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Review
. 2015 May;109(3):107-22.
doi: 10.1179/2047773215Y.0000000013. Epub 2015 Apr 18.

Killing the hypnozoite--drug discovery approaches to prevent relapse in Plasmodium vivax

Brice Campo, Omar Vandal, David L Wesche, Jeremy N Burrows
Review

Killing the hypnozoite--drug discovery approaches to prevent relapse in Plasmodium vivax

Brice Campo et al. Pathog Glob Health. 2015 May.

Abstract

The eradication of malaria will only be possible if effective, well-tolerated medicines kill hypnozoites in vivax and ovale malaria, and thus prevent relapses in patients. Despite progress in the 8-aminoquinoline series, with tafenoquine in Phase III showing clear benefits over primaquine, the drug discovery challenge to identify hypnozoiticidal or hypnozoite-activating compounds has been hampered by the dearth of biological tools and assays, which in turn has been limited by the immense scientific and logistical challenges associated with accessing relevant human tissue and sporozoites. This review summarises the existing drug discovery series and approaches concerning the goal to block relapse.

Keywords: Drug discovery assays; Hypnozoite,; Plasmodium vivax,; Radical cure,; Strategy,.

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Figures

Figure 1
Figure 1
Liver stage life cycle of Plasmodium spp. A proportion of vivax sporozoites differentiate to a hypnozoite form that ultimately reactivates and proliferates leading to a blood-stage relapse.
Figure 2
Figure 2
Total dose of primaquine versus % cure.
Figure 3
Figure 3
The structures of leading 8-aminoquinolines: primaquine, tafenoquine.
Figure 4
Figure 4
Structures of NPC1161C and enantiomers B and C, and bulaquine.
Figure 5
Figure 5
Structures of quinolones, RC-12 and imidazolidinone – 8e.
Figure 6
Figure 6
Structures of KAI407 and optimised KDU691.
Figure 7
Figure 7
Phylogenetic tree of Plasmodium spp causing malaria in different species adapted from Hall. Branches are not to scale but represent how closely related each species is with each other. The shorter the branch, the closer the genome of each Plasmodium spp. Each plasmodia species is associated with its natural vertebrate host and the number of assembled whole-genome sequences that are publically available, either in public databases or through genome centres is also labelled as described by Hall.
See this image and copyright information in PMC

References

    1. Molyneux ME. History of discoveries, malaria. Encycl Malar. 2014:1–10.
    1. Grassi B, Feletti R. Sui parassiti della malaria. Rif Med. 1890;6:62–4.
    1. Thayer W. Lectures on the malarial fevers. New York: Appleton; 1897.
    1. Rodrigues T, Prudêncio M, Moreira R, Mota MM, Lopes F. Targeting the liver stage of malaria parasites: a yet unmet goal. J Med Chem [Internet] 2011;55((3)):995–1012. [cited 2012 Jul 18]. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22122518. - PubMed
    1. Douglas NM, Simpson JA, Phyo AP, Siswantoro H, Hasugian AR, Kenangalem E et al. Gametocyte dynamics and the role of drugs in reducing the transmission potential of Plasmodium vivax. J Infect Dis [Internet] 2013;208((5)):801–812. [cited 2013 Aug 26]. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid = 3733516&tool.... - PMC - PubMed

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