CRYPTIC DISEASE - DENGUE HEMORRHAGIC FEVER (DHF)/ DENGUE SHOCK SYNDROME(DSS)

Exact pathogenesis is not known

Clinical manifestations 

-severe thrombocytopenia, vascular leakage, and hepatomegaly.

Immunologically:

-4 serotypes, DENV1, DENV2, DENV3, DENV4

-each serotypes has its own antigenic character (induces a different antibody against each type)

-Infection by one serotype will give lifelong immunity against the same serotypes of virus but not other serotype

ANTIBODY DEPENDENT ENHANCEMENT (ADE) effect 

-antibodies raised against one serotype will provide us protection for future infections of the same serotype but induces a massive immune response for different serotype infection

DENGUE VIRUS NON-STRUCTURAL PROTEIN 1 (DENV NS 1)

-Antibodies directed against DENV NS 1 showed cross-reactivity with human platelets and endothelial cells

-this lead to platelet and endothelial cell damage, inflammatory response and abnormal immune responses caused by DEN infection, including cytokine and chemokine production (TNF-a, IL-6, IL-8, and RANTES), complement activation and immune cell activation. 

-hypothesize that anti-DV NS1 is involved in the pathogenesis of DF and DHF/DSS, and this may provide important information in dengue vaccine development

Progression of DHF/DSS

1)effect of virus load

2)virus variation, 

3)abnormal immune responses of the host after DV infection may also account for the progression of DHF/DSS.

Persistent thrombocytopenia post DF hypothesis

a) Dengue virus induces bone marrow suppression

(b) Dengue virus can bind to human platelets in presence of virus specific antibody

and immune mediated clearance of platelets

(c) Spontaneous aggregation of platelets to vascular endothelial cell pre-infected by virus inducing aggregation, lysis and platelet destruction

(d) Anti-platelet antibodies generated after dengue virus infection causes destruction of platelets

References:-

1. http://www.searo.who.int/en/Section10/Section332/Section1985_9826.htm dengue vaccine 
2. http://www.unimas.my/research/ihcm/ihcm_dengue.htm
   
3. http://www.searo.who.int/en/Section10/Section332/Section1985_9804.htm
   
4. http://www.ajtmh.org/cgi/content/full/72/4/370