George A. Nankervis

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.

Acquisition of cytomegalovirus infection in infants following exchange transfusion: a prospective study.

A prospective study of newborn infants who required exchange transfusion was undertaken to evaluate the risk of transmission of cytomegalovirus (CMV). Buffy coat‐, urine‐ and saliva‐saturated throat swabs for viral cultures and serum specimens for CMV complement‐fixing (CF) antibody were obtained from 45 infant‐mother pairs. Buffy coat from the donor blood was cultured and CMV CF titers measured. Viral studies were repeated on infants and mothers at six and 12 weeks after exchange transfusion. Fifteen infants received CMV seropositive blood and 14 infants received CMV seronegative blood. Sixteen infants who did not receive blood or blood products served as controls. Three of 12 antibody‐positive newborns developed infection after getting seropositive blood. One of three antibody‐negative newborns developed infection after getting seropositive blood. The presence of transplacental antibody does not appear to protect the infants. None of the control infants developed CMV infection. None of the infected infants were symptomatic. Although CMV infection in infancy can be acquired by routes other than blood, exchange transfusion with seropositive blood enhances the likelihood of acquiring infection.

Humoral and cell-mediated immune responses to herpesvirus antigens during pregnancy—A longitudinal study

Humoral and cellular immune responses were studied during the second trimester, third trimester, and postpartum periods in 11 pregnant women and in nonpregnant control women. Complement fixing (CF) and indirect hemagglutinating antibody (IHA) titers for herpes simplex type 1 (HSV-1), herpes simplex type 2 (HSV-2), and cytomegalovirus (CMV) were determined. Cellular response was measured by [3H]thymidine uptake by stimulated lymphocytes. Phytohemagglutinin (PHA), HSV-1, HSV-2, and CMV antigens were used as stimulants. No differences in the mean titers of CF and IHA antibodies were found. The cellular response to PHA had a transient decrease (P<0.02) during the third trimester. The cellular response to CMV was significantly lower during the second and third trimesters. A diminished response to HSV-1 antigen was observed during the second and third trimesters; the cellular response to HSV-2, though reduced, was not significantly altered during pregnancy. These data indicate a suppression of cellular responses to various herpesviruses and PHA during pregnancy.

Eight-year serologic evaluation of Edmonston live measles vaccine.

An 8 year follow-up study of recipients of Edmonstons measles vaccines has revealed that the pattern of persistence of circulating HI antibody has been similar in those who were immune prior to vaccine administration and in those who were susceptible at that time. Possibilities for lifelong immunity following administration of live measles vaccine are discussed.

Three Infants with Neonatal Pertussis Because of Its Atypical Presentations, Pertussis in the Neonate May Easily Be Overlooked

at three different Cleveland hospitals. We were not able to discern any epidemiotogic connections among these cases, nor were we able to document any increase in the overall incidence of pertussis in the community; nevertheless, in view of the difficulties in clinical and laboratory diagnosis, and of the underreporting of this disease, data concerning the above points are suspect. ~rl~’e report these cases to remind physicians that the neonate is not protected by transplacental maternal antibody; moreover, in our experience the disease, after presenting atypically, may run a prolonged and complicated

Evaluation of a prescreening blood donor program for prevention of perinatal transfusion-acquired cytomegalovirus (CMV) infection.

The purpose of this study was to evaluate the efficacy of a prescreened CMV seronegative blood donor group in preventing transfusion-acquired CMV infection in premature infants in the perinatal period. Group 0 donors with known CMV seronegative status were recruited to supply blood to the neonatal intensive care nurseries. One hundred and twenty-seven low birth weight infants born of CMV seronegative mothers remained seronegative when blood for transfusion was screened for CMV antibody. Twenty two infants shared six units of CMV seropositive blood due to technical errors or poor sensitivity of the test kit in the initial phase of the study. Fifteen of these patients were in the study group. One infant died of immaturity at four weeks of age and two of the remaining 14 showed asymptomatic CMV infection. Another infant who received granulocyte concentrates from CMV seropositive donors had symptomatic CMV infection. Throughout the 24 month study period, blood supply to the ICN was adequate and timely. The donor seroconversion rate was 0.7% per annum. Only one infant was exposed to the risk of CMV infection due to donor seroconversion. We conclude that the prescreening donor program is a sensible and efficient approach for providing CMV seronegative blood in neonatal transfusion therapy.

Humoral-and cell-mediated immune responses to herpesvirus antigens in patients with cervical carcinoma.

Abstract The humoral and cellular immune responses were studied in 35 patients with cervical carcinoma (Ca Cx) and 32 healthy controls. Complement fixing (CF) and indirect hemagglutinating antibody (IHA) titers for herpes simplex type 1 (HSV-1), herpes simplex type 2 (HSV-2), and cytomegalovirus (CMV), and fluorescent antibody (FA) titers for viral capsid antigen for Epstein-Barr virus (EBV) were determined. Cellular immune response was measured by the technique of [ 3 H]thymidine uptake by stimulated lymphocytes. Phytohemagglutinin (PHA), HSV-1, HSV-2, and CMV antigens were used as stimulants. CF titers (≥ 1:4) to HSV-1, HSV-2, and CMV were present in 34 ( P P P P P P P P