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Infection or presence of pathogen may be identified by:
1. PCR
2. Serology: e.g. ELISADengue infection is a major public health problem and has been reported in most countries and regions. The incubation period for dengue virus infection is 4-7 days. Diseases range from asymptomatic infections and moderate febrile illness (dengue fever) to more severe manifestations such as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). DSS is the most severe clinical syndrome and also presents with coagulation abnormalities, plasma leakage and increased vascular fragility. Loss of body fluids due to increased capillary permeability leads to hypovolemic shock and multi-organ failure.
The pathogenesis of DENV infection is still being explored. The researchers propose that the body's immune response plays a key role in this, due to the fact that they found that DENV infection symptoms are most severe when the host immune system is activated and clears the virus. Most primary infections are usually asymptomatic or mildly symptomatic, and secondary dengue infections may result in severe clinical manifestations such as DSS. Individuals infected with a particular serotype are immunoprotected against re-infection with the same type of infection, but this immune-protection is less effective in the case of infections with other serotypes.
The pathogenesis of dengue is associated with a variety of viral and host factors such as nonstructural protein 1 (NS1) viral antigens, DENV genomic variants, subgenomic RNA, antibody-dependent enhancement (ADE), memory cross-reactive T cells, anti-DENV NS1 antibodies, and autoimmunity. In the acute phase of the disease, soluble secreted lipid particle NS1 (s-NS1) levels are high and correlate with disease severity. NS1 has been observed to be a major contributor to the disruption of endothelial cell monolayer integrity. It destroys the integrity of the endothelial cell monolayer by activating macrophages and human peripheral blood mononuclear cells (PBMCs) via TLR 4, which induces the production of inflammatory cytokines. NS1 also induces shedding of heparan sulfate proteoglycans, leading to disruption of the endothelial glycocalyx layer of human pulmonary vascular endothelial cells and to shedding of sialic acid from the cell surface. All these factors contribute to the increase in vascular permeability in response to the direct action of NS1 antigen.
Figure 1. Complex interplay of viral and host factors in pathogenesis of dengue virus infection
(Source: Bhatt P, et al. 2021)
References
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Dengue virus NS1 secretion is regulated via importin-subunit β1 controlling expression of the chaperone GRp78 and targeted by the clinical drug ivermectin
mBio
Authors: Denolly S, Guo H, Martens M, Płaszczyca A, Scaturro P, Prasad V, Kongmanas K, Punyadee N, Songjaeng A, Mairiang D, Pichlmair A, Avirutnan P, Bartenschlager R.
Live, Attenuated, Tetravalent Butantan-Dengue Vaccine in Children and Adults
N Engl J Med
Authors: Kallás EG, Cintra MAT, Moreira JA, Patiño EG, Braga PE, Tenório JCV, Infante V, Palacios R, de Lacerda MVG, Batista Pereira D, da Fonseca AJ, Gurgel RQ, Coelho IC, Fontes CJF, Marques ETA, Romero GAS, Teixeira MM, Siqueira AM, Barral AMP, Boaventura VS, Ramos F, Elias Júnior E, Cassio de Moraes J, Covas DT, Kalil J, Precioso AR, Whitehead SS, Esteves-Jaramillo A, Shekar T, Lee JJ, Macey J, Kelner SG, Coller BG, Boulos FC, Nogueira ML.
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