Dengue epidemiology in South Vietnam.

<p>The total annual number of dengue cases (blue bars) and relative serotype prevalence (lines) over the period 1994–2008 in the southern 20 provinces of Viet Nam show the characteristic fluctuation in disease incidence and sequential replacements of dominant serotypes. Source of data: Vietnamese Ministry of Health Dengue passive surveillance scheme and kindly provided by the Pasteur Institute, HCMC, Viet Nam. The Hospital for Tropical Diseases is a tertiary referral hospital for infectious diseases.</p

Comparison of age structured dynamics between model (i) and model (ii).

<p>(a) The lines show the proportion of the population at each age (for model (i) (top) and model (ii) (bottom)) who have suffered one (solid dark blue line), two (solid red), three (solid green), four (solid magenta) and any (solid black) dengue infections. For model (ii) the proportion of the population that is at risk of disease (defined as having seen 1, 2 or 3 serotypes) is also plotted (dotted black) for comparison to the equivalent in model (i) (solid dark blue). Generally, in model (ii) people are exposed to dengue at an earlier age, experience heterologous infections younger, and take much longer to become completely immune. (b) For model (i) ((ii)), the blue (green) bar shows how the average age of disease (DHF), determined as heterologous infection, changes with the number of serotypes present whilst the small bars show the change in age of first infection. The increase in the total force of infection with the number of serotypes is shown as dotted lines (model (i): blue, and model (ii): green). (c) For model (i) (blue line) and model (ii) (green line) we observe that increasing acts to decrease the average age of first infection (here estimated as 1/total force of infection) and that for all levels of this value is significantly lower when allowing for third and fourth infection (model (ii)). Parameter values: ((a), (b) and (c)) and (a), (b).</p

Comparison of inter-epidemic period and serotype persistence between model (i) (<i>top</i>) and model (ii) (<i>bottom</i>).

<p>(a) As enhancement increases so too does the epidemic period observed in each model. There is also a trend towards longer periods at lower . However, these trends both appear to be stronger in model (ii). (b) The risk of stochastic extinction within the model is shown as the proportion of time in each model that the prevalence of a particular serotype exists above a specific threshold. In both models there is a low risk of extinction but the risk increases with enhancement; again, this trend is stronger in model (ii).</p

Comparison of synchronisation and single-serotype dominance between model (i) (<i>top</i>) and model (ii) (<i>bottom</i>).

<p>(a) The synchronisation pattern between serotypes 1 and 2 indicates that, for both models, most of parameter space is characterised by desynchronised behaviour i.e. the dynamics of the two serotypes are not ‘locked’ together. (b) Using a measure of single serotype dominance (where 0 corresponds to at least two serotypes being simultaneously dominant and higher values indicate a greater tendency for one serotype to be dominating at any given time), one can observe that in both models the trend is for increasing levels of dominance with increasing enhancement; this trend is more pronounced in model (ii) than model (i).</p

Selection pressures on the DENV genome, analyzed per gene, at different stages of horizontal transmission.

<p>Ratios of the number of non-synonymous (NS) to synonymous (S) SNVs per gene are shown for <b>(A)</b> human- versus mosquito-derived (both abdomen and salivary gland) DENV populations, and <b>(B)</b> mosquito abdomen- versus salivary gland-derived DENV populations. Human-derived samples are a pool of DENV2 patient samples from this study and DENV1 and DENV3 patient samples from the EDEN study [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0004052#pntd.0004052.ref019" target="_blank">19</a>]. Numbers of NS and S SNVs for each gene are indicated in tables below the graphs. *, p < 0.05; Fisher's exact test (M, p = 0.00439; E, p = 0.031; NS1, p = 0.002).</p

Loss and maintenance of SNVs during horizontal transmission.

<p><b>(A)</b> Percentage of SNVs maintained during transmission from human to mosquito and from mosquito abdomen to mosquito salivary gland. <b>(B)</b> Tracking of maintained SNVs. The number of instances of each scenario are shown; these include all occurrences of SNVs that were found to be maintained in more than one mosquito. <b>(C)</b> Percentage of SNVs maintained between members of a human-human transmission pair from the EDEN study.</p

Frequencies of maintained SNVs in the human, mosquito abdomen, and mosquito salivary gland.

<p>Red, non-synonymous SNVs; black, synonymous SNVs. SNV positions mentioned in the text are highlighted with arrows and drawn as dotted lines for ease of viewing.</p

SNVs maintained between EDEN transmission pairs.

<p>NS, non-synonymous; S, synonymous; aa, amino acid.</p><p>SNVs maintained between EDEN transmission pairs.</p

SNVs maintained from human to mosquito.

<p>NS, non-synonymous; S, synonymous; aa, amino acid.</p><p>SNVs maintained from human to mosquito.</p

EV71 Neut-Ab profiles in 8 representative infants.

<p>Shown in panel A are representative Neut-Ab profiles from 4 infants (out of a total of 17 infants) with incident EV71 seroconversion in the first year of life. Similarly, shown in panel B are representative Neut-Ab profiles from 4 infants (out of a total of 37 infants) with incident EV71 seroconversion in the second year of life. The dashed line represents the assay limit of detection.</p