Otto F. Sieber

In utero infection of the fetus by herpes simplex virus

Two newborn premature infants are described in whom infection by herpes simplex virus occurred in utero, probably as a result of transplacental transfer of the virus. Studies in one infant suggest that the fetus produced antibody in utero.

Serum immunoglobulin measurement during the first year of life and in immunoglobulin-deficiency states.

Serum immunoglobulin concentrations at several age intervals during the first year of life have been determined by a capillary immunoprecipitation technique. Immunoglobulin G was present in cord sera and declined during the first six months of life, following which an increase to almost three-fourths of the normal adult level was observed in the next six months. Immunoglobulin A was absent in the cord serum and progressively increased, reaching a level by one year of age approximately one-fifth that of the adult. Immunoglobulin M was present in most cord sera studied and steadily rose to one-half of adult levels by 52 weeks of age. Serum immunoglobulin determinations for selected immunologic deficiency states are reported.

SPONTANEOUS EVOLUTION OF IMMUNE COMPETENCE IN DIGEORGE SYNDROME

Thymic hypofunction and increased susceptibility to infection in the DiGeorge Syndrome have been associated with reduced humoral and cellular immunity. As a result, thymic transplantation has been utilized to modify immune responses, with improved lymphocyte responsiveness to mitogens and antigens being attributed to the effects of therapy.Over the past year we have studied a male infant with the DiGeorge syndrome as documented by 1)characteristic facies, 2)neonatal hypocalcemic tetany, 3)absent thymic shadow, 4) quintallogy of Fallot, 5)antibody deficiency and 6)cellular immune dysfunction. During observation in reverse isolation, serial studies showed spontaneous acquisition of normal levels of serum immunoglobulins and cell mediated immunity as measured in vitro with phytohemagglutinin, concanavalin A, pokeweed and staphylococcal antigens. Macrophage inhibitory factor and interferon were produced. Sheep RBC - lymphocyte “T-rosettes” have remained decreased. At one year of age parathormone levels and growth are normal. Only recurrent otitis media and one episode of pneumonia have occurred.Significantly, we have documented progressive spontaneous improvement in immuno-responsiveness without immunotherapy or transplantation. Thus, spontaneous recovery may occur in selected patients with DiGeorge syndrome, and careful observation of such infants may avoid unnecessary transplantation.

Parainfluenza Virus Immunization: II. The Influence of Age and Maternal Antibody upon Successful Immunization with an Alum-Adsorbed Parainfluenza Type 3 Vaccine

Extract: A newly developed inactivated, alum-adsorbed parainfluenza vaccine was evaluated for its effectiveness in evoking antibody responses in young infants. Immunization consisted of three monthly doses of 0.5 ml each. Four age groups were selected for initiation of immunization; 2 days, 6 weeks, 12 weeks and 24 weeks of age.Successful immunization was achieved when immunization was begun at 24 weeks of age (7 of 8 infants with 4-16 fold increase in antibody titer). Younger infants were successfully immunized if the pre-immunization serum antibody titer was less than 1 : 64 (12/15 [80 %] infants with pre-immunization titers of 1 : 32 or less developed 4-32 fold increase in antibody titer) (fig. 6).Maternal antibody may interfere with immunization with parainfluenza vaccine in infants below the age of 6 months. Some infants, regardless of age, are successfully immunized if the titer of maternal antibody is sufficiently low.Speculation: It is possible that, using a sufficiently potent antigen, parainfluenza virus immunization may be successful regardless of age.

IMMUNOLOGICAL RECONSTITUTION IN SEVERE COMBINED IMMUNODEFICIENCY DISEASE WITH TRANSPLANTATION FROM A NON-COMPATIBLE DONOR

We report the immunological reconstitution of an infant with combined immunodeficiency disease (CID) following transplantation of cells from a donor incompatible by mixed lymphocyte culture (MLC) typing.Previous long term reconstitution in CID has been achieved by transplantation of bone marrow cells either genetically compatible by HL-A typing or more recently, in MLC.Reconstitution has occurred in this infant with CID. No donor cells completely compatible in MLC were available. However, paternal immunocytes reactive in MLC could be eliminated in vitro with a pulse of tritiated thymidine of high specific activity. The remaining immunocytes were MLC compatible with the infants cells. Cells were prepared in vitro in this way on three occasions (twice from peripheral blood and once from bone marrow) and transplanted intraperitoneally over a 4 month period, utilizing increasing numbers of donor cells each time.Now at 12 months of age, the infant exhibits a moderate chronic graft versus host reaction. Immunoglobulins are normal. Cell mediated responsiveness measured in vitro by phytohemagglutinin, pokeweed, and MLC reactivity is present. Skin tests have reverted to negative. B and T lymphocytes are present. This suggests that there is a potential source of cells from non-compatible donors for reconstitution of CID.

Altered reactivity to respiratory syncytial virus: Description of atypical RSV illness and prospective four year follow-up of children previously immunized with an inactivated vaccine

Beginning in July 1966, 424 children ranging from 6 months to 7 years of age were immunized. Mild RSV illness was documented to occur later upon natural exposure to the wild virus in all age groups. Nineteen children in the youngest age group immunized (6–23 mos) were hospitalized with an atypical illness due to RSV. Eleven were hospitalized in 1966–67, 6 in 1967–68, and 2 in 1968–69. Two children had recurrent atypical illness during separate years. The illness was characterized by high fever adn pneumonia with marked bronchiolitic wheezing. Chest films showed prominent multi-segmental infiltrates usually in several lobes. Associated lung complications included: lobar atelectasis, pneumothorax, pneumomediastinum, pneumopericardium, subcutaneous emphysema, and pleural effusions. A diffuse maculopapular rash was present on the neck, trunk and proximal extremitities of 8 (42%) vaccinees in contrast to 1 of 31 (3.2%) control with hospitalized RSV illness (X2 = 9.57, p < 0.01). Of 9 hospitalized vaccinees avilable for prosepective follow-up for 4 years from the time of immunization, 5 (55.6%) were diagnosed by allergists, independently of the investigators, as having either asthma (4) or allergic rhinitis (1). This was in contrast to a diagnosis of an atopic disorder made in 7 of 46 (15.2%) age-matched controls prespectively followed (X2 = 5.01, p < 0.10).

1165 PROSPECTIVE STUDY OF LUNG FUNCTION IN YOUNG CHILDREN FOLLOWING CROUP (C) AND BRONCHIOLITIS (B)

Retrospective studies have suggested that infants who had C and B may have residual lung disease. Thirteen asymptomatic child were studied prospectively following hospitalization for C (mean age 18.5 months)and B(mean age 7.5 months). Initial and follow-up studies included viral cultures, serum IgE, allergy skin tests and lung function tests. Functional residual capacity (FRC), maximal flows at FRC (Vmax FRC) derived from partial flow volume curves and response to exercise were measured in these subjects and 7age-matched normals (N) at the age of 4-7 years.FRC was abnormal in 78% of subjects 2-4 weeks after the initial illness. At 4-7 years of age, baseline abnormalities in Vmax FRC were demonstrated in 46% of C and B children but in none of the N group. Exercise-induced bronchospasm (EIB) was found in all B and C subjects (5/5)but in only 1/7 N subjects challenged (p<.05).Lung function abnormalities occurred independent of allergies. These data suggest that asymptomatic children who have been hospitalized with C and B have an increased prevalence of airway obstruction and EIB 3-6 years following their illness. Supported by NHLBI Grants 14136 and 17153. R.Beckerman is a Fellow of the American Lung Association.

ELEVATED GENTAMICIN LEVELS IN PREMATURE/AZOTEMIC NEWBORNS

Peak serum gentamicin (G) levels were measured by agar diffusion 30 minutes after completion of, and trough levels just prior to, intravenous G infusion (2.4±.1mg/kg) in 44 neonates aged 14 days or less ([Xmacr ] 5.5 days). Gestational ages (GA) ranged from 26-43 weeks ([Xmacr ] 34.4±.7 wks). Serum half-lives (T½), peaks, and troughs ([Xmacr ;[plusmn;SEM) in 23 non-azotemic infants [BUN<15mg% and/or Creatinine (Cr)<1mg%] are presented below:In a group of 21 azotemic infants [BUN≥15mg%. and/or Cr≥1.0mg%.) T½s and troughs were significantly elevated when compared with all non-azotemic infants:Routine monitoring of serum G levels allows drug dosage and timing to be individualized and is particularly important in the azotemic or extremely premature neonate in whom the use of standard neonatal dosage regimens is most likely to produce excessive, potentially toxic, drug levels.