Vaccine-serotype Colonization Research Articles

Dose-specific Effectiveness of 7- and 13-Valent Pneumococcal Conjugate Vaccines Against Vaccine-serotype Streptococcus pneumoniae Colonization in Children.

Reduced-dose pneumococcal conjugate vaccine (PCV) schedules are under consideration in countries where children are recommended to receive 3 doses. Whereas PCV-derived protection against vaccine-serotype colonization is responsible for herd effects of vaccination, dose-specific PCV effectiveness against colonization endpoints is not known. We aimed to assess the performance of differing PCV schedules against vaccine-serotype colonization in children. From 2009-2016, we monitored pneumococcal carriage in southern Israel, where children should receive PCV at ages 2 months, 4 months, and 12 months (2 primary [p] +1 booster [b] schedule). We analyzed nasopharyngeal swabs and vaccination histories from 5928 children aged 0-59 months without symptoms of diseases potentially attributable to pneumococci. Matching individuals on age, sex, ethnicity, visit timing, and recent antibiotic receipt, we measured schedule-specific 7-valent PCV (PCV7) and 13-valent PCV (PCV13) effectiveness against vaccine-serotype colonization in a modified case-control framework. We sampled from the distribution of all possible case-control match assignments for statistical analyses. Receiving 2 primary-series PCV13 doses conferred 53% (95% confidence interval [CI], 32-67%) protection against PCV13-serotype colonization at ages ≤12 months; 1 primary-series dose was not protective. A 2p+1b PCV13 series conferred 40% (95% CI, 4-67%) and 62% (95% CI, 33-83%) protection against PCV13-serotype colonization at ages 13-24 months and 25-59 months, respectively. Estimates suggested greater PCV13-conferred protection against PCV7-targeted serotypes than the 6 PCV13-only serotypes. As compared to children receiving 2p+1b PCV13 dosing, those receiving 1p+1b and 2p+0b schedules experienced 2.05-fold (95% CI, 1.12-5.00) and 3.33-fold (95% CI, 2.28-4.93) greater odds, respectively, of vaccine-serotype pneumococcal colonization at ages 13-24 months. Our results demonstrate real-world effectiveness of 2p+1b PCV dosing against vaccine-serotype colonization. Reduced-dose schedules may confer lower protection against vaccine-serotype carriage during and beyond the first year of life.

Imputing the Direct and Indirect Effectiveness of Childhood Pneumococcal Conjugate Vaccine Against Invasive Pneumococcal Disease by Surveying Temporal Changes in Nasopharyngeal Pneumococcal Colonization.

The limited capability in most low- to middle-income countries to study the benefit of pneumococcal conjugate vaccine (PCV) in protecting against invasive pneumococcal disease (IPD) calls for alternate strategies to assess this. We used a mathematical model to predict the direct and indirect effectiveness of PCV by analyzing serotype-specific colonization prevalence and IPD incidence prior to and following childhood PCV immunization in South Africa. We analyzed IPD incidence from 2005 to 2012 and colonization studies undertaken in human immunodeficiency virus (HIV)-uninfected and HIV-infected child-mother dyads from 2007 to 2009 (pre-PCV era), in 2010 (7-valent PCV era), and in 2012 (13-valent PCV era). We compared the model-predicted changes in IPD incidence with observed changes in IPD incidence, according to HIV status, in children aged 3 months-5 years and in women aged 18-45 years. We observed reductions in vaccine-serotype colonization and IPD due to vaccine serotypes among children and women after PCV introduction. Using the changes in vaccine-serotype colonization data, the model-predicted changes in vaccine-serotype IPD incidence rates were similar to the observed changes in PCV-unvaccinated children and adults, but not among children under age 24 months. Surveillance of colonization prior to and following PCV use can be used to impute the indirect protection afforded by PCV in unvaccinated age groups, including those in high-HIV-prevalence settings.

Pneumococcal Nasopharyngeal Carriage in Young Healthy Children After Pneumococcal Conjugate Vaccine in Turkey.

Aims: To determine the prevalence of nasopharyngeal carriage of Streptococcus pneumoniae in healthy children aged 0-6 years who were vaccinated with pneumococcal conjugate vaccine.Methods: This cross-sectional study was conducted on 150 healthy Turkish children between 1 month and 6 years of age. Serotyping was performed and risk factors of carriage were evaluated.Results: The overall carriage rate was 14%. Vaccine type serotypes were determined in 17 (12.6%) children who received full-dose PCV13 vaccine. The highest carriage rate was observed among children younger than 24 months (76.2%). In multivariate analysis, respiratory infection in recent months, age, attendance at a day-care center and antibiotic usage were not statistically significant risk factors for carriage. Overall, S. pneumoniae strains were considered as penicillin susceptible and antimicrobial resistance was limited.Conclusion: We observed a low rate of pneumococcal carriage in children after PCV13 implementation compared with that of children receiving PCV7. Although it was reduced, vaccine serotype colonization in PCV13-vaccinated children remains persistent.

The potential impact of pneumococcal conjugate vaccine in Africa: Considerations and early lessons learned from the South African experience

The introduction of pneumococcal conjugate vaccine (PCV) into the South African public immunization program since 2009 adopted a novel vaccination schedule of 3 doses at 6, 14 and 40 weeks of age. Over the past 5 y it has been shown that infant PCV immunization in South Africa is effective in reducing the burden of invasive pneumococcal disease (IPD) among HIV-infected and HIV-uninfected children. Furthermore, indirect protection of unvaccinated age-groups (including high risk groups such as HIV-infected adults) against IPD was demonstrated despite the absence of any substantial catch-up campaign of older children. This indirect effect against IPD is corroborated by the temporal reduction in vaccine-serotype colonization among age-groups targeted for PCV immunization as well as unvaccinated HIV-infected and HIV-uninfected adults, which was evident within 2 y of PCV introduction into the immunization program. Vaccine effectiveness has also been demonstrated in children against presumed bacterial pneumonia. The evaluation of the impact of PCV in South Africa, however, remains incomplete. The knowledge gaps remaining include the evaluation of PCV on the incidence of all-cause pneumonia hospitalization among vaccinated and unvaccinated age-groups. Furthermore, ongoing surveillance is required to determine whether there is ongoing replacement disease by non-vaccine serotypes, which could offset the early gains associated with the immunization program in the country.

Acquisition of Streptococcus pneumoniae in South African children vaccinated with 7-valent pneumococcal conjugate vaccine at 6, 14 and 40 weeks of age

BackgroundSeven-valent pneumococcal conjugate vaccine (PCV7) was introduced into the South African immunization program using 6, 14 and 40 weeks dosing schedule (2+1), with no catch-up in older children since April 2009. We investigated pneumococcal colonization acquisition in children who received this schedule and also compared it to historical cohorts of PCV-naïve children (n=123 in 2007) and children who received a 3+1 PCV7 schedule (n=124 in 2005/06). MethodsTwo hundred and fifty children aged 6–12 weeks were enrolled from December 2009 to April 2010. Participants had nasopharyngeal swabs collected on eight occasions between enrolment and 2-years of age. Standard methods were undertaken for bacterial culture and Streptococcus pneumoniae were serotyped using the Quellung method. Pneumococcal and Staphylococcus aureus colonization in the present study was compared to colonization in two historical longitudinal cohorts. ResultsS. pneumoniae was identified in 1081 (61.4%) of 1761 swabs collected in the current cohort. Pneumococcal colonization peaked at 41-weeks of age (76.8%) and decreased to 62.8% by 2-years of age (p=0.002); PCV7-serotype colonization decreased during the same period from 28.6% to 15.6% (p=0.001). Children from the current cohort compared to PCV-naïve children were less likely to be colonized by PCV7-serotypes from 40-weeks to 2-years of age and acquired PCV7-serotypes less frequently. No differences in overall pneumococcal, PCV7-serotype and non-PCV7-serotype colonization or new serotype acquisitions were detected comparing the current cohort to the historical cohort who received the 3+1 PCV7 schedule. Staphylococcus aureus colonization was similar in all three cohorts. ConclusionA 2+1 PCV7 schedule implemented in South Africa was temporally associated with reduced risk of vaccine-serotype colonization compared to historically unvaccinated children. Also, vaccine-serotype acquisition rate using the 2+1 schedule was similar to that in the 3+1 dosing cohort, suggesting that similar indirect protection against pneumococcal disease could be derived from either schedule in South Africa.

Effect of the 13-Valent Pneumococcal Conjugate Vaccine on Nasopharyngeal Colonization by Streptococcus pneumoniae--Alaska, 2008-2012

In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced a 7-valent vaccine (PCV7) that contained all PCV7 serotypes plus 6 additional serotypes (PCV6+). We conducted annual surveys from 2008 to 2012 to determine the effect of PCV13 on colonization by pneumococcal serotypes. We obtained nasopharyngeal swabs for pneumococcal identification and serotyping from residents of all ages at 8 rural villages and children age <60 months at 2 urban clinics. We conducted interviews/medical records review for all participants. A total of 18 207 nasopharyngeal swabs (rural = 16 098; urban = 2109) were collected. From 2008 to 2012, 84% of rural and 90% of urban children age <5 years were age-appropriately vaccinated with a PCV. Overall pneumococcal colonization prevalence remained stable among rural (66%) and urban (35%) children age <5 years, and adults age ≥18 years (14%). Colonization by PCV6+ serotypes declined significantly among rural children age <5 years, urban children age <5, and adults age ≥18 over the course of the study (25%-5%, 22%-9%, 22%-6%, respectively). PCV13 was rapidly introduced into the Alaska childhood immunization schedule and reduced colonization by PCV6+ serotypes among children. Unvaccinated adults also experienced comparable reductions in vaccine serotype colonization indicating substantial indirect protection from PCV13.

Effect of Pneumococcal Conjugate Vaccine on Nasopharyngeal Colonization among Immunized and Unimmunized Children in a Community‐Randomized Trial

Pneumococcal conjugate vaccines (PCVs) prevent vaccine serotype (VT) invasive disease; nonvaccine serotype (NVT) disease increases modestly. The impact of PCV on nasopharyngeal (NP) colonization is essential to understanding disease effects. We conducted a community-randomized controlled trial with catch-up vaccination through age 2 years investigating the effect of 7-valent PCV (PnCRM7) on NP colonization among American Indian infants and their unvaccinated contacts. Infants receiving blinded vaccine at 2, 4, 6, and 12-15 months of age had NP cultures obtained at age 7, 12, and 18 months. Serotype-specific colonization was detected by immunoblot. We enrolled 566 vaccinated and 286 unvaccinated children from 511 households and collected 5157 specimens, of which 3525 (68.4%) had pneumococcus. PnCRM7 vaccinees were less likely to be colonized with VT (odds ratio [OR], 0.40 [95% confidence interval {CI}, 0.23-0.67]) but were more likely to be colonized with NVT pneumococci (OR, 1.67 [95% CI, 1.02-2.78]). PnCRM7 vaccinees were less densely colonized with VT strains than control vaccinees (OR, 0.61 [95% CI, 0.38-0.99]). Day care-attending unvaccinated children in PnCRM7 communities were less likely to have VT colonization than those in control communities (OR, 0.27 [95% CI, 0.07-1.07]). PnCRM7 reduces the risk of VT acquisition and colonization density but increases the risk of NVT acquisition among vaccinees and their household contacts.