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      Establishing Ebola Virus Disease (EVD) diagnostics using GeneXpert technology at a mobile laboratory in Liberia: Impact on outbreak response, case management and laboratory systems strengthening

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          Abstract

          The 2014–16 Ebola Virus Disease (EVD) outbreak in West Africa highlighted the necessity for readily available, accurate and rapid diagnostics. The magnitude of the outbreak and the re-emergence of clusters of EVD cases following the declaration of interrupted transmission in Liberia, reinforced the need for sustained diagnostics to support surveillance and emergency preparedness. We describe implementation of the Xpert Ebola Assay, a rapid molecular diagnostic test run on the GeneXpert platform, at a mobile laboratory in Liberia and the subsequent impact on EVD outbreak response, case management and laboratory system strengthening. During the period of operation, site coordination, management and operational capacity was supported through a successful collaboration between Ministry of Health (MoH), World Health Organization (WHO) and international partners. A team of Liberian laboratory technicians were trained to conduct EVD diagnostics and the laboratory had capacity to test 64–100 blood specimens per day. Establishment of the laboratory significantly increased the daily testing capacity for EVD in Liberia, from 180 to 250 specimens at a time when the effectiveness of the surveillance system was threatened by insufficient diagnostic capacity. During the 18 months of operation, the laboratory tested a total of 9,063 blood specimens, including 21 EVD positives from six confirmed cases during two outbreaks. Following clearance of the significant backlog of untested EVD specimens in November 2015, a new cluster of EVD cases was detected at the laboratory. Collaboration between surveillance and laboratory coordination teams during this and a later outbreak in March 2016, facilitated timely and targeted response interventions. Specimens taken from cases during both outbreaks were analysed at the laboratory with results informing clinical management of patients and discharge decisions. The GeneXpert platform is easy to use, has relatively low running costs and can be integrated into other national diagnostic algorithms. The technology has on average a 2-hour sample-to-result time and allows for single specimen testing to overcome potential delays of batching. This model of a mobile laboratory equipped with Xpert Ebola test, staffed by local laboratory technicians, could serve to strengthen outbreak preparedness and response for future outbreaks of EVD in Liberia and the region.

          Author summary

          We describe a model of a mobile laboratory co-located at an Ebola treatment unit (ETU) equipped with GeneXpert molecular diagnostic platform and automated qRT-PCR test for Ebola virus disease (EVD). The laboratory contributed significantly to the EVD response in Liberia, including supporting surveillance, outbreak detection, contact tracing and management of confirmed cases. The laboratory was run by local laboratory technicians as opposed to international experts on short missions, making it a more sustainable option in prolonged outbreaks and early recovery phases. The redeployment and strategic placement of these GeneXpert instruments to complement EVD isolation facilities throughout the country has strengthened preparedness and response capabilities for future EVD outbreaks in Liberia.

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          Most cited references24

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          Diagnosis of Ebola Virus Disease: Past, Present, and Future.

          Laboratory diagnosis of Ebola virus disease plays a critical role in outbreak response efforts; however, establishing safe and expeditious testing strategies for this high-biosafety-level pathogen in resource-poor environments remains extremely challenging. Since the discovery of Ebola virus in 1976 via traditional viral culture techniques and electron microscopy, diagnostic methodologies have trended toward faster, more accurate molecular assays. Importantly, technological advances have been paired with increasing efforts to support decentralized diagnostic testing capacity that can be deployed at or near the point of patient care. The unprecedented scope of the 2014-2015 West Africa Ebola epidemic spurred tremendous innovation in this arena, and a variety of new diagnostic platforms that have the potential both to immediately improve ongoing surveillance efforts in West Africa and to transform future outbreak responses have reached the field. In this review, we describe the evolution of Ebola virus disease diagnostic testing and efforts to deploy field diagnostic laboratories in prior outbreaks. We then explore the diagnostic challenges pervading the 2014-2015 epidemic and provide a comprehensive examination of novel diagnostic tests that are likely to address some of these challenges moving forward.
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            The Contribution of Ebola Viral Load at Admission and Other Patient Characteristics to Mortality in a Médecins Sans Frontières Ebola Case Management Centre, Kailahun, Sierra Leone, June–October 2014

            This paper describes patient characteristics, including Ebola viral load, associated with mortality in a Médecins Sans Frontières Ebola case management centre (CMC). Out of 780 admissions between June and October 2014, 525 (67%) were positive for Ebola with a known outcome. The crude mortality rate was 51% (270/525). Ebola viral load (whole-blood sample) data were available on 76% (397/525) of patients. Univariate analysis indicated viral load at admission, age, symptom duration prior to admission, and distance traveled to the CMC were associated with mortality (P 10), aged ≥50 years (P = .08, odds ratio = 2) and symptom duration prior to admission less than 5 days (P = .14). The presence of confusion, diarrhea, and conjunctivitis were significantly higher (P < .05) in Ebola patients who died. These findings highlight the importance viral load at admission has on mortality outcomes and could be used to cohort cases with viral loads greater than 10 million copies into dedicated wards with more intensive medical support to further reduce mortality.
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              The role of rapid diagnostics in managing Ebola epidemics

              Ebola emerged in West Africa around December 2013 and swept through Guinea, Sierra Leone and Liberia, giving rise to 27,748 confirmed, probable and suspected cases reported by 29 July 2015. Case diagnoses during the epidemic have relied on polymerase chain reaction-based tests. Owing to limited laboratory capacity and local transport infrastructure, the delays from sample collection to test results being available have often been 2 days or more. Point-of-care rapid diagnostic tests offer the potential to substantially reduce these delays. We review Ebola rapid diagnostic tests approved by the World Health Organization and those currently in development. Such rapid diagnostic tests could allow early triaging of patients, thereby reducing the potential for nosocomial transmission. In addition, despite the lower test accuracy, rapid diagnostic test-based diagnosis may be beneficial in some contexts because of the reduced time spent by uninfected individuals in health-care settings where they may be at increased risk of infection; this also frees up hospital beds. We use mathematical modelling to explore the potential benefits of diagnostic testing strategies involving rapid diagnostic tests alone and in combination with polymerase chain reaction testing. Our analysis indicates that the use of rapid diagnostic tests with sensitivity and specificity comparable with those currently under development always enhances control, whether evaluated at a health-care-unit or population level. If such tests had been available throughout the recent epidemic, we estimate, for Sierra Leone, that their use in combination with confirmatory polymerase chain-reaction testing might have reduced the scale of the epidemic by over a third.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Funding acquisitionRole: MethodologyRole: ResourcesRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: ResourcesRole: Writing – review & editing
                Role: Methodology
                Role: Resources
                Role: Funding acquisitionRole: Project administrationRole: ResourcesRole: Writing – review & editing
                Role: Data curationRole: Project administration
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Funding acquisitionRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Funding acquisitionRole: Writing – review & editing
                Role: Funding acquisitionRole: Writing – review & editing
                Role: Funding acquisitionRole: Writing – review & editing
                Role: Project administrationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS Negl Trop Dis
                PLoS Negl Trop Dis
                plos
                plosntds
                PLoS Neglected Tropical Diseases
                Public Library of Science (San Francisco, CA USA )
                1935-2727
                1935-2735
                5 January 2018
                January 2018
                : 12
                : 1
                : e0006135
                Affiliations
                [1 ] EVD Response Team, World Health Organization, Monrovia, Montserrado, Liberia
                [2 ] Laboratory Deptartment, Academic Consortium Combating Ebola in Liberia, Monrovia, Montserrado, Liberia
                [3 ] EVD West Africa Response Team, Foundation for Innovative New Diagnostics, Geneva, Switzerland
                [4 ] Department of Public Health Emergencies, Ministry of Health, Monrovia, Montserrado, Liberia
                [5 ] EVD Response Team, E-health Africa, Monrovia, Montserrado, Liberia
                [6 ] EVD Response Team, United States Centers for Disease Control and Prevention, Monrovia, Montserrado, Liberia
                Center for Disease Control and Prevention, UNITED STATES
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0002-2683-7154
                Article
                PNTD-D-17-01083
                10.1371/journal.pntd.0006135
                5755746
                29304039
                95617eee-bcbf-41f6-97f1-45a10cff79d3

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

                History
                : 10 July 2017
                : 24 November 2017
                Page count
                Figures: 4, Tables: 2, Pages: 20
                Funding
                The project was jointly funded through a consortium of partners using Ebola Response funding in Liberia. The funders had no role in project design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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