Recovery of virus from the liver of children with fatal dengue: Reflections on the pathogenesis of the disease and its possible analogy with that of yellow fever

Rosen, Léon; Khin, Mi Mi; U, Tin

doi:10.1016/s0923-2516(89)80115-3

Cited by 87 publications

(77 citation statements)

References 12 publications

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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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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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“…Pathological findings reported in patients with DSS include liver centrilobular necrosis, changes in fatty tissue, Kupffer cell hyperplasia, acidophilic bodies, and monocyte infiltration of the portal tracts [2,7]. In fatal cases, DENV-antigen-positive hepatocytes were seen surrounding areas of liver necrosis [8][9][10]. Information about the target tissues and cells suitable for viral infection has been derived from examination of blood samples and tissues collected at autopsy.…”

mentioning

confidence: 99%

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

Ca¹,

Gr²,

Ms³

et al. 2005

Braz J Infect Dis

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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.

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“…Furthermore, the laboratory and histopathologic findings in patients with DHF can mimic those of severe cases of yellow fever (YF) and arenaviral hemorrhagic fever (AHF). All three of these diseases can produce leukopenia, thrombocytopenia, elevated serum transaminase levels, liver necrosis, and Councilman bodies (eosinophilic depositions in hepatocytes) (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). This is an important consideration, since correct diagnosis and early recognition of any of these diseases is essential for their treatment, as well as for the appropriate public health response.…”

Section: Dengue Hemorrhagic Fevermentioning

confidence: 99%

“…Clinically, the two diseases may be similar: acutely ill patients with fever, leukopenia and hemorrhagic manifestations (7)(8)(9)(10)(11)(12)(13). Although YF patients often have icterus, this is not always obvious in people with dark skin.…”

Section: Yellow Fevermentioning

confidence: 99%

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Fiebres virales hemorrágicas en Suramérica

Tesh

2002

biomedica

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This paper reviews the epidemiology and distinguishing features of three viral hemorrhagic fevers (dengue hemorrhagic fever, yellow fever and arenaviral hemorrhagic fever) that have emerged as important public health problems in South America. Although the etiology, natural history and control of the three diseases are different, their clinical manifestations and histopathology findings are similar and can be difficult to differentiate. Consequently, early recognition and correct diagnosis are essential for effective control measures to be initiated.

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Recovery of virus from the liver of children with fatal dengue: Reflections on the pathogenesis of the disease and its possible analogy with that of yellow fever

Cited by 87 publications

References 12 publications

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

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

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

Fiebres virales hemorrágicas en Suramérica

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