Pathologic study of a fatal case of dengue-3 virus infection in Rio de Janeiro, Brazil

Abstract

Dengue hemorrhagic fever (DHF) is a severe febrile disease, characterized by abnormalities in hemostasis and increased vascular permeability, which in some cases results in hypovolemic shock syndrome and in dengue shock syndrome. The clinical features of DHF include plasma leakage, bleeding tendency and liver involvement. We studied the histopathological features of a fatal case of dengue-3 virus infection. The patient, a 63-year old male, presented with an acute onset of severe headache, myalgia and maculopapular rash. Tissue fragments (liver, spleen, lung, heart, kidney and lymph nodes) were collected for light microscopy studies and stained by standard methods. Histopathology revealed severe tissue damage, caused by intense hemorrhage, interstitial edema and inflammation. Some tissue sections were also processed with the immunoperoxidase reaction, which revealed the dengue viral antigen. Dengue-3 virus was isolated and identified with electron microscopy in a C6/36 cell culture inoculated with the patient's serum. Viral particles were detected in the infected cell culture.

Hepatic damage associated with dengue-2 virus replication in liver cells of BALB/c mice

“…8,26,27,29 All histopathological aspects were mainly observed in zone II (midzonal areas) in the liver hepatic acini, and sinusoidal infiltrate was evident in zones I (periportal areas) and II of the acinus, correlating to the findings described in humans. 8,9,27 The detection of steatosis in mice was in agreement with other findings, which showed that it is a microscopic feature in the liver of dengue fatal human cases, 8 normally associated with hepatomegaly. However, although steatosis represents a metabolic disturbance observed in several hepatitis of virus origin such as yellow fever 30 and hepatitis C, 31 its pathogenesis in dengue infections is not fully understood.…”

“…Dengue antigens were detected in hepatocytes, either in the vicinity of portal tract or around central veins, Kupffer cells and vascular endothelium, which correlate to what were observed in fatal human cases. 7,9,36,44,45 These data suggest that DENV replicates in the liver tissue. To confirm such hypothesis, we performed an in situ hybridization using a probe that anneals in a conserved region of the negative strand of viral RNA.…”

“…[7][8][9][26][27][28] In a previous work, we have shown that BALB/c mice intraperitoneally inoculated with a DENV-2, isolated from a human patient, presented viremia and mild focal areas of liver injuries. 11 In this work, mice were inoculated by the i.v.…”

“…1,[3][4][5][6] Histopathology of tissue specimens obtained from DF and DHF patients postmortem indicates that lymphoid organs and also the liver are implicated with DENV replication. [3][4][5][6][7][8][9] Nevertheless, the knowledge obtained from studies in humans alone is insufficient either to clarify the pathogenesis, or to build strategies on the prevention or treatment of dengue disease. Several mouse models have been developed for the studies with dengue; however, none of them were able to mimic the full spectrum of the disease in humans (reviewed in Bente and Rico-Hesse 4 and Yauch and Shresta 10 ).…”

Effect of dengue virus infection on the permeability of vero cells line

“…An autopsy study of 63 years old male patient died due to DHF revealed tissue damaged, caused by intense haemorrhage, interstitial edema and inflammation. Viral antigen was found in inflammatory cells of liver, lung, heart, kidney and lymph nodes, as well as in hepatocytes and endothelial cells [5].…”