Anti-viral therapies may protect against Ebola

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For the first time, UK physicians have demonstrated that antiviral-based therapies have the potential to protect humans from the deadly Ebola virus. The report describes a case-series of eight British health-care workers who were evacuated to the Royal Free Hospital in London, UK after possible accidental exposure to Ebola virus in Sierra Leone between January and March 2015.

Four of the health-care workers were considered to have been at significant risk of exposure to Ebola from needle-stick injuries and were given post-exposure prophylaxis (PEP) with the antiviral drug favipiravir (Toyama Chemical Company), with or without monoclonal antibodies (similar to ZMapp). The other four workers had exposure that was not the result of a sharps injury, and were judged to be at lower risk. They were not given PEP, but were managed by watchful waiting.

None of the health-care workers went on to develop Ebola. All eight healthcare workers remained healthy throughout the 42 day follow-up, with no signs of disease or detectable levels of virus in their blood. The treatment regimen was well tolerated with no serious adverse events reported.

“It is possible that none of these health-care workers were infected with Ebola virus. Therefore, we cannot know for sure whether or not post-exposure prophylaxis prevented the onset of Ebola-virus disease,” says lead author Dr Michael Jacobs from the Royal Free NHS Foundation Trust, London, UK. “However, two of the workers had needle-stick injuries contaminated with fresh blood from patients with Ebola virus disease putting them at very high risk of transmission.”

The risk of Ebola infection for healthcare workers in west Africa is high. By 5 August, 2015, 880 out of 27,862 cases of Ebola were reported in healthcare workers. Yet, for doctors and nurses caring for Ebola patients there are no guidelines to quantify exposure risk, and until now, any evidence that PEP may be beneficial in humans.

According to Jacobs, “We are excited to publish the first report of an antiviral-based post-exposure treatment against Ebola-virus infection in humans. We believe this work justifies further study of this post-exposure treatment to protect health-care workers accidentally exposed to Ebola virus in the field. What is more, a similar approach to treat household contacts of Ebola cases may work to prevent a major route of spread during an epidemic.”

The authors conclude by calling for standardised guidelines about transmission risk and management after potential exposure to be urgently developed and adopted as they have been for many other infections such as HIV and hepatitis B virus.

Writing in a linked Comment, Professor Mark Mulligan and Dr Paul Siebert from Emory University in the US said, “A needed next step is the development of a consensus risk determination algorithm devised by an expert panel, drawing upon all available evidence, endorsed by health organisations, and disseminated to the field. The algorithm could be accompanied by a chart abstraction and case report form to standardise and organise data gathering. These data for recognised exposures could be collated and analysed for an international registry.”

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.

The Lancet material
The Lancet Infectious Diseases article summary


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