Surrogate markers of protective immunity to malaria in humans are needed to rationalize malaria vaccine discovery and development. In an effort to identify such markers, and thereby provide a clue to the complex equation malaria vaccine development is facing, we investigated the relationship between protection acquired through exposure in the field with naturally occurring immune responses (i.e., induced by the parasite) to molecules that are considered as valuable vaccine candidates. We analyzed, under comparative conditions, the antibody responses of each of six isotypes to five leading malaria vaccine candidates in relation to protection acquired by exposure to natural challenges in 217 of the 247 inhabitants of the African village of Dielmo, Senegal (96 children and 121 older adolescents and adults). The status of susceptibility or resistance to malaria was determined by active case detection performed daily by medical doctors over 6 y from a unique follow-up study of this village. Of the 30 immune responses measured, only one, antibodies of the IgG3 isotype directed to merozoite surface protein 3 (MSP3), was strongly associated with clinical protection against malaria in all age groups, i.e., independently of age. This immunological parameter had a higher statistical significance than the sickle cell trait, the strongest factor of protection known against Plasmodium falciparum. A single determination of antibody was significantly associated with the clinical outcome over six consecutive years in children submitted to massive natural parasite challenges by mosquitoes (over three parasite inoculations per week). Finally, the target epitopes of these antibodies were found to be fully conserved. Since anti-MSP3 IgG3 antibodies can naturally develop along with protection against P. falciparum infection in young children, our results provide the encouraging indication that these antibodies should be possible to elicit by vaccination early in life. Since these antibodies have been found to achieve parasite killing under in vitro and in vivo conditions, and since they can be readily elicited by immunisation in naïve volunteers, our immunoepidemiological findings support the further development of MSP3-based vaccine formulations.

The importance of spatial heterogeneity and spatial scales (at a village or neighbourhood scale) has been explored with individual-based models. Our reasoning is based on the Chilean Easter Island (EI) case, where a first dengue epidemic occurred in 2002 among the relatively small population localized in one village. Even in this simple situation, the real epidemic is not consistent with homogeneous models. Conversely, including contact heterogeneity on different scales (intra-households, inter-house, inter-areas) allows the recovery of not only the EI epidemiological curve but also the qualitative patterns of Brazilian urban dengue epidemic in more complex situations.

Genetic analysis of the number of Plasmodium falciparum genotypes per infected person in regions of holoendemic and hyperendemic malaria suggest that in areas of lower transmission intensity, significantly fewer parasite genotypes per infected person should be found. A predominance of single clone infections in the human population could generate the controversial clonal population structure proposed for P. falciparum by Tibayrenc and others. Characterization of P. falciparum from individuals on the Thai-Burmese border, an area of hypoendemic transmission, revealed a higher number of genotypes per infected person than that predicted. Possible reasons for this observation are discussed, with particular attention paid to human migration and multidrug resistance.

Schistosomes, which live as parasitic adults in the blood vessels of mammals, birds and crocodiles, are unique among trematodes because they have separate sexes. Several studies have shown that the sex ratio is often biased towards males. Sexual dimorphism can be very important in several genera (Schistosoma, Heterobilharzia, Schistosomatium), as larger males grip smaller females in a gynecophoric canal. But not all schistomatid species have developed a gynecophoric canal. It is also striking that the number of testes varies widely, from a small number of testes reported (2–7) to a very high number (>500). We tested the hypothesis of trade-off investment by males: muscle (as estimated by the length of the gynecophoric canal) in order to sequester one or a few females, or testes in order to inseminate numerous females. We used recent comparative methods, which need phylogenetic information of the analysed species. We employed a morphological cladistic analysis of the Schistosomatidae and a construction of a phylogenetic supertree of Schistosoma based on available molecular information. Our phylogenetic analysis supports previous hypotheses on the origin and diversification of the schistosomes. The family seems to have originated as parasites of crocodiles (or possibly other related poikilotherms) and to have secondarily evolved within the Aves and then mammals. Our phylogenetic analyses show that (1) the possession of a gynecophoric canal is a plesiomorphic character, and several reductions of this character have occurred during the diversification of the Schistosomatidae; (2) a small number of testes is a plesiomorphic stage, and an increase of testes number has occurred several times. Finally, our comparative analysis suggests that there is a trade-off between investment in muscle or in number of testes (other variables being controlled for). Male competition for access to females seems to follow two ways: investment in testes in order to fertilize a high number of females or investment in muscle in order to hold and sequester one (Schistosoma) or a few females (Heterobilharzia). We show the existence of the trade-off between muscles and testes in connection with a male biased sex ratio. The development of dioecy cannot explain the trade-off between muscles and testes, which instead appears to be a result of sexual selection possibly driven by the male biased sex ratio.