Enteric Diseases
Infectious diarrhea has historically been a substantial cause of morbidity for deployed U.S. military personnel and continues to the present day in those deployed in the global war on terrorism. Pathogenic bacteria, including Campylobacter, enterotoxigenic Escherichia coli (ETEC), and Shigella, are principal causative agents. These pathogens are also major causes of travelers’ diarrhea in civilian populations and endemic diarrheal diseases in young children in resource-limited regions of the globe. While acute infections resolve on their own in three to five days, half of those infected report decrease in job performance and one in ten will go on to develop post-infectious irritable bowel syndrome. The Enteric Diseases Department’s research program is centered on the development of effective countermeasures to prevent or abate bacterial diarrhea, with most efforts aimed at vaccine research and development.
Research efforts for Campylobacter and ETEC include studies of molecular pathogenesis, antigen discovery, and vaccine development and clinical trials. In addition, the department’s Clinical Trials Branch works closely with the Walter Reed Army Institute of Research (WRAIR) Division of Bacterial and Rickettsial Diseases in the clinical evaluation of new Shigella vaccine candidates.
The department is organized into four closely integrated branches: Molecular Biology, Immunology, Biochemistry, and Clinical Trials. Principal investigators within the program work with a number of extramural academic, industry, and government partners to achieve the goal of developing new-generation vaccines against bacterial diarrhea. In the realm of clinical trials, the WRAIR/NMRC facilities afford access to the WRAIR Pilot Bioproduction Facility for scale-up and manufacture of investigational vaccines and with a state-of-the-art outpatient clinical trials center where Phase I safety and immunogenicity trials are conducted.
Enterotoxigenic E. coli
Most Escherichia coli are normal inhabitants of our environment and gastrointestinal tracts and do not cause disease. However, a number of different so-called diarrheagenic E. coli have the ability to colonize the gastrointestinal tract and cause diarrhea in humans and animals. The most common is enterotoxigenic E. coli (ETEC), which causes disease by attaching to the intestinal lining through specialized projections called fimbriae. Once attached, ETEC multiply and produce toxins that stimulate an outpouring of intestinal fluids, which can cause diarrhea and consequent dehydration. NMRC researchers are developing vaccines that would block attachment and toxin activity, interrupting the infection at its earliest stages, which should reduce the number and severity of ETEC diarrhea cases.
Campylobacter jejuni
Campylobacter jejuni is a relatively newly identified pathogen, yet it has been a focus of the Navy enterics research program since its importance was first recognized. A food-borne pathogen, Campylobacter jejuni causes a more severe disease than ETEC, causing high fever, severe stomach cramps, headache, and joint pains in addition to diarrhea. NMRC’s Enteric Diseases Department has identified many surface structures of the bacteria, found how it invades human cells, and characterized many aspects of the immune response. This work continues with the use of comparative genomics, expression arrays, and studies to try to better understand the protective immune response, all of which will enable researchers to develop an effective vaccine.