The pathology of dengue hemorrhagic fever.
An estimated 2.5 billion people are at risk of dengue infection, and of the 100 million cases of dengue fever per year, up to 500,000 develop dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), the life-threatening forms of the infection. The large majority of DHF/DSS occurs as the result of a secondary infection with a different serotype of the virus. While not completely understood, there is evidence that the target cells include dendritic reticulum cells, monocytes, lymphocytes, hepatocytes, and vascular endothelial cells. Viral replication appears to occur in dendritic cells, monocytes, and possibly circulating lymphoid cells, and damage to these and other target cells occurs through immune-mediated mechanisms related to cross-reacting antibodies and cytokines released by dendritic cells, monocytes, and vascular endothelium. There is evidence of a concomitant cellular activation as well as immune suppression during the infection. The activation of memory T cells results in cascades of inflammatory cytokines, including tumor necrosis factor-alpha, interleukins (IL-2, IL-6, and IL-8), and other chemical mediators that increase vascular endothelial permeability or trigger death of target cells through apoptosis. Pathological studies in humans are uncommon, and a suitable animal model of DHF/DSS does not exist. The current treatment of DHF/DSS is symptomatic, and prevention is through vector control. As such, there is a great impetus for the development of vaccines and novel therapeutic molecules to impede viral replication in infected cells or counteract the effects of specific inflammatory mediators on target cells. The role of genetics in relation to resistance to DHF/DSS also requires clarification.
Leong
Anthony S-Y
AS
Hunter Area Pathology Service, Newcastle, NSW, Australia. aleong@mail.newcastle.edu.au
Wong
K Thong
KT
Leong
Trishe Y-M
TY
Tan
Puay Hoon
PH
Wannakrairot
Pongsak
P
D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000473:pathology / Q000821:virology; D003716:Dengue Virus / Q000472:pathogenicity / Q000502:physiology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000821:virology; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D009000:Monocytes / Q000473:pathology / Q000821:virology; D019595:Severe Dengue / Q000276:immunology / Q000473:pathology* / Q000821:virology; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication
D016207:Cytokines