A study led by researchers at the National Institutes of Health (NIH) suggests that hepatitis E virus (HEV) is common among wild rats in the United States. Although hepatitis E disease is very rare among people in the United States, many have HEV antibodies in their blood – evidence that they were once infected with the virus, even though it did not make them sick. The finding raises questions about whether there is any connection between rats and HEV infection in humans. A report of the study appears in the August 1999 issue of the American Journal of Tropical Medicine and Hygiene.

Scientists analyzed blood samples from 239 rats captured in alleyways in Baltimore, MD, along the Mississippi River levee in New Orleans, LA, and in urban and rural areas of Hawaii. Tests revealed that more than 80 percent of the rats had HEV antibodies in their blood, evidence of prior HEV infection. Yamina Kabrane-Lazizi, Ph.D., of the National Institute of Allergy and Infectious Diseases (NIAID) was lead author of the study. Her collaborators included scientists from the National Institute of Neurological Disorders and Stroke, the Johns Hopkins School of Public Health in Baltimore, and the John A. Burns School of Medicine in Honolulu, HI.

Hepatitis E disease generally affects young adults and usually is not life-threatening, except in pregnant women infected with the virus where fatality rates of 15 to 20 percent have been reported. According to the Centers for Disease Control and Prevention (CDC), virtually all cases of hepatitis E disease in the United States have occurred among travelers returning from developing countries, where the disease is endemic and spread through contaminated drinking water. Nevertheless, tests show that between 1 and 5 percent of healthy blood donors in the United States have HEV antibodies in their blood.

"Since hepatitis E is so rare in this country, it’s puzzling that so many people have antibodies to the virus in their blood," says Robert H. Purcell, M.D., chief of the hepatitis viruses section in NIAID’s Laboratory of Infectious Diseases and senior author of the study. "It may be that the high prevalence of HEV antibodies in the absence of disease is due to infection with a strain of HEV that doesn’t cause disease. Another possibility is that animals serve as reservoirs of HEV and pass a weakened form of the virus on to humans."

Dr. Purcell and his colleagues recently isolated HEV from swine in the United States, suggesting one possible source of exposure. However, HEV antibodies are detected primarily among residents of urban areas in the United States, where people rarely encounter pigs. Rats, on the other hand, have been ubiquitous city-dwellers for hundreds of years.

"Our data strongly suggest that many wild rats in the United States are naturally infected by HEV," says Dr. Purcell. "A major question is whether the HEV strain infecting rats is a new strain unique to rats or a variant of already recognized HEV strains."

To answer that question the researchers will need to isolate and characterize the rat virus, something they were unable to do in the current study. Their data suggest that rats become infected with HEV early in life. Other studies have shown that HEV disappears from the blood soon after HEV antibodies are produced. The researchers’ best hope for isolating the virus, therefore, lies in trapping young rats that recently have been infected with HEV.

Dr. Purcell and his colleagues will attempt to pass the virus from infected wild rats to rats raised in the laboratory. In addition to providing clues about the source of HEV antibodies in humans, their efforts could result in an inexpensive new animal model for studying HEV infection, says Dr. Purcell. Currently, scientists must use expensive primate models to study the virus.

"Rat HEV has probably been around a long time," says Dr. Purcell. "We still do not know the source of the high prevalence of HEV antibodies in humans. The possibility that the rat virus plays a role bears further study. It’s important to remember, however, that there is no evidence that rat HEV poses a threat to human health."

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