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Table 1 Immunological parameters as potential biomarkers

From: Predicting outcome from dengue

Immune marker

Disease phase

Comment

Elevated levels

 IL-4, IL-6, IL-8, IL-10

Elevated during the febrile phase, peaking around defervescence

Elevated levels in patients with DSS compared with those with DF, which correlated with markers of disease severity [58]. IL-10 correlated with degree of thrombocytopenia [49],[65]

 TNFa, sTNFR-75, sTNFR-80

Elevated in the febrile phase

Raised levels in severe dengue versus mild disease. Positive correlation with disease severity. sTNFRspredicted children who subsequently went on to develop shock [64],[67]

 IFN-γ

Raised in early febrile phase, peaking prior to defervescence day

DHF was associated with earlier peak IFN-γ levels [49]. Associated with development of severe disease [59]

 MIP-1b, G-CSF, IP-10, MCP-1

Elevated in early febrile phase through to defervescence

Compared with healthy control, MIP-1b and G-CSF were elevated in patients with uncomplicated dengue; MCP-1 in dengue with warning signs; and IP-10 in both groups [62]

 C3a, C4a, C5a,Factor D

Elevated in acute phase

Elevated in DHF compared with DF [68]

 SC5b-9 terminal complement complex

Elevated in acute disease ,peaking day after defervescence

Higher levels were demonstrated in DF/DHF compared with OFI, and correlated with dengue severity [54]

Reduced levels

 RANTES/CCL5

Reduced levels during the acute phase

Reduced during acute phase in patients with dengue compared with healthy controls, and correlated with thrombocytopenia [66]

 IL1-b, IL-2, EGF

Reduced levels during febrile phase

No difference was demonstrated between the severity grades for IL-1b but there was significantly lower levels of IL-2 and EGF in DSS compared with DF [58]

 VEGF, VEGFR2

Altered levels of VEGF and VEGFR2 around day of defervescence

There are mixed reports of VEGF levels

One study demonstrated reduced VEGF levels in DSS compared with DF from 2 days before to 2 days after defervescence [58]. Other studies have shown elevated VEGF levels in DHF compared with DF[69], and a further study demonstrated elevated levels of free VEGF in DHF at the time of plasma leakage, and reduced levels of VEGFR2 [63]

C3, factor H

Reduced levels during acute dengue

Reduced levels were found in patients with DHF compared with those with DF and healthy controls [68]

  1. C, complement; DF, dengue fever; DHF, dengue haemorrhagic fever; DSS, dengue shock syndrome;EGF, epidermal growth factor; G-CSF, granulocyte-colony stimulating factor; IFN, interferon; IL, interleukin; IP, interferon-γ-induced protein; MCP, monocyte chemoattractant protein; MIP, macrophage inflammatory protein; OFI, other febrile illness; RANTES/CCL5, regulated on activation, normal T cell expressed and secreted/chemokine (C-C motif) ligand 5; TNF, tumour necrosis factor; sTNFR, soluble tumour necrosis factor receptor; VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor.