Key facts OF Ebola virus disease

• Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever, is a severe, often fatal illness in humans.
• The virus is transmitted to people from wild animals and spreads in the human population through human-to-human transmission.
• The average EVD case fatality rate is around 50%. Case fatality rates have varied from 25% to 90% in past outbreaks.
• The first EVD outbreaks occurred in remote villages in Central Africa, near tropical rainforests, but the most recent outbreak in west Africa has involved major urban as well as rural areas.
• Community engagement is key to successfully controlling outbreaks. Good outbreak control relies on applying a package of interventions, namely case management, surveillance and contact tracing, a good laboratory service, safe burials and social mobilisation.
• Early supportive care with rehydration, symptomatic treatment improves survival. There is as yet no licensed treatment proven to neutralise the virus but a range of blood, immunological and drug therapies are under development.
• There are currently no licensed Ebola vaccines but 2 potential candidates are undergoing evaluation.

Introduction

A high-level emergency meeting, convened by WHO at the request of several governments and representatives of the pharmaceutical industry, was held on 23 October to look at the many complex policy issues that surround eventual access to experimental Ebola vaccines.

Ways to ensure the fair distribution and financing of these vaccines were discussed in an atmosphere characterized by a high sense of urgency. This sense of urgency was conveyed in many ways – from plans for the different phases of clinical trials to be performed concurrently rather than consecutively, to suggested partnerships for expediting clinical trials, to proposals for getting all development partners moving in tandem and at the same accelerated pace.

More than 90 participants, including some of the world’s leading scientists, came, on short notice, from national and university research institutions, also in Africa, government health agencies, ministries of health and foreign affairs, national security councils, and several offices of Prime Ministers and Presidents. Also represented were national and regional drug regulatory authorities, the MSF (Doctors Without Borders) medical charity, funding agencies and foundations, the GAVI alliance for childhood immunization, and development banks, including the African Development Bank, the European Investment Bank, and the World Bank Group.

Main conclusions reached

Impact of vaccines on further evolution of the epidemic

The meeting concluded that vaccines will have a significant impact on the further evolution of the epidemic in any scenario, from best-case to worst-case.

Financing of vaccine development, clinical trials, and vaccination campaigns

The meeting concluded that funding issues should not be allowed to dictate the vaccine agenda. The funds will be found.

Liability

The meeting concluded that neither affected countries nor industry should be left alone to bear the burden should lawsuits arise following possible adverse reactions to an Ebola vaccine. To respond to this potential problem, a proposal was made to establish a “club” of donors, in collaboration with the World Bank.

The timing and quantity of vaccine supplies

The meeting concluded that the timing and quantity of vaccine doses should not constrain the design of clinical trials. Industry confirmed that enough vaccine doses would be available.

GlaxoSmithKline’s monthly production capacity for purified bulk vaccine was expected to rise from the current figure of 24,000 doses to 230,000 by April 2015, if they can be filled for release. NewLink’s bulk vaccine manufacturing capacity for the Canadian vaccine was noted to vary, according to the dose selected, from 52,000 doses to 5.2 million doses anticipated for the first quarter of 2015.

Design of protocols for phase 2 and phase 3 clinical trials

The meeting concluded that randomized controlled clinical trials were the gold standard in terms of yielding reliable scientific data for the analysis and interpretation of efficacy. A stepped-wedge design could also yield useful and meaningful data during the special circumstances of the current epidemic.

WHO/M. Missioneiro

The 1st batch of experimental vaccines, VSV-EBOV, arrived in October 2014 in Geneva, Switzerland, and were stored at the Geneva University Hospital.

Priority uses of vaccine when supplies are limited

The meeting concluded that health care workers, including medical staff, laboratory staff, burial teams, and facility cleaners, should have first call on vaccine doses while supplies remain limited. Vaccination of health care workers in the three countries was judged feasible during the first quarter of 2015.

Regulatory requirements

The meeting concluded that the licensure and authorization requirements of regulatory authorities should be streamlined and harmonized, enabling the rapid introduction of vaccines for clinical trials and general distribution, yet with no compromise of scientific standards. In order to deliver the number of doses on the schedules proposed by the manufacturers, regulators must work closely with the manufacturers to find ways to overcome a number of regulatory hurdles.

Urgent measures to improve readiness for clinical trials and vaccines

The meeting concluded that two preparatory measures should be given the most urgent priority: community engagement and social mobilization to prepare populations to understand and accept clinical trials and vaccination campaigns, and the building of basic public health infrastructures, especially given the considerable logistical challenges facing health services in Guinea, Liberia, and Sierra Leone.

Coordination and alignment among multiple partners

The meeting concluded that a mechanism or framework must be urgently established, relying on WHO’s convening and coordination powers, to get all partners working in tandem, according to a single agreed plan and aligned with industry’s “critical paths” analysis.

Determination to finish the job

The meeting concluded that all efforts to develop, test, and approve Ebola vaccines must be followed through to completion at the current accelerated pace, even if dramatic changes in the epidemic’s transmission dynamics meant that vaccines were no longer needed.

• Read full meeting report: WHO high-level meeting on Ebola vaccines access and financing
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Ebola virus disease (EVD; also Ebola hemorrhagic fever [EHF]), or simply Ebola, is a disease of humans and other primates caused by ebolaviruses (EBOV). Signs and symptoms typically start between two days and three weeks after contracting the virus as afever, sore throat, muscle pain and headaches. Then, vomiting, diarrhea and rash usually follow, along with decreased function of the liver and kidneys. At this time some people begin to bleed both internally and externally.^[1] Death, if it occurs, follows typically six to sixteen days after symptoms appear and is often due to low blood pressure from fluid loss.^[2]

The virus spreads by direct contact with blood or other body fluids of an infected human or other animal.^[1] Infection with the virus may also occur by direct contact with a recently contaminated item or surface.^[1] Spread of the disease through the air has not been documented in the natural environment.^[3] EBOV may be spread by semen or breast milk for several weeks to months after recovery.^[1][4] Fruit bats are believed to be the normal carrier in nature, able to spread the virus without being affected by it. Humans become infected by contact with the bats or with a living or dead animal that has been infected by bats. After human infection occurs, the disease may also spread between people. Other diseases such as malaria, cholera, typhoid fever, meningitis and other viral hemorrhagic fevers may resemble EVD. Blood samples are tested for viral RNA, viral antibodies or for the virus itself to confirm the diagnosis.^[1]

Control of outbreaks requires coordinated medical services, along with a certain level of community engagement. The medical services include: rapid detection of cases of disease,contact tracing of those who have come into contact with infected individuals, quick access to laboratory services, proper care and management of those who are infected and proper disposal of the dead through cremation or burial.^[1][5] Prevention includes limiting the spread of disease from infected animals to humans.^[1] This may be done by handling potentially infected bush meat only while wearing protective clothing and by thoroughly cooking it before consumption.^[1] It also includes wearing proper protective clothing and washing hands when around a person with the disease.^[1] Samples of body fluids and tissues from people with the disease should be handled with special caution.^[1]

No specific treatment for the virus is available. Efforts to help those who are infected are supportive; they include giving either oral rehydration therapy (slightly sweetened and salty water to drink) or intravenous fluids as well as treating symptoms. This supportive care improves outcomes. The disease has a high risk of death, killing between 25 percent and 90 percent of those infected with the virus, with an average mortality rate of 50 percent. EVD was first identified in an area of Sudan (now part of South Sudan), and in Zaire (now theDemocratic Republic of the Congo). The disease typically occurs in outbreaks in tropical regions of sub-Saharan Africa.^[1] From 1976 (when it was first identified) through 2013, the World Health Organization reported a total of 1,716 cases.^[1][6] The largest outbreak to date is the ongoing epidemic in West Africa, which is centered in Guinea, Sierra Leone and Liberia.^[7][8][9] As of 25 October 2014, 12,008 suspected cases resulting in the deaths of 5,078 have been reported.^[10] Efforts are under way to develop a vaccine.^[1]

what is ebola virus?

Key facts

• Ebola virus disease (EVD), formerly known as Ebola haemorrhagic fever, is a severe, often fatal illness in humans.
• The virus is transmitted to people from wild animals and spreads in the human population through human-to-human transmission.
• The average EVD case fatality rate is around 50%. Case fatality rates have varied from 25% to 90% in past outbreaks.
• The first EVD outbreaks occurred in remote villages in Central Africa, near tropical rainforests, but the most recent outbreak in west Africa has involved major urban as well as rural areas.
• Community engagement is key to successfully controlling outbreaks. Good outbreak control relies on applying a package of interventions, namely case management, surveillance and contact tracing, a good laboratory service, safe burials and social mobilisation.
• Early supportive care with rehydration, symptomatic treatment improves survival. There is as yet no licensed treatment proven to neutralise the virus but a range of blood, immunological and drug therapies are under development.
• There are currently no licensed Ebola vaccines but 2 potential candidates are undergoing evaluation.

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Background

The Ebola virus causes an acute, serious illness which is often fatal if untreated. Ebola virus disease (EVD) first appeared in 1976 in 2 simultaneous outbreaks, one in Nzara, Sudan, and the other in Yambuku, Democratic Republic of Congo. The latter occurred in a village near the Ebola River, from which the disease takes its name.

The current outbreak in west Africa, (first cases notified in March 2014), is the largest and most complex Ebola outbreak since the Ebola virus was first discovered in 1976. There have been more cases and deaths in this outbreak than all others combined. It has also spread between countries starting in Guinea then spreading across land borders to Sierra Leone and Liberia, by air (1 traveller only) to Nigeria, and by land (1 traveller) to Senegal.

The most severely affected countries, Guinea, Sierra Leone and Liberia have very weak health systems, lacking human and infrastructural resources, having only recently emerged from long periods of conflict and instability. On August 8, the WHO Director-General declared this outbreak a Public Health Emergency of International Concern.

A separate, unrelated Ebola outbreak began in Boende, Equateur, an isolated part of the Democratic Republic of Congo.

The virus family Filoviridae includes 3 genera: Cuevavirus, Marburgvirus, and Ebolavirus. There are 5 species that have been identified: Zaire, Bundibugyo, Sudan, Reston and Taï Forest. The first 3, Bundibugyo ebolavirus, Zaire ebolavirus, and Sudan ebolavirus have been associated with large outbreaks in Africa. The virus causing the 2014 west African outbreak belongs to the Zaire species.

Transmission

It is thought that fruit bats of the Pteropodidae family are natural Ebola virus hosts. Ebola is introduced into the human population through close contact with the blood, secretions, organs or other bodily fluids of infected animals such as chimpanzees, gorillas, fruit bats, monkeys, forest antelope and porcupines found ill or dead or in the rainforest.

Ebola then spreads through human-to-human transmission via direct contact (through broken skin or mucous membranes) with the blood, secretions, organs or other bodily fluids of infected people, and with surfaces and materials (e.g. bedding, clothing) contaminated with these fluids.

Health-care workers have frequently been infected while treating patients with suspected or confirmed EVD. This has occurred through close contact with patients when infection control precautions are not strictly practiced.

Burial ceremonies in which mourners have direct contact with the body of the deceased person can also play a role in the transmission of Ebola.

People remain infectious as long as their blood and body fluids, including semen and breast milk, contain the virus. Men who have recovered from the disease can still transmit the virus through their semen for up to 7 weeks after recovery from illness.

Symptoms of Ebola virus disease

The incubation period, that is, the time interval from infection with the virus to onset of symptoms is 2 to 21 days. Humans are not infectious until they develop symptoms. First symptoms are the sudden onset of fever fatigue, muscle pain, headache and sore throat. This is followed by vomiting, diarrhoea, rash, symptoms of impaired kidney and liver function, and in some cases, both internal and external bleeding (e.g. oozing from the gums, blood in the stools). Laboratory findings include low white blood cell and platelet counts and elevated liver enzymes.

Diagnosis

It can be difficult to distinguish EVD from other infectious diseases such as malaria, typhoid fever and meningitis. Confirmation that symptoms are caused by Ebola virus infection are made using the following investigations:

• antibody-capture enzyme-linked immunosorbent assay (ELISA)
• antigen-capture detection tests
• serum neutralization test
• reverse transcriptase polymerase chain reaction (RT-PCR) assay
• electron microscopy
• virus isolation by cell culture.

Samples from patients are an extreme biohazard risk; laboratory testing on non-inactivated samples should be conducted under maximum biological containment conditions.

Treatment and vaccines

Supportive care-rehydration with oral or intravenous fluids- and treatment of specific symptoms, improves survival. There is as yet no proven treatment available for EVD. However, a range of potential treatments including blood products, immune therapies and drug therapies are currently being evaluated. No licensed vaccines are available yet, but 2 potential vaccines are undergoing human safety testing.

Prevention and control

Good outbreak control relies on applying a package of interventions, namely case management, surveillance and contact tracing, a good laboratory service, safe burials and social mobilisation. Community engagement is key to successfully controlling outbreaks. Raising awareness of risk factors for Ebola infection and protective measures that individuals can take is an effective way to reduce human transmission. Risk reduction messaging should focus on several factors:

• Reducing the risk of wildlife-to-human transmission from contact with infected fruit bats or monkeys/apes and the consumption of their raw meat. Animals should be handled with gloves and other appropriate protective clothing. Animal products (blood and meat) should be thoroughly cooked before consumption.
• Reducing the risk of human-to-human transmission from direct or close contact with people with Ebola symptoms, particularly with their bodily fluids. Gloves and appropriate personal protective equipment should be worn when taking care of ill patients at home. Regular hand washing is required after visiting patients in hospital, as well as after taking care of patients at home.
• Outbreak containment measures including prompt and safe burial of the dead, identifying people who may have been in contact with someone infected with Ebola, monitoring the health of contacts for 21 days, the importance of separating the healthy from the sick to prevent further spread, the importance of good hygiene and maintaining a clean environment.

Controlling infection in health-care settings:

Health-care workers should always take standard precautions when caring for patients, regardless of their presumed diagnosis. These include basic hand hygiene, respiratory hygiene, use of personal protective equipment (to block splashes or other contact with infected materials), safe injection practices and safe burial practices.

Health-care workers caring for patients with suspected or confirmed Ebola virus should apply extra infection control measures to prevent contact with the patient’s blood and body fluids and contaminated surfaces or materials such as clothing and bedding. When in close contact (within 1 metre) of patients with EBV, health-care workers should wear face protection (a face shield or a medical mask and goggles), a clean, non-sterile long-sleeved gown, and gloves (sterile gloves for some procedures).

Laboratory workers are also at risk. Samples taken from humans and animals for investigation of Ebola infection should be handled by trained staff and processed in suitably equipped laboratories.

WHO response

WHO aims to prevent Ebola outbreaks by maintaining surveillance for Ebola virus disease and supporting at-risk countries to developed preparedness plans. The document provides overall guidance for control of Ebola and Marburg virus outbreaks:

• Ebola and Marburg virus disease epidemics: preparedness, alert, control, and evaluation

When an outbreak is detected WHO responds by supporting surveillance, community engagement, case management, laboratory services, contact tracing, infection control, logistical support and training and assistance with safe burial practices.

WHO has developed detailed advice on Ebola infection prevention and control:

• Infection prevention and control guidance for care of patients with suspected or confirmed Filovirus haemorrhagic fever in health-care settings, with focus on Ebola

Table: Chronology of previous Ebola virus disease outbreaks

Year	Country	Ebolavirus species	Cases	Deaths	Case fatality
2012	Democratic Republic of Congo	Bundibugyo	57	29	51%
2012	Uganda	Sudan	7	4	57%
2012	Uganda	Sudan	24	17	71%
2011	Uganda	Sudan	1	1	100%
2008	Democratic Republic of Congo	Zaire	32	14	44%
2007	Uganda	Bundibugyo	149	37	25%
2007	Democratic Republic of Congo	Zaire	264	187	71%
2005	Congo	Zaire	12	10	83%
2004	Sudan	Sudan	17	7	41%
2003 (Nov-Dec)	Congo	Zaire	35	29	83%
2003 (Jan-Apr)	Congo	Zaire	143	128	90%
2001-2002	Congo	Zaire	59	44	75%
2001-2002	Gabon	Zaire	65	53	82%
2000	Uganda	Sudan	425	224	53%
1996	South Africa (ex-Gabon)	Zaire	1	1	100%
1996 (Jul-Dec)	Gabon	Zaire	60	45	75%
1996 (Jan-Apr)	Gabon	Zaire	31	21	68%
1995	Democratic Republic of Congo	Zaire	315	254	81%
1994	Cote d'Ivoire	Taï Forest	1	0	0%
1994	Gabon	Zaire	52	31	60%
1979	Sudan	Sudan	34	22	65%
1977	Democratic Republic of Congo	Zaire	1	1	100%
1976	Sudan	Sudan	284	151	53%
1976	Democratic Republic of Congo	Zaire	318	280	88%

Source:

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