Abstract
It is well documented that the density of Plasmodium in its vertebrate host modulates the physiological response induced; this in turn regulates parasite survival and transmission. It is less clear that parasite density in the mosquito regulates survival and transmission of this important pathogen. Numerous studies have described conversion rates of Plasmodium from one life stage to the next within the mosquito, yet few have considered that these rates might vary with parasite density. Here we establish infections with defined numbers of the rodent malaria parasite Plasmodium berghei to examine how parasite density at each stage of development (gametocytes; ookinetes; oocysts and sporozoites) influences development to the ensuing stage in Anopheles stephensi, and thus the delivery of infectious sporozoites to the vertebrate host. We show that every developmental transition exhibits strong density dependence, with numbers of the ensuing stages saturating at high density. We further show that when fed ookinetes at very low densities, oocyst development is facilitated by increasing ookinete number (i.e., the efficiency of ookinete–oocyst transformation follows a sigmoid relationship). We discuss how observations on this model system generate important hypotheses for the understanding of malaria biology, and how these might guide the rational analysis of interventions against the transmission of the malaria parasites of humans by their diverse vector species.
Highlights
The availability of the genomes of man, the mosquito and the malarial parasite has enabled penetrating new studies on the molecular organization of Plasmodium in its two hosts
The relationships between two consecutive parasite stages can saturate at high parasite densities, suggesting that at high parasite densities parasite numbers may have to be reduced substantially to effect an appreciable decrease in parasite transmission
These results may help establish a rational basis for new studies on species of medical importance and further our understanding of how interventions designed to reduce parasite survival within the mosquito might be expected to impact upon transmission
Summary
The availability of the genomes of man, the mosquito and the malarial parasite has enabled penetrating new studies on the molecular organization of Plasmodium in its two hosts. We do not fully comprehend how parasite population densities may affect transmissibility Without this knowledge our understanding of the impact of host responses, or of external intervention, upon the transmission of the parasite through endemic populations will remain incomplete. Plasmodium transforms from macrogametocyte to ookinete, oocyst, and to sporozoite. An important question that has eluded enquiry, is whether the ookinete-oocyst bottleneck and the other developmental transitions through the mosquito are density-dependent. (In this context, a transition is density-dependent when the rate at which such process occurs is determined by the parasite density of the previous stage.) Contributory factors for this omission may include the facts that most previous studies have compared parasite numbers in just two life stages, looked at a single infection intensity, or investigated densities within narrow ranges [11,12,13] An important question that has eluded enquiry, is whether the ookinete-oocyst bottleneck and the other developmental transitions through the mosquito are density-dependent. (In this context, a transition is density-dependent when the rate at which such process occurs is determined by the parasite density of the previous stage.) Contributory factors for this omission may include the facts that most previous studies have compared parasite numbers in just two life stages, looked at a single infection intensity, or investigated densities within narrow ranges [11,12,13]
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