with motility and thus stop Plasmodium transmission at the skin stage [4, 5].

Materials and methods

A screening pipeline was developed that allowed medium-throughput assessment of small molecules as possible inhibitors of sporozoite motility in vitro. This was followed by in vivo testing during transmission from mosquito to mouse.

Results

We tested over 200 compounds selected from a library of drugs approved by the Federal Drug Administration for their potential to interfere with motility. We identified two molecules that inhibited in vitro motility in the nano-molar range. When these two compounds were tested during the transmission by mosquitoes, an ectopically applied drug resulted in a decrease of transmission efficiency while an orally given drug showed no effect on transmission at non-toxic doses.

Authors’ Affiliations

(1)
Centre for Infectious Diseases, Heidelberg University

References

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Copyright

© Douglas et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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