Persistence of Ebola Virus in Ocular Fluid during Convalescence

Varkey, Jay B.; Shantha, Jessica G.; Crozier, Ian; Kraft, Colleen S.; Lyon, G. Marshall; Mehta, Aneesh K.; Kumar, Gautam; Smith, Justine R.; Kainulainen, Markus H.; Whitmer, Shannon; Ströher, Ute; Uyeki, Timothy M.; Ribner, Bruce S.; Yeh, Steven

doi:10.1056/nejmoa1500306

Cited by 409 publications

(363 citation statements)

References 11 publications

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“…Prolonged blood clotting times and increased circulating levels of D-dimers, tissue factor, thrombomodulin and von Willebrand factor have been reported with filovirus infections, and substantially abnormal values for some of these factors have been associated with a fatal outcome [18][19][20][21][22][23] . Complications collectively referred to as 'post-Ebola syndrome' , including musculoskeletal pain, headache and ocular problems, have been noted in a number of survivors of filovirus infection [24][25][26][27][28][29] . In rare cases, encephalitis has also been noted [30][31][32][33] .…”

Section: Clinical Manifestationsmentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

111

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| The filoviruses -Ebola virus and Marburg virus -cause lethal haemorrhagic fever in humans and non-human primates (NHPs). Filoviruses present a global health threat both as naturally acquired diseases and as potential agents of bioterrorism. In the recent 2013-2016 outbreak of Ebola virus, the most promising therapies for post-exposure use with demonstrated efficacy in the gold-standard NHP models of filovirus disease were unable to show statistically significant protection in patients infected with Ebola virus. This Review briefly discusses these failures and what has been learned from these experiences, and summarizes the current status of post-exposure medical countermeasures in development, including antibodies, small interfering RNA and small molecules. We outline how our current knowledge could be applied to the identification of novel interventions and ways to use interventions more effectively. R E V I E W SNATURE REVIEWS | DRUG DISCOVERY VOLUME 17 | JUNE 2018 | 413 © 2 0 1 8 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d . AstheniaMuscular weakness. MyalgiaMuscular pain. ArthralgiaJoint pain. LeukopeniaA condition of having a low number of circulating leukocytes, including neutrophils, eosinophils, basophils, lymphocytes and monocytes. LymphocytopeniaA condition of having a low number of circulating leukocytes, including natural killer cells, T cells and B cells. ThrombocytopeniaA condition of having a low number of circulating thrombocytes, also known as platelets.and Ebolavirus. The Marburgvirus genus contains a single species, Marburg marburgvirus, which contains two members, Marburg virus (MARV) and Ravn virus (RAVV). The Ebolavirus genus consists of five distinct species: Bundibugyo ebolavirus (BDBV), Reston ebolavirus (RESTV), Sudan ebolavirus (SUDV), Tai Forest ebolavirus (TAFV; previously termed 'Côte d'Ivoire ebolavirus' but more commonly known as 'Ivory Coast ebolavirus') and Zaire ebolavirus (EBOV). MARV, RAVV, BDBV, SUDV and EBOV are important human pathogens, with case fatality rates often up to 90% for MARV, RAVV and EBOV, and around 55% for SUDV 8,10 . On the basis of two small outbreaks in 2007 and 2012, BDBV seems to be the least pathogenic, with a case fatality rate of about 40-48% 11,12 . In 1994, TAFV was associated with a number of deaths in chimpanzees and a single symptomatic but non-lethal human infection in the Republic of Côte d'Ivoire 13,14 . RESTV is lethal for macaques but is not thought to cause disease in humans 15 . An outbreak of RESTV was reported in pigs in the Philippines in 2008; however, it remains uncertain whether the disease observed in the pigs was caused by RESTV or other agents reported to have co-infected the animals 16 . Clinical manifestationsClinical and laboratory signs of disease caused by filovirus infection are nonspecific and usually associated with an incubation period of 2-21 days (mean 4-10 days) 8,17 . Illness begins with an abrupt onset of fever, astheni...

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Section: Clinical Manifestationsmentioning

confidence: 99%

Post-exposure treatments for Ebola and Marburg virus infections

Cross

Mire

Feldmann

et al. 2018

Nat Rev Drug Discov

111

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“…A recent report details a 43-year-old American physician who had clinically recovered from EVD 9 weeks prior to developing severe unilateral uveitis. Aqueous humor was obtained from the affected eye, in which viable Ebola virus was detected [45]. While ocular manifestations including uveitis are known to occur in EVD survivors during the convalescent phase, these findings have been thought to be related to delayed immunological factors.…”

Section: Viral Persistencementioning

confidence: 99%

Neurological Complications of Ebola Virus Infection

2016

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Ebola virus disease is one of the deadliest pathogens known to man, with a mortality rate between 25-90% depending on the species and outbreak of Ebola. Typically, it presents with fever, headache, voluminous vomiting and diarrhea, and can progress to a hemorrhagic illness; neurologic symptoms, including meningoencephalitis, seizures, and coma, can also occur. Recently, an outbreak occurred in West Africa, affecting > 28,000 people, and killing > 11,000. Owing to the magnitude of this outbreak, and the large number (>17,000) of Ebola survivors, the medical and scientific communities are learning much more about the acute manifestations and sequelae of Ebola. A number of neurologic complications can occur after Ebola, such as seizures, memory loss, headaches, cranial nerve abnormalities, and tremor. Ebola may also persist in some immunologically privileged sites, including the central nervous system, and can rarely lead to relapse in disease. Owing to these findings, it is important that survivors are evaluated and monitored for neurologic symptoms. Much is unknown about this disease, and treatment remains largely supportive; however, with ongoing clinical and basic science, the mechanisms of how Ebola affects the central nervous system and how it persists after acute disease will hopefully become more clear, and better treatments and clinical practices for Ebola patients will be developed.

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“…Low back and sacroiliac pain and bilateral enthesitis of Achilles tendon have also been reported during the convalescence period [6]. In the current outbreak, around 50% of survivors complained of fatigue.…”

Section: Fatigue and Musculoskeletal Painmentioning

confidence: 65%

Post-Ebolavirus disease syndrome: what do we know?

Carod-Artal

2015

Expert Review of Anti-infective Therapy

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Persistence of Ebola Virus in Ocular Fluid during Convalescence

Cited by 409 publications

References 11 publications

Post-exposure treatments for Ebola and Marburg virus infections

Post-exposure treatments for Ebola and Marburg virus infections

Neurological Complications of Ebola Virus Infection

Post-Ebolavirus disease syndrome: what do we know?

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