Post-exposure prophylaxis against Ebola virus disease with experimental antiviral agents: a case-series of health-care workers

Summary

Background

Although a few international health-care workers who have assisted in the current Ebola outbreak in west Africa have been medically evacuated for treatment of Ebola virus disease, more commonly they were evacuated after potential accidental exposure to Ebola virus. An urgent need exists for a consensus about the risk assessment of Ebola virus transmission after accidental exposure, and to investigate the use of post-exposure prophylaxis (PEP). Experimental vaccines have occasionally been used for Ebola PEP, but newly developed experimental antiviral agents have potential advantages. Here, we describe a new method for risk assessment and management of health-care workers potentially exposed to Ebola virus and report the use of experimental antiviral therapies for Ebola PEP in people.

Methods

We devised a risk assessment and management algorithm for health-care workers potentially exposed to Ebola virus and applied this to eight consecutive individuals who were medically evacuated to the UK from west Africa between January, and March, 2015. PEP with antiviral agents was given to health-care workers assessed to have had substantial risk exposures to Ebola virus. Participants were followed up for 42 days after potential exposure.

Findings

Four of eight health-care workers were classified as having had low risk exposures and managed by watchful waiting in the community. None of these health-care workers developed Ebola virus disease. The other four health-care workers had intermediate or maximum risk exposures and were given PEP with antiviral agents. PEP was well tolerated with no serious adverse effects. None of these four health-care workers, including two with maximum risk exposures from penetrating injuries with freshly used hollow-bore needles, developed Ebola virus disease.

Interpretation

Standardised risk assessment should be adopted and consensus guidelines developed to systematically study the efficacy and safety of PEP with experimental agents. New experimental antiviral treatments are a viable option for PEP against Ebola.

Funding

Royal Free London NHS Foundation Trust.

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.