32 Cytomegalovirus Infection
Cytomegalic inclusion disease (CID) usually occurs as a Subclinical infection followed by periodic reactivation revealed by shedding of the virus. It may be serious in the neonate when infection is transmitted to the fetus in utero.
Clinical Manifestations and Pathology
Cytomegalic infection is characterized histologically by the presence of large cells containing inclusion bodies in the midst of an infiltration of mononuclear cells that may be present in any of the body organs.
In prenatal infections most infants are bom without clinical evidence of disease, although some 10 to 15 percent may show microcephaly, retardation of growth or mental development, hepatosplenomegaly, jaundice, and calcifications in the brain. There may be abnormalities in liver function tests and in hematopoiesis. Some 10 to 30 percent of infants with symptomatic disease die in early life. Evidence of involvement of the central nervous system can develop in the early years of life, even though the child may appear normal. The evidence is manifested as impaired intellect, neuromuscular abnormalities, chorioretinitis, optic atrophy, or hearing loss.
Neonatal infection acquired at birth from an infected cervix or later from the mother’s milk usually goes unnoticed but can be identified by the development of antibodies. In addition, respiratory symptoms including pneumonia, as well as petechial rash and enlargement of the liver and the spleen, may occur. In these cases, however, acute involvement of the central nervous system is rare.
Infection in children is generally asymptomatic and is evidenced only by the development of antibodies and the shedding of virus. Occasionally hepatosplenomegaly and abnormal liver function are found. There is no proof that pharyngitis occurs at the presumed portal of entry.
When infection occurs in adults the clinical picture is similar to infectious mononucleosis, with pharyngitis; Iymphadenopathy; systemic symptoms of fever, chills, and headaches, and occasionally a maculopapular rash being the primary symptoms.
Atypical lymphocytosis is usual, and there may be abnormal liver function.In instances where the disease is transmitted by transfusion of blood or its products, the infectious mononucleosis syndrome usually appears as a posttransfusion episode at 2 to 4 weeks. Immunocompromised patients are at special risk of exogenous infection by transplanted organs or by transfusions, or of activation of the latent state. Death may occur from interstitial pneumonia, often complicated by superinfection with gram-negative organisms, fungi, or other unusual invaders.
Distribution and Incidence
Serologic studies show that cytomegalic inclusion disease has a worldwide distribution. It remains asymptomatic despite prolonged shedding of the virus at periodic reactivation but is not highly communicable. Presumably the virus is spread mainly by contact with oral secretions because it is shed from the salivary glands, and cultures from pharyngeal lymphoid structures commonly are positive. The virus has been isolated from urine, breast milk, semen, and cervix uteri, and consequently the infection may be a sexually transmitted disease.
The most serious aspect of CID is its role as a prenatal disease. Even though the mother is asymptomatic and immune, transmission of the virus to the fetus does occur. Recurrence of infection is the most probable explanation for prenatal infection although, of course, primary infection may occur during pregnancy, and there is evidence suggesting that infection in the offspring is more serious under such circumstances than when infection takes place because of recurrence in a mother protected by antibodies. A recent study has shown that children infected in a day-care center may be the source of infection for pregnant mothers.
With a disease spread mainly by oral secretions, a higher incidence is to be anticipated in those living in crowded and unhygienic surroundings. For example, 100 percent of the women in Tanzania have antibodies by the time they reach childbearing age.
Other studies show seropositivity in 50 to 80 percent of children in boarding schools and orphanages in England as compared to 10 percent to 20 percent in children of the same age attending day schools. In Puerto Rico, between 70 and 80 percent of adults have the antibodies, whereas in London the figure is only 50 to 60 percent. J. A. Hanshaw has pointed out that studies in the United States and the United Kingdom show that from 0.2 to 7.5 percent of newborns are virus positive, making this disease the most common fetal infection. In the United States, the complement-fixing antibody is present in 5 to 25 percent of infants 8 to 24 months of age. In a study of the prevalence of cytomegalovirus excretion in 244 children aged from less than 1 year to 4 years in five day-care centers of a southern city of the United States, each child was tested for viral isolation by mouth swab and urine sample. It was found that 49 percent, 40 percent, 32 percent, 13 percent, or 9 percent of children, depending on the center, were excreting virus. Of the workers at the centers, 50 to 100 percent had antibodies to the virus, as did 56 to 88 percent of the parents.Immunology
Antibodies develop upon infection to last for life. Nevertheless, as in other diseases caused by the her- pesviridae, the presence of circulating antibodies even in high titer does not forestall recrudescences of infection.
History and Geography
Early in this century, pathologists noted the enlarged cells with inclusion bodies in organs of children dying of presumed congenital syphilis. The inclusions were thought to be amebae. In 1921 E. W. Goodpasture and F. B. Talbot noted their similarity to changes found in varicella and guessed they represented viral infection and described the cellular enlargement as “cytomegaly.” The virus was isolated in 1956 by investigators working independently in St. Louis, Boston, and Bethesda. Epidemiological studies became feasible with the recognition of antibodies to the virus in 1968.
A rapid expansion of knowledge concerning epidemiology, incidence, and clinical manifestations continues from the late 1960s.R. H. Kampmeier
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