Characteristics of membrane feeding assay blood donors and mosquito infections

Model takes raw QT-NASBA data from Schneider et al. 2007 (doi:10.5061/dryad.589ft) and Ouédraogo et al. 2009 (doi:10.5061/dryad.hv01f) and fits a mathematical model to estimate the gametocyte density (gam.median) and 95% Bayesian Credible Intervals (gam.lower, gam.upper). These are combined with blood donor and mosquito characteristics from the membrane feeding assays. Column “Host” denotes host id, “Experiment” gives country (0=Burkina, 1=Kenya), age (0=<7 or 1=>=7 years old) and “asexual.cat” is the asexual parasite density category as measured by microscopy (0=none,1=low,2=high). The point estimate for prevalence of oocysts is given from the model outputs “prev.median” together with 95% Bayesian Credible Intervals (prev.lower, prev.upper). Full details are given in the manuscript

Field study design, data analysis and modeling framework.

<p>N = number of observations.</p

Time series dynamics of Pfs230 (a) and Pfs48/45 (b) antibody response against gametocyte density in a simulated malaria infected individual from birth up to day 3000.

<p>Time series dynamics of Pfs230 (a) and Pfs48/45 (b) antibody response against gametocyte density in a simulated malaria infected individual from birth up to day 3000.</p

Generalized linear mixed model (GLMM)^* adjusted effects of Pfs48/45 antibody responses on oocyst intensity.

<p>Generalized linear mixed model (GLMM)^{<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1007034#t002fn002" target="_blank">*</a>} adjusted effects of Pfs48/45 antibody responses on oocyst intensity.</p

Pfs48/45 and Pfs230 antibody prevalence and densities from Field data and model simulations.

<p>Pfs48/45 and Pfs230 antibody prevalence and densities from Field data and model simulations.</p

Characteristics of membrane feeding assay blood donors and mosquito infections

host = id of the host. calib_no = the calibration line number used to convert TTP (time to positivity readouts) from QT-NASBA into gametocyte density. ttp = time to positivity readout from QT-NASBA used to generate gametocyte density estimate. age = age of blood donor. asexual = asexual parasite density of blood donor (estimated using microscopy). no_dissected = number of mosquitoes dissected to determine mosquito infection. no_infected = number of mosquitoes dissected with observable oocyst

The relationship between <i>Pfs</i>25 QT-NASBA gametocyte density and the proportion of infected mosquitoes in membrane feeding experiments.

<p>The solid line indicates the best fitted line (Y  =  0.0176Ln(X) + 0.0187; R² = 0.153). The dashed line indicates the estimated microscopic threshold for gametocyte detection, 8 gametocytes/µL, when screening 100 high power fields (i.e. ∼1000 white blood cells).</p

Baseline characteristics.

*<p>Fever = temperature ≥37.5°C;</p>¥<p>for carriers only;</p>¶<p>defined as fever with a parasite density ≥500 parasites/µL;</p>†<p>only gametocyte densities ≥20 gametocytes/mL were considered <i>Pfs</i>25 QT-NASBA positive.</p

Membrane feeding results.

*<p>by Pfs25 QT-NASBA;</p>¶<p>p-value for a test for trend;</p>¥<p>only the total number of oocysts per batch of fed mosquitoes was recorded, not the number of oocysts of individual mosquitoes. Therefore only a summary measure can be presented and no analyses could be done on individual oocyst densities.</p><p>The total number of samples is lower than 80 because QT-NASBA results were not available for 9 individuals. Two individuals without QT-NASBA results that were gametocyte positive by microscopy were included. The relative contribution to transmission was based on the product of the proportion of infected mosquitoes (4^th row) and the prevalence of this subgroup in the population (1^st row).</p

Protein microarray serological data

Background corrected and normalised microarray median florescence intensity data, for all individuals in the study (n=648). Data from IVTT protein targets are presented along with control targets in tab 1 and 2 (n=762). Data from the gametocyte IVTT protein targets only are presented in tab 3 (n=528)