Human Adaptation of Ebola Virus during the West African Outbreak.
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ABSTRACT:
SUBMITTER: Urbanowicz RA
PROVIDER: S-EPMC5101188 | biostudies-literature | 2016 Nov
REPOSITORIES: biostudies-literature
Publications
Human Adaptation of Ebola Virus during the West African Outbreak.
Urbanowicz Richard A RA McClure C Patrick CP Sakuntabhai Anavaj A Sall Amadou A AA Kobinger Gary G Müller Marcel A MA Holmes Edward C EC Rey Félix A FA Simon-Loriere Etienne E Ball Jonathan K JK
Cell 20161101 4
The 2013-2016 outbreak of Ebola virus (EBOV) in West Africa was the largest recorded. It began following the cross-species transmission of EBOV from an animal reservoir, most likely bats, into humans, with phylogenetic analysis revealing the co-circulation of several viral lineages. We hypothesized that this prolonged human circulation led to genomic changes that increased viral transmissibility in humans. We generated a synthetic glycoprotein (GP) construct based on the earliest reported isolat ...[more]
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Project description:The Ebola virus (EBOV) outbreak in West Africa started in December 2013, claimed more than 11,000 lives, threatened to destabilize a whole region, and showed how easily health crises can turn into humanitarian disasters. EBOV genomic sequences of the West African outbreak revealed nonsynonymous mutations, which induced considerable public attention, but their role in virus spread and disease remains obscure. In this study, we investigated the functional significance of three nonsynonymous mutations that emerged early during the West African EBOV outbreak. Almost 90% of more than 1,000 EBOV genomes sequenced during the outbreak carried the signature of three mutations: a D759G substitution in the active center of the L polymerase, an A82V substitution in the receptor binding domain of surface glycoprotein GP, and an R111C substitution in the self-assembly domain of RNA-encapsidating nucleoprotein NP. Using a newly developed virus-like particle system and reverse genetics, we found that the mutations have an impact on the functions of the respective viral proteins and on the growth of recombinant EBOVs. The mutation in L increased viral transcription and replication, whereas the mutation in NP decreased viral transcription and replication. The mutation in the receptor binding domain of the glycoprotein GP improved the efficiency of GP-mediated viral entry into target cells. Recombinant EBOVs with combinations of the three mutations showed a growth advantage over the prototype isolate Makona C7 lacking the mutations. This study showed that virus variants with improved fitness emerged early during the West African EBOV outbreak.ImportanceThe dimension of the Ebola virus outbreak in West Africa was unprecedented. Amino acid substitutions in the viral L polymerase, surface glycoprotein GP, and nucleocapsid protein NP emerged, were fixed early in the outbreak, and were found in almost 90% of the sequences. Here we showed that these mutations affected the functional activity of viral proteins and improved viral growth in cell culture. Our results demonstrate emergence of adaptive changes in the Ebola virus genome during virus circulation in humans and prompt further studies on the potential role of these changes in virus transmissibility and pathogenicity.
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Project description:Genetic analyses have provided important insights into Ebola virus spread during the recent West African outbreak, but their implications for specific intervention scenarios remain unclear. Here, we address this issue using a collection of phylodynamic approaches. We show that long-distance dispersal events were not crucial for epidemic expansion and that preventing viral lineage movement to any given administrative area would, in most cases, have had little impact. However, major urban areas were critical in attracting and disseminating the virus: preventing viral lineage movement to all three capitals simultaneously would have contained epidemic size to one-third. We also show that announcements of border closures were followed by a significant but transient effect on international virus dispersal. By quantifying the hypothetical impact of different intervention strategies, as well as the impact of barriers on dispersal frequency, our study illustrates how phylodynamic analyses can help to address specific epidemiological and outbreak control questions.
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Project description:BackgroundMicronutrient supplementation is recommended in Ebola virus disease (EVD); however, there are limited data on therapeutic impacts of specific micronutrients.ObjectiveTo evaluate the association between vitamin A supplementation and mortality in EVD.MethodsThis retrospective cohort included patients with EVD admitted to 5 International Medical Corps Ebola Treatment Units (ETUs) in 2 countries during 2014-2015. Protocolized treatments with micronutrients were used at all ETUs: however, because of resource constraints, only a subset of patients received vitamin A. Standardized data on demographics, clinical characteristics, malaria status, and Ebola viral loads (cycle threshold values) were collected. The outcome of interest was mortality between cases treated with 200,000 IU of vitamin A on care days 1 and/or 2, and those not. Propensity scores based on the first 48 h of care were derived using covariates of age, ETU duration, malaria status, cycle threshold values, and clinical symptoms. Patients were matched 1:1 using nearest neighbors with replacement. Mortality between cases treated and not treated with vitamin A was compared using generalized estimating equations to calculate RR with associated 95% CI.ResultsThere were 424 cases analyzed, of which 330 (77.8%) were treated with vitamin A. The mean age was 30.5 y and 40.3% were men. The most common symptoms were diarrhea (85.6%), anorexia (80.7%), and abdominal pain (76.9%). Mortality proportions among cases treated and not treated with vitamin A were 55.0% and 71.9%, respectively. In the propensity-matched analysis, mortality was significantly lower among cases receiving vitamin A (RR = 0.77, 95% CI: 0.59, 0.99; P = 0.041). In a subgroup analysis of patients treated with multivitamins already containing vitamin A, additional vitamin A supplementation did not impact mortality.ConclusionEarly vitamin A supplementation was associated with reduced mortality in patients with EVD, and should be further studied and considered for use in future epidemics.
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Project description:Following its immergence in December 2013, the recent Zaire Ebola virus (EBOV) outbreak in West Africa has spread and persisted for more than two years, making it the largest EBOV epidemic in both scale and geographical region to date. In this study, a total of 726 glycoprotein (GP) gene sequences of the EBOV full-length genome obtained from West Africa from the 2014 outbreak, combined with 30 from earlier outbreaks between 1976 and 2008 were used to investigate the genetic divergence, evolutionary history, population dynamics, and selection pressure of EBOV among distinct epidemic waves. Results from our dataset showed that no non-synonymous substitutions occurred on the GP gene coding sequences of EBOV that were likely to have affected protein structure or function in any way. Furthermore, the significantly different dN/dS ratios observed between the 2014 West African outbreak and earlier outbreaks were more likely due to the confounding presence of segregating polymorphisms. Our results highlight no robust evidence that the 2014 EBOV outbreak is fast-evolving and adapting to humans. Therefore, the unprecedented nature of the 2014 EBOV outbreak might be more likely related to non-virological elements, such as environmental and sociological factors.
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Project description:BackgroundThe WHO declared the 2014 west African Ebola epidemic a public health emergency of international concern in view of its potential for further international spread. Decision makers worldwide are in need of empirical data to inform and implement emergency response measures. Our aim was to assess the potential for Ebola virus to spread across international borders via commercial air travel and assess the relative efficiency of exit versus entry screening of travellers at commercial airports.MethodsWe analysed International Air Transport Association data for worldwide flight schedules between Sept 1, 2014, and Dec 31, 2014, and historic traveller flight itinerary data from 2013 to describe expected global population movements via commercial air travel out of Guinea, Liberia, and Sierra Leone. Coupled with Ebola virus surveillance data, we modelled the expected number of internationally exported Ebola virus infections, the potential effect of air travel restrictions, and the efficiency of airport-based traveller screening at international ports of entry and exit. We deemed individuals initiating travel from any domestic or international airport within these three countries to have possible exposure to Ebola virus. We deemed all other travellers to have no significant risk of exposure to Ebola virus.FindingsBased on epidemic conditions and international flight restrictions to and from Guinea, Liberia, and Sierra Leone as of Sept 1, 2014 (reductions in passenger seats by 51% for Liberia, 66% for Guinea, and 85% for Sierra Leone), our model projects 2.8 travellers infected with Ebola virus departing the above three countries via commercial flights, on average, every month. 91,547 (64%) of all air travellers departing Guinea, Liberia, and Sierra Leone had expected destinations in low-income and lower-middle-income countries. Screening international travellers departing three airports would enable health assessments of all travellers at highest risk of exposure to Ebola virus infection.InterpretationDecision makers must carefully balance the potential harms from travel restrictions imposed on countries that have Ebola virus activity against any potential reductions in risk from Ebola virus importations. Exit screening of travellers at airports in Guinea, Liberia, and Sierra Leone would be the most efficient frontier at which to assess the health status of travellers at risk of Ebola virus exposure, however, this intervention might require international support to implement effectively.FundingCanadian Institutes of Health Research.
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Project description:In 49 patients with known Ebola virus disease outcomes during the ongoing outbreak in Sierra Leone, 13 were coinfected with the immunomodulatory pegivirus GB virus C (GBV-C). Fifty-three percent of these GBV-C(+) patients survived; in contrast, only 22% of GBV-C(-) patients survived. Both survival and GBV-C status were associated with age, with older patients having lower survival rates and intermediate-age patients (21 to 45 years) having the highest rate of GBV-C infection. Understanding the separate and combined effects of GBV-C and age on Ebola virus survival may lead to new treatment and prevention strategies, perhaps through age-related pathways of immune activation.
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Project description:INTRODUCTION:The Ebola virus disease (EVD) outbreak in West Africa, affecting Guinea, Liberia and Sierra Leone from 2014 to 2016, was a substantial public health crisis with health impacts extending past EVD itself. Access to maternal health services (MHS) was disrupted during the epidemic, with reductions in antenatal care, facility-based deliveries and postnatal care. We aimed to identify and describe barriers related to the uptake and provision of MHS during the 2014-2016 EVD outbreak in West Africa. METHODS:In June 2020, we conducted a scoping review of peer-reviewed publications and grey literature from relevant stakeholder organisations. Search terms were generated to identify literature that explained underlying access barriers to MHS. Published literature in scientific journals was first searched and extracted from PubMed and Web of Science databases for the period between 1 January 2014 and 27 June 2020. We hand-searched relevant stakeholder websites. A 'snowball' approach was used to identify relevant sources uncaptured in the systematic search. The identified literature was examined to synthesise themes using an existing framework. RESULTS:Nineteen papers were included, with 26 barriers to MHS uptake and provision identified. Three themes emerged: (1) fear and mistrust, (2) health system and service constraints, and (3) poor communication. Our analysis of the literature indicates that fear, experienced by both service users and providers, was the most recurring barrier to MHS. Constrained health systems negatively impacted MHS on the supply side. Poor communication and inadequately coordinated training efforts disallowed competent provision of MHS. CONCLUSIONS:Barriers to accessing MHS during the EVD outbreak in West Africa were influenced by complex but inter-related factors at the individual, interpersonal, health system and international level. Future responses to EVD outbreaks need to address underlying reasons for fear and mistrust between patients and providers, and ensure MHS are adequately equipped both routinely and during crises.
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Project description:BackgroundIn an attempt to assess the effects of the Ebola viral disease (EVD) on hospital functions in Sierra Leone, the aim of this study was to evaluate changes in provisions of surgery and non-Ebola admissions during the first year of the EVD outbreak.MethodsAll hospitals in Sierra Leone known to perform inpatient surgery were assessed for non-Ebola admissions, volume of surgery, caesarean deliveries and inguinal hernia repairs between January 2014 and May 2015, which was a total of 72 weeks. Accumulated weekly data were gathered from readily available hospital records at bi-weekly visits during the peak of the outbreak from September 2014 to May 2015. The Mann-Whitney U test was used to compare weekly median admissions during the first year of the EVD outbreak, with the 20 weeks before the outbreak, and weekly median volume of surgeries performed during the first year of the EVD outbreak with identical weeks of 2012. The manuscript is prepared according to the STROBE checklist for cross-sectional studies.ResultsOf the 42 hospitals identified, 40 had available data for 94% (2719/2880) of the weeks. There was a 51% decrease in weekly median non-Ebola admissions and 41% fewer weekly median surgeries performed compared with the 20 weeks before the outbreak (admission) and 2012 (volume of surgery). Governmental hospitals experienced a smaller reduction in non-Ebola admissions (45% versus 60%) and surgeries (31% versus 53%) compared to private non-profit hospitals. Governmental hospitals realized an increased volume of cesarean deliveries by 45% during the EVD outbreak, thereby absorbing the 43% reduction observed in the private non-profit hospitals.ConclusionsBoth non-Ebola admissions and surgeries were severely reduced during the EVD outbreak. In addition to responding to the EVD outbreak, governmental hospitals were able to maintain certain core health systems functions. Volume of surgery is a promising indicator of hospital functions that should be further explored.
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Project description:The variety of factors that contributed to the initial undetected spread of Ebola virus disease in West Africa during 2013-2016 and the difficulty controlling the outbreak once the etiology was identified highlight priorities for disease prevention, detection, and response. These factors include occurrence in a region recovering from civil instability and lacking experience with Ebola response; inadequate surveillance, recognition of suspected cases, and Ebola diagnosis; mobile populations and extensive urban transmission; and the community's insufficient general understanding about the disease. The magnitude of the outbreak was not attributable to a substantial change of the virus. Continued efforts during the outbreak and in preparation for future outbreak response should involve identifying the reservoir, improving in-country detection and response capacity, conducting survivor studies and supporting survivors, engaging in culturally appropriate public education and risk communication, building productive interagency relationships, and continuing support for basic research.
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Project description:The 2013-2016 Ebola outbreak in West Africa is the largest on record with 28 616 confirmed, probable and suspected cases and 11 310 deaths officially recorded by 10 June 2016, the true burden probably considerably higher. The case fatality ratio (CFR: proportion of cases that are fatal) is a key indicator of disease severity useful for gauging the appropriate public health response and for evaluating treatment benefits, if estimated accurately. We analysed individual-level clinical outcome data from Guinea, Liberia and Sierra Leone officially reported to the World Health Organization. The overall mean CFR was 62.9% (95% CI: 61.9% to 64.0%) among confirmed cases with recorded clinical outcomes. Age was the most important modifier of survival probabilities, but country, stage of the epidemic and whether patients were hospitalized also played roles. We developed a statistical analysis to detect outliers in CFR between districts of residence and treatment centres (TCs), adjusting for known factors influencing survival and identified eight districts and three TCs with a CFR significantly different from the average. From the current dataset, we cannot determine whether the observed variation in CFR seen by district or treatment centre reflects real differences in survival, related to the quality of care or other factors or was caused by differences in reporting practices or case ascertainment.This article is part of the themed issue 'The 2013-2016 West African Ebola epidemic: data, decision-making and disease control'.
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