[Preliminary study of an attenuated varicella-zoster vaccine (Webster strain) in 27 children without immunologic disorders].
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to S A Plotkin.
Explore the source record for details and available documents.
Laboratory strains and fresh isolates of human cytomegalovirus (HCMV) were tested for sensitivity to acyclovir. Fifty percent inhibition was achieved at about 10 micrograms/ml, but 25 to 100 micrograms/ml was necessary for 90 percent or greater inhibition. Acyclovir was administered intravenously to four patients with congenital cytomegalovirus (CMV) infection. There was only a temporary diminution of virus titer in the urine and no obvious clinical improvement. One child experienced hematuria. Pharmacokinetic studies showed a large volume of distribution and slow excretion of acyclovir with a half-life of approximately three hours.
Three patients in whom herpes zoster infections developed following bone marrow transplantation were treated with acyclovir. The patients experienced pain relief within 24 hours of starting treatment. The progression of their skin lesions halted within 1, 2, and 4 days of therapy, respectively, and healed completely within two weeks of therapy. Pharmacokinetic studies indicated that acyclovir plasma concentration-time profiles approximated biexponential equations. The drug half-lives were 3.91, 3.83, and 3.40 hours, respectively. Acyclovir was not myelotoxic and may be helpful in aborting varicella-zoster virus infections in bone marrow transplant recipients.
Congenital cytomegalovirus (CMV) infections contribute considerably to morbidity and mortality among infants in the United States. In a preliminary study aimed at protecting fetuses from congenital disease we evaluated Towne 125-strain CMV vaccine in ten female pediatric nurses of childbearing age. The women were seen 2, 4, 8, 12, 26, 39, and 52 weeks after vaccination; specimens were obtained for routine laboratory testing, virus isolation, cell-mediated immunity testing, and serologic examination (complement fixation, anticomplement immunofluorescence [ACIF], and neutralization). Local but not systemic reactions were observed in all subjects. Serologic responses appeared at two to four weeks and peaked at four to eight weeks. Mean titers were highest in the ACIF test. A cell-mediated immune response, as assayed by lymphocyte proliferation, was observed in all women, and in most there was a biphasic pattern. Towne 125-strain CMV vaccine seems to be safe and immunogenic in women of childbearing age.
We have studied the growth of eight different viruses on skin fibroblasts from three families each having one or more diabetic members and appropriate controls. The haplotypes of all of the family members had been previously characterized. In addition, we have investigated the growth of mumps virus on the lymphoblast cultures from four families of the same type. Our results show no difference between the growth of these viruses in cells derived from juvenile diabetics and cells derived from nondiabetic siblings and parents even when the haplotypes were identical. However, we noted a striking resistance of human skin fibroblast cultures from both normal and diabetic individuals to Coxsackie B virus infection.
Ninety-one healthy children were immunized with one of three preparations of the OKA strain of live attenuated varicella zoster virus in order to gain sufficient information on safety and immunogenicity to justify vaccine studies in immunosuppressed children. The OKA-Biken vaccine was studied in a dose response trial. Two additional clinical trails were conducted with the OKA strain that was further passaged: a frozen aqueous (OKA-RIT-Aq) form and a lyophilized (OKA-RIT-Ly) form were tested. With each of these vaccines clinical reactivity was minimal and virus shedding, viremia, and transmission of the vaccine virus were absent. Excellent seroconversion rates of 100 and 94% were induced with approximately 500 pfu of OKA-Biken and OKA-RIT-Ly vaccine, respectively. A lower seroconversion rate was noted for OKA-RIT-Aq, presumably on the basis of defective individual vials. Diluted OKA-Biken vaccine induced less seroconversion but even the 5 pfu dose produced antibody responses in 81% of the vaccinees. In vitro specific cellular immune responses to varicella virus antigens were demonstrated in each group of vaccinees, including all but two of those vaccines who failed to seroconvert. The data indicate that two preparations of the OKA strain are sufficiently safe and immunogenic in healthy children to support further studies in immunocompromised children.
Antibody to cytomegalovirus early antigen (CMV-EA) has been demonstrated in acute CMV infection. Other investigators have suggested that antibody to CMV-EA would distinguish acute CMV infection from past infection and could therefore be diagnostically useful. Antibody to CMV-EA has been demonstrated in reactivated CMV infection, in infants with congenital infection, and in pregnant women. Antibody to CMV-EA was studied in renal transplant candidates receiving Towne strain CMV vaccine, healthy adults receiving vaccine, and in asymptomatic, seropositive adults. Most healthy volunteers and renal transplant candidates receiving vaccine developed antibody to CMV-EA; it persisted in some of these adults many months after immunization. Antibody to CMV-EA was also demonstrated in asymptomatic adults with serologic evidence of a past infection. Antibody to CMV-EA is not solely an acute-phase reactant but, at least in some patients, is present in the absence of viral excretion or clinical disease.
Antibody-dependent cell-mediated cytotoxicity (ADCC) against cryopreserved varicella-zoster virus-infected human foreskin fibroblasts was detected in a 51Cr release assay. Target cells, samples of seropositive or seronegative sera, and mononuclear cells obtained by Ficoll-Hypaque centrifugation of human peripheral blood were added to microtiter plate wells and allowed to incubate at 37 degrees C for 4 h. Fibroblasts infected for 48 to 96 h were susceptible to ADCC. Effector cells from seropositive and seronegative normal children were equally active in the assay. Antibody titers were determined by testing serial dilutions of sera in the ADCC assay. Zoster immune globulin had a titer of 204,800. Sera from 40 naturally seropositive individuals were compared by assays for ADCC and fluorescent antibody to membrane antigen. All sera that were negative by fluorescent antibody to membrane antigen (less than 2) were also negative by ADCC (less than 20). All sera that were positive by fluorescent antibody to membrane antigen were also positive by ADCC, but titers of individual sera were frequently 5 to 20 times higher in the ADCC assay.
To define the role of antibody to immediate early antigens of human cytomegalovirus (CMV) in diagnosing acute infection, we studied antibody responses of adult volunteers and renal transplant candidates receiving CMV vaccine. In addition, CMV antibodies in healthy adults were determined. Antibody to pre-early nuclear antigen, one of the immediate early antigens, did not develop in all of the volunteers or renal transplant candidates receiving the vaccine. In those vaccinees who developed an antibody response, the duration of the response was variable. Antibody to pre-early nuclear antigen and immediate early antigens was also detected in some healthy adults with serological evidence of past CMV infection, but without clinical evidence of recent infection. In view of these results, antibody to immediate early antigens and specifically to pre-early nuclear antigen does not appear to be suitable for rapid diagnosis of acute CMV infection.
Epiglottis (more properly supraglottitis) is a potentially life-threatening infection of the supraglottic larynx that is most often caused by Hemophilus influenzae type B (HITB). Intrafamily spread of HITB disease has been described often for meningitis, but is rarely reported in epiglottis. We describe two siblings seen concurrently with HITB epiglottitis and discuss prophylaxis of family members and close contacts.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Two cases of severe Epstein-Barr virus (EBV) pulmonary involvement are described. Both were documented by EBV-specific serology and other causes of respiratory tract infection were excluded by culture and serology. Our first case describes fatal infectious mononucleosis (IM) with severe pneumonia in a patient without a definable immunologic disorder. Previous cases of pulmonary involvement in IM are reviewed.
An automated fluorescent immunoassay system (FIAX) was compared with complement fixation (CF) for measuring antibodies to cytomegalovirus (CMV) and herpes simplex virus (HSV) in clinical specimens. Compared with CF the specificity of FIAX (ability to detect a negative titer) was 95% for CMV and 92% for HSV. The sensitivity of FIAX (ability to detect a positive titer) was 98% for CMV and 95% for HSV. When paired samples were tested for significant titer rises, the concordance of the two assays for CMV was 96% and for HSV 80%. The FIAX assay was found to be reproducible when sera were tested within the same laboratory and in two different laboratories. The assay is fast, simple to perform, and not affected by anticomplementary activity. It is seen as a useful alternative to CF testing in a clinical virology laboratory.
Cytomegalovirus-specific lymphocyte proliferation and immunofluorescent antibody responses were measured serially in five normal adults and eight candidates for renal transplant immunized with Towne strain cytomegalovirus vaccine. All of the normal adults developed cellular and humoral immune responses. Five of the eight immunized renal transplant candidates developed proliferative responses comparable to those of normal adults, although in two instances maximal responses were delayed. Vaccinees developed proliferative responses to antigens prepared from the Towne strain as well as heterologous strains of cytomegalovirus. The appearance of immunofluorescent antibodies was generally delayed for the renal transplant candidates, and two of the individuals who had poor proliferative responses also had low antibody titers.
Explore the source record for details and available documents.