Abstract
BackgroundDescriptions of dengue immunopathogenesis have largely relied on data from South-east Asia and America, while India is poorly represented. This study characterizes dengue cases from Pune, Western India, with respect to clinical profile and pro-inflammatory cytokines.Methodology/Principal FindingsIn 2005, 372 clinically suspected dengue cases were tested by MAC-ELISA and RT-PCR for dengue virus (DENV) aetiology. The clinical profile was recorded at the hospital. Circulating levels of IFN-γ, TNF-α, IL-6, and IL-8 were assessed by ELISA and secondary infections were defined by IgM to IgG ratio. Statistical analysis was carried out using the SPSS 11.0 version.Of the 372 individuals, 221 were confirmed to be dengue cases. Three serotypes, DENV-1, 2 and 3 were co-circulating and one case of dual infection was identified. Of 221 cases, 159 presented with Dengue fever (DF) and 62 with Dengue hemorrhagic fever (DHF) of which six had severe DHF and one died of shock. There was a strong association of rash, abdominal pain and conjunctival congestion with DHF. Levels of IFN-γ were higher in DF whereas IL-6 and IL-8 were higher in DHF cases (p<0.05). The mean levels of the three cytokines were higher in secondary compared to primary infections. Levels of IFN-γ and IL-8 were higher in early samples collected 2–5 days after onset than late samples collected 6–15 days after onset. IFN-γ showed significant decreasing time trend (p = 0.005) and IL-8 levels showed increasing trend towards significance in DHF cases (interaction p = 0.059). There was a significant association of IL-8 levels with thrombocytopenia and both IFN-γ and IL-8 were positively associated with alanine transaminase levels.Conclusions/SignificanceRash, abdominal pain and conjunctival congestion could be prognostic symptoms for DHF. High levels of IL-6 and IL-8 were shown to associate with DHF. The time trend of IFN-γ and IL-8 levels had greater significance than absolute values in DHF pathogenesis.
Highlights
Dengue is caused by infection with any of the four closely related serotypes of dengue virus (DENV) transmitted by Aedes aegypti
The clinical presentations of dengue vary from the selfresolving dengue fever (DF) to the more severe dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS)
Cytokine levels on different post onset days We further investigated whether it was the early (2–5 days of illness) or late (6–15 days of illness) cytokine response, which contributed to differences observed between DF and DHF cases using the interaction term in the general linear model of analysis
Summary
Dengue is caused by infection with any of the four closely related serotypes of dengue virus (DENV) transmitted by Aedes aegypti. Two-thirds of the world’s population is at risk, and about 50 million infections occur worldwide every year with a mortality that can vary from ,1% to 20% depending on the quality of treatment [1]. Dengue is an emergent disease in India with 5,000– 10,000 cases reported per year [2]. The clinical presentations of dengue vary from the selfresolving dengue fever (DF) to the more severe dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). The more severe form, DHF occurs mostly in individuals who acquire a heterotypic secondary infection [4]. Descriptions of dengue immunopathogenesis have largely relied on data from South-east Asia and America, while India is poorly represented. This study characterizes dengue cases from Pune, Western India, with respect to clinical profile and pro-inflammatory cytokines
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