Clinical Aspects of Marburg Hemorrhagic Fever

Mehedi, Masfique; Groseth, Allison; Feldmann, Heinz; Ebihara, Hideki

doi:10.2217/fvl.11.79

Cited by 128 publications

(168 citation statements)

References 93 publications

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“…During midstage disease, patients develop hemorrhagic manifestations, such as gastrointestinal mucosal petechiae and hemorrhage with bloody diarrhea, ecchymoses, and hematemesis. Progression to late stage disease is characterized by convulsions, dementia, severe coagulopathy, systemic shock, and multiorgan failure, often culminating in death (8,(23)(24)(25). The late-stage disease presentation in this model, as evidenced by high viral titers seen in the liver, spleen, and lymphoid tissues and by hematologic changes and coagulopathy, is comparable to the limited data that are available from patients infected with Marburg virus (3,9,24,26,27).…”

Section: Discussionmentioning

confidence: 57%

Temporal Characterization of Marburg Virus Angola Infection following Aerosol Challenge in Rhesus Macaques

Lin

Twenhafel

Connor

et al. 2015

J Virol

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Marburg virus (MARV) infection is a lethal hemorrhagic fever for which no licensed vaccines or therapeutics are available. Development of appropriate medical countermeasures requires a thorough understanding of the interaction between the host and the pathogen and the resulting disease course. In this study, 15 rhesus macaques were sequentially sacrificed following aerosol exposure to the MARV variant Angola, with longitudinal changes in physiology, immunology, and histopathology used to assess disease progression. Immunohistochemical evidence of infection and resulting histopathological changes were identified as early as day 3 postexposure (p.e.). The appearance of fever in infected animals coincided with the detection of serum viremia and plasma viral genomes on day 4 p.e. High (>10 7 PFU/ml) viral loads were detected in all major organs (lung, liver, spleen, kidney, brain, etc.) beginning day 6 p.e. Clinical pathology findings included coagulopathy, leukocytosis, and profound liver destruction as indicated by elevated liver transaminases, azotemia, and hypoalbuminemia. Altered cytokine expression in response to infection included early increases in Th2 cytokines such as interleukin 10 (IL-10) and IL-5 and late-stage increases in Th1 cytokines such as IL-2, IL-15, and granulocyte-macrophage colony-stimulating factor (GM-CSF). This study provides a longitudinal examination of clinical disease of aerosol MARV Angola infection in the rhesus macaque model. IMPORTANCEIn this study, we carefully analyzed the timeline of Marburg virus infection in nonhuman primates in order to provide a wellcharacterized model of disease progression following aerosol exposure. Marburg virus (MARV) is a single-stranded negative-sense RNA virus that belongs to the family Filoviridae (1). The genus Marburgvirus is composed of a single species, Marburg marburgvirus, which includes the subspecies MARV and Ravn virus. The first outbreak of MARV occurred simultaneously in Germany and the former Yugoslavia in August 1967, when laboratory personnel were exposed to the virus through contact with infected tissues from African green monkeys imported from Uganda (2, 3). Seven of the 32 confirmed human cases (mostly primary exposures) succumbed to infection (4,5). From 1975 to 1998, subsequent MARV infections were limited to sporadic cases in selected areas of Africa, until the occurrence of two large outbreaks in the Democratic Republic of the Congo from 1998 to 2000 and Angola from 2004 to 2005 (6, 7). The case fatality rates for these outbreaks were 83% (128/154) and 90% (227/252), respectively, and established MARV disease as an important public health threat (8, 9).There are currently no licensed medical countermeasures to combat infections with filoviruses such as MARV. Due to the high pathogenicity of MARV, it is classified as a biological select agent by the U.S. Department of Health and Human Services (HHS) and a category A bioterrorism agent by the Centers for Disease Control and Prevention (CDC) (1). As such, any MARV research ...

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Section: Discussionmentioning

confidence: 57%

Temporal Characterization of Marburg Virus Angola Infection following Aerosol Challenge in Rhesus Macaques

Lin

Twenhafel

Connor

et al. 2015

J Virol

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“…Another word, "What is the correct diagnosis for "DIC" that is associated with abnormal coagulation profile?" In Ebola, acute fulminating hepatitis/acute hepatic necrosis, especially multifocal necrosis type, occurs without a good explanation [5,[36][37][38][39][40]. With the "two-activation theory" this can be easily explained by endotheliopathyassociated DIT/VMTD causing hepatic microthrombosis and acute hepatic necrosis syndrome, leading to hepatic coagulopathy [5].…”

Section: Microthrombogenesis and Activated Tf Coagulation Pathwaymentioning

confidence: 99%

Pathogenesis of Ebola Viral Haemorrhagic Fever: TTP-like Syndrome Associated with Hepatic Coagulopathy based on "Two Activation Theory of the Endothelium"

Chang¹

2017

J Prev Inf Cntrl

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Ebola viral haemorrhagic fever is a serious haemorrhagic disorder associated with Ebola viral sepsis. The demise of the patient occurs due to severe inflammation, multi-organ dysfunction syndrome and haemorrhage associated with a poorly defined coagulopathy. Ebola virus causes endothelial injury that orchestrates inflammation and multi-organ dysfunction, especially in the liver. To address clinical and hematological features, a novel pathogenesis based on the "two-activation theory of the endothelium" is proposed. Endothelial injury activates endothelial cells that promote various clinical syndromes such as consumptive thrombocytopenia, multi-organ dysfunction and thrombotic microangiopathy.Endotheliopathy initiates two independent molecular events at endothelial cells: 1) Release of inflammatory cytokines, and 2) Activation of the platelet and exocytosis of unusually large von Willebrand factor multimers. The former triggers activation of inflammatory pathway and the latter mediates activation of microthrombotic pathway. In Ebola viral sepsis, activation of inflammatory pathway causes inflammation, but activation of microthrombotic pathway manifests as disseminated intravascular microthrombosis (DIT). The pathogenesis of Ebola viral haemorrhagic fever is hepatic coagulopathy triggered by acute hepatic necrosis as a result of endotheliopathy-associated DIT, which could manifest as TTP-like syndrome.

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“…In addition, phylogenetic analysis of GP gene sequences of EBOV confirmed that epidemic EBOV-Z strains shown close genetic relationships. [7] Ebola Outbreaks According to Ebola Situation Report In West African Countries more than 11,000 deaths and 28500 Suspected Cases are found, Recently there is no conform victim found From Dec 2015 to 6 Jan 2016, due to migration It is spread in European countries, suspected cases found in Spain, Italy and United kingdom, the worldwide Suspected cases shown in Figure 2 (WHO 2016).…”

Section: Ebola Virus Is Precarious Corresponding To Ebola Virus Diseamentioning

confidence: 99%

Past, Present and Future about Ebola Virus Diseases: An Updated Review

Mali¹,

Swapnil²,

Jadhav³

et al. 2016

JPPCM

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Ebola virus is responsible for the Ebola virus diseases. The epidemic of Ebola hemorrhagic fever is a deadly disease of animal can also be transmitted to human and non-human primates. The virulence of Ebola virus involved in several immune evasion mechanisms that include an inhibition of type I interferon responsible for innate immunity, epitope masking, etc. recently Ebola virus is sexually transmitted which was reported in Liberia has associated with new clusters in regions previously declared Ebola-free. There is no appropriate antiviral vaccine or therapy is not available to work against EBOV infection in humans. However, supportive recovery practices are performed include high-fluid intake, ventilator support and broad-spectrum antibiotic therapy. The treatment and diagnosis is very important because these kind of dangerous viruses are possibly used for bio-weapons. The present review describes briefly about virology, epidemiology, pathophysiology, transmission, diagnosis and treatment of Ebola viral disease.

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Clinical Aspects of Marburg Hemorrhagic Fever

Cited by 128 publications

References 93 publications

Temporal Characterization of Marburg Virus Angola Infection following Aerosol Challenge in Rhesus Macaques

Temporal Characterization of Marburg Virus Angola Infection following Aerosol Challenge in Rhesus Macaques

Pathogenesis of Ebola Viral Haemorrhagic Fever: TTP-like Syndrome Associated with Hepatic Coagulopathy based on "Two Activation Theory of the Endothelium"

Past, Present and Future about Ebola Virus Diseases: An Updated Review

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