The slowing of the epidemic of Ebola in West Africa news and reasons to be hosted hope but it is also creating a new problem. With fewer new cases occur, it becomes increasingly difficult to test vaccines and medicines. As a result, conflicts loom on which can test drugs and vaccines for Ebola in Guinea and Sierra Leone.
In Guinea, a large consortium including Médecins Sans Frontières (MSF) and the World Health Organization (WHO) vaccinated the first volunteers at risk of Ebola Monday in a large trial of a vaccine produced Merck and NewLink Genetics. But the team feels threatened because researchers from the National Institutes of Health (NIH) looking to spend another vaccine study in Liberia, where the epidemic came to a virtual halt, Guinea.
The US decision could jeopardize the Guinean trial, said John-Arne R ø Göttingen of the Public Health Institute in Oslo, Norway, which chairs the steering committee of the study. "The two tests may be underway in the same place? I think not," said Marie-Paule Kieny, Assistant Director-General of WHO. "There is a risk if it is not done to neatly, neither trial was conclusive in the end. "
But Clifford Lane, director of clinical research at the National Institute of allergy and infectious diseases in Bethesda, Maryland, part of the NIH said that Guinea, which reported 45 new patients last week, can accommodate both studies. "Guinea is essentially as large as Sierra Leone and Liberia together," he said. "it seems reasonable to least explore the possibility. "
Meanwhile, an international team of test an Ebola drug called TKM-Ebola in Sierra Leone is concerned that the NIH is looking for zmapp extend his trial, another Ebola therapy, from Liberia to Sierra Leone. This movement could prevent researchers to expand their trials TKM-Ebola as expected, or even create direct competition to a processing unit Ebola in the city of Sierra Leone Port Loko where it is already underway.
Before the current outbreak, scientists never had a real chance to test Ebola drugs or vaccines for effectiveness. The products had not moved through Phase I safety studies, and homes were much smaller and still finished in a few months. The current outbreak, which has caused nearly 25,000 cases and over 10,000 deaths, offers a unique opportunity to test candidate vaccines and drugs that could save lives in the future, scientists say.
Ironically, Guinea was first passed over when the vaccine trials were planned. Last October, when some models have suggested more than one million people could get Ebola, scientists, politicians and regulators met in Geneva, Switzerland, to discuss how to move forward with vaccine candidates . At the end of this meeting, plans were agreed to study the vaccine in Sierra Leone and Liberia; Guinea, where the epidemic began, but has had fewer patients, was considered a particularly difficult environment for testing a vaccine. Feeling that was unfair, some participants in the meeting established a working group to design a test for Guinea and make sure that at least some Guineans have quick access to experimental vaccines.
The group came up with an unusual design called a "ring vaccination trial" in which a ring of people around the newly discovered Ebola patient is vaccinated. Whole rings are randomized to be vaccinated immediately or after 21 days. If a lot more people contract Ebola in the last rings, the vaccine is effective.
the NIH study, on the other hand, is designed as a classic randomized controlled trial (RCT) controlled, with one group receiving the genetic -NewLink Merck vaccine candidate, another different group of a vaccine developed by GlaxoSmithKline, and a third group receiving a placebo. the researchers began vaccinating healthy adults in Liberia in early February first to study the degree of vaccine safety are and how much of an immune response they generate. "We think we have a very good safety database and immunogenicity," says Lane.
After several hundred vaccinations, scientists are ready to begin Phase III, where effectiveness is tested. But it will not be possible in Liberia, where one patient was confirmed in the last three weeks, said Lane. "We are committed to trying to complete the study. To do this, we will probably have to work in Guinea and / or Sierra Leone, "he said. The team has reached out to the Guinean Ministry of Health and French researchers working on a drug test in Guinea, "to see if something can be put in place," says Lane. "I hope that a country like Guinea is big enough to make at least two studies. "
no, it's not, said Peter Smith, an epidemiologist at the London School of Hygiene & Tropical Medicine who was asked by wHO to study the issue. (Smith is not directly involved in the ring vaccination trial, but he chairs the board of the Norwegian program of the global health and vaccination research, which is co-funding.) " my conclusion is that it would not be possible to successfully perform both tests in Guinea at the same time (unless a radical change in the epidemiology of the disease in Guinea and the incidence of the disease increases much higher levels than they are today), "he wrote in an e-mail to science Insider.
Allocate a portion of the country to the NIH study and exclusion cases in the field of ring vaccination of the test would not work, Smith said, because the probability of catching Ebola is only big enough in the area around the capital Conakry, where WHO study, MSF has already begun. "It would not only jeopardize the chances of the ring vaccination trial with sufficient power to demonstrate efficacy but also, unless the NIH was prepared to increase significantly the size of their trial the NIH trial would have little or no power to detect effectiveness. "
that Guinea will agree to host the NIH trial and does not know, but there is clearly a need for both groups to speak, R ø Göttingen said. "I hope we can sit down and have a good discussion with them, we have not been able to do it at this stage." A compromise might be to run the two tests one after the other, said Kieny. The ring vaccination trial is expected to enroll 10 rings in late May; the latest vaccinations will take place three weeks later. Add a few months follow, Kieny said, then NIH could begin its own study. "Frankly, they are not ready to start soon now anyway."
Lane said it would probably take 6 to 8 weeks to start the retrial in Guinea. The study should not be delayed further, he argues, in part because the design of the study by WHO-MSF may not be the best to assess the effectiveness of a vaccine. For example, he said, most cases avoided in the trial of ring vaccination would occur shortly after exposure, leaving open how the vaccine protects long term. "If my goal is to get the most effective vaccine as quickly as possible to the greatest possible number of people, I think a RCT is the most direct way," he said.
In Sierra Leone, researchers from Oxford University recently began a trial of TKM-Ebola, a therapeutic experimental Ebola synthetic siRNAs. Now the effort to test the antibody cocktail of zmapp is expanding from Liberia to Sierra Leone and NIH-led. "We hear rumors that the NIH has concluded an agreement with the government of Sierra Leone to conduct the trial in any zmapp Ebola treatment unit, even those who have already tests running," said Peter Horby, the principal investigator of the study TKM-Ebola. "If true, it undermines the ongoing trials and lead to conflict."
Lane said the government of Sierra Leone decide what treatment units will participate, and Port Loko, where TKM-Ebola study is running, are not currently included in the list. "We forgive our local partners," says Lane.
However, Lane says that patients should have access to the most promising experimental drugs available, and data on animal zmapp look better than those for TKM-Ebola. Horby agrees with this assessment, but said he does not know how this translates into humans. (He says his team proposed to test zmapp in Sierra Leone, but has not had access to the product because the Food and Drug Administration of the United States has not approved the study design, in which the patients receiving TKM-Ebola patients are compared to Ebola to another processing units that do not receive the drug.) "It would not be reasonable or ethical to stop a trial well in running a promising product for a promising alternative product, "said Horby.
early study of ring vaccination in Guinea on Monday came exactly one year after the first case of the deadly disease had been diagnosed in the country, alerting the world on what has become the worst Ebola outbreak ever seen. the implementation of the trial was a huge challenge, given the poor infrastructure in Guinea and the general distrust of the health system among the population, said Kieny. "This is a great success," she said. "There was a large participation of the community and no problems with violence."
* Ebola files: Science and Science Translational Medicine made a collection of research and articles on the Ebola virus and the current epidemic available for researchers and the general public.
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