Virology

EBOLA VIRUS DISEASE (EVD)

Written by MicroDok

Ebola virus is found in the viral family, Filoviridae. It is a Filovirus that causes haemorrhagic viral infection or disease in humans. However, Ebola virus disease also occurs in non-human primates including chimpanzees, gorillas and monkeys. Ebola virus like some other viral agents responsible for causing haemorrhagic fever in humans are zoonotic in nature; and this implies that these viruses are mainly animal-borne, and are thus transmitted form animals to humans via direct or indirect contact with the animals that harbour them. Ebola Virus Disease (EVD) which can also be known as Ebola hemorrhagic fever is a severe, often-fatal viral disease that has a case fatality rate of about 90 % according to the World Health Organization (WHO).  EVD is a severe acute viral illness that is often characterized by the sudden onset of unexplained fever, intense body weakness; muscle pain, headache and sore throat with bleeding from different parts of the body in some sever cases. Ebola virus disease was first described in the early 1970s in West Africa where the first disease outbreak occurred. The causative agent of EVD (i.e., Ebola virus) was first isolated during the first epidemic of EVD in Sudan and Zaire (both in Sub-Saharan Africa). The disease was named after a river in the region where the disease outbreak first occurred (particularly in Congo). Particularly, the first species of Ebola virus was discovered in 1976 in what is now known as the Democratic Republic of the Congo (former Zaire) near the Ebola Riverthat the EVD was named after as aforementioned. Since then, outbreaks of Ebola virus infection or disease have appeared sporadically in many parts of Africa especially in the Democratic Republic of the Congo – where morbidity and mortality rates due to EVD is high. Vomiting, diarrhea, rashes all over the body, impaired kidney and liver function, and internal and external bleeding which usually occur in some cases of EVD are other signs and symptoms that characterize EVD in humans. The incubation period of EVD (i.e., the time interval from infection with the Ebola virus to the onset of clinical signs and symptoms of the disease) is usually 2 to 21 days. Several outbreaks of Ebola virus disease have occurred sporadically in parts of Africa, South America, the Middle East and Eastern Europe; and just recently in 2014, another serious outbreak of EVD occurred in Guinea, Sierra Leone and other parts of Africa claiming some thousands of deaths in Africa. Between 2018 and 2019, severe outbreak of Ebola virus infection was recorded in the Democratic Republic of the Congo – where morbidity and mortality rate of the disease was at an alarming level. Bats are believed to be the natural hosts of Ebola virus but monkeys, chimpanzees and other primates can be infected by Ebola virus. Humans can be infected by Ebola virus when they eat infected monkeys, bats and other bush meats infected by the viral pathogen.

The current outbreak of Ebola disease virus which occurred in some parts of Africa before spreading to other parts of the world (including Spain and USA) by importation was caused by the Zaire strain of Ebola virus, which has a mortality rate of about 50 to 90%. Particularly, this recent 2014 epidemic of Ebola disease started in December 6, 2013, in the village of Meliandou, in Guinea where it killed a two-year old boy and then went on to kill his mother, sister and grandmother; and then the Ebola disease virus spread through the human population of Guinea, Liberia, and Sierra Leone. Many parts of the West African sub region were devastated by the virus. Ebola virus is of great public health importance because of its ability to spread to healthcare workers and other non-susceptible individuals. Several outbreaks of Ebola virus disease among humans have appeared sporadically in Africa over the years but the 2014 outbreak of the disease that started in Guinea before spreading to other countries in Africa was one of the most deadly epidemics of the disease. Ebola disease has a very high case fatality rate (CFR), and the lack of proper diagnosis, treatment and vaccine for the disease are other contributing factors to the high mortality rate associated with the disease. The sudden outbreak of EVD when monkeys are not implicated in the disease cause or spread is still a subject of discussion in the medical community. The enigma surrounding the causative agent, actual reservoir and spread of the viral pathogen in human population still remains largely vague. Though EVD is largely known as a zoonotic viral infection (i.e., an animal-borne viral infection transmissible to humans) and one that occurs mainly in bats and other non-human primates, the natural reservoir host of Ebola viruses remains unknown. Ebola virus disease and other viral haemorrhagic fevers are different from other microbial diseases because they occur abruptly and spontaneously and thus claim the lives of their victims especially when proper medical care and support is not administered to infected persons.

SUBSPECIES OF EBOLA VIRUS

Five subspecies of Ebola virus are known to exist and they include:

  • Zaire ebolavirus (EBOV): EBOV was first recognized in 1976 in Democratic Republic of the Congo (formerly Zaire). EBOV has caused several outbreak of haemorrhagic viral fever in parts of Africa especially the Central and West African sub-regions. A transmission electron (TEM) micrograph of Ebola virus is shown in Figure 1. The case fatality rate (CFR) of EBOV is between 50-100 %; and it is the causative agent of the West African epidemic – that caused the recent 2014 outbreak of Ebola. EBOV is the most lethal strain of all the five strains of Ebola virus; and it is responsible for most of the epidemics of EVD in Africa.

Figure 1: Colorized transmission electron micrograph (TEM) revealing some of the ultrastructural morphology displayed by an Ebola virus virion. Ebola virus has a thread-like filamentous structure – taken from the Latin word “filum”, from which the name of the viral family Filoviridae was derived or coined from. CDC.

  • Bundibugyo ebolavirus (BDBV): BDBV first emerged in Uganda where it caused an outbreak of the year 2007. However, the level of case fatality was not as much as is associated with the Zaire ebolavirus (EBOV) that is responsible for majority of the cases in West Africa.
  • Sudan ebolavirus (SUDV): SUDV is only associated with four epidemics of viral haemorrhagic fever including two Ebola epidemics in Sudan in the 1970s; one Ebola epidemic in Uganda in the year 2000, and another Ebola outbreak in Sudan in the years 2004. Unlike the Zaire Ebola virus (EBOV) with CFR of 50-100 %; SUDV has a CFR of about 50 %.
  • Taï Forest ebolavirus (TAFV): TAFV has only been found to infect one individual that eventually recovered from the disease. The exposure of the infected individual actually occurred when a scientist performed a necropsy on a dead chimpanzee in the Tai Forest of Ivory Coast – which is why the virus is also called Ivory Coast Ebola virus.
  • Reston ebolavirus (RESTV): Reston virus only causes disease in nonhuman primates, but not in humans; and it was isolated from infected cynomolgus monkeys imported to the United States and Italy from the Philippines. The Reston ebolavirus was discovered when it caused an outbreak of lethal infection in macaques imported into the United States in 1989 from the Philippines – where the virus is believed to be reserved in animal reservoirs especially nonhuman primates. Bundibugyo ebolavirus (BDBV), Zaire ebolavirus (EBOV), Sudan ebolavirus (SUDV) and Taï Forest ebolavirus (TAFV) are the only subspecies of the Ebola virus that cause disease in humans. However, only BDBV, EBOV, and SUDV have been reported to be responsible for the outbreak of EVD in Africa particularly in Central and West African sub- regions. The Reston ebolavirus has not been found in Africa.

TRANSMISSION OF EVD

The transmission of EVD is mainly via direct body contact with infected patients as well as body fluids from such individuals inclusive of dead victims. Ebola virus is spread in human population through direct body contact with blood or body fluids of an infected person or animal as aforementioned but the virus is transmitted to humans from wild animals including bats and monkeys, and it is then spread in human population via person-to-person contacts. Fruit bats of the Pteropodidae family are considered to be the natural host of the Ebola virus. Food meant for human consumption can be easily contaminated when these bats feed on them; and this can serve as an easy route via which the disease can spread in human population. The body fluids that can help in the transmission of Ebola virus in human population include urine, saliva, sweat, faeces, vomit, breast milk and semen. The virus can also be spread through direct body contact with objects that have been contaminated with the blood or other body fluids of an infected person, whether dead or alive. The risk of infection through the inhalation of contaminated aerosols by healthcare workers has not been reported but this is thought to be low at this time based on case history evidence of the disease. Ebola virus is susceptible to some detergents or chemicals. The virus is readily killed by bleach or sodium hypochlorite, direct sunlight, or drying. Consequently, the machine washing of clothes that have been contaminated with fluids suspected to contain the virus, is recommended to destroy the virus and return the clothing to their germ-free normal state. Ebola virus survives only a short time on surfaces that are in the sun or have dried. It is critical to wash clothes with such detergents to which the virus is susceptible to especially in places where outbreak of EVD has occurred. More so, healthcare workers must ensure adequate personal and environmental hygiene practices when managing and treating patients infected with Ebola virus to avoid contamination. Of particular interest is the fact that previously infected men who have recovered from the EVD can still transmit the virus through their semen to their wives or spouses for up to seven (7) weeks after recovery from the disease. The ritual washing of Ebola victims at funerals has also played a significant role in the spread of the disease in past and recent Ebola outbreaks in some parts of West Africa. And nosocomial transmission of the disease is also common amongst hospital staff that does not use the recommended or appropriate personal protective equipment (PPEs) when attending to severely ill patients that have not been officially recognized as having the Ebola virus infection.

PEOPLE AT RISK OF EBOLA VIRUS INFECTION

Though the actual manner of transmission or spread of the Ebola disease virus from animals including primates and bats to humans may still remain vague; the people mostly at risk of contamination with the causative agent of Ebola disease include healthcare workers who come in contact with infected patient’s fluids including blood, saliva and urine. Healthcare workers including doctors, nurses and laboratory staff who fail to observe and stick to their institution’s recommended infection control measures or guidelines as it regards to handling Ebola virus infected patients and their clinical samples are even at higher risk of infection than those who use their personal protective equipment (PPE) in the care and management of Ebola diseases cases. The family members, friends and relatives of the Ebola virus infected patients are also at higher risk of infection when they come in contact with the infected individual as well as with their body fluids. It is advisable for healthcare workers to always wear their protective clothing such as masks, gloves, gowns, and eye goggles when attending to Ebola infected patients and when handling or processing their samples. The isolation of Ebola infected patients from unprotected persons in the community or hospital environment is critical to prevent the spread of the disease. And direct contact with the corpse of a patient killed by the disease should be avoided as much as possible because the dead body of a patient who died from Ebola virus infection is highly infectious.

 PATHOGENESIS OF EVD

It is worthy of note to state here that all the basic information regarding the pathogenesis of Ebola virus infection in humans have been mainly obtained from laboratory experimentations carried out in nonhuman species including nonhuman primates (e.g., monkeys and chimpanzees), mice and guinea pigs. The data obtained from such studies have been used to extrapolate the disease conditions of the virus in humans. Epidemiological studies involving the observation of patients infected with the virus; and the unique clinical signs and symptoms that they usually present with, have also contributed to the understanding of the disease (EVD). The sporadic and lethal nature of EVD have made it almost impossible to conduct appropriate clinical studies under Ebola disease outbreaks – since most of the tasks of healthcare professionals are mainly geared towards taking care of those infected as well as containing the spread of the disease to non-infected members of the human population. Ebola virus, a Filovirus in the family Filoviridae is classified as a biological class 4 (BSL-4) pathogen because it is a lethal infectious viral agent with a high case fatality rate (CFR) of between 50-100 %. Ebola virus enters the host body through mucosal surfaces, breaks, and abrasions in the skin, or by parenteral introduction through contaminated needles or other sharp objects that pierces the body. Direct body contact with ebola-infected patients or cadavers of individuals killed by the viral pathogen is another route of transmission of the disease especially in places where ebola disease occurs sporadically. Other body fluids of infected individuals including semen, blood, nasal secretions and genital secretions are additional sources of infection. The consumption of some wild animals including chimpanzees, fruit bats and monkeys in some West and Central African countries have also been associated with some outbreaks of Ebola virus disease (EVD) in these regions. The epidemiologic mode of transmission of Ebola disease virus is well recognized even though its primary source of infection (especially in human population) is still arcane. After invasion of a suitable host cell, the viral particle finds its way to several cells of the host body including the macrophages, monocytes and dendritic cells in the liver, spleen, thymus, and other lymphoid tissues of the infected host’s immune system. Other cell types invaded by the Ebola virus include the endothelial cells, fibroblasts, hepatocytes (cells of the liver), adrenal cortical cells, and the epithelial cells of the body. Ebola virus has a broad cell tropismand this is why the virus infects several tissues/cells of the body. Majorly, EVD is mainly characterized by nonspecific symptoms including fever, vomiting, and severe diarrhea. There is visible haemorrhage or bleeding in some cases of the disease. Patients presenting with these clinical signs and symptoms (especially in Ebola endemic regions) should be carefully scrutinized and followed-up clinically to ensure that the symptoms they are showing are not as a result of Ebola virus infection. After the invasion of these host cells by Ebola virus, there is a multifocal necrosis of the infected tissues and/or cells as the virus replicates in vivo. The replication of the virus is immediately followed by the release of large numbers of new viral particles of Ebola virus into extracellular fluids of the body including blood. The release of the new viral particles into the extracellular fluids characterizes the highly infectious nature of the body fluids of Ebola infected patients. The incubation period of EVD ranges from 2 to 21 days. Clinical signs and symptoms of the disease begin to manifest in the infected individual during these period. However, infected patients who are able to mount an immune response to the viral pathogen will begin to recover within 7 to 10 days after initial infection. For such individuals, a period of prolonged convalescence is initiated – within which the infected persons start to recuperate gradually. Several organs of the body are infected including the dysfunction of the gastrointestinal tract (GIT) and the impairment of the host’s immune system especially the adaptive immune system. The dysfunction of the individual’s GIT results in vomiting and diarrhea; and these conditions can lead to acute depletion of the body’s electrolytes (i.e., loss of excess fluids from the body). It can also result to shock and hypotension – which if not carefully managed clinically, can result to casualty or death.

 LABORATORY DIAGNOSIS OF EVD

Early clinical and/or laboratory diagnosis of patients or people infected with Ebola virus (especially at the first few days of infection) is usually challenging due to the fact that EVD presents with clinical signs and symptoms that are akin to other infectious diseases. Nevertheless, once EVD has been implicated in the disease state of the individual, the patient should be isolated and treated immediately. Samples should be aseptically collected and analyzed for the trace of the causative agent of the supposed viral infection. The clinical and/or laboratory diagnoses of EVD should be undertaken with caution since the disease has similar symptoms with other microbial diseases including but not limited to malaria, typhoid fever, shigellosis, cholera, leptospirosis, plague, rickettsiosis, relapsing fever, meningitis, hepatitis and other viral haemorrhagic fevers. It is important to first of all rule out these diseases before a proper diagnosis of EVD can be made. Clinical samples from EVD patients are highly infectious and should be treated as biohazard risk specimens. Such samples should be analyzed by well trained laboratory personnel in appropriate biological containment facility or laboratory (BSL-4 Lab) in order to avoid disease spread and possible contamination of the investigator or researcher working on the sample. Several techniques are available for the laboratory diagnosis of EVD from clinical samples of infected patients; and some of these methods include:

  • Cell/tissue culture for viral isolation.
  • Use of transmission electron microscopy to determine the electrograph or structure of the infecting viral pathogen.
  • Enzyme-linked immunosorbent assay (ELISA).
  • Antigen detection tests to detect viral proteins or antigens.
  • Serum neutralization test.
  • Reverse transcriptase polymerase chain reaction (RT-PCR) assay for determining the gene sequence of the infecting virus.

 TREATMENT/IMMUNIZATION FOR EVD

Ebola virus disease (EVD) is usually treated using a supportive type of therapy to sustain the patient’s life. The treatment of EVD is mainly based on the maintenance of the patient’s electrolytes and other normal physiological conditions of the body including the renal system of the body. Since the EVD patient may lose fluids during the disease episodes due to diarrhea, it is vital to balance the patient’s electrolytes and body fluids in order to save their lives. EVD patients are frequently dehydrated. Thus, they need a steady supply of intravenous fluids or oral rehydration with solutions that contain the appropriate lost electrolytes from the body. The oxygen supply level of the individual should also be maintained and their blood pressure levels should also be at optimum level. Stopping the bleeding in the infected individual is also another important supportive therapy given to Ebola virus infected patients. All these clinical management strategies given to EVD patients is what culminate into the supportive type of therapy abovementioned. Ebola virus infected individuals should also be treated for other secondary or complicating microbial infection devoid of the primary EVD. The main impediment to the timely treatment of EVD is the difficulty in the diagnosis of the disease at the onset. Some signs and symptoms of EVD are akin to other microbial and/or viral infections as aforesaid; and these are some contributing factors to the difficulty in early diagnosis of EVD. Timely treatment of EVD especially with the use of supportive therapy as aforesaid saves the lives of those infected with the deadly virus. There is currently no specific treatment or chemotherapy to treat and manage EVD cases. However, an experimental drug known as ZMAPP (sourced from tobacco plant) was introduced in the recent 2014 outbreak of EVD in Africa. ZMAPP is still an experimental drug that is undergoing clinical trials before it can be certified safe for use worldwide. Vaccine development for ebola disease is proving putative; and currently, there is an experimental vaccine against Ebola virus (rVSV-ZEBOV-GP Ebola vaccine). The experimental vaccine currently in use and approved by the World Health Organization (WHO) for vaccinating over 90,000 people at risk of ebola virus infection in the Democratic Republic of Congo is found to have a success rate of about 97.5 %. This experimental vaccine is an rVSV-ZEBOV-GP Ebola vaccine made by Merck & Co; and the vaccine contains a live attenuated virus harmless to humans. Researchers have genetically engineered the virus to carry an Ebola glycoprotein – which helps in triggering the host (human) immune system to produce powerful antibodies to attack the invading Ebola virus. The geographical distribution of new and total confirmed cases of Ebola virus disease in Africa between 2014 and 2016 is presented in Figure 2. Currently, the rVSV-ZEBOV-GP Ebola vaccine is safe and effective and can be used for vaccinating the human population against Ebola virus infection. With proper care and management, some EVD patients will recover and bounce back to their normal state. The Ebola virus outbreaks by viral species and size of the outbreak since 1976 when the Ebola virus disease (EVD) was first discovered near the Ebola River in what is now the Democratic Republic of Congo is shown in Figure 3.

Figure 2: Geographical distribution of new and total confirmed cases of Ebola (May, 2015 Report). Source: WHO.

Figure 3. Ebola virus outbreaks by viral species and size of the outbreak Since 1976. CDC

 PREVENTION AND CONTROL OF EVD

Ebola virus disease (EVD) is a deadly haemorrhagic viral infection that spreads like wildfire in human population after an outbreak. Effective preventive and control measures are crucial to the containment of the disease. The prevention and control of Ebola virus infection or EVD outbreak is quite different from other microbial diseases inclusive of other viral infection due to the sporadic nature of the disease and the high infectious and mortality nature of the disease agent. Though accidentally transmitted from animals to humans; Ebola disease is highly infectious in human population. Once infected, human infections become highly communicable to non-infected members of the community via human contacts; and the recent outbreak of EVD in some parts of Africa between 2017 and 2019 rightly attest to the highly infectious and extremely transmission nature of Ebola virus in human population. The prevention of EVD according to the Center for Disease Prevention and Control (CDC) is very challenging since the main route of transmission of the disease from animals to human beings still remains unknown. It is still largely unknown how humans are affected with Ebola virus. Outbreaks of Ebola virus disease should be reported to local health authorities who will take the proper action to contain the disease spread. Ebola disease is a notifiable disease that must be reported to the local health authorities once an outbreak has occurred. Such a measure will help the local health authority to move into action in order to contain and stop the spread of the disease outbreak while administering adequate medical care to the already infected human population. The CDC is an international public health organization that surveys and monitors disease spread especially during an epidemic; and they have Epidemic Intelligence Service Officers – that go into communities to assist local health authorities in the containment of an epidemic (Figure 4).

Figure 4: CDC’s Epidemic Intelligence Service Officers (in protective sealed suits) responding to a disease outbreak in a local community in Africa. CDC.

No authentic or generalized control measure or activities have been instituted or established for the effective control of Ebola virus infection. This is due in part to the fact that the actual natural reservoirs of Ebola virus still remain indistinguishable and the sporadic outbreak and spread of the disease has defied some notable infection control practices ever known. However, for the effective control of Ebola virus infection especially in regions where the disease is endemic, the occasional use of isolation facilities still remains one of the most valuable methods of controlling Ebola disease outbreak or spread. Aside this, the effectual observance of instituted infection control measures by healthcare workers who assist in the management of the disease outbreak will also go a long way in halting the spread of the disease. Special medical attention should always be given to Ebola virus infected patients in order to avoid the spread of the disease. And this is why the use of isolation facilities in outbreaks of Ebola disease is paramount as this will not only help to ensure that the infected individual gets proper care but such isolation facilities will help to stop the spread of the deadly virus to other non-infected members of the community. In the containment of Ebola disease outbreak, contact tracing is usually used by healthcare workers and epidemiologists to locate possible contacts of infected persons with non-infected members of the population. Contact tracing is defined as an epidemiological tool used by epidemiologists and public health personnel to trace and find every person who may have directly or indirectly come in contact with an individual infected with a highly infectious disease or pathogen. In contact tracing, the suspect individuals who may have come in contact with the diseased patient are identified as fast as possible, and once located, such individuals are placed under the watch or surveillance of public health personnel – whose duty it is to observe the identified persons over the stipulated incubation period of the disease being investigated. For example, individuals who made contacts with an Ebola infected patient are identified and watched for 21 days (the incubation period of Ebola disease) – in order to find out whether such persons will come down with the clinical signs and symptoms of EVD. Identified individuals who do not show any clinical sign or symptom of the disease are released and allowed to go home. However, those individuals that come down with the clinical signs and symptoms of EVD within the stipulated incubation period of 21 days are immediately isolated. The isolated and infected patients are also tested for the presence of antibodies to Ebola virus and then treated for the disease. Through contact tracing, all the individuals who made contacts with an infected person are identified and watched in order to break the chain of transmission of the disease. It is vital to know that any contact missed during this process is a “red alert” for health personnel because one missed contact during this process will perpetuate the spread of the infectious disease agent from one person to another and from one geographical location to another. Through contact tracing, new cases of an infectious disease can be rapidly identified so that they can be isolated, tested and treated in order to stop the further transmission of the disease to non-infected and susceptible members of the human population.

Based on their level of risk, contact with an infected individual can be very low or no recognized risk; low risk; moderate risk or high risk. Contacts with body fluids of infected persons and contaminated needle puncture are high risk contacts. Low risk contacts include contacts that have to do with close face-to-face contacts with feverish patients such as that obtainable during the physical examination of a sick patient in the hospital or community where the disease outbreak occurred. Moderate risk contacts has to do with healthcare workers who fail to wear their personal protective clothing when attending to sick patients with cough and vomiting episodes. Special protective clothing and other personal protective equipment (PPE) as aforementioned should always be worn by healthcare workers when attending to Ebola virus infected patients (Figure 5).

Figure 5: Illustration of protective Ebola suit. Ebola disease is a highly infectious viral haemorrhagic fever; and health workers are easily infected by body fluids of infected patients especially when proper infection control measures are not put in place when treating and taking care of Ebola patients. The wearing of protective Ebola suit as illustrated in this diagram during a disease outbreak will help to contain disease contraction and spread within a defined geographical location. Aprons, boots, gloves, overalls, masks, respirators, surgical caps, scrubs and goggles are part of the recommended personal protective equipment (PPEs) to be worn by healthcare givers during the outbreak of a highly infectious disease. Some of these equipment or materials form part of the infection control measures carried out in hospitals even during patient care, treatment and the processing of patients samples in the laboratory.

These PPEs should also be used when working on highly infectious patients samples both in the hospital environment and in the fields where a disease outbreak must have occurred. In very low or no recognized risk contacts, the contacts have to do with sitting around a sick person in a transportation system or in an office. Primates including gorillas, chimpanzees, monkeys and non-primates such as bats and other wild animals are believed to be involved in the transmission of Ebola virus to humans. Some of these animals are also considered to be reservoirs of the lethal virus – from which human infections are likely to occur accidentally (Figure 6). The best method of prevention for EVD is by raising awareness in the community of the possible risk factors that can predispose people to becoming infected by the virus. In Africa, human contacts with infected dead or living animals including bats, chimpanzees, monkeys and gorillas have caused some outbreaks of EVD. And when the general public is fashioned with such vital information about EVD especially in regions where the disease occurs sporadically or is endemic, people will take the necessary precautionary measures to avoid being infected by the haemorrhagic viral pathogen.                

Figure 6: Illustration of Ebola ecology. Ebola virus is acquired from wild animals including bats, monkeys, gorillas, chimpanzees and deer; and human-to-human transmission of the disease is possible and predominant in epidemic regions. Source: CDC.

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