Researchers from Sri Lanka and Korea have shown beneficial outcome in their studies. In our study also we have found a very high specificity and negative predictive value in this regards. Our study included only secondary dengue patients as classically they are known to suffer from higher chances of complications immediately after fever subsides.
Hi
TNFa levels appear to be more predictive than IL-10 in severity. TNFa binds to PECAM-1 at endothelial gap junctions, allowing passage of activated CTL, but also plasma and RBC. IL-10 is a TH2 cytokine, essential for memory CTL and slowing the massive CTL response to DV infections in primary DV. There are a lot of moving pieces, but pre-existing, semi-neutralizing IgG to a different serotype, and infection with a virulent strain of SE Asian DV-2, along with poor clinical management, appear to be the major risk factors for severe dengue.
Bruce
Dear Bruce, Thank you for your reply. This is a nice paper that you have posted.
When we opted to start our project we had to keep it in mind that we work in a resource poor set up. Among the most predictive markers we have found a few promising according to our literature search. As you have correctly mentioned TNFa is better than IL-10 according to several studies like the mentioned one. But we, as clinical researchers, wanted to pick something which would not add too much extra burden to the poor patients as dengue is somewhat endemic with periodic epidemicity in this region of south east Asia.
If you search you will find that ELISA kit for TNFa is about 1.5-2 times costlier than that of IL-10. That is the main reason that we opted for IL-10 rather than TNFa.
Hopefully if the price comes down in near future we could go for it too.
Since you are a specialist in this field could you please let me know where the difference lies as in molecular and ultrastructural level that makes secondary dengue so severe from clinical aspect ? We are working specifically on secondary dengue. I shall be highly obliged if you could share anything regarding the pathological processes that makes secondary dengue behave differently than primary dengue. Is it only quantitative amplification of same processes of primary dengue or is it something else?
- Warm Regards: Dr. Aniruddha Ghosh
Hi
There are 3 main factors in determining dengue severity on secondary infections:
1. Strain-SE Asian strains have a change at a.a. 390 in the env glycoprotein from Asp to Asn. This allows more efficient binding and infection in vivo.
2. Presence of semi-neutralizing (hetero-serotypic) IgG that binds to, but does not attract complement-mediated destruction of the virion. The activated macrophages with up-regulated Fc receptors engulf, and are infected at higher rates than in primary infections. These infected macs secrete much higher levels of TNFa, leading to hemorrhage and shock
3. Clinical management. Prompt attention to fluid balance, avoiding hypovolemic shock and fluid overload, is key to successful outcomes in secondary dengue.
Check out this paper
Cheers
Bruce
Thank you Bruce for your reply.
It helped me to comprehend the topic better.
Stay healthy stay blessed
Aniruddha
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