Characterisation of #infectious #Ebola virus from the ongoing #outbreak to guide #response activities in the #DRC: a #phylogenetic and in vitro analysis (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Characterisation of infectious Ebola virus from the ongoing outbreak to guide response activities in the Democratic Republic of the Congo: a phylogenetic and in vitro analysis

Laura K McMullan, PhD, Mike Flint, PhD, Ayan Chakrabarti, MS, Lisa Guerrero, MPH, Michael K Lo, PhD, Danielle Porter, PhD, Stuart T Nichol, PhD, Christina F Spiropoulou, PhD, César Albariño, PhD

Published: July 09, 2019 / DOI: https://doi.org/10.1016/S1473-3099(19)30291-9

 

Summary

Background

The ongoing Ebola virus outbreak in the Ituri and North Kivu Provinces of the Democratic Republic of the Congo, which began in July, 2018, is the second largest ever recorded. Despite civil unrest, outbreak control measures and the administration of experimental therapies and a vaccine have been initiated. The aim of this study was to test the efficacy of candidate therapies and diagnostic tests with the outbreak strain Ituri Ebola virus. Lacking a virus isolate from this outbreak, a recombinant Ituri Ebola virus was compared with a similarly engineered Makona virus from the 2013–16 outbreak.

Methods

Using Ebola virus sequences provided by organisations in DR Congo and a reverse genetics system, we generated an authentic Ebola virus from the ongoing outbreak in Ituri and North Kivu provinces. To relate this virus to other Ebola viruses in DR Congo, we did a phylogenetic analysis of representative complete Ebola virus genome sequences from previous outbreaks. We evaluated experimental therapies being tested in clinical trials in DR Congo, including remdesivir and ZMapp monoclonal antibodies, for their ability to inhibit the growth of infectious Ituri Ebola virus in cell culture. We also tested diagnostic assays for detection of the Ituri Ebola virus sequence.

Findings

The phylogenetic analysis of whole-genome sequences from each Ebola virus outbreak suggests there are at least two Ebola virus strains in DR Congo, which have independently crossed into the human population. The Ituri Ebola strain initially grew slower than the Makona strain, yet reached similar mean yields of 3 × 10 7 50% tissue culture infectious dose by 72 h infection in Huh-7 cells. Ituri Ebola virus was similar to Makona in its susceptibility to inhibition by remdesivir and to neutralisation by monoclonal antibodies from ZMapp and other monoclonal antibodies. Remdesivir inhibited Ituri Ebola virus at a 50% effective concentration (EC 50) of 12nM (with a selectivity index of 303) and Makona Ebola virus at 13nM (with a selectivity index of 279). The Zmapp monoclonal antibodies 2G4 and 4G7 neutralised Ituri Ebola virus with a mean EC 50 of 0·24 μg/mL and 0·48 μg/mL, and Makona Ebola virus with a mean EC 50 of 0·45 μg/mL and 0·2 μg/mL. The Xpert Ebola and US Centers for Disease Control and Prevention real-time RT-qPCR diagnostic assays detected Ituri and Makona Ebola virus sequences with similar sensitivities and efficiencies, despite primer site binding mismatches in the Ituri Ebola virus.

Interpretation

Our findings provide a rationale for the continued testing of investigational therapies, confirm the effectiveness of the diagnostic assays used in the region, and establish a paradigm for the use of reverse genetics to inform response activities in an outbreak.

Funding

US Centers for Disease Control and Prevention.

Keywords: Ebola; Ebola-Makona; Ebola-Ituri; Antivirals; Monoclonal Antibodies; Zmapp; Remdesivir; DRC.

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#Reproductive #health #sequelae among women who survived #Ebola virus disease in #Liberia (Int J Gynaecol Obstet., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Int J Gynaecol Obstet. 2019 May 10. doi: 10.1002/ijgo.12858. [Epub ahead of print]

Reproductive health sequelae among women who survived Ebola virus disease in Liberia.

Godwin CL1,2, Wohl DA3, Fischer Nd WA4, Singh K1, Hawks DA5, Devore EE6, Brown J7.

Author information: 1 Department of Maternal and Child Health, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, USA. 2 FHI 360, Durham, USA. 3 Division of Infectious Disease, University of North Carolina School of Medicine, Chapel Hill, USA. 4 Division of Pulmonary and Critical Care Medicine, University of North Carolina School of Medicine, Chapel Hill, USA. 5 Institute for Global Health & Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, USA. 6 Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, USA. 7 Eternal Love Winning Africa Hospital, Monrovia, Liberia.

 

Abstract

OBJECTIVE:

To estimate the incidence of failed pregnancy and menstrual irregularities among Liberian women who had survived Ebola virus disease (EVD) and to identify host-specific and disease-specific factors associated with these outcomes.

METHODS:

A cross-sectional questionnaire-based study was conducted between August 10, 2016, and February 7, 2017. The study population comprised 111 women aged 18-45 years who had survived EVD and were enrolled in the Longitudinal Liberian Ebola Survivor study based at the Eternal Love Winning Africa Hospital, Monrovia, Liberia. Self-reported data on outcomes related to pregnancy and menstrual changes since recovery from EVD were collected.

RESULTS:

In all, 29 (26.1%) of the participants had become pregnant since surviving EVD. Of the 23 women whose pregnancies continued to term, 10 (43.4%) reported live birth, 11 (47.8%) reported spontaneous abortion, and two (8.7%) reported stillbirth. Of the 105 women who reported having regular menstruation before EVD, 27 (29.0%) reported experiencing irregular menstruation for unknown reasons after EVD. In bivariate logistic models, no associations were found between failed pregnancy or irregular menstruation and any of the factors of interest.

CONCLUSIONS:

Adverse pregnancy outcomes and irregular menstruation were frequently reported among EVD survivors in Liberia.

This article is protected by copyright. All rights reserved.

KEYWORDS: Ebola virus disease; Liberia; Menstruation; Post-Ebola sequelae; Pregnancy; Spontaneous abortion; Stillbirth; Survivor

PMID: 31074837 DOI: 10.1002/ijgo.12858

Keywords: Ebola; Pregnancy; Liberia.

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Impact of #Intravenous #Fluid #Therapy on #Survival Among Patients with #Ebola Virus Disease: An #International Multisite Retrospective Cohort Study (Clin Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Clin Infect Dis. 2019 May 3. pii: ciz344. doi: 10.1093/cid/ciz344. [Epub ahead of print]

Impact of Intravenous Fluid Therapy on Survival Among Patients with Ebola Virus Disease: An International Multisite Retrospective Cohort Study.

Aluisio AR1, Yam D2, Peters JL3, Cho DK3, Perera SM4, Kennedy SB5, Massaquoi M5, Sahr F6, Smit MA7, Liu T2, Levine AC1.

Author information: 1 Department of Emergency Medicine, Brown University Alpert Medical School, Providence, RI, USA. 2 Center for Statistical Sciences, Department of Biostatistics, Brown University School of Public Health, Providence, RI, USA. 3 Brown University, Providence, RI, USA. 4 International Medical Corps, Washington, DC, USA. 5 Ministry of Health, Monrovia, Liberia. 6 Sierra Leone Ministry of Defense, Freetown, Sierra Leone. 7 Division of Infectious Diseases, Children’s Hospital Los Angeles, Los Angeles, CA, USA.

 

Abstract

BACKGROUND:

Intravenous fluid (IVF) is a frequently recommended intervention in Ebola Virus Disease (EVD), yet its impact on patient outcomes remains unclear.

METHODS:

This retrospective cohort study evaluated patients with EVD admitted to five Ebola Treatment Units (ETU) in West Africa. The primary outcome was the difference in 28-day survival between cases treated and not treated with IVF. To control for demographic and clinical factors related to both IVF exposure and survival, cases were compared using propensity score matching. To control for time-varying patient and treatment factors over the course of ETU care, a marginal structural proportional hazards model (MSPHM) with inverse probability weighting was used to assess for 28-day survival differences.

RESULTS:

Among 424 EVD positive cases with data for analysis, 354 (83.5%) were treated with IVF at some point during their ETU admission. Overall, 146 (41.3%) cases treated with IVF survived, while 31 (44.9%) cases not treated with any IVF survived (p=0.583). Matched propensity score analysis found no significant difference in 28-day survival between cases treated and not treated with IVF during their first 24 and 48 hours of care. Adjusted MSPHM survival analyses also found no significant difference in 28-day survival for cases treated with IVF (27.3%) compared to those not treated with IVF (26.9%) during their entire ETU admission (p=0.893).

CONCLUSION:

After adjustment for patient and treatment-specific time varying factors, there was no significant difference in survival among patients with EVD treated with IVF as compared to those not treated with IVF.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

KEYWORDS: Ebola Virus Disease; West Africa; intravenous fluid; marginal structural models; survival

PMID: 31050703 DOI: 10.1093/cid/ciz344

Keywords: Ebola; West Africa.

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Effectiveness of #Dettol #Antiseptic Liquid for #Inactivation of #Ebola Virus in Suspension (Sci Rep., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Sci Rep. 2019 Apr 29;9(1):6590. doi: 10.1038/s41598-019-42386-5.

Effectiveness of Dettol Antiseptic Liquid for Inactivation of Ebola Virus in Suspension.

Cutts TA1,2, Ijaz MK3,4, Nims RW5, Rubino JR3, Theriault SS6,7,8.

Author information: 1 Applied Biosafety Research Program, Canadian Science Centre for Human and Animal Health, 1015 Arlington Street, Winnipeg, MB, R3E 3P6, Canada. 2 J. C. Wilt Infectious Diseases Research Centre, Public Health Agency of Canada, 745 Logan Street, Winnipeg, MB, R3E 3L5, Canada. 3 Research & Development, RB, One Philips Parkway, Montvale, New Jersey, 07645, USA. 4 Medgar Evers College of the City University of New York (CUNY), 1650 Bedford Ave, Brooklyn, New York, 11225, USA. 5 RMC Pharmaceutical Solutions, Inc., 1851 Lefthand Circle, Suite A, Longmont, Colorado, 80501, USA. 6 Applied Biosafety Research Program, Canadian Science Centre for Human and Animal Health, 1015 Arlington Street, Winnipeg, MB, R3E 3P6, Canada. steven.theriault@canada.ca. 7 J. C. Wilt Infectious Diseases Research Centre, Public Health Agency of Canada, 745 Logan Street, Winnipeg, MB, R3E 3L5, Canada. steven.theriault@canada.ca. 8 Department of Microbiology, The University of Manitoba, Winnipeg, MB, R3T 2N2, Canada. steven.theriault@canada.ca.

 

Abstract

The efficacy of Dettol Antiseptic Liquid (DAL) for inactivating Ebola virus (Makona C07 variant) (EBOV/Mak) within an organic load in suspension was evaluated per ASTM E1052-11. Three DAL lots were evaluated at dilutions of 1:10, 1:20, and 1:40, with contact times of 0.5, 1, 5, and 10 min. Approximately 7 log10 tissue culture infectious dose50 (TCID50) of EBOV/Mak was exposed to DAL at ambient temperature. Each dilution tested reduced the infectious EBOV/Mak titer by ~5 log10 within one min. Detectable virus was still present after an 0.5-min exposure, but each DAL dilution caused >4 log10 reduction within this time. Detection of virus below the limit of detection of the TCID50 assay was assessed by inoculating flasks of Vero E6 cells with undiluted neutralized sample and evaluating the cultures for cytopathic effect after 14 days incubation. No infectious virus was detected with this non-quantitative method in samples subjected to DAL for 5 or 10 min, regardless of the dilution evaluated. The rapid and substantial inactivation of EBOV/Mak by DAL suggests that use of this hygiene product could help prevent the spread of Ebola virus disease during outbreaks.

PMID: 31036865 DOI: 10.1038/s41598-019-42386-5

Keywords: Antiseptic; Dettol; Ebola-Makona.

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#Inflammatory and #Humoral Immune Response during #Ebola Virus #Infection in #Survivor and #Fatal Cases Occurred in #SierraLeone during the 2014⁻2016 #Outbreak in West Africa (Viruses, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Viruses. 2019 Apr 23;11(4). pii: E373. doi: 10.3390/v11040373.

Inflammatory and Humoral Immune Response during Ebola Virus Infection in Survivor and Fatal Cases Occurred in Sierra Leone during the 2014⁻2016 Outbreak in West Africa.

Colavita F1, Biava M2, Castilletti C3, Lanini S4, Miccio R5, Portella G6, Vairo F7, Ippolito G8, Capobianchi MR9, Di Caro A10, Lalle E11.

Author information: 1 National Institute for Infectious Diseases “L. Spallanzani”, IRCCS, Via Portuense 292, 00149 Rome, Italy. francesca.colavita@inmi.it. 2 National Institute for Infectious Diseases “L. Spallanzani”, IRCCS, Via Portuense 292, 00149 Rome, Italy. mirella.biava@inmi.it. 3 National Institute for Infectious Diseases “L. Spallanzani”, IRCCS, Via Portuense 292, 00149 Rome, Italy. concetta.castilletti@inmi.it. 4 National Institute for Infectious Diseases “L. Spallanzani”, IRCCS, Via Portuense 292, 00149 Rome, Italy. simone.lanini@inmi.it. 5 EMERGENCY-NGO, Via Santa Croce 19, 20122 Milan, Italy. rossella.miccio@emergency.it. 6 EMERGENCY-NGO, Via Santa Croce 19, 20122 Milan, Italy. gina.portella@emergency.it. 7 National Institute for Infectious Diseases “L. Spallanzani”, IRCCS, Via Portuense 292, 00149 Rome, Italy. francesco.vairo@inmi.it. 8 National Institute for Infectious Diseases “L. Spallanzani”, IRCCS, Via Portuense 292, 00149 Rome, Italy. giuseppe.ippolito@inmi.it. 9 National Institute for Infectious Diseases “L. Spallanzani”, IRCCS, Via Portuense 292, 00149 Rome, Italy. maria.capobianchi@inmi.it. 10 National Institute for Infectious Diseases “L. Spallanzani”, IRCCS, Via Portuense 292, 00149 Rome, Italy. antonino.dicaro@inmi.it. 11 National Institute for Infectious Diseases “L. Spallanzani”, IRCCS, Via Portuense 292, 00149 Rome, Italy. eleonora.lalle@inmi.it.

 

Abstract

Ebola virus (EBOV) infection is characterized by an excessive inflammatory response, a loss of lymphocytes and a general paralysis of the immune system, however pathophysiological mechanisms are not fully understood. In a cohort of 23 fatal and 21 survivors of ebola virus disease (EVD) cases admitted to the Emergency Ebola-Treatment-Center in Goderich (Freetown, Sierra Leone) during the 2014 to 2016 EBOV epidemic in Western Africa, we analyzed the pathway-focused gene expression profile of secreted proteins involved in the immune response and the levels of specific anti-EBOV IgM and IgG from the time of admission till discharge or death. We observed a dysregulated inflammatory response in fatal patients as compared to survivors, mainly consisting of the upregulation of inflammatory mediators, whose extent directly correlated with viremia levels. The upregulation persisted and intensified during the late phase of infection. Relevant differences were also found in humoral immunity, as an earlier and more robust EBOV antibody response was observed in survivor patients.

KEYWORDS: antibody; cytokines; ebola virus; immune response; inflammation; sierra leone

PMID: 31018522 DOI: 10.3390/v11040373

Keywords: Ebola; Ebola-Makona; Sierra Leone; Immunopathology.

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Comprehensive #Clinical and Laboratory #Followup of a #Female Patient With #Ebola Virus Disease: #SierraLeone Ebola Virus #Persistence Study (Open Forum Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Open Forum Infect Dis. 2019 Feb 26;6(3):ofz068. doi: 10.1093/ofid/ofz068. eCollection 2019 Mar.

Comprehensive Clinical and Laboratory Follow-up of a Female Patient With Ebola Virus Disease: Sierra Leone Ebola Virus Persistence Study.

Liu WJ1, Sesay FR2, Coursier A3, Knust B4, Marrinan JE3, Whitmer S4, McDonald SLR3, Gaillard P3, Liu Y1, Su Q1, Zhang Y1, Crozier I3, Ariyarajah A3, Carino M3, Massaquoi T2, Broutet N3, Xu W1, Wu G1, Ströher U4, Gao GF1, Formenty P3, Sahr F2, Deen GF5; Sierra Leone Ebola Virus Persistence Study Group.

Collaborators (11): Bangura J, Jambai A, James F, Wurie A, Yamba F, Sahr F, Fornah H, Kamara R, Massaquoi TA, Sesay FR, Davies T.

Author information: 1 NHC Key Laboratory of Medical Virology and Viral Diseases, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China. 2 The Sierra Leone Ministry of Defense, Freetown, Sierra Leone. 3 World Health Organization, Geneva, Switzerland. 4 Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, Georgia. 5 The Sierra Leone Ministry of Health and Sanitation, Freetown, Sierra Leone.

 

Abstract

The clinical, virologic, and immunologic findings in a female Ebola virus disease patient are described. During the long-term follow-up, Ebola virus RNA was detectable in vaginal fluid before 36 days after symptom onset, with nearly an identical genome sequence as in acute phase blood. Ebola-specific T cells retained activation at 56 days after disease onset.

KEYWORDS: Ebola virus; clinical sequelae; immune responses; virus genome; virus persistence

PMID: 30949523 PMCID: PMC6440679 DOI: 10.1093/ofid/ofz068

Keywords: Ebola; Ebola-Makona; Sierra Leone.

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#Determinants of #transmission #risk during the late stage of the West African #Ebola #epidemic (Am J Epidemiol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Am J Epidemiol. 2019 Apr 3. pii: kwz090. doi: 10.1093/aje/kwz090. [Epub ahead of print]

Determinants of transmission risk during the late stage of the West African Ebola epidemic.

Robert A1, Edmunds WJ1, Watson CH1, Henao-Restrepo AM2, Gsell PS2, Williamson E3, Longini IM4, Sakoba K5, Kucharski AJ1, Touré A5, Nadlaou SD5, Diallo B6, Barry MS5, Fofana TO5, Camara L5, Kaba IL5, Sylla L5, Diaby ML5, Soumah O5, Diallo A5, Niare A5, Diallo A5, Eggo RM1.

Author information: 1 Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, UK. 2 World Health Organization, Geneva, Switzerland. 3 Department of Medical Statistics, London School of Hygiene &Tropical Medicine, UK. 4 Department of Biostatistics, University of Florida, USA. 5 WHO Ebola vaccination team, Guinea. 6 WHO Ebola vaccination team, Guinea, Ministry of Health, Guinea.

 

Abstract

Understanding risk factors for Ebola transmission is key for effective prediction and design of interventions. We used data on 860 cases in 129 chains of transmission from the latter half of the 2013-16 Ebola outbreak in Guinea. Using negative binomial regression, we determined characteristics associated with the number of secondary cases resulting from each infected individual. We found that attending an Ebola Treatment Unit was associated with a 38% decrease in secondary cases (Incident rate ratio (IRR) 0.62, 95%CI: 0.38, 0.99) in individuals that did not survive. Unsafe burial was associated with a higher number of secondary cases (IRR 1.82, 95%CI: 1.10, 3.02). The average number of secondary cases was higher for the first generation of a transmission chain (mean = 1.77), compared with subsequent generations (mean = 0.70). Children were least likely to transmit (IRR 0.35 (95%CI: 0.21, 0.57) compared with adults, whereas older adults were associated with higher numbers of secondary cases. Men were less likely to transmit than women (IRR 0.71 (95%CI: 0.55, 0.93)). This detailed surveillance dataset provided an invaluable insight into transmission routes and risks. Our analysis highlights the key role that age, receiving treatment, and safe burial played in the spread of EVD.

© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

KEYWORDS: Ebola; Guinea; Multiple imputation; Regression analysis; Risk factors

PMID: 30941398 DOI: 10.1093/aje/kwz090

Keywords: Ebola; Ebola-Makona; West Africa.

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