Lumbar puncture in meningitis?
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Biomedical subjects
Publications and source records attributed to S P Gotoff.
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There are a number of promising strategies to prevent necrotizing enterocolitis (NEC). These included induction of intestinal maturation with prenatal or postnatal steroids, passive immunization with oral immunoglobulin, modification of enteral feedings, administration of oral antibiotics to decrease bacterial overgrowth while avoiding the development of resistant strains, and acidification of oral fluids to prevent bacterial overgrowth. The initial results need to be confirmed, but it is likely that one or more of these prevention measures will lower the incidence of NEC in the future.
An ELISA was developed to measure IgM antibody to albumin-coupled native capsular polysaccharide of type III group B streptococcus (GBS). The assay was standardized by two double-label methods that agreed within 33%. In quantitative assays, the range of IgM antibody to type III GBS in the sera of 94 adult pregnant women was 1.2-50.6 micrograms/ml (median, 5.4), while each of 38 cord serum samples contained less than 0.03 micrograms/ml IgM antibody. Neonatal rats were passively immunized with a serially diluted human serum containing 15 micrograms/ml IgM and undetectable IgG antibody to type III GBS. The rats were protected against lethal infection with an IgM antibody concentration of 0.5 micrograms/ml. In single serum samples from 31 healthy infants less than 2 years old and serial specimens from 5 infants with type III GBS infections, specific IgM antibody was detectable by 3 months of age. Levels greater than or equal to 0.5 micrograms/ml were present in all samples from infants greater than 7 months of age. The acquisition of specific IgM antibody is inversely correlated with the age-limited incidence of type III GBS infections in young children.
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This article reviews available studies on prevention of neonatal group B streptococcal infections with antimicrobial prophylaxis. The data show that short-term administration of ampicillin to parturients with prenatal streptococcal colonization and perinatal risk factors effectively prevents these serious infections. A strong case can be made for prenatal screening for group B streptococcal carriage to identify mothers whose babies are at risk.
Most cases of neonatal group B streptococcal disease with early onset have an intrapartum pathogenesis. Attack rates are increased substantially in infants born to mothers with prenatal group B streptococcal colonization and various perinatal risk factors (premature labor, prolonged membrane rupture, or intrapartum fever). In a randomized controlled trial, we studied the effect of selective intrapartum prophylaxis with ampicillin in 160 such high-risk women. In infants born to mothers who received intravenous ampicillin during labor, as compared with controls who received no treatment, neonatal colonization with group B streptococci was present in 8 of 85 (9 percent) versus 40 of 79 (51 percent; P less than 0.001), colonization at multiple (greater than or equal to 3) sites was observed in 3 of 85 (4 percent) versus 24 of 79 (30 percent; P less than 0.001), and bacteremia occurred in none of 85 versus 5 of 79 (6 percent; P = 0.024). The side effects of ampicillin were limited to a single episode of urticaria in a mother who had no history of penicillin allergy. We conclude that intrapartum ampicillin prophylaxis in women with positive prenatal cultures for group B streptococci who have certain perinatal risk factors can prevent early-onset neonatal group B streptococcal disease.
We determined the serum concentration of human IgG antibody to the native capsular polysaccharide of group B Streptococcus (GBS) type III needed to passively protect mice against lethal homologous challenge. Antibody was measured by an ELISA, standardized by two methods, and corrected for nonprecipitating antibody. A concentration of 1.3 micrograms of IgG antibody to GBS type III/ml protected 126 (97%) of 130 mice from an 80%-96% lethal dose bacterial challenge. Concentrations of IgG antibody to GBS type III in sera from 42 infected infants were less than or equal to 0.3 micrograms/ml. Concentrations of antibody ranged from less than 0.02 to 21.7 micrograms/ml in sera from 102 unselected pregnant women (median, 0.05 microgram/ml); 13% had concentrations greater than or equal to 1.3 microgram/ml. Levels in 25 women colonized with GBS type III who gave birth to normal infants were significantly higher and ranged from 0.1 to 10.7 microgram/ml (median, 0.78 micrograms/ml). In a study of transplacental passage of antibody, protective levels were found in a number of infants with gestational ages between 28 and 36 weeks.
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With emphasis on work from our laboratory, this paper briefly reviews previous studies which have established the basis for immunity to group B streptococcal infections. Quantitative data are presented on the concentration of antibody to the type-specific polysaccharides of group B streptococci in normal adults and infected infants, the protective level in experimental animals, and the influence of prematurity on transplacental passage of antibody. The role of the polymorphonuclear leukocyte in immunity to group B streptococcal infections is critical as supported by in vitro and in vivo experiments as well as clinical observations. Strategies for prevention include antimicrobial chemoprophylaxis and active immunization. Alternative approaches to adjunctive therapy such as administration of specific immune globulin, polymorphonuclear leukocytes, and exchange transfusions are discussed.
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Strain differences have been postulated to explain the observation that group B Streptococcus type III (GBS III) late-onset disease occurs in only a fraction of colonized infants. To determine the distribution of type-specific polysaccharide antigen (Ag) in GBS III, Ag was measured by rocket immunoelectrophoresis in both supernatant fluids and EDTA extracts and by radial immunodiffusion in multiple HCl extracts of the pellet from cultures of 10 strains of GBS III. Capsular Ag was defined as the sum of Ag in EDTA extracts + Ag in multiple HCl extracts. Both Ag in EDTA extracts and Ag in supernatant fluids correlated with capsular Ag (r = 0.94). GBS III strains were obtained from the blood of 19 infants with late-onset sepsis, from the cerebrospinal fluid or blood of 22 infants with late-onset meningitis, and from mucosal surfaces of both 18 infants and 12 mothers of infants with low levels of type-specific antibody and asymptomatic colonization. Mean values of Ag in supernatant fluids in strains from infants with late-onset sepsis (1.50 +/- 0.08 micrograms/ml) and late-onset meningitis (1.67 +/- 0.09 micrograms/ml) were significantly greater than those in asymptomatic colonization strains (1.14 +/- 0.05 micrograms/ml; P less than 0.001). The number of organisms required for a 50% lethal dose in the chick embryo, determined in 29 strains, was inversely related to Ag in supernatant fluids (r = -0.60). The demonstration that the quantity of capsular Ag produced by GBS III strains is related to their virulence in chick embryos and to their invasiveness in susceptible infants supports the hypothesis that Ag is a virulence factor in humans.
We studied the concentration of circulating human immunoglobulin G (IgG) antibody to the native capsular polysaccharide of group B streptococcus (GBS) type Ib necessary to protect mice against lethal challenge by laboratory and clinical GBS Ib strains. Antibody was measured by an enzyme-linked immunosorbent assay in which native polysaccharide antigen coupled to human serum albumin was used. The assay was standardized by a quantitative precipitation test, using native antigen and specific human IgG antibody purified by affinity chromatography. IgG anti-GBS Ib antibody level-protection curves for 90% lethal dose challenge of mice were sigmoidal. The curves of whole serum and affinity-chromatographed IgG anti-GBS Ib were superimposable. The serum concentrations of human antibody required for complete protection of mice varied with the infecting strain and ranged from 0.038 to 0.175 microgram/ml. Protective levels of human IgG anti-GBS Ib were lower than those we found previously for homologous protection against GBS Ia challenge (range, 0.25 to 1.0 microgram/ml).
Human IgG antibody to the type-specific polysaccharide antigen of group B Streptococcus type Ia in the sera of mice was measured by enzyme-linked immunosorbent assay, previously standardized by quantitative precipitation, 24 hr after passive immunization with human serum or affinity-chromatographed antibody. The concentrations of antibody needed to protect mice against 90% lethal dose challenge varied with the bacterial inoculum and ranged from 0.25 to 1 microgram/ml using five strains of group B Streptococcus type Ia. Affinity-chromatographed antibody gave results comparable to serum, indicating the specificity of the antibody and the absence of other humoral factors in protection with this serum. Sera from 11 infected infants and their mothers had concentrations of antibody of less than or equal to 0.17 micrograms/ml, below the protective level delineated in the experimental model. Twelve percent of 50 adult women and 36% of 25 women colonized with group B Streptococcus type Ia had antibody levels of greater than or equal to 1 microgram/ml.
Between 1973 and 1981, 61 cases of neonatal group B streptococcal early-onset disease occurred among 32,384 infants born at Michael Reese Hospital and Medical Center, Chicago. Forty-one (67%) of the 61 affected infants were bacteremic at birth, implying intrapartum acquisition of infection. No significant deviations from the overall attack rate of 1.9 per 1,000 live births were associated with maternal demographic factors, but increased attack rates were associated with birth weights of less than or equal to 2.5 kg (7.9 per 1,000), rupture of amniotic membranes greater than 18 hr before birth (7.6 per 1,000), and intrapartum fever (6.5 per 1,000). Forty-five (74%) of the 61 affected infants and 15 (94%) of the 16 with fatal outcome had one or more of these three perinatal risk factors. Based on an intrapartum vaginal carriage rate of 16.7% among parturients with perinatal risk factors, an attack rate of 45.5 per 1,000 was estimated for infants born to colonized "high-risk" parturients, a subgroup comprising approximately 3% of our obstetric population. These findings provide a compelling epidemiologic rationale for trials of selective intrapartum chemoprophylaxis of neonatal group B streptococcal early-onset disease.