Variable number of tandem repeats in clinical strains of Haemophilus influenzae

An algorithm capable of identifying short repeat motifs was developed and used to screen the whole genome sequence available for Haemophilus influenzae, since some of these repeats have been shown to affect bacterial virulence. Various di- to hexanucleotide repeats were identified, confirming and extending previous findings on the existence of variable-number-of-tandem-repeat loci (VNTRs). Repeats with units of 7 or 8 nucleotides were not encountered. For all of the 3- to 6-nucleotide repeats in the H. influenzae chromosome, PCR tests capable of detecting allelic polymorphisms were designed. Fourteen of 18 of the potential VNTRs were indeed highly polymorphic when different strains were screened. Two of the potential VNTRs appeared to be short and homogeneous in length; another one may be specific for the H. influenzae Rd strain only. One of the primer sets generated fingerprint-type DNA banding patterns. The various repeat types differed with respect to intrinsic stability as well. It was noted for separate colonies derived from a single clinical specimen or strains passaged for several weeks on chocolate agar plates that the lengths of the VNTRs did not change. When several strains from different patients infected during an outbreak of lung disease were analyzed, increased but limited variation was encountered in al

Effect of Seven-Valent Pneumococcal Conjugate Vaccine on Staphylococcus aureus Colonisation in a Randomised Controlled Trial

Background: Heptavalent pneumococcal conjugate vaccine (PCV7) shifts nasopharyngeal colonisation with vaccine serotype pneumococci towards nonvaccine serotypes. Because of the reported negative association of vaccine serotype pneumococci and Staphylococcus aureus in the nasopharynx, we explored the effect of PCV7 on nasopharyngeal colonisation with S. aureus in children and parents. Methodology/Principal Findings: This study was part of a randomised controlled trial on the effect of PCV7 on pneumococcal carriage, enrolling healthy newborns who were randomly assigned (1: 1: 1) to receive PCV7 (1) at 2 and 4 months of age (2) at 2, 4 and 11 months or (3) no PCV7 (controls). Nasopharyngeal colonisation of S. aureus was a planned secondary outcome. Nasopharyngeal swabs were obtained from all children over a 2-year period with 6-months interval and from one parent at the child's age of 12 and 24 months and cultured for Streptococcus pneumoniae and S. aureus. Between July 2005 and February 2006, 1005 children were enrolled and received either 2-doses of PCV7 (n = 336), 2+1-doses (336) or no dose (n = 333) before PCV7 implementation in the Dutch national immunization program. S. aureus colonisation had doubled in children in the 2+1-dose group at 12 months of age compared with unvaccinated controls (10.1% versus 5.0%; p = 0.019). A negative association for co-colonisation of S. pneumoniae and S. aureus was observed for both vaccine serotype (adjusted odds ratio (aOR) 0.53, 95% confidence interval (CI) 0.38-0.74) and nonvaccine serotype pneumococci (aOR 0.67, 95% CI 0.52-0.88). Conclusions/Significance: PCV7 induces a temporary increase in S. aureus colonisation in children around 12 months of age after a 2+1-dose PCV7 schedule. The potential clinical consequences are unknown and monitoring is warranted

Combination vaccine against invasive meningococcal B and pneumococcal infections: Potential epidemiological and economic impact in the Netherlands

Background: Streptococcus pneumoniae and Neisseria meningitidis group B are among the main causes of invasive bacterial meningitis infections in infants. Worldwide, these diseases lead to significant mortality, morbidity and costs. The societal impact is especially severe since the majority of cases occur in very young infants. A combination vaccine consisting of 9-valent conjugated pneumococcal and meningococcal B components is currently being developed. The aim of this study was to estimate the potential impact and cost effectiveness from the societal perspective of vaccinating infants in The Netherlands with this combination pneumococcal and meningococcal B vaccine versus no vaccination. Methods: A Markov cycle model was developed using epidemiological and healthcare resource use data from 1996 to 2001. This model was used to project the annual costs, benefits and health gains associated with vaccinating all newborns. The base year for the costing was 2003 and all costs and health effects were discounted at 4%. The results of the analysis are expressed in costs per QALY and both probabilistic and univariate sensitivity analyses were used to identify the robustness of the results. Results: Annually, an average of 755 cases of invasive pneumococcal and meningococcal B infection occurred in infants aged 0-10 years in The Netherlands. Introduction of the combination vaccine would prevent 201 cases of meningococcal B meningitis and 165 cases of invasive pneumococcal disease per year. Additionally, 3410 cases of pneumococcal pneumonia and 46 350 cases of otitis media would be prevented. Vaccination would save 35 lives per year and prevent 71 cases of severe sequelae. This translates into 860 life-years gained, or 1128 QALYs gained. Alongside these health gains, vaccination would prevent €17 681 370 of direct medical and indirect costs attributable to meningococcal and pneumococcal infections in The Netherlands. Depending on vaccine price, cost effectiveness varied from €3160 (vaccine price per dose €20) to €32 170 (vaccine price €60 per dose) per QALY. Base-case cost effectiveness (vaccine price €40) was €17 700 per QALY. The model was most sensitive to changes in incidence, vaccine price and duration of protective efficacy. Conclusion: Our results suggest that the introduction of a combination meningococcal B and pneumococcal vaccine into the Dutch infant vaccination programme is potentially cost effective compared with no vaccination

Prevention of meningococcal serogroup B infections in children: A protein-based vaccine induces immunologic memory

Immunologic memory against meningococci was studied in 177 children (100 children were 10-11 years old and 77 were 5-6 years old) 2.5 years after vaccination with hexavalent meningococcal outer membrane vesicle (OMV) vaccine or hepatitis B (HepB) vaccine. Children were revaccinated with monovalent P1.7h,4 meningococcal OMV vaccine. Serum bactericidal antibodies (SBAs) were measured before revaccination and after 4-6 weeks. A minimum 4-fold increase in SBAs against serosubtype P1.7h,4 was detected in 48.5% of the children after hexavalent meningococcal vaccine and in 8.9% after HepB vaccine. Of the initial responders given hexavalent meningococcal vaccine, 78% had 4-fold increase in SBAs against strain P1.4. Thus, immunologic memory is present in toddlers and school-aged children previously given 3 hexavalent meningococcal vaccinations. Booster vaccination with monovalent P1.7h,4 meningococcal OMV vaccine induces a significant increase in SBAs against serosubtype P1.7h,4 and cross-reactivity against other serosubtypes in the hexavalent vaccine