Predicting mosquito infection from Plasmodium falciparum gametocyte density and estimating the reservoir of infection

Abstract

Transmission reduction is a key component of global efforts to control and eliminate malaria; yet, it is unclear how the density of transmission stages (gametocytes) influences infection (proportion of mosquitoes infected). Human to mosquito transmission was assessed using 171 direct mosquito feeding assays conducted in Burkina Faso and Kenya. Plasmodium falciparum infects Anopheles gambiae efficiently at low densities (4% mosquitoes at 1/µl blood), although substantially more (>200/µl) are required to increase infection further. In a site in Burkina Faso, children harbour more gametocytes than adults though the non-linear relationship between gametocyte density and mosquito infection means that (per person) they only contribute slightly more to transmission. This method can be used to determine the reservoir of infection in different endemic settings. Interventions reducing gametocyte density need to be highly effective in order to halt human-mosquito transmission, although their use can be optimised by targeting those contributing the most to transmission. DOI:http://dx.doi.org/10.7554/eLife.00626.001.

Keywords: Gametocyte; Human; Malaria; Mathematical Model; Mosquito; Reservoir of infection.

Figure 1.. The relationship between gametocyte density and mosquito infection and the impact this will have on the effectiveness of gametocytocidal interventions.

(A) The relationship between Plasmodium falciparum gametocyte density and the percentage of Anopheles gambiae mosquitoes that develop oocysts. Point colour, shading, and shape denote characteristics of the blood donor, such as location (blue = Burkina Faso; red = Kenya), asexual parasite density as measured by microscopy (no fill colour = none detectable, light shading = 1–1000 parasites per microlitre, dark shading ≥1000 µl⁻¹), or host age (<6 years old = square, ≥6 years old = circle). The size of the point is proportional to the number of mosquitoes dissected. Coloured horizontal and vertical lines indicate 95% Bayesian credible intervals (CIs) around point estimates. The solid black line indicates the best-fit model, whereas the grey shaded area indicates the uncertainty around this line. The inset shows the relationship at very low gametocyte densities (on a logarithmic scale). The outputs show the shape of the relationship for a child with no detectable asexual parasites. A full description of data used to fit the model are given in Figure 1—source data 1. Regression coefficients and a measure of goodness-of-fit of the different models are given in Figure 1—source data 2. Panel (B) shows how efficacious transmission-reducing interventions would need to be (on the vertical axis) at decreasing gametocyte density in order to reduce human to mosquito transmission (contour lines). The best-fit line from (A) is used to illustrate the percentage reduction in mosquito infection that would be achieved according to the pre-intervention host’s gametocyte density (on the horizontal axis) for an intervention, which reduces gametocyte density by a given percentage (which is assumed to be constant over different gametocyte densities). The colours represent the percentage reduction in mosquito infection that would be achieved, ranging from red (low, 0–10% reduction) to darker hues of blue (high, 70–80% and 80–90% reduction, see legend). The 90–100% reduction in transmission is hardly visible and would correspond to nearly 100% efficacious interventions at the top of the graph. DOI: http://dx.doi.org/10.7554/eLife.00626.003

Figure 2.. Age patterns of gametocyte density and estimates of the age profile of the human reservoir of infection.

(A) Results from a cross-sectional survey conducted in a high transmission setting in Burkina Faso showing how the mean number of gametocytes per microlitre of blood (including 0s) changes with host age. The distribution of gametocytes among hosts is highly overdispersed. A full description of data used to fit the model are given in Figure 2—source data 1 with the best-fit parameter estimates shown in Figure 2—source data 2. The relationship between gametocyte density and oocyst prevalence shown in Figure 1A is used to predict the percentage of mosquitoes that will become infected after biting a host of a certain age. This is shown in panel (B), which can be interpreted as the contribution of each age group towards the human to mosquito transmission. In both figures, the black solid line shows the best-fit model and the grey shaded area indicates the uncertainty (95% Bayesian credible Interval, CI) having fitted the model to the individual data (a total of 412 individuals). For illustrative purposes, the data are grouped into seven bins, namely 0–5, 5–10, 10–15, 15–20, 20–30, 30–40, 40–50, and ≥50 year olds, and the size of the point is proportional to the number of individuals in the group. In Figure 1A, the 10–15 and 15–20 year groups appear lower than the best-fit line due to sampling artefacts generated by the highly overdispersed data. Vertical lines indicate the 95% CI around grouped estimates. DOI: http://dx.doi.org/10.7554/eLife.00626.006