Malaria

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Molecular and Biochemical Parasitology
Published as: Mol Biochem Parasitol. 2010 August ; 172(2): 57–65.

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Malaria gametocytogenesis
David A. Baker⁎ Department of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK.

Abstract
Male and femalegametocytes are the components of the malaria parasite life cycle which are taken up from an infected host bloodstream by mosquitoes and thus mediate disease transmission. These gamete precursors are morphologically and functionally quite distinct from their asexual blood stage counterparts and this is reflected in their distinct patterns of gene expression, cellular development and metabolism.Recent transcriptome, proteome and reverse genetic studies have added valuable information to that obtained from traditional studies. However, we still have no answer to the fundamental question regarding sexual development: ‘what triggers gametocytogenesis’? In the current climate of eradication/elimination, tackling transmission by killing gametocytes has an important place on the agenda becausemost antimalarial drugs, whilst killing asexual blood stage parasites, have no effect on the transmissible stages.

Graphical abstract
A stage V Plasmodium falciparum gametocyte in a blood film fixed with methanol and stained with Giemsa. We do not understand how differentiation to these sexual forms occurs in the host, but if it could be prevented with drugs then this would be a valuable tool tocontrol malaria transmission.

© 2010 Elsevier B.V. This document may be redistributed and reused, subject to certain conditions.
⁎

Tel.: +44 (0)20 7927 2664; fax: +44 (0)20 7636 8739. david.baker@lshtm.ac.uk. This document was posted here by permission of the publisher. At the time of deposit, it included all changes made during peer review, copyediting, and publishing. The U.S. NationalLibrary of Medicine is responsible for all links within the document and for incorporating any publisher-supplied amendments or retractions issued subsequently. The published journal article, guaranteed to be such by Elsevier, is available for free, on ScienceDirect.

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Keywords Malaria; Plasmodium; Gametocyte; Parasite;Drug; Differentiation

1 Introduction
Malaria is caused by protozoa of the genus Plasmodium; these are apicomplexan parasites and are part of the alveolate grouping [1]. As well as other animal pathogens such as
Published as: Mol Biochem Parasitol. 2010 August ; 172(2): 57–65.

Baker

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Toxoplasma, Crytptosporidium, Theileria and Eimeria, alveolates also comprise free livingciliate protozoa such as Paramecium and Tetrahymena and also the dinoflagellates. Asexual proliferation of malaria parasites within the red blood cells of a human host leads to the pathology and symptoms of malaria. The malaria parasite life cycle also comprises a phase of sexual reproduction which takes place in the mosquito vector, but the actual switch to sexual development occurs in the vertebratehost, with the formation of male and female gamete precursors (gametocytes), and is a prerequisite for transmission of disease [2]. This review will focus on our current knowledge of the biology of gametocytes and their development, and will highlight how the parasite genome sequence and post-genomic approaches have advanced our understanding of this important life cycle stage. The majority ofthe information has been derived from research carried out on the major human pathogen Plasmodium falciparum where the blood stages can readily be cultured in vitro [3], but also the rodent malaria parasite Plasmodium berghei which is a genetically more amenable system and provides an important in vivo model [4]. It is encouraging that advances in our knowledge are being made continuously, though...