Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Cunha MS

PROVIDER: S-EPMC9433511 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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

Cunha Mariana Sequetin MS de Moura Coletti Thaís T Guerra Juliana Mariotti JM Ponce César Cliento CC Fernandes Natalia Coelho Couto Azevedo NCCA Résio Rodrigo Albegaria RA Claro Ingra Morales IM Salles Flávia F Lima Neto Daniel Ferreira DF Sabino Ester E

Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] 20220702 3

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-o ...[more]

PMID: 35779208

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Project description:BACKGROUND: A better description of the clinical and laboratory manifestations of fatal patients with dengue hemorrhagic fever (DHF) is important in alerting clinicians of severe dengue and improving management. METHODS AND FINDINGS: Of 309 adults with DHF, 10 fatal patients and 299 survivors (controls) were retrospectively analyzed. Regarding causes of fatality, massive gastrointestinal (GI) bleeding was found in 4 patients, dengue shock syndrome (DSS) alone in 2; DSS/subarachnoid hemorrhage, Klebsiella pneumoniae meningitis/bacteremia, ventilator associated pneumonia, and massive GI bleeding/Enterococcus faecalis bacteremia each in one. Fatal patients were found to have significantly higher frequencies of early altered consciousness (?24 h after hospitalization), hypothermia, GI bleeding/massive GI bleeding, DSS, concurrent bacteremia with/without shock, pulmonary edema, renal/hepatic failure, and subarachnoid hemorrhage. Among those experienced early altered consciousness, massive GI bleeding alone/with uremia/with E. faecalis bacteremia, and K. pneumoniae meningitis/bacteremia were each found in one patient. Significantly higher proportion of bandemia from initial (arrival) laboratory data in fatal patients as compared to controls, and higher proportion of pre-fatal leukocytosis and lower pre-fatal platelet count as compared to initial laboratory data of fatal patients were found. Massive GI bleeding (33.3%) and bacteremia (25%) were the major causes of pre-fatal leukocytosis in the deceased patients; 33.3% of the patients with pre-fatal profound thrombocytopenia (<20,000/µL), and 50% of the patients with pre-fatal prothrombin time (PT) prolongation experienced massive GI bleeding. CONCLUSIONS: Our report highlights causes of fatality other than DSS in patients with severe dengue, and suggested hypothermia, leukocytosis and bandemia may be warning signs of severe dengue. Clinicians should be alert to the potential development of massive GI bleeding, particularly in patients with early altered consciousness, profound thrombocytopenia, prolonged PT and/or leukocytosis. Antibiotic(s) should be empirically used for patients at risk for bacteremia until it is proven otherwise, especially in those with early altered consciousness and leukocytosis.

Dataset Information

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

Publications

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

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