Malaria's Missing Number: Calculating the Human Component of R0 by a Within-Host Mechanistic Model of Plasmodium falciparum Infection and Transmission
Figure 1
Illustration of asexual, sexual, and infectivity outputs.
Our mechanistic P. falciparum infection model was used to simulate three individuals' host-parasite dynamics. (A) Schematic representation of the P. falciparum life cycle. The parasite is transmitted to humans though the bite of an infected mosquito. Motile forms (sporozoites) travel to the liver where they proliferate as liver stage parasites that and are then released into the blood. Parasites then adopt ∼48 hr cycles of red blood cell (RBC) invasion, asexual blood stage replication, and egress. Some intra-erythrocytic parasites differentiate into sexual forms (gametocytes) for uptake by further mosquito bites. Asexual parasites avoid immune capture by antigenic variation, primarily PfEMP1 cycling. (B) Individual log10 asexual parasitemias presented as a function of the number of days post emergence of parasites from the liver into the bloodstream. The inset depicts the first 50 days of infection; triangles above indicate the first day of fever. The black line is the level of detectability by microscopy (10 parasitized red blood cells (PRBC)/µL). (C) Daily gametocytemias of the same three individuals. (D) Estimated probability of human-to-mosquito transmission. Areas under the infectivity curves are equivalent to the number of fully infectious days. Although the model predicts the persistence of long-lived low-level and sub-detectable infections (as observed in malaria therapy), this panel illustrates how the bulk of infectivity usually occurs early in the course of infection.