Clonal Diversity of the Malaria Parasite Plasmodium Mexicanum: Diversity Over Time and Space, and Effects on the Parasite’s Transmission, Infection Dynamics and Virulence

摘要

The biology of malaria parasites, Plasmodium spp., may be influenced by the presence of genetically distinct conspecific clones within a single infection, resulting in competition for host resources and transmission, and increased virulence for the vertebrate host. The extent of within host diversity, however, may be limited because overall clonal diversity could be reduced by the transmission biology of Plasmodium and variation in local prevalence. I examined clonal diversity of a natural malaria parasitehost association, P. mexicanum in its hosts, the western fence lizard, Sceloporus occidentalis, and sandflies, Lutzomyia vexator and L. stewarti, at a site in California (u22Hoplandu22). Using microsatellite markers I characterized for the parasite, I examined (i) diversity within and among infections over time and space, (ii) transmission success of clones into both vector and lizard, (iii) the effects of clonal diversity on the parasiteu27s infection dynamics and virulence for the lizard. From 1996 to 2006, clonal diversity varied both temporally and spatially, with slightly more multiclonal infections detected during years of high vs. low parasite prevalence (88% vs. 78% for sites with the highest prevalence at Hopland). Spatially, low prevalence sites (u3c 1% of lizards infected) had fewer multiclone infections (50%). Thus, even when prevalence drops over time, or at sites with chronically low prevalence, clonal diversity of the parasite remains high. Using natural and induced infections in the lizard, I found that multiclonal infections are no more infectious to vectors than single-clone infections, and almost all clones transfer successfully when the insect takes a blood meal. A competition experiment demonstrated that infections block new genotypes from entering a lizard host. Thus, multiclone infections are likely to be established when vectors feed on a complex infection and transmit those parasite clones to an uninfected lizard. The transmission biology of Plasmodium thus allows for the maintenance of genetic diversity in the parasite population. Finally, I examined the effects of multiclonality on the parasiteu27s infection dynamics and virulence to the lizard host. Induced infections harboring a single or multiple clones had similar overall growth rates and maximal parasitemia, but multiclonal infections had significantly higher investment in gametocytes, suggesting competition for transmission. In addition, variation in parasite growth and density was greater for multiclonal infections, with approximately 1/3 displaying high replication rates and final parasitemia. Virulence measures indicated that weight change and proportion of immature erythrocytes was consistent for infections with 1, 2, 3 or u3e 3 clones, but the highly diverse infections had greater blood hemoglobin and glucose and more rapid clotting rates. Compared with the noninfected control lizards, highly diverse infections (3+) had higher blood glucose levels but similar hemoglobin levels. I have found that genetic diversity of the malaria parasite Plasmodium mexicanum varies both temporally and spatially, although overall diversity remains high. The transmission dynamics of the parasite maintains high genetic diversity within infections. Additionally, diversity within hosts plays a significant role in variation of infection dynamics and virulence.