[Show abstract][Hide abstract] ABSTRACT: Congenital cytomegalovirus (CMV) infection occurs in approximately 1% of newborns in the United States. A phase II evaluation was done of ganciclovir for the treatment of symptomatic congenital CMV infection. Daily doses of 8 or 12 mg/kg were administered in divided doses at 12-h intervals for 6 weeks. Clinical and laboratory evaluations sought evidence of toxicity, quantitative virologic responses in urine, plasma drug concentrations, and clinical outcome. A total of 14 and 28 babies received 8 and 12 mg/kg/day, respectively. Five additional babies received ganciclovir on a compassionate plea basis. Significant laboratory abnormalities included thrombocytopenia (< or = 50,000/mm3) in 37 babies and absolute neutropenia (< or = 500 mm3) in 29 babies. Quantitative excretion of CMV in the urine decreased; however, after cessation of therapy, viruria returned to near pretreatment levels. Hearing improvement or stabilization occurred in 5 (16%) of 30 babies at 6 months or later, indicating efficacy.
The Journal of Infectious Diseases 05/1997; 175(5):1080-6. · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Knowledge of the natural history of symptomatic congenital cytomegalovirus (CMV) infection in the newborn is essential in order to anticipate complications and assess the potential benefit from antiviral therapy. To define the disease course we reviewed data on 106 neonates with symptomatic congenital CMV infection diagnosed and managed by the investigators. Petechiae, jaundice and hepatosplenomegaly were each noted in 70% or more patients. Microcephaly was noted in 54 of 102 (53%) at birth. Elevated alanine aminotransferase, conjugated hyperbilirubinemia and thrombocytopenia were seen in 83, 81 and 77%, respectively. Eighty-six percent had at least two of the manifestations highly suggestive of congenital infection. Platelet count fell to its nadir during the second week of life whereas elevated alanine aminotransferase and direct bilirubin persisted past the first month. In spite of the difficulty in assessing central nervous system function in the newborn, evidence of damage was present in the majority. Seventy-two had microcephaly, poor suck, lethargy/hypotonia or seizures. Abnormal computerized tomographic scan was present in 16 of 20 (80%) and decreased hearing in 20 of 39 (56%). Cerebrospinal fluid protein was greater than 120 mg/dl in 24 of 52 (46%) and this elevation was associated with neurologic abnormalities as well as hearing loss. The mean length of hospital stay was 13 and 22.4 days for term and preterm infants, relatively. Thirteen infants (12%) died during the first 6 weeks of life. Disseminated CMV infection with multiorgan involvement was evident in 7 of 9 at postmortem examination. We conclude that neonates with symptomatic congenital CMV infection have a multi-system disease with significant morbidity and mortality.
[Show abstract][Hide abstract] ABSTRACT: Despite the use of vidarabine, herpes simplex virus (HSV) infection in neonates continues to be a disease of high morbidity and mortality. We undertook a controlled trial comparing vidarabine with acyclovir for the treatment of neonatal HSV infection.
Babies less than one month of age with virologically confirmed HSV infection were randomly and blindly assigned to receive either intravenous vidarabine (30 mg per kilogram of body weight per day; n = 95) or acyclovir (30 mg per kilogram per day; n = 107) for 10 days. Actuarial rates of mortality and morbidity among the survivors after one year were compared overall and according to the extent of the disease at entry into the study (infection confined to the skin, eyes, or mouth; encephalitis; or disseminated disease).
After adjustment for differences between groups in the extent of disease, there was no difference between vidarabine and acyclovir in either morbidity (P = 0.83) or mortality (P = 0.27). None of the 85 babies with disease confined to the skin, eyes, or mouth died. Of the 31 babies in this group who were treated with vidarabine and followed for a year, 88 percent (22 of 25) were judged to be developing normally after one year, as compared with 98 percent (45 of 46) of the 54 treated with acyclovir (95 percent confidence interval for the difference, -4 to 24). For the 71 babies with encephalitis, mortality was 14 percent with vidarabine (5 of 36) and with acyclovir (5 of 35); of the survivors, 43 percent (13 of 30) and 29 percent (8 of 28), respectively, were developing normally after one year (95 percent confidence interval for the difference, -11 to 39). For the 46 babies with disseminated disease, mortality was 50 percent (14 of 28) with vidarabine and 61 percent (11 of 18) with acyclovir (95 percent confidence interval for the difference, -20 to 40); of the survivors, 58 percent (7 of 12) and 60 percent (3 of 5), respectively, were judged to be developing normally after one year (95 percent confidence interval for the difference, -40 to 50). Both medications were without serious toxic effects.
In this multicenter, randomized, blinded study there were no differences in outcome between vidarabine and acyclovir in the treatment of neonatal HSV infection. The study lacked statistical power to determine whether there were sizable differences within the subgroups of those with localized HSV, encephalitis, or disseminated disease.
New England Journal of Medicine 03/1991; 324(7):444-9. DOI:10.1056/NEJM199102143240703 · 55.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A total of 432 patients underwent brain biopsy for presumptive herpes simplex encephalitis. Three patient groups were identified. The first group, 195 patients (45%), had herpes simplex encephalitis confirmed by the isolation of herpes simplex virus from brain tissue at biopsy (193 patients) or autopsy (2 patients). The second group, 95 patients (22%), had diseases that were identified but that were not caused by herpes simplex virus. Three subgroups were recognized: (1) 38 patients (9%) with treatable disease, (2) 40 patients (9%) with nontreatable but diagnosed viral infection, and (3) 17 patients (4%) with identified diseases neither of viral etiology nor treatable. The third group, 142 patients (33%), remained without a diagnosis. Clinical presentation of patients in the second group was similar to that of those with herpes simplex encephalitis and those without a diagnosis. Patients in the subgroup with nontreatable but diagnosed viral infections had the greatest likelihood of returning to normal.
JAMA The Journal of the American Medical Association 08/1989; 262(2):234-9. · 35.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Using radioimmunoassay followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, we compared serial IgG precipitin antibody responses to cytomegalovirus (CMV) proteins in three groups of 29 pregnant women who had primary CMV infection. Five women had CMV mononucleosis, and four of them infected their fetuses. Twenty-four women had subclinical infection, and eight infected their fetuses. There were no qualitative differences in the precipitin responses against the virus-encoded proteins in three different infected cellular antigens (cytoplasmic, nuclear, and high-speed pellet) between these three groups of women. There was also no qualitative difference in responses whether the infection was clinically apparent or subclinical. Quantitation by densitometer, however, revealed that women with mononucleosis and those with subclinical infection who infected their fetuses had a more intense and prolonged antibody response than did women with subclinical infection who failed to transmit CMV in utero.
The Journal of Infectious Diseases 12/1988; 158(5):917-24. DOI:10.1093/infdis/158.5.917 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We determined serial IgG antibody responses to cytomegalovirus (CMV)-encoded proteins in sera collected over a one-year interval from 14 subjects with CMV mononucleosis. Antigens from infected human fibroblasts included three components: cytoplasmic, nuclear, and high-speed pellet. Antibody was detected by radioimmunoprecipitation followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Twenty to 21 bands were observed with the cytoplasmic component, whereas 10 and 9, respectively, were seen with the nuclear and high-speed pellet antigens. The most intense reactions occurred with the higher-molecular-mass proteins (50-215 kDa) by using the cytoplasmic and high-speed antigens and with the more rapidly migrating proteins (less than 50 kDa) by using the nuclear antigen. The precipitin responses increased for three months or more after onset of symptoms with the nuclear and high-speed pellet antigens but peaked within one to two months with the cytoplasmic antigen.
The Journal of Infectious Diseases 11/1987; 156(4):615-21. DOI:10.1093/infdis/156.4.615 · 6.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We studied 16 218 pregnant women from two income groups to determine the incidence of primary cytomegalovirus (CMV) infection and its consequences for the offspring. In the high-income groups, 64.5% of the women were seronegative for CMV and 1.6% had primary CMV infection. In the low-income group, only 23.4% of the women were seronegative for CMV, but 3.7% experienced a primary infection. The rate of transmission in utero was similar in the two groups (39% and 31%). Congenital infections were more frequent in the low-income group; however, primary CMV accounted for 25% of the congenital infections in this group, in contrast to 63% of the high-income cases. Infections acquired early and late in gestation had similar rates of transmission in utero, but three infants (8%) with symptomatic congenital infection and five infants (13.5%) who have developed significant handicaps were exposed in the first half of pregnancy. Primary CMV infection during pregnancy poses a 30% to 40% risk of intrauterine transmission and adverse outcome is more likely when infection occurs within the first half of gestation.
[Show abstract][Hide abstract] ABSTRACT: A total of 208 patients underwent brain biopsy for presumptive herpes simplex encephalitis and were randomized to receive either vidarabine, vira-A, at 15 mg/kg/day, or acyclovir, at 30 mg/kg/day for ten days. 69 patients (33%) had biopsy-proven disease; 37 received vira-A and 32 acyclovir. With the exception of age, patient populations were balanced for demographic characteristics. Overall survival for acyclovir recipients was 72% compared with 46% for vira-A-treated patients 18 months after therapy (p = 0.008). After adjustment for differences of age between treatment populations by multivariant regression analyses, acyclovir treatment remained superior to vidarabine therapy (p = 0.041). Mortality varied according to the level of consciousness at the onset of therapy. For lethargic, semicomatose and comatose patients, mortality was 42%, 46%, and 67%, respectively, for the vira-A-treated patients and 0%, 25% and 25%, respectively, for acyclovir-treated patients. Six months post-therapy morbidity assessments revealed five (14%) vira-A versus 12 (38%) acyclovir recipients who had returned to normal function, while eight (22%) and three (9%), respectively, had moderate debility. Outcome differences were significant (p = 0.02; Wilcoxon, 2-sample test) using an adapted scoring system. Age and Glasgow coma scale greater than 10 predicted the best outcome following acyclovir treatment. Disoriented patients who flex and respond by eye to pain had no mortality and 50% returned to normal. These data indicate that acyclovir is the treatment of choice for biopsy-proven herpes simplex encephalitis.
[Show abstract][Hide abstract] ABSTRACT: We studied 16 218 pregnant women from two income groups to determine the incidence of primary cytomegalovirus (CMV) infection and its consequences for the offspring. In the high-income group, 64.5% of the women were seronegative for CMV and 1.6% had primary CMV infection. In the low-income group, only 23.4% of the women were seronegative for CMV, but 3.7% experienced a primary infection. The rate of transmission in utero was similar in the two groups (39% and 31%). Congenital infections were more frequent in the low-income group; however, primary CMV accounted for 25% of the congenital infections in this group, in contrast to 63% of the high-income cases. Infections acquired early and late in gestation had similar rates of transmission in utero, but three infants (8%) with symptomatic congenital infection and five infants (13.5%) who have developed significant handicaps were exposed in the first half of pregnancy. Primary CMV infection during pregnancy poses a 30% to 40% risk of intrauterine transmission and adverse outcome is more likely when infection occurs within the first half of gestation.
JAMA The Journal of the American Medical Association 11/1986; 256(14):1904-8. DOI:10.1001/jama.1986.03380140074025 · 35.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Congenital cytomegalovirus infection occurs in about 1% of live births. Although symptomatic congenital infection often results in severe developmental deficits and mental retardation, about 90% have asymptomatic infection. Previous studies of the intellectual development in children with asymptomatic congenital cytomegalovirus have resulted in mixed findings. To control for the effects of hearing impairment (which occurs in about 15% of asymptomatic children) on intelligence scores, we tested 18 prospectively followed, normally hearing, school-aged children with asymptomatic congenital cytomegalovirus (15 black, ten male) and 18 controls matched for age, sex, race, school grade, and socioeconomic status. Children were tested via the Wechsler Intelligence Scale for Children-Revised, the Kaufman Assessment Battery for Children, and the Wide Range Achievement Test. Multivariate analysis revealed no differences between groups on intelligence scores or subscales, achievement scores, or incidence of learning disabilities (defined as significant discrepancy between intelligence and achievement), and mean scores for both groups were very close to national norms. It is concluded that the 25,000 children born in the United States each year with asymptomatic congenital cytomegalovirus and normal hearing are not likely to be at increased risk of mental impairment.
[Show abstract][Hide abstract] ABSTRACT: Congenital CMV (C-CMV) infection occurs in around 1% of births and can result in a variety of CNS problems. Although symptomatic newborns usually have problems, 90% of C-CMV infected newborns are asymptomatic (ASX). Around 10% of them have hearing loss, but whether mental retardation (MR) or learning disability (LD) occur in the ASX group is not clear. We studied 18 normal hearing, school aged children with ASX C-CMV (15 black, 10 male), and 18 controls matched for age, sex, race, grade and socioeconomic status (predominantly middle class) as determined by the parents' education and occupation. Instruments included Wechsler Intelligence Scale for Children-Revised (WISC-R), the Wide Range Achievement Test (WRAT) and the Kaufman Assessment Battery for Children (K-ABC). LD was defined as FSIQ (WISC-R) or MPC (K-ABC) ≥ 90 and a score on any WRAT subtests or K-ABC Achievement Scale two or more years below age-appropriate. Mean IQ's (WISC-R), MPC (K-ABC), WRAT scores and frequency of LD were:
Pediatric Research 04/1985; 19(4). DOI:10.1203/00006450-198504000-00063 · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Approximately 5-10% of infants infected in utero with cytomegalovirus (CMV) exhibit clinically apparent disease at birth with the remainder having subclinical infection. Although the maternal immune response has been implicated as a virulence factor in congenital infection, conventional serologic techniques have failed to clarify the role of transplacentally acquired maternal anti-CMV antibodies in the prevention of symptomatic congenital infection. To further elucidate the effect of maternal antibody on the development of symptomatic infection, we have utilized the Western immunoblot procedure to investigate both the quantity and the antigen-specificity of anti-CMV antibodies in the cord sera of 6 infants with symptomatic disease and 10 asymptomatic, congenitally infected infants. Both groups acquired CMV as a result of primary maternal infection. Antibodies directed against virion glycoproteins and capsid proteins were detected in both groups; however as a group, a stronger response was noted in sera from asymptomatic infants. Unexpectedly, maternal sera obtained at delivery from 12/16 of the infants contained a greater quantity of anti-CMV antibodies as well as reacting with additional virion proteins not detected by cord sera. These results indicated that transplacental passage of maternal anti-CMV antibodies was incomplete in the majority of infants studied. Furthermore, our findings suggested that maternal antibodies may play a role in the prevention of symptomatic congenital CMV infection which was not previously appreciated.
Pediatric Research 04/1984; 18. DOI:10.1203/00006450-198404001-01061 · 2.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Eighty-five immunocompromised patients were entered into a randomized, controlled, crossover study of mucocutaneous herpes simplex virus (HSV) infections. Thirty-nine patients (group A) received vidarabine for seven days followed by placebo for an additional seven days. Forty-six patients (group B) received the reverse regimens. Therapy did not significantly accelerate healing for the total population as assessed by loss of virus from lesions, cessation of lesion formation, and time to crusting. Group A patients demonstrated accelerated loss of pain from lesions (P = 0.0099) and defervescence (P = 0.03). Patients in group A who had HSV type 1 (HSV-1) infections or who were over 40 years of age did clear virus from lesions more rapidly (P = 0.04 and P = 0.03, respectively). No toxicity or significant adverse effects could be attributed to vidarabine administration. Benefit from vidarabine therapy is limited to immunocompromised patients over 40 years of age with HSV-1 infections.
The Journal of Infectious Diseases 02/1984; 149(1):1-8. DOI:10.1093/infdis/149.1.1 · 6.00 Impact Factor