Molecular Evidence of Sexual Transmission of Ebola Virus

Mate, Suzanne; Kugelman, Jeffrey R.; Nyenswah, Tolbert; Ladner, Jason T.; Wiley, Michael R.; Cordier-Lassalle, Thierry; Christie, Athalia; Schroth, Gary P.; Gross, Stephen; Davies-Wayne, Gloria; Shinde, Shivam A.; Murugan, Ratnesh; Sieh, Sonpon; Badio, Moses; Fakoli, Lawrence; Taweh, Fahn; Wit, Emmie de; Doremalen, Neeltje van; Munster, Vincent J.; Pettitt, James; Prieto, Karla; Humrighouse, Ben W.; Ströher, Ute; Diclaro, Joseph W.; Hensley, Lisa E.; Schoepp, Randal J.; Safronetz, David; Fair, Joseph N.; Kuhn, Jens H.; Blackley, David J.; Laney, A. Scott; Williams, Desmond E.; Lo, Terrence; Gasasira, Alex; Nichol, Stuart T.; Formenty, Pierre; Kateh, Francis; Cock, Kevin M. De; Bolay, Fatorma K.; Sánchez-Lockhart, Mariano; Palacios, Gustavo

doi:10.1056/nejmoa1509773

Cited by 389 publications

(350 citation statements)

References 17 publications

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“…In rare cases, encephalitis has also been noted [30][31][32][33] . Filoviruses have also been detected by PCR and/or virus isolation in the breast milk 34,35 and semen [36][37][38][39] of survivors. The persistence of filoviruses in semen is particularly concerning, with detection in one individual occurring 565 days after discharge from an EBOV treatment centre in Liberia 38 .…”

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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“…Sensory examination cannot be performed symptoms, although at decreasing rates over time (with all survivors who were tested at 2-3 months after onset having EBOV RNA-positive semen, 65% of survivors positive at 4-6 months after onset, and 26% positive at 7-9 months after onset) [42]. These findings are of further interest given the potential for sexual transmission of EVD, as in the previously mentioned March 2015 case in Liberia [15]. Owing to risk of sexual transmission during convalescence, Ebola survivors are now recommended to practice safe sex with barrier protection for at least 12 months after recovery from EVD [43].…”

Section: Viral Persistencementioning

confidence: 87%

“…Although seemingly rare, Ebola can also be transmitted through sexual contact, even in the convalescent phase, as Ebola virus can persist in semen for months after recovery from the illness [14]. A case of Ebola occurred in a woman in March 2015 whose only known Ebola contact was via unprotected sex with an EVD survivor; after genetic analysis it was confirmed that survivor's and the patient's Ebola virus genomes were identical and that the transmission likely occurred from sexual contact [15]. Butchering and handling of bushmeat, including nonhuman primates and bats, have also previously been associated with outbreaks of Ebola [16].…”

Section: Clinical Properties Transmissionmentioning

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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“…Variability in lethality might also relate to factors such as time from disease onset to presentation for care, quality of care available, patient demographics, or variant of infecting virus. 14,[22][23][24] Accurate viral load measurement is also important in interpreting Ebola virus persistence in and transmission risk from immuneprivileged body compartments and fl uids, 25 including the male gonads or semen, [25][26][27][28] eyes, 29 CNS, 30 breast milk, 31 and the intrauterine space in pregnant women. 32 Additionally, Ebola virus has occasionally been found in sweat and urine, 33 and in atypical or asymptomatic cases.…”

Section: Importance Of Fi Lovirus Load Determinationmentioning

confidence: 99%

Essentials of filoviral load quantification

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Griensven

Honko

et al. 2016

The Lancet Infectious Diseases

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Quantitative measurement of viral load is an important parameter in the management of fi lovirus disease outbreaks because viral load correlates with severity of disease, survival, and infectivity. During the ongoing Ebola virus disease outbreak in parts of Western Africa, most assays used in the detection of Ebola virus disease by more than 44 diagnostic laboratories yielded qualitative results. Regulatory hurdles involved in validating quantitative assays and the urgent need for a rapid Ebola virus disease diagnosis precluded development of validated quantitative assays during the outbreak. Because of sparse quantitative data obtained from these outbreaks, opportunities for study of correlations between patient outcome, changes in viral load during the course of an outbreak, disease course in asymptomatic individuals, and the potential for virus transmission between infected patients and contacts have been limited. We strongly urge the continued development of quantitative viral load assays to carefully evaluate these parameters in future outbreaks of fi lovirus disease.

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Molecular Evidence of Sexual Transmission of Ebola Virus

Cited by 389 publications

References 17 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

Essentials of filoviral load quantification

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