Apoptosis in tissues from fatal dengue shock syndrome

BackgroundApoptosis, or programmed cell death, has been implicated in dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) pathogenesis.ObjectivesTo determine the in vivo apoptosis contribution to the pathogenesis of fatal DHF/DSS during a Cuban dengue epidemic.Study designWe detected apoptosis by the TdT-mediated dUTP Nick-End Labeling (TUNEL) technique and dengue virus (DENV) antigens by an immunohistochemical assay in different tissues from six individuals who died of DHF/DSS during the Santiago de Cuba DENV-2 epidemic in 1997.ResultsDENV antigens were immunolocalized mainly in hepatocytes. Apoptotic cells were found in five of the six cases studied. Apoptosis was demonstrated in liver, brain, intestinal and lung tissues. Severe brain hypoxia and ischemia in the studied subjects during DHF/DSS probably might induce apoptosis in cerebral cells. Apoptotic microvascular endothelial cells (ECs) in pulmonary and intestinal tissues, a finding only previously reported in vitro, are likely related to vascular plasma leakage manifested by the individuals.ConclusionsApoptosis was demonstrated in cerebral cells, white blood cells, intestinal and pulmonary microvascular ECs from Cuban fatal cases of DHF/DSS. As far as we know, these findings have not been previously reported in DHF/DSS. Our results indicate there is very likely an in vivo contribution of apoptosis to the pathophysiological mechanisms of DHF/DSS.