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1.  Effect of Age and Vaccination With a Pneumococcal Conjugate Vaccine on the Density of Pneumococcal Nasopharyngeal Carriage 
This study evaluated the impact of age and pneumococcal vaccination on the density of pneumococcal nasopharyngeal carriage. Among colonized individuals, density decreased with increasing age. Time-trends analysis revealed that pneumococcal vaccination appeared to lower the density of nasopharyngeal carriage.
Background. This study evaluated the impact of age and pneumococcal vaccination on the density of pneumococcal nasopharyngeal carriage.
Methods. A cluster-randomized trial was conducted in rural Gambia. In 11 villages (the vaccine group), all residents received 7-valent pneumococcal conjugate vaccine (PCV-7), while in another 10 villages (the control group), only children <30 months old or born during the study period received PCV-7. Cross-sectional surveys (CSSs) were conducted to collect nasopharyngeal swabs before vaccination (baseline CSS) and 4, 12, and 22 months after vaccination. Pneumococcal density was defined using a semiquantitative classification (range, 1–4) among colonized individuals. An age-trend analysis of density was conducted using data from the baseline CSS. Mean pneumococcal density was compared in CSSs conducted before and after vaccination.
Results. Mean bacterial density among colonized individuals in the baseline CSS was 2.57 for vaccine-type (VT) and non–vaccine-type (NVT) pneumococci; it decreased with age (P < .001 for VT and NVT). There was a decrease in the density of VT carriage following vaccination in individuals older than 5 years (from 2.44 to 1.88; P = .001) and in younger individuals (from 2.57 to 2.11; P = .070) in the vaccinated villages. Similar decreases in density were observed with NVT within vaccinated and control villages. No significant differences were found between vaccinated and control villages in the postvaccination comparisons for either VT or NVT.
Conclusions. A high density of carriage among young subjects might partly explain why children are more efficient than adults in pneumococcal transmission. PCV-7 vaccination lowered the density of VT and of NVT pneumococcal carriage in the before-after vaccination analysis.
Clinical Trials Registration. ISRCTN51695599.
doi:10.1093/cid/cis554
PMCID: PMC3423933  PMID: 22700830
2.  Effect of Pneumococcal Vaccination on Nasopharyngeal Carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus in Fijian Children 
Journal of Clinical Microbiology  2012;50(3):1034-1038.
The 7-valent pneumococcal conjugate vaccine (PCV7) reduces carriage of vaccine type Streptococcus pneumoniae but leads to replacement by nonvaccine serotypes and may affect carriage of other respiratory pathogens. We investigated nasopharyngeal carriage of S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus in Fijian infants participating in a pneumococcal vaccine trial using quantitative PCR. Vaccination did not affect pathogen carriage rates or densities, whereas significant differences between the two major ethnic groups were observed.
doi:10.1128/JCM.06589-11
PMCID: PMC3295152  PMID: 22170924
3.  Nasopharyngeal flora in children with acute otitis media before and after implementation of 7 valent pneumococcal conjugate vaccine in France 
Background
Several studies have investigated the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal (Sp) and staphylococcal (Sa) nasopharyngeal (NP) carriage. Few have investigated the impact on Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mc) carriage. We aimed to compare the NP carriage rates in young children with acute otitis media (AOM) before and after PCV7 implementation in France.
Methods
Prior to PCV7 implementation, we performed 4 successive randomized trials with NP samples. These studies compared several antibiotic regimens for treating AOM in young children (6 to 30 months). After PCV7 implementation, to assess the impact of the vaccination program on NP flora, young children with AOM were enrolled in a prospective surveillance study. In each study, we obtained an NP sample to analyze the carriage rates of Sp, Hi, Mc and Sa and the factors influencing the carriage. Standardized history and physical examination findings were recorded; the methods used for NP swabs (sampling and cultures) were the same in all studies.
Results
We enrolled 4,405 children (mean age 13.9 months, median 12.8). Among the 2,598 children enrolled after PCV7 implementation, 98.3% were vaccinated with PCV7. In comparing the pre- and post-PCV7 periods, we found a slight but non-significant decrease in carriage rates of pneumococcus (AOR = 0.85 [0.69;1.05]), H. influenzae (AOR = 0.89 [0.73;1.09]) and S. aureus (AOR = 0.92 [0.70;1.19]). By contrast, the carriage rate of M. catarrhalis increased slightly but not significantly between the 2 periods (AOR = 1.08 [0.95;1.2]). Among Sp carriers, the proportion of PCV7 vaccine types decreased from 66.6% to 10.7% (P < 0.001), penicillin intermediate-resistant strains increased from 30.3% to 43.4% (P < 0.001), and penicillin-resistant strains decreased greatly from 22.8% to 3.8% (P < 0.001). The proportion of Hi ß-lactamase-producing strains decreased from 38.6% to 17.1% (P < 0.001).
Conclusion
The carriage rates of otopathogen species (Sp, Hi, Mc) and Sa did not significantly change in children with AOM after PCV7 implementation in France. However, we observed significant changes in carriage rates of PCV7 vaccine serotypes and penicillin non-susceptible Sp.
doi:10.1186/1471-2334-12-52
PMCID: PMC3323894  PMID: 22397629
4.  High Nasopharyngeal Carriage of Non-Vaccine Serotypes in Western Australian Aboriginal People Following 10 Years of Pneumococcal Conjugate Vaccination 
PLoS ONE  2013;8(12):e82280.
Background
Invasive pneumococcal disease (IPD) continues to occur at high rates among Australian Aboriginal people. The seven-valent pneumococcal conjugate vaccine (7vPCV) was given in a 2-4-6-month schedule from 2001, with a 23-valent pneumococcal polysaccharide vaccine (23vPPV) booster at 18 months, and replaced with 13vPCV in July 2011. Since carriage surveillance can supplement IPD surveillance, we have monitored pneumococcal carriage in western Australia (WA) since 2008 to assess the impact of the 10-year 7vPCV program.
Methods
We collected 1,500 nasopharyngeal specimens from Aboriginal people living in varied regions of WA from August 2008 until June 2011. Specimens were cultured on selective media. Pneumococcal isolates were serotyped by the quellung reaction.
Results
Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis were carried by 71.9%, 63.2% and 63.3% respectively of children <5 years of age, and 34.6%, 22.4% and 27.2% of people ≥5 years. Of 43 pneumococcal serotypes identified, the most common were 19A, 16F and 6C in children <5 years, and 15B, 34 and 22F in older people. 7vPCV serotypes accounted for 14.5% of all serotypeable isolates, 13vPCV for 32.4% and 23vPPV for 49.9%, with little variation across all age groups. Serotypes 1 and 12F were rarely identified, despite causing recent IPD outbreaks in WA. Complete penicillin resistance (MIC ≥2µg/ml) was found in 1.6% of serotype 19A (5.2%), 19F (4.9%) and 16F (3.2%) isolates and reduced penicillin susceptibility (MIC ≥0.125µg/ml) in 24.9% of isolates, particularly 19F (92.7%), 19A (41.3%), 16F (29.0%). Multi-resistance to cotrimoxazole, tetracycline and erythromycin was found in 83.0% of 23F isolates. Among non-serotypeable isolates 76.0% had reduced susceptibility and 4.0% showed complete resistance to penicillin.
Conclusions
Ten years after introduction of 7vPCV for Aboriginal Australian children, 7vPCV serotypes account for a small proportion of carried pneumococci. A large proportion of circulating serotypes are not covered by any currently licensed vaccine.
doi:10.1371/journal.pone.0082280
PMCID: PMC3857785  PMID: 24349245
5.  Pneumococcal Antibody Concentrations and Carriage of Pneumococci more than 3 Years after Infant Immunization with a Pneumococcal Conjugate Vaccine 
PLoS ONE  2012;7(2):e31050.
Background
A 9-valent pneumococcal conjugate vaccine (PCV-9), given in a 3-dose schedule, protected Gambian children against pneumococcal disease and reduced nasopharyngeal carriage of pneumococci of vaccine serotypes. We have studied the effect of a booster or delayed primary dose of 7-valent conjugate vaccine (PCV-7) on antibody and nasopharyngeal carriage of pneumococci 3–4 years after primary vaccination.
Methodology/Principal Findings
We recruited a subsample of children who had received 3 doses of either PCV-9 or placebo (controls) into this follow-up study. Pre- and post- PCV-7 pneumococcal antibody concentrations to the 9 serotypes in PCV-9 and nasopharyngeal carriage of pneumococci were determined before and at intervals up to 18 months post-PCV-7. We enrolled 282 children at a median age of 45 months (range, 38–52 months); 138 had received 3 doses of PCV-9 in infancy and 144 were controls. Before receiving PCV-7, a high proportion of children had antibody concentrations >0.35 µg/mL to most of the serotypes in PCV-9 (average of 75% in the PCV-9 and 66% in the control group respectively). The geometric mean antibody concentrations in the vaccinated group were significantly higher compared to controls for serotypes 6B, 14, and 23F. Antibody concentrations were significantly increased to serotypes in the PCV-7 vaccine both 6–8 weeks and 16–18 months after PCV-7. Antibodies to serotypes 6B, 9V and 23F were higher in the PCV-9 group than in the control group 6–8 weeks after PCV-7, but only the 6B difference was sustained at 16–18 months. There was no significant difference in nasopharyngeal carriage between the two groups.
Conclusions/Significance
Pneumococcal antibody concentrations in Gambian children were high 34–48 months after a 3-dose primary infant vaccination series of PCV-9 for serotypes other than serotypes 1 and 18C, and were significantly higher than in control children for 3 of the 9 serotypes. Antibody concentrations increased after PCV-7 and remained raised for at least 18 months.
doi:10.1371/journal.pone.0031050
PMCID: PMC3282700  PMID: 22363544
6.  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.
doi:10.1128/CVI.00435-09
PMCID: PMC2837970  PMID: 20107006
7.  Impact of More Than a Decade of Pneumococcal Conjugate Vaccine Use on Carriage and Invasive Potential in Native American Communities 
The Journal of Infectious Diseases  2011;205(2):280-288.
Background. We assessed the impact of 12 years of pneumococcal conjugate vaccine (PCV7) use on pneumococcal nasopharyngeal carriage and serotype-specific invasive disease potential among Native Americans.
Methods. Families were enrolled in a carriage study from 2006 to 2008; nasopharyngeal specimens and risk factor information were collected monthly for 7 visits. Pneumococcal carriage prevalence was compared with that before (1998–2000) and during (2001–2002) PCV7 introduction. We compared invasive disease incidence and carriage prevalence before and after PCV7 introduction to estimate changes in serotype-specific invasive potential.
Results. We enrolled 1077 subjects from 302 households. There was an absolute reduction in carriage prevalence of 8.0% (95% confidence interval [CI], 4.5%–11.4%) in children aged <5 years and 3.1% (95% CI, 1.1%–5.1%) in adults. In children aged <5 years, vaccine-serotype carriage prevalence decreased by 22.8% (95% CI, 20.1%–25.3%), and nonvaccine serotype (NVT) increased by 15.9% (95% CI, 12.4%–19.3%). No significant change was detected in serotype-specific invasive potential after PCV7 introduction.
Conclusions. Pneumococcal carriage prevalence decreased in all ages since PCV7 introduction; vaccine-serotype carriage has been nearly eliminated, whereas the prevalence of NVT carriage has increased. The increase in the NVT invasive disease rate seems to be proportional to the increase in colonization prevalence.
doi:10.1093/infdis/jir730
PMCID: PMC3244367  PMID: 22128315
8.  Pre-Vaccination Nasopharyngeal Pneumococcal Carriage in a Nigerian Population: Epidemiology and Population Biology 
PLoS ONE  2012;7(1):e30548.
Background
Introduction of pneumococcal vaccines in Nigeria is a priority as part of the Accelerated Vaccine Introduction Initiative (AVI) of the Global Alliance for Vaccines and Immunisation (GAVI). However, country data on the burden of pneumococcal disease (IPD) is limited and coverage by available conjugate vaccines is unknown. This study was carried out to describe the pre vaccination epidemiology and population biology of pneumococcal carriage in Nigeria.
Methods
This was a cross sectional survey. Nasopharyngeal swabs (NPS) were obtained from a population sample in 14 contiguous peri-urban Nigerian communities. Data on demographic characteristics and risk factor for carriage were obtained from all study participants. Pneumococci isolated from NPS were characterised by serotyping, antimicrobial susceptibility and Multi Locus Sequencing Typing (MLST).
Results
The prevalence of pneumococcal carriage was 52.5%. Carriage was higher in children compared to adults (67.4% vs. 26%), highest (≈90%) in infants aged <9 months and reduced significantly with increasing age (P<0.001). Serotypes 19F (18.6%) and 6A (14.4%) were most predominant. Potential vaccine coverage was 43.8%, 45.0% and 62% for PCV-7, PCV-10 and PCV-13 respectively. There were 16 novel alleles, 72 different sequence types (STs) from the isolates and 3 Sequence Types (280, 310 and 5543) were associated with isolates of more than one serotype indicative of serotype switching. Antimicrobial resistance was high for cotrimoxazole (93%) and tetracycline (84%), a third of isolates had intermediate resistance to penicillin. Young age was the only risk factor significantly associated with carriage.
Conclusions
Pneumococcal carriage and serotype diversity is highly prevalent in Nigeria especially in infants. Based on the coverage of serotypes in this study, PCV-13 is the obvious choice to reduce disease burden and prevalence of drug resistant pneumococci. However, its use will require careful monitoring. Our findings provide sound baseline data for impact assessment following vaccine introduction in Nigeria.
doi:10.1371/journal.pone.0030548
PMCID: PMC3265474  PMID: 22291984
9.  Effects of Community-Wide Vaccination with PCV-7 on Pneumococcal Nasopharyngeal Carriage in The Gambia: A Cluster-Randomized Trial 
PLoS Medicine  2011;8(10):e1001107.
In a cluster-randomized trial conducted in Gambian villages, Anna Roca and colleagues find that vaccination of children with pneumococcal conjugate vaccines reduced vaccine-type pneumococcal carriage even among nonvaccinated older children and adults.
Background
Introduction of pneumococcal conjugate vaccines (PCVs) of limited valency is justified in Africa by the high burden of pneumococcal disease. Long-term beneficial effects of PCVs may be countered by serotype replacement. We aimed to determine the impact of PCV-7 vaccination on pneumococcal carriage in rural Gambia.
Methods and Findings
A cluster-randomized (by village) trial of the impact of PCV-7 on pneumococcal nasopharyngeal carriage was conducted in 21 Gambian villages between December 2003 to June 2008 (5,441 inhabitants in 2006). Analysis was complemented with data obtained before vaccination. Because efficacy of PCV-9 in young Gambian children had been shown, it was considered unethical not to give PCV-7 to young children in all of the study villages. PCV-7 was given to children below 30 mo of age and to those born during the trial in all study villages. Villages were randomized (older children and adults) to receive one dose of PCV-7 (11 vaccinated villages) or meningococcal serogroup C conjugate vaccine (10 control villages). Cross-sectional surveys (CSSs) to collect nasopharyngeal swabs were conducted before vaccination (2,094 samples in the baseline CSS), and 4–6, 12, and 22 mo after vaccination (1,168, 1,210, and 446 samples in CSS-1, -2, and -3, respectively).
A time trend analysis showed a marked fall in the prevalence of vaccine-type pneumococcal carriage in all age groups following vaccination (from 23.7% and 26.8% in the baseline CSS to 7.1% and 8.5% in CSS-1, in vaccinated and control villages, respectively). The prevalence of vaccine-type pneumococcal carriage was lower in vaccinated than in control villages among older children (5 y to <15 y of age) and adults (≥15 y of age) at CSS-2 (odds ratio [OR] = 0.15 [95% CI 0.04–0.57] and OR = 0.32 [95% CI 0.10–0.98], respectively) and at CSS-3 (OR = 0.37 [95% CI 0.15–0.90] for older children, and 0% versus 7.6% for adults in vaccinated and control villages, respectively). Differences in the prevalence of non-vaccine-type pneumococcal carriage between vaccinated and control villages were small.
Conclusions
Vaccination of Gambian children reduced vaccine-type pneumococcal carriage across all age groups, indicating a “herd effect” in non-vaccinated older children and adults. No significant serotype replacement was detected.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The prevention of pneumococcal disease, especially in children in developing countries, is a major international public health priority. Despite all the international attention on the UN's Millennium Development Goal 4—to reduce deaths in children under five years by two-thirds between 1990 and 2015—pneumonia, sepsis, and meningitis together compose more than 25% of the 10 million deaths occurring in children less than five years of age. Streptococcus pneumoniae is a leading bacterial cause of these diseases, and the World Health Organization estimates that approximately 800,000 children die each year of invasive pneumococcal disease.
Pneumococcal conjugate vaccines are currently available and protect against the serotypes that most commonly cause invasive pneumococcal disease in young children in North America and Europe. Such vaccines have been highly successful in reducing the incidence of invasive pneumococcal disease in both vaccinated children and in the non-vaccinated older population by reducing nasopharyngeal carriage (presence of pneumococcal bacteria in the back of the nose) in vaccinated infants, resulting in decreased transmission to contacts—the so-called herd effect. However, few countries with the highest burden of invasive pneumococcal disease, especially those in sub-Saharan Africa, have introduced the vaccine into their national immunization programs.
Why Was This Study Done?
The features of pneumococcal nasopharyngeal carriage and invasive pneumococcal disease in sub-Saharan Africa are different than in other regions. Therefore, careful evaluation of the immune effects of vaccination requires long-term, longitudinal studies. As an alternative to such long-term observational studies, and to anticipate the potential long-term effects of the introduction of pneumococcal conjugate vaccination in sub-Saharan Africa, the researchers conducted a cluster-randomized (by village) trial in The Gambia in which the whole populations of some villages were immunized with the vaccine PCV-7, and other villages received a control.
What Did the Researchers Do and Find?
With full consent from communities, the researchers randomized 21 similar villages in a rural region of western Gambia to receive pneumococcal conjugate vaccine or a control—meningococcal serogroup C conjugated vaccine, which is unlikely to affect pneumococcal carriage rates. For ethical reasons, the researchers only randomized residents aged over 30 months—all young infants received PCV-7, as a similar vaccine had already been shown to be effective in young infants. Before immunization began, the researchers took nasopharyngeal swabs from a random selection of village residents to determine the baseline pneumococcal carriage rates of both the serotypes of pneumococci covered by the vaccine (vaccine types, VTs) and the serotypes of pneumococci not covered in the vaccine (non-vaccine types, NVTs). The researchers then took nasopharyngeal swabs from a random sample of 1,200 of village residents in both groups of villages in cross-sectional surveys at 4–6, 12, and 22 months after vaccination. Villagers and laboratory staff were unaware of which vaccine was which (that is, they were blinded).
Before immunization, the overall prevalence of pneumococcal carriage in both groups was high, at 71.1%, and decreased with age. After vaccination, the overall prevalence of pneumococcal carriage in all three surveys was similar between vaccinated and control villages, showing a marked fall. However, the prevalence of carriage of VT pneumococci was significantly lower in vaccinated than in control villages in all surveys for all age groups. The prevalence of carriage of NVT pneumococci was similar in vaccinated and in control villages, except for a slightly higher prevalence of NVT pneumococci among vaccinated communities in adults at 4–6 months after vaccination. The researchers also found that the overall prevalence of pneumococcal carriage fell markedly after vaccination and reached minimum levels at 12 months in both study arms and in all age groups.
What Do These Findings Mean?
These findings show that vaccination of young Gambian children reduced carriage of VT pneumococci in vaccinated children but also in vaccinated and non-vaccinated older children and adults, revealing a potential herd effect from vaccination of young children. Furthermore, the immunological pressure induced by vaccinating whole communities did not lead to a community-wide increase in carriage of NVT pneumococci during a two-year period after vaccination. The researchers plan to conduct more long-term follow-up studies to determine nasopharyngeal carriage in these communities.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001107.
The World Health Organization has information about pneumococcus
The US Centers for Disease Control and Prevention provides information about pneumococcal conjugate vaccination
doi:10.1371/journal.pmed.1001107
PMCID: PMC3196470  PMID: 22028630
10.  Carriage of Streptococcus pneumoniae 3 Years after Start of Vaccination Program, the Netherlands 
Emerging Infectious Diseases  2011;17(4):584-591.
To evaluate the effectiveness of the 7-valent pneumococcal conjugate vaccine (PCV7) program, we conducted a cross-sectional observational study on nasopharyngeal carriage of Streptococcus pneumoniae 3 years after implementation of the program in the Netherlands. We compared pneumococcal serotypes in 329 prebooster 11-month-old children, 330 fully vaccinated 24-month-old children, and 324 parents with age-matched pre-PCV7 (unvaccinated) controls (ages 12 and 24 months, n = 319 and n = 321, respectively) and 296 of their parents. PCV7 serotype prevalences before and after PCV7 implementation, respectively, were 38% and 8% among 11-month-old children, 36% and 4% among 24-month-old children, and 8% and 1% among parents. Non-PCV7 serotype prevalences were 29% and 39% among 11-month-old children, 30% and 45% among 24-month-old children, and 8% and 15% among parents, respectively; serotypes 11A and 19A were most frequently isolated. PCV7 serotypes were largely replaced by non-PCV7 serotypes. Disappearance of PCV7 serotypes in parents suggests strong transmission reduction through vaccination.
doi:10.3201/eid1704101115
PMCID: PMC3377405  PMID: 21470445
Streptococcus pneumoniae; nasopharyngeal colonization; heptavalent pneumococcal conjugate vaccine; infectious disease transmission; herd immunity; parents; infants; bacteria; research
11.  Streptococcus pneumoniae Carriage in the Gaza Strip 
PLoS ONE  2012;7(4):e35061.
Background
Pneumococcal infections cause major morbidity and mortality in developing countries. We report the epidemiology of S. pneumoniae carriage in a developing region, the Gaza strip, and evaluate the theoretical coverage of carriage strains by pneumococcal conjugate vaccines (PCVs).
Methodology
In 2009 we conducted a cross-sectional survey of S. pneumoniae carriage in healthy children and their parents, living throughout the Gaza strip. Data were collected and nasopharyngeal swabs were obtained. Antibiotic susceptibilities were determined by Vitek-2 and serotypes by the Quellung reaction.
Principal Findings
S. pneumoniae carriage was detected in 189/379 (50%) of children and 30/376 (8%) of parents. Carriage prevalence was highest in children <6 months of age (63%). Significant predictors for child carriage were number of household members and DCC attendance. The proportion of pediatric and adults isolates with serotypes included in PCV7 were 32% and 20% respectively, and 46% and 33% in PCV13 respectively. The most prominent non-vaccine serotypes (NVT) were 35B, 15B/C and 23B. Penicillin-nonsusceptible strains were carried by70% of carriers, penicillin-resistant strains (PRSP) by 13% and Multi-drug-resistant (MDR) by 30%. Of all PRSP isolates 54% belonged to serotypes included in PCV7 and 71% in the PCV13. Similarly, 59% and 73% of MDR-SP isolates, would theoretically be covered by PCV7 and PCV13, respectively.
Conclusions
This study demonstrates that, PCV13-included strains were carried by 46% and 33% of pediatric and adult subjects respectively. In the absence of definitive data regarding the virulence of the NVT strains, it is difficult to predict the effect of PCVs on IPD in this region.
doi:10.1371/journal.pone.0035061
PMCID: PMC3335158  PMID: 22539955
12.  Risk factors for serotype 19A carriage after introduction of 7-valent pneumococcal vaccination 
Background
After the implementation of 7-valent pneumococcal conjugate vaccine (PCV7), in several countries, serotype 19A is now the serotype most frequently involved in pneumococcal diseases and carriage. To determine factors potentially related to 19A nasopharyngeal (NP) carriage we analyzed data from an ongoing prospective French national surveillance study of pneumococcal NP carriage in young children.
Methods
NP swabs were obtained from children aged 6 to 24 months, either during routine check-ups with normal findings, or when they presented with acute otitis media (AOM). The swabs were sent for analysis to the French National Reference Centre for Pneumococci. Factors influencing pneumococcal carriage and carriage of penicillin non-susceptible (PNSP), 19A and PNS-19A were investigated by multivariate logistic regression.
Results
From 2006 to 2009, 66 practitioners enrolled 3507 children (mean age 13.6 months), of whom, 98.3% of children had been vaccinated with PCV7 and 33.4% of children attended daycare centres (DCC). Serotype 19A was found in 10.4% of the overall population, 20.5% of S. pneumoniae carriers (n = 1780) and 40.8% of PNSP carriers (n = 799). Among 19A strains, 10.7% were penicillin-susceptible, 80% intermediate and 9.3% fully resistant. Logistic regression analysis showed that the main factors associated with PNSP carriage were AOM (OR = 3.09, 95% CI [2.39;3.98]), DCC (OR = 1.70, 95% CI [1.42;2.03]), and recent antibiotic use (OR = 1.24, 95% CI [1.05;1.47]. The main factors predictive of 19A carriage were recent antibiotic use (OR = 1.81, 95% CI [1.42;2.30]), AOM (OR = 1.67, 95% CI [1.11;2.49]), DCC (OR = 1.56, 95% CI [1.21;2.2] and young age, <12 months (OR = 1.51, 95% CI [1.16;1.97]).
Conclusion
In a population of children aged from 6 to 24 months with a high rate of PCV7 vaccination coverage, we found that antibiotic exposure, DCC attendance and AOM were linked to 19A carriage.
doi:10.1186/1471-2334-11-95
PMCID: PMC3101155  PMID: 21501471
13.  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.
Methods
We conducted cross sectional surveys of pneumococcal carriage in Aboriginal children 0 to 6 years of age living in remote Aboriginal communities (RACs) in 2003 and 2005. Nasal secretions were collected and processed according to published methods.
Results
902 children (mean age 25 months) living in 29 communities in 2003 and 818 children (mean age 35 months) in 17 communities in 2005 were enrolled. 87% children in 2003 and 96% in 2005 had received two or more doses of 7PCV. From 2003 to 2005, pneumococcal carriage was reduced from 82% to 76% and reductions were apparent in all age groups; 7PCV-type carriage was reduced from 11% to 8%, and 23PPV-non-7PCV-type carriage from 31% to 25% respectively. Thus non-23PPV-type carriage increased from 57% to 67%. All these changes were statistically significant, as were changes for some specific serotypes. Shifts could not be attributed to vaccination alone. The top 10 of 40 serotypes identified were (in descending order) 16F, 19A, 11A, 6C, 23B, 19F, 6A, 35B, 6B, 10A and 35B. Carriage of penicillin non-susceptible (MIC > = 0.12 μg/mL) strains (15% overall) was detected in serotypes (descending order) 19A, 19F, 6B, 16F, 11A, 9V, 23B, and in 4 additional serotypes. Carriage of azithromycin resistant (MIC > = 2 μg/mL) strains (5% overall), was detected in serotypes (descending order) 23B, 17F, 9N, 6B, 6A, 11A, 23F, and in 10 additional serotypes including 6C.
Conclusion
Pneumococcal carriage remains high (~80%) in this vaccinated population. Uptake of both pneumococcal vaccines increased, and carriage was reduced between 2003 and 2005. Predominant serotypes in combined years were 16F, 19A, 11A, 6C and 23B. Antimicrobial non-susceptibility was detected in these and 17 additional serotypes. Shifts in serotype-specific carriage suggest a need more research to clarify the association between pneumococcal vaccination and carriage at the serotype level.
doi:10.1186/1471-2334-9-121
PMCID: PMC2736967  PMID: 19650933
14.  Age-Dependent Prevalence of Nasopharyngeal Carriage of Streptococcus pneumoniae before Conjugate Vaccine Introduction: A Prediction Model Based on a Meta-Analysis 
PLoS ONE  2014;9(1):e86136.
Introduction
Data on the prevalence of nasopharyngeal carriage of S.pneumoniae in all age groups are important to help predict the impact of introducing pneumococcal conjugate vaccines (PCV) into routine infant immunization, given the important indirect effect of the vaccine. Yet most carriage studies are limited to children under five years of age. We here explore the association between carriage prevalence and serotype distribution in children aged ≥5 years and in adults compared to children.
Methods
We conducted a systematic review of studies providing carriage estimates across age groups in healthy populations not previously exposed to PCV, using MEDLINE and Embase. We used Bayesian linear meta-regression models to predict the overall carriage prevalence as well as the prevalence and distribution of vaccine and nonvaccine type (VT and NVT) serotypes in older age groups as a function of that in <5 y olds.
Results
Twenty-nine studies compromising of 20,391 individuals were included in the analysis. In all studies nasopharyngeal carriage decreased with increasing age. We found a strong positive linear association between the carriage prevalence in pre-school childen (<5 y) and both that in school aged children (5–17 y olds) and in adults. The proportion of VT serotypes isolated from carriers was consistently lower in older age groups and on average about 73% that of children <5 y among 5–17 y olds and adults respectively. We provide a prediction model to infer the carriage prevalence and serotype distribution in 5–17 y olds and adults as a function of that in children <5 years of age.
Conclusion
Such predictions are helpful for assessing the potential population-wide effects of vaccination programmes, e.g. via transmission models, and thus assist in the design of future pneumococcal conjugate vaccination strategies.
doi:10.1371/journal.pone.0086136
PMCID: PMC3900487  PMID: 24465920
15.  The Prevalence and Risk Factors for Pneumococcal Colonization of the Nasopharynx among Children in Kilifi District, Kenya 
PLoS ONE  2012;7(2):e30787.
Background
Pneumococcal conjugate vaccines (PCV) reduce nasopharyngeal carriage of vaccine-serotype pneumococci but increase in the carriage of non-vaccine serotypes. We studied the epidemiology of carriage among children 3–59 months old before vaccine introduction in Kilifi, Kenya.
Methods
In a rolling cross-sectional study from October 2006 to December 2008 we approached 3570 healthy children selected at random from the population register of the Kilifi Health and Demographic Surveillance System and 134 HIV-infected children registered at a specialist clinic. A single nasopharyngeal swab was transported in STGG and cultured on gentamicin blood agar. A single colony of pneumococcus was serotyped by Quellung reaction.
Results
Families of 2840 children in the population-based sample and 99 in the HIV-infected sample consented to participate; carriage prevalence was 65.8% (95% CI, 64.0–67.5%) and 76% (95% CI, 66–84%) in the two samples, respectively. Carriage prevalence declined progressively with age from 79% at 6–11 months to 51% at 54–59 months (p<0.0005). Carriage was positively associated with coryza (Odds ratio 2.63, 95%CI 2.12–3.25) and cough (1.55, 95%CI 1.26–1.91) and negatively associated with recent antibiotic use (0.53 95%CI 0.34–0.81). 53 different serotypes were identified and 42% of isolates were of serotypes contained in the 10-valent PCV. Common serotypes declined in prevalence with age while less common serotypes did not.
Conclusion
Carriage prevalence in children was high, serotypes were diverse, and the majority of strains were of serotypes not represented in the 10-valent PCV. Vaccine introduction in Kenya will provide a natural test of virulence for the many circulating non-vaccine serotypes.
doi:10.1371/journal.pone.0030787
PMCID: PMC3282706  PMID: 22363489
16.  Contribution of vaccines to our understanding of pneumococcal disease 
Pneumonia is the leading cause of mortality in children in developing countries and is also the leading infectious cause of death in adults. The most important cause of pneumonia is the Gram-positive bacterial pathogen, Streptococcus pneumoniae, also known as the pneumococcus. It has thus become the leading vaccine-preventable cause of death and is a successful and diverse human pathogen. The development of conjugate pneumococcal vaccines has made possible the prevention of pneumococcal disease in infants, but has also elucidated aspects of pneumococcal biology in a number of ways. Use of the vaccine as a probe has increased our understanding of the burden of pneumococcal disease in children globally. Vaccination has also elucidated the clinical spectrum of vaccine-preventable pneumococcal infections; the identification of a biological niche for multiple pneumococcal serotypes in carriage and the differential invasiveness of pneumococcal serotypes; the impact of pneumococcal transmission among children on disease burden in adults; the role of carriage as a precursor to pneumonia; the plasticity of a naturally transformable pathogen to respond to selective pressure through capsular switching and the accumulation of antibiotic-resistance determinants; and the role of pneumococcal infections in hospitalization and mortality associated with respiratory viral infections, including both seasonal and pandemic influenza. Finally, there has been a recent demonstration that pneumococcal pneumonia in children may be an important cause of hospitalization for those with underlying tuberculosis.
doi:10.1098/rstb.2011.0032
PMCID: PMC3146770  PMID: 21893542
vaccine; pneumonia; pneumococcus
17.  Nasopharyngeal Pneumococcal Carriage of Children Attending Day Care Centers in Korea: Comparison between Children Immunized with 7-valent Pneumococcal Conjugate Vaccine and Non-immunized 
Journal of Korean Medical Science  2011;26(2):184-190.
To confirm the effect of 7-valent pneumococcal conjugate vaccine (PCV7), pneumococcal nasopharyngeal (NP) carriage was compared between vaccinated (3 + 1 doses PCV7) and non-vaccinated children. Vaccinated subjects were recruited from highly vaccinated regions (≥ 60%), Seoul and Incheon whereas control subjects were recruited from Jeju Island where vaccination rates are low (< 15%). NP swabs were obtained from 400 children aged 18-59 months. Serotype and antibiotic susceptibility was analyzed. Pneumococcal carriage rate was 18.0% (36/200) and 31.5% (63/200) for the vaccinated and control group, respectively. Among those vaccinated, 41.7% (15/36) of the serotypes were vaccine-related type (VRT: 6A, 6C, 19A) with the most common serotype 6C. The next common type was non-typable/non-capsule 30.6% (11/36) followed by non-vaccine type 16.7% (6/36) and vaccine type (VT) serotypes were found in only 11.1% (4/36). In contrast, 52.4% (33/63) of the isolates in the control group were VT. Resistance rates for penicillin and erythromycin were lower in the vaccine group (vaccine vs control; penicillin 45.2% vs 71.4%, erythromycin 74.2% vs 90.5%, P < 0.05). Multi-drug resistance was also lower in vaccinated subjects (vaccine vs control; 45.2% vs 69.8%, P < 0.05). PCV7 reduces carriage in VT which leads to replacement of pneumococci by antibiotic susceptible VRT or non-vaccine type strains.
doi:10.3346/jkms.2011.26.2.184
PMCID: PMC3031000  PMID: 21286007
Streptococcus pneumoniae; Heptavalent Pneumococcal Conjugate Vaccine; Epidemiology; Child Day Care Centers
18.  Long-Term Effects of Pneumococcal Conjugate Vaccine on Nasopharyngeal Carriage of S. pneumoniae, S. aureus, H. influenzae and M. catarrhalis 
PLoS ONE  2012;7(6):e39730.
Background
Shifts in pneumococcal serotypes following introduction of 7-valent pneumococcal conjugate vaccine (PCV-7) may alter the presence of other bacterial pathogens co-inhabiting the same nasopharyngeal niche.
Methodology/Principal Findings
Nasopharyngeal prevalence rates of S. pneumoniae, S. aureus, H. influenzae and M. catarrhalis were investigated before, 3 and 4.5 years after introduction of PCV-7 in the national immunisation program in children at 11 and 24 months of age, and parents of 24-month-old children (n≈330/group) using conventional culture methods. Despite a virtual disappearance of PCV-7 serotypes over time, similar overall pneumococcal rates were observed in all age groups, except for a significant reduction in the 11-month-old group (adjusted Odds Ratio after 4.5 years 0.48, 95% Confidence Interval 0.34–0.67). Before, 3 and 4.5 years after PCV-7 implementation, prevalence rates of S. aureus were 5%, 9% and 14% at 11 months of age (3.59, 1.90–6.79) and 20%, 32% and 34% in parents (1.96, 1.36–2.83), but remained similar at 24 months of age, respectively. Prevalence rates of H. influenzae were 46%, 65% and 65% at 11 months (2.22, 1.58–3.13), 52%, 73% and 76% at 24 months of age (2.68, 1.88–3.82) and 23%, 30% and 40% in parents (2.26, 1.58–3.33), respectively. No consistent changes in M. catarrhalis carriage rates were observed over time.
Conclusions/Significance
In addition to large shifts in pneumococcal serotypes, persistently higher nasopharyngeal prevalence rates of S. aureus and H. influenzae were observed among young children and their parents after PCV-7 implementation. These findings may have implications for disease incidence and antibiotic treatment in the post-PCV era.
doi:10.1371/journal.pone.0039730
PMCID: PMC3382588  PMID: 22761879
19.  Virulence of Streptococcus pneumoniae serotype 6C in experimental otitis media 
Increases in colonization with serotypes of Streptococcus pneumoniae not contained within the 7-valent pneumococcal conjugate vaccine (PCV) have been reported among children following introduction. Serotype 6C has emerged as prevalent in nasopharyngeal colonization and acute otitis media (AOM), though it is uncommonly recovered from children with invasive pneumococcal disease. Vaccine serotypes within PCV7 have been replaced by nonvaccine serotypes without significant changes in the overall carriage rate. We hypothesize 1) that serotypes vary in their ability to evade host defenses and establish AOM following colonization and 2) the observed reduction in pneumococcal otitis results from a reduced disease potential by some ‘replacement serotypes’. We compared the capacity of S. pneumoniae serotypes 6C and 19A to produce experimental otitis media (EOM) in a chinchilla model. The proportion of chinchillas that developed culture positive EOM and density of middle ear infection was evaluated. EOM was found in 28/82 (34%) ears challenged with 6C compared to 13/18(72.2%) with 19A [p=0.0003]. When disease due to 6C did occur, it was characterized by lowdensity infection. Our findings demonstrate that challenge with serotype 6C results in EOM less frequently than 19A. These data support the need for greater knowledge regarding differences among serotypes to produce AOM.
doi:10.1016/j.micinf.2012.02.008
PMCID: PMC3382049  PMID: 22414497
Streptococcus pneumoniae; complement; virulence
20.  Prevalent Multidrug-resistant Nonvaccine Serotypes in Pneumococcal Carriage of Healthy Korean Children Associated with the Low Coverage of the Seven-valent Pneumococcal Conjugate Vaccine 
Objectives
Our previous longitudinal multicenter-based carriage study showed that the average carriage rate of Streptococcus pneumoniae was 16.8% in 582 healthy children attending kindergarten or elementary school in Seoul, Korea. We assessed serotype-specific prevalence and antimicrobial resistance among colonizing pneumococcal isolates from young children in the era of low use of the seven-valent pneumococcal conjugate vaccine (PCV7).
Methods
Serotypes were determined by an agglutination test with specific antisera or by a multiplex polymerase chain reaction (PCR) assay. An antimicrobial susceptibility test was performed with broth microdilution in Korean 96-well panels from Dade-MicroScan (Sacramento, CA, USA).
Results
Pneumococcal colonization patterns were dynamic and longterm persistent carriage was rare, which indicated a sequential turnover of pneumococcal strains. Of the 369 pneumococci (except for 23 killed isolates), 129 (34.9%) isolates were PCV7 vaccine serotypes (VTs); 213 (57.8%) isolates were nonvaccine serotypes (NVTs); and the remaining 27 (7.2%) isolates were nontypable (NT). The highest rates of multidrug resistance (MDR) were observed in VTs (86.0%; 111/129 isolates) and NVTs (70.0%; 149/213 isolates).
Conclusion
This study overall showed the frequent carriage of VTs and NVTs with MDR in healthy children attending kindergarten or elementary school. Efforts should be directed toward reducing the extensive prescription of antibiotics and using new broader vaccines to reduce the expansion of MDR strains of NVTs in our community.
doi:10.1016/j.phrp.2013.10.004
PMCID: PMC3922100  PMID: 24524020
multidrug-resistant strains; nasal carriage; nonvaccine serotypes; Streptococcus pneumoniae
21.  Systematic Review of the Indirect Effect of Pneumococcal Conjugate Vaccine Dosing Schedules on Pneumococcal Disease and Colonization 
The Pediatric Infectious Disease Journal  2013;33(Suppl 2 Optimum Dosing of Pneumococcal Conjugate Vaccine For Infants 0 A Landscape Analysis of Evidence Supportin g Different Schedules):S161-S171.
Background:
To aid decision making for pneumococcal conjugate vaccine (PCV) use in infant national immunization programs, we summarized the indirect effects of PCV on clinical outcomes among nontargeted age groups.
Methods:
We systematically reviewed the English literature on infant PCV dosing schedules published from 1994 to 2010 (with ad hoc addition of 2011 articles) for outcomes on children >5 years of age and adults including vaccine-type nasopharyngeal carriage (VT-NP), vaccine-type invasive pneumococcal disease (VT-IPD) and syndromic pneumonia.
Results:
Of 12,980 citations reviewed, we identified 21 VT-IPD, 6 VT-NP and 9 pneumonia studies. Of these 36, 21 (58%) included 3 primary doses plus PCV or pneumococcal polysaccharide vaccine (PPV23) booster schedule (3+1 or 3+PPV23), 5 (14%) 3+0, 9 (25%) 2+1 and 1 (3%) 2+0. Most (95%) were PCV7 studies. Among observational VT-IPD studies, all schedules (2+1, 3+0 and 3+1) demonstrated reductions in incidence among young adult groups. Among syndromic pneumonia observational studies (2+1, 3+0 and 3+1), only 3+1 schedules showed significant indirect impact. Of 2 VT-NP controlled trials (3+0 and 3+1) and 3 VT-NP observational studies (2+1, 3+1 and 3+PPV23), 3+1 and 3+PPV23 schedules showed significant indirect effect. The 1 study to directly compare between schedules was a VT-NP study (2+0 vs. 2+1), which found no indirect effect on older siblings and parents of vaccinated children with either schedule.
Conclusions:
Indirect benefit of a 3+1 infant PCV dosing schedule has been demonstrated for VT-IPD, VT-NP and syndromic pneumonia; 2+1 and 3+0 schedules have demonstrated indirect effect only for VT-IPD. The choice of optimal infant PCV schedule is limited by data paucity on indirect effects, especially a lack of head-to-head studies and studies of PCV10 and PCV13.
doi:10.1097/INF.0000000000000084
PMCID: PMC3940524  PMID: 24336058
pneumococcal conjugate vaccine; nasopharyngeal carriage; pneumonia; pneumococcal disease; indirect effects
22.  Nasopharyngeal Carriage of Pneumococci Four Years after Community-Wide Vaccination with PCV-7 in The Gambia: Long-Term Evaluation of a Cluster Randomized Trial 
PLoS ONE  2013;8(9):e72198.
Background
A village-randomized trial of a seven-valent pneumococcal-conjugate-vaccine (PCV-7) conducted in rural Gambia showed a decrease of vaccine-type (VT) and a non-significant increase in non-vaccine-type (NVT) nasopharyngeal carriage of pneumococci two years after vaccination. Here, we report findings four years after vaccination.
Methods
PCV-7 was given to all children below 30 months of age enrolled in the trial and to those born during its course in all study villages. Villages were randomized (older children and adults) to receive PCV-7 (wholly vaccinated villages) or serogroup-C-meningococcal-conjugate-vaccine (partly vaccinated villages). Cross-sectional surveys (CSS) to collect nasopharyngeal swabs were conducted before and at various intervals after vaccination. Sixteen of these randomized villages (8 wholly vaccinated and 8 partly vaccinated) participated in a CSS conducted four years after vaccination started.
Results
Four years after vaccination, the prevalence of VT pneumococcal carriage was slightly higher in partly than in wholly vaccinated villages [6.4% versus 3.9% (p = 0.120)] compared to 24.4% in the pre-vaccination CSS (p<0.001). Prevalence of NVT four years after vaccination was similar between study groups [32.7% versus 29.8% (p = 0.392), respectively] compared to 51.1% in the pre-vaccination CSS (p<0.001). Four years after vaccination started, lower prevalence of serotype 6A was detected in wholly vaccinated than in partly vaccinated villages (1.6% versus 3.5%, p = 0.093) whilst the prevalence of serotype 19A was similar between groups (2.9% versus 2.5%, p = 0.779). The most prevalent serotype 19A clone was ST 847. The most prevalent serotype 6A clone before vaccination was ST3324 whilst after vaccination ST913 and ST1737 predominated. Fourteen out of 26 STs detected among the serotype 6A isolates were new while no new 19A serotype ST was found.
Conclusions
The decline in prevalence of VT pneumococci seen shortly after PCV-7 vaccination was sustained four years later with only a small difference between study arms. No significant serotype replacement was detected.
Trial Registration
ClinicalTrials.gov ISRCTN51695599
doi:10.1371/journal.pone.0072198
PMCID: PMC3785494  PMID: 24086259
23.  Pneumococcal Carriage in Young Children One Year after Introduction of the 13-Valent Conjugate Vaccine in Italy 
PLoS ONE  2013;8(10):e76309.
Background
In mid 2010, the 7-valent pneumococcal conjugate vaccine (PCV7) was replaced by the 13-valent conjugate vaccine (PCV13) for childhood immunization in Italy. Our objective in this study was to obtain a snapshot of pneumococcal carriage frequency, colonizing serotypes, and antibiotic resistance in healthy children in two Italian cities one year after PCV13 was introduced.
Methods
Nasopharyngeal swabs were obtained from 571 children aged 0-5 years from November 2011-April 2012. Pneumococcal isolates were serotyped and tested for antimicrobial susceptibility. Penicillin and/or erythromycin non-susceptible isolates were analyzed by Multi Locus Sequence Typing (MLST).
Results
Among the children examined, 81.2% had received at least one dose of PCV7 or PCV13 and 74.9% had completed the recommended vaccination schedule for their age. Among the latter, 57.3% of children had received PCV7, 27.1% PCV13, and 15.6% a combination of the two vaccines. The overall carriage rate was 32.9%, with children aged 6-35 months the most prone to pneumococcal colonization (6-23 months OR: 3.75; 95% CI: 2.19-6.43 and 24-35 months OR: 3.15, 95%CI: 2.36-4.22). A total of 184 pneumococcal isolates were serotyped and divided into PCV7 (5.4%), PCV13 (18.0%), and non-PCV13 (82.0%) serotypes. Serotypes 6C, 24F, and 19A were the most prevalent (10.3%, 8.6%, and 8.1%, respectively). The proportion of penicillin non-susceptible (MIC >0.6 mg/L) isolates was 30.9%, while 42.3% were erythromycin resistant. Non-PCV13 serotypes accounted for 75.4% and 70.8% of the penicillin and erythromycin non-susceptible isolates, respectively.
Conclusions
Our results revealed low rates of PCV7 and PCV13 serotypes in Italian children, potentially due to the effects of vaccination. As the use of PCV13 continues, its potential impact on vaccine serotypes such as 19A and cross-reactive serotypes such as 6C will be assessed, with this study providing a baseline for further analysis of surveillance isolates.
doi:10.1371/journal.pone.0076309
PMCID: PMC3790677  PMID: 24124543
24.  Nasopharyngeal Carriage and Transmission of Streptococcus pneumoniae in American Indian Households after a Decade of Pneumococcal Conjugate Vaccine Use 
PLoS ONE  2014;9(1):e79578.
Background
Young children played a major role in pneumococcal nasopharyngeal carriage, acquisition, and transmission in the era before pneumococcal conjugate vaccine (PCV) use. Few studies document pneumococcal household dynamics in the routine-PCV7 era.
Methods
We investigated age-specific acquisition, household introduction, carriage clearance, and intra-household transmission in a prospective, longitudinal, observational cohort study of pneumococcal nasopharyngeal carriage in 300 American Indian households comprising 1,072 participants between March 2006 and March 2008.
Results
Pneumococcal acquisition rates were 2–6 times higher in children than adults. More household introductions of new pneumococcal strains were attributable to children <9 years than adults ≥17 years (p<0.001), and older children (2–8 years) than younger children (<2 years) (p<0.008). Compared to children <2 years, carriage clearance was more rapid in older children (2–4 years, HRclearance 1.53 [95% CI: 1.22, 1.91]; 5–8 years, HRclearance 1.71 [1.36, 2.15]) and adults (HRclearance 1.75 [1.16, 2.64]). Exposure to serotype-specific carriage in older children (2–8 years) most consistently increased the odds of subsequently acquiring that serotype for other household members.
Conclusions
In this community with a high burden of pneumococcal colonization and disease and routine PCV7 use, children (particularly older children 2–8 years) drive intra-household pneumococcal transmission: first, by acquiring, introducing, and harboring pneumococcus within the household, and then by transmitting acquired serotypes more efficiently than household members of other ages.
doi:10.1371/journal.pone.0079578
PMCID: PMC3894936  PMID: 24465365
25.  Increase in the Prevalence of the Newly Discovered Pneumococcal Serotype 6C in the Nasopharynx after Introduction of Pneumococcal Conjugate Vaccine 
The Journal of infectious diseases  2009;199(3):320-325.
Background
Because pneumococcal serotype 6C was previously not distinguished from serotype 6A, the impact of the 7-valent pneumococcal conjugate vaccine (PCV7) on the carriage of serotype 6C is unknown.
Methods
The nasopharyngeal (NP) prevalence of the 6C serotype was determined using 1326 pneumococcal isolates collected from 7 cohorts of Massachusetts children between 1994 and 2007. Initially, the isolates were serotyped using the quellung reaction; subsequently, stored specimens of all putative 6A isolates were tested for 6C using monoclonal antibodies. The opsonophagocytic and antibiotic susceptibilities of the isolates were determined.
Results
The prevalence of 6A was 9.6% (33/343) before 2001, 8.0% (18/226) in 2004, and 2.9% (12/416) in 2007. In contrast, the prevalence of 6C was 0.6% (2/343) before 2001, 2.2% (5/226) in 2004, and 8.7% (36/416) in 2007 (P < .001 for 2/343 vs. 36/416). 6C isolates from 2007 were more susceptible to antibiotics than were 6A isolates. PCV7 induced a low ability to opsonize different isolates of 6C.
Conclusions
Among NP isolates, the prevalence of 6C isolates has increased and the prevalence of 6A isolates has decreased since the introduction of PCV7 in Massachusetts in 2000. The observed increase in serotype 6C prevalence may be explained by the induction by PCV7 of low amounts of functional anti-6C antibody, compared with anti-6A and anti-6B antibodies.
doi:10.1086/596064
PMCID: PMC2743180  PMID: 19099489

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