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Age-structured gametocyte allocation links immunity to epidemiology in malaria parasites

Richard E Paul12*, Sarah Bonnet34, Christian Boudin5, Timoleon Tchuinkam3 and Vincent Robert56

Author Affiliations

1 Laboratoire d'Entomologie Médicale, Institut Pasteur de Dakar, 36 Avenue Pasteur, BP 220 Dakar, Sénégal

2 Laboratoire de Génétique de la réponse aux infections chez l'homme, Institut Pasteur, 28 rue de Dr. Roux, F-75724, Paris cedex 15, France

3 Laboratoire IRD de Recherche sur le Paludisme, Organisation de Coordination pour la lutte Contre les Endemies en Afrique Centrale, P.O. Box 288, Yaounde, Cameroon

4 Ecole Nationale Vétérinaire de Nantes, Service de parasitologie, UMR ENVN/INRA 1034 Interactions Hôte-Parasite-Milieu, Atlanpole-La Chantrerie, B.P. 40706, 44307 Nantes cedex 03, France

5 UR Paludisme Afro-tropical, Institut de Recherche pour le Développement, B.P.1386 Dakar, Sénégal

6 Institut de Recherche pour le Développement/Muséum National d'Histoire Naturelle, 61 rue Buffon, case courrier 52, 75231 Paris cedex 05, France

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Malaria Journal 2007, 6:123  doi:10.1186/1475-2875-6-123

Published: 12 September 2007

Abstract

Background

Despite a long history of attempts to model malaria epidemiology, the over-riding conclusion is that a detailed understanding of host-parasite interactions leading to immunity is required. It is still not known what governs the duration of an infection and how within-human parasite dynamics relate to malaria epidemiology.

Presentation of the hypothesis

Immunity to Plasmodium falciparum develops slowly and requires repeated exposure to the parasite, which thus generates age-structure in the host-parasite interaction. An age-structured degree of immunity would present the parasite with humans of highly variable quality. Evolutionary theory suggests that natural selection will mould adaptive phenotypes that are more precise (less variant) in "high quality" habitats, where lifetime reproductive success is best. Variability in malaria parasite gametocyte density is predicted to be less variable in those age groups who best infect mosquitoes. Thus, the extent to which variation in gametocyte density is a simple parasite phenotype reflecting the complex within-host parasite dynamics is addressed.

Testing the hypothesis

Gametocyte densities and corresponding infectiousness to mosquitoes from published data sets and studies in both rural and urban Cameroon are analysed. The mean and variation in gametocyte density according to age group are considered and compared with transmission success (proportion of mosquitoes infected). Across a wide range of settings endemic for malaria, the age group that infected most mosquitoes had the least variation in gametocyte density, i.e. there was a significant relationship between the variance rather than the mean gametocyte density and age-specific parasite transmission success. In these settings, the acquisition of immunity over time was evident as a decrease in asexual parasite densities with age. By contrast, in an urban setting, there were no such age-structured relationships either with variation in gametocyte density or asexual parasite density.

Implications of the hypothesis

Gametocyte production is seemingly predicted by evolutionary theory, insofar as a reproductive phenotype (gametocyte density) is most precisely expressed (i.e. is most invariant) in the most infectious human age group. This human age group would thus be expected to be the habitat most suitable for the parasite. Comprehension of the immuno-epidemiology of malaria, a requisite for any vaccine strategies, remains poor. Immunological characterization of the human population stratified by parasite gametocyte allocation would be a step forward in identifying the salient immunological pathways of what makes a human a good habitat.