In October, a man was left to die in a Spanish airport after bags of cocaine he was smuggling burst in his stomach. A companion told health-care workers the Nigerian-born Spanish resident had completed a return flight from Madrid to Istanbul with no other stops, but the man was left unattended for nearly an hour after collapsing due to infection fears, and subsequently died from lack of timely care.
The degree of fear of Ebola in some communities and among health-care workers is not supported by the facts about the disease, nor by the science of viral transmission processes and incubation periods. As nurses, it is essential we are fully informed and able to provide reassurance about the true causes of the Ebola outbreak, its likely progress, and the risk to communities outside the west African nations in which this tragedy is unfolding.
The Ebola virus is named after the river in northern Zaire (now the Democratic Republic of Congo) where the first victim of the second outbreak of Ebola virus disease (EVD) was exposed to the virus. There have been 23 identified outbreaks of Ebola in humans since it first appeared in 1976, with 1716 confirmed cases up to 2013. (1) The number of outbreaks and cases has been increasing since 2000.2 There have also been a high number of outbreaks in wild primates (chimpanzees, monkeys and the great apes), which have devastated whole populations.
EVD causes a viral haemorrhagic fever similar to that which occurs with Marburg virus disease, Rift Valley fever, Lassa fever, yellow fever and dengue fever. Five different species of Ebola virus have been identified, ranging in virulence against humans from non-pathogenic to causing 90 per cent mortality. The current epidemic in west Africa is from the Zaire strain, which has the highest mortality rate--60 to 90 per cent--of the various strains. (2)
The danger of a pathogen depends on both its infectiousness (its ability to be transmitted from person to person) and its virulence (its ability to cause disease in an infected host). EVD is one of the most virulent infections known but, until the most recent outbreak, was not sufficiently infectious to be a highly successful pathogen. Previous outbreaks were in isolated rural regions and victims died before infecting many others. The spread of the virus to urban areas with overcrowded living conditions, poor public infrastructure, poorly funded health services and low levels of health and scientific literacy, has enabled EVD to become a much "better" pathogen. If, as some believe, the Zaire strain in this outbreak is becoming less virulent, infectious hosts will survive longer, giving the virus a greater chance of being transmitted, increasing its survival and prolonging the outbreak.
WHERE DOES EBOLA COME FROM?
Recent studies on the filoviridae family--the virus family which encompasses the Ebola and Marburg viruses--demonstrate it has existed in animals for thousands of years, but there is scant information about how the family of viruses has evolved and where it resides between outbreaks. Most viruses that are endemic to an area have a host species where they form a reservoir. A reservoir animal species is one where the virus persists after a mild or even asymptomatic infection. There may be little or no transmission of the virus under normal circumstances, but transmission may increase sporadically following changes in the health or environment of the reservoir species. Possible triggers that increase viral transmission (either within the same species or to other animals) include stress, pregnancy, co-infection with other pathogens, or change in food sources. (2) Humans, primates and other animals that have a high mortality rate to EVD are end hosts, not reservoir species.
Fruit bats are the most likely wild reservoir for EVD in Africa. Also called flying foxes, they are known to carry a large number of viruses that are pathogenic to humans--eg Hendra virus, rabies and severe acute respiratory syndrome (SARS). Bat meat is popular in equatorial Africa and, if poorly cooked, could cause viral transmission. This is true for meat from other animals infected by bats (transmission may be from eating the bats or contact with bat urine, faeces or saliva), or from fruit that could be contaminated by bats. (3)
Fruit bat populations carrying the virus were originally believed to be confined to equatorial African regions (Sudan, Democratic Republic of Congo, Uganda, Kenya, Republic of the Congo, Angola and Gabon). A single case, acquired from an infected troop of chimpanzees in Cote d'Ivoire in 1994, was from a separate species of the virus, and the first indication that EBV might not be confined to a single region. A further species of Ebola--the Reston Ebola virus--has been found in the Philippines in primates and in pigs. This species of the virus is not pathogenic in humans, although workers exposed to the infected animals did show an immune response to the virus, indicating exposure. (2) Antibodies to EVD and the closely related Marburg virus have been found in the blood of fruit bats in the Philippines, China and Bangladesh. A non-pathogenic variety of Ebola has even been identified in species of bats from Spain, France and Portugal. (4)
A recent analysis of outbreaks of EVD in Africa has shown the environmental conditions required for circulation of the virus within wild bat populations cover a wider area of Africa than originally assumed. The area of risk for EVD is now thought to span 22 countries in central and west Africa and contains more than 16 million people. Given the high population in these at-risk areas, the relatively small number of outbreaks indicates transmission to humans is actually quite rare. (5,6)
The current outbreak in west Africa has arisen from a single cross-over event (mammal to human) which occurred in Guinea, when a two-year-old boy was exposed to an infected fruit bat in December 2013. It then spread to Sierra Leone through a single event--12 people attending the funeral of a victim in Guinea, returned home with the disease. By examining the virus genome, researchers have identified the outbreak is due to a single cross-species transmission event, not multiple exposures to infected animals. (7) This supports the public health measures being used to contain the disease--tracking contacts rather than trying to eliminate potential animal carriers. (8)
Ebola and Marburg are two different viruses belonging to the filoviridae family. The Marburg virus was responsible for an outbreak of haemorrhagic illness in Germany and the former Yugoslavia in the 1960s, following importation of monkeys from Africa for research purposes. This led to the identification of the filoviridae family--viruses composed of long filaments or strands when seen under electron microscopy. Filoviridae are enveloped, negative sense, single strand RNA viruses.
An RNA virus has ribonucleic acid as its genetic material, rather than deoxyribonucleic acid (DNA), which is the common genetic material in humans. The RNA occurs in a single strand, again unlike human genetic material where our DNA occurs in a double strand of matched nucleic acids. A negative sense virus has its RNA strand in a "backward" form. This must be copied by specific enzymes after the virus infects a host cell to make a positive-sense strand and allow the virus to replicate. Many viruses have an envelope, or membrane, surrounding their genetic material, which is created when they bud off from an infected cell. The envelope has glycoprotein spikes embedded in it that allow the virus to attach to host cells and fuse with them.
The functional implications of the structure of the Ebola virus include:
* Enveloped viruses require a continuously moist environment, do not readily get transmitted via airborne mechanisms and will not survive being exposed to drying conditions. They are also vulnerable to chemical disinfection--so chlorine bleach can be used to decontaminate exposed surfaces.
* Single-strand RNA viruses copy poorly, so they mutate rapidly. While there is no current suggestion the virus is becoming more virulent, it may possibly become so, or may mutate to evade the actions of drugs and vaccines being developed to manage EVD. (2)
* The glycoprotein spikes in the viral envelope determine which host cells the virus can attach and fuse with--called tissue tropism. The Ebola virus has very broad tissue tropism, meaning it can infect a number of different cells and subseguently create a wide range of symptoms. Notably, it exhibits no tropism for respiratory tract cells, so the likelihood of successful airborne transmission, as with the influenza virus, is low. (9)
Viruses act by invading host cells and releasing their genetic material, which then co-opts host cell activity to make thousands of copies of the viral genes. At the same time, the virus takes over the protein synthesis machinery inside the cell and produces the proteins reguired to assemble and package the new viral genetic copies. Eventually the virus (composed of the genetic material and its protein complex) exits the cell, ready to infect neighbouring cells or to exit the host and infect another victim.
Viruses can exit cells by shedding (an example of this is the HIV virus, where the cell survives) or by causing the cell to disintegrate, and, in the process, the virus coats itself with a portion of the cell's membrane. This is the mechanism by which Ebola leaves body cells, destroying the infected cell as it exits.
TRANSMISSION OF EBOLA
The average number of infections one individual passes on over the duration of the infectious period of a disease is referred to as the basic reproductive ratio or [R.sub.0]. The higher the [R.sub.0], the more difficult it is to contain an outbreak. For the current outbreak of EVD, the [R.sub.0] is calculated as 1-2. Comparing this with [R.sub.0] figures for common diseases shows that, while virulent, EVD is not exceptionally contagious:
* HIV/Aids and SARS: 2-5
* Pertussis (whooping cough): 12-17
* Measles: 12-18
The Ebola virus enters the body through mucous membranes, conjunctiva, breaks in the skin or via parenteral routes. Ingestion of poorly cooked meat (especially organ meat) of infected animals creates exposure via the oral route. In human-to-human transmission, direct contact with infected or deceased patients is required, although transmission via aerosolised droplets has been demonstrated under experimental conditions. (10) It is considered virtually impossible for the Ebola virus to mutate sufficiently to change its mode of transmission from droplet (where the virion is surrounded by a protective layer of body fluids) to airborne dry particles.
Virions (the virus plus its membrane envelope) and infectious viral particles have been found in body secretions of infected individuals and may persist for up to three months in patients who have recovered. Blood, vomitus, faeces, nasal discharge, tears, sweat, semen, genital discharge and breast milk have all been confirmed to contain live virus or viral RNA in infected patients.
The higher the viral load, the more infectious these body discharges are. In recovered patients, there is a risk the virus could be transmitted via sexual contact. This has not been demonstrated in past outbreaks, but caution dictates that recovered patients be advised to abstain or use condoms for 90 days after recovery. (11) There is also evidence that infants of infected mothers have a high death rate, but whether this is due to close skin contact or transmission via breast milk is unknown. (2)
The Ebola virus is capable of infecting a wide range of cells in the body but its initial targets are immune cells, which is a key factor in its ability to cause severe disease. Its first targets are white blood cells, and in particular dendritic cells and monocytes/macrophages, which are the very cells required for initiating an immune response to invading pathogens.
Dendritic cells are found in the epithelial tissues lining mucous membranes and are responsible for identifying invading pathogens, ingesting them and then presenting them to the lymphocytes to trigger the humoral immune responses--the development of specific T- and B-lymphocytes, memory cells and antibodies against the pathogen. Monocytes and macrophages perform a similar role in our tissues and bloodstream. Together, these cells also initiate innate immune reactions that should hold a pathogen at bay until the body is able to develop an effective humoral immune defence.
By preferentially targeting these "first responders", Ebola cripples its victim's defences and prevents the timely and effective mounting of lymphocyte-directed immune attack. Once inside the cells, the Ebola virus begins replicating and is carried to lymph nodes and further into the body. The liver, spleen and adrenal glands are major targets, and invasion of the cells in these organs contributes to the specific clinical appearance of EVD. (2) The Ebola virus also produces another factor that inhibits the immune response: virally infected cells are induced to secrete a soluble glycoprotein (sGP) that binds to neutrophils and prevents their activation. (10)
Initial signs and symptoms of EVD are similar to those of most viral infections--fever, sore throat, malaise, weakness, headache and myalgia (aching muscles). These symptoms arise as nonspecific inflammatory mediators are released in response to the presence of the virus. At this point, the patient becomes infectious as they are beginning to shed live virus in their body secretions. As the virus infects liver, spleen and adrenal cells, the clinical course of the disease becomes more specific.
Patients with a high viral load exhibit a profound decrease in the number of circulating lymphocytes in their system. Ebola does not directly attack lymphocytes, so the cause of this is not known, but may be due to effects of sGP. Loss of lymphocytes further impairs the body's ability to mount an effective defence against EVD. Patients with nonfatal (or asymptomatic) disease are able to mount a strong, early inflammatory response to infection, followed by high production of antibodies. Early leukopeania (low white blood cell levels) and absence of inflammatory markers (interleukins and tumour necrosis factor) are strong indicators the patient will die. (2,10)
Invasion of hepatocytes by the virus may lead to decreased synthesis of clotting factors and other plasma proteins. In turn, this contributes to the risk of haemorrhage for people with EVD, although fewer than half of infected patients exhibit bleeding (10) and frank haemorrhage has occurred in only 18 per cent of patients in the current outbreak. (12)
Infection of the adrenal cortex causes disruption of steroid synthesis and contributes to profound hypotension, loss of sodium and hypovolaemia experienced in the later stages of EVD.
Ebola also invades endothelial cells and destroys them. This results in leakage of plasma proteins and water into the extravascular spaces, producing severe oedema and contributing to hypotension and shock. Also, the damaged endothelium can cause widespread activation of clotting factors, leading to the development of disseminated intravascular coagulation (DIC).
With the development of DIC, microemboli occur throughout the vascular system and, as platelets and clotting factors are all used up, bleeding occurs both internally and superficially. The development of petechiae (red/purple spots on the skin), bruising, mucosal haemorrhage and uncontrolled bleeding at venepuncture sites can contribute to hypotension and shock, but blood loss is rarely massive unless it occurs through the gastrointestinal tract. (2)
Invasion of the mucosal cells of the GI tract is evidenced by severe diarrhoea and vomiting that occur after the initial symptoms, usually within five days. A patient can lose eight to 10 litres per day in diarrhoea. Anorexia and abdominal pain accompany these GI effects and the patient starts to suffer hypovolaemic shock, along with electrolyte deficits. Failure of the mucosal barrier also allows invasion of bowel flora into the systemic circulation, leading to development of sepsis. (2)
Other signs and symptoms include a rash (that will desquamate [peel] in survivors), chest pain and shortness of breath. Cerebral oedema may occur, accompanied by severe headache, confusion and seizures. Pregnant women may miscarry. Patients most frequently die with multi-organ failure and septic shock.
WHO IS MOST VULNERABLE TO EVD?
The most commonly reported incubation period for EVD is two to 21 days. About 95 per cent of cases fall within this incubation period but 98 per cent of cases fall with an incubation period of one to 42 days, hence the World Health Organisation's requirement of 42 days Ebola-free to declare an outbreak contained. (13) Mean incubation times in the west Africa outbreak appear to be nine to 11 days.
The incidence of EVD is higher in adults than children, although it is not known if this is due to physiological factors or that children tend to have less contact with symptomatic patients. Younger adults and children are also more likely to survive infection, but again the mechanisms underlying this are not known. (14) There is no difference in infection rates based on gender, although exposure mechanisms may differ between men and women. The high incidence in Africans is most probably due to geography, and there is no evidence to suggest ethnicity plays a role in vulnerability to the virus, although this has yet to be conclusively demonstrated. (10)
Increased vulnerability to EVD appears to relate to the speed with which the virus is able to overwhelm innate immune defences. This, in turn, is determined by the dose of Ebola the patient is exposed to. Route of infection has a major influence on exposure, incubation times, and severity of disease--direct inoculation, such as needlestick injury, has a much shorter incubation than other routes of infection, and is associated with very high mortality. During an outbreak in 1976 in the former Zaire, 85 patients were infected due to reuse of contaminated needles and syringes. All 85 died. (15)
There is currently no cure for EVD. Infected individuals can only be provided with supportive care, which is near impossible to deliver adequately in west Africa, where there is limited access to basic equipment and virtually none to tertiary care facilities. Health services in these nations have been rapidly overwhelmed and support from developed nations has been slow. Currently WHO calculates the case fatality rate in west Africa as 70 per cent, while in treatment centres outside Africa, the fatality rate is 25 per cent. (18)
Supportive care includes:
* Managing hypovolaemia.
* Correcting electrolyte imbalance.
* Maintaining blood pressure and oxygenation.
* Pain relief.
* Treating secondary bacterial infections.
* Support/replacement of organ function (eg renal dialysis).
* Managing DIC and cerebral oedema.
Some infectious disease specialists are calling for less focus on experimental therapies and more effort in providing improved supportive care on the ground in west Africa. (18) MUST--maximum use of supportive therapies--involves intravenous fluids, electrolyte replacement, nasogastric tube feeding, and access to drugs that limit diarrhoea and vomiting and manage secondary sepsis. The total cost of these interventions would be less than US$600 per patient. (18)
However, a high fatality rate is likely, even with implementation of MUST, so developing curative therapies remains an important goal. (18) Experimental therapies for preventing and managing EVD are being fast-tracked and a number are expected to enter the field before the end of this year. (19) A number of these therapies have been administered to patients being managed in Europe and the US, but there is no way to tell if the provision of intensive care or the treatments themselves made a difference to outcomes for these patients. (19) In addition, the ethical issues involved in the introduction of these potential therapies are numerous and complex. Randomised controlled trials may be denying some patients potentially life-saving therapies, but, given the high mortality rate of EVD, without controlled trials it is impossible to tell if the drugs are doing harm. (19)
Possible therapies include:
 TKM-Ebola: This drug inhibits viral RNA and has been successful in monkeys, but there is very little data for humans. It carries a risk of triggering explosive cytokine release--something EVD patients are already experiencing.
 ZMapp: This cocktail of genetically-engineered antibodies provides passive immunity. It has proven efficacy in monkeys and has been administered to several EVD patients in the US, but has been used alongside other therapies and supportive care, so efficacy is uncertain. Neither this drug nor TKM-Ebola can be manufactured in quantities sufficient to address the current outbreak. (19)
 Plasma transfusion from recovered patients: The recovered person's antibodies provide passive immunisation. This has been successful for other viral infections and, as with ZMapp, has been used to manage EVD patients alongside other therapies. It has no demonstrated efficacy in monkeys but supply would not be a major issue. (19)
 Brincidofovir: This is an antiviral drug already in phase III trials for other viral infections. It is known to kill the Ebola virus in vitro, but cannot be tested in monkeys because it gets rapidly inactivated. It has been used for US patients, and is more readily available than ZMapp or TKM-Ebola. (19)
 Favipiravir: This influenza drug, developed in Japan, cures EVD in mice, but the disease takes a very different course in rodents than in humans. So the drug's success with mice cannot be directly applied to the human experience. Other antiviral drugs, eg those used for HIV, have no ability to kill the Ebola virus. (10,19)
Claims have been made on the internet by alternative therapy practitioners about EVD, its causes and cures, including the promotion of homeopathy, herbalism, megadoses of vitamin C and essential oils. Despite claims by proponents of these various therapies, there have been no clinical trials in the management of EVD or indeed any other viral infections, and no other reliable evidence is forthcoming.
Essential in managing EVD is preventing the spread of the virus. Every person contracting EVD is passing it on to one or two others. In previous outbreaks, geographical isolation has ensured minimal spread, but once it entered the urban populations of west Africa, transmission through the population was no longer limited by isolation. Contact tracing and precautionary isolation, while essential to contain the outbreak, is hampered by lack of infrastructure, and by cultural barriers --including traditional funeral practices and the stigma of the disease.
Cultural barriers are also impeding reintegration of EVD survivors back into their communities. In the long term, recovered patients may experience ongoing health issues including skin peeling and hair loss, fatigue, weakness and failure to gain weight. There may also be issues with joint and muscle pain, orchiditis, blindness and sensitivity to light. Many survivors are suffering from post-traumatic stress and dealing with loss of family and employment. (16)
To place Ebola in perspective--since the outbreak (and at the time of writing) Ebola has infected 14,500 people with 5200 reported deaths. (17) In comparison, in 2012, malaria was responsible for 627,000 deaths and measles 122,000 deaths. HIV/Aids, which was first identified at around the same time as EVD has, in that time, infected more than 75 million people and killed 36 million.
EVD is a frightening disease because it is swiftly fatal for many people who catch it. Essential to managing this outbreak is the ability to trace and isolate contacts of infectious patients. It is highly likely that in developed nations, contact tracing and precautionary measures will be sufficient to contain any potential outbreak.
For nurses, an in-depth understanding of the facts about EVD can help them reassure people who are feeling anxious about this disease.
After reading this article and completing the accompanying online learning activities, you should be able to:
* Explain the history of Ebola virus disease (EVD).
* Describe the organism that causes EVD and its modes of transmission.
* Explain the signs and symptoms of EVD.
* Provide rationales for current approaches to managing and containing EVD.
Earn two hours of CPD
By reading this article and doing the associated online learning activities, you can receive a certificate for two hours of continuing professional development (CPD).
Go to www.cpd4nurses.co.nz to complete the learning activities for this article. The online service for this article is FREE.
These articles are supplied by CPD4nurses, an independent education company. CPD4nurses is not an NZNO service.
* References for this article can be found at www.cpd4nurses.co.nz.
Georgina Casey, RN, BSc, PGDipSri, MPhil (nursing), is the director of CPD4nurses.co.nz. She has an extensive background in nursing education and clinical experience in a wide variety of practice settings.
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|Publication:||Kai Tiaki: Nursing New Zealand|
|Article Type:||Disease/Disorder overview|
|Date:||Dec 1, 2014|
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