Active Ebola Virus Replication and Heterogeneous Evolutionary Rates in EVD Survivors.
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ABSTRACT:
SUBMITTER: Whitmer SLM
PROVIDER: S-EPMC5809616 | biostudies-literature | 2018 Jan
REPOSITORIES: biostudies-literature
Publications
Active Ebola Virus Replication and Heterogeneous Evolutionary Rates in EVD Survivors.
Whitmer Shannon L M SLM Ladner Jason T JT Wiley Michael R MR Patel Ketan K Dudas Gytis G Rambaut Andrew A Sahr Foday F Prieto Karla K Shepard Samuel S SS Carmody Ellie E Knust Barbara B Naidoo Dhamari D Deen Gibrilla G Formenty Pierre P Nichol Stuart T ST Palacios Gustavo G Ströher Ute U
Cell reports 20180101 5
Following cessation of continuous Ebola virus (EBOV) transmission within Western Africa, sporadic EBOV disease (EVD) cases continued to re-emerge beyond the viral incubation period. Epidemiological and genomic evidence strongly suggests that this represented transmission from EVD survivors. To investigate whether persistent infections are characterized by ongoing viral replication, we sequenced EBOV from the semen of nine EVD survivors and a subset of corresponding acute specimens. EBOV evolutio ...[more]
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Project description:PURPOSE:We investigate the impact on outcome of different levels of supportive treatment in Ebola virus disease (EVD). The NGO EMERGENCY delivered care sequentially at two Ebola Treatment Centres (ETC) in Sierra Leone: first at Lakka (fluids, symptomatic, antibiotic, antimalaria treatment, and hospital level medical care), and thereafter in Goderich, adding organ support in the only African ETC with an equipped and staffed intensive care unit (ETC-ICU). METHODS:The primary outcome in this retrospective cohort study was in-ETC mortality. Secondarily, we used multivariable logistic regression to investigate the independent impact of the IC on mortality by comparing patients in two ETCs, adjusting for potential confounders, including the viral load (base-10 logarithm in copies/ml) (LVL), modelled as a piecewise linear function. Mortality was plotted versus LVL. Confidence bands were constructed by a bootstrap technique. The number of hospital-free days within 28 was computed to assess the burden of EVD. RESULTS:Data from 229 EVD patients were analysed (123 in Lakka, 106 in Goderich). Crude analysis showed a non-statistically significant difference in mortality (57.7% in Lakka vs 50.0% in Goderich; p?=?0.19). Age and LVL were associated with mortality. Adjusted mortality was lower at the Goderich ICU-ETC (p?=?0.055). This difference was observed with 80% confidence for patients with LVL between 7.5 and 8.5 copies/ml. Hospital-free days (of 28 days) were greater (7.7 vs 5.5; p?=?0.03) for patients treated in the ICU-ETC. CONCLUSIONS:Provision of critical care to patients with EVD is feasible in resource-limited settings and was associated with improved survival and less time in hospital.
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Project description:There is unequivocal evidence in the literature that epidemics adversely affect the livelihoods of individuals, households and communities. However, evidence in the literature is dominated by the socioeconomic impacts of HIV/AIDS and malaria, while evidence on the impact of the Ebola virus disease (EVD) on households' livelihoods remains fragmented and scant. Our study investigates the effect of the EVD epidemic on the livelihoods of Liberian households using the Sustainable Livelihood Framework (SLF). The study also explores the effect of the EVD epidemic on agricultural production and productive efficiency of farm households using Spatial Stochastic Frontier Analysis (SSFA). We collected data from 623 households across Liberia in 2015, using a systematic random sampling design. Our results indicated that the annual income of sample households from communities where EVD occurred did not differ from the annual income of households from communities where EVD did not occur. Nonetheless, the majority of sample households reported a decrease in their income, compared to their income in the year before the survey. This suggests that the impact of the EVD epidemic might not only have been limited to communities directly affected by the epidemic, but also it may have indirectly affected communities in areas where EVD was not reported. We also found that the community-level incidence of EVD negatively affected crop production of farm households, which may have exacerbated the problem of food insecurity throughout the country. Moreover, we found that the EVD epidemic weakened the society's trust in Liberian institutions. In a nutshell, our results highlight that epidemics, such as the recent EVD outbreak, may have long-lasting negative effects on the livelihoods of a society and their effect may extend beyond the communities directly affected by the epidemics. This means that the nation's recovery from the impact of the epidemic would be more challenging, and the social and economic impacts of the epidemic may extend well beyond the end of the health crisis.
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Project description:Infection with Ebola virus (EBOV) results in a life-threatening disease, with reported mortality rates between 50%-70%. The factors that determine patient survival are poorly understood; however, clinical observations indicate that EBOV viremia may be associated with fatal outcome. We conducted a study of the kinetics of Zaire EBOV viremia in patients with EBOV disease (EVD) who were managed at an Ebola Treatment Centre in Sierra Leone during the recent West African outbreak.Data from 84 EVD patients (38 survivors, 46 nonsurvivors) were analyzed, and EBOV viremia was quantified between 2 and 13 days after symptom onset. Time since symptom onset and clinical outcome were used as independent variables to compare EBOV viral kinetics in survivors and nonsurvivors.In all patients, EBOV viremia kinetics was a quadratic function of time; however, EBOV viremia was 0.94 logarithm (log) copies per ml (cp/ml) (P = 0.011) higher in nonsurvivors than in survivors from day 2 after the onset of symptoms. Survivors reached peak viremia levels at an earlier time after symptom onset than nonsurvivors (day 5 versus day 7) and had lower mean peak viremia levels compared with nonsurvivors (7.46 log cp/ml; 95% CI, 7.17-7.76 vs. 8.60 log cp/ml; 95% CI, 8.27-8.93). Before reaching peak values, EBOV viremia similarly increased both in survivors and nonsurvivors; however, the decay of viremia after the peak was much stronger in survivors than in nonsurvivors.Our results demonstrate that plasma concentrations of EBOV are markedly different between survivors and nonsurvivors at very early time points after symptom onset and may be predicative of outcome. Further studies focused on the early phase of the disease will be required to identify the causal and prognostic factors that determine patient outcome.Italian Ministry of Health; Italian Ministry of Foreign Affairs; EMERGENCY's private donations; and Royal Engineers for DFID-UK.
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Project description:Ebola virus (EBOV) can persist in immunologically protected body sites in survivors of Ebola virus disease, creating the potential to initiate new chains of transmission. From the outbreak in West Africa during 2014-2016, we identified 13 possible events of viral persistence-derived transmission of EBOV (VPDTe) and applied predefined criteria to classify transmission events based on the strength of evidence for VPDTe and source and route of transmission. For 8 events, a recipient case was identified; possible source cases were identified for 5 of these 8. For 5 events, a recipient case or chain of transmission could not be confidently determined. Five events met our criteria for sexual transmission (male-to-female). One VPDTe event led to at least 4 generations of cases; transmission was limited after the other events. VPDTe has increased the importance of Ebola survivor services and sustained surveillance and response capacity in regions with previously widespread transmission.
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Project description:Mathematical modelling has successfully been used to provide quantitative descriptions of many viral infections, but for the Ebola virus, which requires biosafety level 4 facilities for experimentation, modelling can play a crucial role. Ebola virus modelling efforts have primarily focused on in vivo virus kinetics, e.g., in animal models, to aid the development of antivirals and vaccines. But, thus far, these studies have not yielded a detailed specification of the infection cycle, which could provide a foundational description of the virus kinetics and thus a deeper understanding of their clinical manifestation. Here, we obtain a diverse experimental data set of the Ebola virus infection in vitro, and then make use of Bayesian inference methods to fully identify parameters in a mathematical model of the infection. Our results provide insights into the distribution of time an infected cell spends in the eclipse phase (the period between infection and the start of virus production), as well as the rate at which infectious virions lose infectivity. We suggest how these results can be used in future models to describe co-infection with defective interfering particles, which are an emerging alternative therapeutic.
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Project description:The Ebola virus disease epidemic between 2013 and 2016 in West Africa was unprecedented. It resulted in approximately 28.000 cases and 10.000 Ebola survivors. Many survivors face social, economic and health-related predicaments and media reporting is crucially important in infectious disease outbreaks. However, there is little research on reporting of the social situation of Ebola survivors in Liberia.The study used a mixed methods approach and analysed media reports from the Liberian Daily Observer (DOL), a daily newspaper available online in English. We were interested to know how the situation of Ebola survivors was portrayed; in what way issues such as stigma and discrimination were addressed; and which stigma reduction interventions were covered and how. We included all articles on the situation of Ebola survivors in the quantitative and in-depth qualitative analysis published between April 2014 and March 2016.The DOL published 148 articles that portrayed the social situation of Ebola survivors between the 24 months observation period. In these articles, Ebola survivors were often defined beyond biological terms, reflecting on a broader social definition of survivorship. Survivorship was associated with challenges such as suffering from after-effects, social and economic consequences and psychological distress. Almost 50% of the articles explicitly mentioned stigmatisation in their reporting on Ebola survivors. This was contextualised in untrustworthiness towards international responses and the local health care system and inconclusive knowledge on cures and transmission routes. In the majority of DOL articles stigma reduction and engaging survivors in the response was reported as crucially important.Reporting in the DOL was educational-didactical and well-balanced in terms of disseminating available medical knowledge and reflecting the social situation of Ebola survivors. While the articles contextualised factors contributing to stigmatisation throughout the reporting, journalistic scrutiny regarding effectiveness of interventions by government and NGOs was missing.
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