Immunogenicity and serotype-specific efficacy of a 9-valent pneumococcal conjugate vaccine (PCV-9) determined during an efficacy trial in The Gambia.

This study aimed to determine the immunogenicity of a 9-valent pneumococcal conjugate vaccine (PCV-9) in a subgroup of Gambian children enrolled in a large vaccine efficacy trial. To place the antibody results in context, in this paper we also report previously unpublished data on serotype-specific clinical vaccine efficacy from the main trial. In the sub-study, a single 2-4 ml venous blood specimen was collected from 212 Gambian children 4-6 weeks after the administration of a third dose of PCV-9 or placebo. IgG antibodies to pneumococcal serotype 1, 4, 5, 6B, 9V, 14, 18C, 19F and 23F polysaccharides were measured by ELISA. The proportions of infants with antibody concentrations above 0.2, 0.35 and 1.0 microg/ml, and the geometric mean concentrations (GMCs) of anti-pneumococcal polysaccharide antibodies were substantially higher for each serotype in children who received three doses of PCV-9 than those in the placebo group. Among PCV-9 recipients, GMCs ranged between 2.61 and 11.09 microg/ml with the highest being against serotype 14 and the lowest against 9V polysaccharide. The estimated overall protective antibody level for all nine serotypes, based on the vaccine efficacy against vaccine-type invasive pneumococcal disease (IPD) of 77% (95% CI: 51, 90) observed in the trial, was 2.3 microg/ml (95% CI: 1.0, 5.0). The PCV-9 studied was immunogenic in a Gambian population where it was also found to be efficacious.

Design of vaccine equivalence/non-inferiority trials with correlated multiple binomial endpoints.

Immunogenicity trials that study the immune responses to vaccination are often used in the vaccine development process as alternatives to clinical efficacy trials. The comparisons of immune responses among various treatment groups are conducted in a non-inferiority or equivalence framework. When there exists a level of immune response that correlates with protection against disease, it is of interest to compare the proportion of responders as defined as response above a specific level or as a predefined increase in immune levels for post-vaccination levels above pre-vaccination levels. Since vaccines often contain several antigens, the correlations between the immune responses need to be taken into account in the analysis. In this paper, we describe appropriate testing methods for demonstrating the non-inferioritylequivalence of two treatments on each of the binomial endpoints. We conduct a comprehensive simulation study to shed light on how the Type I error and power are affected and to what extent when correlated multiple binomial endpoints are present in the vaccine trials. We also illustrate the computation of power for assessment of non-inferioritylequivalence in real studies.

Cytologic observations on axotomized feline Betz cells. II. Quantitative ultrastructural findings.

Quantitative electron microscopic examination was made of Betz cells of two unoperated cats as well as cats subjected to left lateral funiculotomy 5, 10, 28 and 49 days before sacrifice. The percent cytoplasmic composition of chromatolyzed, right-sided Betz cells contributed by cisternal elements of RER, Golgi apparatus and dense bodies and the percent perikaryal membrane apposed by subsurface cisterns were unchanged from the normal despite marked qualitative alterations of the cytoplasm. However, 49 days postoperatively mitochondrial numerical density of axotomized, right-sided Betz cells was significantly less than at 0, 10 and 28 days post funiculotomy. Importantly, normal-appearing Betz cells ipsilateral to corticospinal tract section showed an increase in mitochondrial numerical density 5 days postoperatively. Operation did not induce change in the % perikaryal coverage by axosomatic boutons. Retraction of axosomatic boutons, though often reported for other neuronal populations undergoing axon reaction, is not a necessary feature of the axon reaction of feline Betz cells.

Resistant ascites in alcoholic liver cirrhosis: course and prognosis.

A group of 29 patients with decompensated cirrhosis of the liver who retained a large amount of ascites under a hospital regimen during two months or longer was identified. The prognosis for this selected group of patients, while grave [during continuous hospitalization 11 out of 29 patients (= 38%) died], is not without hope: 18 patients (62%) improved and could be discharged from the hospital. Their further course was influenced by resumption of alcohol usage. Five of 11 (45.4%) who resumed drinking died due to hepatic causes within 10 months. Of the remaining six only one lost his ascites. Those who abstained (7 patients) remained alive for an average follow-up of 33 months and all lost their ascites. Alcohol resumption significantly decreased both survival (P less than 0.05) and ascites resorption (P less than 0.0015). Continued abstinence from alcohol may thus obviate the need for surgical measures to relieve ascites in these patients.