A fatal case of dengue hemorrhagic fever associated with dengue virus 4 (DENV-4) in Brazil: genomic and histopathological findings

Dengue infection is the most prevalent arthropod-borne viral disease in subtropical and tropical regions, whose primary vector is Aedes aegypti mosquitoes. The mechanisms of dengue virus (DENV) pathogenesis are little understood because we have no good disease models. Only humans develop symptoms (d...

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Bibliographic Details
Published in:	Brazilian journal of microbiology Vol. 53; no. 3; pp. 1305 - 1312
Main Authors:	Cunha, Mariana Sequetin, de Moura Coletti, Thaís, Guerra, Juliana Mariotti, Ponce, César Cliento, Fernandes, Natalia Coelho Couto Azevedo, Résio, Rodrigo Albegaria, Claro, Ingra Morales, Salles, Flávia, Lima Neto, Daniel Ferreira, Sabino, Ester
Format:	Journal Article
Language:	English
Published:	Cham Springer International Publishing 01-09-2022 Springer Nature B.V
Subjects:	Adolescent Aedes aegypti Animals Biomedical and Life Sciences Brain Brazil Cerebellum Clinical Microbiology - Research Paper Dengue - diagnosis Dengue fever Dengue hemorrhagic fever Dengue Virus - physiology Differential diagnosis Endothelial Cells Enzyme-linked immunosorbent assay Fatalities Food Microbiology Genomics Genotypes Heart Hemagglutination inhibition Hepatocytes Humans Immunohistochemistry Infections Infectious diseases Kidneys Life Sciences Liver Lungs Male Medical Microbiology Microbial Ecology Microbial Genetics and Genomics Microbiology Mosquito Vectors Mosquitoes Mycology Pathogenesis Phylogeny Severe Dengue Signs and symptoms Tropical environment Tropical environments Vector-borne diseases Viral diseases Viruses Brazil Immunohistochemistry Phylogeny Dengue virus Whole-genome sequencing
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Summary:	Dengue infection is the most prevalent arthropod-borne viral disease in subtropical and tropical regions, whose primary vector is Aedes aegypti mosquitoes. The mechanisms of dengue virus (DENV) pathogenesis are little understood because we have no good disease models. Only humans develop symptoms (dengue fever, DF, or dengue hemorrhagic fever, DHF) and research has been limited to studies involving patients. Samples from serum, brain, cerebellum, heart, lungs, liver, and kidneys from a 13-year-old male patient that died with hemorrhagic manifestations were sent for differential diagnosis at Adolfo Lutz, using both classical virological methods (RT-qPCR, virus isolation, ELISA, and hemagglutination inhibition test) and immunohistochemistry (IHQ). A DENV serotype 4 was detected by a DENV multiplex RT-qPCR, and the C6/36 cell supernatant was used for NGS using Minion. Lesions were described in the heart, liver, lung, and kidney with positive IHQ in endothelial cells of the brain, cerebellum, heart, and kidney, and also in hepatocytes and Kuppfer cells. A whole genome was obtained, revealing a DENV-4 genotype II, with no evidence of secondary dengue infection.
Bibliography:	ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3
ISSN:	1517-8382 1678-4405
DOI:	10.1007/s42770-022-00784-4