Moreover, TNF-, which is located on the HLA Class-III sub-region of Major histocompatibility complex (MHC), is known to be upregulated in DHF [126, 128]
Moreover, TNF-, which is located on the HLA Class-III sub-region of Major histocompatibility complex (MHC), is known to be upregulated in DHF [126, 128]. which can cross-react with several Cetrorelix Acetate self-antigens such as plasminogen, integrin, and platelet cells. Apart Cetrorelix Acetate from viral factors, several host genetic factors and gene polymorphisms also have a role to play in pathogenesis of DENV infection. This review article highlights the various factors responsible for the pathogenesis of dengue and also highlights the recent advances in the field related to biomarkers which can be used in future for predicting severe disease outcome. Introduction Dengue infection is a major public health problem and has been reported from the Americas, Africa, Southeast Asia, Europe, Western Pacific, and Eastern Mediterranean regions. This arboviral disease is found to be endemic in more than 100 countries and around 96 million infected individuals are symptomatic with varying levels of severity [1, 2]. Dengue is one of the leading causes of significant morbidity and economic burden in different regions across the world including Southeast Asia and the Indian subcontinent [3]. Dengue is a mosquito-borne infection, primarily transmitted by followed by mosquito and other species of genus [1, 4]There are four serotypes of dengue virus which are antigenically distinct namely DENV-1, DENV-2, DENV-3, and DENV-4 [5]. A fifth serotype (DENV-5) has been detected using isolation and genetic sequence analysis in Sarawak state of Malaysia in October 2013 [6]. The incubation period of dengue Cetrorelix Acetate virus infection is 4C7?days. The disease spectrum ranges from asymptomatic infection and moderate febrile illness (dengue fever) to more serious manifestations such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) [7]. The most severe clinical syndrome can manifest in the form of dengue shock syndrome (DSS), which also includes coagulation abnormalities, plasma leakage, and increased vascular fragility. The fluid loss due to increased capillary permeability leads to hypovolemic shock and multi-organ failure [8]. Every year, dengue virus infection results in approximately 20, 000 deaths especially among secondary dengue cases associated with DHF/DSS [8, 9]. Till 2008, dengue was classified according to 1997 WHO classification criteria into dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS) [10]. The current revised WHO 2009 case classification system categorizes symptomatic cases into dengue without warning signs, dengue with warning signs, and severe dengue [11, 12]. The pathogenesis of dengue virus infection and severe dengue manifestations is very complex and not completely understood. The pathophysiological hallmark of DHF/DSS is plasma leakage and deranged hemostasis. Even after being aware of plasma leakage in dengue since the last five decades, the clear-cut mechanism of this manifestation stills remains obscure [13]. The statement that the human immune response plays a key role in the pathogenesis of the disease is favored by the fact that DENV infection displays the most severe form when the virus is being cleared by the host immune system and not with the peak viral load [14]. Various studies have been carried out across the world emphasizing the role of several factors implicated in the pathogenesis of dengue in humans. Despite a plethora of literature available on the pathogenesis of dengue fever, there are still some gaps in our knowledge, which represent a critical challenge in understanding the concepts of disease pathogenesis and severe manifestations. The present article reviews the current concepts of the various mechanisms involved in the pathogenesis of dengue virus infection and gives a comprehensive overview of the multiple factors responsible for severe clinical manifestations of the disease. This review article also gives a brief insight into the recent advances and research in dengue pathogenesis and the role of various biomarkers as early predictors of dengue disease severity. Pathogenesis of Dengue The four dengue virus serotypes (DENV1C4) have a Cetrorelix Acetate 65C70% nucleotide sequence homology and are closely related [15]. Primary infection is defined as the initial or first infection with a certain serotype. Most of primary infections are usually asymptomatic or manifest as a mild febrile illness, MAP2K7 although they can also cause hemorrhagic fever in some patients, especially in infants born to DENV-immune mothers. Subsequent infection with a different serotype is.