While the extent of immune enhancement

While the extent of immune enhancement Dabrafenib manufacturer of susceptibility/infectiousness by different infection sequences has been more difficult to estimate, there is some evidence to suggest that it might also vary between serotypes [14]. Furthermore, recent work suggests that such immune enhancement is important for serotype persistence in the presence of transmission heterogeneity [20]. The potential impact of vaccination on dengue transmission dynamics in Thailand and Vietnam has been explored in two recent publications by Chao et al. [21] and Coudeville et al. [22] using an agent-based model and an age-specific compartmental model, respectively. Both of these studies found that

vaccines with efficacy of 70–90% against all serotypes have the potential to significantly reduce the frequency and magnitude of epidemics on a short to medium term. However, while both of these models do account

for some sources of heterogeneity between serotypes, for example, differences between the serotypes in transmission intensity, they do not systematically examine the potential impact of these heterogeneities in the context of partially effective vaccines. Here, we use an age-stratified dengue transmission model to assess the potential impact of vaccines with high efficacy against dengue serotypes 1, 3 and 4 and low efficacy against dengue serotype 2 in a hyperendemic Thai population. We explore multiple disease/transmission scenarios to identify those that might lead to increases in clinically apparent cases and to identify the potential reductions in disease. Crucially, we evaluate the effects that certain serotype EPZ-6438 heterogeneities may have in the presence of mass-vaccination campaigns. We also explore overall, direct and indirect effects of reducing (or in some cases increasing)

infection and disease in vaccinated individuals vs. reductions in transmission population wide. We formulated a deterministic, age-stratified compartmental dengue transmission model that includes explicit vector dynamics as well as cross-protection and infectiousness enhancement between dengue serotypes. Humans are assumed to be born susceptible and can undergo up to two infections by heterologous serotypes. Mosquito vectors are classified MycoClean Mycoplasma Removal Kit as susceptible or infected by each of the circulating serotypes. We focus on the dengue vaccine being developed by Sanofi-Pasteur that requires three doses to achieve high protection. Vaccination reduces the susceptibility of vaccinated humans to dengue infection. We also allow for immune mediated vaccine induced enhancement in transmissibility. Since the main objective of our study was to explore changes in the number of clinically apparent dengue cases, upon mass-vaccination, we made assumptions about the probability of developing clinically apparent disease following infection. These assumptions also allowed us to calibrate our model with data from surveillance systems.

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