"Every year, scores of gastroenteritis infections occur in Maryland nursing homes, but the cause of these outbreaks has baffled investigators," says Kim Green, Ph.D., a researcher in the Laboratory of Infectious Diseases of the National Institute of Allergy and Infectious Diseases (NIAID) and lead author of the study. "We and our collaborators at the Maryland Department of Health and Mental Hygiene (DHMH) recognized the importance of identifying the etiologic agent or agents so that effective prevention and control strategies could be developed for this illness."
"Extrapolating from our data that 80 percent of nursing home outbreaks over a single winter season were caused by NLVs, we believe that it is likely that there may be a heavier disease burden from this illness in United States nursing homes than previously recognized," the researchers report.
Gastroenteritis is an intestinal illness. Symptoms of the disease may include vomiting, diarrhea, abdominal cramps, fever, chills and headache. Although the illness usually lasts no longer than 48 hours, it can cause serious complications in the elderly, many of whom are already struggling with other illnesses.
Dr. Green and her colleagues evaluated the role of infectious agents in gastroenteritis outbreaks by examining stool and blood samples from Maryland nursing home residents who became ill during a period between November 1987 through February 1988. "At that time, the stool specimens were tested routinely for the presence of major bacterial pathogens, which were detected only very infrequently, leading to the conclusion that the illnesses were presumably viral," says Dr. Feng-Ying C. Lin of the National Institute of Child Health and Human Development, who spearheaded the study while a medical epidemiologist at DHMH. Since then, the availability of a new technique called reverse transcriptase-polymerase chain reaction (RT-PCR) prompted the NIAID scientists to re-examine the specimens for the presence of various enteric viruses. Using this technology, they were able to identify and sequence NLV genes in the stool specimens and compare them with genes from strains that have been circulating globally over the past decade.
"The availability of such technology marks an important advance in efforts to detect and study Norwalk-like viruses," says Albert Kapikian, M.D., assistant chief of NIAID's Laboratory of Infectious Diseases and a co-author of the report. Dr. Kapikian and colleagues in NIAID originally discovered and characterized Norwalk virus in 1972 using immune electron microscopy.
In addition to the RT-PCR technique, the research team also analyzed blood samples by other assays, which also indicated infection with NLVs. The researchers correlated illness to NLV infection if at least 50 percent of individuals in an outbreak shed the virus in stool samples or developed serum antibodies to the virus. Using this definition, investigators identified NLVs as the cause of illness in 16 of the 20 outbreaks.
Upon further examination of NLVs, scientists identified six distinct genetic clusters. Norwalk-like viruses fall into two genetic groups, Genogroup I (GI) and Genogroup II (GII), and each group is further divided into genetic clusters. The predominant virus in the nursing home study, a GII "Bristol-like" virus designated MD-145, was detected in 14 of the 20 outbreaks. Researchers note that this predominant GII virus strain is similar to another common NLV strain that has been circulating in the United States and abroad in recent years.
"We hope the knowledge gained from this study will increase awareness in the medical community that Norwalk-like viruses should be a primary suspect when an acute gastroenteritis outbreak occurs in the nursing home setting," advises Dr. Green.
NLVs are challenging to study since they do not grow in cell cultures, and there is no practical animal model, thus limiting observation of infectivity essentially only to humans, says Dr. Kapikian. However, these obstacles have not slowed NIAID's research efforts into NLVs and the illnesses they cause.
In addition to Dr. Kapikian's success in first identifying Norwalk virus in 1972, NIAID was instrumental in providing a stool suspension containing the Norwalk virus for studies that led to the first cloning of Norwalk virus genes in 1990 by Dr. Mary Estes and colleagues at Baylor College of Medicine. NIAID is also making efforts to develop a diagnostic test that would rapidly identify viral agents of gastroenteritis infections. Researchers hope that such a test will assist in determining the course of therapy indicated in the treatment of acute gastroenteritis infections and promote further research into prevention strategies, such as vaccines, for NLV-associated illnesses.
NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.
Reference:
KY Green et al. A predominant role for Norwalk-like viruses as agents of epidemic gastroenteritis in Maryland nursing homes for the elderly. The Journal of Infectious Diseases 185(2):133-146 (2002).
Press releases, fact sheets and other NIAID-related materials are available on the NIAID Web site at http://www.niaid.nih.gov.
Journal
The Journal of Infectious Diseases