Because outbreaks are sporadic and mainly confined to Africa, the Ebola virus has not been a priority for profit-seeking pharmaceutical companies.

But with the largest ever Ebola outbreak now having killed more than 1,000 people in West Africa, drug companies and doctors are scrambling to see whether any existing medicines or drugs under development can help stem the epidemic.

Options include experimental treatments that have never before been tested on people and some of the world’s most widely used drugs — statins like Lipitor, which are approved to lower cholesterol but might, some advocates say, also help with Ebola.

The search is especially intense among smaller companies whose research has been funded by the government.

Investors, too, are watching the drug makers. Stock in one of the hopefuls, Tekmira, which is based in Canada, has nearly doubled in the last month. Shares of BioCryst Pharmaceuticals, which announced on Wednesday that it was receiving more federal money to test its Ebola drug candidate in monkeys and people, have also been rising.

Experts caution that most of these drugs are so early in development and in such limited quantities that they may not make a difference.

“I wish I had a better story for you, but that’s it,” one official at the Health and Human Services Department said after discussing the relative handful of drugs and vaccines in the pipeline, most of which have yet to be tested even in small clinical trials.

Despite the long odds, two Ebola vaccines could begin initial safety testing in people as early as next month, according to the official, who spoke on the condition of anonymity because his agency did not have formal contracts with some of the companies involved.

While testing will be in healthy volunteers, some of those volunteers might be health care workers who intend to go to Africa.

One of the vaccines was developed by a government laboratory in Canada. The Canadian government on Tuesday said it would donate 800 to 1,000 doses to the World Health Organization, presumably for use in Africa.

That vaccine is licensed to NewLink Genetics, a company in Ames, Iowa. Charles Link, the chief executive, said NewLink could manufacture tens of thousands of doses over the next couple of months.

The other vaccine is being developed by the National Institutes of Health and GlaxoSmithKline. There are 400 doses available now, enough for a clinical trial in healthy adults, the federal official said.

As far as treatments for people already stricken with Ebola, most attention has focused on ZMapp, developed by Mapp Biopharmaceutical of San Diego. The drug, which consists of antibodies that bind to and neutralize the virus, appears to have helped two American aid workers stricken in Liberia. Although the company says it has exhausted its supply — apparently enough to treat only six people — the federal official said he hoped 10 to 50 more treatment courses could be made by the end of the year, enough to begin a small safety study.

Tekmira’s drug uses a technique called RNA interference to silence genes in the Ebola virus. Its early-stage clinical trial in healthy volunteers was halted by the Food and Drug Administration last month because of side effects. But the F.D.A. last week said that the drug was safe enough to test in people actually infected with Ebola.

Mark J. Murray, Tekmira’s chief executive, told analysts Wednesday that the company was exploring possible use of the drug in Africa.

Sarepta Therapeutics has said it has enough experimental drug left over to treat about two dozen people. The company stopped developing the drug, which also uses RNA interference, after the Defense Department halted its funding.

A flu drug being developed by Fujifilm Holdings of Japan has shown some effectiveness against Ebola in mice, and BioCryst also has an antiviral drug that has been tested in mice. The next step is for those drugs to work in monkeys.

“I have shelves full of things that protect rodents that don’t work in monkeys,” said Dr. Thomas W. Geisbert, a professor and Ebola expert at the University of Texas Medical Branch at Galveston. “If it doesn’t protect a monkey, it’s hard to imagine how you would push it forward for use in humans.”

The World Health Organization said on Tuesday that it would be permissible to try to treat Ebola patients with untested medicines, providing certain ethical standards were observed.

Even so, Dr. Marie-Paule Kieny, the organization’s assistant director general, was cautious. “It is very important to not give false hope to anybody that Ebola can be treated now,” she said at a news conference in Geneva.

Since drugs directed specifically at Ebola are still in early development, some doctors are suggesting trying drugs already approved for other uses that are readily available and proved to be relatively safe — like statins. ]

The champion of this idea is Dr. David Fedson, a retired professor and vaccine company executive living in France. He said that although statins did not attack the virus, they might help calm the runaway immune system reaction that could follow infection, which is what inflicts much of the damage on the body.

“The concept of treating the host response is sitting there in front of our noses,” said Dr. Fedson, who has been trying to rally support for his proposal.

So far, however, the W.H.O. had turned up its nose at the idea, he said. Some Ebola experts are also skeptical.

“When you start talking about modulating the immune response, you can have unintended consequences,” said Dr. Geisbert of the University of Texas.

TORONTO -- A prominent law professor is urging the federal government to terminate an American company's licence for a Canadian-made Ebola vaccine.

The company, NewLink Genetics, doesn't have the capacity to develop the much-needed vaccine, argues Amir Attaran, a professor of law and population health at the University of Ottawa.

"The mistake Canada has made has been to keep this bad marriage with NewLink and try to make it better. Canada should either be terminating the licence agreement outright or simply issuing another licence on non-commercial terms to someone else," Attaran told The Canadian Press in an interview.

"Either of those would work. Neither of them have been done. And that's absolutely shameful."

Brian Wiley, NewLink's vice president for business development, said in an email that the company would not comment on Attaran's suggestion.

But he did confirm that a deal announced Monday -- with Genentech, a division of Swiss drugmaker Roche -- does not involve the Ebola vaccine. The deal, which will pay NewLink US$150 million upfront and potentially more than US$1 billion, is for a cancer therapy in early stage testing.

Attaran said he has written to federal Health Minister Rona Ambrose outlining why he believes Canada should strip NewLink of the vaccine licence. Her department's press office did not immediately respond on Monday to queries about Attaran's proposal.

Canada began shipping 800 vials of the vaccine to Geneva on Monday, having donated the vaccine to the World Health Organization. The donated vaccine will be used in clinical trials aimed at determining whether it is safe to use in people and what an effective dose is.

The vaccine, known as VSV-EBOV, was designed by scientists at the National Microbiology Laboratory in Winnipeg. It was licensed to NewLink, of Ames, Iowa, in 2010. NewLink's chief focus is the development of cancer vaccines.

At the time, Canada's options for commercializing the Ebola vaccines or drugs its scientists were developing were limited. Prior to this outbreak, fewer than 3,000 people had been known to have been infected with Ebola, in sporadic outbreaks in poor African countries over a period spanning nearly 40 years.

The prospects for recouping the considerable costs of developing and licensing a drug or vaccine were nil. The major players in the pharmaceutical world -- those with deep pockets and regulatory know-how -- weren't interested.

It appears from filings the company made with the U.S. Securities and Exchange Commission that NewLink paid merely $205,000 for the rights to the vaccine, Attaran said. The company is also required to pay Canada royalties -- the rate will be in "the low single-digit percentage" of the price -- on sales of the vaccine.

Many of those involved in charting the Ebola response believe an effective vaccine will be needed to bring this raging epidemic under control. And although another -- made by scientists at the U.S. National Institutes of Health -- is further along in the testing process, many scientists point to the Canadian vaccine as the better option.

For one thing, the Winnipeg-designed vaccine is expected to require only a single dose. It is thought the American vaccine will require a priming dose followed by a booster with another vaccine that will serve to stimulate the immune system.

A two-dose regimen -- with two different vaccines -- would be hugely challenging to deliver, especially in countries where the health-care systems have collapsed under the weight of the Ebola outbreak.

As well, in studies in primates the Canadian vaccine was shown to be effective at both protecting against infection and mitigating the severity of the disease when given after an animal was infected. There are no data to suggest the American vaccine would work in both pre- and post-exposure scenarios.

Because of these advantages, many are eager to see VSV-EBOV tested and to see the scale up of production of the vaccine.

But the fact that the licence is held by a small company with no experience bringing a product through the regulatory process and with no vaccine production capacity of its own is seen to be impeding the ability to make, test and -- if it is safe and effective -- eventually disseminate the vaccine in Ebola-affected countries.

The first human clinical trial of the vaccine began last week in Bethesda, Md. It had been expected that it and other trials would have begun weeks earlier, but there were delays that people knowledgeable about the process attribute to NewLink's size and inexperience.

In its most recent annual report, filed on March 31 of this year, its Ebola vaccine appears to be almost an afterthought, rating only a single mention. NewLink described itself as a "development stage company" and noted that it has incurred significant losses since its inception. At the end of 2013, the company's accumulated deficit was $136 million.

The company has been receiving significant assistance from the Biomedical Advanced Research and Development Authority, a branch of the U.S. Department of Health and Human Services that fosters development of drugs and vaccines for bio-threats like pandemic influenza and anthrax.

The contract between Canada and NewLink gives the Canadian government some options it could employ if it believes NewLink lacks the capacity to develop the vaccine. And Attaran insisted the government should have exercised one of these options before now.

"West Africa is burning, he said. "It is past time that Canada terminate the contract with them (NewLink)."

Attaran noted that in the four years since it acquired the licence to the vaccine, NewLink had not conducted a single human trial with it until now.

In the licence agreement, Canada retains the ability to make or have made the vaccine for use in Canada during an emergency.

It also has the right to let other manufacturers make the vaccine for use in other countries "for compassionate care purposes" if NewLink has not received regulatory approval for the vaccine in the target country. At the current time NewLink has not received regulatory approval for VSV-EBOV anywhere.

Health authorities and pharmaceutical companies are planning to test several new vaccines to prevent Ebola infection over the next few months, including one that is taken as a tablet, making it easier to deploy in West Africa.

The plans signify that a response to the Ebola outbreak is finally gathering steam. It is still unclear if any of these vaccines will work, however, and even if they do, they may not be ready in time to help stem the current epidemic.

Starting in January, two vaccines will be tested in large studies in the West African countries most affected by the outbreak, the World Health Organization said on Tuesday. At least three other vaccines will begin safety testing in healthy volunteers outside the outbreak zone in the first quarter of 2015.

One of those three is actually a combination of two inoculations being developed by Johnson & Johnson and Bavarian Nordic, a Danish company.

Johnson & Johnson announced early Wednesday that it was committing $200 million to the program, including making an equity investment of about $43 million in Bavarian Nordic to help pay for that company’s part in the project. It says it plans to begin safety trials in January and hopes to produce one million doses in 2015, with 250,000 available for broad application in clinical trials by May.

“Typically, you don’t make hundreds of thousands of vaccines before you know what the safety and immunogenicity is,” said Dr. Paul Stoffels, chief scientific officer of Johnson & Johnson. “This time, we will do that.”

The two most advanced vaccines in terms of development is each undergoing testing in about 250 healthy adult volunteers in the United States and other countries outside the outbreak region.

One of the vaccines was developed by the National Institutes of Health and GlaxoSmithKline. The other was initially developed by the Public Health Agency of Canada and licensed to [NewLink Genetics Corporation], a company in Iowa.

The studies, known as Phase 1 clinical trials, are determining if the vaccines are safe and generate an immune response. Preliminary results are expected by the end of the year, Marie-Paule Kieny, the World Health Organization’s assistant director general for health systems and innovation, said in a news conference in Geneva on Tuesday.

But she said her organization was not waiting for those results. It is already planning the next stage of testing, to be ready to start in January if the vaccines pass the initial tests. Those new trials will take place in the affected countries in West Africa and would involve tens of thousands of doses, she said.

There are various scientific and ethical issues to be worked out, including who should receive the vaccine and whether it would be ethical to give some participants a placebo instead. Initial studies are likely to involve health care workers but might also involve others at high risk of infection.

“We are doing everything we can to produce as many doses as we can as quickly as we can,” said Dr. Ripley Ballou, who leads the vaccine effort for GlaxoSmithKline.

Dr. Ballou said that while Glaxo would not have enough doses to vaccinate millions of Africans against Ebola, there should be enough by sometime next year to help slow the outbreak by protecting health care workers or those close to infected people.

Dr. Kieny said that three other vaccines would be ready early next year to enter Phase 1 testing, starting with the combination from Johnson & Johnson and Bavarian Nordic.

A second is being developed by [Inovio Pharmaceuticals, Incorporated], a small company in Plymouth Meeting, Pa. The third is from [Protein Sciences Corporation] of Meriden, Conn., which already sells a flu vaccine.

Dr. Kieny also said her organization was trying to find out more about vaccines being developed in Russia.

She did not mention the tablet vaccine, which Vaxart, a privately held company in South San Francisco, Calif., is developing.

Wouter Latour, the chief executive, said in an interview that, after recent discussions with the Food and Drug Administration, the company hoped to start a Phase 1 safety trial toward the end of the first quarter of 2015.

“This is ideal to bring to bear on the Ebola crisis,” Dr. Latour said. Not only is it not injected but it is stable at room temperature. Some of the other vaccines must be stored at minus 80 degrees Celsius, which might be difficult in parts of West Africa.

Dr. Latour said Vaxart’s vaccine protected mice against Ebola but is only now being tested in monkeys. But an experimental flu vaccine developed using the same approach has already been tested in a small number of people. It generated immune responses comparable to or even better than approved flu vaccines, the company’s chief scientist said in a presentation last week at the World Vaccine Congress in Brussels.

Another company, Profectus BioSciences of Baltimore, received federal funding last week to move its Ebola vaccine toward clinical trials.

GALVESTON, Tex. — Almost a decade ago, scientists from Canada and the United States reported that they had created a vaccine that was 100 percent effective in protecting monkeys against the Ebola virus. The results were published in a respected journal, and health officials called them exciting. The researchers said tests in people might start within two years, and a product could potentially be ready for licensing by 2010 or 2011.

It never happened. The vaccine sat on a shelf. Only now is it undergoing the most basic safety tests in humans — with nearly 5,000 people dead from Ebola and an epidemic raging out of control in West Africa.

Its development stalled in part because Ebola is rare, and until now, outbreaks had infected only a few hundred people at a time. But experts also acknowledge that the absence of follow-up on such a promising candidate reflects a broader failure to produce medicines and vaccines for diseases that afflict poor countries. Most drug companies have resisted spending the enormous sums needed to develop products useful mostly to countries with little ability to pay.

Now, as the growing epidemic devastates West Africa and is seen as a potential threat to other regions as well, governments and aid groups have begun to open their wallets. A flurry of research to test drugs and vaccines is underway, with studies starting for several candidates, including the vaccine produced nearly a decade ago.

A federal official said in an interview on Thursday that two large studies involving thousands of patients were planned to begin soon in West Africa, and were expected to be described in detail on Friday by the World Health Organization.

Although there are currently no drugs or vaccines approved in the United States to treat or prevent Ebola, health officials have used several experimental drugs in the recent epidemic.

With no vaccines or proven drugs available, the stepped-up efforts are a desperate measure to stop a disease that has defied traditional means of containing it.

“There’s never been a big market for Ebola vaccines,” said [Dr. Thomas William Geisbert (born 1962)], an Ebola expert here at the University of Texas Medical Branch in Galveston, and one of the developers of the vaccine that worked so well in monkeys. “So big pharma, who are they going to sell it to?” Dr. Geisbert added: “It takes a crisis sometimes to get people talking. ‘O.K. We’ve got to do something here.’ ”

[Dr. James Earl Crowe Jr. (born 1961)]the director of a vaccine research center at Vanderbilt University, said that academic researchers who developed a prototype drug or vaccine that worked in animals often encountered a “biotech valley of death” in which no drug company would help them cross the finish line.

To that point, the research may have cost a few million dollars, but tests in humans and scaling up production can cost hundreds of millions, and bringing a new vaccine all the way to market typically costs $1 billion to $1.5 billion, Dr. Crowe said. “Who’s going to pay for that?” he asked. “People invest in order to get money back.”

The Ebola vaccine on which Dr. Geisbert collaborated is made from another virus, V.S.V., for vesicular stomatitis virus, which causes a mouth disease in cattle but rarely infects people. It had been used successfully in making other vaccines.

The researchers altered V.S.V. by removing one of its genes — rendering the virus harmless — and inserting a gene from Ebola. The transplanted gene forces V.S.V. to sprout Ebola proteins on its surface. The proteins cannot cause illness, but they provoke an immune response that in monkeys, considered a good surrogate for humans, fought off the disease.

The vaccine was actually produced in Winnipeg, Manitoba, by the Public Health Agency of Canada. The Canadian government patented it, and 800 to 1,000 vials of the vaccine were produced. In 2010, it licensed the vaccine, known as VSV-EBOV, to NewLink Genetics in Ames, Iowa.

The Canadian government donated the existing vials to the World Health Organization, and safety tests of the vaccine in healthy volunteers have begun.

NewLink’s product is one of two leading vaccines being tested. The other, which uses a cold virus that infects chimpanzees, was developed by researchers at the National Institutes of Health and GlaxoSmithKline. The first tests of an earlier version of it, employing a different cold virus, began in 2003.

Several other vaccine candidates, not as far along, are also in the pipeline and may be ready for safety testing next year. Once any drugs or treatments pass the safety tests, they will be available for use in larger numbers of people, and health officials are grappling with whether they should be tested for efficacy in the traditional way, in which some people at risk are given placebos instead of the active drug.

Governments and the military became interested in making vaccines against Ebola and a related virus, Marburg, during the 1990s after a Soviet defector said the Russians had found a way to weaponize Marburg and load it into warheads. Concerns intensified in 2001 after the Sept. 11 terrorist attacks and anthrax mailings.

“The National Institutes of Health came up with a program called Partnerships in Biodefense that partnered researchers like me with companies, usually small companies,” Dr. Geisbert said.

The government money led to major advances in the laboratory, Dr. Geisbert said, but was insufficient to cover the huge costs of human trials. Nor could the small companies that were involved in the early studies in animals afford to pay for human trials. No finished product came to market.

Dr. Geisbert moved on, working on treatments for Ebola and another version of the V.S.V. vaccine. For the vaccine work, his main collaborator has been [Dr. Heinz Ulrich Feldmann (born 1959)], the chief of virology at the Rocky Mountain Laboratories in Hamilton, Mont., part of the National Institute of Allergy and Infectious Diseases.

The newer version of the vaccine uses a slightly different form of V.S.V., one that Dr. Geisbert said he thought might be less likely to cause side effects, and more likely to gain quick approval because it has been used as the basis for an H.I.V. vaccine and is known to the Food and Drug Administration. But the new version, VesiculoVax, made by Profectus Biosciences in Baltimore, has not yet been tested in humans.

The V.S.V. products are live vaccines, with replicating viruses that may cause a reaction. It is not clear what level of side effects will be considered acceptable.

Chills and nausea are possible, Dr. Geisbert said, but he added, “Who cares, if you survive Ebola?”

Most vaccines are given to prevent disease before people are exposed to it, and the plan is to use Ebola vaccines that way. But the V.S.V. vaccines have also been shown to protect monkeys even after the animals have been exposed to a heavy dose of Ebola — if given soon after exposure.

Researchers hope that they will work that way for people, too. If they do, health workers and family members who have been in contact with a patient might be protected, instead of having to spend 21 days of dread, waiting to see if they get sick.

Dr. Geisbert spends much of his time working with Ebola and other deadly viruses in a Biosafety Level 4 laboratory at the Galveston National Laboratory, where the researchers wear spacesuits that each come with an independent air supply, and visiting journalists are required not to report which floor the labs are on.

This month, one of his tasks is to test the Profectus vaccine and an experimental treatment against the Ebola strain that is causing the current epidemic. The virus is from a species called Ebola Zaire, against which the products have already been shown to work. But different strains within a species can vary genetically by 2 percent to 7 percent, Dr. Geisbert said.

Most of the time, those small variations do not matter, and a drug or treatment that works against one strain will work against all. But once in a while, the difference matters.

“We don’t know for 100 percent certainty until we prove it in animals,” Dr. Geisbert said. “The companies I work with are smart. They want that answer sooner rather than later, before they go investing millions of dollars to put this into humans.”

Public health authorities said on Friday that they hoped to begin trials of Ebola vaccines in disease-ravaged West Africa as early as December and could know around April whether they were effective, clearing the way for possible mass inoculations to stem the epidemic.

“Vaccine is not the magic bullet,” Dr. Marie-Paule Kieny of the World Health Organization said at a news conference in Geneva. “But when ready, they may be a good part of the effort to turn the tide of this epidemic.”

Dr. Kieny, assistant director-general for health systems and innovation for the organization, spoke on Friday about the conclusions of a meeting the day before where government officials, drug companies and others discussed how to test and possibly deploy vaccines most effectively.

Trials in December would be a month earlier than Dr. Kieny had indicated earlier this week. Manufacturers have committed to having millions of vaccine doses available in 2015, with hundreds of thousands ready halfway through the year, she said.

“All previous plans are changing from week to week, and always to a greater involvement and a greater mobilization of all efforts to have more vaccine available more quickly,” Dr. Kieny said.

Although there are currently no drugs or vaccines approved in the United States to treat or prevent Ebola, health officials have used several experimental drugs in the recent epidemic.

Some health experts say that an effective vaccine might now represent the best hope because it has been difficult to slow the spread of the disease using conventional public health measures like isolating patients and tracing their contacts. Efforts are being made to intensify those conventional methods, however, such as building new treatment centers to handle more patients.

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Dr. Kieny said a decision to start mass vaccinations later in 2015 would depend on whether one or more vaccines proved safe and effective, whether there would be enough vaccine available and whether that strategy would be necessary.

Two experimental vaccines are already being tested for safety in healthy volunteers in the United States and other countries outside the outbreak region. One is being developed by the National Institutes of Health and GlaxoSmithKline and the other by the Canadian government and NewLink Genetics. At least five other vaccines could begin human testing in early 2015, Dr. Kieny said.

If the two most advanced vaccines prove safe in initial testing, trials would begin in Liberia and Sierra Leone to see if the vaccines could actually prevent people from getting Ebola.

Dr. Kieny’s announcement provided few details of the trials, which she said were still subject to change. But her comments were consistent with plans discussed Thursday by a United States government official who requested anonymity.

Participants in the trials would include health care workers, who are at high risk of getting infected. But a trial in Liberia would likely include others at high risk, such as burial workers or family members caring for those with Ebola.

The study in Liberia would randomize volunteers to receive the GlaxoSmithKline vaccine, the NewLink vaccine or a vaccine for some other disease — essentially a placebo in terms of preventing Ebola. About 9,000 volunteers would participate in each of the three arms of the study, the federal official said.

In the Sierra Leone trial, everyone at a particular site would be offered vaccination. But different centers would receive the vaccines at different times, allowing comparison of disease rates between sites based on when they received the vaccination. In that trial no one would receive a placebo.

That trial, being planned by the Centers for Disease Control and Prevention, is expected to test the GlaxoSmithKline vaccine but might include others.

Dr. Kieny said that at some point there would also be a trial in Guinea, the third of the three countries most affected by the outbreak.

Some critics have said it would be unethical to offer health care workers treating Ebola patients a placebo. But others have argued that because it is unknown whether the vaccine works, there is no advantage to getting the vaccine instead of the placebo.

Dr. W. Ripley Ballou, who heads the Ebola vaccine effort at GlaxoSmithKline, said that a randomized trial against placebo “gets a definitive answer as quickly as possible” about whether a vaccine is effective, which is in the best interest of the community as a whole.

The meeting Thursday also included discussions of how to pay for the trials and possible vaccine deployment. Dr. Kieny said money could come from donor countries like the United States and Britain, from the World Bank and others. She added that there was a “broad understanding that money will not be an issue.”

Dr. Kieny said that discussions were also under way about indemnifying vaccine manufacturers, because the vaccines would be deployed with much less than the usual testing. That might be a fund to compensate people who suffer side effects from a vaccine, so manufacturers would not bear that financial risk.

The leader of the World Health Organization criticized the drug industry on Monday, saying that the drive for profit was one reason no vaccine had yet been found for Ebola.

In a speech at a regional conference in Cotonou, Benin, Dr. Margaret Chan, the director general of the W.H.O., also denounced the glaring absence of effective public health systems in the worst-affected countries.

At least 13,567 people are known to have contracted the Ebola virus in the latest outbreak, and 4,951 have died, according to the latest data on the W.H.O. website, which was updated on Friday. All but a few of the cases have been in Guinea, Liberia and Sierra Leone.

Dr. Chan said her organization had long warned of the consequences of greed in drug development and of neglect in public health.

Although there are currently no drugs or vaccines approved in the United States to treat or prevent Ebola, health officials have used several experimental drugs in the recent epidemic.

In the midst of the Ebola crisis, she said, these “two W.H.O. arguments that have fallen on deaf ears for decades are now out there with consequences that all the world can see, every day, on prime-time TV news.”

The Ebola virus was discovered in the Democratic Republic of Congo, then known as Zaire, in 1976. But because it was confined to impoverished African countries, Dr. Chan said, there was no incentive to develop a vaccine until this year, when Ebola became a broader threat.

“A profit-driven industry does not invest in products for markets that cannot pay,” she said. “W.H.O. has been trying to make this issue visible for ages. Now people can see for themselves.”

Dr. Chan reiterated her contention that the Ebola crisis “is the most severe acute public health emergency seen in modern times.”

Efforts to find a vaccine have been stepped up in recent months as the disease has spread, with a small outbreak in Nigeria and isolated cases in Mali, Senegal, Spain and the United States. At an emergency meeting in September, the United Nations Security Council declared the Ebola crisis a threat to international security.

Officials at the W.H.O. and at other public health authorities reported on Oct. 24 that they hoped to begin trials of vaccines as early as December, and that it should be known by April whether they are effective.

Researchers have been testing two experimental vaccines in healthy volunteers in the United States and in other countries outside the main outbreak region in West Africa. One of them was developed by the National Institutes of Health and GlaxoSmithKline, and the other by the Canadian government and NewLink Genetics.

Testing on humans of at least five other vaccines could begin in early 2015, W.H.O. officials have said.

Doctors, nurses and other health workers have been especially susceptible to infection because of the way the disease spreads through contact with fluids. In Sierra Leone on Monday, the authorities reported that a fifth local physician had died of the disease, news agencies reported.

The secretary general of the United Nations, Ban Ki-moon, speaking on Monday at a news conference in Vienna, warned against what he called overly strict international restraints on the movement of health workers who are fighting Ebola.

Some countries and some states in the United States have quarantined health professionals returning from Guinea, Liberia or Sierra Leone. Other countries, including Canada and Australia, have gone further, temporarily halting the issuance of visas to citizens of the worst-affected countries.

“The best way to stop this virus is to stop this virus at its source,” Mr. Ban said, “rather than limiting for work, or restricting the movement of people or trade.” He called Ebola health workers “extraordinary people who are giving of themselves — they are risking their own lives.”

A test of an experimental Ebola vaccine recently licensed to Merckhas been temporarily paused after some vaccinated volunteers experienced pain in their joints, a medical center in Geneva announced on Thursday.

But the center, University Hospitals of Geneva, said such reactions were common for vaccines, suggesting it did not think this represented a major setback to the development of the vaccine, which might become an important tool in containing the epidemic in West Africa.

The Merck vaccine is one of two that are in early testing in healthy volunteers at various sites around the world. The other is being developed by GlaxoSmithKline and the United States National Institutes of Health.

If the vaccines prove safe in these early tests and show evidence that they stimulate an immune system response, health authorities plan to conduct larger trials beginning next year in the African countries affected by the outbreak.

The vaccine being tested in Geneva was initially developed by the Public Health Agency of Canada and licensed to NewLink Genetics, a small biotechnology company in Iowa. Last month, NewLink licensed its rights to Merck, a company with far more resources and expertise in developing and manufacturing vaccines.

University Hospitals of Geneva said in a statement on Thursday that it had given the vaccine to 59 volunteers since Nov. 10 and that over all, the vaccine was “very well tolerated.” Some people got fever or muscle pain in the days and hours after the injection, but that was expected and the volunteers had been warned about it.

However, it said, four volunteers then reported mild pain in the joints of the hands and feet 10 to 15 days after the injection, something not expected. The hospital said it therefore decided to halt the injections until Jan. 5, so it could study the situation and update the information about expected side effects that it provides to volunteers.

Joint pain after vaccination “is a well-documented phenomenon which does not worry specialists,” it said. It added, “The temporary interruption of a clinical trial is a standard precautionary measure in such cases.”

The vaccine is also being tested in Canada, Germany and Gabon, and in the United States at the Walter Reed Army Institute of Research and at the National Institutes of Health. These other teams have not observed such inflammation, the Geneva hospital said.

Merck said that the side effect was seen in volunteers receiving a higher dose and that part of the goal for the study was to define the proper dose. It said it understood that the study would continue, using lower doses.

“These events have not been reported at any of the other clinical sites,” the company said in a statement. “It is not known at this time whether these events are related to the vaccine or not.”

Merck paid $30 million initially to NewLink for rights to the vaccine and owes another $20 million when the vaccine enters later-stage testing. Shares of NewLink were down about 5 percent Thursday afternoon.

So far, the GlaxoSmithKline vaccine does not appear to have caused any safety problems, authorities have said.

The two vaccines use different technical approaches. Both are made of viruses that are genetically engineered so that they make a protein from the Ebola virus. The Merck vaccine uses vesicular stomatitis virus, which can cause a mouth disease in livestock but rarely in people. The Glaxo vaccine uses a chimpanzee adenovirus, which causes a type of common cold in chimps but is not known to cause illness in people.

Safety is considered crucial for vaccines because they are typically given to large numbers of healthy people. Indeed, companies developing Ebola vaccines have been seeking some indemnity should side effects emerge once the vaccines are used for mass inoculations, especially since the vaccines are being developed on a crash schedule.

This week, the Department of Health and Human Services said it was granting such liability protection against legal claims brought in the United States for the Glaxo and Merck vaccines, as well as one being developed by Johnson & Johnson.

In related news, Gavi, the Vaccine Alliance, said it was committed to spending up to $300 million to buy up to 12 million courses of Ebola vaccine to immunize people in countries affected by the outbreak. It said it would act as soon as a vaccine was recommended for use by the World Health Organization.

Gavi, once known as the Global Alliance for Vaccines and Immunization, is a public-private partnership funded by various governments, companies and charities including the Bill and Melinda Gates Foundation.

Since 2003, the Defense Threat Reduction Agency has invested more than $300 million to develop medical countermeasures against hemorrhagic fever viruses, and those efforts are paying off today in potential new ways to fight Ebola virus disease.

DTRA’s mission is to protect the United States and its allies from chemical, nuclear, biological and other weapons of mass destruction, and deadly pathogens fall into the WMD category, DTRA Deputy Director Air Force Maj. Gen. John Horner said during a recent interview with DoD News.

“We plan to be in this business for the long term,” he added, “and need to do biosurveillance and strengthen biosecurity worldwide, helping partner countries build their capacity to prevent, treat and monitor the threat of infectious diseases.”

More than 17,290 cases of Ebola virus disease and at least 6,128 deaths have been reported to date in West Africa, according to the World Health Organization and the Centers for Disease Control and Prevention, and the lack of licensed Ebola vaccines and treatments has accelerated efforts, including DTRA’s, to get these medical products into the regulatory approval pipeline.

This year, in coordination with DTRA, the Public Health Emergency Medical Countermeasures Enterprise working group chose three lead candidates –- two vaccines and one treatment –- to go forward in the Food and Drug Administration approval pipeline as part of the U.S. Ebola outbreak response.

The vaccine candidates are recombinant VSV-EBOV, from BioProtection Systems/Newlink Genetics, and ChAd-EBOV from GlaxoSmithKline. DTRA is supporting development of the VSV-EBOV vaccine through a contract with BioProtection Systems/Newlink Genetics. NIAID is supporting the ChAd-EBOV vaccine.

The VSV candidate is based on a recombinant, or genetically engineered, virus from an animal disease called vesicular stomatitis. An Ebola virus protein is engineered into a vesicular stomatitis virus, and the new recombinant virus acts as a vector, or carrier, to deliver the Ebola protein into the human body. Genetic engineering is a healthy way to express proteins like Ebola that prompts the body to produce antibodies to lethal Ebola virus disease without the risk of disease from either virus

The other vaccine is a recombinant chimpanzee adenovirus, or cold virus. In this vaccine, an Ebola virus protein is engineered into a chimpanzee adenovirus to deliver the ChAd-EBOV vaccine into people to produce Ebola antibodies.

Human testing to evaluate the safety of VSV-EBOV is underway at the National Institutes of Health Clinical Center in Bethesda, Maryland and the Walter Reed Army Institute of Research, or WRAIR.

Researchers at the NIH National Institute of Allergy and Infectious Diseases, or NIAID, are conducting an early phase trial to evaluate the VSV-EBOV vaccine for safety and for its ability to generate an immune-system response in healthy adults who receive two injected doses.

At the same time, the WRAIR is testing the VSV-EBOV vaccine as a single dose at its Clinical Trials Center in Silver Spring, Maryland, NIH officials said.

For the ChAd-EBOV vaccine, in early stage clinical trials, again designed to assess vaccine safety and immune response, NIAID will test two versions of ChAd-EBOV.

One is a bivalent, or two-component, version containing genetic material from Ebola Zaire and Ebola Sudan strains. The other is a monovalent, or single-component, version that contains only genetic material from Ebola Zaire, the strain now causing the outbreak in West Africa.

Both vaccines were reviewed by the FDA under an investigational new drug, or IND, application.

“We should begin to see Phase II and III clinical trials take place in West Africa, probably in the January-February timeframe,” Dr. Ronald K. Hann Jr., director of research and development in DTRA’s Chemical and Biological Technologies Department, said.

He explained that these clinical trial phases evaluate the vaccines’ efficacy, or how well they work.

“We spoke to Doctors Without Borders [recently], and they're helping to map out the Phase II-III clinical trial studies that would be taking place in West Africa,” Hann added, “and they're looking at both the [ChAd-EBOV and VSV-EBOV] vaccine candidates to go into those trials.”

Once either vaccine shows protection, according to a DTRA fact sheet, the trial will stop and the vaccine will be distributed in a mass immunization campaign to help end the Ebola epidemic.

The lead therapeutic treatment candidate that DTRA and the Public Health Emergency Medical Countermeasures Enterprise working group named to move forward into the FDA pipeline is called ZMapp, from Mapp Biopharmaceutical.

But as early as 2007, DTRA, NIAID and the U.S. Army Medical Research Institute for Infectious Diseases, or USAMRIID, were funding efforts and working hard to show that the monoclonal antibody basis for the experimental drug actually would work.

ZMapp is a cocktail of three different monoclonal, or genetically engineered, Ebola virus disease antibodies that bind to Ebola virus proteins in the body and neutralize the virus, decreasing the amount of virus the patient's immune system has to fight.

Dr. Erin Reichert, chief of the Translational Medical Division of the Chemical and Biological Technologies Department in DTRA’s Research and Development Directorate, describes the road to development for ZMapp.

“Along with our colleagues at USAMRIID and NIAID, we had a small investment in looking at whether or not monoclonal antibodies or antibody-based therapeutics in general would be an appropriate therapeutic countermeasure for Ebola,” she said.

In the scientific community, as early as 2007, researchers debated the value of this so-called passive immunotherapy, or passive transfer, for treating Ebola.

“We funded researchers at USAMRIID, and NIAD had small investments through small-business grants directly to Mapp Biopharmaceutical to determine once and for all if antibodies could be a viable countermeasure”, Reichert said.

Then in the 2012 timeframe, she added, important publications came out of USAMRIID that changed the way researchers viewed antibodies for filovirus infection. Ebola and Marburg viruses both are filoviruses.

“One of those papers was by [Dr. John M. Dye Jr., now chief in USAMRIID’s Viral Immunology Branch],” Reichert said. “He demonstrated for the first time that antibodies from primates exposed to Ebola virus could be transferred to naive primates to protect them from infection. That opened the door for this as far as a viable countermeasure.”

Also in 2012, she added, DTRA and NIAID “really started putting some dollars against the product and in a very short period of time we were able to accelerate development to a point where, while it is still a [research and development] product, we have a product that could be useful in people.”

ZMapp was developed through a DTRA contract with Mapp Biopharmaceutical and in collaboration with USAMRIID, Defyrus LLC and the Public Health Agency of Canada, according to a DTRA fact sheet.

The ZMapp three-antibody cocktail was discovered in 2014 but the monoclonal antibody research began in 2007.

BARDA is sponsoring the manufacture of ZMapp for Phase I and II clinical studies, which are expected to start in early 2015 at NIAID. Other clinical studies are scheduled to begin in affected African countries in early 2015. ZMapp has been used under an emergency investigational new drug application in Ebola-infected patients in the United States, Africa and elsewhere, according to a White House fact sheet.

“We’ve been working very closely with our interagency partners to develop these vaccines and therapeutics to protect the force against a broad range of filoviruses,” Reichert said.

In response to the West Africa Ebola epidemic, development of vaccines and ZMapp has accelerated to focus specifically on delivering something for Zaire, she added.

“Along with our interagency partners -- HHS as well as JPEO have been really critical –- we’ve been able, in a very short period of time, to push those through the regulatory process to get them to a point where they may have an impact on the current epidemic,” Reichert said.

(Follow Cheryl Pellerin on Twitter @PellerinDoDNews)

As authorities and drug companies hurriedly prepare to begin testing Ebola vaccines in West Africa, they are starting to contemplate a new challenge: whether an ebbing of the outbreak could make it more difficult to determine if the experimental vaccines are effective.

“For this reason, it’s very urgent that we get into the field very quickly to do these clinical trials, because if there are very, very, very few cases of Ebola, as I’m sure you understand, it’s going to be difficult to test whether the vaccines work or not,” Dr. Helen Rees, an adviser to the World Health Organization, said during a news conference on Friday at the organization’s headquarters in Geneva.

Dr. Rees, a professor and viral disease expert at the University of the Witwatersrand in South Africa, led a meeting on Thursday of public health officials, pharmaceutical executives and others to discuss the plans for testing vaccines in Liberia, Guinea and Sierra Leone.

The epidemic has sickened about 21,000 people and killed more than 8,000 of them, the World Health Organization said this week, but there are signs that the epidemic may be coming under control as more treatment centers are built and safer burial practices are used. Still, the evidence is far from conclusive, and experts are mindful that the outbreak surged again last year after the authorities thought it was ebbing.

Dr. Marie-Paule Kieny, an assistant director general of the W.H.O., said two vaccines had been found safe enough in early testing in countries outside the outbreak zone to justify wider testing in the affected countries. But she said it would take two to four weeks more to determine the proper doses.

She said a clinical trial in Liberia could begin as soon as the end of this month, with studies in Sierra Leone and Guinea starting in February.

Dr. Kieny said it could take up to six months to determine if the vaccines are effective. Production has already begun, so if any of the vaccines proves safe and effective, millions of doses could be quickly made available.

Vaccine effectiveness is determined by how many vaccinated people come down with a disease compared with those who are not vaccinated, or vaccinated later. If few new cases of the disease are occurring, it would be harder to see any difference. Dr. Kieny said plans were being made to increase the size of the trial in Liberia if needed.

In Liberia, there were eight confirmed new cases and 40 probable new cases recorded in the five days ending Jan. 2, down from a peak of 300 confirmed new cases a week in August and September, according to the W.H.O. The number of new cases has been falling in Sierra Leone, but it remains the most heavily affected country. In Guinea, it is not clear if case numbers are falling, the health organization said.

If the epidemic continues to ebb, it may be too late for the vaccines to make a difference in this outbreak. Dr. Rees said that a working group had been formed to discuss how to deploy the vaccines, should they prove safe and effective, but that the situation was changing too rapidly to make such a decision now.

“Hopefully, we will have broken the back of this epidemic by the time we finish these trials,” she said.

Even if that is the case, she and Dr. Kieny said, sporadic cases would most likely occur, and vaccinations might be given to people nearby to protect them and help prevent further spread of the disease — a strategy known as ring vaccination. And it might be wise to vaccinate health workers for long-term protection, they said.

The two vaccines that are most advanced in testing are being developed by GlaxoSmithKline and Merck. The Glaxo vaccine is being developed with the National Institutes of Health; Merck’s was originally developed by the Public Health Agency of Canadaand licensed to a small Iowa company, NewLink Genetics, which in turn enlisted Merck.

Testing of the Merck vaccine at a hospital in Switzerland was suspended in December after a number of patients developed pain in the joints of their fingers and toes. Testing resumed this week using a lower dose. Dr. Kieny said the pain was generally transient and mild and “not of sufficient concern to stop the development of this vaccine.”

A third vaccine, being developed by Johnson & Johnson, began early safety testing in volunteers this month. That company is also planning tests in West Africa.

There has been debate over how to conduct the studies. Some experts say testing the vaccines against a placebo would be the surest way to determine whether they work. Others counter that it would be unethical to administer a placebo during a deadly epidemic.

The trials will cover all the approaches, with different designs in each country. In Liberia, the Merck and Glaxo vaccines will be tested against each other and against a control, with about 9,000 people in each of the three arms of the study.

In Sierra Leone, vaccine doses will be given to health care workers and others directly involved in responding to the disease. There will be no placebo, and effectiveness will be determined by looking at whether there are fewer cases of Ebola among workers who are vaccinated earlier compared with those who are vaccinated later. Which vaccine is used will depend on which one appears to be the best after data on immune responses is analyzed, Dr. Kieny said.

Guinea will test using the ring vaccination strategy, vaccinating communities when a case of Ebola occurs. Some communities will be given vaccine right away, and others will receive it later, based on random assignment.

An experimental Ebola vaccine being tested in the West African nation of Guinea during the continuing outbreak of the viral disease has shown promising initial results, according to a report on the clinical trial that was published Friday.

The report, in the British medical journal The Lancet, which analyzed 7,651 individuals, more than 3,500 of whom were vaccinated, indicated that the vaccine “might be highly efficacious and safe in preventing Ebola virus disease.”

“This is good news,” Dr. Margaret Chan, director general of the World Health Organization, said in an interview, while noting that the vaccine was not “a silver bullet” to head off future outbreaks. “There is no replacement for very strong and good, resilient health systems with the capability for surveillance,” she said.

Dr. Sakoba Keita, Guinea’s Ebola response coordinator and one of the study’s authors, said in an email that Guineans hoped the results would “contribute to the rapid control of the next epidemics caused by this disease.”

The clinical trial involved inoculating people who had come into contact with Ebola patients, and the contacts of those contacts. Some clusters of people were vaccinated immediately, while others, assigned randomly, were vaccinated only after 21 days, the maximum incubation period of the virus.

After 10 days, none of those who had been immediately vaccinated subsequently contracted Ebola, whereas 16 of the people eligible for the study who were not immediately vaccinated came down with the disease. The analysis was started at Day 10 to give the vaccine time to set off an immune response and because some of the contacts might already have been incubating the virus.

Those results were highly significant, the authors reported, indicating the vaccine was 75 to 100 percent efficacious. In fact, the researchers observed that there were no Ebola cases in any vaccinated patients after the first six days.

The results are “very encouraging,” said Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Diseases, who was not involved in the trial, which he called a “very difficult study under very difficult circumstances.” He added that the study’s unorthodox design “makes it difficult to get the precise information you need,” but that, “even in the absence of that, the results are impressive.”

Another hope was that vaccinating many of those closest to an Ebola patient might quickly shut down a local outbreak, even among those not vaccinated. Despite tantalizing signs of effectiveness, the findings did not reach statistical significance, perhaps in part because roughly a third of those eligible for immediate vaccination did not consent to participate. In addition, the vaccine was not given to children or pregnant women because its safety in those populations was not yet known.

Because no placebos were used, volunteers knew whether they had received the vaccine, which could have influenced the study’s outcome. Choices like this, some of which were highly contentious on ethical and scientific grounds, were made to be pragmatic in the context of an emergency, said Jeremy Farrar, director of the Wellcome Trust, a major supporter of the research.

The fact that promising results were obtained in spite of certain compromises in scientific rigor, he said, “in a sense vindicates the design and approach that was taken and moves the field forward.”

Some outbreak responders initially opposed the idea of carrying out research in the midst of a dire emergency, but Dr. Farrar said this was imperative.

“You can’t test these things in a period between epidemics,” he said. He and other experts said better and faster approaches to conducting research in outbreaks were needed.

This was the first time in memory that a vaccine’s effectiveness had been studied with a so-called ring vaccination approach, inoculating all of those around the occurrence of an infectious disease, according to one of the study’s senior authors, Dr. John-Arne Rottingen of the Norwegian Institute of Public Health. That vaccination strategy was used to help eradicate smallpox.

“I thought the only way to be successful would be to follow the epidemic and try to vaccinate in high-risk individuals,” Dr. Rottingen said in an interview. This approach ended up producing results even when the country had only a small number of cases, distributed across a large area.

The clinical trial in Guinea “has been more successful than we almost could have hoped for,” Dr. Rottingen said.

Other studies in Liberia and Sierra Leone, where the virus also raged, are continuing and are likely to produce results on safety and immune response but not on the effectiveness of the vaccine given the low numbers of patients in recent weeks, and the design, which did not target contacts of Ebola patients. The World Health Organization reported seven confirmed cases last week in the region, the lowest number of new Ebola patients in well over a year. On Friday, the United Nations announced the end of a special mission for Ebola emergency response.

Vaccinations began in March in Guinea. An independent safety monitoring board recommended that the interim results be published and that the design be altered to provide immediate vaccination to all eligible volunteers.

The study was led by the World Health Organization, the Guinean Health Ministry, Doctors Without Borders, the nonprofit Epicentre research center and the Norwegian Institute of Public Health, among many other contributing organizations. “This shows the power of partnerships,” said Dr. Marie-Paule Kieny, an assistant director general at the W.H.O. and the study’s other senior author.

Researchers working at the Public Health Agency of Canada created the experimental vaccine, rVSV-ZEBOV, which combines a piece of the Zaire Ebola virus’s covering with an animal virus, vesicular stomatitis virus, to set off an immune response against Ebola. It was licensed by NewLink Genetics, a biopharmaceutical company based in Ames, Iowa, in 2010, and then by Merck in November. The W.H.O. and its partners helped organize the study in Guinea after other studies supported by the United States government were planned for Liberia and Sierra Leone, and Guinea requested assistance to start its own. Other experimental Ebola vaccines are also being studied for safety.

The clinical trial included the use of a beer-keg-shaped vaccine storage device, the Arktek. It allowed the vaccines to be transported and kept at minus 80 degrees in outlying areas without electricity, which was deemed necessary because the vaccine’s stability at higher temperatures had not yet been fully tested. The storage device was invented by Global Good, a collaboration between the investment company Intellectual Ventures and Bill Gates.

A World Health Organization committee is expected to consider the results at a meeting next month and begin making recommendations for future use.

Experts familiar with the study said they expected the vaccine would be used for now only to respond to new outbreaks rather than to vaccinate entire populations, because it was not yet known how long protection would last. Doctors Without Borders is recommending that the study be extended so that vaccine can be given to all front-line workers and the contacts of all new cases in the region, said Dr. Bart Janssens, the group’s director of operations.

The next step will be submitting the data from this study and several others, including safety results, to regulatory bodies such as the United States Food and Drug Administration. Then the vaccine can be considered for licensure.

Dr. Mark Feinberg, chief public health and scientific officer at Merck Vaccines, said the company was committed to working with regulatory authorities toward licensure. “In the past, I think there wasn’t a strong belief that we needed an Ebola vaccine or that it would actually be possible to develop an Ebola vaccine,” Dr. Feinberg said. “Now I think there’s unanimity.”

When the Pan American Health Organization put out an alert last May about the first confirmed cases of Zika virus infection in Brazil, the news barely registered. After all, compared with other mosquito-borne viruses, such as potentially life-threatening dengue and yellow fever, Zika seemed pretty harmless. Only 20% of people infected with Zika even become ill, and their symptoms tend to be mild—fever, rash, joint pain, and conjunctivitis.

But in January, nine months after the organization raised the alarm, doctors in Brazil reported a disturbing trend that coincided with Zika’s spread across the country. Since October 2015, more than 4,000 babies in Brazil had been born with abnormally small heads and brains—a rare condition known as microcephaly. Although further analysis lowered that figure by 462 cases, the sharp rise nonetheless has experts worried that Zika could be to blame. For comparison, Brazil reported just 147 cases of microcephaly in 2014.

Zika is also being blamed for an uptick in cases of Guillain-Barré syndrome, a potentially life-threatening disorder in which the body’s immune system attacks the central nervous system and causes paralysis. As with microcephaly, the evidence connecting Zika and Guillain-Barré is still circumstantial. Nevertheless, the link is strong enough for the World Health Organization to declare the Zika outbreak a public health emergency of international concern.

Margaret Chan, WHO’s director-general, said earlier this month that the virus is “spreading explosively” through the Americas, with cases of active virus transmission in at least 26 countries and territories in the Americas. Panic over the virus has prompted health officials in some countries to take the drastic measure of advising women to delay pregnancy for months or longer. In El Salvador, Deputy Health Minister Eduardo Espinoza asked women to avoid becoming pregnant until 2018.

With Zika making headlines for the past month, scientists have been scrambling to get a handle on the virus. Industry, government, and academic scientists have all announced efforts to develop and test treatments and vaccines. But the path ahead for these researchers is long and full of pitfalls. Even though Zika has been around for almost 70 years, surprisingly little is known about the virus and its basic biology. A PubMed search for “Zika virus” turns up mostly case studies.

What we do know is that Zika is a flavivirus, a member of the same family as dengue, yellow fever, and West Nile virus. Zika is primarily transmitted via bites from infected mosquitoes, but in recent weeks doctors have reported that the virus can be sexually transmitted as well.

It was first identified in a monkey in Uganda’s Zika forest in 1947, but only a handful of human Zika cases were reported until a 2007 outbreak in Micronesia’s Yap Island. An outbreak in French Polynesia followed six years later. Last November officials in that country reexamined the cases of microcephaly that followed the outbreak. Before the outbreak, about one case of microcephaly was reported each year. In 2014–15, officials found 17 cases of fetuses and infants with “central nervous system malformations,” which includes microcephaly.

As the case connecting Zika to serious health effects builds, the world would love a vaccine or treatment for the virus. But because so few have studied Zika, drug developers currently have few tools to work with. For example, there’s no commercially available, U.S. Food & Drug Administration-approved test to screen for Zika virus.

Tracking Zika in people is hard because it’s difficult to determine that they’re infected with Zika and not a related flavivirus or that they’re not infected with more than one virus, says Priscilla L. Yang, a flavivirus expert at Harvard Medical School. Simultaneous infection with Zika and another virus could cause health effects that haven’t been seen before.

Scientists can use polymerase-chain-reaction-based methods to distinguish Zika from other flaviviruses. But those tests are accurate only during the short window patients still have the virus in their system—about seven days after infection. By the time a patient has symptoms that warrant a visit to the doctor, the virus is no longer circulating in their bloodstream, Yang notes.

Another option is to look for antibodies against the virus. But Zika and dengue are closely enough related that antibodies to Zika also recognize dengue and vice versa. Making a definitive diagnosis based on antibodies is possible but becomes time-consuming and laborious, Yang says.

For scientists who have compounds that might be effective against Zika, actually testing them has been tough. “We have small molecules that seem to be broadly acting against dengue and West Nile virus,” Yang says. “We want to test them, but getting access to the live virus has been hard.” She’s heard that certain labs known to have the Zika virus have been bombarded with hundreds of requests from researchers.

Even if someone manages to access the live virus and can find a compound that kills it in cells, the researcher will hit another roadblock: To date, no one has published practical animal models of Zika virus to screen potential therapies against. Yang points to a paper from the 1970s in which scientists did an intracranial injection of Zika virus in newborn mice, but she notes that is a poor model because many small molecules can’t slip past the blood-brain barrier.

“We’re basically starting from scratch on this one, unfortunately,” says [Sina A Bavari (born 1959)], chief scientific officer (CSO) at the U.S. Army Medical Research Institute of Infectious Diseases. Bavari and colleagues are currently working with pharma companies to see if they have any compounds that inhibit Zika replication in cells.

They’re primarily interested in compounds that have passed the hurdles of Phase I or Phase II clinical trials but are sitting idle for business reasons. That’s because it can take upward of a year and a half just to get a new compound ready for Phase I. “My worry is that by the time we get something out the door, this outbreak will have already burned out,” Bavari says.

Scientists are also grappling with this question: If only 80% of people infected with Zika have symptoms, who would get the treatment? The most vulnerable patients are pregnant women, but Bavari points out, there’s a high bar when it comes to approving a medication that can be given to them. “They don’t even want to drink caffeine,” he says.

Other scientists are working to develop a vaccine against the Zika virus. Earlier this month President Barack Obama said he would ask Congress for $1.8 billion to combat Zika at home and abroad. Of those funds, $200 million would be used for vaccine development. The U.S. National Institute of Allergy & Infectious Diseases, Sanofi Pasteur, and [NewLink Genetics Corporation] are among the heavy hitters in the vaccine field who’ve said they’ll step up to the plate.

Even so, it could take three to five years before a vaccine is ready, experts say. [Dr. Thomas Patrick Monath (born 1940)], CSO of [NewLink Genetics Corporation]'s infectious disease division, led that firm’s efforts to develop an Ebola vaccine and was CSO at Acambis, where he worked on vaccines for dengue and yellow fever. Monath tells C&EN he thinks a large field trial of 10,000 to 20,000 people across multiple sites will be necessary to determine efficacy once a Zika vaccine is developed. “Only after those trials would you contemplate doing studies in pregnant women,” he says.

Monath also says because so many people who are infected with Zika never show any symptoms, it is more difficult to determine whether the vaccine has actually prevented infections. Still, he thinks a large enough trial should be conclusive.

But some scientists say the emphasis on vaccines is misplaced. “We just don’t know enough about Zika virus right now to run around and vaccinate people,” Bavari says. “Understanding the immunopathology and immunology behind it would be really prudent before starting a full vaccination program.”

Harvard’s Yang says developing a vaccine for every emerging virus is impractical. “Vaccines are, for the most part, specific. You have one virus, and you have one vaccine for it,” she explains. “I don’t think we’ll ever have the luxury of enough resources to get a vaccine against every single possible emerging virus or enough time to do it in a reactive way.”

One area that’s not getting as much attention, she says, is development of broadly acting antivirals that could keep a virus in check while the immune system fights it off. Classical antivirals go after a single viral enzyme, but viruses are quick to develop resistance to them. “If people could identify targets that have the potential to be effective against multiple viral pathogens, it could be game-changing,” Yang says.

[Dr. Hugh Alexander "H. Alex" Brown Jr. (born 1960)], a Vanderbilt University professor who works on antivirals, agrees. “There are so many viruses out there. We need to be working on a much more broad-spectrum approach to infectious disease,” he says. “If we can develop more tools to combat broad categories of viruses, I think we would be much better off than we are today.” [ Note - [Dr. Hugh Alexander "H. Alex" Brown Jr. (born 1960) passed July 25, 2017 ]

In the meantime, scientists agree that the research community needs to be more organized if it’s going to have a real shot at combating Zika. Yang thinks the first steps should be figuring out how to get the necessary reagents to the labs that need them and agreeing on standards so they can compare results and learn from each other’s work. “If you actually want to have some sort of impact, we all need to work together,” she says. In an encouraging sign, earlier this month, major scientific institutions and top research journals agreed to share data relevant to Zika virus.

Bavari agrees scientists need to be better at organizing their efforts, but he has doubts about the direction the community is taking. “The outbreak is moving so quickly that I am worried people will jump and we won’t do the correct research,” he says.

Recalcitrant Mosquito Blamed For Zika’s Spread

With a treatment or vaccine for Zika potentially years away, countries are relying on mosquito control to curb the virus’s spread. Aedes aegypti mosquitoes, which inhabit tropical and subtropical regions, have been named as the culprit in transmitting the virus.

But getting rid of Aedes aegypti is extremely difficult because the mosquitoes don’t seem to be affected by most spraying regimens, says Joseph M. Conlon, an entomologist and technical adviser to the American Mosquito Control Association. According to Conlon, Aedes aegypti feed during the day, but pesticides must be sprayed at dawn or dusk. Also, mosquitoes like to come indoors to feed. So, unless pesticides are sprayed inside homes, chances are good they’re not getting to the insects.

These mosquitoes are very small, and you can’t feel the bites. “Oftentimes you don’t even know you’ve been bitten,” Conlon says.

To get rid of the biting bugs, it’s critical to eliminate any standing water. “I’ve seen Aedes aegypti breeding in discarded soda bottle caps,” Conlon says. “They’re survivors.”

Despite Aedes aegypti’s survival skills, the mosquitoes actually have a fairly limited flight range of about 150 meters. That has made some scientists suspect that because Zika has spread so quickly, the more common Culex mosquito may be transmitting the virus as well. The theory is currently being investigated.

“If that is true, that brings this to a whole different level,” Conlon says. Culex mosquitoes have a much larger range, he notes, but they can usually be controlled through common mosquito abatement programs. ◾