ArticlesPost-exposure prophylaxis against Ebola virus disease with experimental antiviral agents: a case-series of health-care workers
Introduction
The current outbreak of Ebola virus disease in west Africa is unprecedented in scale, both in numbers of cases and geographic spread. As of June 3, 2015, 27 181 cases and 11 162 deaths have been reported, predominantly in Sierra Leone, Liberia, and Guinea.1 Hundreds of UK civilian and military staff have assisted the international humanitarian effort along with nationals of many other countries. Three UK health-care workers have acquired Ebola virus disease in the course of their work in Ebola-treatment units in Sierra Leone and have been medically evacuated to the Royal Free Hospital, London, UK, for treatment. More commonly, health-care workers have been medically evacuated after possible accidental exposure to Ebola virus.
Development of an experimental vaccine, vesicular stomatitis virus-vectored Ebola glycoprotein vaccine (rVSV/ZEBOV-GP), presented the first opportunity to use post-exposure prophylaxis (PEP) in individuals who might have been exposed to Ebola virus. In non-human primates, rVSV/ZEBOV-GP is highly effective as a preventative vaccine, but is less effective for PEP: administration 20–30 min after a lethal challenge with Ebola virus in rhesus macaques protected 50% of the animals from death, but not illness.2, 3 However, the macaque model is characterised by rapid onset of uniformly fatal illness and is therefore more severe than the disease in people, so in theory active immunisation might be more effective as PEP in people. So far, Ebola PEP has been reported three times in people, all with replication-competent rVSV/ZEBOV-GP (Public Health Agency of Canada, Winnipeg, MB, and NewLink Genetics, Ames, IA, USA): one case was reported before the current Ebola outbreak of vaccination 48 h after a laboratory needlestick injury;4 and recently, the vaccine has been administered on two occasions after needlestick injuries with a clean needle in an Ebola-treatment unit.5, 6 None of these individuals developed Ebola virus infection, but it is possible that none had exposure to Ebola virus. All individuals developed a febrile syndrome after vaccination, which was moderate to severe in one case, and all had low positive semiquantitative RT-PCR for Ebola virus GP gene (which is expressed in the live vaccine). These findings complicated clinical and virological assessment and necessitated precautionary use of high-level personal protective equipment by health-care staff.
In view of the disadvantages of active immunisation for Ebola PEP, we developed a new strategy on the basis of the use of experimental antiviral treatments, based on recent encouraging data from studies in animals. Here, we describe a new method for risk assessment and management that was applied to eight consecutive individuals potentially exposed to Ebola virus, and report for the first time, to the best of our knowledge, the use of experimental antiviral treatments for Ebola PEP in people.
Section snippets
Ebola virus exposure in health-care workers
From January to March, 2015, eight individuals were medically evacuated to the Royal Free Hospital after possible accidental Ebola virus exposure (table). All were health-care workers who had provided direct patient care in Ebola-treatment units in Sierra Leone. Ages ranged from 24 years to 52 years and none of the individuals had any substantial comorbidity. Four health-care workers had penetrating needlestick injuries with hollow-bore needles while working in the red zone (where
Risk assessment and post-exposure prophylaxis
For many other infections, such as HIV and hepatitis B virus, guidelines about transmission risk and management after potential exposure are well established. However, for Ebola only one guidance document to our knowledge is available publicly,7 and the risk of Ebola virus transmission as a consequence of different exposures remains poorly characterised.
We anticipated the need to consider PEP against Ebola in potentially exposed health-care workers, both assisting with the humanitarian effort
Antiviral agents as post-exposure prophylaxis
There is little experience of experimental treatments for Ebola virus disease in people and none of the treatments are of proven benefit. WHO has published an ethical framework for use of experimental interventions for the treatment of Ebola virus disease.12 This framework specifically applies to PEP, but there is very little experience of PEP use in people and the risk-benefit ratio for PEP is not the same as for Ebola virus disease treatment.
Several candidate antiviral approaches are
General considerations
Each of the four health-care workers who received PEP was treated entirely in hospital for 10 days. While in hospital, blood was drawn daily for routine haematology and biochemistry to detect any adverse effects of treatment and for Ebola virus RT-PCR to detect subclinical viraemia during the period of maximum risk. After discharge to the community, the health-care workers were actively monitored with twice daily temperature recordings in accordance with the UK public health recommendations.11
Outcomes and discussion
All eight health-care workers remained clinically well and afebrile throughout follow-up. None of the individuals developed Ebola virus disease or detectable Ebola virus RNA in blood. We cannot exclude the unlikely possibility of undetected subclinical infection because convalescent serological studies for Ebola were not available.
The four health-care workers assessed as low risk exposures were managed with watchful waiting. That they remained well supports our risk assessment framework (figure
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