Posted on 24TH JUL 2017
tagged Ebola, Worldwide

A ProMED-mail post
ProMED-mail is a program of the
International Society for Infectious Diseases

In this update:
[1] Research
- Ebola virus / RNA persistence
Experimentally documented in macaques
CSF of Ebola survivors examined
RNA persistence in semen
- Diagnostics
Silicon nanodisks
Demographic analysis
[2] Vaccines
- Market evaluation
[3] Funding
- Canada (Winnipeg) BSL-4 expansion

[1] Research
Ebola virus/RNA persistence
17 Jul 2017: Ebola Persistence Documented in macaques

[In tissue samples from rhesus macaques, researchers find the virus in the same immune-privileged sites where [the Ebola virus] has been found to persist in humans.

Although the [Ebola virus disease (EVD)] outbreak in West Africa that started in 2013 was declared over more than a year ago, the disease lingers on. Many Ebola survivors have suffered from joint aches, vision problems, hearing loss, headaches, and other symptoms, a phenomenon dubbed "post-Ebola syndrome." Researchers studying macaques have a better understanding of why that might be: they've tracked the progression of Ebola virus through various tissues of monkeys who have survived acute infections and found evidence of long-term viral persistence and possible replication.

"They essentially found that the Ebola virus can persist in a number of sites that we consider immune privileged, including the eye, the brain, and the reproductive organs, or the testes," Emory University opthalmologist Steven Yeh, who treated a high-profile case of eye inflammation caused by persistent Ebola virus and studies Ebola persistence, tells The Scientist. "I think it's got implications from the standpoint of Ebola survivorship, as to why Ebola survivors in West Africa will develop long-term survivor complications, like eye disease, central nervous system manifestations, as well as the important public health issue of viral persistence in reproductive organs and the risk of sexual transmission." ...more]

[Byline: Ashley P. Taylor]

17 Jul 2017: Cerebrospinal fluid of survivors of Ebola virus disease examined

[Citation. Billioux BJ, Nath A, Stavale EJ, et al., for the Partnership for Research on Ebola Virus in Liberia (PREVAIL) III Study Group. Cerebrospinal Fluid Examination in Survivors of Ebola Virus Disease. JAMA Neurol. Published online 17 Jul 2017. doi:10.1001/jamaneurol.2017.1460

A new research letter published by JAMA Neurology reports on examinations of cerebrospinal fluid collected from survivors of Ebola virus disease (EVD) to investigate potential Ebola virus persistence in the central nervous system.

Avindra Nath, M.D., of the National Institute of Neurological Disorders and Stroke of the National Institutes of Health, Bethesda, Md., and coauthors collected cerebrospinal fluid (CSF) samples in 2015 from 7 EVD survivors (2 women and 5 men; average age 35) in the PREVAIL study.

The fluid samples were analyzed for Ebola viral RNA. The authors report no Ebola viral RNA was detected in the 7 samples.
"The CSF from all 7 patients undergoing analysis was negative for Ebola viral RNA and showed no signs of inflammation; however, this finding could be related to the relatively long period from resolution of acute EVD to performance of LP [lumbar puncture to collect the CSF]," according to the article.

The article suggests that, alternately, if Ebola virus is dormant in the central nervous system of EVD survivors and is cell associated, it may not be released into CSF. Additionally, any release of virus from reservoirs into the CSF would be expected to cause acute meningoencephalitis, the authors write.

"Thus, EVD survivors should be monitored for neurologic symptoms suggestive of EVD relapse in the CNS [central nervous system] because of the potential for Ebola virus transmission during relapse," the research letter concludes.]

Abstract. With the extent of the recent Ebola virus disease (EVD) epidemic in West Africa (including over 28 000 cases and 17 000 or more survivors), many aspects of Ebola virus have become clearer, including acute manifestations, sequelae, and the possibility of relapse and persistence. Neurologic complications are becoming more commonly recognized in EVD during the acute phase, with long-term sequelae. More remarkable, however, is the potential for persistence and relapse of EVD in the central nervous system (CNS), as in the case of a nurse who developed meningoencephalitis with seizures, cranial nerve involvement, and radiculitis 9 months after EVD recovery. Ebola virus was recovered from the cerebrospinal fluid (CSF) at higher levels than from the blood, indicating viral replication in the CNS. This case reveals the need to determine the role of the CNS as a potential reservoir for Ebola virus after initial clinical recovery.]

22 Jul 2017: Ebola Virus RNA detection in semen more than 2 years after resolution of acute Ebola Virus infection

[Citation. Fischer W.A., Brown J., Wohl D.L., et al. (22 Jul 2017). Ebola Virus RNA detection in semen more than two years after resolution of acute Ebola Virus infection. Oxford Academic DOI: https://doi.org/10.1093/ofid/ofx155

Abstract. Among 149 men who survived Ebola Virus Disease (EVD) donating semen 260-1016 days after EVD onset, Ebola virus (EBOV) RNA was detected in 13 (9 percent). Of 137 men donating semen 2 years after EVD onset, 11 (8 percent) had an EBOV RNA-positive specimen. The mechanism underlying the persistence of EBOV RNA in semen is unclear, as is whether the detection of viral RNA represents the presence of infectious virus.]

19 Jul 2017: Partnering with U.S. Army to improve Ebola detection

[To catch a serial killer, homicide detectives must quickly and accurately find clues. Trace evidence left at a crime scene will eventually reveal the killer's presence and identity, but the detectives 1st have to know what to look for.

Like a criminal hiding in plain sight, contagious pathogens spread by capitalizing on the delay between initial infection and telltale symptoms in their hosts. That reality was painfully clear during the 2014 Ebola outbreak where clinics struggled to prevent transmission from patients to caregivers overwhelmed by the disease. The deadly virus travelled across continents before its symptoms were detected and the infected patients were quarantined.

Fortunately, the 2014 epidemic subsided, but recent cases in the Congo indicate the virus is still an active threat. In preparation for future outbreaks, researchers are racing to equip field clinicians with diagnostic tools that will detect virus-infected individuals early to prevent new epidemics.

One of those tools is a nanotechnology platform developed by engineer Tony Hu, PhD that detects disease molecules in blood samples. In this assay, diluted patient blood samples are mixed with porous silicon nanodisks (pSiNDs). A machine called a mass spectrometer (MS) measures the mass of all the molecules bound by these pSiNDs. The method, known as pSiND-MS, is very sensitive and can identify specific amino acid sequences of peptides belonging to viruses like [the Ebola virus].

"Ebola is a disease, but it is also a family. For each strain, the treatment can be different. We want to develop a method that only uses one step, one method [to identify these strains]," Tony Hu explained.

Hu, a researcher at the Virginia Piper Center for Personal Diagnostics at ASU's Biodesign Institute and faculty at the Ira A. Fulton Schools of Engineering, previously applied the pSiND-MS method to tuberculosis testing and succeeded in reducing the diagnosis time from days to mere hours. He plans to apply a similar approach to Ebola by using the pSiND-MS method to improve detection of 3 telltale biomarkers in Ebola patient blood samples.

These 3 biomarkers are peptide sequences. The virus produces one of these peptides, Ebola antigen VP40, soon after infection. The other 2 peptides, Serum Amyloid A and alpha-1-antichymotrypsin, are produced by the patient's immune system in response to the infection.
"Once you enrich the antigen directly from the blood, then we have some special way to digest this antigen and profile their fragment picture landscape on the mass spec," says Hu.

All 3 peptides are detectable in blood samples even before viral particles themselves are detectable. They are a trio of clues that reveal in just 2 hours whether a person has contracted Ebola.

Thanks to a new grant from the National Institute of Health (NIH) Hu's lab will partner with the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) to improve and expand the rapid Ebola test even further. Hu's lab is located at ASU's Biodesign Institute, but USAMRIID's Biosafety Level-4 facility in Fort Detrick, Maryland will conduct all the Ebola experiments.]

21 Jul 2017: Analysis of patient data from laboratories during the Ebola virus disease outbreak in Liberia, April 2014 to March 2015

[Citation. Foruse Y., Fallah M., Oshitani H., et al. (21 Jul 2017). Analysis of patient data from laboratories during the Ebola virus disease outbreak in Liberia, April 2014 to March 2015. PLOS Neglected tropical diseases. https://doi.org/10.1371/journal.pntd.0005804

Abstract [edited]. An outbreak of Ebola virus disease (EVD) in Liberia began in March 2014 and ended in January 2016. Epidemiological information on the EVD cases was collected and managed nationally; however, collection and management of the data were challenging at the time because surveillance and reporting systems malfunctioned during the outbreak. EVD diagnostic laboratories, however, were able to register basic demographic and clinical information of patients more systematically. Here we present data on 16 370 laboratory samples that were tested between 4 Apr 2014 and 29 Mar 2015. A total of 10 536 traceable individuals were identified, of whom 3897 were confirmed cases (positive for Ebola virus RNA). There were significant differences in sex, age, and place of residence between confirmed and suspected cases that tested negative for Ebola virus RNA. Age (young children and the elderly) and place of residence (rural areas) were the risk factors for death due to the disease. The case fatality rate of confirmed cases decreased from 80 percent to 63 percent during the study period. These findings may help support future investigations and lead to a fuller understanding of the outbreak in Liberia.]

[2] Vaccines
21 Jul 2017: Global Ebola Virus Vaccine market 2017 - Bavarian Nordic, Crucell, Fab Entech, Inovio Pharmaceuticals, Microbiotix

[Ebola Virus Vaccine Market analyzed the industry region, including the product price, profit, capacity, production, capacity utilization, supply, demand and industry growth rate etc. In the end, the report introduced new project SWOT analysis, investment feasibility analysis, and investment return analysis to 2022.

The recent report on the Ebola virus vaccine market throws light on the various factors governing the market across the globe. The report, entitled "Ebola Virus Vaccine" assesses the growth of the Ebola virus vaccine market and estimates the valuation of the overall market by the end of the forecast period. The report provides an overview of the market and lists down the key drivers and restraints that will affect the market during the forecast horizon. Analysis of Porter's "Five Forces on Ebola Virus Vaccine Market in the World" has been mentioned in the report. The report also compiles insightful information about the key players in the market.

The report segments the Ebola virus vaccine market in the globe on the basis of product types and end-use application segments. The report analyzes the entire value chain of the Ebola virus vaccine market and forecasts the market size and revenue to be generated by each of the segments. Various micro- and macro-economic factors governing the global Ebola virus vaccine market has been mentioned in the report. The present global slow growth of the economy and the impact of governments' latest initiatives have been taken into account while forecasting the growth of the Ebola virus vaccine market in the region.

The report discusses in detail the vendor landscape of the Ebola virus vaccine market. The market has been analyzed on the basis of market attractiveness and investment feasibility. The report lists down the key players in the Ebola virus vaccine market and provides crucial information about them such as business overview, revenue segmentation, and product offerings. Through SWOT analysis, the report analyses the growth of the key players during the forecast horizon.

The report determines the leading players in the global market. The company profiles of the major participants operating in the global Ebola virus vaccine market have been reviewed in this study.]

[No mention of a comparison of the efficacy of the different vaccines, but this is just a market analysis. - Mod.LK]

[3] Funding
20 Jul 2017: National Microbiology Lab in Winnipeg gets USD 5 million to expand Ebola containment lab

[The federal government is putting millions more into Canada's National Microbiology Lab in Winnipeg to help detect high-risk infectious diseases such as Ebola and various types of avian influenza faster.

The USD 5 million will be used to convert current Level 3 containment laboratory space to the "highest level of biosafety," the federal government said in a news release on Thu [20 Jul 2017]. The facility already holds a Containment Level 4 lab, which will be expanded by the investment.

Health Minister Jane Philpott made the announcement at the Canadian Science Centre for Human and Animal Health, which houses the National Microbiology Laboratory in Winnipeg.

The increased space will help staff at the lab better respond to [Ebola virus disease (EVD)], Middle East respiratory syndrome, and new types of avian influenza quicker amid the increased global demand for investigation of cases.

Containment Level 4 laboratories are equipped to diagnose, research and develop vaccines for Ebola and Nipah virus.

In November 2016, a Winnipeg employee at the level 4 lab was potentially exposed to the Ebola virus. The worker noticed a split in his protective suit while working with pigs that had been exposed to [the Ebola virus].

The worker was put in isolation for 21 days and was eventually cleared to return to work.

The government said emergency protocols for accidental exposure were implemented following the incident.]

[Compiled by: Celeste Whitlow ]

Communicated by:

[A map of the DR Congo can be seen at https://www.independent.co.ug/ebola-in-drc, and a HealthMap/ProMED-mail map of the DRC at http://healthmap.org/promed/p/194.

Maps of the 3 countries affected by the 2014 Ebola outbreak in West Africa can be accessed at:
Liberia http://healthmap.org/promed/p/54
Guinea http://healthmap.org/promed/p/45
Sierra Leone http://healthmap.org/promed/p/46. - Mod.LK]

See Also
Ebola update (32): news, research, vaccine, funding 20170716.5179848
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Ebola update (30): news, research, non-governmental organization, vaccines 20170629.5140988
Ebola update (29): news, vaccine, research, funding 20170618.5113468
Ebola update (28): DR Congo, Uganda, research 20170607.5090956
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Ebola update (23): DRC, news, vaccine 20170519.5047049
Ebola update (21): Congo DR, News, Research, Vaccine
Ebola update (20): Congo DR, news, vaccine, update 20170515.5037761
Ebola update (19): Congo DR, Nigeria preparedness 20170514.5035550
Ebola update (18): Congo DR, vaccine 20170513.5034029
Ebola update (17): Congo DR, vaccine, research 20170512.5031411
Ebola update (16): news, research, vaccines, funding 20170428.5000661
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Ebola update (72): vaccine, research, NGO, media 20161226.4724859
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Ebola update (50): Liberia, Sierra Leone, research 20160724.4366266
Ebola update (49): Sierra Leone, research, history 20160717.4350351
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Ebola update (47): Liberia, US preparedness, funding, research 20160703.4323924