To investigate whether dengue-2 patients with and without dengue hemorrhagic fever had different virus load, immune mediators, or T helper (Th) reaction, we simultaneously measured virus load, immune mediators and the Th1/Th2 transcription factors T-bet/GATA-3 mRNA expression in a large outbreak of dengue-2 infections in Southern Taiwan. Results showed that virus load was not significantly different between patients with and without dengue hemorrhagic fever. Patients with dengue fever had higher IFN-gamma levels, but patients with dengue hemorrhagic fever had significantly higher IL-10 levels. Further studies showed that patients with dengue hemorrhagic fever had a significantly lower T-bet than those with dengue fever, but GATA-3 mRNA expression in peripheral blood leukocytes was not significant difference between both groups. In conclusion, altered Th1 reaction as reflected by lower T-bet mRNA expression associated with higher IL-10 levels might be involved in the pathogenesis of dengue hemorrhagic fever.

The incidence of dengue fever (DF) is estimated to have increased 30-fold in the past 50 years. The incidence of dengue haemorrhagic fever (DHF), a life-threatening complication of DF, is also increasing. The need for better classification of the severity of dengue infections has been proposed in order to clarify different entities of dengue infections. We defined a class of patients with DF with bleeding tendency (DF w/B) to differentiate further the varying pathogenesis among DF, DF w/B and DHF. In a hospital-based study in Taiwan, we compared clinical features, biochemistry and immune mediators among patients with DHF, DF w/B and DF. Results showed that DF w/B patients, similar to DHF patients, had a higher rate of secondary dengue infection (P<0.001) as well as higher IL-10 (P=0.023) and lower IFNgamma (P=0.009) levels than DF patients. In contrast, DHF patients had significantly higher soluble vascular cell adhesion molecule 1 levels than DF w/B patients (P=0.038) and DF patients (P<0.001). This study provides new insight into the different immune mechanisms of DF, DF w/B and DHF. DF involves a Th1 reaction and DF w/B involves an altered Th2 reaction, whereas DHF involves an altered Th2 reaction and augmented vascular insult.

Japanese encephalitis (JE) is the most common mosquito-borne encephalitis in the Asia-Pacific region. Patients with JE usually present neuronal involvement, but other organ involvement is relatively rare. Employing human neuroblast-derived (NB) cell lines and different blood cells (erythrocytes, lymphocytes, granulocytes and monocytes), the neurotropism and persistency of Japanese encephalitis virus (JEV) in human cells was investigated. ). Two different strains of JEV revealed a similar infectivity to different leukocytes and four NB cell lines. In a kinetic study, it was found that JEV-infected monocytes possessed a high viability (90 %) after infection for 5 days, while JEV-infected neuroblastoma cells suffered cell apoptosis in 2 days and decreased viability to less than 1 % in 5 days. Further studies showed that monocytes could take up JEV rapidly, displaying a log scale increase of intracellular JEV titres in 9 h after infection. Significantly, extracellular production of JEV by monocytes started in 12 h, peaked in 3 days and persisted for more than 3 weeks. These results suggest that JEV-infected monocytes may play an important role in harbouring JEV for eventual transmission to NB cells and that modulation of JEV-induced NB cell apoptosis may be useful in treating patients with JE.