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Myocarditis is a general set of mechanisms that manifest themselves into the inflammation of the heart muscle. In 2017, more than 3 million people were affected by this disease worldwide, causing about 47,000 deaths. Many aspects of the origin of this disease are well known, but several important questions regarding the disease remain open. One of them is why some patients develop a significantly localised inflammation while others develop a much more diffuse inflammation, reaching across large portions of the heart. Furthermore, the specific role of the pathogenic agent that causes inflammation as well as the interaction with the immune system in the progression of the disease are still under discussion. Providing answers to these crucial questions can have an important impact on patient treatment. In this scenario, computational methods can aid specialists to understand better the relationships between pathogens and the immune system and elucidate why some patients develop diffuse myocarditis. This paper alters a recently developed model to study the myocardial oedema formation in acute infectious myocarditis. The model describes the finite deformation regime using partial differential equations to represent tissue displacement, fluid pressure, fluid phase, and the concentrations of pathogens and leukocytes. A sensitivity analysis was performed to understand better the influence of the most relevant model parameters on the disease dynamics. The results showed that the poroelastic model could reproduce local and diffuse myocarditis dynamics in simplified and complex geometrical domains. [ABSTRACT FROM AUTHOR]

Background: An effective yellow fever (YF) vaccine has been available since 1937. Nevertheless, questions regarding its use remain poorly understood, such as the ideal dose to confer immunity against the disease, the need for a booster dose, the optimal immunisation schedule for immunocompetent, immunosuppressed, and pediatric populations, among other issues. This work aims to demonstrate that computational tools can be used to simulate different scenarios regarding YF vaccination and the immune response of individuals to this vaccine, thus assisting the response of some of these open questions. Results: This work presents the computational results obtained by a mathematical model of the human immune response to vaccination against YF. Five scenarios were simulated: primovaccination in adults and children, booster dose in adult individuals, vaccination of individuals with autoimmune diseases under immunomodulatory therapy, and the immune response to different vaccine doses. Where data were available, the model was able to quantitatively replicate the levels of antibodies obtained experimentally. In addition, for those scenarios where data were not available, it was possible to qualitatively reproduce the immune response behaviours described in the literature. Conclusions: Our simulations show that the minimum dose to confer immunity against YF is half of the reference dose. The results also suggest that immunological immaturity in children limits the induction and persistence of long-lived plasma cells are related to the antibody decay observed experimentally. Finally, the decay observed in the antibody level after ten years suggests that a booster dose is necessary to keep immunity against YF. [ABSTRACT FROM AUTHOR]

Background: Myocarditis is defined as the inflammation of the myocardium, i.e. the cardiac muscle. Among the reasons that lead to this disease, we may include infections caused by a virus, bacteria, protozoa, fungus, and others. One of the signs of the inflammation is the formation of edema, which may be a consequence of the interaction between interstitial fluid dynamics and immune response. This complex physiological process was mathematically modeled using a nonlinear system of partial differential equations (PDE) based on porous media approach. By combing a model based on Biot’s poroelasticity theory with a model for the immune response we developed a new hydro-mechanical model for inflammatory edema. To verify this new computational model, T2 parametric mapping obtained by Magnetic Resonance (MR) imaging was used to identify the region of edema in a patient diagnosed with unspecific myocarditis. Results: A patient-specific geometrical model was created using MRI images from the patient with myocarditis. With this model, edema formation was simulated using the proposed hydro-mechanical mathematical model in a two-dimensional domain. The computer simulations allowed us to correlate spatiotemporal dynamics of representative cells of the immune systems, such as leucocytes and the pathogen, with fluid accumulation and cardiac tissue deformation. Conclusions: This study demonstrates that the proposed mathematical model is a very promising tool to better understand edema formation in myocarditis. Simulations obtained from a patient-specific model reproduced important aspects related to the formation of cardiac edema, its area, position, and shape, and how these features are related to immune response. [ABSTRACT FROM AUTHOR]