Administration of high doses of respiratory syncytial virus immune globulin is a safe and effective means of preventing lower respiratory tract infection in infants and young children at high risk for this disease.
Oral famciclovir, 250 mg, given twice daily for 4 months is an effective, well-tolerated treatment for the suppression of genital herpes in women with frequent recurrences, but single daily doses produced less complete suppression of genital herpes.
Infants with cardiopulmonary disease develop severe illness from respiratory syncytial virus (RSV) infection. Safety, feasibility, and pharmacokinetics of intravenous gamma globulin (IVIG) to prevent RSV illness were studied in 23 high-risk infants in a phase I trial. IVIG with an RSV neutralizing antibody titer of 1:1,100 in 5% solution was given monthly over a 2-to 4-h period in a clinical setting during the RSV season. The first group (n = 7) received 500 mg/kg of body weight, the second group (n = 9) received 600 mg/kg, and the third group (n = 7) received 750 mg/kg. Serum was drawn prior to infusion and 2, 14, and 30 days after infusion. Total immunoglobulin G and RSV A2 and RSV neutralizing antibody levels were obtained after the first IVIG infusion. Two children developed mild reversible pulmonary edema (group receiving 600 mg/kg per dose), and one developed hives and wheezing during one infusion (group receiving 500 mg/kg per dose). Twelve children developed subsequent RSV infection during two RSV seasons (November to April) over a 2-year follow-up period; 9 of 12 developed infection during the infusion year. Eleven illnesses were mild; one child died of progressive RSV illness (group receiving 500 mg/kg per dose). A cumulative infusion effect was not observed. IVIG appears safe and feasible in an outpatient setting, and at 750 mg/kg per dose, a target RSV antibody level of 21:100 was achieved.Respiratory syncytial virus (RSV) is the most common cause of serious respiratory illness in young children (2, 8). Children at greatest risk of serious or fatal RSV lower respiratory tract illness include those with bronchopulmonary dysplasia and congenital heart disease (10-12, 21, 22). Because the level of morbidity is so great in these populations, prevention of serious RSV lower respiratory tract illness is an important goal.It is unlikely that a live vaccine will be available in the near future to prevent high-risk young children from developing serious RSV infection. Vaccine development is proceeding cautiously because of the problem in developing a live vaccine which is safe, stable, and immunogenic and to avoid the serious pulmonary complications seen 20 years ago with the use of a formalin-inactivated vaccine (18
He was treated with a further course of acyclovir (1 5 g/m2 surface area/day) followed, in view of the possibility of a resistant organism, by a course of intravenous vidarabine. On this regime his fever, conscious level, and hemiplegia improved. After discharge he is left with a mild right facial weakness and a mild persisting dysphasia.Findings in blood and cerebrospinal fluid in the three children during thefirst and second
A new enzyme-linked immunosorbent assay (ELISA) respiratory syncytial virus antigen detection kit (Ortho Diagnostics, Inc., Raritan, N.J.) was compared with virus culture and with the indirect fluorescent antibody test (FAT) by using fresh nasal washings from children with suspected respiratory syncytial virus infection. Both uncentrifuged nasal washings and pellets from centrifuged split specimens were examined by ELISA. The ELISA was considered positive when the optical density was greater than the mean background optical density plus 0.15. Specimens positive by ELISA but negative by culture and FAT were reexamined in an ELISA blocking assay. Of 337 uncentrifuged specimens, 124 (37%) were positive by culture, 107 (32%) were positive by FAT, and 166 (49%) were positive by ELISA. Blocking assays showed that 21 of 30 (70%) of the seemingly false-positive ELISA tests were, in fact, true-positives and that the cultures and FATs were falsely negative. A patient specimen was considered positive when it was positive by virus culture, FAT, or blocking assay. The sensitivity, specificity, and positive predictive value of the ELISA test were 88, 94, and 95%, respectively. Centrifugation of nasal washings raised the sensitivity from 88 to 92% but reduced the specificity from 94 to 81%. We conclude that the Ortho ELISA test of uncentrifuged nasal washings is more sensitive than virus culture or indirect FAT and is highly specific.
A 47-year-old man had recurrent signs and symptoms of brainstem encephalitis over a 4-year period. Although CSF viral cultures were repeatedly negative, herpes simplex virus type 1 (HSV-1) DNA was detected in CSF by polymerase chain reaction (PCR). HSV-1-specific antibodies were absent at the time of the first positive PCR test, but CSF seroconversion to high HSV-1-specific antibody titer subsequently occurred. CSF antibody to cytomegalovirus (CMV) and varicella-zoster virus (VZV) was not detectable, nor could CMV, VZV, or Epstein-Barr virus nucleic acid be detected by CSF by PCR. This is the first report of the use of CSF PCR for the rapid antemortem diagnosis of herpetic brainstem encephalitis.
Eighteen children from 3 weeks to 6.9 years of age were given an oral acyclovir suspension for herpes simplex or varicella-zoster virus infections. Thirteen patients who were 6 months to 6.9 years old received 600 mg/M2 per dose, and three infants and two children less than 2 years old were given 300 mg/M2 per dose. The drug was given four times a day, except to one infant who was treated with three doses a day. Among the 13 children who received the 600-mg/M2 dose, the maximum concentration in plasma (Cmax) was 0.99 0.38 p,g/ml (mean + standard deviation), the time to maximum concentration (Tmax) was 3.0 0.86 h, the area under the curve (AUC) was 5.56 2.17 p,g h/ml, and the elimination half-life (tl/2) was 2.59 0.78 h. The three infants less than 2 months of age who received the 300-mg/M2 dose had a Cmax of 1.88 ± 1.11 ,g/ml, a Tmax of 4.10 ± 0.48 h, an AUC of 6.54 ± 4.32 ,ugg h/ml, and a tl/2 of 3.26 ± 0.33 h. The acyclovir suspension was well tolerated by young children. No adverse effects requiring discontinuation of the drug occurred.Acyclovir [9-(2-hydroxyethoxymethyl)guanine] is a nucleoside analog which inhibits the replication of herpes simplex virus (HSV) and varicella-zoster virus (VZV). Acyclovir administered parenterally is effective for the treatment of neonatal HSV infections, HSV encephalitis, and genital HSV infections (3,25,26). In immunosuppressed patients, intravenous acyclovir is useful for the therapy and suppression of HSV infections and for the therapy of VZV infections (6,9,10,14,(18)(19)(20). The oral administration of acyclovir is of benefit for the therapy and suppression of genital HSV infections in the normal adult host (2,5,9,11,17,23) and for the treatment and suppression of recurrent mucocutaneous HSV infections in immunocompromised patients (14,22).Pharmacokinetic information is available for acyclovir administered intravenously to adults and children and for the capsule formulation given to adults (4,18). The pharmacology of oral acyclovir tablets has been investigated in children (12,13). A liquid suspension formulation of the drug was developed for children and other patients who cannot ingest medications in solid form. The purpose of our study was to determine the pharmacokinetics and tolerance of acyclovir suspension in children.(This work was presented in part at the 26th Interscience
Optimal conditions are described for the recovery of cell culture-derived varicella-zoster virus (VZV). Of the cells tested, human embryonic lung fibroblasts were the most sensitive. Storage and handling procedures were examined to determine the stability of VZV in viral transport medium. When the initial VZV titer was high (2 x 104 PFU/ml) 40% of the VZV survived room temperature for 24 h and 75% of the VZV remained viable for this long at 4°C. Recovery was 5to 10-fold less at lower initial VZV titers (<2 x 103 PFU/ml). Other factors which influenced VZV recovery included freezing at-20°C, the use of cotton or
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