NIAID Diagnostic Test Identifies Norovirus Outbreaks

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Noroviruses are perhaps best known for ruining cruise ship vacations, but they also wreak havoc in other closed settings such as day care centers, dormitories and nursing homes. Worldwide, they are the most common cause of acute gastroenteritis, an illness that can lead to abdominal cramps, diarrhea, and vomiting in all age groups.

The Centers for Disease Control and Prevention (CDC) estimate that each year noroviruses cause more than 20 million cases of acute gastroenteritis in the United States. Noroviruses are highly contagious; as few as 18 virus particles are thought to be sufficient to cause infection. They are easily spread through contaminated food or water, from person to person, and by touching contaminated surfaces. Symptoms may last only a few days; however, for infants, older adults or people with underlying diseases, the infection can be severely debilitating and require hospitalization. While there is no vaccine to prevent norovirus infection, early detection is critical to controlling the spread of disease outbreaks, especially within a closed community.

Researchers have worked for years to develop diagnostic tools for norovirus. These efforts reached an important milestone recently when the U.S. Food and Drug Administration (FDA) approved the first screening test for the preliminary identification of norovirus. The test, called the RIDASCREEN¨ Norovirus 3rd Generation Antigen Enzyme Immunoassay (EIA), is based in part on technology developed by National Institute of Allergy and Infectious Diseases (NIAID) scientists.

Human noroviruses cannot yet be grown in the laboratory, making it difficult for researchers to study their interaction with immune cells. Dr. Kim Y. Green and her team in NIAID's Laboratory of Infectious Diseases used genetic engineering to sidestep this challenge. They modified the DNA of another family of viruses, called baculoviruses, to carry the gene that encodes the protein shell, or capsid, of several norovirus strains. When grown in insect cells, the modified baculoviruses express virus-like particles (VLPs) that mimic the norovirus capsid. The capsid contains antigens that stimulate the immune system to produce antibodies that attack the virus. These VLPs can be purified in large quantities for use as diagnostic reagents and potential vaccine candidates.

Diagnostics manufacturer R-Biopharm AG licensed the recombinant baculoviruses from NIAID in 2004 and used the virus-derived VLPs to create monoclonal antibodies against norovirus. In R-Biopharm's RIDASCREEN¨ test, these antibodies serve to capture a norovirus antigen from a stool sample. If the antigen is present, the antibodies bind to it so it can be detected in later steps of the test.

In 2011, the FDA approved the marketing of R-Biopharm's RIDASCREEN¨ as the first test for the preliminary identification of norovirus outbreaks. The test is for use in situations where a number of people have simultaneously contracted gastroenteritis, and there is a clear potential avenue for virus transmission such as a shared location or food. The ability of the test to detect a norovirus outbreak becomes greater as the number of patient samples increases, so while the test is not recommended for diagnosing norovirus infection in sporadic cases of gastroenteritis, it is useful for the preliminary screening of multiple stool samples.

RIDASCREEN¨ allows medical workers to identify norovirus infections at or near the location of the outbreak, eliminating the need to send samples to a secondary facility. According to R-Biopharm AG, the test yields results in less than two hours, enabling faster implementation of outbreak control procedures that can halt the spread of illness. In March 2011, the CDC updated its norovirus outbreak management and disease prevention guidelines to reflect the approval of RIDASCREEN¨.

NIAID's contribution to the RIDASCREEN¨ test is its latest accomplishment in a decades-long commitment to better understand noroviruses and develop new strategies for preventing, detecting, and treating norovirus infections. In 1972, NIAID researcher Dr. Albert Z. Kapikian and his colleagues first identified norovirus, initially called Norwalk virus, as a cause of acute epidemic gastroenteritis. NIAID scientists continue to pursue the development of vaccines and antiviral compounds against norovirus, including research on possible experimental systems to facilitate study of the immune response to norovirus infection in cells and in animals.