|Year : 2015 | Volume
| Issue : 3 | Page : 118-125
Ebola outbreak 2014-2015: An update
Varun Goel1, Tarun Goel2, Dinesh Kumar1
1 Division of Clinical Microbiology and Molecular Medicine, Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi, India
2 Department of Medicine, Holy Family Hospital, New Delhi, India
|Date of Web Publication||30-Sep-2015|
Division of Clinical Microbiology and Molecular Medicine, Department of Laboratory Medicine, All India Institute of Medical Sciences, New Delhi - 110 029
Source of Support: Nil., Conflict of Interest: There are no conflicts of interest.
The 2014–2015 Ebola epidemic is the largest in history, affecting multiple countries in West Africa. In late July 2014, the World Health Organization (WHO) declared the outbreak a Grade 3 emergency, its highest level of any emergency response. In early August, they declared it a public health emergency of international concern, meaning it is a serious public health event that endangers international public health. Indeed, by the end of September 2014, the United Nations stated the outbreak is “a threat to international peace and security.” Guinea located on the Atlantic coast of West Africa, is the first country in this geographical region in which an outbreak of Ebola virus disease has occurred. Cases having been confirmed in other countries include Guinea, Liberia, and Sierra Leone. There were a small number of cases reported in Nigeria and Mali and a single case reported in Senegal; however, these cases were contained with no further spread in these countries. Confirmed imported cases have occurred in the United States, Italy, Spain, and the United Kingdom. The WHO declared the end of the Ebola outbreak in Liberia on May 9, 2015 but on June 29, routine surveillance again detected a new confirmed case of Ebola in Liberia. On November 18, 2014, India has quarantined a man who was cured of Ebola in Liberia. As of August 21, 2015, the cumulative number of probable, suspected, and laboratory-confirmed cases attributed to Ebola virus (EBOV) is 28,036, including 11,301 deaths. Zaire EBOV strain has been identified as causative agent for 2014 Ebola epidemic.
Keywords: Disease outbreaks, Ebola virus disease, filovirus, Zaire Ebola virus
|How to cite this article:|
Goel V, Goel T, Kumar D. Ebola outbreak 2014-2015: An update
. MAMC J Med Sci 2015;1:118-25
| Introduction|| |
On March 23, 2014 World Health Organization's (WHO) African Regional Office reported on a new outbreak of Ebola virus (EBOV) (Zaire Ebola virus species [ZEV]), which began in December 2013 in the Republic of Guinea. Since then cases have been reported in five additional West African countries. The world woke up to the present outbreak with scare since it is one of the largest and most widespread outbreak with the possibility of natural disease transmission from the affected African countries which was never considered so seriously. In late July, the WHO declared the outbreak a Grade 3 emergency, and later on 8th August, a “public health emergency of international concern.” This is a legally binding international instrument on disease prevention, surveillance, control, and response., As an example, the decision to quarantine certain areas in West Africa has brought hardship to more than a million people but may be essential for containment. WHO released an update on November 12, 2014 that says the number of new cases is decreasing in the hardest-hit nation of Liberia and in Guinea, where the outbreak began. But the disease is further spreading in Sierra Leone. The virus is spreading either intensely or less rapidly, depending on the region. As of August 21, 2015, this outbreak has 28,036 reported cases resulting in 11,301 deaths. This article reviews the present knowledge about the epidemiology, ecology, disease manifestation, pathogenesis, and case management of Ebola fever.
| The Current Outbreak|| |
Guinea in West Africa is the first country to report an Ebola virus disease (EVD) outbreak with more than one case. The index case, a 2-year-old boy, a resident of Meliandou Village of Guéckédou, died on December 6, 2013. Three of his family members along with two healthcare workers who had come in contact with the index case had also died of EBOV infection. In spite of the first case being reported in December 2013, it was not reported to the WHO as Ebola until March 2014. This significant delay caused the virus to take hold in the community as sufficient control measures were not taken for a considerable time. The infection then spread to the neighbouring villages, and finally crossed the Guinea border and entered sequentially to neighbouring countries of Liberia, Sierra Leone, Nigeria, and Senegal., This is the largest Ebola outbreak ever reported, both in terms of case numbers and geographical spread. It is also the first time the disease has affected large cities. According to a WHO situation report released on November 12, 2014, transmission remains intense in Guinea, Liberia, and Sierra Leone, and case incidence is still increasing in Sierra Leone. The first EVD outbreaks occurred in remote Central African villages, near tropical rainforests, but the most recent outbreak in West Africa has involved major urban, as well as rural areas.
One of the growing international concerns is imported EVD cases possibility. One of the United Kingdom military workers in Sierra Leone while volunteering as a nurse tested positive for Ebola, was the first person in the world to be treated with the experimental Ebola drug MIL 77 and was released from hospital after making a full recovery. Similarly, an Italian health care worker who had been working at an Ebola treatment center in Sierra Leone was confirmed for Ebola virus. To date, countries having reported imported cases ex-West Africa: Nigeria, Senegal, Spain, United States, Italy, United Kingdom, and Mali. On November 18, 2014, India quarantined a man who was cured of Ebola in Liberia because of the possibility that he may spread the virus through sex. Although his blood samples were repeatedly found free of the disease, the deadly virus showed up in his semen. The outbreak has been controlled in Congo, a democratic republic which is unrelated to the West Africa outbreak. Nigeria, Senegal, and Liberia were declared free of Ebola on 20th October, 17th October and 9th May, 2015 respectively. As of June 29, routine surveillance again detected a new confirmed case of Ebola in Liberia. No active transmission is going on in Senegal, Nigeria, Spain, United States, Mali, United Kingdom, and Italy [Figure 1]. The United Nations (UN) has created a special mission to help contain the outbreak., This is the first time that the UN has created a mission for a public health emergency.
|Figure 1: 2014 Ebola outbreak in West Africa -Case counts (updated August 21, 2015). aGuinea, Sierra Leone have experienced widespread transmission but are transitioning to being declared free of Ebola. bOn May 13, 2015, Centers for Disease Control and Prevention changed the country classification for Liberia to a country with former widespread transmission and current, established control measures. cThere are currently no cases of Ebola in Senegal, Nigeria, Spain, the United States, Mali, the United Kingdom, and Italy|
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The 2014 Ebola outbreak in West Africa was described by the director general of the WHO on October 13, 2014, as "unquestionably the most severe acute public health emergency in modern times." Phylogenetic studies indicate Ebola 2014 outbreak is an independent zoonotic event as divergence from Central African strain had occurred at around a decade back in 2004, and have been circulating among the bat population in Guinea. In comparison to previous outbreaks, this outbreak differs in magnitude (past outbreaks had a few hundred cases) and its first ever appearance in West African countries (Guinea, Liberia, Sierra Leone, and Nigeria). The "Guinea strain" is a variant of the ZEV, but as such hemorrhagic manifestations are not as apparent this time around, leading to the use of the term EVD instead of Ebola hemorrhagic fever., It has caused significant mortality, with a reported case fatality rate (CFR) of about 71%.,
| Epidemiology|| |
The filoviruses were first recognized in 1967, in polio vaccine plant workers in Marburg, Germany when the inadvertent importation of infected monkeys from Uganda resulted in explosive outbreaks of severe illness who came into direct contact with the animals. The causative agent, designated Marburg virus, has caused a number of outbreaks in Africa, including one in Uganda that was recognized in the beginning of October 2014, and was declared over in November 2014.
The other genus, EBOV, was first identified in 1976 in Yambuku, a village near the Ebola river in Zaire from which the disease takes its name. Historically, EVD outbreaks often occurred in small villages close to or located in tropical rainforests. EVD in humans is caused by four of five viruses of the genus EBOV. Of the fourEBOVs, Bundibugyo virus, Sudan virus, Taï Forest virus, and EBOV (formerly ZEV), ZEV, is the most dangerous and is responsible for the largest number of outbreaks. The fifth virus, Reston virus, has caused disease in other primates. The virus causing the 2014 West African outbreak belongs to the Zaire species.,
| Viral Morphology|| |
EBOV and Marburg virus constitute the family Filoviridae in the order of Mononegavirales. Filoviruses are enveloped, nonsegmented, negative-stranded RNA viruses of varying morphology. Filovirus virions are bacilliform in shape, but particles can also appear as branched, circular, U or 6-shaped and long filamentous forms (Latin filum: Thread). EBOV particles have a uniform diameter of 80 nm but can greatly vary in length, with lengths up to 14,000 nm. The genome consists of seven genes in the order 3'-UTR-NP-VP35-VP40-GP-VP30-VP24-L-5'-UTR. Virulence factors and host responses, which seem to be partly detrimental to the host are still undermined in EBOV.
| Transmission|| |
As per popular misconception even in many health care workers, Ebola does not spread through the air, by water, or in general, by food. It is believed that the first patient becomes infected through contact with an infected animal, such as a fruit bat or primate (apes and monkeys), which is called a spillover event after which person-to-person transmission follows. However, in Africa, Ebola may be spread as a result of handling bushmeat (wild animals hunted for food) and contact with infected bats. There is no evidence that mosquitoes or other insects can transmit EBOV. When an infection occurs in humans, the virus can be spread to others through direct contact, blood or body fluids of a person who is sick with Ebola, virus contaminated needles and infected fruit bats or primates (apes and monkeys).,
EBOV has been found in the semen of some men and genetic material (RNA) from the virus by reverse transcription polymerase chain reaction (RT-PCR) had been identified 199 days after symptom onset. This is well beyond the period of virus detection in the survivor blood or recovery from illness. It appears that the amount of virus decreases over time and eventually leaves the semen. EBOV RNA has also been detected by RT-PCR in vaginal fluid from one woman 33 days after onset of symptoms. Investigations of several recent Ebola cases in West Africa have suggested sexual transmission from survivors but have not been confirmed.
| Ecology|| |
EVD is a classical zoonotic disease. The viral RNA PCR and serologic evidence suggests three species of fruit bats; Hypsignathus monstrosus, Epomops franqueti, and Monycteris torquata are the likely reservoir for EBOV.,, Spill over from bats is believed to cause outbreaks. Nonhuman primates that are susceptible to infection are regarded as the dead end hosts. Introduction into humans may have then occurred through exposures related to hunting and consumption of fruit bats, as has been suspected in EBOV outbreaks in Gabon. Besides this, the risk of virus replication and transmission increases due to alteration or scarcity of diet, as well as physiological conditions like pregnancy.
| Clinical Features|| |
After an incubation period of 2–21 days, the disease usually starts abruptly and is characterized by fever, chills, malaise, and myalgia. Abdominal pain is sometimes associated with hyperamylasaemia and true pancreatitis. Subsequent signs and symptoms indicate multisystem involvement like prostration, nausea, vomiting, abdominal pain, diarrhoea, chest pain, shortness of breath, cough, conjunctival injection, postural hypotension, oedema, headache, confusion, and coma. One of the differential features is the appearance of maculopapular rash associated with erythema at around 5–7 days of illness which later is followed by desquamation. In the end stage, metabolic disturbances, diffuse coagulopathy, and circulatory collapse may supervene.,
CFRs ranges from 70% to 90% for ZEV. Since in 2014 Ebola outbreak, no hemorrhagic manifestations were noted at the time of diagnosis in majority of the patients, the term "EVD" has been proposed instead of "Ebola hemorrhagic fever," which would help in early recognition of cases.,
| Pathogenesis|| |
The route of EBOV entry in the patient can be either through mucous membranes, breaks in the skin, or parenteral. After the virus enters it infects a variety of cells, including monocytes, macrophages, dendritic cells, endothelial cells, fibroblasts, hepatocytes, adrenal cortical cells, and epithelial cells. The incubation period may range from 6 to 10 days and may be related to the infection route. From the initial infection site, EBOV migrates to regional lymph nodes and subsequently to the liver, spleen, and adrenal gland. Lymphocytes undergo apoptosis resulting in decreased lymphocyte counts although not infected by EBOV. Hepatocellular necrosis, impairment of clotting factors and subsequent coagulopathy occur. Hypotension and impaired steroid synthesis can occur due to adrenocortical necrosis. EBOV appears to trigger a release of proinflammatory cytokines interferon (IFN)-γ, IFN-α, interleukin-2 (IL-2), IL-10, and tumor necrosis factor alpha with subsequent vascular leak and impairment of clotting ultimately resulting in multiorgan failure and shock.,,
| Diagnosis|| |
The Centers for Disease Control and Prevention (CDC) case definition for possible EVD is: (1) Elevated body temperature or subjective fever or symptoms, including severe headache, fatigue, muscle pain, vomiting, diarrhoea, abdominal pain, or unexplained hemorrhage; and (2) an epidemiologic risk factor such as contact with a symptomatic Ebola-infected patient within the 21 days before the onset of symptoms. Relevant epidemiological history is necessary to distinguish EVD from other infectious diseases such as malaria, typhoid fever, leptospirosis, relapsing fever, anthrax, chikungunya, yellow fever, and meningitis. In endemic countries, classical epidemiological history like travel to jungle, eating or hunting of bats or animals, and exposure to cave, close contact with sick patients or dead bodies helps in clinching the suspicion for EBOV infection. In nonendemic countries, patient with a history of travel to endemic countries or outbreak affected localities should be suspected for EBOV infection.
In laboratories where diagnostic testing is carried out, biosafety level 4-equivalent containment is required. Nonspecific laboratory indicators include low white blood cell and platelet counts and elevated liver enzymes. International normalized ratio and partial thromboplastin time prolongation is well-described in previous reports of Ebola infection, although these derangements have not been reported as a major feature in the 2014 West African outbreak.
Laboratory diagnosis is performed only in designated national and international laboratories. For antibody detection, blood/serum samples are either gamma eradiated or heat inactivated, whereas for nucleic acid detection, RNA isolation from clinical material can be done by treating with guanidium isothiocyanate that degrades the viral protein and makes the sample noninfectious.
The diagnostic tests employed at various stage of illness are described in [Table 1]. Negative serology test does not rule out the possibility of infection, as patient with the severe fatal infection may not mount any antibody response. Confirmatory tests include Western blot and indirect immunofluorescence assay on acetone-fixed infected cells inactivated by gamma radiation.
Multiplex PCR and micro-array-based tests have also been developed but only available in specialized centers. Many new in vitro diagnostics platforms have been approved like RealStar Filovirus Screen PT-PCR Kit 1.1 (detects filovirus-specific RNA using QIAamp Viral RNA Kit), ReEBOV Antigen Rapid Test Kit (detect Ebola matrix protein VP40 for RNA extraction), Xpert ® Ebola Assay (RT-PCR assay with extraction and amplification in the cartridge itself).
A point-of-care EVD test (ReEBOV Antigen Rapid Test; Corgenix) with 100% sensitivity and 92% specificity is faster than and as sensitive as a conventional laboratory-based molecular method used for clinical testing can accurately predict within minutes if an individual has EVD.
As the primary mode of person-to-person transmission is contact with contaminated blood, secretions or body fluids, people who have had close physical contact with patients should be kept under strict surveillance. Their body temperature should be checked twice a day, with immediate hospitalization and strict isolation in case of the onset of fever. Male Ebola survivors should be offered semen testing at 3 months after disease onset, and then, for those who test positive, every month thereafter until their semen tests negative for virus twice by RT-PCR, with an interval of 1-week between tests. Survivors who are potentially infected with EBOV should be quarantined for 21 days. WHO does not recommend any travel or trade restrictions be applied except in cases where individuals have been confirmed, suspected of being infected or had contact with cases of EVD.
| Treatment|| |
Management of patient is mainly supportive and symptomatic treatment which constitutes rehydration with oral and intravenous fluids, broad spectrum antibiotics, and management of organ failure. Currently no prophylactic or therapeutic vaccines are approved.,, Many experimental treatment modalities are summarized in [Table 2]. An oral nucleotide analog, brincidofovir, was authorized by the Food and Drug Administration for emergency use in patients with Ebola infection on October 6, 2014, after activity against EBOV in vitro was demonstrated. WHO meeting on September 4 and 5, 2014 to identify novel therapies prioritized convalescent whole blood or plasma infusion, ZMapp (a cocktail of three monoclonal antibodies), and TKM-Ebola (an interfering RNA molecule used to block expression of two viral replication genes).,
| Vaccine Development|| |
Despite ongoing research in this field, no approved vaccines are available to prevent the spread of EBOV., Promising vaccines under various clinical trial phases are those that are derived from adenoviruses, filovirus-like particles or vesicular stomatitis Indiana virus as these are well known to provide protection in nonhuman primates. The WHO expert panel that convened in September 2014 has identified the ChAd3 (GlaxoSmithKline) and rVSV (NewLink Genetics and Merck) vaccines as the most advanced candidates for use in the West African outbreak. Both have been shown to be safe and well-tolerated in humans in Phase I clinical trials. The Sierra Leone trial to introduce a vaccine (STRIVE) is combined Phase 2 and 3 clinical trial designed to assess the safety and efficacy of the rVSV-ZEBOV or vesicular stomatitis virus ZEV vaccine. Other candidate vaccines in development include recombinant influenza candidate Ebola vaccine (Russian Federal Ministry of Health [MoH]), an oral adenovirus candidate (Vaxart), vesicular stomatitis virus candidate (Profectus Biosciences), a DNA vaccine (Inovia), and a recombinant rabies vaccine (Jefferson University).
| Preventing Transmission|| |
CDC and WHO recommendations include isolation of hospitalized patients with known or suspected EVD; hand hygiene; the use of standard, contact, and droplet precautions; and the correct use of appropriate personal protective equipment (PPE).,, If possible, aerosol-generating procedures should be avoided.
To avoid direct contact with blood and other body fluids of the patients with viral hemorrhagic fevers, "barrier nursing" using face shields (or goggles), masks, rubber gloves, etc., is recommended. Raising awareness of risk factors by community engagement and protective measures that individuals can take is an effective way to reduce human transmission. Animal products including meat should be thoroughly cooked before consumption. Outbreak containment measures including immediate safe burial of the dead, identifying people who may have been in contact with someone infected with Ebola, monitoring the health of contacts for 21 days, separating healthy from the sick, and careful personal hygiene.
For Ebola outbreak preparedness in resource-limited countries a sustainable low cost, energy efficient, and health facility design using natural ventilation (NATVENT) for control of infection is recommended by WHO. WHO has designed wards for infectious diseases in Sierra Leone to manage patients with severe infectious diseases safely based on NATVENT technology.
| Role of International Agencies in Ebola Response|| |
CDC, along with others (the United States, Government agencies, the WHO, and international partners), is taking active steps to respond to the Ebola outbreak in West Africa. CDC activated its Emergency Operations Center to help coordinate technical assistance and disease control activities with partners. Thousands of CDC staff members have provided logistics, staffing, communication, analytics, management, and other support functions for the response. CDC personnel are deployed to West Africa to assist with response efforts, including surveillance, contact tracing, data management, laboratory testing, and health education. CDC experts have been deployed to nonaffected border countries to conduct assessments of Ebola preparedness in those countries.
Most of the time, outbreaks are managed by the WHO's International Committee on Scientific and Technical Coordination. WHO strategic Ebola response plan 2015 has been:
- Stop transmission of the EBOV in all affected countries
- Prevent new outbreaks of the EBOV in new areas and countries including a high level of vigilance for imported cases
- Safely reactivate essential health services
- Fast-track Ebola research and development especially of better therapies and vaccines
- Coordinate national and international Ebola response including training and support member states for the implementation of national capacities for epidemic preparedness and response in the context of the International Health Regulations (2005), including laboratory capacities and early warning alert and response systems.
Médecins Sans Frontières (MSF) West Africa Ebola response started in March 2014 and includes activities in Guinea, Liberia, and Sierra Leone. Around 9600 patients were admitted to MSF Ebola management centres and 5149 patients confirmed with Ebola while 2425 patients recovered from at its center.
| Maintaining Commitment and Preparedness-Everywhere|| |
Low-income countries in Africa, as well as governmental and research institutions are not adequately equipped in diagnostics, active reporting, tracking, prompt healthcare facilities and accessible, and affordable treatment to combat the Ebola infection. Though cities with an international airport are theoretically at risk of an imported case, the need for preparedness is the greatest in countries that share boundaries or have extensive travel and trade relations with the hardest-hit countries. Countries requiring the greatest need for preparedness are with weak public health infrastructures and little or no diagnostic capacity to detect cases early. WHO has developed a comprehensive “event management system” to prepare better, respond faster, and manage resources more effectively in case of outbreaks like Ebola and ensure accurate and timely communications between key international public health professionals and other collaborating partners in the Global Outbreak Alert and Response Network (GOARN). A public health surveillance and the alert system should be in place at healthcare facilities, border crossings with affected countries, including at land crossings, seaports, and airports.
| Ebola in Indian Perspective|| |
There are close to 45,000 Indians in the affected countries. There are fears that the virus will spread unchecked if it arrives in India, so efforts are being made to spread awareness and reduce panic. However, in India, with its huge population, dense population in cities and poor sanitation in many areas could pose a challenge if any cases did arrive, as it is harder to isolate patients and trace their contacts for observation. These elements could make containing Ebola cases more challenging than in some other countries. India with its large number of epidemiologists, laboratory scientists, doctors, and nurses who are experienced in epidemic control can help support the diagnosis, the training of health workers, or clinical services in Ebola treatment units.
The Government of India (GOI) has seriously considered EVD treatment and has heightened surveillance and tracking systems at both national and state levels for early detection of cases. All states and union territory (UT) administrations are being requested to identify nodal officers and designate hospitals with isolation wards for responding to any possible cases. International airports have been put on high alert, and passengers are being asked about travel to affected countries, with facilities made available for quarantine and isolation of suspected cases. Capacity building of health care workers is underway, and various guidelines have been developed. The MoH in collaboration with WHO, India Office is preparing a comprehensive contingency plan for EVD. As an additional precaution while WHO recommends 21 days of observation from the last day that person came in contact with Ebola patient, MoH and Family Welfare (FW), GOI recommends 30 days of observation advisory for families staying and travellers visiting/returning after visiting West African countries affected with EVD.
GOI has taken a proactive stand to control EVD. India is among the top five financial contributors to the UNs' Ebola response. Also, IEC material (tri-fold pamphlets) is being prepared for travellers and health care providers. For capacity building of health care workers training courses were organized for master trainers and rapid response team of states/UTs including lectures, demonstrations of putting on (donning) and removing (doffing) PPE, collection, packaging and transportation of samples, and mock drills at points of entry.,
The MoH and FW, GOI, has issued several guidelines for effective management of the situation in case the virus gets entry into the country. Testing is currently performed at the National Institute of Virology, Pune and the National Centre for Disease Control, Delhi. All hospitals have been asked to be prepared in case of an outbreak. It is expected that the preventive measures will ensure the safety of our population as has been seen effectively during the localized outbreaks of Crimean Congo hemorrhagic fever and avian influenza.
| Conclusion|| |
The 2014 Ebola epidemic is the largest in history, affecting multiple countries in West Africa. The causative agent has now been identified as an outlier strain of ZEV. A multipronged comprehensive approach including international coordination and surveillance, supporting the societies and economies, and a well-functioning responsive public health system is needed for the EBOV outbreak prevention.
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Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2]