Science to the rescue in West Africa? The World Health Organization is launching a crash programme to test experimental treatments on people who have Ebola, in an emergency bid to stem the epidemic. The move will get round regulatory barriers that have so far stopped one promising drug that is almost fully tested from being used in the epidemic.
“This is absolutely unprecedented,” said Marie-Paule Kieny, head of innovation at the WHO, on 5 September, after a meeting in Geneva, Switzerland, of drug developers, regulators and African health authorities had approved the plan. “We must move as fast as possible.”
WHO ethical guidelines allow treatments that have passed initial safety tests but haven’t yet been fully tested and approved to be used to try and save lives – as long as information is gathered to help establish whether the treatment works. The Geneva meeting agreed to test two experimental vaccines and a handful of other treatments on this basis. This includes treating patients with blood from Ebola survivors and using drugs that have halted Ebola in mice and monkeys.
Gathering data on whether the treatments work will not be easy, because health care workers in the epidemic zone are already overwhelmed just caring for patients. Additional staff will be needed to run the trials, says Fred Haydenof the University of Virginia at Charlottesville, who was at the Geneva meeting and will help to evaluate the testing protocols starting next week.
“Even taking additional blood samples in the circumstances of many of the existing treatment centres will not be without significant challenges,” says Peter Smith of the London School of Hygiene and Tropical Medicine.
There are now around 500 new cases per week, and this will number in the thousands by October if the rate of spread is not slowed, says Chris Dye, a senior epidemiologist at the WHO. That depends on isolating cases and their contacts, but with little help on offer at treatment centres, people are not reporting sick relatives, or isolating themselves.
In an “exceptional measure” such as was called for in the WHO’s “roadmap” for controlling the epidemic, Sierra Leone plans to make everyone in the country stay indoors from 19 to 21 September, while teams go from door to door to find cases.
The aid group Médecins Sans Frontières says this will drive cases further underground. But Hayden hopes the experimental medications that the WHO wants to release will have the opposite effect, inducing people to seek out treatment centres earlier in the infection, and reducing spread.
Kieny says the aim is to evaluate different treatments at different sites, allowing clear comparisons to be made to quickly determine which ones work.
One treatment to be trialled is the use of blood or plasma from people who have survived Ebola, because it is loaded with anti-Ebola antibodies. Blood from survivors seemed to save seven of eight patients in a central African outbreak in 1995. US Army researchers reported in 2012 that plasma from monkeys who were vaccinated for Ebola, then survived infection with the virus, protected non-immune monkeys even when it was given two days after they were infected.
Plasma or blood from Ebola survivors could be used widely in Africa before the end of the year, if facilities can be found to collect it safely. It has already been used on a few cases in Sierra Leone and Liberia, including Kent Brantly, an infected US missionary, says Margaret Harris of the WHO. Brantly, who survived, also received an experimental antibody-based drug, ZMapp.
Only a few hundred doses of ZMapp will be available by December, says the WHO, and they need to be kept frozen, which could be difficult in West Africa. Similarly, by March next year the Canadian firm Tekmira might be able to make 900 doses of a small RNA treatment called TKM-Ebola that interferes with viral replication, however it requires slow infusion into the patient, which could also be difficult.
More promising might be two wide-spectrum antiviral drugs, BCX4430 andfavipiravir. Both resemble the nucleotide molecules that make up the virus’s RNA genome, and fool the virus’s RNA-copying enzyme – but not a human’s – into using them, crippling viral replication.
In fact it seems only regulatory red tape, of the sort the WHO now wants to eliminate, has prevented the use of favipiravir in the outbreak so far. A candidate anti-flu drug, it has already been extensively tested in humans, and was reported in March to save mice from Ebola even when given six days after infection. Japan is giving some to Nigeria and 10,000 doses are available.