The branch devotes considerable resources to developing vaccines for diarrheal diseases, particularly the primary cause of bacterial dysentery (Shigella flexneri and S. dysenteriae). Its experimental vaccines are generally of two types: live-attenuated vaccines, which contain modified strains of pathogens that can, though weakened, induce a strong immune response; and sub-unit vaccines, which contain very small parts of pathogenic microorganisms, selected for their ability to trigger an immune response.

The branch devotes considerable resources to developing vaccines for diarrheal diseases, particularly the primary cause of bacterial dysentery (Shigella flexneri and S. dysenteriae).

Because enteric and diarrheal diseases are a major cause of death for children in the developing world, they were recently targeted by the worldwide Global Enteric Multicenter Study (GEMS) led by Dr. Myron Levine of the University of Maryland, a study of more than 20,000 pediatric subjects at seven sites in sub-Saharan Africa and Southeast Asia, the results of which were reported in May 2013. As Dr. Malabi Venkatesan, who leads the branch’s live Shigella vaccine program, pointed out, these areas are, not coincidentally, where WRAIR’s overseas laboratories – the U.S. Army Medical Research Unit-Kenya (USAMRU-K) and the Armed Forces Research Institute of Medical Sciences (AFRIMS, headquartered in Bangkok, Thailand) – conduct several infectious disease research programs. “The GEMS study,” said Venkatesan, “showed that the Shigella bacteria was a leading cause of moderate to severe diarrhea in these areas.” WRAIR researchers are developing both live and sub-unit vaccines for Shigella; both of which were manufactured on site at WRAIR and are currently being evaluated in clinical trials.

While Shigella has been a focus for WRAIR researchers for years, said Oaks, the pathogen comprises one piece of the branch’s broader effort. “What we are working on,” he said, “is a diarrheal disease vaccine. We’re part of a larger program funded by the Military Infectious Diseases Research Program. That includes work done by the Naval Medical Research Center, and here at WRAIR. We work together. And the ultimate goal is to actually make a diarrheal disease vaccine for Shigella, Campylobacter, and ETEC [enterotoxigenic Escherichia coli].”

The Bacterial Diseases Branch is also responsible for one of WRAIR’s newest initiatives, launched in response to an epidemic of multidrug-resistant organism infections in health care facilities and among wounded warriors. Established in 2009, the Multidrug-resistant Organism Repository and Surveillance Network (MRSN), under the leadership of Col. Emil Lesho, collects and characterizes these organisms at medical facilities throughout the Army in order to inform best clinical practices, influence policy, and enhance infection prevention and control efforts. Currently comprised of a microbiological laboratory, an organism repository containing more than 15,000 isolated pathogens, and seven Army hospitals, the MRSN is available to Navy and Air Force facilities, and is poised to expand to all Army hospitals – and perhaps to all U.S. military hospitals. The network has already helped halt the progress of a fatal outbreak of methicillin-resistant Staphylococcus aureus (MRSA) in a hospital’s neonatal intensive care unit, and promises to be increasingly useful as it matures. “The MRSN is already affecting policy,” said Oaks, “leading to improved infection control in health care facilities.”

The branch’s research outcomes include the development of methods to identify and diagnose infectious agents as rapidly as possible. In partnership with WRAIR’s overseas laboratories, the Bacterial Diseases Branch is developing methods, such as mass spectrometry, that enable technicians to identify infectious agents in a fraction of the time taken by traditional culturing and microscopy, which can take two to three days.

As Venkatesan pointed out, a mass spectrometer – typically about the size of a walk-in closet – isn’t of much use in a wartime theater. “Our diagnostics people are also working on making kits that can be used by a medic to make a rapid determination of whether a person is suffering from a viral disease or a bacterial disease. It’s a simplified tool, but important, so that field personnel can know not to give an antibiotic to a person who may be suffering from a viral disease. There [is] a whole range of diagnostic kits and equipment being evaluated to fit different settings and circumstances.”

 

Viral Diseases

The recent redevelopment of the adenovirus oral vaccine for serotypes 4 and 7, said acting Viral Disease Branch Laboratory Director Maj. Richard Jarman (Lt. Col. Stephen Thomas, director of Viral Diseases, was deployed during the preparation of this article), illustrates the necessity of the military’s involvement in this research: Diseases that aren’t regarded as a threat by most Americans can have a profound effect on military readiness and end strength.