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INFLUENCE OF CHEMOTHERAPY ON THE PLASMODIUM GAMETOCYTE SEX RATIO OF MICE AND HUMANS

Plasmodium species, the etiologic agents of malaria, are obligatory sexual organisms. Gametocytes, the precursors of gametes, are responsible for parasite transmission from human to mosquito. The sex ratio of gametocytes has been shown to have consequences for the success of this shift from vertebrate host to insect vector. We attempted to document the effect of chemotherapy on the sex ratio of two different Plasmodium species: Plasmodium falciparum in children from endemic area with uncomplicated malaria treated with chloroquine (CQ) or sulfadoxine-pyrimethamine (SP), and P. vinckei petteri in mice treated with CQ or untreated. The studies involved 53 patients without gametocytes at day 0 (13 CQ and 40 SP) followed for 14 days, and 15 mice (10 CQ and 5 controls) followed for five days. During the course of infection, a positive correlation was observed between the time of the length of infection and the proportion of male gametocytes in both Plasmodium species. No effects of treatment (CQ versus SP for P. falciparum or CQ versus controls for P. vinckei petteri) on the gametocyte sex ratio were found for either Plasmodium species. This indicates that parasites do not respond to chemotherapy by altering their sex allocation strategy, even though, in the case of P. falciparum, they apparently increase their overall investment in sexual stages. This suggests that malaria parasite species respond to different environmental cues for their sex differentiation and sex determination.

Received March 8, 2004. Accepted for publication June 9, 2004.

Acknowledgments: We thank El Hadj Bâ for the microscopic examinations. Arthur M. Talman, Richard E. L. Paul, Olivier Domarle, Frédéric Ariey, and Vincent Robert are members of the Grand Program Horizontal Anopheles of the Institut Pasteur. We are very grateful to the reviewers for their constructive criticism.

Financial support: Fieldwork was support in part by the Institut de Recherche pour le Développement and PAL+. Richard E. L. Paul was supported by the Institut Pasteur and the French Ministère de la Recherche (Programme de Recherches Fondamentales en Microbiologie, Maladies Infectieuses et Parasitologie).

Authors’ addresses: Arthur M. Talman, Groupe de Recherche sur le Paludisme, Institut Pasteur de Madagascar, BP 1274, Antananarivo 101, Madagascar and Department of Biological Sciences, Imperial College, Exhibition Road, SW7 2AZ London, United Kingdom, E-mail: atalman{at}pasteur.mg. Richard E. L. Paul, Unité de Biochimie et Biologie Moléculaire des Insectes, Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cedex 15, France, E-mail: rpaul{at}pasteur.sn. Cheikh S. Sokhna and Jean-François Trape, UR Paludisme Afro-Tropical, Institut de Recherche pour le Développement, BP 1386, Dakar, Senegal, E-mails: sokhna{at}ird.sn and trape{at}ird.sn. Olivier Domarle and Frédéric Ariey, Groupe de Recherche sur le Paludisme, Institut Pasteur de Madagascar, BP 1274, Antananarivo 101, Madagascar, E-mails: domarle{at}pasteur.mg and ariey{at}pasteur.mg. Vincent Robert, Groupe de Recherche sur le Paludisme, Institut Pasteur de Madagascar, BP 1274, Antananarivo 101, Madagascar and Unité de Recherche Paludisme Afro-Tropical, Institut de Recherche pour le Développement, BP 1386, Dakar, Senegal, Telephone: 261-20-22-412-72, Fax: 261-20-22-415-34, E-mail: robert{at}pasteur.mg.