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Experimental drugs and vaccines poised to take on Ebola

Endgame for outbreak in West Africa might hinge on treatments still under development

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4:42pm, August 20, 2014

EBOLA IN WEST AFRICA  The public health response to Ebola has centered on a “hot spot” where three counties meet. 

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As the Ebola virus outbreak continues to run amok in West Africa, scientists are looking ahead to the possibly pivotal use of experimental drugs and vaccines against the disease. It will take months to test, produce and deploy the therapies. But researchers hold out hope that these products — even incompletely vetted — might help to turn the tide against an illness that has defied public health efforts to bring it under control.

The treatments’ use could engender enough hope to encourage people with symptoms — and their close contacts — to come to hospitals, which researchers say would limit the spread of the lethal virus. Having experimental drugs and especially vaccines in hand could also help in recruiting and maintaining adequate levels of hospital staff, who are at high risk of catching the virus.

Using still-experimental drugs has downsides: Even if the treatments help some patients, it will be hard to determine their true effectiveness.  And failed treatments could exacerbate the despair and distrust already hampering public health efforts.

Still, public health officials and bioethics experts say the situation in West Africa is dire enough to warrant putting candidate therapies into use after minimal human safety testing. As of August 19, more than 2,200 people have been infected and more than 1,200 have died, the World Health Organization reports. Earlier this month, WHO declared the outbreak an international public health emergency that is not under control.

The outbreak has hit a thickly populated part of West Africa and spread among the contiguous countries Liberia, Guinea and Sierra Leone. None have encountered Ebola before, and the region has been racked by poverty, civil wars, corrupt government and upheaval. All of the countries have deficient health systems that have suffered even more during the outbreak as some workers abandon their posts.

Daniel Bausch, an infectious disease physician at Tulane University in New Orleans, relates an incident in Kenema, Sierra Leone. Dressed in biohazard gear, he and a WHO doctor entered the hospital there in July and were stunned to find only two workers amid 55 patients. The nurses were gone. Some were demanding higher wages for hazardous work, but many had simply left after seeing their colleagues become sick, he says. Patients were in beds and on the floor, the hospital contaminated.

“You get into a negative cycle in which it becomes a riskier environment for the nurses who do choose to keep working,” he says. “That happened in Kenema.” Even as basic public health measures slowed the outbreak in some other parts of Sierra Leone, it spun out of control in the region served by the Kenema hospital, he says.

Turning to drugs

In an opening salvo against the Ebola virus, six people have received a test drug called ZMapp, made by Mapp Biophharmaceutical of San Diego. But supplies of that compound are exhausted and making more will take months. So WHO and the U.S. Department of Health and Human Services have pulled together experts to pore over research on other candidate drugs and vaccines. The goal is to decide which products to put into rapid safety tests, says Bausch, who is among those advising WHO. In the best-case scenario, WHO officials say, some of these test drugs could reach the field later this year — after safety testing in human volunteers. All have so far been tested only in monkeys and other animals. While ZMapp uses antibodies, other approaches combine that strategy with other antiviral agents or use RNA interference to thwart the virus.

Having a drug, even an imperfect one, would have an impact beyond the individuals receiving it, Bausch says. A drug could change the mindset of people who have been in contact with patients but who are not themselves sick. Many hesitate to get tested because hospitals have no way to treat Ebola, he says. Refusal to get tested extends disease transmission if these contacts turn out to harbor the virus and develop an infection. Word of a drug could induce people to come in for testing. “Getting them out of circulation,” he says, “could end the outbreak.”

While giving experimental drugs such as ZMapp to patients has passed muster with bioethicists, the use of such drug candidates would still leave scientists with a poor understanding of how effective they are. About half of Ebola patients in West Africa survive without treatment, says physician Kevin Donovan of Georgetown University, making it difficult to distinguish whether a survivor who received a trial drug benefited from it.

Vaccines could play a role as well. WHO Assistant Director-General Marie-Paule Kieny said at an August 12 news briefing that safety testing of two experimental Ebola vaccines could start in late September. One comes from Canada’s National Microbiology Laboratory in Winnipeg, which announced last week that it will make available 800 to 1,000 doses of a vaccine that tested well in monkeys. Another vaccine is being readied by U.S. federal labs and GlaxoSmithKline. WHO will oversee who gets any test vaccines, with distribution unlikely until 2015.

Doctors, nurses and other clinical staff will be at the front of the line for such shots, says William Schaffner, an infectious disease physician at Vanderbilt University in Nashville, Tenn. “A lot of transmission occurs during the course of health care,” he says. Having a vaccine could encourage health care workers to stay on the job.

Nearly 10 percent of deaths in this outbreak have occurred in health care workers, says Kieny, adding that laboratory workers and those burying bodies would get high priority for vaccination as well.

But a lightly tested vaccine would come with caveats. It is unknown whether a single dose will protect fully, Schaffner says, so vaccinated health care workers will have to keep their guard up. They will need to continue to don biohazard suits and take other extraordinary precautions. If a vaccinated person comes down with Ebola, he says, it would hurt vaccine credibility.

Giving an experimental vaccine to relatives or other contacts of patients would seem like the next logical step, Bausch says, but could be difficult and might not yield much information about the vaccine. Those living amid the Ebola outbreak might well distrust the idea of getting a shot they may not need, and might not welcome later visits to their homes to draw blood to test for immune responses, Bausch says. “There’s an incredible stigma” attached to having Ebola in West Africa, he says. Even survivors “don’t admit they had it.”

That could complicate work on another treatment approach, called a “convalescent serum.” It would be derived from the blood of an infected person who had fended off the virus and developed antibodies against it. That research is still in its early stages, he says.

Worst one yet

Two dozen Ebola outbreaks have hit Africa since 1976. The current one has caused far more casualties than any other, WHO says, even though public health authorities have taken the same approach used previously: identifying and isolating infected people, tracing contacts of ill people for 21 days and having health care workers wear spacesuit-looking biohazard gear when monitoring the sick or handling dead bodies.

While the endgame for this Ebola outbreak remains as unclear as the animal that passed the virus to people (SN Online: 8/11/14), better understood is how the outbreak spun out of control, despite the efforts of Doctors Without Borders and other groups on the ground in Africa. “Resources were spread pretty thin early on,” says Thomas Geisbert, a virologist at the University of Texas Medical Branch at Galveston.

The extensive surveillance of contacts that had contained transmission in past outbreaks wasn’t achievable in West Africa, and rumors and misinformation have plagued work there. Episodes of lawlessness have complicated matters. Last weekend looters stormed a Liberian hospital and took mattresses and other infected supplies, risking further virus transmission.

Keiji Fukuda, WHO assistant director-general for health security, says WHO is targeting resources in the region where the three countries come together, including the Kenema area. “This is a consistent big hot spot,” he says. “It’s important to put this out.”

Nigeria also has 12 cases of Ebola, all stemming from an infected individual who flew there from Liberia. The sick people are being isolated, and more than 200 of their contacts are being monitored. Scientists hope the Nigeria mini-outbreak can be quelled. “But the jury is still out,” Bausch says.

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