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Stanford Report, February 23, 2000

Researchers explore how children infect parents with common virus

BY KRISTA CONGER

Kids in day care learn about sharing: sharing ideas, sharing toys and, unavoidably, sharing germs as well. Most parents are resigned to the fact that their children will bring home not just hugs and kisses for mom and dad, but also cold and flu viruses. They may not be aware, however, that kids can bring home another common infection -- one that is usually unnoticeable or causes only mild symptoms in healthy people but that can be dangerous to unborn fetuses or family members whose immune systems are not functioning normally.

Now Stanford researchers are looking for volunteers to participate in a study of how healthy adults respond to their first bout with the culprit -- human cytomegalovirus, or HCMV. By monitoring uninfected parents and child-care workers in close contact with small children, the researchers hope to be able to watch the natural patterns of transmission as the normally harmless virus travels from person to person.

"We're basically just studying what happens in nature," said Kristen Savola, MD, a postdoctoral researcher in the department of infectious diseases and a study investigator. "We are hoping to see at least some people convert from uninfected to infected," she said.

Such a conversion would allow the researchers to spy on the first meeting between the virus and its host. They hope that by watching how a person's immune system reacts when confronted by the attacker, they can learn how to design a vaccine to protect those most vulnerable to the damaging effects of infection.

Finding uninfected study participants is not easy. HCMV infection is a natural occurrence that affects 50 to 85 percent of adults worldwide. The virus, a member of the herpesvirus family, is spread through contact with bodily fluids such as saliva, urine, feces, breast milk and sexual secretions. Infection usually causes no noticeable symptoms in healthy children and adults, although a few unlucky adult victims may experience fevers, fatigue and jaundice after their first exposure. No cure for HCMV infection exists, but most healthy people harbor the virus for a lifetime with no ill effects.

Pregnant women exposed to the virus for the first time during their pregnancy, however, run the risk of serious birth defects in their unborn fetuses. If the fetus becomes infected in utero, it has about a 10 percent chance of exhibiting symptoms of HCMV infection after birth, which can include mental retardation, progressive hearing loss, developmental disabilities and visual defects. HCMV is the leading infectious cause of hearing loss in the United States. In contrast, women who are HCMV-positive prior to their pregnancy have a low risk of giving birth to an infant with symptomatic congenital HCMV infection.

HCMV can also wreak havoc in individuals whose immune systems are compromised, either by HIV infection or by immunosuppressive drugs administered after organ transplantation. These people can suffer from pneumonia, hepatitis and retinitis as a result of their HCMV infection.

Those susceptible to HCMV infection can catch the virus from both adults and children, but kids are the best bet for a virus on the move. Children can shed infectious viral particles in their urine and saliva for up to five years after congenital infection. In contrast, adults shed virus only intermittently and unpredictably throughout their lives. Uninfected adults who have only casual contact with children have about a two percent chance per year of becoming infected, but the risk of acquiring an HCMV infection jumps to up to 10 to 50 percent per year for susceptible parents and care-givers in the direct line-of-fire.

Savola is aiming to recruit 100 HCMV-negative child-care workers, or parents who have children under 2.5 years old who attend day care. Partners of HCMV-positive women who are breastfeeding will also be recruited since HCMV can be transmitted through breast milk to a child, who can then expose the susceptible partner.

Volunteers will first be asked to donate a blood sample to determine their HCMV status. Those selected to participate in the yearlong study will provide a urine sample once a month. If the researchers spot a new infection, they will conduct additional blood tests to learn how the body responds to the virus.

If you are a healthy adult who meets the above criteria and are interested in volunteering for the study, please call Savola at 498-7423. Participants will be paid $35 for the initial screening. Those selected to continue in the study will be paid for the monthly urine samples and for any further testing that may be required if an infection is detected.

Savola's collaborators include Cornelia Dekker, MD, medical director of the Stanford-LPCH Vaccine Program; Ann Arvin, MD, professor of pediatrics; and Harry Greenberg, MD, senior associate dean of research and professor of medicine.

The study is one of several conducted as part of the Stanford-LPCH Vaccine Program under the direction of Dekker, Arvin and Greenberg. The purpose of the vaccine program is to promote vaccine development by conducting clinical trials designed to define important immune responses and to test existing vaccine candidates. SR