|Year : 2017 | Volume
| Issue : 1 | Page : 1-9
Ebola virus disease in the light of epidemiological triad
Gurmeet Kaur, Sandeep Sachdeva, Diwakar Jha, Anika Sulania
Department of Community Medicine, North DMC Medical College, Hindu Rao Hospital, Delhi, India
|Date of Web Publication||11-Jan-2017|
Department of Community Medicine, North DMC Medical College, Hindu Rao Hospital, Delhi - 110 007
Ebola virus disease (EVD) is one of the most virulent pathogens among viral hemorrhagic fevers affecting economically deprived countries of the world with reported case fatality rates of up to 90% due to multiorgan failure and severe bleeding complications. The most recent outbreak of 2014 has set the alarm bell ringing across the globe for increased focus, funding, research, and development toward the control and management of this emerging viral communicable disease that has a potential pandemic threat. This manuscript review and update current knowledge with regard to epidemiology of EVD problem statement, historical perspective, agent, host, environment, reservoir of infection, routes of transmission, pathogenesis, clinical features, laboratory diagnosis, management, and control. The review was undertaken using the key words epidemiology, public health, outbreak control of Ebola virus, EVD, emerging disease, and/or pandemic disease through medical search engines and abstracting databases such as Pubmed, Google Scholar, and websites of international health agencies such as the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC).
Keywords: Burial practices, communicable disease, emerging disease, environment, epidemiology, infection, public health, risk exposure, surveillance, transmission
|How to cite this article:|
Kaur G, Sachdeva S, Jha D, Sulania A. Ebola virus disease in the light of epidemiological triad. Trop J Med Res 2017;20:1-9
| Introduction|| |
Ebola virus disease (EVD) is a zoonotic disease caused by an RNA virus of the family Filoviridae and genus Ebola virus leading to severe hemorrhagic fever and fulminant septic shock. In the 2014 outbreak though with the roots being discovered in late 2013, events in West Africa changed the perception of EVD from an exotic tropical disease to a global health security and threat. This review manuscript describes the current update with regard to disease burden, historical insight, agent, host, environment, reservoir, source, routes of transmission, pathogenesis, clinical features, laboratory diagnosis, and control and management of EVD.
| Problem Statement|| |
The first outbreak occurred in Zaire (Congo) in 1976 followed by several outbreaks within Africa (except one in the Philippines, Italy, and the USA). [Figure 1] depicts the affected countries in Western Africa during the most recent outbreak. On August 8, 2014, the World Health Organization (WHO) declared the EVD outbreak in West Africa as a Public Health Emergency of International Concern, emphasizing the need for international focus and cooperation to control the outbreak. The imported EVD case in Nigeria resulted in a small outbreak and similar imported cases in USA and Spain, which at first appeared to have been well-contained eventually led to infection among health care workers. EVD has an average case fatality rate of 50% while it was 76% in the 2014 outbreak in Guinea, Liberia, and Sierra Leon but was found to be slightly less (61%) in hospitalized patients., Globally there were a total of 28,639 reported confirmed, probable and suspect cases of EVD in affected countries with 11,316 deaths (Feb 2016) with a similar proportion in males and females. As per WHO notification, human to human transmission ended in Sierra Leone (Nov 2015); Guinea (Dec 2015) and Liberia (Jan 2016). These countries have entered into a 90-days period of enhanced surveillance adults aged 15-44 years are three to four times more likely to be affected than children aged less than 14 years. A total of 874 confirmed health worker infections and 509 deaths were reported in the abovementioned countries.
| Historical Perspective|| |
The discovery of Ebola began in Yambuku village in Zaire where a Belgian nun became ill, and a Belgian doctor sent her blood sample for investigation. Dr. Peter Piot, a clinical microbiologist, who saw this spaghetti-shaped virions under the electron microscope could not come to a conclusion. He mistook it to be the Marburg virus and sent the photo to other experts in the world; however, they confirmed that it was not the Marburg virus. The nun died and several villagers were affected by a similar illness and were dying. Piot travelled to Yambuku to investigate the epidemic through a detailed history and maps to make connections and within 3 months carried out extensive isolation of cases and contacts. They thought of naming the virus after the Yambuku village but realized that it would stigmatize the village, so they named the virus after the nearest river, the Ebola river.
Historically, EVD outbreaks often occurred in small villages close to or located in tropical rainforests and remained restricted to a limited area [Table 1]. The rising trend of EVD outbreaks have occurred due to increased movement of people into previously inaccessible areas and increased consumption of bush meat. [Figure 2] depicts Ebola outbreak (cases and death) in the African continent according to the years. The roots of current outbreak emanated some-where during December 2013 but it is not known with certainty how the index case became infected. Genetic similarities among the samples of current outbreak suggest a single event of virus transmission from the natural reservoir followed by sustained human-to-human transmission.
| Agent Factors|| |
Ebola virus contains single-stranded negative RNA linear genome, about 18-19 kb in size and encodes seven genes (NP, VP35, VP40, VP30, VP24, L, and GP). Five genetically distinct Ebola virus species within the genus Ebola virus are known [Zaire Ebola virus (ZEBOV), Sudan Ebola virus (SEBOV), Tai Forest Ebola virus, Bundibugyo Ebola virus (BEBOV), and Reston Ebola virus (REBOV)]. The genomes of the five different Ebola viruses (BEBOV, ZEBOV, REBOV, SEBOV, and Taο Forest Ebola virus) are different in sequence, number, and location of gene overlaps. However, REBOV species is reported to cause disease only in nonhuman primates; ZEBOV, SEBOV, and BEBOV are responsible for most of the Ebola hemorrhagic fever (EHF) outbreaks but ZEBOV constitutes a particularly serious threat to both human and animals in sub-Saharan Africa with case fatality rates as high as 90%.
| Reservoir of Infection|| |
Fruit bats of the Pteropodidae family are considered to be the natural reservoirs of Ebola virus.
| Source of Infection|| |
The virus is transmitted from wildlife to people through contact with infected fruit bats and through intermediate hosts such as monkeys, apes, or pigs that become infected through contact with bat saliva or feces. Ebola virus can infect humans by direct contact with the blood and body fluids of infected animals such as apes, gorillas, and monkeys.,, No evidences show that pet cat/dogs, mosquitoes, or other insects can transmit Ebola virus. Human-to-human transmission occurs through direct contact with organs, blood, secretions of the body and other fluids (such as urine, feces, semen, breast milk, mucus, vomit) of an infected person and materials contaminated with these fluids., Infected syringes and needles are other ways by which the virus can be transmitted while air or water does not spread EVD. Breaches in the control of infections and universal precautions have resulted in frequent infections among health workers. Direct contact with the body of a deceased person during burial ceremonies is another classic way by which Ebola can be transmitted.
| Period of Infectivity|| |
The incubation period of Ebola virus is 2-21 days and therefore, it is recommended that infected individuals be isolated for at least 21 days. Latest studies have shown that Ebola transmission occurs when there is a high viral load in body fluids. The person remains infectious as long as the virus is present in the blood and body fluids while those who have completely recovered from EBV cannot spread it further. Ebola virus has been detected in the semen of recovered patients and such patients are advised to abstain from sex or use condoms for three months after being cured. There is no evidence yet on when women recovering from the Ebola virus can resume breastfeeding.
| Host Factors|| |
AGE AND SEX--All ages and both sexes show an equal preponderance for the disease.
IMMUNITY--Ebola infection interferes with proper functioning of the innate immune system. EBOV proteins blunt the human immune response to viral infections by interfering with the cells' ability to produce and respond to interferon proteins such as interferon-alpha, beta, and gamma. By inhibiting these immune responses, EBOV quickly spreads throughout the body.,,
| Environment|| |
SEASON--Human EVD outbreaks in Africa suggest that the onset of these outbreaks was associated with conditions with high absolute humidity and low temperature. Previous outbreaks in humans have been observed in both dry and wet seasons., Seasonal migration of fruit bats may result in increased contact with humans and other animals. Bats naturally host many viruses that are highly pathogenic to other mammals. It has been hypothesized that the flight activities of bats maintain a high body temperature and metabolic rate, which mimic the effect of febrile immune response in limiting the virulence of a virus that may otherwise be highly pathogenic. Seasonal and behavioral factors such as long migratory flight may influence body temperature and metabolic rate in bats. This may result in altered susceptibility to and severity of Ebola infection. Reduction in susceptibility and severity may have bidirectional effects on Ebola transmission dynamics. While less severe infections may allow infected bats to remain active in transmitting the virus, reduction in susceptibility may reduce the overall infection rate among the bat population.,,,,, Peaks in mortality due to EVD in chimpanzees, gorillas, and duikers (a type of antelope) were observed to coincide with some of the previous human outbreaks. EVD outbreaks in nonhuman primates have mostly been reported to occur at the end of rainy seasons. However, it has been unclear whether this was due to earlier humid conditions or current dry conditions.
| Mode of Transmission|| |
EVD is a zoonotic disease and each outbreak in the human population is initiated by a (single) introduction from an animal reservoir. Ebola viruses enter the human body via mucosal surfaces, abrasions, and injuries in the skin or by direct parental transmission. It is likely that for the index case, infection occurs after human contact with primates, for example, due to hunting or consumption of infected animals while other mammals such as antelopes and rodents have also been mentioned as potential reservoirs. Due to the high viral loads seen in the body fluids of EVD patients, human-to-human transmission can easily occur. This transmission seems to take place through body fluid contact and not by airborne transmission (e.g., infective aerosols). When hygiene and personal protective measures are not adequate, the risk is considerable. Furthermore, cultural aspects such as local funeral ceremonies with potential contact with body fluids from patients who have died from EVD contributed to the magnitude of this outbreak.
Sylvatic Ebola fever
In the tropical rainforests, Ebola occurs in monkeys and chimpanzees that consume half-eaten fruits left over by fruit bats. These infected monkeys then pass the virus to other monkeys by coming in contact of the body fluids of infected monkeys, chimpanzees, or pigs, etc. Humans entering the forest come in contact with these infected monkeys or pigs due to hunting, bush meat preparation, and logging of woods; thus, humans enter the cycle and convert the virus from the enzootic cycle to the epizootic cycle of transmission [Figure 3].
| Clinical Features|| |
The symptoms of EVD begin with fever, headache, fatigue, sore throat, and muscle pain, which later progress to anorexia, nausea, diarrhea, vomiting, rash, abdominal pain, cough, shortness of breath, postural hypotension, edema, headache, confusion, and coma. In certain cases, a maculopapular rash develops after 5-7 days of the symptoms., Hemorrhagic complications such as mucosal hemorrhages, nose bleeding, vomiting/coughing up of blood, blood in the stool, petechiae, ecchymoses, and uncontrollable bleeding from venipuncture sites are seen in severe cases, along with other features such as severe metabolic disturbances, convulsion, shock, and multiple organ failure. These complications are the most common causes of death in EBV-infected patients. [Figure 4] depicts the usual progression of EBV in humans.
|Figure 4: Clinical feature of EBV in humans as observed in 2014 outbreak|
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| Laboratory Diagnosis|| |
Ebola after enters the body at the cellular level docks with the cell membrane and then viral RNA is released into the cytoplasm leading to the production of new viral proteins. New viral genomes rapidly coated in protein create cores, viral cores, stack up in cell, migrate to the cell surface and produce transmembrane proteins, then push through cell surface and become enveloped by cell membrane ssRNA genome mutations, which are capable of rapid mutation, very adaptable in evading host defenses and environmental change, can cause direct infection of tissues, immune dysregulation, hypovolemia, vascular collapse, electrolyte abnormalities, multiorgan failure, septic shock, disseminated intravascular coagulation (DIC), and coagulopathy.
Virus isolation and serology
It is difficult to diagnose Ebola virus in the early stages due to nonspecific symptoms, which coexist in patients who are suffering from common diseases such as malaria and typhoid fever. Seroconversion of the EVD can be detected in the blood only when patient symptoms suggest a high level of virus load inside the body. This requires 3 days in order to reach for viral detectable levels. Laboratory test conducted in diagnosis such as antigen-capture enzyme-linked immunosorbent assay (ELISA) testing, immunoglobin M (IgM) ELISA, and polymerase chain reaction (PCR) using specific primers are used within a few days of the onset of symptoms. Immunohistochemistry testing, PCR, and virus isolation could be tested [Table 2]. A team of international scientists under Cambridge University released a dataset in 2015 that allows the global scientific community to monitor the pathogen's evolution on a real-time basis. Sequencing the genome of a virus tells us how it spreads and changes while passing from one person to another. Rapid sequencing (in a matter of days) enables epidemiologists to decipher the source of individual strains and helps to eliminate the need to rely upon Ebola patients to detail their travel history as different strains can be tracked without difficulty.
After 3 days of the symptoms, the Ebola virus usually reaches detectable levels in blood and cannot be ruled out earlier than 3 days by any test. Even during the convalescent stage, the virus can be isolated from the blood, semen, tears, urine, feces, vaginal secretions, and milk [Figure 5]. IgM enzyme-linked ELISA, antigen-capture ELISA, PCR, and virus isolation are the diagnostic tests available and IgM and IgG antibodies are used later in the disease course for the diagnosis of Ebola [Table 2].
|Figure 5: Detection of virus from different body fluids during the acute and convalescent phases|
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Laboratory findings in EVD include coagulation derangements such as prothrombin time (PT) and prolonged prothrombin time (PTT) prolonged, and leukopenia followed by neutrophilia, thrombocytopenia (50,000-100,000/mL range), and elevated liver enzyme: Elevation serum aspartate aminotransferase (AST) > alanine transferase (ALT) and renal defects that include proteinuria and increased creatinine. Early and well-regulated inflammatory response with elevated interlukin (IL)-6 concentration and IL-1beta presence in a symptomatic patient is indicative of a good outcome while a defective innate immune reaction with excessive macrophage/monocyte activation with release of interleukin-10, absent antibody response and elevated concentration of interleukin-1RA, and neopterin after a few days of the onset of disease are associated with a fatal outcome. According to a study, lymphoid depletion and lymphopenia associated with Zaire Ebola virus was most likely due to lymphocyte apoptosis via Fas/Fas ligand (FasL) interaction. The excessive macrophage/monocyte activation leads to a "cytokine storm" triggering disseminated intravascular coagulation, hypotension, and vascular dysfunction, resulting in multiple organ failure, vascular collapse, and shock. According to a recent study, elevated thrombomodulin and ferritin levels have been associated with the death and hemorrhage in Ebola virus-infected patients.
| Prevention of Ebola|| |
Various case definitions and risk assessment as advocated for EBV for priority attention include:
Person under investigation
A person who has both consistent symptoms and risk factors as follows:
- Clinical criteria--Fever (>38.6°C or 101.5°F) and additional symptoms such as severe headache, muscle pain, vomiting, diarrhoea, abdominal pain, or unexplained haemorrhage; and epidemiologic risk factors within the past 21 days before the onset of symptoms such as contact with blood or other body fluids or human remains of a patient known to have or suspected to have EVD; residence in or travel to an area where EVD transmission is active; or direct handling of bats or nonhuman primates from disease-endemic areas
- Suspected case: Any person, alive or dead, suffering or having suffered from a sudden onset of high fever and having had contact with: A suspected, probable, or confirmed Ebola or Marburg case; a dead or sick animal (for Ebola) or any person with the sudden onset of high fever and at least three of the following symptoms, i.e., headache, vomiting, anorexia/loss of appetite, diarrhoea, lethargy, stomach pain, aching muscles or joints, difficulty swallowing, breathing difficulties, and hiccup or any person with inexplicable bleeding or any sudden, inexplicable death
- Probable case: Any suspected case evaluated by a clinician or any deceased suspected case (where it was not possible to collect specimens for laboratory confirmation) having an epidemiological link with a confirmed case
- Confirmed case: A case with laboratory-confirmed diagnostic evidence of Ebola virus infection
- Laboratory confirmed case: Any suspected or probable cases with a positive laboratory result. Laboratory-confirmed cases must test positive for the virus antigen, either by the detection of virus RNA by reverse transcriptase-polymerase chain reaction (RT-PCR) or by detection of IgM antibodies directed against Marburg or Ebola
- Noncase: Any suspected or probable case with a negative laboratory result. "Non-case" showed no specific antibodies, RNA, or specific detectable antigens.
| Evd Risk Assessment|| |
Percutaneous (e.g., needle stick) or mucous membrane exposure to blood or body fluids of a person with Ebola while the person was symptomatic or exposure to the blood or body fluids (including but not limited to feces, saliva, sweat, urine, vomit, and semen) of a person with Ebola while the person was symptomatic without appropriate personal protective equipment (PPE) or processing blood or body fluids from an Ebola patient without appropriate PPE or standard biosafety precautions or direct contact with a dead body without appropriate PPE in a country with widespread transmission or cases in urban areas with uncertain control measures or having lived in the immediate household and provided direct care to a person with Ebola while the person was symptomatic.
Some risk exposure
In countries with widespread transmission or cases in urban areas with uncertain control measures: Direct contact while using appropriate PPE with a person with Ebola while the person was symptomatic or with the person's body fluids, any direct patient care in other health care settings or close contact in households, health care facilities, or community settings with a person with Ebola while the person was symptomatic. Close contact is defined as being present at a close proximity for a prolonged period of time while not wearing appropriate PPE within approximately 3 feet (1 meter) of a person with Ebola while the person was symptomatic. Public health action and supervision of the movement of persons infected with EVD is shown in [Table 3] according to risk exposure.
|Table 3: Public health monitoring and movement/restriction of people with EBV according to risk exposure |
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| Control Measures|| |
The health system capacity of developing countries involved in EVD outbreak is very low and requires both short- and long-term control measures. The international community gave an overwhelming, decisive but delayed response. Some of the generic and specific viral control measures include:,,,,,
- Plans for emergency care including adequate quarantine facilities
- Prompt diagnosis and isolation of the suspected patient
- Symptomatic management
- Adequate laboratory facilities and support
- Proper surveillance, case management, and contact tracing
- Health education and removal of stigma/myth/misconception
- Restriction of the movement of people suffering from EBV
- Training of health care providers
- Universal precaution including provision and availability of logistics/equipment
- Safe burial practices
- Personal and safe hand hygiene
- Dedicated transport facilities for a person infected with EBV
- Change in dietary practices, especially of tribal natives
- Promotion of sanitary environmental conditions
- Home-protective kits
- Recording, reporting, and incident management system
- Development and strengthening of communication channels
- Overall socioeconomic and infrastructure development
- International commitment, research, and funding.
| Ebola Vaccine and Drugs|| |
The disease always had an epicenter in African countries. Since 1976, no attempt were made to create the vaccine against the deadly disease until at present, when the localized problem has surmounted to become a global threat. Currently, there are no effective and target vaccines or treatments which are approved for human use. [Table 4] and [Table 5] describes the potential Ebola vaccine and drugs in different stages of research and development.
|Table 4: List of EBV vaccine that is actively being developed for clinical use |
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|Table 5: List of EBV drug that is actively being developed for clinical use |
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Is India safe from EBV?
The current situation is unlikely to favor establishment of EBV in India because of the following:
- Bats: Absence of Pteropiridae family bats in India; febrile immune response of bats resulting in attenuation of viral load; and localized flight range of bats in the African subcontinent
- Environment: Absence of high absolute humidity and low temperature, along with rains for the breeding of Ebola virus
- Virus: Absence of virus in the Indian subcontinent.
- Surveillance at major international airports, especially during the risk period.
But this does not rule out India to be safe from Ebola as it can be imported through any case/incubating Ebola traveler visiting India. The Government of India has issued standard operating guidelines for the surveillance, control, and management of EBV disease in accordance with the WHO protocols. India has health organization quarantine centers at 24 airports with all international airports and sea ports to be equipped with thermal scanners in the near future. The government has identified about 10 laboratories in the country that will handle testing if a case is reported and in New Delhi, Dr. Ram Manohar Lohia Hospital has been designated as nodal hospital and National Centre for Disease Control (NCDC) as a nodal surveillance institution for EVD outbreak. Since we are still not clear about the epidemiology of Ebola, all international health regulations need to be followed for prevention of a viral outbreak. While urgent steps have been taken by India and other countries to enhance their preparedness and response capacities, the international focus must be on containment of outbreak at the source.
The Dean, North Delhi Municipal Corporation (DMC) Medical College and Hindu Rao Hospital, Delhi-110007 for constant encouragement, advice, and guidance.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]