Research highlights the role of viral sequence analysis in improving our overall understanding of hepatitis A cases in the U.S.

Novel use of genetic testing methods helped public health officials control and limit the further spread of four outbreaks of foodborne hepatitis A virus in 2003 related to the consumption of green onions, according to a detailed analysis published in the October 15 issue of The Journal of Infectious Diseases, now available online.

The authors of the study, Joseph J. Amon, PhD, MSPH, and colleagues at the Centers for Disease Control and Prevention (CDC), explained that these molecular epidemiologic methods had not previously been used in an ongoing investigation of a hepatitis A virus outbreak. The methods, involving genetic sequencing analysis of virus found in blood samples from infected individuals, have greatly improved understanding of outbreaks of other foodborne pathogens, but are time-consuming and not widely available.

In September 2003, Tennessee, North Carolina, and Georgia reported a total of 422 cases of foodborne hepatitis A virus infection to CDC. Preliminary investigations suggested clustering of reported cases among patrons of three unrelated restaurants. Investigators identified green onions as the likely culprit in the outbreak by interviewing infected and uninfected restaurant patrons. In addition to these standard techniques, the researchers also compared viral RNA sequences from case patients and individuals concurrently ill with hepatitis A virus infection in non-outbreak settings in the United States and Mexico.

Viral RNA sequences from patients in the three states, plus patients involved in a subsequent outbreak in Pennsylvania in October 2003 (the latter recently described in the Sept. 1 issue of the New England Journal of Medicine), were slightly different from each other. The viral sequence from each outbreak, however, was identical to one or more sequences isolated from northern Mexican residents infected with hepatitis A virus. The researchers concluded that the sources of the green onions served in restaurants in Tennessee and Georgia were three farms in northern Mexico.

Dr. Amon and colleagues credited the viral sequencing techniques with helping them to identify the relationships between the outbreaks in four separate locations, and to define the scope of the outbreaks quickly. The sequencing allowed them to determine if cases reported in other states were related to the four original outbreaks and provided reassurance that a larger outbreak was not occurring. The molecular epidemiologic methods also enabled public health officials to respond quickly to the later Pennsylvania outbreak. As a result, consumers were warned of the potential risk, and entry of green onions from four Mexican farms into the state was banned.

"This research highlights the role of viral sequence analysis in improving our overall understanding of the roughly 50 percent of hepatitis A cases in the U.S. that are from an unknown source," Dr. Amon said. "Just as the E. coli-contaminated beef outbreaks in the early 1990s prompted changes in epidemiological surveillance that have increased our knowledge of foodborne bacteria, the 2003 hepatitis A outbreaks demonstrated the potential for integrated molecular surveillance to provide a better understanding of the epidemiology of hepatitis A and facilitate rapid responses to outbreaks."