Eli Gold

Congenital and postnatally acquired cytomegalovirus infections: Long-term follow-up

To determine long-term outcome of children with inapparent congenital cytomegalovirus infection, an assessment of congenitally infected children observed since birth was undertaken. Children with early postnatal acquisition of CMV infection were also evaluated. Cognitive, behavioral, neurologic, audiometric, and speech and language evaluations were performed in 48 patients, including 17 congenitally infected children, 10 children with postnatal infection, and 21 uninfected control subjects. Mean IQ of the three groups of children did not differ significantly. Behavioral, neurologic, speech and language examinations similarly failed to distinguish differences among the three groups. Audiologic abnormalities were present in four congenitally infected children, including one child with a severe unilateral sensorineural loss; in none of the children was hearing loss functionally significant. No hearing abnormalities were detected in postnatally infected children. Although inapparent CMV infection can result in audiologic sequelae, the continued lack of cognitive, behavioral, and neurologic sequelae in these school-age children reemphasizes the need to focus attention on prevention of primary maternal CMV infection to avoid the potentially devastating effects of intrauterine CMV infection.

Inapparent congenital cytomegalovirus infection. A follow-up study.

Abstract A follow-up study on 15 children with congenital cytomegalovirus infection was undertaken to assess physical and mental development in their first four years of life. Infection was inapparent at birth in all children except one. Assessment included a complete physical examination, psychologic testing and virologic studies. None of the children who appeared normal at birth and at one year manifested any late sequelae at four years of age. The mean IQ of the infected children was 85.2, whereas that of the eight controls was 86.5. Eleven of the 15 children (73 per cent) were excreting virus; nine of these had detectable cytomegalovirus complement-fixing antibody. All seven males tested had viruria, as compared to four out of eight females (p<0.05). Complement-fixation titers in virus-negative children were not significantly different from titers in virus-positive children. (N Engl J Med 288:1370–1372, 1973)

Postnatally acquired cytomegalovirus infections in infants of CMV-excreting mothers

A prospective study of cytomegalovirus-excreting pregnant women allowed us to identify a group of infants at high risk of acquiring CMV infection. Eighty-one infants free of CMV infection at birth were observed during the first year of life. Twenty-one became infected with CMV; 16 (76%) of these were detected within the first 14 weeks of life. Placental cultures from two of the 21 infants were CMV positive. The geometric mean cord blood antibody titers of postnatally infected and uninfected infants did not differ significantly. Clinical symptoms, including hepatosplenomegaly, lymphadenopathy, or pneumonia, occurred in association with CMV infection in seven infants. Postnatally acquired CMV infections can be symptomatic, and by virtue of their prevalence, constitute an important health problem.

A prospective study of maternal cytomegalovirus infection and its effect on the fetus

In order to define the effects of maternal cytomegalovirus infection in pregnancy and to identify risk factors associated with delivery of a cytomegalovirus-infected infant, a cohort of 1089 adolescents were prospectively evaluated during pregnancy. One hundred twenty-four subjects (11.4%) manifested cytomegaloviruria during pregnancy. Primary cytomegalovirus infection, defined virologically and serologically, occurred in three subjects. Infants of 119 cytomegalovirus-excreting mothers were cultured at birth, with detection of 12 congenital infections (10%), including one infant delivered of a mother with a third-trimester primary infection. A high titer of urinary virus or a fourfold or greater increase in antibody during the third trimester was significantly associated with delivery of a congenitally infected infant. All maternal and infant infections were asymptomatic. None of the congenitally infected infants manifested adverse effects during the first year of life. Our data demonstrate that pregnant women with cytomegaloviruria are at increased risk of being delivered of congenitally infected infants, particularly if active infection occurs late in pregnancy. If the maternal infection represents reactivation, overall probability of a poor fetal outcome is low.

DIFFERENCES IN INTERFERON CONTENT IN TISSUES OF MICE OF VARIOUS AGES INFECTED WITH COXSACKIE B1 VIRUS.

Summary Mice 24 hours to 6 weeks old were infected with Coxsackie B1 virus. Their tissues were assayed for virus and interferon content. It was demonstrated that adult mice produced interferon in all the tissues which became infected, whereas suckling mice produced small amounts of interferon in their livers only. There is a direct relationship between interferon titers and rapidity with which virus disappears from the tissues. A hypothesis is offered that the difference in outcome of Coxsackie B1 infection in the suckling and older mouse is in large part to be explained by inability of the cells of the immature animal to elaborate interferon.

Tryptose phosphate broth as supplementary factor for maintenance of HeLa cell tissue cultures.

Summary A mixture of tryptose phosphate broth, 15 to 25%, maintenance solution (MS), 67.5 to 77.5%, and chicken serum, 7.5%, maintained HeLa cells in tissue culture for at least 10 days. During this period HeLa cells increased 3 to 5 fold in number. Furthermore, smaller quantities of ARD, AD and Type I poliomyelitis viruses could be detected and significantly more ARD virus could be propagated in HeLa cells maintained in this medium than in cells supported with maintenance solution and chicken serum alone.

Screening of newborn infants for cytomegalovirus infection

Infants in a newborn nursery of a general hospital were studied for the presence of congenital cytomegalovirus infection. During a period of 13 weeks, 8 infected infants were detected. Intracerebral calcifications were demonstrated in one of these infants; the remaining 7 appeared normal in the newborn period.

Immune Status of Children One to Four Years of Age as Determined by History and Antibody Measurement

Abstract Measurement of serum antibody levels in children one to four years old, living in three city and one suburban census tract, revealed that 63 per cent of the total study population were susceptible to rubella and approximately 33 per cent had inadequate titers of measles antibody. Antitoxin levels to diphtheria and tetanus were low in 24 and 7 per cent respectively of the entire study group. A large proportion (57 per cent) of these children had serum antibody levels of less than 10 to one or more types of poliovirus. Many had low antibody levels after the recommended number of immunizations; others had not received adequate poliomyelitis vaccine. Although those with low levels may not contract paralytic disease, if reinfected with wild poliovirus, they may spread the infectious agent to susceptible persons in the environment. Increased effort should be made to immunize all preschool children. Advisory committees should consider the need for periodic reimmunization. (N Engl J Med 289:231–235, 1973)

Simian Virus 40 in Polio Vaccine: Follow-Up of Newborn Recipients

Soon after birth, when susceptibility to carcinogens should be enhanced, a group of children received oral polio vaccine which was later found to contain significant amounts of simian virus 40. Eight years after the incident, no cancer deaths have been observed among the vaccinated children, but continued surveillance is needed before concluding that simian virus 40 is innocuous to man.

PRIMARY INFECTION WITH CYTOMEGALOVIRUS DURING PREGNANCY

Since the majority of postnatal cytomegalovirus (CMV) infections are unrecognized, the risk to the fetus of primary CMV infection at various times during pregnancy has not been meticulously assessed. During a prospective study of over 3000 pregnant teenagers, 8 patients with primary CMV infection defined as virologic as well as serologic conversion from negative to positive, were identified and followed. Asymptomatic primary infection occurred during the 1st trimester in one patient, during the 2nd trimester in 4 patients, and during the 3rd trimester in 3 patients. All 8 infants were asymptomatic but 4 (50%) were congenitally infected; all 3 neonates of the 3rd trimester converters and one of the 4 infants of the 2nd trimester converters. The single 1st trimester converter delivered an uninfected infant at term despite cytomegaloviremia during the 1st and 2nd trimesters as well as consistent viruria and intermittent positive throat and cervical cultures throughout her pregnancy. Placenta cultures of 6 converters resulted in one CMV isolate from an infected neonate born to a 3rd trimester converter. Primary CMV infection during pregnancy results in an infected infant in a significant percentage of patients, particularly if the infection occurs during the 3rd trimester. Nevertheless, primary CMV infection can occur during any trimester without resulting in an infant with any of the stigmata of cytomegalic inclusion disease at birth.