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Hum Pathol. 2014 Jun;45(6):1221-33. doi: 10.1016/j.humpath.2014.01.022. Epub 2014 Feb 20.

Pathologic highlights of dengue hemorrhagic fever in 13 autopsy cases from Myanmar.

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Department of Medical Research (Lower Myanmar), Yangon, Myanmar.
Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
National Health Laboratory, Yangon, Myanmar.
Intensive Care Unit, Yangon Children Hospital, Yangon, Myanmar.
Dengue Hemorrhagic Fever Research Unit, Mahidol University, Bangkok, Thailand.
Division of Molecular Medicine, Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Dengue Hemorrhagic Fever Research Unit, Mahidol University, Bangkok, Thailand; Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development Agency, Bangkok, Thailand. Electronic address:
Dengue Vaccine Initiative, International Vaccine Institute, Seoul, South Korea. Electronic address:


Vascular permeability, thrombocytopenia, liver pathology, complement activation, and altered hemostasis accompanying a febrile disease are the hallmarks of the dengue hemorrhagic fever/dengue shock syndrome, a major arthropod-borne viral disease that causes significant morbidity and mortality throughout tropical countries. We studied tissues from 13 children who died of acute dengue hemorrhagic fever/dengue shock syndrome at the Childrens' Hospital, Yangon, Myanmar. Dengue viral RNA from each of the 4 dengue viruses (DENVs) was detected by reverse transcriptase polymerase chain reaction in 11 cases, and dengue viral proteins (envelope, NS1, or NS3) were detected in 1 or more tissues from all 13 cases. Formalin-fixed and frozen tissues were studied for evidence of virus infection using monoclonal antibodies against DENV structural and nonstructural antigens (E, NS1, and nonsecreting NS3). In the liver, DENV infection occurred in hepatocytes and Kupffer cells but not in endothelial cells. Liver damage was associated with deposition on hepatocytes of complement components of both classical and alternative pathways. Evidence of dengue viral replication was observed in macrophage-like cells in spleens and lymph nodes. No dengue antigens were detected in endothelial cells in any organ. Germinal centers of the spleen and lymph nodes showed a marked reduction in the number of lymphocytes that were replaced by eosinophilic deposits, which contained dengue antigens as well as immunoglobulins, and complement components (C3, C1q, and C9). The latter findings had previously been reported but overlooked as a diagnostic feature.


Complement activation; Dengue; Dengue antigens; Germinal center; Pathology

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