By Marie McCullough
INQUIRER STAFF WRITER
A pervasive but little-known herpesvirus has emerged as the cause of a common childhood disease, a threat to organ transplant patients, and possibly even the trigger for some cases of multiple sclerosis.
Human herpesvirus 6, or HHV-6, is a cousin of the notorious organisms that cause chicken pox, genital sores and mouth sores.
In recent years, scientists have begun to understand how important the virus may be, according to an article in the current issue of the journal Emerging Infectious Diseases.
HHV-6 was discovered 13 years ago and is now known to be in the blood of virtually all humans. The virus, which has two variations, is probably transmitted through saliva and infects almost everyone within the first year or two of life, said Caroline Breese Hall, a professor of pediatrics at the University of Rochester.
"I don't know another agent that is so contagious that it causes almost
universal infection by age 2," she said.
In about 30 percent of children under age 2, HHV-6 infection causes roseola, which has long been considered a mysterious but innocuous childhood disease. Roseola begins with a sudden high fever. After about three days, the fever goes away and a blistery rash appears for a few days.
Most babies have no serious complications, but occasionally, the fever is accompanied by nausea and convulsions - symptoms that terrify parents. Hall's research suggests that a quarter of all emergency-room visits for children less than a year old are due to HHV-6 infection. Her work also suggests that children who don't develop roseola suffer other, undefined HHV-6 diseases characterized by fevers and symptoms involving ears, stomachs or other organs.
A big problem, she said, is that HHV-6 childhood diseases are easily confused with unrelated illnesses. Some pediatricians - particularly those who may not know HHV-6 causes roseola - guess they are battling a bacterial infection and give antibiotics. Not only are antibiotics ineffective against viral infections, but they may make the confusion worse. For example, if the roseola rash appears, the doctor may assume it's an allergic reaction to the antibiotic and warn against using the drug in the future.
One solution to this dilemma would be a rapid blood test for HHV-6, experts agree. Hall and other researchers are trying to develop such a test.
Another solution would be a vaccine against the virus.
"I think it's possible to develop a vaccine, but there hasn't been much interest in that because people haven't appreciated the cost of this illness," Hall said. "Thirteen percent of babies who come into the emergency room because of HHV-6 infections wind up being hospitalized." Like other herpesviruses, HHV-6 never goes away, but is subdued by the immune system. In healthy people, HHV-6 usually lives harmlessly in lymph nodes and brain cells, continues to reproduce in salivary glands, and is shed in saliva.
But also like other herpesviruses, HHV-6 can become a renewed threat if the immune system is weakened by AIDS or immune-suppressing drugs. Organ- and bone marrow-transplant patients, who take such drugs to prevent organ rejection, are particularly vulnerable. HHV-6 reactivation may cause pneumonia, encephalitis, hepatitis, fever, rash or even organ rejection. Often, HHV-6 attacks in combination with other latent herpesviruses.
"Each of these viruses is a pathogen [disease agent] in its own right, and in combination . . . may produce disease far more serious . . . than it would alone," said Gabriella Campadelli-Fiume, a virologist at the University of Bologna in Italy, who wrote the journal article about HHV-6.
The danger of HHV-6 is "on the radar screen" at most transplant centers, said Philip Pellett, a herpesvirus expert at the Centers for Disease Control and Prevention. Some centers have even begun treating transplant patients who develop serious HHV-6 infection with ganciclovir, one of the few available anti-viral drugs.
The possible link between HHV-6 and multiple sclerosis is controversial, but has been the focus of much research in the last few years, Campadelli-Fiume said.
MS is a progressive, incurable and mysterious disease that attacks the protective covering of nerve fibers in the brain and spinal cord, gradually causing paralysis. The disease is believed to be an autoimmune reaction, and viruses have long been suggested as the trigger.
Although there is clear evidence that HHV-6 can attack nerve cells, studies of virus reactivation in MS patients have been inconclusive. Several studies indicate that these patients have unusual HHV-6 distribution in their brains, but the significance is not clear. Pellett said some investigators advocate testing the anti-viral drug acyclovir on MS patients to see if it helps them. Ganciclovir would be too toxic for such trials.
"Obviously, we don't have the answers," Hall said. "If HHV-6 plays a
role in MS, I think it's only in certain forms of MS."
The identification of HHV-6 is part of a leap in understanding of herpesviruses that has been boosted by AIDS research and better techniques for growing cells in the lab, Pellett said.
Researchers have so far identified eight herpesviruses - the types that
cause chicken pox, genital sores and mouth sores , two lesser-known types
that cause mononucleosis, and the latest - herpesviruses 6, 7 and 8. Little
is known about HHV-7 and HHV-8. Pellett speculated there may even be one
or two undiscovered types lurking in human cells.