Abstract
Secondary dengue infections are frequently associated with increased risk for dengue hemorrhagic fever and dengue shock syndrome. Surprisingly, we observed no dengue hemorrhagic fever cases among 353 hospitalized dengue-infected patients including 212 with primary, and 141 with secondary dengue 1 infection in China. To explore virological and immunological mechanisms which may account for this unexpected clinical observation, we assessed dengue viremia, type I interferon and inflammatory cytokine levels in these patients. While the levels of viremia and inflammatory cytokines are indistinguishable between primary and secondary infections, IFNα levels are significantly higher in primary than that in secondary infection. However, IFNα levels are positively correlated with dengue viremia levels (p<0.0001), but negatively correlated with the platelet counts (p<0.0001) and serum ALT levels (p = 0.0003). These results provide direct in vivo evidence that clinical dengue disease severity is affected by both viral and human immune factors.
Highlights
Dengue viruses cause dengue fever in 50–100 million people annually, but only a small fraction of infections develop into dengue hemorrhagic fever and dengue shock syndrome (DHF/ DSS)
We built on our previous observation that DHF/DSS cases were absent among 353 hospitalized Chinese patients with either primary or secondary dengue 1 infection (DENV1) [6] to explore the possible virological and immunological mechanisms that influence dengue disease severity
While both IFNa and IFNb have anti-dengue activity in vitro, previous clinical studies had limited to the measurement of IFNa levels, and most had been performed in subjects with either DENV2 or DENV3 infections [10,11,21]
Summary
Dengue viruses cause dengue fever in 50–100 million people annually, but only a small fraction of infections develop into dengue hemorrhagic fever and dengue shock syndrome (DHF/ DSS). IFNa secretion is detected in dengueinfected primary human monocytes and plasmacytoid dendritic cells only 20 to 24 hours post virus inoculation [18,19,20]. While both IFNa and IFNb have anti-dengue activity in vitro, previous clinical studies had limited to the measurement of IFNa levels, and most had been performed in subjects with either DENV2 or DENV3 infections [10,11,21]. We performed, for the first time, a large-scale measurement of both IFNa and IFNb in patients with DENV1 infection
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