Kinetics of Antibody Persistence following Administration of a Combination Meningococcal Serogroup C and Haemophilus influenzae Type b Conjugate Vaccine in Healthy Infants in the United Kingdom Primed with a Monovalent Meningococcal Serogroup C Vaccine

The kinetics of antibody persistence following the administration of a combination meningococcal serogroup C and Haemophilus influenzae type b (Hib) conjugate vaccine (Menitorix) in the second year of life in children primed with two doses of one of three monovalent meningococcal serogroup C (MCC) vaccines was investigated. The study subjects were administered either Menitorix at 12 to 15 months of age, followed by the seven-valent pneumococcal conjugate vaccine (PCV7) and the measles, mumps, and rubella vaccine 4 to 6 weeks later, or all three vaccines concomitantly at 12 to 15 months of age. Blood samples were collected before and 1, 2, 12, and 24 months after the boosting. Sera were analyzed for meningococcal serogroup C serum bactericidal antibody (SBA) and IgG as well as Hib-polyribosylribitol phosphate (PRP)-specific IgG. The antibody persistence data from this study were compared to those of a prior study of Southern et al. (Clin. Vaccine Immunol. 14:1328-1333, 2007) in which children were given three primary doses of a vaccine containing both the MCC and the Hib vaccines but were boosted only with a Hib conjugate vaccine. The magnitude of the meningococcal SBA geometric mean titer was higher for those subjects primed with the MCC vaccine conjugated to tetanus toxoid (NeisVac-C) than for those primed with one of two MCC vaccines conjugated to CRM₁₉₇ (Menjugate or Meningitec) up to 1 year following boosting. Two years after boosting, the percentages of subjects with putatively protective SBA titers of ≥8 for children primed with NeisVac-C, Menjugate, and Meningitec were 43%, 22%, and 23%, respectively. Additional booster doses of the MCC vaccine may be required in the future to maintain good antibody levels; however, there is no immediate need for a booster during adolescence, as mathematical modeling has shown that persisting herd immunity is likely to control disease for a number of years.A booster dose of meningococcal serogroup C conjugate (MCC) and Haemophilus influenzae type b (Hib) conjugate vaccine was introduced in September 2006 in England and Wales for children in the second year of life in the form of a combined vaccine, Menitorix (GlaxoSmithKline [GSK]), which has tetanus toxoid (TT) as the carrier protein. In England and Wales, infants receive a combined diphtheria toxoid (D), TT, acellular pertussis (aP₅), inactivated poliovirus (IPV), and Hib-TT conjugate vaccine (DTaP₅/IPV/Hib-TT; Pediacel; Sanofi Pasteur) at 2, 3, and 4 months of age; MCC vaccination at 3 and either 4 or 5 months of age; and a seven-valent pneumococcal conjugate vaccine (PCV7; Prevenar; Wyeth Vaccines) at 2 and 4 months of age. Three different MCC vaccine manufacturers'' vaccines are available: two are conjugated to CRM₁₉₇, a nontoxigenic natural variant of diphtheria toxin (Meningitec [Wyeth Vaccines] and Menjugate [Novartis Vaccines]), and one is conjugated to TT (NeisVac-C; Baxter Bioscience). Although the data obtained following the administration of the current primary vaccine series in the United Kingdom have been reported (16), antibody persistence following boosting with Menitorix and priming with two doses of each of the licensed MCC vaccines has not been reported. This report details the immunogenicity data for those receiving the MCC and Hib vaccines, by primary MCC vaccine, for before and at 1, 2, 12, and 24 months after a booster dose of Menitorix administered at 12 to 15 months of age. The rates of antibody decline for those receiving the Hib and MCC vaccines are also compared.     

A pilot study on the effects of Aroclor 1254 ingestion by rhesus and cynomolgus monkeys as a model for human ingestion of PCBs

A pilot study using female cynomolgus (Macaca fascicularis) and female rhesus (Macaca mulatta) monkeys was conducted to study the effects of chronic ingestion of polychlorinated biphenyls (PCBs). Four control and four treated monkeys of each species received an apple juice-gelatin mixture containing 0 and 280 μg Aroclor 1254/kg body weight/day, respectively, 5 days/wk. The cynomolgus monkeys, which were mature monkeys with a poor breeding history, were treated for approximately 55 wk, while the rhesus monkeys, which were just attaining sexual maturity, were treated for approximately 120 wk. After 38 wk on test, the treated and control rhesus monkeys were mated with untreated males. The clinical signs resulting from the Aroclor 1254 ingestion were similar for both species, and the time of onset after initiation of treatment was not appreciably different between the two species. Several treatment and interspecies differences were found with regard to the haematological and serum biochemistry parameters monitored, but age differences between the two species may have contributed to these findings. Periodic analysis of adipose tissue, blood and faecal specimens for PCBs suggested that the rhesus monkey retained more of the ingested PCB than did the cynomolgus monkey. Following mating, all of the treated rhesus monkeys aborted within 30–60 days after becoming pregnant, while all of the control monkeys had viable offspring.     

GPs' classification of headache: is primary headache underdiagnosed?

With a high economic, social, and personal burden, headache remains an important health problem. How UK GPs diagnose headache in the UK is unknown. In this study, a large primary care database was used and diagnostic categories were described for 91121 adult patients with new-onset headache, that is, patients who had not consulted for headache in the previous year. Seventy per cent of headaches were not given a diagnostic label, 24% were diagnosed as primary, and 6% as secondary headaches. It is suggested that GPs' difficulty in diagnosing headache presentations contributes to the high level of morbidity and unmet need in this disease.     

Cephamycins, a New Family of β-Lactam Antibiotics. IV. In Vivo Studies

Cephamycin A was found to be more active in vivo than cephamycin B. In comparison with cephamycin C, cephamycin A was more active against gram-positive organisms but less active against gram-negative organisms. Given subcutaneously, cephamycin C had good in vivo gram-negative activity, comparing favorably with cephalothin and cephaloridine against cephalosporin-susceptible organisms. In general, against the gram-negative organisms, it was more active than cephalothin or cephalosporin C and about as active as cephaloridine. In addition, cephamycin C protected mice against beta-lactamase-producing Proteus cultures, including clinically isolated strains. The compound is remarkably nontoxic. Cephamycin C was detected in the serum and recovered from the urine of treated mice to about the same extent as cephaloridine. Like cephaloridine and cephalosporin C, cephamycin C must be excreted mainly by glomerular filtration, because the use of probenecid did not enhance the therapeutic effectiveness nor concentrations of these agents in the sera of treated mice.     

Temporal summation in myopia and its implications for the investigation of glaucoma

Purpose

We have previously demonstrated the upper limit of complete spatial summation (Ricco's area) to increase in non-pathological axial myopia compared to non-myopic controls. This study sought to investigate whether temporal summation is also altered in axial myopia to determine if this aspect of visual function, like in glaucoma, is influenced by reductions in retinal ganglion cell (RGC) density.

Methods

Achromatic contrast thresholds were measured for a GIII-equivalent stimulus (0.43° diameter) of six different stimulus durations (1–24 frames, 1.1–187.8 ms) in 24 participants with axial myopia (mean spherical refractive error: −4.65D, range: −1.00D to −11.25D, mean age: 34.1, range: 21–57 years) and 21 age-similar non-myopic controls (mean spherical refractive error: +0.87D, range: −0.25D to +2.00D, mean age: 31.0, range: 18–55 years). Measurements were performed at 10° eccentricity along the 90°, 180°, 270° and 360° meridians on an achromatic 10 cd/m² background. The upper limit of complete temporal summation (critical duration, CD) was estimated from the data with iterative two-phase regression analysis.

Results

There was no significant difference (p = 0.90, Mann–Whitney U-test) in median CD between myopes (median: 44.3 ms; IQR: 26.5, 51.2) and non-myopes (median: 41.6 ms; IQR: 27.3, 48.5). Despite RGC numbers underlying the stimulus being significantly lower in the myopic group (p < 0.001), no relationship was observed between the CD estimate and co-localised RGC number (Pearson's r = −0.13, p = 0.43) or ocular length (Pearson's r = −0.08, p = 0.61).

Conclusions

Unlike spatial summation, temporal summation is unchanged in myopia. This contrasts with glaucoma where both temporal and spatial summation are altered. As such, perimetric methods optimised to test for anomalies of temporal summation may provide a means to differentiate between conditions causing only a reduced RGC density (e.g., myopia), and pathological processes causing both a reduced RGC density and RGC dysfunction (e.g., glaucoma).