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Title: The impact of supplementary immunization activities on measles transmission dynamics and implications for measles elimination goals: A mathematical modelling study
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Journal of Theoretical Biology
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Sponsoring Org:
National Science Foundation
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  1. In this paper, we compare the performance between systems of ordinary and (Caputo) fractional differential equations depicting the susceptible-exposed-infectious-recovered (SEIR) models of diseases. In order to understand the origins of both approaches as mean-field approximations of integer and fractional stochastic processes, we introduce the fractional differential equations (FDEs) as approximations of some type of fractional nonlinear birth and death processes. Then, we examine validity of the two approaches against empirical courses of epidemics; we fit both of them to case counts of three measles epidemics that occurred during the pre-vaccination era in three different locations. While ordinary differential equations (ODEs) are commonly used to model epidemics, FDEs are more flexible in fitting empirical data and theoretically offer improved model predictions. The question arises whether, in practice, the benefits of using FDEs over ODEs outweigh the added computational complexities. While important differences in transient dynamics were observed, the FDE only outperformed the ODE in one of out three data sets. In general, FDE modeling approaches may be worth it in situations with large refined data sets and good numerical algorithms. 
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    Measles and rubella vaccinations are highly effective at reducing disease prevalence; however, logistic issues related to subcutaneous administration and vaccine wastage limit the extent of vaccination coverage. Microneedle (MN) patches can increase coverage by easing logistics through simplified administration and improved stability. This study demonstrates the thermostability of a bivalent measles and rubella vaccine MN patch. The data show that rubella vaccine stability requires pH buffering during drying; potassium phosphate buffer at neutral pH is optimal for both vaccines. Screening 43 excipients for their ability to retain potency during drying and storage yields sucrose‐threonine‐potassium phosphate buffer formulation at pH 7.5 as an optimal formulation. MN patches made with this formulation have no significant loss of vaccine titer after 1 month and remain within a one log10titer loss cutoff after 3–4 months at 5, 25, and 40 °C. Finally, these patches are shown to be immunogenic in juvenile rhesus macaques. This work demonstrates the potential for MN patches for measles and rubella vaccination to be removed from the cold chain, which is expected to decrease vaccine cost and wastage, and increase vaccination coverage.

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