Antivirals May Work Against Ebola

Beth Skwarecki

August 27, 2015

Four healthcare workers who had needlestick injuries while providing direct patient care to patients with Ebola in Sierra Leone did not go on to develop the disease after they were treated with postexposure prophylaxis. The postexposure prophylaxis included the experimental antiviral Favipiravir (Toyama Chemical of Japan). Two of the workers were also treated with anti-Ebola monoclonal antibodies.

"We cannot know whether or not [postexposure prophylaxis] prevented the onset of Ebola virus disease in any of these individuals. However, two individuals...had very high risk for Ebola virus transmission and these are the first reported cases of transcutaneous, hollow-bore needlestick injuries contaminated with fresh blood that have not resulted in Ebola virus transmission," Michael Jacobs, PHD, MBBS, FRCP, DTM&H, from the Department of Infection at the Royal Free London NHS Foundation Trust, and colleagues write in an article published online August 25 in the Lancet Infectious Diseases.

The team developed a risk assessment algorithm for deciding who should receive treatment. They managed four other workers with "watchful waiting." Two of those had skin-to-skin contact with patients with early Ebola disease, one had an eye splash while removing protective equipment, and another tore their protective equipment while in a treatment unit.

"No consensus exists about which levels of risk warrant [postexposure prophylaxis] and whether any should be managed by watchful waiting," the authors write. They count their algorithm as a tentative success because none of the eight patients ended up developing the disease.

All eight patients worked directly with patients with Ebola in Sierra Leone and were evacuated to the United Kingdom for treatment between January and March 2015. None had any substantial comorbidity.

Previous published reports of postexposure prophylaxis for patients with Ebola used the experimental vesicular stomatitis virus-vectored Ebola glycoprotein vaccine. Patients who received the vaccine experienced moderate to severe febrile syndromes and, after treatment, tested positive for Ebola glycoprotein. The vaccine was only partially effective in animals when given after exposure. Because of these drawbacks, the team chose to use antiviral drugs and antibodies instead of the vaccine.

Two patients were considered at "maximum" risk of contracting the virus. One had a needlestick injury, through gloves, from a needle used to draw blood from a patient with Ebola; the other had a similar injury from an intravenous catheter insertion needle. Both were given Favipiravir within 10 hours after exposure and continued on a regimen that involved loading doses in the first day and maintenance doses for a total of 10 days afterward. Without data to guide treatment, the team chose a higher dose of the drug than had been used in influenza trials, and for a longer duration, to cover the period when patients were judged to be at maximum risk of developing the disease.

Those two patients were also treated with monoclonal antibodies at days 2 and 5 after exposure. One patient received two doses of MIL77, which had not been used in humans before; the other received one dose of ZMab and one of MIL77.

Two other patients were judged to be at "intermediate" risk. One had a needlestick injury through potentially contaminated gloves with a potentially contaminated needle. The other had a needlestick injury with a clean needle through potentially contaminated gloves. Both were treated with Favipiravir but not monoclonal antibodies. All four patients tolerated treatment well.

"We had very little data to base our treatment decisions on. Although an evidence base is lacking, development of international consensus guidelines about exposure risk and the appropriateness of PEP in different situations is urgently needed," the authors write.

"A needed next step is the development of a consensus risk determination algorithm devised by an expert panel, drawing on all available evidence, endorsed by health organisations, and disseminated to the field," Mark Mulligan, MD, and Paul Siebert, MD, from the Division of Infectious Diseases at Emory University in Atlanta, Georgia, write in an accompanying comment. They suggest that Ebola researchers follow in the footsteps of an international consortium in the early days of HIV/AIDS, which performed a retrospective case-control analysis of healthcare workers who had been exposed to the virus.

The authors and commentators have disclosed no relevant financial relationships.

Lancet Infect Dis. Published online August 25, 2015. Article full text, Comment extract

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