Mathematical Modelling of Immune Parameters in the Evolution of Severe Dengue

dc.contributor.author	Malavige, G.N., Premaratne, M.K., Perera, S.S.N., Jayasinghe, S.
dc.date.accessioned	2018-11-12T06:25:14Z
dc.date.available	2018-11-12T06:25:14Z
dc.date.issued	2017-02-15
dc.identifier.citation	Malavige, G.N., Premaratne, M.K., Perera, S.S.N., Jayasinghe, S. (2017). "Mathematical Modelling of Immune Parameters in the Evolution of Severe Dengue", Computational and Mathematical Methods in Medicine, pp. 1-9	en_US
dc.identifier.uri	http://dr.lib.sjp.ac.lk/handle/123456789/7348
dc.description	1. Introduction Sri Lanka has experienced a marked increase in dengue from 2004 to 2014. The increase from the year 2013 to 2014 was 47.4% (from 32,063 to 47,246) [1]. Although the overall mortality rate is low, every patient carries the potential risks of developing dengue hemorrhagic fever (DHF).The current case fatality is around 0.2–0.3% and early diagnosis and optimum care should be able to reduce these figures further. Under these circumstances it would be greatly beneficial if DHF could be predicted early. The infection is spread by a mosquito that acts as the vector for the disease. After entering the body from a bite, the incubation period lasts for about 4–10 days. Although the majority of the infected individuals develop asymptomatic disease, approximately 10% develop symptoms such as high fever, diarrhea, retroorbital pain, joint and muscle pains, or more severe forms of clinical disease associated with fluid leakage [2]. With the symptomatic febrile phase there are changes in the platelet count, lymphocyte count, NS1 antigen levels, IgG antibody levels, and other parameters including cytokines levels. After a variable period (about 3 to 5 days) a minority of symptomatic patients enter a phase of fluid loss from the intravascular compartment through capillaries (i.e., called the “critical phase” to denote its importance in management). This stage lasts for 48 hours and it is crucial that patient receive adequate amounts of fluid to counter the fluid leak during this period. If the degree of severity increases, the organs of the patient gradually fail resulting in the death of the patient. Themediation of fluid leak is through cytokines acting on the vascular endothelium, and currently there is evidence to link it to platelet activating factor (PAF) [3]. Hindawi Publishing Corporation Computational and Mathematical Methods in Medicine Volume 2017, Article ID 2187390, 9 pages https://doi.org/10.1155/2017/2187390 2 Computational and Mathematical Methods in Medicine One marker of severity is the persistence of the dengue NS1 antigen.This indicates the presence of dengue virus and its presence during the period of 5-6 days after illness is associated with more severe disease [4]. Dengue NS1 itself appears to be associated with vascular leak and triggers the production of many inflammatory cytokines. The virus has the ability to destroy platelets and reduce its production in the marrow thus reducing the platelet count [5]. Hence the platelet count is a significant marker in determining the severity of dengue and a count less than 20,000 platelets/mm3 is an indicator of severe dengue [6]. The severity of illness increases depending on whether it is the primary or the secondary infection, and in the latter the antibodies developeddue to theprimarydengue infection stimulate a stronger immune mediated illness (i.e., known as antibody dependent enhancement) [7]. The changes in the dengue virus specific IgG reveal whether the patient is having a secondary or a primary infection. High levels of dengue virus specific IgG indicate a secondary infection [6]. The lymphocyte indicates how the body is recovering from the disease. A lymphocyte count below 1,500 cells/mm3 is associated with more severe stages of dengue [6]. Viral dynamics during primary and secondary infections has been researched upon [8] and these viral dynamic models elaborate on the immune response and its dynamics in the body. However most of the researches focus on the effects of a single parameter on the severity of dengue. This study is an attempt to develop a mathematical model based on the cumulative effects of risks indicated by platelet count, lymphocyte count, dengue NS1 antigen, and dengue virus specific IgG levels and other parameters from published data.	en_US
dc.language.iso	en	en_US
dc.publisher	Hindawi Publishing Corporation	en_US
dc.title	Mathematical Modelling of Immune Parameters in the Evolution of Severe Dengue	en_US
dc.title.alternative	Computational and Mathematical Methods in Medicine	en_US
dc.type	Article	en_US
dc.identifier.doi	10.1155/2017/2187390	en_US