Severe respiratory syncytial virus disease in Alaska native children. RSV Alaska Study Group.

Hospitalization rates for respiratory syncytial virus (RSV) infection range from 1 to 20/1000 infants. To determine the rate and severity of RSV infections requiring hospitalization for infants in the Yukon-Kuskokwim (YK) Delta of Alaska, a 3-year prospective surveillance study was conducted. The annual rate of RSV hospitalization for YK Delta infants <1 year of age was 53-249/1000. RSV infection was the most frequent cause of infant hospitalization. RSV disease severity did not differ among non-high-risk infants in the YK Delta and at Johns Hopkins Hospital (JHH). On average, 1/125 infants born in the YK Delta required mechanical ventilation for RSV infection. During the peak season, approximately $1034/child <3 years of age was spent on RSV hospitalization in the YK Delta. In YK Delta infants

Immunotherapy of respiratory syncytial virus pneumonia following bone marrow transplantation.

Respiratory syncytial virus (RSV) pneumonia is a well-recognized complication of bone marrow transplantation with a high mortality rate. We describe two patients who developed RSV pneumonia within the first 3 weeks following allogeneic bone marrow transplantation. These patients had significant oxygen requirements and radiographic infiltrates. Both were treated with aerosolized ribavirin and given a single 1.5 gm/kg dose of intravenous immune globulin containing high levels of RSV neutralizing activity (RSV-IG). Both patients showed subjective and objective improvement after RSV-IG, never required mechanical ventilation, and were discharged without an oxygen requirement within 2 weeks after therapy. RSV microneutralization activity was measured in serum and nasal secretions. Mean serum microneutralization activity increased from 2279 microneutralization units (Mu)/ml to 18082 Mu/ml after RSV-IG. Peak serum microneutralization activity achieved with RSV-IG was higher than that achieved in a series of other immunocompromised adults with RSV pneumonia given either multiple doses of standard IVIG or no immune globulin therapy. RSV-IG may be beneficial in the treatment of RSV pneumonia in severely immunocompromised patients.

Comparison of antibody concentrations and protective activity of respiratory syncytial virus immune globulin and conventional immune globulin.

Relative to conventional immune globulins (IG, 13 lots), IGs prepared from donors with high activity by microneutralization assay to respiratory syncytial virus (RSVIG, 8 lots) had significantly higher neutralizing antibodies to 6 RSV strains (mean enrichment, 5.2-fold; range, 2.6- to 10.0-fold). In contrast, IgG antibody concentrations to whole RSV, fusion protein, or glycoproteins of A and B strains were similar in RSVIG and IG. Treatment of cotton rats with RSVIG at 0.5 g/kg 24 h before RSV challenge reduced RSV by 99% in the lungs (P < .001). RSVIG at 5.0 g/kg reduced RSV by 99% in the nose. IG at 5.0 g/kg had efficacy similar to that of RSVIG at 0.5 g/kg. Serum plaque-reduction neutralization titers of 1/390 resulted in 99% reduction of lung RSV and titers of 1/3500 resulted in 99% reduction in nose RSV. Relative to IG, RSVIG is enriched selectively in RSV neutralizing antibodies and has approximately 10 times greater protective activity in cotton rats.

Saponin adjuvant induction of ovalbumin-specific CD8+ cytotoxic T lymphocyte responses.

The ability of a saponin adjuvant, QS-21, to induce OVA-specific, class I MHC Ag-restricted CTL was investigated using different forms of soluble OVA and OVA adsorbed onto alum as immunogens. C57BL/6 mice were immunized with soluble native or denatured OVA in formulations that contained increasing quantities of QS-21, and CTL responses were measured using EL4 and E.G7-OVA cells as targets and splenic mononuclear cells as effectors. Ag-specific CTL responses were produced but only if the QS-21 adjuvant was used. Similar responses were induced using alum-adsorbed OVA when mixed with the QS-21 adjuvant but not when used alone. The CTL were specific for an epitope present on the OVA258-276 synthetic peptide, which contains the dominant CTL epitope recognized by C57BL/6 mice. The CD8+ subpopulation of lymphocytes in immune mice was not increased in spleens but increased significantly in vitro after culture with soluble OVA. The CTL activity of splenic mononuclear cell preparations was totally destroyed by treatment with mAb specific to the CD8 Ag plus complement. The ability of the QS-21 adjuvant to induce class I MHC Ag-restricted CTL after immunization with soluble proteins is a characteristic unique to saponin adjuvants.

Evaluation of a commercially available direct immunofluorescent staining reagent for the detection of respiratory syncytial virus in respiratory secretions.

A commercially-available direct immunofluorescence (IF) reagent (Imagen; Boots-Celltech, Slough, Berkshire, United Kingdom) was similar in sensitivity and specificity to the conventional indirect IF test for the detection of respiratory syncytial virus in respiratory secretions. Both IF tests were more sensitive than culture, particularly for specimens transported from outside the institution.

Fibroblast radiosensitivity and intraocular fibrovascular proliferation following radiotherapy for bilateral retinoblastoma.

A 5-day-old female patient was found to have large hereditary retinoblastomas in the posterior pole of each eye. The patient received radiation treatment over a 39-day period, with each retina receiving 4600 rad. Two weeks after the complete treatment the tumours had regressed to approximately one-quarter of their original size. By 14 weeks following completion of radiotherapy the patient had developed in each eye extensive iris neovascularisation with progressive closure of the filtration angles, secondary glaucoma, and retinal detachments resulting from fibrovascular proliferation on the retinal surface. Radiosensitivity studies were from separate conjunctival biopsies obtained before and after radiation. These showed a D0 (calculated survival curve parameters, defined in the Methods section) in the exponential growth phase of 110 prior to radiation and a postirradiation exponential growth phase D0 of 70. Karotype studies showed several chromosomal abnormalities following radiotherapy. The clinical course and pathology findings are thought to represent an unusually severe orbital and ocular response to radiation therapy. These findings are consistent with our hypothesis that some patients with hereditary retinoblastoma may have a defect in the accumulation repair of x-irradiation induced DNA damage.