Malaria therapy, experimental, and epidemiological studies have shown that erythrocyte Duffy blood group-negative people, largely of African ancestry, are resistant to erythrocyte Plasmodium vivax infection. These findings established a paradigm that the Duffy antigen is required for P. vivax erythrocyte invasion. P. vivax is endemic in Madagascar, where admixture of Duffy-negative and Duffy-positive populations of diverse ethnic backgrounds has occurred over 2 millennia. There, we investigated susceptibility to P. vivax blood-stage infection and disease in association with Duffy blood group polymorphism. Duffy blood group genotyping identified 72% Duffy-negative individuals (FY*B ES /*B ES ) in community surveys conducted at eight sentinel sites. Flow cytometry and adsorption-elution results confirmed the absence of Duffy antigen expression on Duffy-negative erythrocytes. P. vivax PCR positivity was observed in 8.8% (42/476) of asymptomatic Duffy-negative people. Clinical vivax malaria was identified in Duffy-negative subjects with nine P. vivax monoinfections and eight mixed Plasmodium species infections that included P. vivax (4.9 and 4.4% of 183 participants, respectively). Microscopy examination of blood smears confirmed blood-stage development of P. vivax, including gametocytes. Genotyping of polymorphic surface and microsatellite markers suggested that multiple P. vivax strains were infecting Duffy-negative people. In Madagascar, P. vivax has broken through its dependence on the Duffy antigen for establishing human blood-stage infection and disease. Further studies are necessary to identify the parasite and host molecules that enable this Duffyindependent P. vivax invasion of human erythrocytes.erythrocyte | evolution | DARC | Madagascar

The in vitro activities of new organometallic chloroquine analogs, based on 4-amino-quinoleine compounds bound to a molecule of ferrocene, were evaluated against chloroquine-susceptible, chloroquine-intermediate, and chloroquine-resistant, culture-adaptedPlasmodium falciparum lineages by a proliferation test. One of the ferrocene analogs totally restored the activity of chloroquine against chloroquine-resistant parasites. This compound, associated with tartaric acid for better solubility, was highly effective. The role of the ferrocene in reversing chloroquine resistance is discussed, as is its potential use for human therapy.

The protozoan Plasmodium falciparum has a complex life cycle in which asexual multiplication in the vertebrate host alternates with an obligate sexual reproduction in the anopheline mosquito. Apart from the apparent recombination advantages conferred by sex, P. falciparum has evolved a remarkable biology and adaptive phenotypes to insure its transmission despite the dangers of sex. This review mainly focuses on the current knowledge on commitment to sexual development, gametocytogenesis and the evolutionary significance of various aspects of gametocyte biology. It goes further than pure biology to look at the strategies used to improve successful transmission. Although gametocytes are inevitable stages for transmission and provide a potential target to fight malaria, they have received less attention than the pathogenic asexual stages. There is a need for research on gametocytes, which are a fascinating stage, responsible to a large extent for the success of P. falciparum.

No abstract

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.