Slower rates of clearance of viral load and virus-containing immune complexes in patients with dengue hemorrhagic fever

Background. Although previous studies have revealed the contribution of an initial high level of dengue virus replication to the severe and potentially life-threatening diseases dengue hemorrhagic fever (DHF) and dengue shock syndrome, the involvement of dengue virus in the immuopathological processes during the transition from fever to defervescence, which is a critical stage in determining the progression to DHF, has not been appreciated. Previously, we reported that dengue virus can be detected in the immune complexes of patients with DHF during this period. Methods. We investigated plasma dengue viral load, virus in immune complexes, antibody response, complements, and cytokines for 54 patients with dengue fever ( a relatively mild form of disease) and 49 patients with DHF. The patients had confirmed secondary infection with dengue virus type 2 from a large outbreak in southern Taiwan in 2002. Results. Patients with DHF had a significantly higher viral load and a slower rate of clearance than patients with dengue fever. For viral loads > 5.7 log RNA copies/mL on the day of defervescence, the positive and negative predictive values for DHF are 0.88 and 0.95, respectively. A higher level and slower decline of dengue virus containing immune complexes ( and a subsequently higher elevation of C5a and soluble interleukin 2 receptor) were found in patients with DHF, compared with patients with dengue fever. Conclusions. These findings indicate that slower rates of clearance of viral load and virus-containing immune complexes are associated with subsequent immune activation and contribute to the progression of DHF at this critical stage. Moreover, viral load on the day of defervescence can predict cases of DHF.