Safety and immunogenicity of a subunit respiratory syncytial virus vaccine in children 24 to 48 months old.

A subunit vaccine for respiratory syncytial virus (RSV) consisting of purified fusion glycoprotein (designated PFP-1) was tested in children 24 to 48 months old. Two doses of 20 micrograms (n = 13) and 50 micrograms (n = 10) were compared with a saline (n = 24) placebo control group. Local and systemic reactions, reported within 96 hours postvaccination, were mild, transient, and did not differ significantly from the control cohort. Long term follow-up through at least one, and in some cases two, RSV seasons showed no serious RSV illness in vaccinees at any time. There was, therefore, no evidence of disease enhancement postvaccination. In the 20-micrograms cohort, 92% responded to vaccination by a 4-fold increase in enzyme-linked immunosorbent titer to the F glycoprotein and 42% had a 4-fold or greater rise in neutralizing titer to the A2 virus. In the 50-micrograms cohort 100% responded by enzyme-linked immunosorbent to the F glycoprotein and 70% responded by A2-neutralizing titers. The neutralizing titers in the vaccinated cohorts were similar to those seen previously in adults. These data show the ability of the subunit vaccine to boost existing immunity and to prime for a response to natural virus exposure in children who were seronegative at the time of vaccination.

Detection of HTLV-III RNA in lungs of patients with AIDS and pulmonary involvement.

A majority of pediatric patients and rare adult patients with the acquired immunodeficiency syndrome (AIDS) develop a chronic respiratory disorder referred to as "lymphocytic interstitial pneumonitis" (LIP). Efforts to identify an infectious agent responsible for this process so far have failed. In this study, frozen sections of lungs from patients with AIDS and pulmonary disease were tested by in situ molecular hybridization for the presence of cells infected with human T-cell lymphotropic virus type III (HTLV-III) and expressing viral RNA. In the case of an infant with LIP, a relatively high frequency (0.1%) of cells in the lung were found to be positive for HTLV-III RNA. This number is the lower limit of total cells infected since the in situ hybridization technique as applied in this study depends on expression of HTLV-III genes, and previous evidence indicates that a proportion of cells infected with HTLV-III may not express viral RNA. Moreover, this degree of infection of the lung is likely limited to LIP, since in ten patients with AIDS and pulmonary diseases other than LIP, only 0% to 0.002% of cells in lung were positive for viral RNA expression. Thus, HTLV-III may play a direct causal role in the development of LIP in infected patients, implicating its involvement in yet another of the diverse clinical diseases associated with this virus.

Antibody responses in adult volunteers to pneumococcal polysaccharide types 19F and 19A administered singly and in combination.

The immunogenicity of the two major group 19 pneumococcal polysaccharides, types 19F and 19A, was studied in human volunteers. Antibody responses after vaccination with either 50 micrograms of type 19F polysaccharide, 50 micrograms of type 19A polysaccharide, or 25 micrograms of both polysaccharides premixed in a single injection revealed that the combined vaccine was immunogenic for both types, but that the optimal immunogen for each was the homologous polysaccharide. We concluded that vaccination with type 19F polysaccharide antigen, included in the current pneumococcal vaccine, does not induce a satisfactory heteroimmunogenic response to type 19A.

Group C Neisseria meningitidis variant polysaccharide vaccines in children.

The currently United States-licensed group C Neisseria meningitidis vaccine, composed of the O-acetyl-positive capsular polysaccharide, is poorly immunogenic and does not afford protection from disease to infants and young children. Group C N. meningitidis O-acetyl-negative polysaccharide vaccine induces higher titers in adults than does the O-acetyl-positive vaccine. We compared the immunogenicity of these vaccines in 2-year-old children. Reactions were minimal and did not differ between the two vaccines. The postvaccination geometric mean titer was twofold greater in the O-acetyl-negative group (1.58 versus 0.73 micrograms of antibody per ml). The rates of decline in titer were similar in both groups. Further study regarding immunogenicity of and the anamnestic response to the O-acetyl-negative vaccine is warranted in the age group (less than 18 months) at highest risk for invasive meningococcal disease.

Natural history of group B streptococcus colonization and its therapy during pregnancy.

Seven hundred twenty-two pregnancies were studied in a private-practice setting to determine the natural history of colonization by group B streptococcus (GBS) over time. The colonization rate remained constant at 7% to 8% in each trimester, with 19% of the women colonized at some time during pregnancy. The organism was lost spontaneously at some time during pregnancy in 51%. Treatment of third-trimester pregnant women and their husbands with penicillin G resulted in a significant reduction in GBS colonization at delivery as compared to an untreated control group. If other factors are considered, however, routine culturing for GBS in pregnant women and treatment of those harboring the organism with penicillin G are not recommended.

Gangrene of the genitalia in children with pseudomonas sepsis.

The incidence of Pseudomonas aeruginosa bacteremia is increasing. Successful management is based upon early and aggressive therapy of the bacteremia and the usually associated granulocytopenia. A small number of such patients present with ecthyma gangrenosum, a characteristic skin lesion. During the last 4 years 5 children with acute leukemia and granulocytopenia presented to our hospital with these lesions. Although they occur most frequently on the extremities, buttocks or perineal region 2 of our patients had only isolated lesions of the external genitalia, resulting in gangrene of the penis in 1 and gangrene of the labia majora in the other. The gross and histologic pathology is reviewed. Recognition of this characteristic skin lesion enables the prompt institution of appropriate therapy.

Potential bacteremia in pediatric practice.

The potential consequences of bacteremia are considerable in all infants but particularly in those from 3 to 24 months of age with temperatures of 38.3 degrees C or more. Physicians have been advised to scrutinize these patients carefully with a variety of diagnostic tests and to treat their conditions vigorously if bacteremia is seriously considered or proved. We undertook to determine how often primary care pediatric practitioners encounter such patients "at risk" for bacteremia. Among the practices of nine pediatricians in Monroe County, New York, involving 220 practice days throughout 1977 and 4,151 patient visits, we found 145 instances of potential bacteremia. Depending, then, on the season of the year, practitioners may face this diagnostic and management dilemma as often as once each day. Therefore, laboratory means for determining those infants at highest risk for bacteremia or for rapidly diagnosing bacteremia will need to be readily available to practitioners.

Comparative immunogenicity of vaccines prepared from capsular polysaccharides of group C Neisseria meningitidis O-acetyl-positive and O-acetyl-negative variants and Escherichia coli K92 in adult volunteers.

Three structurally and antigenically similar capsular polysaccharides, two derived from group C Neisseria meningitidis (O-acetyl-positive and O-acetyl-negative variants) and one from Escherichia coli K92, which cross-reacts with polysaccharide from group C N. meningitidis, were compared for their ability to induce anticapsular and bactericidal antibodies to group C N. meningitidis in adult volunteers. All three vaccines elicited group C-specific serum antibodies. The vaccine derived from the O-acetyl-negative variant was the most immunogenic of the three vaccines. With use of radiolabeled O-acetyl-positive group C N. meningitidis polysaccharide antigen, the geometric mean titers of antibody in serum were 41.7 microgram/ml to the O-acetyl-negative variant, 22.8 microgram/ml to the O-acetyl-positive variant, and 7.1 microgram/ml to E. coli K92. Antibodies induced by all three vaccines were bactericidal for both of the group C N. meningitidis polysaccharide variants. An inverse relation between the comparative immunogenicity of the O-acetyl-negative polysaccharide and the virulence of group C N. meningitidis was found.

Teichoic acid serology in staphylococcal infections of infants and children.

Counterimmunoelectrophoresis and gel diffusion were utilized for the detection and titration of antibodies to staphylococcal teichoic acids in various disease states caused by coagulase-positive staphylococcus in infants and children. Serum samples were obtained on admission and serially for 2 to 12 weeks during illness. Teichoic acid antibodies were found by CIE in 12 of 21 patients (57%) with invasive CPS disease with bacteremia (Group A), in two of 17 patients (12%) with CPS infection without bacteremia (Group B), in none of 27 patients with bacteremia and/or invasive infections caused by organisms other than CPS (Group C), and in none of 24 noninfected, hospitalized patients or healthy children (Group D). Gel diffusion was useful for titrating antibodies in seropositive sera. Teichoic acid serology is a useful adjunct in the diagnosis of invasive CPS infections. The presence of these antibodies by CIE and gel diffusion may help to identify patients with endothelial or metastatic infections associated with staphylococcal bacteremia.

The lack of nurse-infant transmission of type B hepatitis in a special care nursery.

Twenty-four infants cared for by a nurse who developed acute B hepatitis with HBsAg present in her serum and saliva were examined for serologic evidence of hepatitis B virus transmission. None of the infants had HBsAg by radioimmunoassay or anti-HBc by complement fixation. One infant had anti-HBs whose transient presence was consistent with passive acquisition. Using sensitive serologic tests, no identifiable risk to newborn infants in a special care nursery could be documented as a result of exposure to a nurse who developed acute type B hepatitis during their period of care.

Herpesvirus infection in the newborn. Its treatment by exchange transfusion and adenosine arabinoside.

A case is reported of herpesvirus infection in the newborn following maternal genital herpesvirus infection. The rationale for treating a newborn infant with signs of disseminated herpesvirus infection by exchange transfusion in addition to adenosine arabinoside is discussed. Because of the lack of data concerning therapy for a disease with a 50 to 100% mortality rate, it is important to present material such as this in order to provide information about possible new therapeutic modalities.

Antiviral chemotherapy and neonatal herpes simplex virus infecition: a pilot study--experience with adenine arabinoside (ARA-A).

Among 13 neonates with herpes simplex virus (HSV) infection, eight had disseminated disease, one localized CNS disease, and in four the infection was confined to the skin and eyes. Ara-A, a purine nucleoside with anti-viral activity against DNA-VIRUSES, WAS GIVEN (10 TO 20 MG/MG/DAY) BY A CONTINUOUS 12-HOUR INTRAVENOUS DRIP FOR 10 TO 15 DAYS. In all, ara-A administration was begun within three to eight days after the appearance of skin vesicles which represented the hallmark of the disease. Both diagnosis and ara-A treatment were much delayed in one infant without skin vesicles and four infants whose skin vesicles appeared late, long after the occurrence of CNS damage. In this group of infants with disseminated disease, four died and one infant was left with severe neurological deficits. Eight infants (four with disseminated and four with localized skin disease) with skin vesicles as the earliest sign of infection received ara-A early, within three days after the onset of neurologic signs. All survived with no neurologic deficit at 6 months to 1 year of age. There was no apparent toxicity of ara-A to the bonemarrow, liver, or kidney.

Localization of endovascular infection by selective catheterization with serial cultures.

Pseudomonas infection developed at the suture line of an aortic graft in a patient 13 years after the operation. The site of the infection was localized by quantitative blood cultures taken with the aid of selective arterial catheterization. This technique may be of great help in localizing the source of endovascular infection in difficult cases.