A Health Care Worker with Ebola Virus Disease and Adverse Prognostic Factors Treated in Sierra Leone

O’Shea, Matthew K.; Clay, Katherine; Craig, Douglas A.; Moore, Alastair; Lewis, Stephen; Espina, Melanie; Praught, Jeff; Horne, Simon; Kao, Raymond; Johnston, Andy

doi:10.4269/ajtmh.15-0461

Cited by 8 publications

(6 citation statements)

References 12 publications

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“…Granulocytosis, thrombocytopenia, and elevated BUN and CRE levels are common characteristics of severe disease caused by RVFV and other pathogenic viruses, such as Ebola virus and Crimean-Congo hemorrhagic fever (CCHF) virus (38)(39)(40). Serum samples from 26 patients from the 2000 outbreak of RVFV in Saudi Arabia showed increased WBC and decreased platelets in fatal cases relative to levels in survivors (6,41).…”

Section: Discussionmentioning

confidence: 99%

Peripheral Blood Biomarkers of Disease Outcome in a Monkey Model of Rift Valley Fever Encephalitis

Wonderlich

Caroline

McMillen

et al. 2018

J Virol

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Rift Valley Fever (RVF) is an emerging arboviral disease of livestock and humans. Although the disease is caused by a mosquito-borne virus, humans are infected through contact with, or inhalation of, virus-laden particles from contaminated animal carcasses. Some individuals infected with RVF virus (RVFV) develop meningoencephalitis, resulting in morbidity and mortality. Little is known about the pathogenic mechanisms that lead to neurologic sequelae, and thus, animal models that represent human disease are needed. African green monkeys (AGM) exposed to aerosols containing RVFV develop a reproducibly lethal neurological disease that resembles human illness. To understand the disease process and identify biomarkers of lethality, two groups of 5 AGM were infected by inhalation with either a lethal or a sublethal dose of RVFV. Divergence between lethal and sublethal infections occurred as early as 2 days postinfection (dpi), at which point CD8 T cells from lethally infected AGM expressed activated caspase-3 and simultaneously failed to increase levels of major histocompatibility complex (MHC) class II molecules, in contrast to surviving animals. At 4 dpi, lethally infected animals failed to demonstrate proliferation of total CD4 and CD8 T cells, in contrast to survivors. These marked changes in peripheral blood cells occur much earlier than more-established indicators of severe RVF disease, such as granulocytosis and fever. In addition, an early proinflammatory (gamma interferon [IFN-γ], interleukin 6 [IL-6], IL-8, monocyte chemoattractant protein 1 [MCP-1]) and antiviral (IFN-α) response was seen in survivors, while very late cytokine expression was found in animals with lethal infections. By characterizing immunological markers of lethal disease, this study furthers our understanding of RVF pathogenesis and will allow the testing of therapeutics and vaccines in the AGM model. Rift Valley Fever (RVF) is an important emerging viral disease for which we lack both an effective human vaccine and treatment. Encephalitis and neurological disease resulting from RVF lead to death or significant long-term disability for infected people. African green monkeys (AGM) develop lethal neurological disease when infected with RVF virus by inhalation. Here we report the similarities in disease course between infected AGM and humans. For the first time, we examine the peripheral immune response during the course of infection in AGM and show that there are very early differences in the immune response between animals that survive infection and those that succumb. We conclude that AGM are a novel and suitable monkey model for studying the neuropathogenesis of RVF and for testing vaccines and therapeutics against this emerging viral pathogen.

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Section: Discussionmentioning

confidence: 99%

Peripheral Blood Biomarkers of Disease Outcome in a Monkey Model of Rift Valley Fever Encephalitis

Wonderlich

Caroline

McMillen

et al. 2018

J Virol

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“…3 Despite the prevalence of malaria in countries at risk for EVD outbreaks, little data exist pertaining to Ebola virus and malaria parasite co-infection. One case report 4 describes a health-care worker co-infected with Ebola virus and Plasmodium falciparum with multiorgan failure, and a retrospective study 5 of patients in Liberia showed a prevalence of co-infection of 15%. The antimalarial amodiaquine might have activity against Ebola virus.…”

Section: Introductionmentioning

confidence: 99%

Characteristics and survival of patients with Ebola virus infection, malaria, or both in Sierra Leone: a retrospective cohort study

Waxman

Aluisio

Rege

et al. 2017

The Lancet Infectious Diseases

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“…The level of sophistication of these interventions varies from basic oral rehydration therapy without laboratory investigations in the most resource poor settings, through to invasive fluid, electrolyte and blood product management, mechanical ventilation, and haemodialysis with full laboratory and radiology support in intensive care units in developed countries [42]. Even within countries most affected by EVD, the level of supportive care varied widely [59,60]. Whether increasing sophistication of supportive care is associated with improved outcomes is not proven, however, one could not dispute this intuitively.…”

Section: Supportive Carementioning

confidence: 99%

Ebola virus disease: An update on current prevention and management strategies

Trad

Naughton

Yeung

et al. 2017

Journal of Clinical Virology

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a b s t r a c tEbola virus disease (EVD) is characterised by systemic viral replication, immuno-suppression, abnormal inflammatory responses, large volume fluid and electrolyte losses, and high mortality in under-resourced settings. There are various therapeutic strategies targeting EVD including vaccines utilizing different antigen delivery methods, antibody-based therapies and antiviral drugs. These therapies remain experimental, but received attention following their use particularly in cases treated outside West Africa during the 2014-15 outbreak, in which 20 (80%) out of 25 patients survived. Emerging data from current trials look promising and are undergoing further study, however optimised supportive care remains the key to reducing mortality from EVD.Crown

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A Health Care Worker with Ebola Virus Disease and Adverse Prognostic Factors Treated in Sierra Leone

Cited by 8 publications

References 12 publications

Peripheral Blood Biomarkers of Disease Outcome in a Monkey Model of Rift Valley Fever Encephalitis

Peripheral Blood Biomarkers of Disease Outcome in a Monkey Model of Rift Valley Fever Encephalitis

Characteristics and survival of patients with Ebola virus infection, malaria, or both in Sierra Leone: a retrospective cohort study

Ebola virus disease: An update on current prevention and management strategies

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