Ebola (EVD)

There has been a lot of talk going on in the country about a viral and vital disease which goes by the name Ebola and this has resulted in fright among some people situated in different locations around the country; especially those regions bordering Uganda. Ebola broke loose in Uganda in late July and has so far resulted in the infection of 53 people (about 16 of these people have since passed on).
Many know the final effects of the disease i.e. death, but how much do people really know about it?
In this post, we shall look at some information related to Ebola in an effort to help people better understand the disease.

Just what is Ebola?

Ebola virus disease (EVD) (or Ebola hemorrhagic fever (EHF)) is the name for the human disease which may be caused by any of four of the five known ebola viruses. These four viruses are: Bundibugyo virus (BDBV), Ebola virus (EBOV), Sudan virus (SUDV), and Taï Forest virus (TAFV, formerly and more commonly Côte d’Ivoire Ebola virus (Ivory Coast Ebolavirus, CIEBOV)). EVD is a viral hemorrhagic fever (VHF), and is clinically nearly indistinguishable from Marburg virus disease (MVD).

The name comes from Ebola River in Republic of the Congo where it was first found.
The five characterised Ebola species are:
• Zaire ebolavirus (ZEBOV) -Also known simply as the Zaire virus, ZEBOV has the highest case-fatality rate of the ebolaviruses, up to 90% in some epidemics, with an average case fatality rate of approximately 83% over 27 years. There have been more outbreaks of Zaire ebolavirus than of any other species. The first outbreak took place on 26 August 1976 in Yambuku. Mabalo Lokela, a 44 year-old schoolteacher, became the first recorded case. The symptoms resembled malaria, and subsequent patients received quinine. Transmission has been attributed to reuse of unsterilized needles and close personal contact.
• Sudan ebolavirus (SEBOV) -Like the Zaire virus, SEBOV emerged in 1976; it was at first assumed to be identical with the Zaire species. SEBOV is believed to have broken out first amongst cotton factory workers in Nzara, Sudan, with the first case reported as a worker exposed to a potential natural reservoir. Scientists tested local animals and insects in response to this; however, none tested positive for the virus. The carrier is still unknown. The lack of barrier nursing (or “bedside isolation”) facilitated the spread of the disease. The most recent outbreak occurred in May, 2004. 20 confirmed cases were reported in Yambio County, Sudan, with five deaths resulting. The average fatality rates for SEBOV were 54% in 1976, 68% in 1979, and 53% in 2000 and 2001.
• Reston ebolavirus (REBOV) -Discovered during an outbreak of simian hemorrhagic fever virus (SHFV) in crab-eating macaques from Hazleton Laboratories (now Covance) in 1989. Since the initial outbreak in Reston, Virginia, it has since been found in non-human primates in Pennsylvania, Texas and Siena, Italy. In each case, the affected animals had been imported from a facility in the Philippines, where the virus has also infected pigs. Despite its status as a Level 4 organism and its apparent pathogenicity in monkeys, REBOV did not cause disease in exposed human laboratory workers.
• Côte d’Ivoire ebolavirus (CIEBOV)-Also referred to as Taï Forest ebolavirus and by the English place name, “Ivory Coast”, it was first discovered among chimpanzees from the Taï Forest in Côte d’Ivoire, Africa, in 1994.Necropsies showed blood within the heart to be brown; no obvious marks were seen on the organs; and one necropsy displayed lungs filled with blood. Studies of tissues taken from the chimpanzees showed results similar to human cases during the 1976 Ebola outbreaks in Zaire and Sudan. As more dead chimpanzees were discovered, many tested positive for Ebola using molecular techniques. The source of the virus was believed to be the meat of infected Western Red Colobus monkeys, upon which the chimpanzees preyed. One of the scientists performing the necropsies on the infected chimpanzees contracted Ebola. She developed symptoms similar to those of dengue fever approximately a week after the necropsy, and was transported to Switzerland for treatment. She was discharged from the hospital after two weeks and had fully recovered six weeks after the infection.
• Bundibugyo ebolavirus-On November 24, 2007, the Uganda Ministry of Health confirmed an outbreak of Ebolavirus in the Bundibugyo District. After confirmation of samples tested by the United States National Reference Laboratories and the CDC, the World Health Organization confirmed the presence of the new species. On 20 February 2008, the Uganda Ministry officially announced the end of the epidemic in Bundibugyo, with the last infected person discharged on 8 January 2008. An epidemiological study conducted by WHO and Uganda Ministry of Health scientists determined there were 116 confirmed and probable cases of the new Ebola species, and that the outbreak had a mortality rate of 34% (39 deaths).

Which are some of the signs and symptoms of Ebola?

The most detailed studies on the frequency, onset and duration of EVD clinical signs and symptoms were performed during the 1995 outbreak in Kikwit, Zaire (EBOV) and the 2007-2008 outbreak in Bundibugyo, Uganda (BDBV) The mean incubation period, best calculated currently for EVD outbreaks due to EBOV infection, is 12.7 days (standard deviation = 4.3 days), but can be as long as 25 days. EVD begins with a sudden onset of an influenza-like stage characterized by general malaise, fever with chills, arthralgia and myalgia, and chest pain. Nausea is accompanied by abdominal pain, anorexia, diarrhea, and vomiting. Respiratory tract involvement is characterized by pharyngitis with sore throat, cough, dyspnea, and hiccups. The central nervous system is affected as judged by the development of severe headaches, agitation, confusion, fatigue, depression, seizures, and sometimes coma.

Hemorrhage
All patients show some extent of coagulopathy and impaired circulatory system symptomology. Bleeding from mucous membranes and puncture sites is reported in 40-50% of case, while maculopapular rashes are evident in approximately 50% of cases. Sources of bleeds include hematemesis, hemoptysis, melena, and aforementioned bleeding from mucous membranes (gastroinestinal tract, nose, vagina and gingiva). Diffuse bleeding, however, is rare, and is usually exclusive to the gastrointestinal tract.

Causes
EVD is caused by four of five viruses classified in the genus Ebolavirus, family Filoviridae, order Mononegavirales: Bundibugyo virus (BDBV), Ebola virus (EBOV), Sudan virus (SUDV), and Taï Forest virus (TAFV). The fifth virus, Reston virus (RESTV), is thought to be apathogenic for humans and therefore not discussed here.
Genus Ebolavirus: species and their EVD-causing viruses
Species name Virus name (Abbreviation)
Bundibugyo ebolavirus (accepted) Bundibugyo virus (BDBV; previously BEBOV)
Sudan ebolavirus Sudan virus (SUDV; previously SEBOV)
Taï Forest ebolavirus Taï Forest virus (TAFV; previously CIEBOV)
Zaire ebolavirus* Ebola virus (EBOV; previously ZEBOV)
Table legend: “*” denotes the type species and “accepted” refers to a taxon that has been accepted by the Executive Committee of the ICTV but that has yet to be ratified.

Risk factors

Traces of EBOV were detected in the carcasses of gorillas and chimpanzees during outbreaks in 2001 and 2003, which later became the source of human infections. However, the high lethality from infection in these species makes them unlikely as a natural reservoir.
Plants, arthropods, and birds have also been considered as possible reservoirs; however, bats are considered the most likely candidate.
Bats drop partially eaten fruits and pulp which are eventually eaten by terrestrial mammals such as gorillas and duikers. This chain of events forms a possible indirect means of transmission from the natural host to animal populations which have led to research towards viral shedding in the saliva of bats. Fruit production, animal behavior and other factors vary at different times and places which may trigger outbreaks among animal populations. Transmission between natural reservoirs and humans are rare and outbreaks are usually traceable to a single index case where an individual has handled the carcass of a gorilla, chimpanzee, or duiker. The virus then spreads person-to-person, especially within families, hospitals and during some mortuary rituals where there is contact among individuals.
The virus has been confirmed to be transmitted through body fluids. Transmission through oral exposure and through conjunctiva exposure is likely and has been confirmed in non-human primates. Filoviruses are not naturally transmitted by aerosol. They are, however, highly infectious as breathable 0.8–1.2 micrometre droplets in laboratory conditions- because of this potential route of infection, these viruses have been classified as Category A biological weapons.
All epidemics of Ebola have occurred in sub-optimal hospital conditions where practices of basic hygiene and sanitation are often either luxuries or unknown to caretakers and where disposable needles and autoclaves are unavailable or too expensive. In modern hospitals with disposable needles and knowledge of basic hygiene and barrier nursing techniques, Ebola has never spread on a large scale. In isolated settings such as a quarantined hospital or a remote village, most victims are infected shortly after the first case of infection is present. The quick onset of symptoms from the time the disease becomes contagious in an individual makes it easy to identify sick individuals and limits an individual’s ability to spread the disease by traveling. Because bodies of the deceased are still infectious, some doctors had to take measures to properly dispose of dead bodies in a safe manner despite local traditional burial rituals.
The most important indicator that may lead to the suspicion of EVD at clinical examination is the medical history of the patient; in particular, the travel and occupational history (which countries were visited?) and the patient’s exposure to wildlife (exposure to bats, bat excrement, nonhuman primates?). EVD can be confirmed by isolation of ebolaviruses from or by detection of ebolavirus antigen or genomic or subgenomic RNAs in patient blood or serum samples during the acute phase of EVD. Ebolavirus isolation is usually performed by inoculation of grivet kidney epithelial Vero E6 or MA-104 cell cultures or by inoculation of human adrenal carcinoma SW-13 cells, all of which react to infection with characteristic cytopathic effects. Filovirions can easily be visualized and identified in cell culture by electron microscopy due to their unique filamentous shapes, but electron microscopy cannot differentiate the various filoviruses alone despite some overall length differences. Immunofluorescence assays are used to confirm ebolavirus presence in cell cultures. During an outbreak, virus isolation and electron microscopy are most often not feasible options. The most common diagnostic methods are therefore RT-PCR in conjunction with antigen-capture ELISA which can be performed in field or mobile hospitals and laboratories. Indirect immunofluorescence assays (IFAs) are not used for diagnosis of EVD in the field anymore.
Ebola viruses are highly infectious as well as contagious.
As an outbreak of Ebola progresses, bodily fluids from diarrhea, vomiting, and bleeding represent a hazard. Due to lack of proper equipment and hygienic practices, large-scale epidemics occur mostly in poor, isolated areas without modern hospitals or well-educated medical staff. Many areas where the infectious reservoir exists have just these characteristics. In such environments, all that can be done is to immediately cease all needle-sharing or use without adequate sterilization procedures, isolate patients, and observe strict barrier nursing procedures with the use of a medical-rated disposable face mask, gloves, goggles, and a gown at all times, strictly enforced for all medical personnel and visitors. The aim of all of these techniques is to avoid any person’s contact with the blood or secretions of any patient, including those who are deceased.
Vaccines have successfully protected nonhuman primates; however, the six months needed to complete immunization made it impractical in an epidemic. To resolve this, in 2003, a vaccine using an adenoviral (ADV) vector carrying the Ebola spike protein was tested on crab-eating macaques. The monkeys were challenged with the virus 28 days later, and remained resistant. In 2005, a vaccine based on attenuated recombinant vesicular stomatitis virus (VSV) vector carrying either the Ebola glycoprotein or Marburg glycoprotein successfully protected nonhuman primates, opening clinical trials in humans. By October, the study completed the first human trial; giving three vaccinations over three months showing capability of safely inducing an immune response. Individuals were followed for a year, and in 2006, a study testing a faster-acting, single-shot vaccine began. This study was completed in 2008. The next step is to try the vaccine on a strain of Ebola that is closer to the one that infects humans.
There are currently no Food and Drug Administration-approved vaccines for the prevention of EVD. Many candidate vaccines have been developed and tested in various animal models. Of those, the most promising ones are DNA vaccines or are based on adenoviruses, vesicular stomatitis Indiana virus (VSIV) or filovirus-like particles (VLPs) as all of these candidates could protect nonhuman primates from ebolavirus-induced disease. DNA vaccines, adenovirus-based vaccines, and VSIV-based vaccines have entered clinical trials.
Contrary to popular belief, ebolaviruses are not transmitted by aerosol during natural EVD outbreaks. Due to the absence of an approved vaccine, prevention of EVD therefore relies predominantly on behavior modification, proper personal protective equipment, and sterilization/disinfection.
On 6 December 2011 the development of a successful vaccine against Ebola for mice were reported. Unlike the predecessors it can be freeze-dried and thus stored for long periods in wait for an outbreak. The research will be presented in Proceedings of National Academy of Sciences.

In endemic zones
The natural maintenance hosts of ebolaviruses remain to be identified. This means that primary infection cannot necessarily be prevented in nature. The avoidance of EVD risk factors, such as contact with nonhuman primates or bats, is highly recommended but may not be possible for inhabitants of tropical forests or people dependent on nonhuman primates as a food source.
During outbreaks
Since ebola viruses do not spread via aerosol, the most straightforward prevention method during EVD outbreaks is to avoid direct (skin-to-skin) contact with patients, their excretions and body fluids, or possibly contaminated materials and utensils. Patients should be isolated and medical staff should be trained and apply strict barrier nursing techniques (disposable face mask, gloves, goggles, and a gown at all times). Traditional burial rituals, especially those requiring embalming of bodies, should be discouraged or modified, ideally with the help of local traditional healers.

In the laboratory
Ebolaviruses are World Health Organization Risk Group 4 Pathogens, requiring Biosafety Level 4-equivalent containment. Laboratory researchers have to be properly trained in BSL-4 practices and wear proper personal protective equipment.
There is currently no FDA-approved ebolavirus-specific therapy for EVD. Treatment is primarily supportive in nature and includes minimizing invasive procedures, balancing fluids and electrolytes to counter dehydration, administration of anticoagulants early in infection to prevent or control disseminated intravascular coagulation, administration of procoagulants late in infection to control hemorrhaging, maintaining oxygen levels, pain management and administration of antibiotics or antimycotics to treat secondary infections. Hyperimmune equine immunoglobulin raised against EBOV has been used in Russia to treat a laboratory worker who accidentally infected herself with EBOV—but the patient died anyway. Experimentally, recombinant vesicular (VSIV) expressing the glycoprotein of EBOV or SUDV has been used successfully in nonhuman primate models as post-exposure prophylaxis. Such a recombinant post-exposure vaccine was also used to treat a German researcher who accidentally pricked herself with a possibly EBOV-contaminated needle. Treatment might have been successful as she survived. However, actual EBOV infection could never be demonstrated without a doubt. Novel, very promising, experimental therapeutic regimens rely on antisense technology. Both small interfering RNAs(siRNAs) and phosphorodiamidate morpholino oligomers (PMOs) targeting the EBOV genome could prevent disease in nonhuman primates.

Prognosis
Prognosis is generally poor (average case-fatality rate of all EVD outbreaks to date = 68%). If a patient survives, recovery may be prompt and complete, or protracted with sequelae, such asorchitis, arthralgia, myalgia, desquamation or alopecia. Ocular manifestations, such as photophobia, hyperlacrimation, iritis, iridocyclitis, choroiditis and blindness have also been described. Importantly EBOV and SUDV are known to be able to persist in the sperm of some survivors, which could give rise to secondary infections and disease via sexual intercourse.
(Source: Wikipedia)