Human herpes viruses cause a variety of illnesses, ranging from cold sores and genital herpes to mononucleosis and some cancers. Researchers discussed this complex virus family at a symposium update during the 38th Annual Meeting of the Infectious Diseases Society of America (IDSA).

Cytomegalovirus

Cytomegalovirus (CMV) affects one percent of live births, making it the most common congenital infection in the United States. CMV infection can devastate newborns by producing mental retardation cerebral palsy, and hearing loss.

The Institute of Medicine noted in a recent report that the development of a CMV vaccine would demonstrate clear cost-effective benefits. "[There is] no question that it is a national priority to prevent CMV infection," Robert Pass, MD, University of Alabama, Birmingham, told the infectious disease specialists.

But development of a vaccine will be difficult, because CMV infection does not confer complete immunity. Studies have shown that while most transmission to the fetus occurs during a mother's initial CMV infection, transmission can also occur during a recurrent infection.

Dr. Pass and colleagues conducted a study to determine whether a history of maternal CMV infection diminishes the risk of congenital CMV. The study included 3,397 women who had already given birth to a child and who could possibly become pregnant again. Of these women, 84 percent were seropositive (infected in the past) at their previous delivery, while 16 percent were seronegative (uninfected). Of the seronegative, 26 percent seroconverted (became infected) before their subsequent pregnancies about 30 months later. The women who were considered immune to CMV-because of documented infection-still transmitted the infection to one percent of newborns, and women who were not immune transmitted CMV about four percent of the time. "The risk is clearly lower if the mother has immunity versus no immunity, but still the rate is one percent, even in immune mothers," he observed.

The success of a CMV vaccine has been hindered by a number of other factors. For instance, there is no animal model in which to study CMV infection. CMV is a very large virus (hard to develop a vaccine for), and the virus can persist in the form of chronic infection. Four vaccines are currently in clinical trials. Because CMV is fairly prevalent, reducing exposure to the virus is impossible. Vaccines remain the best hope of preventing congenital CMV infection.

Epstein-Barr Virus

The Epstein-Barr virus (EBV) is a common virus associated with mononucleosis and with more serious lymphoproliferative disease, including T cell lymphoma, a form of cancer. In the acute illness stage, up to ten percent of the total B cell population may be infected, which stimulates a potent immune response. EBV infects a wide range of cells, not only B cells but also T lymphocytes, epithelial cells, and myocytes. Even when EBV-infected B cells are eliminated, a reservoir of latent EBV infection remains, said John L. Sullivan, MD, University of Massachusetts, Worcester.

Other lymphoproliferative disorders can arise due to EBV, often after a long latency period. These include Burkitt's lymphoma (a childhood tumor largely seen in Africa), immunoblastic lymphoma (often fatal), T cell lymphomas, X-linked lymphoproliferative disease, and 50 percent of cases of Hodgkin's disease.

X-linked lymphoproliferative disease has been documented in only about 100 persons worldwide. Aspects of this disorder include immunodeficiency, the development of lymphoma or Hodgkin's disease, aplastic anemia, and liver destruction; the mortality rate is 70-80 percent. In X-linked lymphoproliferative disease, EBV infection transforms a normal person into a globally immunodeficient one. Two years ago, researchers identified the gene responsible for this rare susceptibility to EBV virus.

Kaposi's Sarcoma

Several characteristics of Kaposi's sarcoma-one of the malignant tumors of connective tissue-caused researchers to believe this tumor was due to an infectious agent. Yuan Chang, MD, Columbia University, New York, discussed her findings supporting this theory at the IDSA meeting. When Kaposi's sarcoma began appearing in homosexual men with acquired immunodeficiency syndrome (AIDS), several epidemiological features offered compelling evidence that an infectious agent was responsible. The fact that Kaposi's sarcoma occurred much more frequently in homosexual men than in other immunosuppressed persons or in HIV-positive hemophiliacs suggested it was transmitted sexually, and the predominance of Kaposi's sarcoma in certain geographic pockets, especially Africa, was also consistent with person-to-person transmission. It is now known that over half of HIV-positive Ugandans are infected with what has been named the Kaposi's sarcoma herpes virus (KSHV). It is not known why the virus is so much more prevalent in Africa than elsewhere, she said.

"Virus-induced tumor formation is a biological accident," Dr. Chang pointed out. "There is no evolutionary advantage to a virus causing a tumor, since it kills the host, but in a non-natural host with a genetic mutation, or in an immunosuppressed person (such as an AIDS patient), the balance of factors favors the virus. It became clear that Kaposi's sarcoma-all types of it-is caused by a herpes virus," she said.

The Kaposi's sarcoma virus has many routes of transmission, but in the United States this transmission is largely sexual. People with a large number of sexual partners are the most likely to develop infection. Non-sexual routes of transmission are also suspected, although they have not been confirmed. In Zambia, for instance, the illness increases with age (unlike HIV). Non-sexual transmission is also responsible for infections that develop in organ recipients whose donors test positive for KSHV, she added.

Human Herpes Virus 6

"The human herpes virus 6 (HHV6), which was discovered 15 years ago, has a confusing but captivating 'curriculum vitae.' It is acquired with alacrity and ubiquity," said Caroline B. Hall, MD, of the University of Rochester, New York.

HHV6 is the infectious agent of roseola (meaning "rash of roses", also known as 6th Disease). High fever, followed by a rash, characterizes the illness, which occurs mainly in young children.

Dr. Hall and colleagues studied over 3,000 children and found all had "passive antibodies" at birth, meaning they acquired immunity from their mothers. However, this immunity wanes, and virtually all children become infected before 18 months of age. The virus is widespread in the environment and is probably easily transmitted in a variety of ways. Further, it persists for years in many people, for reasons that are unknown, she confirmed.

HHV6 virus causes 20 percent of the acute febrile illnesses evaluated in children six to 12 months of age, and ten percent of those evaluated in children one to two years old. While most children recover easily from infection, central nervous system symptoms occasionally occur with roseola. In fact, roseola infection is the most frequent cause of seizures in children 12-15 months of age seen in the emergency department, one study found.

"HHV6 can be found in the DNA of the cerebrospinal fluid in children for the first time-and in 46 percent of previously infected healthy children," she reported. "This is associated with an increase in seizures."

"HHV6 definitely is in the brain," she maintained. In adults, researchers suspect an association between HHV6 and multiple sclerosis, since HHV6 DNA levels are increased in the brains of persons with multiple sclerosis but not in normal controls. While infection in adults is less common, HHV6 can cause a mononucleosis-like illness, with swollen lymph nodes and possibly more serious illnesses. While healthy people usually recover easily, the virus can cause bone marrow suppression in immunocompromised persons, such as AIDS patients and organ transplant recipients.