EBOLA/EVD [to 20 December 2014]
Public Health Emergency of International Concern (PHEIC); “Threat to international peace and security” (UN Security Council)
Our extensive coverage of Ebola/EVD activity continues – including detailed coverage of UNMEER and other INGO/agency activity now available at the end of this digest. Please also note that many of the organizations and journals we cover continue to publish important EVD content which is threaded throughout this edition.
WHO: Ebola response roadmap – Situation report 17 December 2014
A total of 18,603 confirmed, probable, and suspected cases of Ebola virus disease (EVD) have been reported in five affected countries (Guinea, Liberia, Mali, Sierra Leone, and the United States of America) and three previously affected countries (Nigeria, Senegal and Spain) in the seven days to 14 December (week 50). There have been 6915 reported deaths (case definitions are provided in Annex 1).
Reported case incidence is fluctuating in Guinea and declining in Liberia. In Sierra Leone, there are signs the increase in incidence has slowed, and that incidence may no longer be increasing. The case fatality rate in the three intense-transmission countries among all cases for whom a definitive outcome is recorded is 70%. For those patients recorded as hospitalized, the case fatality rate is 60% in each of Guinea and Sierra Leone, and 58% in Liberia.
Interventions in the three most-affected countries continue to progress in line with the UN Mission for Ebola Emergency Response aim to isolate and treat 100% of EVD cases and bury safely and with dignity 100% of EVD-related fatal cases by 1 January, 2015. At a national level, there is now sufficient bed capacity in EVD treatment facilities to treat and isolate all reported EVD cases in each of the three countries, although the uneven distribution of beds and cases means serious shortfalls persist in some districts. At a national level, each country has sufficient capacity to bury all people known to have died from Ebola, although it is possible that in some areas capacity remains inadequate. Every district that has reported a case of EVD in the three intense-transmission countries has access to a laboratory within 24 hours from sample collection. All three countries report that more than 80% of registered contacts associated with known cases of EVD are being traced. Social mobilization continues to be an important component of the response to curb the spread of disease. Community engagement promotes burial practices that are safe and culturally acceptable, and the isolation and appropriate treatment of patients with clinical symptoms of EVD….
WHO Ebola R&D Effort – vaccines, therapies, diagnostics
18 December update
Since August, when the Ebola outbreak was declared a global public health emergency, WHO has convened a series of consultations and high-level meetings with key experts and stakeholders involved in the research, development, regulation and funding of potential medical solutions for Ebola. Based on concerted expert advice, the best evidence available, and ethical oversight, WHO has prioritized a number of products for further investigation through human testing. These products include two candidate vaccines, two antiviral drugs and convalescent whole blood and plasma. In addition, WHO is working on a number of emergency procedures with countries and other partners for assessment and fast-track development of adapted diagnostics, as well as joint reviews of vaccine clinical trial protocols.
Two vaccine candidates are currently being tested in humans – the cAd3-ZEBOV vaccine, developed by GlaxoSmithKline (GSK) in collaboration with the United States National Institutes for Health, and the rVSV-ZEBOV vaccine, developed by NewLink Genetics and Merck Vaccines USA, in collaboration with Health Canada. Both vaccines have shown to be safe and efficacious in animals and initial phase 1 trial results published in November reported that the GSK vaccine is safe. Further Phase 1 results are expected to emerge during December to January.
Phase I clinical trials of the cAd3-ZEBOV vaccine in healthy adults are nearing completion in the United Kingdom, United States, Mali and Switzerland. For the rVSV-ZEBOV vaccine, trials are well advanced or near completion in Canada, the United States, Gabon, Germany, and Switzerland. Trials in Kenya are due to begin this week. All trials are under the auspices of national research institutions in the countries where they are taking place.
Phase II clinical trials of the cdA3-ZEBOV vaccine are expected to begin in Cameroon, Ghana, Mali, Nigeria and Senegal in early 2015. These will test for safety and capacity to induce an immune response in larger numbers and in broader populations, including children. In order to accelerate ethical and regulatory approval of these trials, WHO convened ethics and regulatory experts from the five countries to meet in Geneva on 15-16 December, to agree on a joint review of the trial protocol presented by GSK, the company developing the vaccine. The outcome was provisional approval of the trials pending some minor adjustments to the protocol application requested by the countries concerned. Experts from Guinea, Liberia and Sierra Leone also participated in the meeting.
Phase III clinical trials are planned to start in the first quarter of 2015 in Guinea, Liberia and Sierra Leone to assess the extent to which the vaccines protect against EVD and to gauge the feasibility of full deployment.
Two other vaccines – one developed by Johnson & Johnson and the other by Novavax – are due to enter clinical trials in the coming weeks.
More about Vaccines
Blood and blood products
Transfusion of whole blood and plasma from recovered Ebola patients has been prioritized for use as an investigational therapy. Convalescent whole blood donated by EVD recovered patients is currently being administered in Sierra Leone in a trial run by the government. A trial of convalescent plasma has begun in Liberia – under the auspices of ClinicalRM (a clinical research organization) with the US government and the Bill and Melinda Gates Foundation; and Guinea is planning to start a plasma trial in the next weeks through a partnership between its National Blood Transfusion Service, and institutes in Belgium, the UK and France, and MSF.
Assessments of national capacities for delivering safe blood products outside of clinical trial settings and plans for recovery and strengthening of national blood transfusion services in the three countries are expected to continue in the coming months.
A number of pre-existing medicines already approved for treating non-Ebola diseases have been considered for re-purposing to treat Ebola because they have demonstrated efficacy against the virus in test tubes (in vitro). The advantage of considering re-purposing of drugs is that these are readily available, and their safety is known. So far only one of these has demonstrated sufficient activity in animals infected with EVD to warrant testing in clinical trials. This is favipiravir (Toyama, Japan), for which clinical trials have started in Gueckedou, Guinea. Trials are being run by Inserm, MSF and the Guinean government. In addition, one other re-purposed drug, amiodarone, has been used to treat patients in Sierra Leone, but it is not yet known if it has any benefit.
Other products that are still under development and are not yet approved for any disease are also being taken into small efficacy trials early in 2015. One of these is brincidofovir (Chimerix, USA) which was originally developed for treating cytomegalovirus but has activity against Ebola virus.
Others are medicines that were specifically developed for Ebola, including the monoclonal antibody cocktail ZMapp (Leafbio, USA) and small inhibitory ribonucleic acid (siRNA) (Tekmira, USA, Canada). All of these have been used compassionately in a few expatriated Ebola patients. While promising, these medicines are still under development and are not available in quantities adequate for large-scale clinical trials or deployment.
The scientific community is currently testing in monkeys a wide range of other drugs that have been proposed as potential therapies and will be taking the most promising into clinical trials.
More about Therapies
In September, WHO introduced an emergency procedure under its Prequalification Programme for rapid assessment of Ebola diagnostics for UN procurement to affected countries. The first diagnostic was accepted in November. In the same month, WHO called on manufacturers to develop rapid and easy to use point-of-care diagnostics that are better suited for use in the affected countries, where health infrastructure and trained personnel are largely lacking. The call was followed by a consultation, on 12 December, where diagnostic experts joined WHO and the NGO FIND to plan for accelerated development, production and deployment of adapted and rapid Ebola tests.
As a result, two types of rapid diagnostics are expected to be ready for clinical trials in early 2015. The most promising type is a rapid, integrated nucleic acid PCR test, which is believed to be more effective in case finding. The other type is an antigen test that is easier to use but may be less reliable.
More about Diagnostics
WHO will continue to work with key stakeholders and partners on potential interventions to accelerate verification, development, testing and, if safety and efficacy are found, deployment of Ebola medical products. Mindful of the risks involved in compressing clinical trials and data gathering in short timeframes, WHO is also providing technical guidance to affected countries and is strongly advocating for patient safety and strict ethical oversight throughout the testing phases and potential deployment. In parallel, WHO is actively supporting community engagement activities in African countries where trials are already taking place.
At the same time, WHO has begun work with Ebola affected countries, development partners and financing institutions on recovery and building resilient health systems.
WHO: Phase II clinical trial application for ChAd3 Ebola vaccine reviewed by national regulators
18 December 2014 – During a meeting convened by WHO on 15-16 December 2014, representatives from African national regulatory authorities and ethics committees reviewed an application for Phase II clinical trials of the chimpanzee adenovirus serotype-3 (ChAd3) Ebola vaccine.
The two-day review provided a forum for a thorough discussion on all aspects of the proposed trials. Reviewing countries requested additional documentation from the manufacturer of the vaccine, GlaxoSmithKline, before authorization of the trials. The submission of additional information, and subsequent review by the countries planning to host the trials, is expected to take place by the end of January. If these steps are completed to the satisfaction of the national authorities, Phase II trials are likely to begin in February.
Regulatory and ethics officials from the countries where the Phase II trials were being considered (Cameroon, Ghana, Mali, Nigeria and Senegal) were present, as well as from the countries most affected by the ongoing Ebola outbreak (Guinea, Liberia and Sierra Leone, as observers).
:: Announcement of meeting to review Phase II clinical trial application for ChAd3 Ebola vaccine
:: Summary of the meeting to review Phase II clinical trial application for ChAd3 Ebola vaccine pdf, 299kb.
WHO and partners release manual on psychological first aid during Ebola outbreaks
In times of outbreaks, it is critical that helpers be equipped with the know-how to provide humane, supportive and practical help for people who are distressed, in ways that respect their dignity, culture and abilities.
Consequently, WHO and partners released their first facilitator’s manual, to provide helpers with a comprehensive orientation and materials for use when offering psychological first aid to people affected by an Ebola outbreak. More specifically, this facilitator’s manual includes:
– information on how to prepare for giving an orientation and tips for facilitators
– a full day orientation agenda and a step-by-step description of each module, including learning objectives, narrative and tips for the facilitator
– slides and instructions for group exercises and discussions
– annexes which provide supporting materials to print as handouts for participants.
This facilitator’s manual is to be used together with the guide Psychological first aid during Ebola virus disease outbreaks, launched September 2014.
:: Facilitation manual: Psychological first aid during Ebola disease outbreaks
:: Guide: Psychological first aid during Ebola virus disease outbreaks