Journal Article > LetterFull Text
Nature. 2015 June 17; Volume 524 (Issue 7563); 97-101.; DOI:10.1038/nature14594
Carroll MW, Matthews DA, Hiscox JA, Elmore MJ, Pollakis G, et al.
Nature. 2015 June 17; Volume 524 (Issue 7563); 97-101.; DOI:10.1038/nature14594
West Africa is currently witnessing the most extensive Ebola virus (EBOV) outbreak so far recorded. Until now, there have been 27,013 reported cases and 11,134 deaths. The origin of the virus is thought to have been a zoonotic transmission from a bat to a twoyear-old boy in December 2013 (ref. 2). From this index case the virus was spread by human-to-human contact throughout Guinea, Sierra Leone and Liberia. However, the origin of the particular virus in each country and time of transmission is not known and currently relies on epidemiological analysis, which may be unreliable owing to the difficulties of obtaining patient information. Here we trace the genetic evolution of EBOV in the current outbreak that has resulted in multiple lineages. Deep sequencing of 179 patient samples processed by the European Mobile Laboratory, the first diagnostics unit to be deployed to the epicentre of the outbreak in Guinea, reveals an epidemiological and evolutionary history of the epidemic from March 2014 to January 2015. Analysis of EBOV genome evolution has also benefited from a similar sequencing effort of patient samples from Sierra Leone. Our results confirm that the EBOV from Guinea moved into Sierra Leone, most likely in April or early May. The viruses of the Guinea/Sierra Leone lineage mixed around June/July 2014. Viral sequences covering August, September and October 2014 indicate that this lineage evolved independently within Guinea. These data can be used in conjunction with epidemiological information to test retrospectively the effectiveness of control measures, and provides an unprecedented window into the evolution of an ongoing viral haemorrhagic fever outbreak.
Journal Article > Short ReportFull Text
Morbidity and Mortality Weekly Report. 2014 November 14; Volume 63; 1067-71.
Sharma A, Heijenberg N, Peter C, Bolongei J, Reeder B, et al.
Morbidity and Mortality Weekly Report. 2014 November 14; Volume 63; 1067-71.
WHAT IS ALREADY KNOWN ABOUT THIS TOPIC?
Lofa County in Liberia has one of the highest numbers of reported cases of Ebola virus disease (Ebola) in West Africa. Government health offices, nongovernmental organizations, and technical agencies coordinated response activities to reduce transmission of Ebola in Lofa County. The intensity and thoroughness of activities increased in response to the resurgence of Ebola in early June.
WHAT IS ADDED BY THIS REPORT?
Trends in new reported cases, admissions to the dedicated Ebola treatment unit in the town of Foya, and test results of community decedents evaluated for Ebola virus suggest transmission of Ebola virus decreased in Lofa County as early as August 17, 2014, following rapid scale-up of response activities after a resurgence of Ebola in early June.
WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?
A comprehensive Ebola response strategy developed with participation from the local community and rapidly scaled up following resurgence of Ebola might have reduced the spread of Ebola virus in Lofa County. The strategy implemented in Lofa County might serve as a model for reducing transmission of Ebola virus in other affected areas.
Lofa County in Liberia has one of the highest numbers of reported cases of Ebola virus disease (Ebola) in West Africa. Government health offices, nongovernmental organizations, and technical agencies coordinated response activities to reduce transmission of Ebola in Lofa County. The intensity and thoroughness of activities increased in response to the resurgence of Ebola in early June.
WHAT IS ADDED BY THIS REPORT?
Trends in new reported cases, admissions to the dedicated Ebola treatment unit in the town of Foya, and test results of community decedents evaluated for Ebola virus suggest transmission of Ebola virus decreased in Lofa County as early as August 17, 2014, following rapid scale-up of response activities after a resurgence of Ebola in early June.
WHAT ARE THE IMPLICATIONS FOR PUBLIC HEALTH PRACTICE?
A comprehensive Ebola response strategy developed with participation from the local community and rapidly scaled up following resurgence of Ebola might have reduced the spread of Ebola virus in Lofa County. The strategy implemented in Lofa County might serve as a model for reducing transmission of Ebola virus in other affected areas.
Journal Article > ResearchFull Text
PLOS Med. 2016 March 1; Volume 13 (Issue 3); DOI:10.1371/journal.pmed.1001967
Sissoko D, Laouenan C, Folkesson E, M’Lebing A, Beavogui A, et al.
PLOS Med. 2016 March 1; Volume 13 (Issue 3); DOI:10.1371/journal.pmed.1001967
Ebola virus disease (EVD) is a highly lethal condition for which no specific treatment has proven efficacy. In September 2014, while the Ebola outbreak was at its peak, the World Health Organization released a short list of drugs suitable for EVD research. Favipiravir, an antiviral developed for the treatment of severe influenza, was one of these. In late 2014, the conditions for starting a randomized Ebola trial were not fulfilled for two reasons. One was the perception that, given the high number of patients presenting simultaneously and the very high mortality rate of the disease, it was ethically unacceptable to allocate patients from within the same family or village to receive or not receive an experimental drug, using a randomization process impossible to understand by very sick patients. The other was that, in the context of rumors and distrust of Ebola treatment centers, using a randomized design at the outset might lead even more patients to refuse to seek care. Therefore, we chose to conduct a multicenter non-randomized trial, in which all patients would receive favipiravir along with standardized care. The objectives of the trial were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak, and to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD. The trial was not aimed at directly informing future guidelines on Ebola treatment but at quickly gathering standardized preliminary data to optimize the design of future studies.
Journal Article > Short ReportFull Text
Euro Surveill. 2014 December 11
Baggi FM, Taybi A, Kurth A, Van Herp M, Di Caro A, et al.
Euro Surveill. 2014 December 11
Journal Article > Short ReportFull Text
Euro Surveill. 2015 January 22; Volume 20 (Issue 3); DOI:10.2807/1560-7917.ES2015.20.3.21017
Moreau M, Spencer C, Gozalbes JG, Colebunders R, Lefevre A, et al.
Euro Surveill. 2015 January 22; Volume 20 (Issue 3); DOI:10.2807/1560-7917.ES2015.20.3.21017
Journal Article > ResearchFull Text
mSphere. 2017 August 30; Volume 2 (Issue 4); DOI:10.1128/mSphereDirect.00325-17
Carroll MW, Haldenby S, Rickett NY, Palyi B, Garcia-Dorival I, et al.
mSphere. 2017 August 30; Volume 2 (Issue 4); DOI:10.1128/mSphereDirect.00325-17
In this study, samples from the 2013-2016 West African Ebola virus outbreak from patients in Guinea with Ebola virus disease (EVD) were analyzed to discover and classify what other pathogens were present. Throat swabs were taken from deceased EVD patients, and peripheral blood samples were analyzed that had been taken from patients when they presented at the treatment center with acute illness. High-throughput RNA sequencing (RNA-seq) and bioinformatics were used to identify the potential microorganisms. This approach confirmed Ebola virus (EBOV) in all samples from patients diagnosed as acute positive for the virus by quantitative reverse transcription-PCR in deployed field laboratories. Nucleic acid mapping to Plasmodium was also used on the patient samples, confirming results obtained with an antigen-based rapid diagnostic test (RDT) conducted in the field laboratories. The data suggested that a high Plasmodium load, as determined by sequence read depth, was associated with mortality and influenced the host response, whereas a lower parasite load did not appear to affect outcome. The identifications of selected bacteria from throat swabs via RNA-seq were confirmed by culture. The data indicated that the potential pathogens identified in the blood samples were associated with translocation from the gut, suggesting the presence of bacteremia, which transcriptome data suggested may induce or aggravate the acute-phase response observed during EVD. Transcripts mapping to different viruses were also identified, including those indicative of lytic infections. The development of high-resolution analysis of samples from patients with EVD will help inform care pathways and the most appropriate general antimicrobial therapy to be used in a resource-poor setting.
IMPORTANCE
Our results highlight the identification of an array of pathogens in the blood of patients with Ebola virus disease (EVD). This has not been done before, and the data have important implications for the treatment of patients with EVD, particularly considering antibiotic stewardship. We show that EVD patients who were also infected with Plasmodium, particularly at higher loads, had more adverse outcomes than patients with lower levels of Plasmodium. However, the presence of Plasmodium did not influence the innate immune response, and it is likely that the presence of EBOV dominated this response. Several viruses other than EBOV were identified, and bacteria associated with sepsis were also identified. These findings were indicative of bacterial translocation across the gut during the acute phase of EVD.
IMPORTANCE
Our results highlight the identification of an array of pathogens in the blood of patients with Ebola virus disease (EVD). This has not been done before, and the data have important implications for the treatment of patients with EVD, particularly considering antibiotic stewardship. We show that EVD patients who were also infected with Plasmodium, particularly at higher loads, had more adverse outcomes than patients with lower levels of Plasmodium. However, the presence of Plasmodium did not influence the innate immune response, and it is likely that the presence of EBOV dominated this response. Several viruses other than EBOV were identified, and bacteria associated with sepsis were also identified. These findings were indicative of bacterial translocation across the gut during the acute phase of EVD.
Journal Article > ResearchFull Text
Nature. 2016 May 4; Volume 533 (Issue 7601); 100-104.; DOI:10.1038/nature17949
Ruibal P, Oestereich L, Ludtke A, Becker-Ziaja B, Wozniak DM, et al.
Nature. 2016 May 4; Volume 533 (Issue 7601); 100-104.; DOI:10.1038/nature17949
Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD. In particular, very little is known about human immune responses to Ebola virus. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4(+) and CD8(+) T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.
Journal Article > ResearchFull Text
Clin Infect Dis. 2015 May 19 (Issue 5)
Strecker T, Palyi B, Ellerbrok H, Jonckheere S, De Clerck H, et al.
Clin Infect Dis. 2015 May 19 (Issue 5)
Reliable reverse-transcriptase polymerase chain reaction (RT-PCR)-based diagnosis of Ebola virus infection currently requires a blood sample obtained by intravenous puncture. During the current Ebola outbreak in Guinea, we evaluated the usability of capillary blood samples collected from fingersticks of patients suspected of having Ebola virus disease (EVD) for field diagnostics during an outbreak emergency.