3 research outputs found
Lassa Fever in Post-Conflict Sierra Leone
No full textBackground: Lassa fever (LF), an often-fatal hemorrhagic disease caused by Lassa virus (LASV), is a major public health threat in West Africa. When the violent civil conflict in Sierra Leone (1991 to 2002) ended, an international consortium assisted in restoration of the LF program at Kenema Government Hospital (KGH) in an area with the world's highest incidence of the disease. Methodology/Principal Findings Clinical and laboratory records of patients presenting to the KGH Lassa Ward in the post-conflict period were organized electronically. Recombinant antigen-based LF immunoassays were used to assess LASV antigenemia and LASV-specific antibodies in patients who met criteria for suspected LF. KGH has been reestablished as a center for LF treatment and research, with over 500 suspected cases now presenting yearly. Higher case fatality rates (CFRs) in LF patients were observed compared to studies conducted prior to the civil conflict. Different criteria for defining LF stages and differences in sensitivity of assays likely account for these differences. The highest incidence of LF in Sierra Leone was observed during the dry season. LF cases were observed in ten of Sierra Leone's thirteen districts, with numerous cases from outside the traditional endemic zone. Deaths in patients presenting with LASV antigenemia were skewed towards individuals less than 29 years of age. Women self-reporting as pregnant were significantly overrepresented among LASV antigenemic patients. The CFR of ribavirin-treated patients presenting early in acute infection was lower than in untreated subjects. Conclusions/Significance: Lassa fever remains a major public health threat in Sierra Leone. Outreach activities should expand because LF may be more widespread in Sierra Leone than previously recognized. Enhanced case finding to ensure rapid diagnosis and treatment is imperative to reduce mortality. Even with ribavirin treatment, there was a high rate of fatalities underscoring the need to develop more effective and/or supplemental treatments for LF.Version of Recor
Metagenomic sequencing at the epicenter of the Nigeria 2018 Lassa fever outbreak
No full textThe 2018 Nigerian Lassa fever season saw the largest ever recorded upsurge of cases, raising concerns over the emergence of a strain with increased transmission rate. To understand the molecular epidemiology of this upsurge, we performed, for the first time at the epicenter of an unfolding outbreak, metagenomic nanopore sequencing directly from patient samples, an approach dictated by the highly variable genome of the target pathogen. Genomic data and phylogenetic reconstructions were communicated immediately to Nigerian authorities and the World Health Organization to inform the public health response. Real-time analysis of 36 genomes and subsequent confirmation using all 120 samples sequenced in the country of origin revealed extensive diversity and phylogenetic intermingling with strains from previous years, suggesting independent zoonotic transmission events and thus allaying concerns of an emergent strain or extensive human-to-human transmission.sponsorship: L.E.K., S.T.P., R.H., R.V., M.W.C., and J.A.H. acknowledge funding by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections at the University of Liverpool in partnership with Public Health England (PHE), in collaboration with Liverpool School of Tropical Medicine. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, the Department of Health, or Public Health England. L.E.K. has received travel expenses and accommodation from Oxford Nanopore to speak at conferences regarding this work. L.E.K. has received some reagents free of charge from Oxford Nanopore in support of her Ph.D. project. M.W.C. has received reagents free of charge from Oxford Nanopore in support of previous projects not related to the work presented in this manuscript. L.E.K. and M.W.C. have not received other financial compensation nor hold shares. P.L. and M.A.S. acknowledge funding from the European Research Council under the European Union's Horizon 2020 research and innovation program (grant 725422-ReservoirDOCS) and from the Wellcome Trust Collaborative Award, 206298/Z/17/Z. P.L. acknowledges support by the Special Research Fund, KU Leuven ("Bijzonder Onderzoeksfonds," KU Leuven, OT/14/115), and the Research Foundation-Flanders (" Fonds voor Wetenschappelijk Onderzoek - Vlaanderen," G066215N, G0D5117N, and G0B9317N). M.A.S. acknowledges support under National Science Foundation grant DMS 1264153. This study was supported by the German Federal Ministry of Health through support of the WHO Collaborating Centre for Arboviruses and Hemorrhagic Fever Viruses at the Bernhard Nocht Institute for Tropical Medicine (agreements ZMV I 1-2517WHO005 and ZMV I 1-2517WHO010) and through the Global Health Protection Program (agreement ZMVI1-2517-GHP-704), the German Federal Ministry for Economic Cooperation and Development through the Rapid Deployment Expert Group to Combat Threats (SEEG), the European Union's Horizon 2020 research and innovation program to S.G. (grant 653316-EVAg), and the German Research Foundation (DFG) to S.G. and D.U.E. (GU 883/4-1). D.U.E. acknowledges fellowships from Alexander von Humboldt Foundation and Kirmser Foundation. The funders had no role in the design and interpretation of the data and preparation of the manuscript. (National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emerging and Zoonotic Infections at the University of Liverpool, Public Health England (PHE), Liverpool School of Tropical Medicine, European Research Council under the European Union's Horizon 2020 research and innovation program|725422-ReservoirDOCS, Wellcome Trust Collaborative Award|206298/Z/17/Z, Special Research Fund, KU Leuven ("Bijzonder Onderzoeksfonds," KU Leuven)|OT/14/115, Research Foundation-Flanders ("Fonds voor Wetenschappelijk Onderzoek - Vlaanderen")|G066215N, Research Foundation-Flanders ("Fonds voor Wetenschappelijk Onderzoek - Vlaanderen")|G0D5117N, Research Foundation-Flanders ("Fonds voor Wetenschappelijk Onderzoek - Vlaanderen")|G0B9317N, National Science Foundation|DMS 1264153, German Federal Ministry of Health through WHO Collaborating Centre for Arboviruses and Hemorrhagic Fever Viruses at the Bernhard Nocht Institute for Tropical Medicine|ZMV I 1-2517WHO005, German Federal Ministry of Health through WHO Collaborating Centre for Arboviruses and Hemorrhagic Fever Viruses at the Bernhard Nocht Institute for Tropical Medicine|ZMV I 1-2517WHO010, German Federal Ministry of Health through Global Health Protection Program|ZMVI1-2517-GHP-704, German Federal Ministry for Economic Cooperation and Development through the Rapid Deployment Expert Group to Combat Threats (SEEG), European Union's Horizon 2020 research and innovation program|653316-EVAg, German Research Foundation (DFG)|GU 883/4-1, Alexander von Humboldt Foundation, Kirmser Foundation, Oxford Nanopore, National Institute of Allergy and Infectious Diseases|U19AI135995)status: Publishe
Clinical Illness and Outcomes in Patients with Ebola in Sierra Leone
No full textBackground;Limited clinical and laboratory data are available on patients with Ebola virus disease (EVD). The Kenema Government Hospital in Sierra Leone, which had an existing infrastructure for research regarding viral hemorrhagic fever, has received and cared for patients with EVD since the beginning of the outbreak in Sierra Leone in May 2014. Methods;We reviewed available epidemiologic, clinical, and laboratory records of patients in whom EVD was diagnosed between May 25 and June 18, 2014. We used quantitative reverse-transcriptase–polymerase-chain-reaction assays to assess the load of Ebola virus (EBOV, Zaire species) in a subgroup of patients. Results;Of 106 patients in whom EVD was diagnosed, 87 had a known outcome, and 44 had detailed clinical information available. The incubation period was estimated to be 6 to 12 days, and the case fatality rate was 74%. Common findings at presentation included fever (in 89% of the patients), headache (in 80%), weakness (in 66%), dizziness(in 60%), diarrhea (in 51%), abdominal pain (in 40%), and vomiting (in 34%). Clinical and laboratory factors at presentation that were associated with a fatal outcome included fever, weakness, dizziness, diarrhea, and elevated levels of blood urea nitrogen, aspartate aminotransferase, and creatinine. Exploratory analyses indicated that patients under the age of 21 years had a lower case fatality rate than those over the age of 45 years (57% vs. 94%, P=0.03), and patients presenting with fewer than 100,000 EBOV copies per milliliter had a lower case fatality rate than those with 10 million EBOV copies per milliliter or more (33% vs. 94%, P=0.003). Bleeding occurred in only 1 patient.Conclusions; The incubation period and case fatality rate among patients with EVD in Sierra Leone are similar to those observed elsewhere in the 2014 outbreak and in previous outbreaks. Although bleeding was an infrequent finding, diarrhea and other gastrointestinal manifestations were common. (Funded by the National Institutes of Health and others.)Organismic and Evolutionary BiologyVersion of Recor
