Monday, December 22, 2014

DoD Scientists Work Globally to Improve Disease Diagnostics

By Cheryl Pellerin
DoD News, Defense Media Activity

FORT DETRICK, Md., Dec. 22, 2014 – At the U.S. Army Medical Research Institute of Infectious Diseases here, scientists who develop and refine diagnostics do more than work in a laboratory. Some take their disease-identifying tools into the field and try them out on a virus’s home turf.

That’s what virologist Dr. Randal J. Schoepp as doing in Sierra Leone in 2006, working as part of a collaborative project to develop and refine diagnostic tests for Lassa fever, a hemorrhagic virus endemic to Sierra Leone, Liberia and Guinea.

Schoepp is chief of the Applied Diagnostics Department in the Diagnostics Systems Division at USAMRIID. Since March 2014, he’s spent a total of 12 weeks in West Africa, where he and colleagues support the U.S. Ebola response.

“What’s better than to have an opportunity to take diagnostics that we develop in the laboratory out and look at a real-world situation?” he asked. “Because a lot of these things work just fine in the lab, but … they might not work well with African serum or at 80 degrees.”

The Sierra Leone project, funded by the Armed Forces Health Surveillance Center’s Global Emerging Infections Surveillance and Response System, or GEIS, began looking for Lassa fever in patient samples but also found many other viruses, including Ebola.

Undiagnosed Fever-causing Diseases

The research team found evidence of dengue fever, West Nile, yellow fever, Rift Valley fever, chikungunya, Marburg and Ebola viruses in patient samples collected in Sierra Leone, Liberia and Guinea between 2006 and 2008.

The Ebola finding was surprising in a region that had reported only one case of Ebola, the Tai Forest strain, in Cote d’Ivoire in 1994. And the strain found in Sierra Leone turned out to be Zaire, the most virulent Ebola strain and the one causing West Africa’s current outbreak.

In a research paper about the Ebola finding published in the Centers for Disease Control and Prevention’s Emerging Infectious Diseases journal in July, first author Schoepp said the research shows that Ebola had been circulating in the region since 2006, nine years before the current outbreak.

“We're trying not only to improve the [diagnostics] capacity of a host country, but to understand what diseases we’ll find there,” he said.

Developing and Refining Diagnostic Tests

USAMRIID has been working in the region since 2006, when it began the collaborative project to develop and refine diagnostic tests for the Lassa fever virus. In addition to providing laboratory testing and training support for the current Ebola outbreak, USAMRIID has provided more than 10,000 Ebola assays to support lab capability in Sierra Leone and Liberia.

In the USAMRIID Applied Diagnostics Department, Schoepp said, he and his colleagues work primarily on immunodiagnostics development, test and evaluation. Immunodiagnostics use antibodies to detect a virus or virus products, or antibodies that result from infections with a virus.

In this work, he said, “we partner with a lot of the overseas GEIS labs.”

Global Infectious Disease Surveillance

One of GEIS’s funded laboratories is the Naval Medical Research Unit-3, or NAMRU-3, the largest DoD overseas lab, formally established in Cairo in 1946. Scientists there conduct research on a range of diseases and perform infectious disease surveillance to support military personnel deployed to Africa, the Middle East and Southwest Asia.

NAMRU-3 also has a Ghana Detachment in Accra that is part of the Noguchi Memorial Institute for Medical Research, with a laboratory and administrative spaces where the detachment’s manager and technicians work.

“We work with the Ghana Detachment out of NAMRU-3,” Schoepp said. “I have a colleague there from NAMRU-3 that has just been sent to the Ghana Detachment because it's closer to Liberia, and NAMRU-3 wants to build capabilities in Liberia.”

The Ghana Detachment was established to build a partnership between the U.S. Navy and Ghana for lab- and field-based infectious disease research and to perform clinical and field trials of new drugs and vaccines against malaria, according to a State Department fact sheet.

In Ghana, research collaboration among NAMRU-3, the Ghana Ministry of Health and the Noguchi Institute began in 1995 and recently was formalized.

Infectious Disease Research Collaboration

Accomplishments there include creating a West African military collaboration for disease surveillance for flu, sexually transmitted infections and acute febrile, or fever-causing, illnesses. Upcoming efforts include research collaborations with GEIS, one involving malaria resistance and another involving immunology, or how the body protects itself from disease.

Another GEIS-funded lab is NAMRU-6, hosted by the Peruvian Navy and collocated at their hospital in Lima. This lab conducts research and surveillance on infectious diseases that threaten military operations in the region, including malaria, dengue fever and yellow fever.

“We do a lot of work with USAMRU-K in Nairobi,” Schoepp said, referring to the U.S. Army Medical Research Unit-Kenya.

Twelve Army soldiers and two DoD civilians make up USAMRU-K. Assigned to the unit are two U.S. Embassy staff members and more than 600 contracted Kenya Medical Research Institute or Henry Jackson Foundation-Medical Research International employees.

Immunodiagnostics for Overseas Labs

USAMRU-K headquarters is in Nairobi, Kenya, on the campus of the Kenya Medical Research Institute. Primary operational sites in Kenya include Nairobi, Kericho Field Station and Kisumu Field Station.

“My program in GEIS is to help with and provide immunodiagnostics to the overseas labs,” Schoepp said.

“I try to do this collaboratively,” he added. “I don't want to be ‘Diagnostics R Us’ and just hand out diagnostics, because diagnostics interpretation is as important as the test you're using. If you don't understand the test, your interpretation can be completely wrong.”

The virologist said he also works with scientists in Mongolia, “because one of the hemorrhagic fevers I have an interest in and the DoD has an interest in is Crimean Congo hemorrhagic fever,” or CCHF.

Stalking a Tick-borne Virus

CCHF is a widespread hemorrhagic disease caused by a tick-borne virus that causes severe outbreaks. Cases have a fatality rate of 10 percent to 40 percent. CCHF is endemic in Africa, the Balkans, the Middle East and Asian countries south of the 50th parallel north, the geographical limit of the main tick carrier, according to the World Health Organization.

“CCHF is a very plastic virus, meaning it has a lot of variability among strains, and we don't even understand how plastic it is,” Schoepp said. “We know what strains are in Russia but we have very little idea what strains are in China, and Mongolia sits right between them.”

So Schoepp, in collaboration with a colleague, traveled to Mongolia, got to know several scientists there and began working with them, he said.

Building Host Country Capacity

“We’re looking at over 2,000 human samples from five different regions in Mongolia for antibodies to CCHF, and corresponding to that we have ticks from livestock from the same villages where we're working with the virology folks to attempt to isolate the virus out of those ticks and identify it,” Schoepp explained.

The scientists are hoping to find CCHF, and they’ll also look for any other tick-derived diseases that may be circulating in the populations, he said.

These and other collaborations in the United States and around the world allow USAMRIID to protect troops worldwide, respond to international public health emergencies, identify undiagnosed febrile illnesses that are circulating in host countries, build the country’s capacity to identify diseases, and test their medical diagnostics in settings where diseases naturally occur.

After spending 12 weeks in West Africa between since March, Schoepp said, he wants to go back there to continue his search for undiagnosed febrile diseases.

“I'm going to try to mimic in Liberia what we had in Sierra Leone,” he said. “The infrastructure is better in Liberia, and we know bits and pieces [about what infectious diseases are there], but nobody knows the whole story. It's a chance for me to go in and tell another story.”

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