Immunogenicity of Fractional Doses of Tetravalent A/C/Y/W135 Meningococcal Polysaccharide Vaccine: Results from a Randomized Non-Inferiority Controlled Trial in Uganda

Meningitis are infections of the lining of the brain and spinal cord and can cause high fever, blood poisoning, and brain damage, as well as result in death in up to 10% of cases. Epidemics of meningitis occur almost every year in parts of sub-Saharan Africa, throughout a high-burden area spanning Senegal to Ethiopia dubbed the “Meningitis Belt.” Most epidemics in Africa are caused by Neisseria meningitidis (mostly serogroup A and W135). Mass vaccination campaigns attempt to control epidemics by administering meningococcal vaccines targeted against these serogroups, among others. However, global shortages of these vaccines are currently seen. We studied the use of fractional (1/5 and 1/10) doses of a licensed vaccine to assess its non-inferiority compared with the normal full dose. In a randomized trial in Uganda, we found that immune response and safety using a 1/5 dose were comparable to full dose for three serogroups (A, Y, W135), though not a fourth (C). In light of current shortages of meningococcal vaccines and their importance in fighting meningitis epidemics around the world, we suggest fractional doses be taken under consideration in mass vaccination campaigns

Tetanus after a minor injury leading to death in a previously non-immunized, elderly, Norwegian woman

Tetanus vaccination is part of the Norwegian childhood vaccination program. An elderly woman injured her arm and leg after a minor fall on her outdoor stairs. Two weeks later she presented with trismus. This developed into tetanic spasms, obstructed airways and the need for a tracheostomy. She died 14 days later due to pneumonia and multi-organ failure. ELISA for tetanus toxoid IgG was negative, probably because the patient was born before the introduction of tetanus vaccination in the Norwegian childhood vaccination program. Lack of adherence to the vaccination programs should be considered in patients presenting with symptoms resembling diseases they normally would be protected from. Although the patient presented with typical symptoms the diagnosis was not suspected initially, probably due to the rareness of this disease in Norway

Sequence Type and emm Type Diversity in Streptococcus pyogenes Isolates Causing Invasive Disease in Norway between 1988 and 2003 ▿

The incidence of invasive group A streptococcal disease has increased in Norway since the 1980s. Analysis of 100 isolates recovered from 1988 to 2003 showed an increased genotypic diversity over time, while the prevalence of the strain that dominated in 1988, sequence type (ST)-28/emm-1, decreased. Necrotizing fasciitis was often associated with ST-15/emm-3

Impact of a Pneumococcal Conjugate Vaccination Program on Carriage among Children in Norway▿

In July 2006, the seven-valent pneumococcal conjugate vaccine (PCV7) was introduced in Norway with a reduced (2 doses + 1 boost) dose schedule. Post-PCV7 shifts in pneumococcal reservoirs were assessed by two point prevalence studies of nasopharyngeal colonization among children in day care centers, before (2006) and after (2008) widespread use of PCV7. Nasopharyngeal swabs were obtained from 1,213 children, 611 in 2006 and 602 in 2008. A total of 1,102 pneumococcal isolates were recovered. Serotyping, multilocus sequence typing, and antimicrobial drug susceptibility testing were performed on all isolates. Although carriage of PCV7 serotypes decreased among both vaccinated and unvaccinated children, the overall prevalence of pneumococcal carriage remained high (80.4%) after vaccine introduction. The pneumococcal populations were diverse, and in the shift toward non-PCV7 serotypes, expansion of a limited number of established clonal complexes was observed. While non-antimicrobial-susceptible clones persisted among PCV7 serotypes, antimicrobial resistance did not increase among non-PCV7 serotypes. Direct and indirect protection of PCV7 against nasopharyngeal colonization was inferred from an overall decrease in carriage of PCV7 serotypes. No preference was found for nonsusceptible clones among the replacing non-PCV7 serotypes

Phenotypic and Genotypic Characterization of Streptococcus pneumoniae Strains Colonizing Children Attending Day-Care Centers in Norway▿

A cross-sectional study of nasopharyngeal colonization with Streptococcus pneumoniae was performed among 573 children attending 29 day-care centers (DCCs) in Norway prior to the start of mass vaccination with the heptavalent pneumococcal conjugate vaccine (PCV-7). A sensitive sampling method was employed, including transport in an enrichment broth and serotyping of pneumococci directly from the broth, in addition to traditional single-colony isolation from blood agar plates. The prevalence of carriage was high, peaking at 88.7% in 2-year-olds. More than one serotype was isolated from 12.7% of the carriers. Of 509 isolates obtained, 227 (44.6%) belonged to the PCV-7 serotypes. Penicillin nonsusceptibility was rare (1.8% of the isolates). Nonsusceptibility to erythromycin (5.9%), clindamycin (2.0%), and tetracycline (5.5%) was associated with PCV-7 serotypes (P < 0.001). Multilocus sequence typing was performed on the whole strain collection, revealing 102 sequence types (STs), of which 31 (30.4%) were novel. Eleven isolates (2.2%) belonged to the England14-9 clone, and 19 isolates (3.7%) belonged to, or were single-locus variants of, the Portugal19F-21 clone. The pneumococcal populations within the DCCs were composed of a majority of isolates with STs shared between the DCCs and a minority of isolates with STs unique for each DCC. The highest numbers of different STs, including novel STs, were found within the most frequent serotypes. Our study indicates that carriage of S. pneumoniae is highly prevalent among children in Norwegian DCCs, with a genetically diverse pneumococcal population consisting of unique microepidemic DCC populations

Response to third rubella vaccine dose

Limited data exist on the immunogenicity of a third dose of the measles, mumps, and rubella vaccine (MMR). In this study, our aim was to evaluate the long-term rubella immunogenicity afforded by two childhood MMR doses of the Norwegian vaccination program in a cohort of conscripts and to determine the effect of an additional dose of MMR vaccine, in order to inform vaccination policy. Blood samples from Norwegian conscripts (n = 495) taken both before and eight months after administration of a dose of MMR vaccine were tested using an enzyme immunoassay to measure anti-rubella IgG. Concentrations <5 IU/mL were regarded as negative, 5.0-9.9 IU/mL as equivocal, and ≥10 IU/mL as positive. Overall, the seropositivity before vaccination was 84.6%, and 99.0% of the conscripts had anti-rubella IgG concentrations ≥5 IU/mL. The seropositivity after vaccination was 94.5%, and 99.8% of the conscripts had antibody concentrations ≥5 IU/mL. The geometrical mean IgG concentrations increased from 21.4 IU/mL before vaccination to 28.9 IU/mL after. Four out of five conscripts, with seronegative concentrations before administrations of an additional MMR dose, had equivocal or seropositive results following vaccination. The cohort of young adults in Norway, which was eligible for two childhood MMR doses, was protected against rubella, and efforts should be made to maintain high vaccine coverage to ensure immunity in the future. A third dose of MMR administered in early adulthood led to an increase in the antibody concentration in our cohort and seroconversion for the majority of seronegative persons

Combined Administration of Meningococcal Serogroup B Outer Membrane Vesicle Vaccine and Conjugated Serogroup C Vaccine Indicated for Prevention of Meningococcal Disease Is Safe and Immunogenic

MenBvac and Menjugate are safe and efficacious vaccines. The purpose of this study was to evaluate safety and immunogenicity of the combination (MenB/C) of the lyophilized active components of the conjugated group C vaccine Menjugate when reconstituted with the full liquid group B outer membrane vesicle vaccine MenBvac compared to MenBvac and Menjugate given separately. At 6-week intervals, healthy adults were given one dose of MenB/C followed by two doses of MenBvac (MenB/C group), three doses of MenBvac (MenB group), or one dose of Menjugate and two doses of placebo (MenC group). Injection site reactions were frequent in all groups. However, most reactions were short lasting and mild or moderate in intensity, and the vaccines were found to be well tolerated, with no vaccine-related serious adverse events. MenB/C was immunogenic with regard to both serogroup B and C meningococci. Both the serum bactericidal assay and the enzyme-linked immunosorbent assay analyses showed that the immune responses of the combination vaccine were similar to the immune responses of its separate components MenBvac and Menjugate for both serogroup B and C. In conclusion, the combined MenB/C vaccine is safe and immunogenic. The two vaccines do not interact negatively with each other and can easily be administered in the same syringe. The induced immune responses suggest that the combined vaccine is likely to confer protection against systemic group B disease caused by the vaccine strain as well as against group C meningococcal disease