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Confronting Ebola at its Origins: GVN Member, The South African National Institute for Communicable Diseases, Deploys their Mobile Diagnostic Laboratory to Sierra Leone Prof. dr hab. Janusz T. Paweska & Dr. Petrus Jansen van Vuren Centre for Emerging and Zoonotic Disease of the National Institute for Communicable Diseases, Johannesburg, South Africa The 2014/15 outbreak of Ebola virus disease is the largest ever reported of this deadly, highly infectious, hemorrhagic disease since its initial discovery in humans in 1976. The current outbreak was first recognized in March, 2014 in Guinea and has since crossed international boundaries into Sierra Leone and Liberia where case numbers have now surpassed those recorded in the country of origin. Due to international travel of infected individuals, both medical professionals and non-professionals, the virus has also been introduced and caused smaller outbreaks in Mali, Nigeria, Spain and the United States. A worldwide response was launched. Like the infectious agent, this approach crosses interdisciplinary, geographical, cultural and socio-political boundaries and includes research, professional and public education, clinical care and respectful, safe disposition of the remains of those who died from the illness. In this paper, we aim to reduce fears of the unknown and encourage continued efforts to conquer the epidemic by describing the nature of the infectious agent, by providing a brief overview of its history, scope, and impact and by detailing a specific response that is being used to confront Ebola at its source. What Is EBOLA? Ebola is a short hand name for a group of viral infections caused by more than one type (species) of virus from the same origin (genus). In the early stages of infection, the patient has no symptoms and cannot transmit the disease to others. However, within 4 to 21 days after exposure, the patient develops a fever over 101 (F) and can then transmit the virus to others. Flu-like symptoms rapidly progress to severe vomiting and diarrhea with internal and external bleeding of a hemorrhagic nature. The likelihood of death is high with or without treatment with a mortality rate of approximately 30% to 90% depending on the specific viral infection. The virus is transmitted in body fluids and secretions including blood, sweat, urine, vomit, stool, tears, saliva, and mucous which puts family members, friends with close personal contact, caregivers, laboratory personnel, sanitation workers and funeral personnel at high, but not insurmountable, risk for infection. Understanding the nature of the virus spread aids in reducing fear and enhancing safe practices. Ebola viruses The ebola viruses belong to a family called Filoviridae. The Filoviridae family consists of two genera, Ebolavirus and Marburgvirus that comprise some of the most virulent pathogens known to humans. The genus Ebolavirus is divided into five species: Zaïre, Sudan, Taï Forest, Bundibugyo, and Reston ebolavirus. Four of these five species are known to cause disease in humans: Zaïre, Sudan, Taï Forest and Bundibugyo ebolavirus. The most virulent is the Zaïre ebolavirus, with case fatality rate (CFR) up to 90 percent, followed by Sudan ebolavirus (CFR: ~50%), and Bundibugyo ebolavirus (CFR: ~30%). Only a single known human infection with Taï Forest ebolavirus has been recorded, which caused a less severe non-fatal disease. Reston ebolavirus was discovered in monkeys used in research facilities, imported from the Philippines, but has not been shown to cause any disease in humans. FAMILY Genus Species Causes Human Fatality disease? Ebolavirus Filoviridae Marburgvirus Zaïre ebolavirus Yes <90% Sudan ebolavirus Yes ~50% Taï Forest ebolavirus Yes 0%* Bundibugyo ebolavirus Yes ~30% Reston ebolavirus No Marburg marburgvirus Yes <90% Ravn marburgvirus Yes unkn** * Only a single non-fatal case has been recorded ** In the only large outbreak where Ravn virus was involved, it was co-circulating with Marburg marburvirus thus the fatality rate could not be established. Fatality rate is presumably the same as for Marburg marburgvirus as these two are also clinically indistinguishable Current available sequence analysis data of 99 Zaïre ebolavirus (ZEBOV) genomes from 78 patients in Sierra Leone indicates that the 2014 West African genetic variant likely diverged from central African lineages about 10 years ago. It appears that a single animal-to-human transmission of the ZEBOV occurred in December 2013 in the deep-forest area of south-eastern Guinea. Since then, human-to-human transmission accounts for the continuing and widespread infection throughout Guinea, Liberia, and Sierra Leone. Many of the identified virus genome sequence differences compared to previously known strains alter protein sequences and other biological targets. Thus, they should be monitored for their impact on diagnostics, vaccines, and therapies that are critical to an effective outbreak response. It is not clear whether the virulence or transmissibility of the 2014 ZEBOV in West Africa is substantially different from the virus lineages associated with earlier outbreaks. The greater spread and apparent lower CFR of the current outbreak may be caused either by factors external to, or inherent virulence of the virus. Such factors include population density and medical care in some affected areas that is more effective than in the remote villages affected in earlier EVD outbreaks. Scope and Impact of Ebola Virus Disease The 2014 Ebola virus disease (EVD) epidemic in Western Africa caused by Zaire ebolavirus (ZEBOV) is the largest in the recorded history of both the disease and public health control efforts. The EVD outbreak, only officially recognized in March 2014, rapidly became the deadliest occurrence of the disease since its discovery in 1976. As of 20 January 2015, (at the time of writing) the World Health Organization (WHO) reported a total number of 21 689 cases in Guinea, Sierra Leone, Liberia, Mali, Nigeria, Spain and the United States of America, of which 8626 were fatal infections. Currently there is only documented active transmission in the three worst affected countries of Guinea, Sierra Leone and Liberia. There are at least two EVD outbreak-related concerns. First, if the virus were to spread to a large city in one of the countries with modest health care infrastructures and crowded, sub-standard living conditions (slums), the scale of the outbreak would substantially enlarge. This already seems to be the case, as exemplified by high number of cases in Monrovia, Liberia and Freetown, Sierra Leone. Secondly, the spread of ZEBOV to large and densely populated cities with limited health care resources may increase the likelihood of a change or mutation of the virus -- the evolutionary trajectory of the virus such as a change of ZEBOV shedding patterns and/or virulence. For these and other reasons, there is a need for a continued rapid, coordinated, and properly matched international response to stop the epidemic. Vulnerable Populations Because the Ebola virus is carried in body fluids, anyone who has even minor or minimal physical contact with the secretions of a symptomatic, infected person is at high risk for contracting the disease. This includes family members and friends who come in close physical contact with the patient, healthcare workers, laboratory personnel, sanitation workers and those preparing the deceased for burial or other disposal. The vulnerability of health-care workers in contracting EVD is particularly tragic. By 15 January 2015, 825 cases among medical staff in the three West African countries and 493 deaths were reported by the WHO. This occurs in the backdrop of countries with severely understaffed medical systems, thus even further decreasing the ability to properly care for and isolate infected individuals, and putting those doctors and nurses left at higher risk by forcing them to work longer hours. The figures are likely underestimates, given the difficulty in collecting the data. The current epidemic, which most likely began in late 2013 in Guinea, reached historic proportions in the middle of 2014. When the virus entered large cities, it quickly outmatched the health-care systems in West Africa and outraced the response from the global health community. The fact that EVD cases were imported into urban areas from the original EVD epidemic boundaries, coupled with global travel and trade, raises concerns that the outbreak can extend around the world. Concerns for public health safety are magnified because, at this time, we lack specific therapies and vaccines for EVD. Confronting EBOLA: The Problem and a Practical Response It has been difficult to track the current EVD outbreak due to a short supply of specialized laboratories capable of conducting research and handling potentially infected blood samples from EVD suspected cases in West Africa. The laboratories are essential to diagnosing and treating patients. Undiagnosed and unmanaged patients pose a severe risk to families and communities and contribute to the cyclical transmission pattern currently being seen. That interrupting chains of Ebola virus transmission depends heavily on laboratory support cannot be overstated. This support is needed not only to confirm or discard suspected cases, but also guide triage and clinical decisions, aid contact tracing, and facilitate the early detection of cases in people with an exposure history. As a part of the World Health Organization’s Global Outbreak Alert Response Network (WHOGOARN) response to the Ebola outbreak in West Africa, Professor Janusz Paweska, Head of the Centre for Emerging and Zoonotic Disease (CEZD) of the National Institute for Communicable Diseases (NICD) and his team successfully established an Ebola Mobile Laboratory (EML) in Freetown, Sierra Leone in the second half of August 2014. In addition to his scientific and administrative roles at NICD, Professor Paweska is a member of the Global Virus Network (GVN) based in Baltimore, Maryland. The goal of the GVN is to strengthen medical research and response to current viral causes of human disease and to prepare for new viral pandemic threats. GVN meets its mission in four ways: Support for cutting-edge research, training the next generation of medical virologists, public education, and advocacy. The operation of the NICD Ebola Mobile Laboratory in Sierra Leone is financially, technically and logistically supported by the NICD, the Ministry of Health of the Republic of South Africa, WHOGOARN, Sierra Leonean Ministry of Health and Sanitation, the International Atomic Energy Agency, and Centers for Disease Control and Prevention, USA. On 25 August 2014, the NICD EML was visited by the President of the Republic of Sierra Leone, Mr. Ernest Bai Koroma, other governmental officials and local health authorities. The President thanked the South African Government and the NICD for deploying EML staff to his country and stressed the importance of the diagnostic capacity in fighting the Ebola outbreak. The same day Prof. Janusz Paweska declared the NICD EML was at full operational capacity and tested its first blood samples from EVD suspected cases. The major activities of the laboratory include: logistics, processing specimens, reporting and training. Logistically, the EML performs operational checklists of biocontainment devices, preparation of decontamination solutions and other logistical arrangements to ensure uninterrupted operation (e.g. timely purchasing and delivery of petrol for generators). Processing specimens includes receiving specimens, data logging and matching clinical specimens with EVD case investigation forms, “hot” processing and aliquoting of specimens, extraction and molecular testing of viral nucleic acid from patient specimens, interpreting and recording results. Updated results are entered into the Ebola report database. The results also are reported, consultation sought and provided to the National Disease Prevention Center, the WHO Ebola Coordination Center and local doctors and hospitals, including Ebola Treatment Units. The South Africa NICD EML staff members are also training Sierra Leonean diagnosticians in biosafety and Ebola assays procedures. The NICD EML teams consist of, on average, four members in each team rotating in Sierra Leone every 4-6 weeks. Up to January 2015, 6 teams had been deployed. It is envisaged that the operation will be maintained until June 2015 requiring deployment of 4 additional teams, but due to the constantly evolving situation in West Africa, this approach might be revised. Before they begin their missions, teams undergo in-house pre-deployment training at the NICD in South Africa, followed by 3-4 days additional training on site in Freetown by the preceding team. The NICD EML is also greatly supported by the national Sierra Leonean staff that are trained by the NICD EML members in operational, biosafety and diagnostic procedures. The total financial costs of the NICD EML operation in Sierra Leone up to June 2015 are estimated to be about 1million USA dollars. The full cost in terms of personal efforts in the face of high-risk work is immeasurable; the benefits in terms of successful confinement and conquest of this epidemic through international cooperative programs such as this are yet to be actualized. But, there is no doubt, the problem is being confronted at its origins—a central focus of GVN’s mission. "Addendum: Dr. Paweska is the Director of GVN's Center of Excellence at the NICD, South Africa. In this role, he works with Center Directors globally to identify collaborative opportunities to advance research, support training of the next generation of virology leaders, educate publics and advocate for the field. To learn more about GVN and its Centers of Excellence worldwide, visit www.gvn.org" Ebola posters and messages highly visible in Freetown, at the road sides, shops and public buildings as part of the Ebola awareness health campaign efforts. Sierra Leonean governmental delegation visiting the South African NICD Ebola Mobile Laboratory in Freetown, at Lakka Tuberculosis Hospital compound (left). Prof. Janusz Paweska demonstrating to the President of the Republic of Sierra Leone, Dr Ernest Bai Koroma, and Dr Abdul Kamara, the Manager of the National Laboratory Services, a purified air powered respirator equipped with double shrouded full face hood used in biocontainment negative pressure chamber during handling and processing of specimens collected from Ebola virus disease suspected cases. Dr. Petrus Jansen van Vuren (left) and Prof. Janusz T. Paweska (right) dressed in personal protective equipment (scrubs, Tyvek suits, surgical gown, triple surgical gloves, gumboots, overshoes and PAPR with full face hood) processing blood collected from EVD suspected cases in Sierra Leone in negatively pressurized glove-box within the biocontainment negative pressure chamber. South African Ebola Mobile Laboratory, Freetown- Lakka, Sierra Leone, September 2014. Dr Petrus Jansen van Vuren (SA NICD) training the Sierra Leonean staff in Ebola PCR diagnostics (left). Ms Busisiwe Mogodi (South Africa) and Mr Kesela Conneh (Sierra Leone) matching clinical specimens samples with EVD case investigation forms before accessing for “hot”’ processing and inactivation in the glove-box (right). Prof. Janusz Paweska and members of the 1st & the 2ed (left, September 2014), and the 3rd (right, November 2014) South African NICD Ebola Mobile Laboratory teams, Sierra Leone, Freetown. Prof. Janusz T. Paweska visiting a village in Sierra Leone during his second Ebola outbreak response mission, December 2014. References: Nishiura H & Chowell G. Early transmission dynamics of Ebola virus disease (EVD), West Africa, March to August 2014. Euro Surveill 2014, 19 (36): pii=20894. Kelly JD. Make diagnostic centres a priority for Ebola crisis. Nature 2014, 513 (11 Sept.), p.145. Gire SK, et al. Genomic surveillance elucidate Ebola virus oriding during the 2014 outbreak. Science 2014 Sept 12:345(6202):1369-1372, doi.1126/science.1259657.