Lymphocytic choriomeningitis virus: an unrecognized teratogenic pathogen.

Lymphocytic choriomeningitis virus (LCMV), the first member of the arenavirus family to be isolated, is the causative agent of a zoonosis acquired from chronically viremic mice or hamsters (1). The clinical spectrum of acquired human LCMV infection ranges from inapparent and asymptomatic to, in rare instances, severely symptomatic, systemic, and fatal central nervous system (CNS) disease. Intrauterine LCMV infection has resulted in fetal or neonatal death, as well as hydrocephalus and chorioretinitis in infants (2-6). We have diagnosed congenital LCMV infection in three infants (7) and have collated published and unpublished data on three additional affected infants (8, G.R. Istre, pers. comm.). This report briefly summarizes the salient features of the infection in five of these six American infants and outlines the similarities between these and features observed earlier in Europe. We suggest that LCMV is a more frequent cause of CNS disease in newborns than previously recognized. Congenital LCMV infection was first recognized in Great Britain in an infant who died at 12 days of age (3). Subsequently, fetal infection with spontaneous abortion (2) and congenital infection in liveborn infants with hydrocephalus and chorioretinitis were documented in Germany (4), France (6), and Lithuania (5). We have recently documented congenital LCMV infection in three infants from Arizona (7) and have obtained information regarding three additional neonates from Arizona, Nebraska (8), and Texas (G.R. Istre, pers. comm.). Detailed clinical and laboratory data are available for five of the six infants. All displayed nonobstructive hydrocephalus with periventricular calcifications, chorioretinitis, and psychomotor retardation. One of the five infants had sensorineural deafness. None of the infants had cardiac abnormalities. Two infants have had follow-up ophthalmologic and audiologic examinations which have shown neither the progression of chorioretinitis nor the development of new auditory deficits. Toxoplasma gondii, cytomegalovirus, Herpes simplex virus, rubella, enterovirus, and Treponema pallidum infections were excluded by culture or serology in all infants. The diagnosis of congenital LCMV infection was confirmed in all infants by immunofluorescence antibody (IFA) and enzyme-linked immunosorbent assays (ELISAs). In addition, serum, CSF, urine, and throat wash specimens from two infants were injected into Vero cell monolayers. Neither cytopathic effect nor LCMV antigens were detected after incubation. Because virus isolation was only attempted after the disease was first diagnosed when the children were 10 months of age, failure to isolate LCMV was not unanticipated. Laboratory diagnosis of LCMV infection is generally made by serologic techniques. IFA is a more sensitive diagnostic method than either complement fixation or neutralizing antibody techniques (9,10). The newer ELISAs are now being used to evaluate congenitally infected infants. Testing the child’s serum and CSF and a simultaneously obtained serum specimen from the mother yields the maximum information if done as soon after birth as possible. The mothers of four of the five infants in this report had a history of febrile illness during pregnancy, in contrast to a minority of mothers of affected infants previously reported. Typical LCMV infection in adults is a biphasic disease with fever, malaise, myalgias, anorexia, nausea, vomiting, pharyngitis, cough, and adenopathy followed by defervescence and a second phase of CNS disease. However, CNS symptoms may appear without any prodrome or may never develop. Meningitis and meningoencephalitis are the most frequent neurologic manifestations of disease, although myelitis, Guillain-Barré syndrome, and sensorineural deafness have been reported (11). Between 1941 and 1958, 8% to 11% of viral CNS syndromes in hospitalized patients in a Washington, D.C., medical center were etiologically associated with LCMV (12). Arthritis, parotitis, orchitis, myocarditis, and rash have also been noted (13). Clinical interest in LCMV, however, has not been maintained, and the disease is rarely considered despite improved serodiagnostic methods. Although a history of contact with rodents and their excreta is of diagnostic utility, it is not universally present. A maternal history of rodent exposure was elicited for three of our five infants. Wild mice (Mus musculus) and hamsters infected in utero with LCMV during maternal viremia develop both persistent viremia and viruria. The Dispatches