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Early in the development of respiratory syncytial virus (RSV) vaccines severe disease occurred in children after receipt of formalin-inactivated RSV vaccine. Continuing efforts to develop an appropriately attenuated and immunogenic live RSV vaccine have given opportunities to assure that live vaccines are safe through surveillance of children after vaccination. In the present study, the rate of RSV-associated upper respiratory tract illness in 388 children was lower in RSV vaccinated children than in controls (14% versus 20% in a 6-24 month old group and 16% versus 25% in infants). Additionally, there was no evidence that vaccination predisposed to more severe lower respiratory tract illness. Thus infection with a series of live attenuated RSV vaccines did not result in enhanced disease upon infection with wild type RSV. The impact of RSV during this surveillance will inform the design of future efficacy studies with RSV vaccines.

OBJECTIVE. The goal was to evaluate the safety, tolerability, and efficacy of an investigational, refrigerator-stable formulation of live attenuated influenza vaccine (cold-adapted influenza vaccine-trivalent) against culture-confirmed influenza, acute otitis media, and effectiveness outcomes in young children in day care over 2 consecutive influenza seasons. METHODS. Children 6 to RESULTS. A total of 1616 subjects (vaccine: 951 subjects; placebo: 665 subjects) in year 1 and 1090 subjects (vaccine: 640 subjects; placebo: 450 subjects) in year 2 were able to be evaluated for efficacy. The mean age at first vaccination was 23.4 ± 7.9 months. In year 1, the overall efficacy of the vaccine against influenza subtypes similar to the vaccine was 85.4%; efficacy was 91.8% against A/H1N1 and 72.6% against B. In year 2, the overall efficacy was 88.7%; efficacy was 90.0% against H1N1, 90.3% against A/H3N2, and 81.7% against B. Efficacy against all episodes of acute otitis media associated with culture-confirmed influenza was 90.6% in year 1 and 97.0% in year 2. Runny nose or nasal discharge after dose 1 in year 1 was the only reactogenicity event that was significantly more frequent with cold-adapted influenza vaccine-trivalent (82.3%) than placebo (75.4%). CONCLUSIONS. Cold-adapted influenza vaccine-trivalent was well tolerated and effective in preventing culture-confirmed influenza illness in children as young as 6 months of age who attended day care.

Live attenuated influenza vaccine (LAIV; FluMist) is a trivalent vaccine containing cold-adapted influenza vaccine viruses that infect and replicate in cells lining the nasopharynx to induce immunity. Recovery of viruses (shedding) is measured by culture of nasal specimens. Shedding of vaccine viruses is not equated with transmission because transmission requires more virus than is detected in many nasal swabs. Previous studies with LAIV did not detect transmission to close contacts. The primary objective of this study was to estimate the probability of transmission to placebo contacts in a day care setting.One hundred ninety-seven healthy children aged 9 to 36 months attending day care were randomized to receive vaccine or placebo. Postvaccination viral shedding, safety, genotype and phenotype of shed viruses and probability of transmission were assessed.Eighty percent of 98 vaccine recipients shed at least one vaccine strain. No clinically significant differences in solicited adverse events attributable to vaccine occurred; safety profiles were similar in both groups. Vaccine virus isolates retained their phenotypic characteristics (cold adaptation and temperature sensitivity) and did not revert at nucleotides known to confer an attenuating phenotype. There was one confirmed transmission of a vaccine strain to a single placebo recipient. According to the Reed-Frost model, the calculated probability of transmission to a child after contact with a single vaccinated child was 0.58% (95% confidence interval, 0-1.7%). There was no increased reactogenicity or other safety concerns in the recipient child.Young children in a day care setting had a high rate of shedding and a low rate of transmission. No clinically significant illness occurred among children who received vaccine or placebo or in the child to whom the vaccine virus was transmitted.

Background This study examined the transmissibility between young children of an intranasally administered live attenuated human parainfluenza virus type 3 (HPIV3)- cp 45 vaccine candidate. Methods Eighty subjects were enrolled in playgroups among whom there was at least one infected vaccinee in close contact with a seronegative placebo recipient over 21 days without a confounding infection with wt HPIV3. Following vaccination viral cultures were obtained on nine occasions to detect shedding and transmission of HPIV3 cp 45. Serum antibody titers were measured before and 7 weeks after vaccination. Results No child fulfilled the criteria for transmission of HPIV3 cp 45 giving a risk of transmission of 0.04 (95% CI 0.01–0.19), hence establishing that HPIV3 cp 45 is less infectious than wt HPIV3 and risk of transmission is not a limitation to further clinical development of this vaccine candidate.

Objective. During the 2 decades in which effective antiviral therapies have been available for neonatal herpes simplex virus (HSV) disease, changes have been documented not only in the outcomes of infected infants, but also in the natural history of the disease itself. Numerous studies previously have reported that early institution of antiviral therapy is beneficial to the outcome of the disease. The objective of this study was to provide an update of neonatal HSV disease to identify means by which future improvements in the management of HSV-infected neonates can be made. Design/Methods. Neonates enrolled in 2 studies of parenteral acyclovir for the treatment of neonatal HSV disease provided the data source. The National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted the studies between 1981 and 1997. A total of 186 patients are summarized, all of whom were treated with acyclovir. Demographic and clinical characteristics of these patients are reported. Results. Comparisons between patients treated in the periods between 1981–1988 and 1989–1997 according to extent of disease revealed that the mean time between the onset of disease symptoms and initiation of therapy has not changed significantly from the early 1980s to the late 1990s. Of all patients evaluated, 40% had fetal scalp monitors during the delivery process. A significant minority of patients did not have skin vesicles at the time of their presentation and did not develop them during the acute HSV disease (39% of patients with disseminated disease; 32% of patients with central nervous system [CNS] disease; and 17% of patients with skin, eye, and/or mouth disease). Among patients with CNS disease, mortality was associated with prematurity. Among patients with disseminated HSV disease treated with acyclovir at 30 mg/kg/d, mortality was associated with aspartate transaminase elevations of ≥10 times the upper limit of normal at the time of initiation of acyclovir therapy. Mortality was also associated with lethargy at initiation of antiviral therapy for patients with disseminated disease. Patients' morbidity status was associated with the extent of disease (skin, eye, and/or mouth disease vs CNS vs disseminated). For those patients with CNS disease, morbidity was also associated with seizures at initiation of antiviral therapy. Conclusion. Data presented in the current comparison of neonatal HSV disease over the 2 periods (1981–1988 vs 1989–1997) demonstrate that no progress has been made in decreasing the interval between onset of HSV symptoms and initiation of antiviral therapy. Additional strides in the improvement of disease outcome may occur only if the interval between onset of symptoms and initiation of therapy is shortened. The means by which this will be accomplished lie in increased consideration of neonatal HSV infections in acutely ill infants. Specific data and recommendations to facilitate this goal are contained within.

Objective. The objective of this investigation was to establish the safety of high-dose (HD) acyclovir for the treatment of neonatal herpes simplex virus (HSV) disease. In addition, an estimate of therapeutic efficacy was sought, both with respect to mortality and to morbidity. Virologic efficacy of HD acyclovir was also assessed. Participants. Infants who were ≤28 days old and whose disease was considered to be caused by HSV were enrolled in this study. Patients with central nervous system (CNS; N = 28) or disseminated (N = 41) HSV infection were offered participation in the trial. A small number of patients with HSV disease limited to the skin, eyes, or mouth (SEM; N = 10) or whose disease was clinically consistent with HSV but who did not have virologic confirmation of infection (N = 9) also were enrolled on a compassionate basis. Only patients with virologically confirmed HSV disease were included in efficacy analyses. All enrolled patients were included in safety analyses. Methods. The study was an open-label evaluation of intravenous acyclovir at dosages higher than the 30 mg/kg/d standard dosage approved by the US Food and Drug Administration. The first 16 patients enrolled received intermediate-dose (ID) acyclovir (45 mg/kg/d), and the next 72 patients received HD acyclovir (60 mg/kg/d). Acyclovir was administered in 3 divided daily doses for 21 days. Neonates were assessed prospectively throughout treatment and at scheduled follow-up visits for the first 4 years of life. Data were compared with those of a previous National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group trial in which patients received standard-dose (SD) acyclovir for 10 days and in which identical methods (with the exception of acyclovir dosage and duration of therapy) were used. Results. Six (21%) of 29 HD acyclovir recipients whose HSV disease remained localized to the SEM or CNS experienced neutropenia. One of the 6 had an absolute neutrophil count The survival rate for the patients with disseminated HSV disease treated with HD acyclovir was significantly higher than for those in the previous study treated with SD acyclovir, with an odds ratio (OR) of 3.3 (95% confidence interval [CI]: 1.4–7.9). For patients with CNS disease, however, survival rates were similar for the HD and SD groups. To assess the effect of HD acyclovir on survival for the entire population with neonatal HSV disease, the Cox proportional hazards regression analysis was performed with stratification for disease category (CNS versus disseminated). In performing this analysis, differences in mortality for each disease category were weighted to allow statistical comparison of the treatment dosage groups (HD, ID, and SD). This analysis indicated that the survival rate for patients treated with HD acyclovir was statistically significantly higher than for patients treated with SD acyclovir (OR: 3.3; 95% CI: 1.5–7.3). Recipients of HD acyclovir had a borderline significant decrease in morbidity compared with SD recipients, after stratification for the extent of disease (SEM vs CNS vs disseminated) and controlling for the potential confounding factors of HSV type (HSV-1 vs. HSV-2), prematurity, and disease severity (seizures). Patients treated with HD acyclovir were 6.6 times (adjusted OR; 95% CI: 0.8–113.6) as likely to be developmentally normal at 12 months of age as patients treated with SD therapy. Conclusion. These data support the use of a 21-day course of HD (60 mg/kg/d) intravenous acyclovir to treat neonatal CNS and disseminated HSV disease. Throughout the course of HD acyclovir therapy, serial ANC determination should be made at least twice weekly. Decreasing the acyclovir dosage or administering granulocyte colony-stimulating factor should be considered if the ANC remains below 500/mm3 for a prolonged period.

Intranasal trivalent, cold-adapted, live attenuated influenza vaccine (CAIV-T) is a promising alternative to inactivated vaccine for protection against influenza in children. However, correlates of immunity are not well defined. To determine the mucosal immune response to CAIV-T, 19 children ages 15-55 months were randomized to receive two doses of CAIV-T or placebo. Influenza-specific IgA to the haemagglutinin of each of three contemporary strains was measured in nasal washes collected pre- and postvaccination using a kinetic enzyme-linked immunosorbent assay. After two doses of study drug, 62, 69 and 85% of CAIV-T recipients demonstrated a mucosal IgA response to influenza A/H1N1, A/H3N2, and B strains respectively; in comparison, 33, 0 and 17% of placebo recipients demonstrated an IgA response to the same strains (p = 0.35, 0.01 and 0.01). Overall, seropositive vaccinees were 4.5 times more likely to develop a mucosal immune response than an HAI response (p = 0.015). Two doses of CAIV-T induce a mucosal IgA response to all three influenza vaccine antigens in the majority of children. In addition, a mucosal antibody response may be the only indication of a vaccine take in a seropositive child.

Thirty-five children

Objective. To evaluate the efficacy of high titer respiratory syncytial virus (RSV) immune globulin (RSVIG) in the treatment of previously healthy children hospitalized with proven RSV lower tract infection (LRI). Method. Infants and young children ≤2 years of age with RSV LRI of ≤4 days duration, and respiratory scores ≥2.5 were enrolled. Results. One hundred and one previously healthy children hospitalized with RSV LRI received either 1500 mg/kg of RSVIG (RespiGam, MedImmune Inc, Gaithersburg, MD) or albumin placebo in a randomized, double-blind, placebo-controlled trial. Forty-six RSVIG and 52 recipients of placebo met all eligibility criteria. Demographic characteristics of the two groups were similar. More RSVIG recipients (46% vs 29%) had an SaO2 ≤85% at entry than did placebo recipients, but a higher proportion of placebo recipients required intensive care unit (ICU) care and mechanical ventilation at study entry. The mean RSV hospital stay was 5.52 ± 0.69 days (SE) for placebo and 4.58 ± 0.40 days for RSVIG. Additionally, there was an interaction between treatment group and entry respiratory score, which led to subgroup analysis. Children with modest respiratory illness did not receive any benefit from RSVIG therapy. RSVIG recipients with more severe illness (entry respiratory scores ≥3.0) had 1.6 fewer hospital days and 2.7 days less ICU stays. Conclusion. RSVIG infusions seemed safe and generally well tolerated. Although some beneficial effect trends were seen for those with more severe disease who were treated there was no evidence that treatment with RSVIG resulted in reduced hospitalization and reduced ICU stays in all children with RSV disease.

1126 children, 2 months to 3 years old, received a single intranasal dose of 10 4 , 10 6 , or 10 7 TICD 50 of cold adapted (ca) A/Kawasaki/9/86 (H1N1) and A/Beijing/352/89 (H3N2) or placebo, in a double blind, placebo-controlled, safety and immunogenicity trial. No reactogenicity attributable to vaccine was demonstrated. A single bivalent 10 6 or 10 7 dose produced high rates of seroconversion to H1N1 (77%) and H3N2 (92%) in seronegative children > 6 months old; serologic responses were lower to H1N1 ( P P = 0.01) in younger infants. A single 10 6 dose of bivalent ca influenza A vaccine can be immunogenic in children, but response is age dependent.

Background. Respiratory syncytial virus (RSV) is the most important viral respiratory pathogen of infancy and childhood. Much has been written about inpatients with severe disease. Inpatients, however, represent only a minority of RSV-infected children. We studied the characteristics of symptomatic outpatient RSV infection in healthy children to gain a better understanding of RSV disease and to provide a background for the testing of intervention strategies in children without high-risk conditions. Methods. A total of 1113 children were followed during 20 consecutive RSV seasons. Signs and symptoms of respiratory infection were monitored. Cultures were obtained for febrile upper respiratory infection, acute otitis media, and lower respiratory infection (LRI). Rates of febrile upper respiratory infection, acute otitis media, LRI, and hospitalization were calculated. Given those rates, numbers of children needed to demonstrate efficacy of a vaccine product were calculated. Results. Mild disease from RSV infection lacked some of the classic features of RSV infection seen in hospitalized children. Involvement of the lower respiratory tract was, however, noted to be much higher in RSV infection than it was in infection with other viral respiratory pathogens. LRI was, therefore, considered the best candidate endpoint for vaccine trials. A product with 60% efficacy could be proven, with a power of 0.8, to be efficacious with as few as 1500 infants. Conclusions. RSV infection is common and often involves the lower respiratory tract, even in outpatients. Our 20-year study of RSV infection provides a basis for calculation of sample sizes to be used in trials of vaccine candidates. respiratory syncytial virus, outpatient, epidemiology, vaccine, bronchiolitis.

Background. Neonatal herpes simplex virus (HSV) infections limited to the skin, eyes and mouth (SEM) can result in neurologic impairment. A direct correlation exists between the development of neurologic deficits and the frequency of cutaneous HSV recurrences. Thus, the National Institutes of Allergy and Infectious Diseases Collaborative Antiviral Study Group conducted a Phase I/II trial of oral acyclovir therapy for the suppression of cutaneous recurrences after SEM disease in 26 neonates. Methods. Infants ≤1 month of age with virologically confirmed HSV-2 SEM disease were eligible for enrollment. Suppressive oral acyclovir therapy (300 mg/m 2 /dose given either twice daily or three times per day) was administered for 6 months. Results. Twelve (46%) of the 26 infants developed neutropenia (

Abstract 3212 Introduction: Children with sickle cell disease (SCD) have a significantly increased risk of invasive pneumococcal disease (IPD) and mortality, primarily attributable to functional asplenia. Penicillin prophylaxis and PPSV23 have been shown to dramatically reduce those risks, but strain resistance to penicillin has increased. Furthermore, PPSV23 is less effective in children Methods: We conducted a phase 3, open-label, single-arm study to evaluate the safety, tolerability, and immunogenicity of 2-doses of PCV13 given 6 months apart to children 6 to less than 18 years of age with SCD previously immunized with PPSV23 more than 6 months prior to study entry. Blood samples were collected prior to and 1 month after each dose. Serotype-specific immunoglobulin (IgG) geometric mean concentrations (GMCs) and fold rises (GMFRs) were determined. Local pain, redness and swelling, and fever, vomiting, diarrhea, headache, fatigue, muscle pain and joint pain were recorded in an ediary for 7 days after each dose. Serious adverse events (SAEs) were reported throughout the study. Results: We enrolled 158 subjects; 51.9% were males. All subjects were previously vaccinated with PPSV23; 12 subjects had received 2 to 6 doses. The mean age at enrollment was 13.3 (±3.08) years. All subjects received dose 1; 146 subjects received dose 2. One of the 12 subjects who did not complete the vaccination phase withdrew due to local pain and systemic events reported after dose 1. Subjects responded very well to a single dose of PCV13 (see Table). The prevaccination/postdose 1 IgG GMFRs ranged from 1.73 (serotype 5) to 7.01 (serotype 4). The antibodies declined over 6 months and subjects responded well to a second dose of PCV13; however the IgG GMCs were generally lower than after the first dose (see Table). The postdose 2/postdose 1 IgG GMFRs were 91.7% and 88.5% of subjects reported local reactions, and 87.5% and 89.3% of subjects reported systemic events after dose 1 or dose 2, respectively. Most of the SAEs were due to vaso occlusive crisis and only one was assessed by the investigator as related to the study vaccine. No deaths occurred. Conclusions: Children with SCD previously vaccinated with PPSV23 responded well to PCV13. A second dose did not enhance the immune response, likely due to the short interval (6 months) and high levels of persisting antibody. Pending analysis of functional antibody responses assessed by opsonophagocytic activity (OPA) will further describe the immune responses of PCV13 in this population. Disclosures: De Montalembert: Novartis: Speakers Bureau. Abboud:Novartis: Speakers Bureau. Fiquet:Vaccines Clinical Research Pfizer Global Research and Development : Employment. Piga:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Jiang:Pfizer Inc: Employment. Pereira:Vaccines Clinical Research Pfizer Global Research and Development: Employment. Emini:Pfizer Inc.: Employment, Equity Ownership. Gruber:Pfizer: Employment. Gurtman:Pfizer: Employment. Scott:Pfizer: Employment.

Influenza viruses recovered from 14 children 2-10 days after vaccination with an egg-grown, cold-adapted influenza B vaccine (B/AA/1/86) were analyzed. Hemagglutination-inhibition (HI) assays using monoclonal antibodies did not detect antigenic differences between the vaccine strain and the viruses recovered from the vaccinees. Furthermore, nucleotide sequence analysis of the HA1 region did not reveal any changes compared to the sequence of the vaccine strain. These findings indicate that influenza B vaccine hemagglutinin is genetically stable during replication in human vaccinees.

Infants with respiratory syncytial virus infection have low serum vitamin A levels. We treated 21 respiratory syncytial virus-infected children with 12,500 to 25,000 IU of oral vitamin A. Vitamin A levels were normalized at 6 h, and none of the children experienced vitamin A toxicity or exacerbation of respiratory illness. Vitamin A treatment of previously healthy respiratory syncytial virus-infected infants at these doses is safe and well tolerated.

We report four cases of necrotizing fasciitis that occurred following varicella in children ranging in age from 2 to 8 years. The only organism isolated from each of these patients was Streptococcus pyogenes or group A beta-hemolytic Streptococcus (GABHS). Each child recovered; however, three required repeated surgical debridements in addition to therapy with antibiotics. An interesting finding in these patients was the development of hyponatremia and/or hypocalcemia. M-typing and T-typing of the isolates demonstrated that the GABHS strain in two children who attended the same school was M5; M1 and M3 strains were identified in the other two children. In addition to the children described in this series, eleven other cases of children with necrotizing fasciitis following varicella have been reported in the English-language literature since 1970. We believe that these cases provide further evidence that varicella is an important risk factor for necrotizing fasciitis that is caused by more-virulent strains of GABHS.

Healthy adult subjects (n = 198) were randomized to receive bivalent cold-adapted (ca) influenza A vaccine containing 10(7.4) TCID50 each of A/Kawasaki/9/86 (H1N1) and A/Los Angeles/2/87 (H3N2) by either nose drops (ND) or large-particle aerosol (LPA). All subjects had received monovalent inactivated influenza B vaccine intramuscularly in the previous year. Ninety percent of LPA recipients and 82% of ND recipients preferred intranasal administration to their previous experience with intramuscular vaccine. Twenty-six (27%) of 98 LPA recipients and 47 (49%) of 97 ND recipients reported swallowing vaccine (P = .008). Fever was observed uncommonly (< or = 5%), and incidence of respiratory symptoms was comparable between groups. Fourfold or greater hemagglutination antibody response to at least one of the influenza A vaccine viruses was significantly more frequent after LPA (64%) than ND vaccination (43%; P = .005). LPA administration of ca influenza to the nasopharynx was well tolerated, safe, and more immunogenic than ND delivery.

The origin of human adenovirus type 4 (Ad4), an important pathogen and candidate vaccine vector, has been the subject of speculation. Ad4 is unusual among adenoviruses, because it is the single known serotype of subgroup E. Some biological and biochemical properties of Ad4 resemble those of serotypes from subgroups B and C. The length of Ad4 fiber is intermediate between that of subgroup B and C fibers. We sequenced the Ad4 fiber gene, locus of the determinant(s) of adenovirus serotype. The number of repeating DNA sequence motifs in the shaft domain of the Ad4 fiber gene is consistent with its reported length. Regional phylogenetic analysis of Ad4 was undertaken, comparing DNA sequences of early genes and fiber genes from representative adenoviruses. The Ad4 fiber gene has close phylogenetic relationship to subgroup C fiber genes. This is in distinct contrast to the closer relationship of Ad4 to subgroup B adenoviruses in early gene sequences, distributed across the left 70% of the viral genome. We propose that Ad4 originated by recombination of genomes resembling contemporary subgroup B and subgroup C adenoviruses. This event may have occurred so recently that divergence of subgroup E serological determinants has yet to be observed.

The effects of passive respiratory syncytial virus (RSV) immune serum given as preinoculation prophylaxis, postinoculation prophylaxis, and as therapy on d 5 after inoculation were evaluated in an illness model of RSV infection in BALB/c mice. Pre- and postinoculation prophylaxis reduced RSV replication in lung after primary RSV infection and prevented illness. Day 5 treatment did not affect peak titer of RSV in lung but resulted in more rapid recovery from illness than seen in untreated mice. Prophylaxis prevented antibody responses and lymphocytic infiltrates in lung after primary RSV infection. Treatment caused diminished antibody and pathologic responses. Prophylaxis increased susceptibility to reinfection, although illness after rechallenge was mild. Mice treated therapeutically were less susceptible to reinfection than mice treated prophylactically, but they also experienced mild illness after rechallenge. Passive antibody prophylaxis and treatment of RSV infection are promising approaches to attenuating lower respiratory tract illness from primary RSV infection. The ability to measure illness endpoints and pathology make the BALB/c mouse model of RSV infection a useful system for the preclinical evaluation of immunoprophylactic and immunotherapeutic modalities.

Fifty children, 6 months to 2 years of age, were vaccinated intranasally with a trivalent preparation containing 10(6) TCID50 each of H1N1 and H3N2 and 10(4) (n = 14) or 10(6) (n = 36) TCID50 of B live, attenuated, cold-adapted (ca) influenza strains. The same doses were administered as monovalent vaccines to 69 comparably aged children. Forty-five controls were given placebo. No clinically significant adverse reactions to vaccines were observed. Of children seronegative to H1N1 or H3N2, > or = 90% were infected by these vaccine strains. Trivalent vaccine containing 10(4) TCID50 of B infected only 27% of children seronegative to B (3/11), which was markedly reduced from the 88% infection rate (7/8) following monovalent B vaccine of the same dose (P = .02); increasing the B dose to 10(6) TCID50 increased the infection rate to 81% (21/26). Replication of ca influenza viruses in tissue culture matched vaccine responses. Trivalent ca influenza vaccines can be formulated that are safe and immunogenic in young children.

Efficacy of Trivalent Live Attenuated Intranasal Influenza Vaccine against Monovalent Influenza H1N1 Challenge in Children

RESPIRATORY SYNCYTIAL VIRUS IMMUNE HUMAN GLOBULIN, (RSVIg) AS TREATMENT OF RSV LOWER RESPIRATORY TRACT INFECTIONS (LRI) IN CHILDREN. † 1085

• In 1985, we enrolled 189 school-age children by family in a double-blind study to determine protection against influenza by a single dose of cold-recombinant bivalent A vaccine or commercial trivalent inactivated vaccine compared with placebo. All children in school or day care, 3 to 18 years of age, in an enrolled family received the same preparation. Following vaccination, 60% and 21% of cold-recombinant bivalent A vaccine recipients and 73% and 83% of trivalent inactivated vaccine recipients demonstrated fourfold or greater response in hemagglutination-inhibition antibody titer to A/H1N1 and A/H3N2, respectively. Sixty-seven percent of all trivalent inactivated vaccine recipients demonstrated a fourfold or greater serologic response to H1N1, H3N2, and influenza B following a single dose of vaccine. During the 1985-1986 influenza B/Ann Arbor epidemic, heterotypic protection afforded by the influenza B/USSR component of trivalent inactivated vaccine was 62% compared with placebo. A single dose of trivalent inactivated vaccine protected schoolage children, 6 to 19 years of age, from influenza B infection; the rate of protection was 64% against infection and 73% against febrile illness. (AJDC.1990;144:595-600)

We studied the effects of combined administration of human immunoglobulin (IVIG) and ribavirin aerosol on respiratory syncytial virus (RSV) infection in cotton rats (Sigmodon hispidus). Cotton rats assigned to receive combined therapy were administered Gamimune, a preparation of purified IVIG with a high titer of anti-RSV neutralizing activity, intraperitoneally 24 h prior to intranasal RSV challenge and then treated with ribavirin aerosol 3 days after challenge. Lung viral titers from these cotton rats (geometric mean titers [GMT] log10 = 0.15 +/- 0.5) were lower than titers from untreated animals (GMT, log10 = 3.7 +/- 0.6) and animals treated with either IVIG alone (GMT, log10 = 1.8 +/- 0.9) or ribavirin alone (GMT, log10 = 1.9 +/- 1.1). Only one of 12 cotton rats treated with both IVIG and ribavirin had a demonstrable titer of virus after RSV challenge. When IVIG administration was delayed until day 3 after virus challenge, lung viral titers were still lowest in animals receiving both IVIG and ribavirin. In comparison, there was no additive antiviral effect between IVIG and ribavirin against RSV infections of HEp-2 cells in vitro. Pathologic changes on histologic examination of pulmonary tissues from animals challenged with RSV were least prominent in animals treated with both IVIG and ribavirin. Despite the apparent absence of in vitro additive antiviral effect, combined use of IVIG and ribavirin was more efficacious against RSV infection in the cotton rat than use of either agent alone.

BackgroundStaphylococcus aureus is a common cause of healthcare-acquired morbidity and mortality and increased healthcare resource utilization. A prophylactic vaccine is being developed that may reduce this disease burden.MethodsVolunteers in good general health aged 50–85 (n=312) and 18–24 (n=96) years were randomized to receive a single intramuscular dose of one of three dose levels of a non-adjuvanted, 3-antigen S. aureus vaccine (SA3Ag) or placebo. SA3Ag antigens included capsular polysaccharides 5 and 8 (CP5 and CP8), each conjugated to cross-reactive material 197 (CRM197), and recombinant clumping factor A (ClfA). Safety, tolerability, and immunogenicity were evaluated.ResultsAt day 29 post-vaccination, robust immune responses were observed in both age cohorts at all three SA3Ag dose levels. In the primary analysis population, the 50- to 85-year age stratum, geometric mean-fold-rises in competitive Luminex® immunoassay antibody titers from baseline ranged from 29.2 to 83.7 (CP5), 14.1 to 31.0 (CP8), and 37.1 to 42.9 (ClfA), all (P

We performed serial serologic tests for cytomegalovirus (CMV) antibody in 177 children born to low- and middle-income families in Houston from 1975 to 1983. Mean duration of participation in the study was 4.8 years (range 1 to 9.6 years). Most rapid acquisition of antibody occurred during the first and second years of life, 13.6% and 12%, respectively; thereafter, annual acquisition varied from 1.5% to 4.6%, up to 10 years. Overall, 59 (33%) of the group were known to seroconvert by age 10 years. This was a minimal figure because of loss to follow-up. Analysis by the Kaplan-Meier method indicated that the probability of remaining seronegative was 65% at age 6 years, and 58% at age 8 years. Variables positively related to seroconversion by multivariate analysis were order of birth, seroconversion in a family member, and breast-feeding. During the first year of life, acquisition of CMV antibody was related to the seroimmune status of the mother. The variables of socioeconomic status, race, age of the mother, and attendance in a day care center did not appear to be related to seroconversion in these children.

BACKGROUND: In two clinical trials, low-grade fever was observed more frequently after coadministration than after separate administration of two recommended routine pediatric vaccines. Since fever is an important issue with vaccine tolerability, we performed this open-label study on the efficacy and safety of prophylactic use of paracetamol (acetaminophen, Benuron(R)) in children administered routine 7-valent pneumococcal conjugate vaccine (PCV-7) coadministered with hexavalent vaccine (diphtheria-tetanus-acellular pertussis-hepatitis B, polio, Haemophilus influenzae type b vaccine [DTPa-HBV-IPV/Hib]) in Germany. METHODS: Healthy infants (N = 301) who received a 3-dose infant series of PCV-7 and DTPa-HBV-IPV/Hib plus a toddler dose were randomly assigned 1:1 to prophylactic paracetamol (125 mg or 250 mg suppositories, based on body weight) at vaccination, and at 6--8 hour intervals thereafter, or a control group that received no paracetamol. Rectal temperature and local and other systemic reactions were measured for 4 days post vaccination; adverse events were collected throughout the study. RESULTS: In the intent-to-treat population, paracetamol reduced the incidence of fever >=38[degree sign]C, but this reduction was only significant for the infant series, with computed efficacy of 43.0% (95% confidence interval [CI]: 17.4, 61.2), and not significant after the toddler dose (efficacy 15.9%; 95% CI: -19.9, 41.3); results were similar in the per protocol (PP) population. Fever >39[degree sign]C was rare during the infant series, such that there were too few cases for assessment. After the toddler dose, paracetamol effectively reduced fever >39[degree sign]C, reaching statistical significance in the PP population only (efficacy 79%; 95% CI: 3.9, 97.7). Paracetamol also reduced reactogenicity, but there were few significant differences between groups after any dose. No vaccine-related serious adverse events were reported. CONCLUSIONS: Paracetamol effectively prevented fever and other reactions, mainly during the infant series. However, as events were generally mild and of no concern in either group our data support current recommendations to administer paracetamol to treat symptoms only and not for routine prophylaxis.Trial registration: NCT00294294.