USAMRIID supports Ebola Virus Disease outbreak response in West Africa

By Caree Vanderlinden, Army MedicineNovember 4, 2014

USAMRIID supports Ebola Virus Disease outbreak response in West Africa
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USAMRIID supports Ebola Virus Disease outbreak response in West Africa
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USAMRIID supports Ebola Virus Disease outbreak response in West Africa
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FORT DETRICK, Md. (Oct. 22, 2014) -- From on-site laboratory support in Liberia, to training of key personnel, to accelerated research efforts on diagnostic, vaccine and treatment approaches, the U.S. Army Medical Research Institute of Infectious Diseases is playing a significant role in assisting the Ebola Virus Disease outbreak response in West Africa.

Ebola virus causes a severe, often fatal hemorrhagic disease in humans and non-human primates. Currently there are no licensed vaccines or drugs to fight the disease, and case fatality rates as high as 90 percent have been reported in past outbreaks. As of Oct. 15, the World Health Organization reported at least 8,997 cases and 4,493 deaths in seven affected countries. These include Guinea, Liberia, Nigeria, Senegal, Sierra Leone and Spain, as well as the first-ever case of Ebola diagnosed in the U.S.

That patient, a man who had recently traveled from Liberia to the U.S., died Oct. 8.

The U.S. Department of Defense is supporting the U.S. Agency for International Development as part of a U.S. whole of government response effort to the Ebola virus outbreak, as announced by President Barack Obama on Sept. 16. U.S. military personnel are deploying to West Africa in support of the effort, called Operation United Assistance. In addition to setting up a regional staging base to facilitate transportation of equipment, supplies and personnel, the U.S. military is establishing additional treatment centers in Liberia and providing medical personnel to train health-care workers in the region.

At the U.S. Army Medical Research Institute of Infectious Diseases, known as USAMRIID, the response effort spans the institute's research and support divisions and there is no sign of the operational tempo slowing any time soon, according to Col. Erin P. Edgar, commander of the institute.

"This is definitely not business as usual," he said.

Late September, USAMRIID was asked to provide training to deploying U.S. forces, according to Lt. Col. Neal E. Woollen, who directs the institute's biosecurity program. Several personnel have volunteered to serve on mobile training teams that travel to deploying units to train and certify troops who will be working in Ebola-affected areas of West Africa. Training is focused on proper wearing of protective equipment, as well as decontamination procedures.


Since April 2014, USAMRIID and the National Institute of Allergy and Infectious Diseases-Integrated Research Facility have provided personnel, training and diagnostic laboratory support to the Liberian Institute for Biomedical Research on a continuous rotational basis, according to Randal J. Schoepp, Ph.D., chief of USAMRIID's Applied Diagnostics branch. He and several others helped to set up an Ebola virus testing laboratory in Liberia and trained local personnel to run diagnostic tests on suspected Ebola hemorrhagic fever clinical samples.

Schoepp said USAMRIID has been working on a collaborative project in West Africa since 2006 (see sidebar article below). Because the team was working on disease identification and diagnostics in the region, he added, "We had people on hand who were already evaluating samples and volunteered to start testing right away when the current Ebola outbreak started."

In addition to providing laboratory testing and training support for the current outbreak, USAMRIID has provided more than 10,000 Ebola laboratory tests, referred to in the medical community as assays, to support laboratory capabilities in Liberia and Sierra Leone. The institute also supplied personal protective equipment to Metabiota Inc., a non-government organization involved in the testing.

Edgar called the project "a great example of medical diplomacy at work."

"This collaboration allows USAMRIID to bring our expertise to bear in responding to an international health crisis," he said. "In addition, it enables us to test the medical diagnostics that we develop in a real-world setting where these diseases naturally occur."


USAMRIID research led to the only assay currently authorized to diagnose Ebola in U.S. citizens, according to David A. Norwood, Ph.D., chief of USAMRIID's Diagnostic Systems Division. The assay, which detects the Zaire strain of Ebola virus in patient samples, is called the Ebola Zaire Real-Time PCR Assay Test Kit. It was developed, manufactured and tested with help from the U.S. Army Medical Materiel Development Activity.

While the test has not been approved by the U.S. Food and Drug Administration, the FDA has authorized its use under an Emergency Use Authorization, granted in August 2014. According to Norwood, the EUA provides a legal basis for the use of unapproved medical products, including diagnostics, in a declared emergency when there are no alternatives. The test is available at authorized DOD laboratories in the U.S. and overseas, as well as select CDC Laboratory Response Network state public health labs throughout the country for testing U.S citizens.

"This assay is also being used in West Africa for rapid diagnosis of host nation patients," said Norwood. "So there is no disparity between the diagnostic capabilities that are being used in-country and those that are available for testing U.S. citizens. While the labeling and execution is somewhat different for regulatory purposes for testing U.S. citizens, the same capability is available for diagnostic testing for everyone."

Issuance of the EUA was a collaborative effort among several agencies: Medical Countermeasure Systems, U.S. Army Medical Command; Health Affairs, Readiness Division, Health Care Operations Directorate; Joint Program Executive Office Critical Reagents Program; the DOD Clinical Laboratory Improvement Program Office; and the recipient laboratories, including five DOD labs and 15 CDC-LRN state public health laboratories.


USAMRIID is leading the evaluation of several promising Ebola medical countermeasure candidates, including therapeutics and vaccines, according to scientific director Sina Bavari, Ph.D.

Bavari, an expert at building public-private partnerships, says the current outbreak offers researchers an opportunity to accelerate the development of medical products to prevent and treat the disease through collaboration with pharmaceutical companies and other government agencies.

Among the products being evaluated by USAMRIID are four potential therapies, including synthetically made, small-molecule drugs that have shown efficacy against a broad range of viral diseases, according to Bavari. One of these drugs, known as BCX4430, has been tested in animal models at USAMRIID; its parent company is in the process of filing an Investigational New Drug application with the FDA to begin Phase I clinical trials in humans.

Two other compounds of interest are oral favipiravir, dubbed T-705, which is already in Phase III clinical trials as a potential influenza treatment, and AL-8176, currently is in Phase II clinical trials for Respiratory Syncytial Virus.

"If we can evaluate a drug that's already in development for another use, and show that it has potential against Ebola virus, that saves us years of research and development," Bavari explained.

The fourth therapeutic candidate being studied at USAMRIID is Z-Mapp, a "cocktail" of three antibodies, one of which was developed by USAMRIID. This drug made headlines when it was used to treat a handful of people infected during the current outbreak, including two American aid workers who contracted Ebola in Liberia and recovered at Emory University Hospital in Atlanta, Georgia.

Previous studies at USAMRIID with an earlier version of Z-Mapp showed that it could protect monkeys from Ebola even when administered five days after infection, according to John M. Dye, Ph.D., branch chief for viral immunology. He said additional studies of Z-Mapp in nonhuman primates will begin at USAMRIID later this month. Those efforts will help to determine dosing -- the optimal amounts of antibody that can be safely administered and still provide protection.

In addition, there are a number of Ebola virus vaccine platforms in various stages of development, Dye said. Two that have been studied extensively at USAMRIID are the VLP (virus-like particle) and the VRP (virus replicon particle) vaccine approaches. Other vaccine approaches include those based on adenovirus (currently in Phase I clinical trials) as well as the rVSV (recombinant vesicular stomatitis virus) platform.

USAMRIID's Division of Medicine is providing medical monitor support to the Phase I clinical trial of the rVSV vaccine, scheduled to begin this month at the Walter Reed Army Institute of Research.

According to Bavari, USAMRIID is continuing to investigate potential treatments and vaccine candidates for Ebola, with several laboratory and nonhuman primate studies scheduled for the near future. The success of these research efforts will depend, in part, on future funding levels.


It's not often that USAMRIID scientists get to take their expertise out of the laboratory and into a field setting. For Schoepp, the experience has been "rewarding," though he says he'll be ready to stay home for a while after completing his fourth trip to West Africa in just six months.

"What makes me really proud is that the laboratory staff we trained [in West Africa] jumped right into the fray, and thanks to the training we provided, they didn't even blink," said Schoepp. "They started testing right away; they knew what to do."

While the scientists at the Liberian Institute for Biomedical Research put in long, hot hours wearing protective gear in the laboratory, their work environment is far from the only challenge they face, according to Schoepp. Diagnostics personnel are under a great deal of pressure to run the tests accurately, because the results they provide to the health care team literally can mean the difference between life and death for a patient.

"It's critical to diagnose Ebola-infected individuals, of course, but it's also important to tell people they're not infected," he said. "Being able to give them an answer -- so they can go home and not worry -- that's pretty satisfying."


Q: What is Ebola Virus Disease?

A: Ebola Virus Disease, formerly known as Ebola Hemorrhagic Fever, is a preventable, but often deadly illness, that results from infection with the Ebola virus. EVD first appeared in 1976, in two simultaneous outbreaks in Sudan and what is now the Democratic Republic of Congo. Scientists believe the source of the virus is most likely bats, and other animals can also become infected. An outbreak in people begins when an individual or small group of people become infected by eating uncooked or undercooked meat from infected game animals, such as bats and monkeys, also known as "bush meat." Once people are infected, the virus can be spread from person to person. Fortunately, people infected with Ebola can only spread the virus to others after they become ill. EVD is preventable, and people can avoid being exposed by following good personal hygiene practices and using appropriate protective equipment when they may have contact with ill patients. There are currently no licensed vaccines or specific treatments for EVD, but several new products are currently being tested on humans. Patients who sought care soon after symptoms started have survived with only supportive care, such as balancing the patient's fluids and electrolytes and treating for any complicating infections.

Q: How is Ebola virus spread?

A: Ebola enters the human population from direct contact with infected animals. It then spreads from person to person by direct contact with blood, secretions, organs or other bodily fluids (such as sweat, vomit and diarrhea) of infected people. Only people who have symptoms of Ebola, or have recently died from Ebola, can transmit the virus to others, and the risk of spreading the infection to others increases as the disease progresses. Objects or surfaces contaminated with an EVD patient's blood or other body fluids are also possible sources of infection. Ebola is not spread through the air like a common cold or by casual contact (like sitting next to someone or having a conversation). Ebola is not spread through drinking water, eating cooked food or being bitten by insects like mosquitoes or ticks. Just being in a country where people are ill with EVD is not dangerous. One can avoid being exposed to Ebola virus by understanding how it is spread and by taking basic preventive measures.

Q: What are the signs and symptoms of EVD?

A: EVD is an illness that can start two to 21 days after becoming infected with the virus, but typically illness begins in eight to 10 days. The most common symptoms of EVD are fever, tiredness, loss of appetite, vomiting, diarrhea, headache and stomach pain. Rash, red eyes and the bleeding some people think of when they hear about Ebola are not commonly seen. The most common signs and symptoms of EVD are not unique to this infection, and they are the same as more common diseases found in Africa, such as malaria or influenza. Even "food poisoning" or a heat injury can also cause these symptoms.

Q: There is a lot of stuff about Ebola on the internet, some of it claiming information is being withheld or covered up, and that Ebola is more dangerous than we're being told. I also read that Ebola has spread to the United States. How do I know what to believe?

A: There is a lot of information available online about a variety of subjects from a variety of different sources. As with any important subject, especially medical or scientific matters, you should only get your information from reputable sources. For Ebola, these include the World Health Organization, the Centers for Disease Control and Prevention and the U.S. Army Public Health Command. Remember, the internet is full of people who don't understand Ebola, but who can easily share incorrect information in blog posts, videos or on social media. While Ebola is a serious and potentially deadly infection, it requires direct contact with blood or body fluids of infected people who have symptoms. Our Soldiers are at low risk because they will not be in close proximity to patients with Ebola and are trained on preventive and protective measures. For cases in a developed country like the U.S., our public health system is prepared and can quickly prevent any spread.

Here are the links to reputable sources of information about Ebola virus:

• WHO --

• CDC --



Sierra Leone Samples: Evidence of Ebola in West Africa in 2006

A study published in July 2014, in the journal, Emerging Infectious Diseases, showed that Ebola virus has been circulating in the region since at least 2006 -- well before the current outbreak.

According to first author Randal J. Schoepp, Ph.D., of USAMRIID, between 500 and 700 samples are submitted each year to the Kenema Government Hospital Lassa Diagnostic Laboratory in Sierra Leone. Generally, only 30 to 40 percent of the samples test positive for Lassa fever, so the aim of this study was to determine which other viruses had been causing serious illnesses in the region.

Using assays developed at USAMRIID that detect the presence of IgM, an early protein produced by the body to ward off infection, the research team found evidence of dengue fever, West Nile, yellow fever, Rift Valley fever, chikungunya, Ebola and Marburg viruses in the samples collected between 2006 and 2008. About two-thirds of the patients had been exposed to these diseases, and nearly 9 percent tested positive for Ebola virus.

In addition, of the samples that tested positive for Ebola, the vast majority reacted to the Zaire strain, which was unexpected, according to the authors.

"Prior to the current outbreak, only one case of Ebola had ever been officially reported in this region, and it was from the Ivory Coast strain," said Schoepp. "We were surprised to see that Zaire -- or a variant of Zaire -- was causing infection in West Africa several years ago."

The laboratory testing site in Kenema has been supported by the Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance and Response System. In collaboration with the host country, the site enables collection of samples that can be used in research toward new medical countermeasures, and allows USAMRIID to evaluate the performance of previously developed laboratory tests using samples collected on site. USAMRIID hopes to eventually obtain viral isolates for medical countermeasure development and receive data on the performance of the diagnostic assays.

Other contributors to the work include the Department of Defense Joint Program Executive Office-Critical Reagents Program, the Defense Threat Reduction Agency Cooperative Biological Engagement Program and the DTRA Joint Science and Technology Office.

Related Links:

U.S. Army Pubic Health Command: Ebola Virus Disease

U.S. Army news, information about Army's response to Ebola threat

Natick plays key role in helping to fight spread of Ebola

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