Report of a fatal case of dengue infection with hepatitis: Demonstration of dengue antigens in hepatocytes and liver apoptosis

Couvelard, Anne; Marianneau, Philippe; Bedel, Christophe; Drouet, Marie-Thérèse; Vachon, F; Hénin, Dominique; Denis, Vincent

doi:10.1016/s0046-8177(99)90230-7

Cited by 187 publications

(182 citation statements)

References 14 publications

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“…In line with our results (Fig. 1), it was demonstrated that involvement of the liver, especially during DHF, may cause hepatocellular necrosis in the midzonal area, and that DENV antigen can be detected in Councilman bodies [6][7][8]. Moreover, reticular GBWT has previously been demonstrated in severe DHF cases and is used as a reliable sign of plasma leakage [9].…”

Section: Discussionsupporting

confidence: 89%

Fatal dengue hemorrhagic fever imported into Germany

Schmidt‐Chanasit

Tenner-Rácz

Poppert³

et al. 2011

Infection

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Dengue virus (DENV) is an arthropod-borne virus (family Flaviviridae) causing dengue fever or dengue hemorrhagic fever. Here, we report the first fatal DENV infection imported into Germany. A female traveler was hospitalized with fever and abdominal pain after returning from Ecuador.Due to a suspected acute acalculous cholecystitis, cholecystectomy was performed. After cholecystectomy, severe spontaneous bleeding from the abdominal wound occurred and the patient died. Postmortem analysis of transudate and tissue demonstrated a DENV secondary infection of the patient and a gallbladder wall thickening (GBWT) due to an extensive edema.

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Section: Discussionsupporting

confidence: 89%

Fatal dengue hemorrhagic fever imported into Germany

Schmidt‐Chanasit

Tenner-Rácz

Poppert³

et al. 2011

Infection

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“…Subsequently, the increased number of infected cells present targets for CD4 + and CD8 + T cells, resulting in large quantities of interleukin (IL)-10, IL-2, interferon (IFN)-γ and TNF that, singly or in combination, might contribute to endothelial damage and altered haemostasis. Virions released from infected cells might also directly damage endothelial cells and the uptake of the non-structural protein NS1 by hepatocytes might promote viral infection of the liver [47][48][49] . During DHF, the complement cascade is also activated and the levels of the complement activation products C3a and C5a correlate with the severity of illness 49 .…”

Section: Dengue Virus Pathogenesismentioning

confidence: 99%

Dengue: a continuing global threat

et al. 2010

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Dengue fever and dengue haemorrhagic fever are important arthropod-borne viral diseases. Each year, there are ~50 million dengue infections and ~500,000 individuals are hospitalized with dengue haemorrhagic fever, mainly in Southeast Asia, the Pacific and the Americas. Illness is produced by any of the four dengue virus serotypes. A global strategy aimed at increasing the capacity for surveillance and outbreak response, changing behaviours and reducing the disease burden using integrated vector management in conjunction with early and accurate diagnosis has been advocated. Antiviral drugs and vaccines that are currently under development could also make an important contribution to dengue control in the future.Dengue is the most important arthropod-borne viral infection of humans. Worldwide, an estimated 2.5 billion people are at risk of infection, approximately 975 million of whom live in urban areas in tropical and sub-tropical countries in Southeast Asia, the Pacific and the Americas 1 . Transmission also occurs in Africa and the Eastern Mediterranean, and rural Europe PMC Funders GroupAuthor Manuscript Nat Rev Microbiol. Author manuscript; available in PMC 2015 February 19. Published in final edited form as:Nat Rev Microbiol. 2010 December ; 8(12 0): S7-16. doi:10.1038/nrmicro2460. Europe PMC Funders Author ManuscriptsEurope PMC Funders Author Manuscripts communities are increasingly being affected. It is estimated that more than 50 million infections occur each year, including 500,000 hospitalizations for dengue haemorrhagic fever, mainly among children, with the case fatality rate exceeding 5% in some areas [1][2][3][4] . The geographical areas in which dengue transmission occurs have expanded in recent years (FIG. 1), and all four dengue virus serotypes (DENV-1-4) are now circulating in Asia, Africa and the Americas, a dramatically different scenario from that which prevailed 20 or 30 years ago (FIG. 2). The molecular epidemiology of these serotypes has been studied in an attempt to understand their evolutionary relationships 11 .This Review will provide an update on our understanding of the pathogenesis of this successful pathogen, how we diagnose and control infection and the progress that has been made in vaccine development. Dengue virus pathogenesisDengue viruses belong to the genus flavivirus within the Flaviviridae family. DENV-1-4 evolved in non-human primates from a common ancestor and each entered the urban cycle independently an estimated 500-1,000 years ago 12 . The virion comprises a spherical particle, 40-50 nm in diameter, with a lipopolysaccharide envelope. The positive singlestrand RNA genome (FIG. 3), which is approximately 11 kb in length, has a single open reading frame that encodes three structural proteins -the capsid (C), membrane (M) and envelope (E) glycoproteins -and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5 [18][19][20] . ADE occurs when mononuclear phagocytes are infected through their Fc receptors by immune complexes that form between DE...

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“…The analysis of the liver tissue showed extensive cell cytopathic effects as vacuolization and intracellular edema; the architecture of the hepatic lobules was partially destroyed; sinusoids were partially collapsed; only a minimal and diffusely distributed mononuclear inflammatory infiltrate was visible; blood vessels were dilated; In humans, DENV has been frequently isolated from the liver, and the antigens have been detected in Kupffer cells and hepatocytes (Rosen et al 1989, Bhamarapravati 1997, Couverland et al 1999. Liver function tests showed high levels of serum aspartate transaminase (AST) and serum alanine transaminase (ALT) activity, indicating hepatic injury (Kuo et al 1992, Nguyen et al 1997, Mohan et al 2000.…”

Section: One Of the Main Difficulties In Studying Dengue Virus Infectmentioning

confidence: 99%

Morphological studies in a model for dengue-2 virus infection in mice

Barth

Barreto²,

Paes

et al. 2006

Mem. Inst. Oswaldo Cruz

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One of the main difficulties in studying dengue virus infection in humans and in developing a vaccine is the absence of a suitable animal model which develops the full spectrum of dengue fever, dengue haemorrhagic fever, and dengue shock syndrome. It is our proposal to present morphological aspects of an animal model which shows many similarities with the dengue infection in humans. BALB/c mice were intraperitoneally infected with non-neuroadapted dengue virus serotype 2 (DENV-2). Histopathological and morphometrical analyses of liver tissue revealed focal alterations along the infection, reaching wide-ranging portal and centrolobular veins congestion and sinusoidal cell death. Additional ultrastructural observations demonstrated multifocal endothelial injury, platelet recruitment, and alterated hepatocytes. Dengue virus antigen was detected in hepatocytes and in the capillar endothelium of the central lobular vein area. Liver function tests showed high levels of aspartate transaminase and alanine transaminase enzyme activity. Lung tissue showed interstitial pneumonia and mononuclear cells, interseptal oedema, hyperplasia, and hypertrophy of the bronchiolar epithelial cells. DENV-2 led to a transient inflammatory process, but caused focal alterations of the blood-exchange barrier. Viremia was observed from 2nd to 11th day p.i. by isolation of DENV-2 in C6/36 mosquito cell line inoculated with the supernatant of macerated liver, lung, kidney, and cerebellum tissues of the infected mice.Key words: dengue-2 virus -BALB/c mice -liver -viremia -ultrastructure -histopathology Dengue viruses (DENV) are mosquito-borne RNAviruses that are classified serologically into four antigenically distinct types (DENV-1, 2, 3, 4). They infect millions of people in tropical and subtropical regions of the world and may cause a mild to debilitating febrile illness, the classical dengue fever (DF), the dengue haemorrhagic fever (DHF), and dengue shock syndrome (DSS). However, the pathogenesis of human dengue infection (DEN) remains not sufficiently known, and no successful vaccine is available as yet (Eckels 1993). The studies on pathogenesis, pharmacodynamics, and prophylaxis of DHF have been hampered due to the lack of a suitable animal model (Bhamarapravati 1993).DENV have been inoculated into numerous species of animals by a variety of routes. Studies on laboratory mice and non-human primates remain the most wellcharacterized models (Cole & Wisseman 1969, Marchette et al. 1973, Boonpucknavig et al. 1981, Hotta et al. 1981a,b, Chaturvedi et al. 1991, Wu et al. 1995.Several studies indicated that mice are a permissive host for DENV (Meiklejhon et al. 1952, Lin et al. 1998, Johnson & Roehrig 1999. However, no infectious model that mimics DHF/DSS has yet been reported (Huang et al. 2000). Until now the great majority of mice models of DENV infection deal with suckling or young mice infected by an intracerebral route of inoculation (Nath et al. 1983, Raut et al. 1996 and with mouse-neuroadapted DENV (Desprès et al. 1998, Atrasheuskaya e...

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Report of a fatal case of dengue infection with hepatitis: Demonstration of dengue antigens in hepatocytes and liver apoptosis

Cited by 187 publications

References 14 publications

Fatal dengue hemorrhagic fever imported into Germany

Fatal dengue hemorrhagic fever imported into Germany

Dengue: a continuing global threat

Morphological studies in a model for dengue-2 virus infection in mice

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