Costs of crowding for the transmission of malaria parasites

Abstract

The utility of using evolutionary and ecological frameworks to understand the dynamics of infectious diseases is gaining increasing recognition. However, integrating evolutionary ecology and infectious disease epidemiology is challenging because within-host dynamics can have counterintuitive consequences for between-host transmission, especially for vector-borne parasites. A major obstacle to linking within- and between-host processes is that the drivers of the relationships between the density, virulence, and fitness of parasites are poorly understood. By experimentally manipulating the intensity of rodent malaria (Plasmodium berghei) infections in Anopheles stephensi mosquitoes under different environmental conditions, we show that parasites experience substantial density-dependent fitness costs because crowding reduces both parasite proliferation and vector survival. We then use our data to predict how interactions between parasite density and vector environmental conditions shape within-vector processes and onward disease transmission. Our model predicts that density-dependent processes can have substantial and unexpected effects on the transmission potential of vector-borne disease, which should be considered in the development and evaluation of transmission-blocking interventions.

Keywords: Anopheles stephensi; Plasmodium berghei; density dependence; disease transmission; fitness costs; life-history strategies; programmed cell death; vector-borne disease.

Figure 1

Generation of different infection densities. Mean ± SE Density of HD and RD lines for (A) ookinete (based on between 5 and 6 replicate infections and between 20 and 24 cultures per line) and (B) oocyst (based on 12 cages per line with 10 mosquitoes per cage) stage parasites.

Figure 2

Parasite proliferation reduced at high densities. Log sporozoite density per mosquito at day 21 shown as: (A) mean ± SE per density treatment and condition (based on 6 replicate cages with 10 mosquitoes dissected per cage), or (B) in relation to mean oocyst density for per cage. Each point represents one cage of mosquitoes with 10 individuals dissected per cage at each stage for regular density line (triangles) or the high density line (circles) under either standard conditions (solid symbols) or restricted conditions (open symbols). The line shows the predicted relationship from the minimal model.

Figure 3

The effect of parasite line and environmental conditions on vector survival. Cumulative proportion of mosquitoes surviving after receiving a control uninfected blood meal (blue), infection with the regular density line (RD; yellow) or the high density line (HD; red) under standard or restricted glucose and water conditions. Top panels show survival up to day 21 (when the sporozoites reach the salivary glands) and bottom panels show the full 50 days over which mortality was recorded. Each point represents the mean survival for between 4 and 6 cages and the error bars show the standard error of the mean.

Figure 4

Using a mathematical model to quantify the cumulative impact of density-dependent parasite development (A) and vector mortality (B) on overall transmission (C). (A) The fitted relationship between oocyst density and the number of sporozoites in the salivary glands (solid black line). Open orange circles are cages under restricted conditions, purple filled circles are cages under standard conditions and pink squares denote data from (Sinden et al. 2007). (B) The change in the number of bites (dashed line) and infectious bites (solid line) during the lifetime of the mosquito. (C) The overall impact on transmission as defined as the number of parasites available to establish a new infection weighted by the number of hosts bitten. Colours in (B) and (C) denote standard (purple) and restricted (orange) mosquito conditions.