Randomized,double-blind,controlled trial of pneumococcal vaccination in renal transplant recipients

Renal transplant recipients are at increased risk for developing invasive pneumococcal disease but may have a poor response to pneumococcal polysaccharide vaccine (PPV23). For them, pneumococcal conjugate vaccine (PCV7) may be more immunogenic. Patients were given a single dose of PPV23 or PCV7 in our randomized, controlled, double-blind trial. Immunogenicity was assessed 8 weeks after vaccination by serotype-specific enzyme-linked immunosorbent assay (ELISA) and opsonophagocytic assay (OPA). Baseline demographics, renal function, time since transplantation, and immunosuppression were comparable. In the PCV7 group, the vaccine response rate was improved for serotypes 23F (P=.046) and 6B (P=.067), and mean fold increases in antibody titer were higher for serotypes 23F (P=.046) and 9V (P=.09). The response rate and mean fold increase in OPA titers were not significantly different between groups. There was a trend toward enhanced immunogenicity for PCV7 by ELISA. However, functional antibody responses were not different.     

Immunogenicity of a combined schedule of 7‐valent pneumococcal conjugate vaccine followed by a 23‐valent polysaccharide vaccine in adult recipients of heart or lung transplants

R. Gattringer, H. Winkler, S. Roedler, P. Jaksch, H. Herkner, H. Burgmann. Immunogenicity of a combined schedule of 7‐valent pneumococcal conjugate vaccine followed by a 23‐valent polysaccharide vaccine in adult recipients of heart or lung transplants.
Transpl Infect Dis 2011: 13: 540–544. All rights reserved Abstract: A combined schedule of 7‐valent pneumococcal conjugate vaccine (PCV7) followed by 23‐valent pneumococcal polysaccharide vaccine (PPV23) was evaluated retrospectively in 26 adult recipients of heart or lung transplants. PCV7 was immunogenic in these patients but there appeared to be no benefit from the additional PPV23 dose.     

Donor immunization with pneumococcal conjugate vaccine and early protective antibody responses following allogeneic hematopoietic cell transplantation

Patients undergoing hematopoietic cell transplantation (HCT) are at increased risk for infections with Streptococcus pneumoniae and have long-lasting, impaired antibody responses to pneumococcal polysaccharide vaccines. We examined whether donor immunization with a heptavalent pneumococcal conjugate vaccine (PCV7) would elicit protective antibody responses to additional doses of vaccine administered early after transplantation. Ninety-six patients scheduled to receive an allogeneic hematopoietic cell transplant were randomized with their donors to receive either a dose of PCV7 vaccine or no vaccine before transplantation. All patients received PCV7 at 3 months, 6 months, and 12 months following transplantation, and serotype-specific antibody concentrations were determined after each dose. Following HCT, geometric mean antibody concentrations of patients in the immunized donor group were significantly higher for 5 of the 7 vaccine serotypes after one dose (P <.05) and for 4 of the 7 serotypes after 2 doses of vaccine (P <.03). Sixty-seven percent of patients in the immunized donor group had presumed protective IgG concentrations more than or equal to 0.50 microg/mL to all 7 serotypes following the first dose of vaccine compared to 36% in the unimmunized donor group (P =.05). After the third dose of vaccine, both groups had more than 60% of patients with concentrations at least 0.50 microg/mL to all vaccine serotypes. Donor immunization enhances early antibody responses of patients undergoing HCT to pneumococcal conjugate vaccine. A 3-dose schedule of PCV7 vaccine at 3, 6, and 12 months is immunogenic in these patients regardless of donor immunization.     

Pneumococcal Vaccination in Adults: What Can We Learn From Observational Studies That Evaluated PCV13 and PPV23 Effectiveness in the Same Population?

IntroductionFifteen and 20-valent pneumococcal conjugate vaccines (PCV15; PCV20) were recently licensed to prevent pneumococcal disease in adults. In the absence of efficacy or effectiveness data for these new vaccines, studies comparing 23-valent pneumococcal polysaccharide vaccine (PPV23) and PCV13 might help inform decision-making on how to best implement expanded-valency PCVs. Comparing PPV23 and PCV13 is problematic, as no head-to-head clinical trials evaluated efficacy. Comparing effectiveness results across observational studies that vary by population, design, and outcomes is difficult. To address these limitations, we undertook a narrative review of studies that assessed PPV23 and PCV13 vaccine effectiveness (VE) in the same adult populations.MethodsWe conducted a literature search in PubMed and Google Scholar and screened 525 studies using a standardized evaluation framework.ResultsNine studies met inclusion criteria, all from high-income countries. None evaluated invasive pneumococcal disease (IPD) alone. VE against vaccine-type pneumococcal pneumonia ranged from 2 to 6% for PPV23 and 41 to 71% for PCV13. VE against pneumococcal pneumonia or severe pneumococcal disease (IPD or pneumococcal pneumonia) ranged from ?10 to 11% for PPV23, 40 to 79% for PCV13, and 39 to 83% for sequential PCV13/PPV23. VE against all-cause pneumonia or lower respiratory tract infection ranged from ?8 to 3% for PPV23 and 9 to 12% for PCV13.ConclusionsOverall, PCV13 demonstrated better protection than PPV23 against pneumococcal disease and all-cause respiratory outcomes in the included studies. Where evaluated, sequential PCV13/PPV23 vaccination showed little benefit over PCV13 alone. Results support the use of PCVs to protect against pneumococcal disease and respiratory infections in adults.     

Heptavalent pneumococcal conjugate vaccine elicits similar antibody response as standard 23-valent polysaccharide vaccine in adult patients with RA treated with immunomodulating drugs

The objectives of the study were to compare antibody response in immunosuppressed patients with rheumatoid arthritis (RA) after vaccination with heptavalent pneumococcal conjugate vaccine (PCV7) to that of RA patients and healthy controls vaccinated with 23-valent polysaccharide vaccine (PPV23) and to study the impact of disease and/or treatment characteristics and type of vaccine on antibody response following pneumococcal vaccination in patients with RA. In total, 253 RA patients treated with methotrexate (MTX), anti-TNF blockers as monotherapy or anti-TNF + MTX were vaccinated with a single dose (0.5 ml) of PCV7. In addition, 149 RA patients receiving corresponding treatments and 47 healthy controls were vaccinated with a single dose (0.5 ml) of PPV23. Serotype-specific IgG to 23F and 6B were measured at vaccination and 4–6 weeks after vaccination using ELISA. Antibody response ratio (ARR), i.e. ratio between post-/prevaccination antibody levels, was compared between corresponding treatment groups. Differences in ARR were analysed using analysis of variance. Positive antibody response (posAR) was defined as equal to or greater than twofold increase in prevaccination antibody levels. Possible predictors of posAR were analysed using logistic regression model. Corresponding RA treatment groups showed similar ARR and posAR for both serotypes regardless of vaccine type. Higher age at vaccination and concomitant MTX were identified as predictors of impaired posAR for both serotypes tested, whereas type of vaccine did not influence posAR significantly. PCV7 elicits similar antibody response as PPV23 in patients with RA receiving immunosuppressive treatment. In RA patients, higher age and MTX treatment but not type of vaccine predicted impaired posAR.     

Pneumococcal conjugate vaccine provides early protective antibody responses in children after related and unrelated allogeneic hematopoietic stem cell transplantation

Following allogeneic hematopoietic stem cell transplantation (alloHSCT), children are at risk of life-threatening pneumococcal infections. Whereas vaccination with polysaccharide vaccines fails to elicit protective immunity in most alloHSC transplant recipients, pneumococcal conjugate vaccines may effectively prevent invasive disease by eliciting T-cell-dependent antibody responses. Here, we report safety and immunogenicity in 53 children immunized with a regimen of 3 consecutive doses of a heptavalent pneumococcal conjugate vaccine (7vPCV) in monthly intervals starting 6 to 9 months after alloHSCT. Immunization was well tolerated with no vaccine-related serious adverse events. Serologic response rates evaluable in 43 patients ranged from 41.9% to 86.0% and 58.1% to 93.0% after 2 and 3 vaccinations, respectively, with 55.8% and 74.4% of patients achieving protective antibody levels to all 7 vaccine serotypes. Our study provides the first evidence that vaccination with 7vPCV is safe and elicits protective antipneumococcal antibody responses in pediatric recipients of related or unrelated donor alloHSC transplants within the first year following transplantation. This trial was registered at www.clinicaltrials.gov as NCT00169728.     

Kinetics of antibody concentration and avidity for the assessment of immune response to pneumococcal vaccine among children with bone marrow transplants

The kinetics of the immune response to the 23-valent pneumococcal polysaccharide vaccine (PPV) were studied in 38 children who received bone marrow transplants (BMTs). Anti-pneumococcal antibody concentrations increased 1 and 3 months after vaccination for all 5 serotypes tested, but, in 21 children, the vaccine was not adequately immunogenic. Children vaccinated <18 months after receiving a BMT had a 4.2-fold increased odds of poor response (P=. 06). Antibody concentrations returned close to baseline levels 9 months after vaccination. Avidity declined significantly as early as 1 month after vaccination and remained low thereafter. Antibody concentration responses to PPV were superior among 9 healthy control children (P=.001); 37 of 38 children with a BMT elicited adequate, persistent immune responses to Haemophilus influenzae conjugate vaccine. Immune responses to PPV in children with a BMT are suboptimal, short lived, and associated with declining avidity. The different kinetics of antibody concentration and avidity indicate that both markers should be used for evaluating pneumococcal vaccines in this high-risk population.     

Emerging pneumococcal carriage serotypes in a high-risk population receiving universal 7-valent pneumococcal conjugate vaccine and 23-valent polysaccharide vaccine since 2001

Background  

In Australia in June 2001, a unique pneumococcal vaccine schedule commenced for Indigenous infants; seven-valent pneumococcal conjugate vaccine (7PCV) given at 2, 4, and 6 months of age and 23-valent pneumococcal polysaccharide vaccine (23PPV) at 18 months of age. This study presents carriage serotypes following this schedule.     

Routine Pneumococcal Vaccination of Children Provokes New Patterns of Serotypes Causing Invasive Pneumococcal Disease in Adults and Children

IntroductionRoutine vaccination of infants with protein-conjugated 7-valent pneumococcal vaccine (PCV7) begun in 2000 initiated a sea change of prevalent serotypes (STs) in invasive pneumococcal disease (IPD). The authors investigated in 1 community all STs causing IPD during 5 years before (PRE) and 2, 5-year periods after (POST1 and POST2) its initiation and found that PCV7 adversely affected ST coverage of 23-valent pneumococcal polysaccharide vaccine (PPV23) among adults.MethodsFrom 1996–2010, 620 consecutive Streptococcus pneumoniae IPD strains from adults (521) and children (99) hospitalized with IPD in Huntington, WV, were collected. Each strain was typed by Quellung reaction. The Marshall University Institutional Review Board approved this study.ResultsBy 6 to 10 years after the initiation of PCV7, IPD in children decreased significantly, whereas IPD in adults increased significantly. In both adults and children, IPD due to PCV7 STs decreased significantly. In adults with IPD, PCV7 STs were replaced by several non-PCV7 STs including STs contained in PPV23 but not in PCV7 and STs not contained in either vaccine. IPD due to 4 nonsusceptible STs included in PCV7 decreased from PRE to POST1 and POST2. IPD due to nonsusceptible STs not included in PCV7 increased from PRE to POST1 and POST2.ConclusionsRoutine PCV7 decreased IPD in children but not in adults. Predominant STs changed—children exhibited fewer PCV7 STs and adults exhibited fewer PCV7 and PPV23 STs—reducing vaccine coverage and increasing the risk of replacement STs causing IPD in adults.     

Systemic reaction to pneumococcal vaccine: How common in pediatrics?

The 23-valent-polysaccharide pneumococcal vaccine (PPV23) is currently recommended for patients at high risk for invasive disease from Streptococcus pneumoniae. It is also frequently used in the evaluation of patients with suspected immunodeficiency. Reports of systemic adverse reactions are rare. Our objective is to describe a patient with an apparent systemic reaction to PPV23 and review our hospital's 2-year experience with pneumococcal vaccine. Chart review of 173 patients given PPV23 between January 1, 2004 and December 31, 2005 revealed five who had significant adverse reactions, including local cellulitis, fever, and vomiting. Variables considered included age at immunization, indication for PPV23, and prior pneumococcal vaccines. The mean age of all patients given PPV23 during the defined time period was 8.6 years, and the most common indication for vaccination was recurrent infection. Of those patients who had adverse reactions, the mean age was 6.5 years. The time from prior pneumococcal vaccination was a mean of 20 months in children who did not have an adverse reaction. None of the patients who had an adverse reaction had documentation of receiving PPV23 before. Local reactions to PPV23 occur in approximately 50% of recipients, and revaccination of immunocompetent individuals increases the risk for local reaction. Systemic reactions are less common and only occur in approximately 1% of recipients. Our patient had no identifiable risk factors for development of an adverse reaction. Additional studies are indicated to determine whether there are identifiable risk factors for the development of adverse reactions to PPV23.     

Immunogenicity of pneumococcal vaccination of patients with cochlear implants

BACKGROUND: Pneumococcal meningitis is a rare but potentially fatal complication of cochlear implantation. METHODS: A prospective study was conducted of the immunogenicity of pneumococcal vaccination in 174 patients with cochlear implants (CIs). The cohort was divided into groups of patients with impaired hearing due to meningitis (P(1)), cranial malformations (P(2)), or an unknown cause (P(3)) and was stratified by age as follows: <2 years (A(1)), 2-5 years (A(2)), and >5 years (A(3)). We determined immunoglobulin (Ig) levels for IgG subclasses 1-4 and serum concentrations of antibodies against pneumococci before and 4-6 weeks after vaccination. Group A(1) received the 7-valent pneumococcal conjugate vaccine (PCV-7), group A(2) received PCV-7 or the 23-valent pneumococcal polysaccharide vaccine (PPV-23), and group A(3) received PPV-23. RESULTS: IgG, IgM, and IgG1 levels were significantly lower in group P(1), compared with the other patient groups and with historic data for healthy control subjects, suggesting a decreased antibody response. Group P(1) had lower levels of pneumococcal antibodies, compared with groups P(2) and P(3) before vaccination (P<.05, pneumococcal serotypes 4 and 9V). Irrespective of the underlying condition, all patients showed a sufficient antibody response after 1 dose of vaccine. In children 2-5 years of age, PCV-7 was significantly more immunogenic than PPV-23. CONCLUSIONS: PCV-7 should be administered to all CI recipients younger than 6 years and older than 6 years who are at an increased risk for bacterial meningitis. CI recipients with a history of bacterial meningitis should undergo immunological evaluation.     

Donor immunization with Haemophilus influenzae type b (HIB)-conjugate vaccine in allogeneic bone marrow transplantation

Bone marrow transplant patients are at increased risk for infections with polysaccharide encapsulated organisms and respond poorly to polysaccharide vaccines. We evaluated the effect of donor immunization with Haemophilus influenzae type b (HIB) polysaccharide-conjugate vaccine on recipient antibody responses following allogeneic bone marrow transplantation. Thirty-two allogeneic transplant patients and their donors were immunized before transplantation with HIB-conjugate, tetanus toxoid and 23-valent pneumococcal vaccines. Following transplantation, patients received HIB-conjugate and tetanus toxoid vaccines at 3, 6, 12, and 24 months and 23-valent pneumococcal vaccine at 12 and 24 months. Thirty-three patients with unimmunized donors were immunized following transplantation in an identical manner. Patients whose donors were immunized had significantly higher total anti-HIB antibody concentrations at 3 months (P = .0001), 6 months (P = .0001), 12 months (P = .0001), and 24 months (P = .002) after transplant compared with patients whose donors were unimmunized. Higher antitetanus toxoid antibody concentrations were also noted in patients with immunized donors, whereas donor immunization with pneumococcal vaccine had no effect on antibody concentrations following transplantation. Donor immunization with HIB-conjugate vaccine resulted in higher antibody concentrations in patients as early as 3 months after allogeneic transplantation and may be an effective strategy to prevent HIB infections.     

Pneumococcal disease in adult solid organ transplantation recipients

In solid organ transplant(SOT) recipients, Streptococcus pneumoniae can cause substantial morbidityand mortality ranging from non-invasive to invasive diseases, including pneumonia, bacteremia, and meningitis, with a risk of invasive pneumococcal disease 12 times higher than that observed in non-immunocompromised patients. Moreover, pneumococcal infection has been related to graft dysfunction. Several factors have been involved in the risk of pneumococcal disease in SOT recipients, such as type of transplant, time since transplantation, influenza activity, and nasopharyngeal colonization. Pneumococcal vaccination is recommended for all SOT recipients with 23-valent pneumococcal polysaccharides vaccine. Although immunological rate response is appropriate, it is lower than in the rest of the population, decreases with time, and its clinical efficacy is variable. Booster strategy with 7-valent pneumococcal conjugate vaccine has not shown benefit in this population. Despite its relevance, there are few studies focused on invasive pneumococcal disease in SOT recipients. Further studies addressing clinical, microbiological, and epidemiological data of pneumococcal disease in the transplant setting as well as new strategies for improving the protection of SOT recipients are warranted.     

Conjugate pneumococcal vaccine in HIV-infected Ugandans and the effect of past receipt of polysaccharide vaccine

We investigated the immunogenicity of a 7-valent conjugate pneumococcal vaccine (CPV) in human immunodeficiency virus-infected Ugandan adults and measured the effect of past pneumococcal polysaccharide vaccine (PPV) receipt given as part of a controlled trial. Two doses of CPV, 4 weeks apart, were given to 54 past PPV recipients and 55 past placebo recipients (84% female; median CD4 cell count, 251 cells/ microL [range, 1-936 cells/ microL]). Postvaccination anticapsular immunoglobulin G (IgG) concentrations were directly correlated with CD4 cell count (P < .01 for all serotypes). There were significant increases in anticapsular IgG concentrations for all serotypes after the first dose (P < .01) and for all serotypes except 14 and 9V after the second dose. Past receipt of PPV did not affect vaccine response.     

Long-term Comparative Immunogenicity of Protein Conjugate and Free Polysaccharide Pneumococcal Vaccines in Chronic Obstructive Pulmonary Disease

Background.?Although the 23-valent pneumococcal polysaccharide vaccine (PPSV23) protects against invasive disease in young healthy persons, randomized controlled trials in chronic obstructive pulmonary disease (COPD) have demonstrated no benefit in the intention-to-treat population. We previously reported that the 7-valent diphtheria-conjugated pneumococcal polysaccharide vaccine (PCV7) is safe and induced greater serotype-specific immunoglobulin G (IgG) and functional antibody than did PPSV23 1 month after vaccination. We hypothesized that these advantages would persist at 1 and 2 years. Methods.?One hundred eighty-one patients with moderate to severe COPD were randomized to receive PPSV23 (n?=?90) or PCV7 (1.0?mL; n?=?91). We measured IgG by enzyme-linked immunosorbent assay and assessed functional antibody activity by a standardized opsonophagocytosis assay, reported as a killing index (OPK). We determined differences in IgG and OPK between vaccine groups at 1 and 2 years. Results.?Relative to PPSV23, PCV7 induced greater OPK at both 1 and 2 years for 6 of 7 serotypes (not 19F). This response was statistically greater for 5 of 7 serotypes at 1 year and 4 of 7 at 2 years. Comparable differences in IgG were observed but were less often statistically significant. Despite meeting Centers for Disease Control and Prevention criteria for PPSV23 administration, almost 50% of individuals had never been vaccinated. No differences in the frequency of acute exacerbations, pneumonia, or hospitalization were observed. Conclusions.?PCV7 induces a greater functional antibody response than PPSV23 in patients with COPD that persists for 2 years after vaccination. This superior functional response supports testing of conjugate vaccination in studies examining clinical end points. Clinical Trials Registration: NCT00457977.     

Early hematopoietic reconstitution after clinical stem cell transplantation: evidence for stochastic stem cell behavior and limited acceleration in telomere loss

Our inability to purify hematopoietic stem cells (HSCs) precludes direct study of many aspects of their behavior in the clinical hematopoietic stem cell transplantation (HSCT) setting. We indirectly assessed stem/progenitor cell behavior in the first year after HSCT by examining changes in neutrophil telomere length, X-inactivation ratios, and cycling of marrow progenitors in 25 fully engrafted allogeneic HSCT recipients. Donors were sampled once and recipients at engraftment and 2 to 6 months and 12 months after HSCT. Telomere length was measured by an in-gel hybridization technique, X-inactivation ratios were measured by the human androgen receptor assay, and cell cycle status was determined by flow cytometric analysis of pyronin Y- and Hoechst 33342-stained CD34(+)CD90(+) and CD34(+)CD90(-) marrow cells. Compared with their donors, recipients' telomeres were shortened at engraftment (-424 base pairs [bp]; P <.0001), 6 months (-495 bp; P =.0001) after HSCT, and 12 months after HSCT (-565 bp; P <.0001). There was no consistent pattern of change in telomere length from 1 to 12 months after HSCT; marked, seemingly random, fluctuations were common. In 11 of 11 informative recipients, donor X-inactivation ratios were faithfully reproduced and maintained. The proportion of CD34(+)CD90(+) progenitors in S/G(2)/M was 4.3% in donors, 15.7% at 2 to 6 months (P <.0001) after HSCT, and 11.5% at 12 months after HSCT (P <.0001, versus donors; P =.04, versus 2-6 months). Cycling of CD34(+) CD90(-) progenitors was largely unchanged. We infer that (1) HSCT-induced accelerated telomere loss is temporary and unlikely to promote graft failure or clonal hematopoietic disorders and (2) the striking fluctuations in telomere length and variation in pattern of telomere loss reflect stochastic determination of HSC fate after HSCT.     

Combined schedules of pneumococcal conjugate and polysaccharide vaccines: is hyporesponsiveness an issue?

Streptococcus pneumoniae is a major cause of morbidity and mortality in children less than 5 years of age. Prevention of pneumococcal disease and death in children in the developing world through vaccination with recently developed, highly efficacious pneumococcal conjugate vaccines (PCVs) is now possible. Schedules combining PCV with 23-valent pneumococcal polysaccharide vaccine (PPV23) have been studied and proposed as a means to expand disease protection against serotypes not included in the PCVs. Studies of group A and C meningococcal polysaccharide vaccine and repeated doses of PPV23 in adults and children have shown that a state of immune tolerance, or hyporesponsiveness, can develop to repeated polysaccharide vaccine antigen exposures. In this Review, we describe the evidence for and against this hyporesponsiveness and explore the possible mechanisms for such an occurrence.     

Indirect effect of conjugate vaccine on adult carriage of Streptococcus pneumoniae: an explanation of trends in invasive pneumococcal disease

BACKGROUND: Use of heptavalent protein-polysaccharide pneumococcal conjugate vaccine (PCV7) has been associated with decreases in PCV7-type invasive pneumococcal disease and nasopharyngeal (NP) carriage in children. Vaccine use has also indirectly decreased the rate of invasive disease in adults, presumably through decreased transmission of pneumococci from vaccinated children to adults. METHODS: We conducted NP carriage surveys in 8 villages in Alaska in 1998-2004. Streptococcus pneumoniae isolates were characterized by serotype and antimicrobial susceptibility. We analyzed trends in serotype distribution, antibiotic resistance, and factors associated with adult carriage of PCV7-serotype pneumococci before and after the introduction of PCV7 in 2001. RESULTS: We collected 15,598 NP swabs; overall, 52% of adults living in the villages surveyed participated in the colonization study. The proportion of adult carriers with PCV7-type pneumococcal carriage decreased from 28% of carriers in 1998-2000 to 4.5% of carriers in 2004 (P<.0001). Among adults, the proportion of colonizing isolates that were resistant to penicillin decreased from 13% in 1998-2000 to 6% in 2004 (P=.05), whereas the percentage of isolates with intermediate susceptibility to penicillin increased from 12% in 1998-2000 to 19% in 2004 (P<.01). Adults were more likely to carry PCV7-type pneumococci if they lived with a child <5 years old or if they lived with a child who had not been age-appropriately vaccinated with PCV7. CONCLUSIONS: Pediatric vaccination with PCV7 has resulted in decreased PCV7-type pneumococcal carriage among adults and helps to explain recent decreases in the rate of PCV7-type invasive pneumococcal disease among adults.     

Impact of a conjugate vaccine on community-wide carriage of nonsusceptible Streptococcus pneumoniae in Alaska

BACKGROUND: Streptococcus pneumoniae is a leading cause of invasive bacterial disease and pneumonia among children. Antimicrobial resistance among pneumococci has increased in recent years and complicates treatment. The introduction of heptavalent pneumococcal conjugate vaccine (PCV7) could reduce acquisition of antimicrobial-resistant pneumococci. METHODS: We obtained 1350 nasopharyngeal swabs for culture from 1275 children aged 3-59 months presenting at 3 clinics in Anchorage, Alaska, during the winters of 2000, 2001, and 2002, as PCV7 was being introduced into the routine immunization schedule. We recorded the frequency of use of antibiotics as well as the dates of doses of PCV7 for enrolled children. We used multivariate logistic regression modeling to identify independent risk factors for overall carriage of pneumococci and carriage of PCV7-type pneumococci, cotrimoxazole-nonsusceptible (COT-NS) pneumococci, or penicillin-nonsusceptible (PCN-NS) pneumococci. RESULTS: The proportion of children who were up-to-date for age, with respect to PCV7 vaccination, increased from 0% in 2000 to 55% in 2002. Carriage of PCV7-type pneumococci decreased by 43% (P<.0001). Risk of carriage of PCV7-type pneumococci was lower in 2002 than in 2000, independent of vaccination status, suggesting an indirect effect of vaccination. Carriage of COT-NS, but not PCN-NS, pneumococci also decreased (38%; P=.02), not only among vaccinated children but also among unvaccinated children without recent use of antibiotics. CONCLUSIONS: Introduction of PCV7 into the routine infant immunization schedule in a community with a high prevalence of antimicrobial-resistant pneumococci appears to reduce transmission of PCV7 vaccine serotypes and COT-NS pneumococci but has no impact on overall carriage of pneumococci or carriage of PCN-NS pneumococci.     

Incidence of invasive pneumococcal disease among elderly people in Southern Catalonia, Spain, 2002-2009: an increase in serotypes not contained in the heptavalent conjugate vaccine

Population-based surveillance study conducted among persons ≥ 65 years old in Southern Catalonia, Spain during 2002-2009. All cases with isolation of pneumococcus from normally sterile bodily fluids were included. Incidence rates of invasive pneumococcal disease (IPD) as well as rates of infections caused by serotypes included in the heptavalent pneumococcal conjugate vaccine (PCV7) and the 23-valent polysaccharide pneumococcal vaccine (PPV23) were compared for early (2002-2005) and contemporary (2006-2009) periods. Mean incidence rate (per 100,000 population-year) of IPD across study period was 48.0 [95% CI (confidence interval): 30.1-72.5]. Incidence rates for PCV7 serotypes slightly decreased by 21% between 2002-2005 and 2006-2009 (from 9.2 to 7.3; p = 0.511) whereas rates of IPD due to nonPCV7 serotypes largely increased by 172% (from 15.6 to 42.4; p < 0.001) during the same period. For PPV23 but nonPCV7 types, incidence rates increased by 146% (from 10.9 to 26.9; p < 0.001) whereas rates for nonPPV23 serotypes increased by 237% (from 4.6 to 15.5; p = 0.001). As an overall effect of these changes, the incidence of all IPD increased by a significant 69% (95% CI: 29%-110%). Specific incidence rates of serotypes 6A (from 1.7 to 4.1; p = 0.182), 7F (from 1.7 to 5.7; p = 0.052) and 19A (from 0.6 to 6.2; p = 0.004) substantially increased between both periods. According to these findings, Southern Catalonia region can be classified as a mesoendemic area of pneumococcal infections among elderly people, with a recent increase incidence of some nonPCV7 serotypes (especially 19A).