Comparison of systemic mosquito infection kinetics among DENV isolates.

<p>A logistic 3-parameter model was fitted to all permutations of isolates, with isolates from the same group being forced to share the same parameters. Panel (A) represents the isolate grouping that maximizes the probability function for systemic infection dynamics. This isolate grouping had the lowest AIC value among all tested permutations (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1007187#ppat.1007187.s005" target="_blank">S5 Fig</a>). For each isolate group, data points represent the empirical measurements color-coded by isolate and the black line is the logistic fit of the group. An affinity matrix among isolates was derived from AIC values obtained from all model comparisons (<a href="http://www.plospathogens.org/article/info:doi/10.1371/journal.ppat.1007187#ppat.1007187.s005" target="_blank">S5 Fig</a>). Panel (B) shows the dendrogram obtained from a hierarchical clustering analysis performed on the affinity scores. The distance between isolates corresponds to the number of times two isolates shared the same groupings with respect to their AIC. The red dotted line shows the cut-off value leading to the best AIC-based isolate grouping.</p

Description of DENV type 1 isolates used in this study.

<p>The blood meal titer refers to the concentration of infectious viral particles (expressed in log₁₀-transformed focus-forming units per mL) measured in the artificial blood meal offered to mosquitoes. The passage history refers to the number of prior amplifications in C6/36 cells.</p

Simulated effect of variation in mosquito infection dynamics on the risk and magnitude of dengue outbreaks.

<p>A stochastic agent-based model was run 100 times for each combination of mean values of the three parameters (<i>K</i>, <i>B</i>, <i>M</i>) describing the kinetics of systemic mosquito infection. Other parameters, such as relative mosquito density, biting rate and human viral dynamics were held constant. Panel (A) shows the proportion of simulations that resulted in ≥100, <100 and no secondary human infections using the <i>K</i>, <i>B</i> and <i>M</i> values empirically measured for the eight DENV isolates. Panel (B) shows the total number of humans that became infected during large-scale dengue outbreaks (≥100 secondary human infections) using the empirical <i>K</i>, <i>B</i> and <i>M</i> values of the eight DENV isolates. In both panels, isolates are color-coded according to their AIC-based group of systemic mosquito infection kinetics.</p

Parameter estimates of systemic infection kinetics for each DENV isolate.

<p>Parameter values for each isolate were inferred from the cumulative change in the proportion of mosquitoes with a systemic DENV infection over time post exposure using model optimization. <i>K</i> is the saturation level and represents the maximum proportion of mosquitoes with a systemic infection. <i>B</i> is the slope factor and represents the maximum slope of the cumulative function scaled by <i>K</i>. Δt is derived from <i>B</i> and represents the time required to rise from 10% to 90% of the saturation level. <i>M</i> is the lag time and represents the time at which the absolute increase in cumulative proportion is maximal, which is also when the systemic infection prevalence equals <i>K</i>/2. Background shading (grey scale) indicates the best isolate groupings as determined by the AIC method.</p

Variation in the kinetics of systemic mosquito infection between DENV isolates.

<p>(A) The cumulative prevalence of systemic infection over time post virus exposure is shown for each DENV isolate. Data points represent the observed prevalence at each time point with their size being proportional to the sample size (number of mosquitoes tested). Dashes represent the 95% confidence interval of the prevalence. Lines correspond to the fitted values obtained with a 3-parameter logistic model. (B) The daily rate of new systemic infections (instantaneous velocity) over time post virus exposure is shown for each DENV isolate. It was calculated as the first derivative of the cumulative systemic infection function and is equivalent to the frequency distribution of lag time values among individual mosquitoes. In both graphs, the lower right panel shows the merged fitted values for all isolates.</p

Neutralizing antibodies for DENV serotypes 1–4.

<p>Reactivity profile according to the number of seroneutralized serotypes detected in 78 out of 90 randomly selected DENV ELISA positive samples.</p

Number of sera with neutralizing antibodies to DENV serotypes 1–4 according to (i) the neutralized serotype(s), (ii) the dominant serotype, (iii) the Island and (iv) the age class.

<p>Presented data concern a subset of 90 randomly selected DENV ELISA positive samples. (* Numbers may not add up as one individual serum may react with more than one serotype).</p

IgM antibodies to DENV, WNV, CHIKV and RVFV in 364 sera collected from Grande Comore, Moheli and Anjouan.

<p>IgM antibodies to DENV, WNV, CHIKV and RVFV in 364 sera collected from Grande Comore, Moheli and Anjouan.</p

IgG antibodies to each arbovirus according to living Island and to the status of serum donors (n = 400).

<p>The positivity criteria is a Absorbance Ratio to the cut-off value >1.1.</p

Distribution of the study sample according to gender, age class and island.

<p>Distribution of the study sample according to gender, age class and island.</p