Gametocyte Sex Ratio: The Key to Understanding Plasmodium falciparum Transmission?

• Published in: Trends in parasitology 2019-03, Vol.35 (3), p.226-238
• Main Authors: Tadesse, Fitsum G., Meerstein-Kessel, Lisette, Gonçalves, Bronner P., Drakeley, Chris, Ranford-Cartwright, Lisa, Bousema, Teun
• Format: Article
• Language: English
• Subjects: Animals; antimalarials; commitment to gametocytes; Culicidae; Culicidae - parasitology; diagnosis; diagnostic techniques; females; gametocytes; Host-Parasite Interactions; Humans; malaria; Malaria, Falciparum - parasitology; Malaria, Falciparum - transmission; males; parasites; Plasmodium falciparum; Plasmodium falciparum - physiology; Sex Ratio; Transcriptome; transcriptomics; transmission
• ISSN: 1471-4922; 1471-5007
• DOI: 10.1016/j.pt.2018.12.001

A mosquito needs to ingest at least one male and one female gametocyte to become infected with malaria. The sex of Plasmodium falciparum gametocytes can be determined microscopically but recent transcriptomics studies paved the way for the development of molecular methods that allow sex-ratio assessments at much lower gametocyte densities. These sex-specific gametocyte diagnostics were recently used to examine gametocyte dynamics in controlled and natural infections as well as the impact of different antimalarial drugs. It is currently unclear to what extent sex-specific gametocyte diagnostics obviate the need for mosquito feeding assays to formally assess transmission potential. Here, we review recent and historic assessments of gametocyte sex ratio in relation to host and parasite characteristics, treatment, and transmission potential. Recent RNA sequencing studies have uncovered a number of P. falciparum gametocyte sex-specific targets and provided new insights in gametocyte biology. After decades when gametocyte sex-ratio research was restricted to nonhuman malarias or in vitro experiments, molecular tools for assessing gametocyte sex ratio are now increasingly available for use in natural P. falciparum infections. Evidence that gametocyte sex ratio is influenced by total gametocyte density and antimalarial treatment, and improves predictions of transmission potential, highlight the relevance of understanding the gametocyte sex ratio during natural infections. The finding that the most widely used P. falciparum gametocyte marker Pfs25 is expressed predominantly by female gametocytes and has non-negligible levels of background expression in asexual parasites necessitates a re-evaluation of existing gametocyte data.