Ebola virus

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Ebola virus (EBOV), a filovirus, is one of the most feared viral haemorrhagic fevers. The infection is known as Ebola (Ebola fever, Ebola virus disease, EVD, Ebola haemorrhagic fever).

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Ebola river, Congo

The genus Ebolavirus presently has the following known species (named after the places where they were first identified):

  1. Zaire ebolavirus (ZEBOV)
  2. Sudan ebolavirus (SEBOV )
  3. Reston ebolavirus (REBOV)
  4. Cote d'Ivoire ebolavirus (CIEBOV)
  5. Bundibugyo ebolavirus (BEBOV - named after Bundibugyo in Western Uganda)

The Zaire species (ZEBOV) has a case fatality rate of up to 90%. A 2007 Ugandan outbreak had a case fatality rate of about 25%. The 2014 outbreak in Guinea, Sierra Leone and Liberia had an initial case fatality rate of 65%.

Fruit bats are a possible natural reservoir and primates tend to be susceptible. Preparing or handling uncooked meat from host species is a possible source of the infection.

Contents

Genome

  • RNA ~19 kilobases negative-stranded
  • Encodes 7 structural and one non-structural protein - from 3' end:
    1. Nucleoprotein
      • Associated with viral RNA in ribonucleoprotein complex
    2. Viron protein 35 (VP35)
      • Blocks activation of interferon regulatory factor 3
      • Associated with viral RNA in ribonucleoprotein complex
    3. VP40
    4. Glycoprotein
    5. Envelope glycoprotein differs between species eg GP(Z) for ZEBOV and GP(S/G) for SEBOV
    6. VP30
      • Associated with viral RNA in ribonucleoprotein complex
    7. VP24
      • Interferes with type 1 interferon signalling
    8. Polymerase L protein
      • An RNA-dependent RNA polymerase
      • Associated with viral RNA in ribonucleoprotein complex and with VP35 makes up polymerase complex

Structure

Have a rod-like nucleocapsid and are normally filamentous. Sometimes described as a shepherd's crook.

Clinical features

Incubation

Usually said to be two to 21 days.

A study of over 3000 cases in the 2014 Ebola outbreak found that:

"The mean incubation period was 11.4 days, and did not vary by country. Approximately 95% of the case patients had symptom onset within 21 days after exposure, which is the recommended period for follow-up of contacts."[1]

Signs and symptoms

EVD presents as a non-specific severe acute viral illness usually with sudden onset

  • Fever
  • Intense weakness
  • Muscle pain
  • Headache
  • Sore throat

Later may follow vomiting, diarrhoea, rash, impaired renal and hepatic function and sometimes both internal and external haemorrhage.

WHO Classification

  • Suspected
    • Any person, alive or dead, who has (or had) sudden onset of high fever and had contact with a suspected, probable or confirmed Ebola case, or a dead or sick animal OR any person with sudden onset of high fever and at least three of the following symptoms: headache, vomiting, anorexia/loss of appetite, diarrhoea, lethargy, stomach pain, aching muscles or joints, difficulty swallowing, breathing difficulties, or hiccup; or any person with unexplained bleeding OR any sudden, unexplained death.
  • Probable
    • Any suspected case evaluated by a clinician OR any person who died from ‘suspected’ Ebola and had an epidemiological link to a confirmed case but was not tested and did not have laboratory confirmation of the disease
  • Definite
    • Serological confirmation in a probable or suspected case

Investigations

Note extreme bio risk hazard

  • Usually
    • Low white blood count
    • Low platelet count
    • Elevated liver enzymes
  • Serology
    • Antibody-capture enzyme-linked immunosorbent assay (ELISA)
    • Antigen detection tests
    • Serum neutralization test
    • Reverse transcriptase polymerase chain reaction (RT-PCR) assay
    • Electron microscopy
    • Virus isolation by cell culture.

Treatment

Treatment is supportive with strict precautions to avoid contact with body fluids. It was reported in August 2014 that an experimental cocktail of 3 monoclonal antibodies called ZMapp,[2] developed as part of a long standing research program has been tried with apparent success in 2 victims. The technology uses a tobacco virus vector to allow rapid ramp up of production within tobacco plants of murine origin antibodies (but humanised). The original test of concept was based on primate trials.[3][4][5][6][7]. Treatment options including the antivirals favipiravir and brincidofovir are likely to be defined during 2015 in an unprecedented biotechnological response to a significant infectious disease where such developments had been underfunded until 2014.

Prevention

The virus in man is classically not regarded as human to human transmissible until the index case is symptomatic with a fever. However in pregnant adults viral presence in blood has been documented for just over 2 days before symptoms, and in the urine for 1 day. Accordingly there may be a slight window of risk before symptoms in the immunosuppressed but to date no clear transmission chains have been reported in those exposed before symptoms. The evolving strategy of disease control is strict isolation control and vaccination of all contacts (from mid 2015).

Transmission control

Strict isolation is necessary as people are infectious as long as their blood and secretions contain the virus. Like many other viruses there appear to be super-spreaders, in Ebolas case mainly among the young and elderly, who are responsible for a disproportionate number of cases[8]. Control is obtainable with as many patients as possible receiving care in isolation hospital beds or, if these are at capacity, confined to home or another community setting with precautions to reduce risk for disease transmission (including not mixing with others and safe burial). This is because both scenarios have delivered less than 1 new infected patient per case in outbreaks, even with inadequate healthcare system capacity in rural areas.

  1. Case identification
    1. Fever (if known contact isolate)
    2. Blood sample
    3. Serology
  2. Respond
    1. Isolate
    2. Patient interview to identify all contacts since symptoms
      • In pregnancy best to identify contacts in previous 2 days before symptoms
    3. Monitor contacts for 21 days after exposure
    4. Any new case go to beginning
  3. Prevent
    1. Infection control (Protective clothing and disinfection with bleach)
    2. Safe burial
    3. Removal of bush meat from diet
  • Semen has remained infective for over 6 months[9] and as traces of EBOV RNA have been recovered for up to 9 months[10] the current WHO recommendation is use of condoms indefinitely in survivors until more is known[11]: EBOV has been detected in the semen of convalescent patients by virus isolation (82 days) after disease onset and a case of late relapse with symptoms consistent with meningo-encehalitis at 10 months is suspected[12] ... Marburg virus has also been isolated from the semen and linked conclusively to sexual transmission 13 weeks into convalescence.[13]
  • EBOV has been reported in ocular fluid 22 days after infection with posterior uveitis up to 3 months after infection so it is likely that immune-privileged organs could harbour the infection for this long[14].
  • Usually 21 days without transmission suggests control.

Vaccination

As of 2015 two vaccines are in clinical trials[15][16]. Transient arthritis is a side effect of the replication-competent recombinant vesicular stomatitis virus expressing ZEBOV-glycoprotein. A phase 2 trial of one of the vaccines has been so successful in interrupting disease transmission of the Zaire ebola virus serotype, that it is likely to be adopted as part of standard transmission interruption in future outbreaks of this strain[17]. There is the potential of ramp up to millions of doses availability by the end of the year.

History

It was first detected in 1976 in two near simultaneous outbreaks in Nzara, Southern Sudan and Yambuku, near the Ebola river, Congo by different strains. Outbreaks may be associated with deforestation. The Reston variant has caused outbreaks in laboratory monkeys that have resulted in minor disease in man. The Sudan variant affects Uganda and Sudan typically in low grade prolonged outbreaks. The most recent Congo outbreak was a different Zaire strain to the serious West African outbreak. Vaccination to interrupt the transmission chain became feasible in 2015.

2014 Ebola outbreak

This refers to the West African Ebola outbreak from late 2013 which became an epidemic although a smaller and not insignificant outbreak occurred separately in the Congo in 2014. (see timeline below). This was perceived to create a risk to other countries, and many countries established a response including e.g. airport screening, guidance to various settings about how to identify possible cases and what to do if they identify any. The outbreak was severe as it occurred in countries that had no previous experience, with very poor health intra-structure, with a tradition of funeral practices (explains 60-80% of cases) that encouraged dissemination including importation into urban environments where health infra structure had no history of good infection control practices despite past Lassa fever outbreaks. Further past outbreaks have been controlled in rural settings where international response is able to 'flood' the transmission chain. International capacity did not exist to respond to this urban public health crisis, although the issue that WHO systems were designed to respond to local, focal, short term health emergencies not global, sustained emergencies had been identified in a 2010 review of the response to the 2009 H1N1 influenza outbreak. Even international manufacturing capacity for personal protective equipment did not exist. Retrospective analysis of the 27 (out of 3400, 13 died in first year) Médecins Sans Frontières (MSF) staff who became infected has identified that most caught the virus in the community, rather than when caring for suspected/known cases. The case fatality rate has been 71% in those cared for in Africa and 26% for those treated or evacuated to a well resourced healthcare facility. International media coverage peaked in August when two American and one British healthcare worker required medical evacuation, in October when USA and Spain confirmed local transmission in healthcare workers who had been issued with inadequate equipment and in January when an UK nurse returning to the country was diagnosed with a controversial delay. WHO officially declared the end of active transmission in June 2016 although further cases may occur due to chronic carriage in recovered patients.

Guidance issued for the 2014 outbreak

See UK Ebola Outbreak guidance from 2014 for details of UK guidance etc. This has had several revisions.

Timeline of the 2014 outbreak

Timeline adapated from BMJ[18] and WHO report[19]

  • December 2012 - January 2013: Sudan strain outbreak in Uganda in 6 cases with 50% mortality.
  • 26 December 2013: Retrospectively identified first case in 2 year old child, in Meliandou in Guéckédou prefecture, Forest District, Guinea[20]. One of the house guests came from Sierra Leone and returned there when she became ill. She died and started a slow smoldering outbreak that was unrecognised for months.
  • 24 January 2014: First alert by head of the Meliandou health post. By then spread to relatives and staff Gueckedou hospital and into four subdistricts. Initial investigations by Médecins Sans Frontières (MSF) isolated bacteria but no follow up.
  • 1 February 2014: Virus reached Conakry, the capital of Guinea with a member of the index cases extended family who died in hospital
  • 13 March 2014: First alert of unidentified disease, suspected to be Lassa fever
  • 21 March 2014: Filovirus cause confirmed. Next day Ebola (Zaire strain) virus outbreak confirmed in Guinea.
  • 23 March 2014: WHO announces outbreak with 49 cases and 29 deaths to date. Ebola reported in Liberia at the end of the month
  • 30 March 2014:Two cases confirmed in Foya district, Lofa county, Liberia, near border with Guinea
  • 4 April 2014: Angry mob attacks MSF staff at Macenta
  • 10 May 2014: Burial of an infected traditional healer in Sokoma, Kailahun district, Sierra Leone, near border with Guinea sets off 365 Ebola related death chain of transmission which also spreads to Liberia
  • May 2014: Ebola reported in Sierra Leone. Despite official reports suggesting control in Guinea international responders suspect gross under reporting.
  • June 2014: Outbreak established in capital of Liberia, Monrovia with local healthcare resources overwhelmed by beginning of September. Kailahun, then city of Kenema in Sierra Leone outbreak recognised very quickly but healthcare facilities overwhelmed.
  • 23 June 2014: MSF declares that the outbreak is “out of control,” with more than 60 hotspots where the cases have been reported. 337 people were confirmed dead at that stage. First case reported in Freetown.
  • 20 July 2014: A diplomat arrives at Nigeria’s Lagos airport with Ebola symptoms (his sister had died from Ebola) , triggering concern worldwide that the disease could spread internationally by plane
  • 25 July 2014: Sierra Leone’s top Ebola doctor, Dr Sheik Umar Khan. succumbs to the disease and dies on 29th of July. More than 100 medical workers are known to be among the dead
  • 31 July 2014: WHO announces $100m to upscale the effort to contain the disease, and secretary general Margaret Chan warns of “catastrophic numbers of dead” if the disease is not brought under control. WHO staff and aid agencies on the ground say there are signs in some areas that numbers of new infections are beginning to fall. In total, 729 people are confirmed dead. The same day, the US announces the bringing forward of a clinical trial of a possible vaccine
  • 1 August 2014: Two infected US citizens are flown home from Liberia where they had been working with Ebola patients. They are treated with experimental treatment which subsequently seems to be very effective in early infection. One close contact of the Lagos case who fled the city, where he was under quarantine, is first treated at a Port Harcourt hotel.
  • 8 August 2014:WHO Emergency Committee chaired by Dr Sam Zaramba, meets to evaluate outbreak in context of international health regulations and next day WHO declares outbreak of international concern. Exit screening recommended but no trade or travel bans
  • 10 August 2014:Doctor who treated contact of first Nigerian case becomes ill in Port Harcourt unrecognised at time
  • 11 August 2014:WHO consensus statement that experimental vaccines and therapies ethically acceptable.
  • August 2014: International response in Kailahun suspended as community transmission had made it too dangerous. Health care workers in Kenema go on strike on 30th August. The tent response starts with WHO in Kenema so infected members of families can self-isolate.
  • 24 August 2014:Ebola outbreak in Boemde distrct, Equateur province, Congo
  • 29 August 2014:Ebola case confirmed in Dakar, Senegal in traveller by road from his home in Guinea.By good fortune Dakar had Pasteur Institute and ability to immediately create a dedicated isolation facility.
  • 2 September 2014:A minor Ebola outbreak in the Democratic Republic of Congo is confirmed to be a different strain from the West African outbreak[21].
  • 3 September 2014: A well characterised breakdown in infection control practices related to a patient breaking quarantine and hiding their potential infective status allows the Lagos. Nigeria outbreak to spread to Port Harcourt[22]. Many secondary care clinicians are potentially exposed emphasising the unprecedented high proportion of doctors, nurses, and other health care workers who have been infected[23]. A minor Ebola outbreak in the Democratic Republic of Congo is confirmed to be a different strain from the West African outbreak[24].
  • 18 September 2014:Eight member response team murdered.
  • 22 September 2014: Modelling by CDC demonstrates control possible with 70% compliance with standard isolation practice. Compliance with hospital isolation in some outbreak areas had been less than 10%. The model assumes 2.5 times under-reporting to WHO in the main outbreak countries as of 29th August based upon observation on the ground. This means over 21,000 cases will have occurred by the end of September. Cases in Liberia were doubling every 15–20 days, and those in Sierra Leone were doubling every 30–40 days[25]
  • 23 September 2014:Two members of a response team seriously injured when relatives uncovered appropriately buried grave and remove highly infectious body. Forecariah outbreak in western Guinea associated with 80% mortality and a mob of 3000 forcing all health care responders out of the town.
  • 30 September 2014: Case arrives unsuspected in Dallas, Texas. Lofa County, Liberia outbreak comes under control due to good community engagement.
  • 4 October 2014:Congo outbreak last case.
  • 10 October 2014: The first case of transmission outside Africa is confirmed in a nurse in Spain. Transmission to a healthcare worker in Texas is confirmed on 12 October. In both cases a breakdown in current best infection control practice is suspected. As of 8 October total Ebola virus disease cases were 8399 (with 4033 deaths ) reported to WHO from Guinea, Liberia, Nigeria, Senegal, Sierra Leone, Spain, and the USA.
  • 17 October 2014:Senegal declared Ebola free with only index case infected
  • 20 October 2014:Nigeria declared Ebola free proving that effective infection control and contract chasing measures for ebola can work in urban environments. The outbreak had 19 cases. 7 deaths, including the protocol officer who meet the index Nigerian case at the airport, and several healthcare workers who were not notified by the index patients of their contact history.
  • 23 October 2014: A 2 year old with Ebola is imported into Mali.
  • 25 October 2014: A Grand Imam from Siguiri prefecture in Guinea admitted to Pasteur Clinic. Bamako, Mali triggering chain of 7 cases and 5 deaths.
  • 21 November 2014: Congo outbreak declared over by WHO. This outbreak was controlled easily in classic manner due to rapid recognition and mobilisation of international response.
  • November 2014:WHO reports that Gonly 64 of 194 member states have the essential surveillance, data management, and other obligatory capacities of the International Health Regulations
  • December 2014:Convalescent sera trials commence. Favipiravir commences clinical trials. Several cases in international healthcare workers, most responding to experimental treatments and best supportive treatment. Outbreak starts to come under control in Guinea and Sierra Leone
  • 29 December 2014:Healthcare worker develops Ebola 1 day after return to UK from Sierra Leone
  • 19 January 2015: WHO declares outbreak in Mali officially over as 42 days have elapsed since last case
  • January 2015:Phase 2 trials Ebola vaccine (GlaxoSmithKline) commence. Merck vaccine production ramped up for release early 2015. Brincidofovir trials and field trails point of care diagnostic kits from February.
  • March 2015: So far over 23 500 reported cases with over 9500 reported deaths. Transmission still active but marked falls in Sierra Leone and Liberia. WHO declares UK Ebola free.
  • April 2015: Outbreak in Guinea continues to simmer.
  • 9 May 2015: WHO declares Liberia outbreak over (prematurely).
  • 14 June 2015:WHO reports 27,305 confirmed, probable, and suspected cases of EVD in Guinea, Liberia and Sierra Leone, with 11 169 reported deaths as outbreak almost under control.
  • 30 June 2015:Case who had already died discovered in Liberia
  • 31 July 2015:Ring vaccination successfully interrupts transmission in Guinea. 7 new confirmed cases of EVD reported in the week to 26 July with 27,748 confirmed, probable, and suspected cases of EVD in Guinea, Liberia and Sierra Leone and 11 279 reported deaths.
  • October 2015:Resurgent meningitis first confirmed as late risk in the UK after 9 months and semen remains infective for over 6 months.
  • 4 November 2015: Only remaining transmission chain is hoped to be around Forecariah, Guinea. To date 28,607 cases of EVD with 11,314 deaths assigned to this outbreak worldwide
  • 20 November 2015 Three new cases in Liberia.
  • 29 Dec 2015 Just over 2 years after index case WHO declares Guinea has no known Ebola transmission chains.
  • 15 Jan 2016 Sierra Leone reports a case a few hours after WHO reports no known transmission chains in West Africa.
  • 29 Mar 2016 WHO declares end of the Public Health Emergency of International Concern regarding the Ebola virus disease outbreak in West Africa.Sporadic cases continue, in particular in Guinea. There had been 28646 cases and 11323 deaths attributed to this date.
  • 27 Apr 2016 Results of phase 1 trials of the two major candidate vaccines for Ebola are reported formally
  • 9 June 2016 WHO declares the end of the most recent outbreak of Ebola virus disease in Liberia


WHO Ebola outbreak response

  • The faults in WHO response was subject to this formal report Will Ebola change the game? Ten essential reforms before the next pandemic. The report of the Harvard-LSHTM Independent Panel on the Global Response to Ebola Lancet DOI: http://dx.doi.org/10.1016/S0140-6736(15)00946-0. This resulted in ten recommendations:
    1. The global community must agree on a clear strategy to ensure that governments invest domestically in building such capacities and mobilise adequate external support to supplement efforts in poorer countries. This plan must be supported by a transparent central system for tracking and monitoring the results of these resource flows. Additionally, all governments must agree to regular, independent, external assessment of their core capacities.
    2. WHO should promote early reporting of outbreaks by commending countries that rapidly and publicly share information, while publishing lists of countries that delay reporting. Funders should create economic incentives for early reporting by committing to disburse emergency funds rapidly to assist countries when outbreaks strike and compensating for economic losses that might result. Additionally, WHO must confront governments that implement trade and travel restrictions without scientific justification, while developing industry-wide cooperation frameworks to ensure private firms such as airlines and shipping companies continue to provide crucial services during emergencies.
    3. A dedicated centre for outbreak response with strong technical capacity, a protected budget, and clear lines of accountability should be created at WHO, governed by a separate Board.
    4. A transparent and politically protected WHO Standing Emergency Committee should be delegated with the responsibility for declaring public health emergencies.
    5. An independent UN Accountability Commission should be created to do system-wide assessments of worldwide responses to major disease outbreaks.
    6. Governments, the scientific research community, industry, and non-governmental organisations must begin to develop a framework of norms and rules operating both during and between outbreaks to enable and accelerate research, govern the conduct of research, and ensure access to the benefits of research.
    7. Additionally, research funders should establish a worldwide research and development financing facility for outbreak-relevant drugs, vaccines, diagnostics, and non-pharmaceutical supplies (such as personal protective equipment) when commercial incentives are not appropriate.
    8. For a more timely response in the future, we recommend the creation of a Global Health Committee as part of the UN Security Council to expedite high-level leadership and systematically elevate political attention to health issues, recognising health as essential to human security.
    9. Additionally, decisive, time-bound governance reforms will be needed to rebuild trust in WHO in view of its failings during the Ebola epidemic. With respect to outbreak response, WHO should focus on four core functions: supporting national capacity building through technical advice; rapid early response and assessment of outbreaks (including potential emergency declarations); establishing technical norms, standards, and guidance; and convening the global community to set goals, mobilise resources, and negotiate rules. Beyond outbreaks, WHO should maintain its broad definition of health but substantially scale back its expansive range of activities to focus on core functions (to be defined through a process launched by the WHO Executive Board).
    10. The Executive Board should mandate good governance reforms, including establishing a freedom of information policy, an Inspector General's office, and human resource management reform, all to be implemented by an Interim Deputy for Managerial Reform by July 2017. In exchange for successful reforms, governments should finance most of the budget with untied funds in a new deal for a more focused WHO. Finally, member states should insist on a Director-General with the character and capacity to challenge even the most powerful governments when necessary to protect public health[26].
  • See WHO Ebola outbreak

External links

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References

  1. Ebola virus disease in West Africa--the first 9 months of the epidemic and forward projections. The New England journal of medicine. 2014 Oct 16; 371(16):1481-95.(Link to article – subscription may be required.)
  2. Information in public domain on ZMapp® from Leafbio accessed 5 August 2014
  3. Zeitlin L, Pettitt J, Scully C, Bohorova N, Kim D, Pauly M, Hiatt A, Ngo L, Steinkellner H, Whaley KJ, Olinger GG. Enhanced potency of a fucose-free monoclonal antibody being developed as an Ebola virus immunoprotectant. Proceedings of the National Academy of Sciences of the United States of America. 2011 Dec 20; 108(51):20690-4.(Link to article – subscription may be required.)
  4. Olinger GG, Pettitt J, Kim D, Working C, Bohorov O, Bratcher B, Hiatt E, Hume SD, Johnson AK, Morton J, Pauly M, Whaley KJ, Lear CM, Biggins JE, Scully C, Hensley L, Zeitlin L. Delayed treatment of Ebola virus infection with plant-derived monoclonal antibodies provides protection in rhesus macaques. Proceedings of the National Academy of Sciences of the United States of America. 2012 Oct 30; 109(44):18030-5.(Link to article – subscription may be required.)
  5. Pettitt J, Zeitlin L, Kim do H, Working C, Johnson JC, Bohorov O, Bratcher B, Hiatt E, Hume SD, Johnson AK, Morton J, Pauly MH, Whaley KJ, Ingram MF, Zovanyi A, Heinrich M, Piper A, Zelko J, Olinger GG. Therapeutic intervention of Ebola virus infection in rhesus macaques with the MB-003 monoclonal antibody cocktail. Science translational medicine. 2013 Aug 21; 5(199):199ra113.(Link to article – subscription may be required.)
  6. Qiu X, Audet J, Wong G, Pillet S, Bello A, Cabral T, Strong JE, Plummer F, Corbett CR, Alimonti JB, Kobinger GP. Successful treatment of ebola virus-infected cynomolgus macaques with monoclonal antibodies. Science translational medicine. 2012 Jun 13; 4(138):138ra81.(Link to article – subscription may be required.)
  7. Qiu X, Audet J, Wong G, Fernando L, Bello A, Pillet S, Alimonti JB, Kobinger GP. Sustained protection against Ebola virus infection following treatment of infected nonhuman primates with ZMAb. Scientific reports. 2013; 3:3365.(Epub) (Link to article – subscription may be required.)
  8. Wong G, Liu W, Liu Y, Zhou B, Bi Y, Gao GF. MERS, SARS, and Ebola: The Role of Super-Spreaders in Infectious Disease. Cell host & microbe. 2015 Oct; 18(4):398-401.(Print) (Link to article – subscription may be required.)
  9. Mate SE, Kugelman JR, Nyenswah TG et al. Molecular Evidence of Sexual Transmission of Ebola Virus NEJM
  10. Deen GF, Knust B, Broutet N et al. Ebola RNA Persistence in Semen of Ebola Virus Disease Survivors — Preliminary Report NEJM DOI: 10.1056/NEJMoa1511410
  11. WHO: Semen and EBOV accessed 18 April 2015
  12. Wise J. Scottish Ebola nurse is readmitted to isolation unit in London. BMJ (Clinical research ed.). 2015; 351:h5426.(Epub)
  13. ERROR: Download of reference details rejected. Click on the link - PMID:17940942
  14. Brief Report: Persistence of Ebola Virus in Ocular Fluid during Convalescence. The New England journal of medicine. 2015 Jun 18; 372(25):2469.(Link to article – subscription may be required.)
  15. Agnandji ST, Huttner A, Zinser ME, Njuguna P, Dahlke C, Fernandes JF, Yerly S, Dayer JA, Kraehling V, Kasonta R, Adegnika AA, Altfeld M, Auderset F, Bache EB, Biedenkopf N, Borregaard S, Brosnahan JS, Burrow R, Combescure C, Desmeules J, Eickmann M, Fehling SK, Finckh A, Goncalves AR, Grobusch MP, Hooper J, Jambrecina A, Kabwende AL, Kaya G, Kimani D, Lell B, Lemaître B, Lohse AW, Massinga-Loembe M, Matthey A, Mordmüller B, Nolting A, Ogwang C, Ramharter M, Schmidt-Chanasit J, Schmiedel S, Silvera P, Stahl FR, Staines HM, Strecker T, Stubbe HC, Tsofa B, Zaki S, Fast P, Moorthy V, Kaiser L, Krishna S, Becker S, Kieny MP, Bejon P, Kremsner PG, Addo MM, Siegrist CA. Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe - Preliminary Report. The New England journal of medicine. 2015 Apr 1.(Epub ahead of print) (Link to article – subscription may be required.)
  16. Regules JA, Beigel JH, Paolino KM, Voell J, Castellano AR, Muñoz P, Moon JE, Ruck RC, Bennett JW, Twomey PS, Gutiérrez RL, Remich SA, Hack HR, Wisniewski ML, Josleyn MD, Kwilas SA, Van Deusen N, Mbaya OT, Zhou Y, Stanley DA, Bliss RL, Cebrik D, Smith KS, Shi M, Ledgerwood JE, Graham BS, Sullivan NJ, Jagodzinski LL, Peel SA, Alimonti JB, Hooper JW, Silvera PM, Martin BK, Monath TP, Ramsey WJ, Link CJ, Lane HC, Michael NL, Davey RT, Thomas SJ. A Recombinant Vesicular Stomatitis Virus Ebola Vaccine - Preliminary Report. The New England journal of medicine. 2015 Apr 1.(Epub ahead of print) (Link to article – subscription may be required.)
  17. Henao-Restrepo AM, Longini IM, Egger M et al. Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial Lancet 2015 http://dx.doi.org/10.1016/S0140-6736(15)61117-5
  18. Arie S. Ebola: an opportunity for a clinical trial? BMJ (Clinical research ed.). 2014; 349:g4997.(Epub)
  19. One year into the Ebola epidemic: a deadly, tenacious and unforgiving virus WHO Jan 2015
  20. Baize S, Pannetier D, Oestereich L, Rieger T, Koivogui L, Magassouba N, Soropogui B, Sow MS, Keïta S, De Clerck H, Tiffany A, Dominguez G, Loua M, Traoré A, Kolié M, Malano ER, Heleze E, Bocquin A, Mély S, Raoul H, Caro V, Cadar D, Gabriel M, Pahlmann M, Tappe D, Schmidt-Chanasit J, Impouma B, Diallo AK, Formenty P, Van Herp M, Günther S. Emergence of Zaire Ebola Virus Disease in Guinea - Preliminary Report. The New England journal of medicine. 2014 Apr 16.(Epub ahead of print) (Link to article – subscription may be required.)
  21. Virological analysis: no link between Ebola outbreaks in west Africa and Democratic Republic of Congo WHO 2 September 2014
  22. Ebola situation in Port Harcourt, Nigeria WHO 3 September 2014
  23. Unprecedented number of medical staff infected with Ebola WHO 24 August 2014
  24. Virological analysis: no link between Ebola outbreaks in west Africa and Democratic Republic of Congo WHO 2 September 2014
  25. Meltzer MI et al. Estimating the Future Number of Cases in the Ebola Epidemic — Liberia and Sierra Leone, 2014–2015 CDC Morbidity and Mortality Weekly Report (MMWR) 22 Sept 2014
  26. Will Ebola change the game? Ten essential reforms before the next pandemic. The report of the Harvard-LSHTM Independent Panel on the Global Response to Ebola Lancet DOI: http://dx.doi.org/10.1016/S0140-6736(15)00946-0
  27. Advisory Committee on Dangerous Pathogens (ACDP). Management of Hazard Group 4 viral haemorrhagic fevers and similar human infectious diseases of high consequence. London: Department of Health, 2014 (19 November); 103 pages