Dengue fever (DF) is usually a self-limited febrile disease. A small percentage of patients experience a severe and prolonged illness characterized by capillary leakage which may progress to hypovolemic shock (dengue hemorrhagic fever/dengue shock syndrome; DHF/DSS). Hemorrhage of unknown etiology may accompany either DF or DHF/DSS. This investigator recently demonstrated that Thai patients with either DF or DHF/DSS develop antibodies potentially cross-reactive to plasminogen in a high percentage o cases. These antibodies were shown to be a consequence of immune recognition of a site in the dengue virus E protein (the major antigen of the virus) which has sequence similarity to plasminogen. Thai patients wit Japanese encephalitis (JE) virus infection did not develop this antibody, although the cross-reactive site is largely conserved in the JE virus E protein. Concomitantly, hemorrhage is not a feature of JE virus infection. A relationship of plasminogen cross-reactive antibodies to hemorrhage was suggested by the data but not proven. This year, we related the occurrence of plasminogen cross-reactive antibodies to hemorrhage in 88 children hospitalized in Tahiti with dengue virus, serotype 3, infection These patients presented with or without hemorrhage. Detection of cross-reactive antibodies in acute and/or in convalescent sera was associated with the occurrence of hemorrhage, paralleled that of antibodies to the cross- reactive site in the dengue virus E, and was more frequent in patients experiencing a secondary infection than in those experiencing a primary one In contrast, plasminogen cross-reactive antibodies did not correlate with the occurrence of DHF/DSS, as was the case in the Thai study, or with thrombocytopenia. Thus, our results were consistent with the possibility that plasminogen cross-reactive antibodies play a role in the etiology of hemorrhage in dengue virus infection. These data are being submitted for publication. We plan future prospective studies to confirm these results.
