| Abstract|| |
Background: The recent Ebola outbreak notified in West Africa recorded 6,553 cases and 3,083 deaths till 30th September 2014. This is the longest reported outbreak, suggesting poor preparedness and inadequate public health response. Learning from these experiences can help taking future disease-control measures in West Africa and elsewhere. Materials and Methods: This scoping study was done to summarize a range of evidences available on the current “Ebola Viral Disease” (EVD) outbreak. All articles in English language related to the epidemiology of Ebola in humans, published between 1st March and 30th September 2014, were considered for review. Search engines, such as PubMed and Google Scholar, were used to search for the following keywords: “Ebola,” “Ebola Virus,” “Ebola Viral Disease,” and “Ebola Hemorrhagic Fever.” Snowballing using cross-references was done to find related literature on EVD. Related websites, blogs, and published news articles were reviewed. Studies of varying designs were considered without any quality assessment. Results: This is the first ever Ebola outbreak affecting large urban communities. Factors that worsened the outbreak were as follows: Weak health systems, unfavorable cultural practices, poverty, illiteracy, mistrust for the government, extensive cross-border movement, slow response from international agencies, and lack of tested treatment and prevention strategies. Simple measures of universal precaution, isolation and tracking of contacts, supportive treatment, and appropriate burial practices were difficult to implement. Conclusions: The outbreak in West Africa illustrates serious weaknesses in the ability of the international communities to respond to these outbreaks. Cost of setting up an infrastructure for early effective response is insignificant compared to the huge social and economic cost of the outbreak. Strong health system, improved preparedness, and effective community participation are imperative for control.
Keywords: Ebola, lessons, outbreak, scoping
|How to cite this article:|
Bhatnagar N, Grover M, Kotwal A, Chauhan H. Study of recent Ebola virus outbreak and lessons learned: A scoping study. Ann Trop Med Public Health 2016;9:145-51
|How to cite this URL:|
Bhatnagar N, Grover M, Kotwal A, Chauhan H. Study of recent Ebola virus outbreak and lessons learned: A scoping study. Ann Trop Med Public Health [serial online] 2016 [cited 2017 Mar 30];9:145-51. Available from: http://www.atmph.org/text.asp?2016/9/3/145/181658
| Introduction|| |
First recognized near Ebola River valley during an outbreak in Zaire in 1976, intermittent outbreaks of Ebola Virus Disease (EVD) have occurred in remote areas of Central Africa in ensuing 27 years, with mortality rates ranging from 50% to 90% The recent EVD outbreak was notified on 13th March 2014 in Guinea with the disease confined to three districts, causing 49 cases and 29 deaths. The outbreak continued to affect defined area for nearly a month before spreading to the bordering districts and Liberia. A large number of cases were reported with no access to the basic treatment measures due to debilitated health-care systems and already fatigued, scarce health workers. the epidemic continued to peak till November spreading globally to developed parts of the world in September and October. Extent and rate of spread of disease warranted United Nations Security Council to adopt resolution on 18th September, declaring outbreak a “threat to international peace and security” with a military type of response needed for control. This unprecedented nature of the current outbreak warrants understanding of the epidemiology and lacunas in counter measures initiated to aid in future disease control measures.
| Materials and Methods|| |
Scoping studies (or scoping reviews) represent an increasingly popular approach of reviewing health research evidence. It is a process of summarizing a range of evidences in order to convey the breadth and depth of a field. Authors conducted a scoping study of recent EVD outbreak to examine the extent, range, and nature of research activity published. Search engines, such as PubMed and Google Scholar, were used to search for the following keywords: “Ebola,” “Ebola Virus,” “Ebola Viral Disease,” and “Ebola Hemorrhagic Fever.”. All the articles related to epidemiology and control of recent Ebola outbreak published from 1st March 2014 to 30th September 2014 on humans in English language were considered for review. The date filters were added to have studies focused on the current outbreak. Snowballing using cross-references was done to find the related literature on EVD. The websites of the Center for Disease Control, Atlanta and the World Health Organization (WHO), African Region were used to track outbreak. Blogs and news articles published on Ebola were also reviewed. Studies of varying designs were considered without any quality assessment. The aim was to comprehensively document the epidemiology of outbreak, control measures initiated, and lacunas in outbreak control.
A total of 148 articles were found in PubMed out of which 128 were considered for detailed review. In Google Scholar using similar search strategy, out of 30 additional articles 14 were considered relevant for the present study. Articles on other viral hemorrhagic fevers, infection control practices, and molecular and biochemical studies of Ebola virus were not included in the review. After the review of 142 articles from PubMed and Google Scholar, 58 comprehensive articles were selected and the rest were excluded on the basis of theoretical saturation of the published material [Figure 1].
| Results|| |
The major part of review content included news, editorial, comments, letters, and case reports published during the period of outbreak. Other articles (20 in PubMed and 10 in Google Scholar) were published on disease modeling, testing of treatment modalities, and review of current Ebola outbreak comparing it with the previous outbreaks. This article attempts to comprehensively review the recent Ebola outbreak.
Detection and progress of the outbreak
The epidemic was detected in March and continued in April with nearly 226 cases and 149 deaths involving 6 districts in Guinea and Liberia. At the end of May, the cases in Guinea surged along with one district in each of Liberia and Sierra Leone. In the months of June and July, the cases in Sierra Leone increased, along with continued reporting of cases and deaths from other affected parts. In August, the outbreak spread in five countries of West Africa (Guinea, Liberia, Sierra Leone, Nigeria, and Senegal) along with an epidemiologically unlinked outbreak in Democratic Republic of Congo., On 8 August, the WHO declared this epidemic to be a Public Health Emergency of International Concern (PHEIC) – only third disease to be declared so after H1N1 in 2009 and Polio in 2014. In September, the outbreak was spread in the densely populated Nigerian city of Lagos that raised concerns as this was a densely populated city with population roughly equivalent to that of Guinea, Sierra Leone, and Liberia combined., The arrival of Ebola in the developed world was certified with a case being detected in the USA. Till 30th September 2014, 6,553 (probable, suspect, and confirmed) cases and 3,083 deaths were reported. Assuming no significant change in control measures, cumulative reported numbers of confirmed and probable cases was predicted to be 5,740 in Guinea, 9,890 in Liberia, and 5,000 in Sierra Leone, exceeding 20,000 in total by November. The epidemiological modeling by Meltzer et al. stated that if 70% patients are appropriately managed by December 2014, then epidemic is likely to end by 20 January 2015 restricting the outbreak to maximum of 27,000 cases that could otherwise impact 1.4 million lives., With the doubling time of outbreak ranging from 15 days to 30.2 days, West Africa is likely to turn into an endemic zone for Ebola that will continue transmission in future.
Epidemiological triad for the current outbreak
Ebola virus is an agent here in the epidemiology of disease transmission and belongs to the larger group of Filoviradae. Ebola-virus genus is comprised of five species: Zaire, Sudan, Taı¨ Forest, Bundibugyo, and Reston, each associated with consistent case fatality and well-identified endemic area. The current outbreak is caused by Zaire species of Ebola virus, the most lethal subtype is classified as Category A bio-terrorism agent by the Center for Disease Control and Prevention.,
Bats are the sources of high viral diversity and high-profile zoonotic viruses worldwide. The probable natural hosts for the disease are fruit bats, particularly species of the genera Hypsignathus monstrosus, Epomops franqueti, and Myonycteris torquata. Unknown transmission cycle that exists within bats are considered as reservoir of virus. Ebola virus is set to persist in reservoirs of endemic areas. There is a need to assess the circulation of virus in bats of Guinean forest. A total of 276 bats were tested in Bangladesh. Five (3.5%) bats were positive for antibodies against Ebola Zaire and Reston viruses; however, no virus was detected by polymerase chain reaction (PCR). These bats might be a reservoir for Ebola or Ebola-like viruses, and extend the range of filoviruses to mainland Asia. Thus there is a felt need of a unified, global surveillance strategy for filoviruses and multi-disciplinary approaches to understand dynamics in bat populations to prevent such devastating disease outbreaks.
Cowling et al. found that lower temperature and higher absolute humidity associated with EVD outbreak. The chain of transmission involves humans, apes and other mammalian species developing severe disease and working as end hosts. They acquire infection by accidental exposure of virus through consumption of plants or water contaminated with bat secretion or bodily fluids. Moreover, it has been reported that virus's genome is changing frequently even in the current outbreak and it is important to track such changes as this forms the basis of treatment and prevention modalities. Ninety genomes from 78 Ebola patients were analyzed by Gire et al. Ho observed rapid accumulation of inter-host and intra-host genetic variation. This West African variant diverged from central African lineages around 2004, and had sustained human-to-human transmission, with no evidence of additional zoonotic sources.
Ebola virus multiplies in all cells including endothelial cells, macrophages and parenchymal cells. These antigens cause direct damage and surge of cytokines that renders IFN ineffective which further intensify the severity of illness. Clinical improvement occurs when viral antibodies are formed and their titer increase in blood along with a drop of antigen levels. In fatal cases this response has been reported to be inhibited with extensive spleen and lymph node damage. EVD has short 14-21 day course whereby it starts with mild fever and myalgia, quickly progressing to death due to bleeding disorders. The long incubation period of 2-21 days (11.1 days in the current outbreak) results in clinical signs and symptoms developing late in the course of disease. Early signs are similar to any viral hemorrhagic fever with appearance of maculo-papular rash in nearly 50% of cases. Bleeding through mouth, puncture sites and reddening of eyes are early symptoms with poor prognosis.
Human to human transmission through body secretions is the only mode of transmission known till date. The infectious dose is less than ten viral particles. Exposures such as per-cutaneous, mucous membrane exposure or direct skin contact with body fluids of person with a confirmed or suspected EVD without appropriate personal protective equipment (PPE), makes an individual susceptible to disease. Men who have recovered from the disease can continue to transmit the virus in semen for nearly 7 weeks after recovery. Confirmed case is a case with signs and symptoms of Ebola the laboratory confirmed diagnostic evidence of Ebola virus infection by any one of following: Immunoglobulin M (IgM) [enzyme-linked immunosorbent assay (ELISA)], antigen detection and reverse transcription PCR (RT-PCR).
Factors favoring spread of current outbreak
Geographical isolation of communities involved in previous outbreaks and limited scope of spread had eased the process of outbreak curtailment by authorities earlier. However, in current outbreak, for the first time EBV invaded a large habitation, spreading to the densely populated capital city of West African country (Conakry, Guinea)., The possible reasons for continued transmission are as follows:
- Weak public health systems in the affected countries: Despite all affected countries being signatories to International Health Regulations (2005), limited progress has been made to build and maintain core epidemiological and laboratory capacities to detect and respond to the diseases. This resulted in large number of health-care workers acquiring infection due to the lack of availability or knowledge of PPE available. Dr. Sheikh Humarr Khan, a dedicated physician and researcher on viral hemorrhagic diseases, died in early days of EVD outbreak. Similarly, Dr. Brisbane and his dedicated team members succumbed to disease at the John F Kennedy Memorial Center in Monrovia due to poor isolation facilities in the hospital. In fact, many such tragedies went undocumented. For most health workers who survived, unexpected long course of outbreak further fatigued them. Supplementing ailing health system even with basic supplies and man power required enormous and robust response and resources were deficit by 46%. On 1 August, the international community launched a US $100 million plan to scale up the efforts to stem the outbreak. The World Bank offered $200 million emergency funding to help effected countries contain the outbreak.
- Poverty: A majority of population depend upon bush meat as a source of protein in the diet. The handling of bush meat and it's transport across the borders has been proposed as a possible means of introducing virus in the population.
- The migration of fruit bats, considered as reservoir of virus due to human interference in the central African region, has been proposed as a reason for shift of foci of outbreak to West Africa.
- Unfavorable cultural practices and traditional beliefs exist such as customary washing, touching, and kissing of dead bodies to ward off evil spirits. This along with inadequate disposal of dead bodies contributed to rapid spread of infection. This was in direct opposition to measures suggested by the WHO to control the spread of outbreak: Whereby only trained personnel wearing PPE should handle remains during the outbreak and remains should be wrapped in sealed and leakproof material and buried promptly.,
- Mistrust for the government and NGOs: A high level of illiteracy meant that the messages disseminated by responders did not meet their purported objectives. Initial belief of people was that governments are trying to inflate the number of cases and deaths to procure international aid. This resulted in resistance to adopt recommended public health preventive measures and a poor health-seeking behavior. High case fatality fuelled a misunderstanding that being taken away by medical teams to treatment centers means certain death. This made isolation of infected persons extremely difficult and favored the spread of the disease.
- Extensive movement across borders of homogenous community for trade and socialization facilitated rapid spread of infection. This further complicated the process of contact tracing with several contacts loss to follow up. Travel bans were likely ineffective in stopping cross-border journeys on secondary roads, and bush meat was available in the local markets and villages, even if the demand decreased. Policies developed (and the ways that they were communicated) by the authorities raised anxiety and fuelled rumors in the community that led to counterproductive behaviors.
- Slow response by national and international agencies: Adequate, timely response by the international community was lacking. Nearly 3 months were taken between first case reported and disease being confirmed. In another 5 months 1,000 deaths occurred before the WHO declared this to be a public health emergency. Delayed, inadequate response measures gave the virus a leeway to spread. Moreover, adequate response measures must be initiated at the health centers to immediately identify patient suffering from Ebola through symptom and travel history and thereby putting him in isolation. Losing the patient in the first contact can spread the disease further in the community.
- Moreover, with only experimental vaccines or medicines currently available and that too in very limited quantities, our preparedness is grossly insufficient to deal with such a dangerous potential pandemic.
Proposed public health measures
Vague understanding of disease epidemiology especially at field level made risk assessment and response measures difficult. Considering the mode of transmission of disease, immediate priorities for control are early diagnosis with patient isolation, contact tracing, strict adherence to biosafety guidelines in laboratories, barrier nursing procedures, use of PPE by health-care workers, disinfection of contaminated objects, and safe burials., Gloves, gowns, goggles, and a fluid resistant face mask to cover the nose and mouth are generally adequate for PPE. If copious amounts of blood, emesis, or diarrhea are present, higher levels of PPE, e.g., double gloving, shoe, and leg covers are recommended.
Along with effective use of PPE, effective tracking of Ebola patients and contacts is warranted. Centers for Disease Control, Atlanta developed tool to track contacts and manage outbreak. The Field Management Information System enables workers to map contacts geographically. It tracked relationships between patients and contacts, automatically generated reports and created diagrams to show disease transmission.
Tracking of cases need to be followed up with management of Ebola affected patients in isolation centers. Isolation centers for Ebola in the outbreak effected Sierra Leone had the low-risk area, containing pharmacy, dressing rooms, laundry, laboratory, water-chlorination points, and staff meeting area; and high-risk area, where patients are admitted and staff needed full PPE.,
The disease is detected through ELISA early in the course of disease and through antibody assay late in the course of the disease. The treatment of the disease has not undergone human safety trials but some hold promising solutions. Still, the use of experimental treatment modalities was introduced along with several ethical considerations., ZMapp contains antibodies against three Ebola virus glycoprotein epitopes  and TKM-Ebola, made by an “interfering” RNA molecule to silence expression of genes that virus needs to replicate. TKM-Ebola is the only treatment modality that entered Phase 1 trial, later halted by the Food and Drug Administration (FDA). Vaccine candidate, ChAd-EBO made by GlaxoSmithKline (GSK), uses chimpanzee adenovirus to deliver Ebola gene that codes for an immunity-provoking antigen. All animals given the vaccine were protected after inoculation of a lethal dose of the Ebola virus. The second vaccine, VSV-EBO, originally developed in Canada and currently licensed to a US company, NewLink Genetics, uses a vesicular stomatitis virus to deliver Ebola antigens. Animals that were given the vaccine were all protected against the Ebola virus, when they received the vaccine 21 days before the infection. Moreover, they were not intended to be used for population based approach e.g. health-care workers in the field are likely to be the prime candidates. Required stock of vaccines is expected to be available only by November-December. Favipiravir is a candidate drug with successful animal trials in laboratory. Use of drugs, such as Interferon, Statins, ACE Inhibitors, and Angiotensin receptor blockers are encouraged to modulate the body response to the viral agent and contain damage. Along with the list of experimental treatment modalities available there is a need of timely administering the treatment as significant delay that is noted in many cases. Moreover, these experimental drugs can undergo small-scale trials for safety and efficacy in which people with Ebola receive treatment in an organized manner and outcomes are systematically recorded. Experimental vaccines are also proposed to undergo step wedge trial that analyzes what happens to people at similar risk who receive vaccine at different times. The way those who are vaccinated can be compared with those who are yet to receive a shot. But this process has its own limitations. Lamontagne et al. has documented the need to better utilize intravenous catheters, fluids, and electrolyte replacement therapies that are readily available, but used sparingly. Simple supportive interventions can prevent deaths attributable to hypovolemia and metabolic abnormalities. Current outbreak has reemphasized the need of trained primary care workers over more qualified specialists.
| Conclusion|| |
Well-coordinated international response is warranted during an outbreak. In the current outbreak, international response was delayed due to chronic underfunding of the WHO and inability to mount an adequate initial response to manage the outbreak. There needs to be a clear thinking on how does the world responds to such a disaster.,
The lack of vaccines and medications for Ebola virus disease is an evidence that markets cannot reliably supply treatments for epidemic diseases and rather governments should equip themselves well. Strong health system and improved preparedness (Epidemiological and Lab core capacities) at the site of outbreak is required. Improved and sensitive communication by health officials with the media, community leaders, health professionals, and general public is necessary to reduce misinformation and improve compliance with prevention and control measures have been proven effective.,
West Africa outbreak illustrates serious weaknesses in the international community ability to respond to outbreaks. It is now necessary to hammer home a truism that the cost of setting up an infrastructure for early effective response is small compared to the huge social and economic cost of the deadly outbreak. Even when the understanding of disease epidemiology is not crystal clear, simple supportive interventions, provided timely and efficiently, can compensate for the lack of effective vaccines or antimicrobials. Some of these lessons are universal and can be applied in future to control epidemics anywhere in the world.
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Conflicts of interest
Authors declare no competing financial interests.
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Nidhi Bhatnagar, Department of Community Medicine, Army College of Medical Sciences, Delhi Cantonment, New Delhi
Source of Support: None, Conflict of Interest: None