Carriage Of Streptococcus Research Articles

Impact of Antimicrobial Treatment for Acute Otitis Media on Carriage Dynamics of Penicillin-Susceptible and Penicillin-Nonsusceptible Streptococcus pneumoniae.

Despite concerns that antimicrobial treatment of prevalent infections may select for drug-resistant bacteria, the effects of antimicrobial treatment on colonization dynamics have not been well quantified. We measured impacts of antimicrobial treatment on nasopharyngeal carriage of penicillin-susceptible Streptococcus pneumoniae (PSSP) and penicillin-nonsusceptible (PNSP) lineages at the end of treatment and 15, 30, and 60 days after treatment in a previously conducted randomized, double-blinded, placebo-controlled trial of amoxicillin-clavulanate for stringently defined acute otitis media. In intention-to-treat analyses, immediate treatment with amoxicillin-clavulanate reduced PSSP carriage prevalence by 88% (95% confidence interval [CI], 76%-96%) at the end of treatment and by 27% (-3%-49%) after 60 days but did not alter PNSP carriage prevalence. By the end of treatment, 7% of children who carried PSSP at enrollment remained colonized in the amoxicillin-clavulanate arm, compared with 61% of PSSP carriers who received placebo; impacts of amoxicillin-clavulanate persisted at least 60 days after treatment among children who carried PSSP at enrollment. Amoxicillin-clavulanate therapy reduced PSSP acquisition by >80% over 15 days. Among children who carried PNSP at enrollment, no impacts on carriage prevalence of S. pneumoniae, PSSP, or PNSP were evident at follow-up visits. Although the absolute risk of carrying PNSP was unaffected by treatment, antimicrobial therapy conferred a selective impact on colonizing pneumococci by accelerating clearance and delaying acquisition of PSSP.

Evaluation of different infant vaccination schedules incorporating pneumococcal vaccination (The Vietnam Pneumococcal Project): protocol of a randomised controlled trial

IntroductionWHO recommends the use of pneumococcal conjugate vaccine (PCV) as a priority. However, there are many countries yet to introduce PCV, especially in Asia. This trial aims to evaluate different...

Risk factors for carriage of Streptococcus pneumoniae in children

BackgroundDuring the past decades Streptococcus pneumoniae has developed significant resistance to many classes of antimicrobial drugs. Potential risk factors for colonization of the nasopharynx by Streptococcus pneumoniae in children and for carriage of drug resistant strains were examined.MethodsBetween 2007 and 2008 nasopharyngeal swabs were collected from 402 children 6 months to 5 years old visiting the public sector immunization centers and outpatient departments as well as offices of paediatricians from private practice in Nicosia district in Cyprus. Information on demographic characteristics and potential risk factors of participating children were collected using a standardized questionnaire distributed to parents.ResultsIn multivariable analyses we found that attendance at day care center, having siblings in the family and having both parents originating from Cyprus, statistically increased the risk of pneumococcal colonization. Full immunization with PCV7 appears to be a protective factor against colonization by pneumococcus. Previous administration of antimicrobials during the last month prior to specimen collection appeared to be the most consistent risk factor for carrying a non susceptible strain of Streptococcus pneumoniae to either penicillin or erythromycin. Factors such as age, nationality, previous or current breastfeeding, passive exposure to cigarette smoke and attendance in a day care center do not appear as independent risk factors for colonization by non susceptible strains.ConclusionsPrudent use of antibiotics especially for upper respiratory tract infections in children as well as increased vaccination coverage by the pneumococcal conjugate vaccines could prove effective in reducing levels of colonization by drug resistant pneumococcal strains.

Antibiotic Resistance of Potential Otopathogens Isolated From Nasopharyngeal Flora of Children With Acute Otitis Media Before, During and After Pneumococcal Conjugate Vaccines Implementation

To re-evaluate antibiotic strategies for acute otitis media (AOM) in young children, we analyzed the trends of nasopharyngeal carriage and antibiotic resistance of Streptococcus pneumoniae (Sp), Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mc) isolated from young children with AOM during a 16-year period. This cross-sectional study analyzed from 2001 to 2016 the nasopharyngeal carriage of Sp, Hi and Mc of young children with AOM. Medical history and physical findings were reported. Periods were defined by pneumococcal conjugate vaccine (PCV) introduction. We separately analyzed the 13-valent PCV (PCV13) period, which started after 2013. During the study, 12,973 children with AOM were enrolled by 138 pediatricians. By comparing the first and last PCV periods, the proportion of children in day care centers and that of AOM with conjunctivitis significantly increased. The proportion of penicillin nonsusceptible Sp carriage significantly decreased during the study, with 0.8% of penicillin-resistant strains isolated in the PCV13 period, but that of β-lactamase-producing Hi continually increased to 23.6% in 2016. The level of Mc β-lactamase-producing strains remained high (>97%). In the PCV13 period, the main predictors of β-lactamase-producing Hi carriage were conjunctivitis (adjusted odds ratio = 6.0, 95% confidence interval [4.7-7.7]) and attending a day care center (2.4 [1.7-3.5]). In the PCV13 period, the proportion of penicillin-resistant Sp carriage was very low and that of β-lactamase-producing Hi carriage did not exceed 20% among children with AOM and without conjunctivitis. Our results suggest that amoxicillin may remain the first-line antibiotic treatment for AOM in young children except for those with conjunctivitis, for which amoxicillin-clavulanate is still the best antibiotic.

Dynamics of Colonization of Streptococcus pneumoniae Strains in Healthy Peruvian Children

BackgroundAlthough asymptomatic carriage of Streptococcus pneumoniae (Spn) is common, acquisition of the bacteria is the first step in disease pathogenesis. We examined the effect of introduction of the 7-valent pneumococcal vaccine on Spn carriage patterns in a cohort of Peruvian children.MethodsWe used data from a prospective cohort study that collected monthly nasopharyngeal samples from children under 3 years of age. Spn isolates were serotyped using Quellung reactions, and bacterial density was determined by quantitative polymerase chain reaction. Changes in Spn carriage patterns, including the rate of carriage and number and density of serotypes carried over time, were evaluated before (2009) and after widespread vaccination with PCV7 (2011). Using all pneumococcal detections from each child and year, we identified serotypes that were present both at first and last detection as “persisters” and serotypes that replaced a different earlier type and were detected last as “recolonizers.”ResultsNinety-two percent (467/506) of children in 2009 and 89% (451/509) in 2011 carried Spn at least once. In 2009 and 2011, rates of carriage were 9.03 and 9.04 Spn detections per person-year, respectively. In 2009, 23F, a serotype included in PCV7, was the only type identified as a persister and 6A, 15B, and 19A were identified as recolonizer serotypes. In 2011, 6B and 7C were persister serotypes and 13 was a frequent recolonizer serotype.ConclusionsOverall Spn carriage among children under 3 in Peru was similar before and after introduction of PCV7; however, serotype-specific rates and longitudinal carriage patterns have shifted.

Nasopharyngeal carriage of Streptococcus pneumoniae among HIV-infected and -uninfected children

Nasopharyngeal carriage is a precursor for pneumococcal disease and can be useful for evaluating pneumococcal conjugate vaccine (PCV) impact. We studied pre-PCV pneumococcal carriage among HIV-infected and -uninfected children in Mozambique. Between October 2012 and March 2013, we enrolled HIV-infected children age <5 years presenting for routine care at seven HIV clinics in 3 sites, including Maputo (urban-south), Nampula (urban-north), and Manhiça (rural-south). We also enrolled a random sample of HIV-uninfected children <5 years old from a demographic surveillance site in Manhiça. A single nasopharyngeal swab was obtained and cultured following enrichment in Todd Hewitt broth with yeast extract and rabbit serum. Pneumococcal isolates were serotyped by Quellung reaction and multiplex polymerase chain reaction. Factors associated with pneumococcal carriage were examined using logistic regression. Overall pneumococcal carriage prevalence was 80.5% (585/727), with similar prevalences among HIV-infected (81.5%, 339/416) and HIV-uninfected (79.1%, 246/311) children, and across age strata. Among HIV-infected, after adjusting for recent antibiotic use and hospitalization, there was no significant association between study site and colonization: Maputo (74.8%, 92/123), Nampula (83.7%, 82/98), Manhiça (84.6%, 165/195). Among HIV-uninfected, report of having been born to an HIV-infected mother was not associated with colonization. Among 601 pneumococcal isolates from 585 children, serotypes 19F (13.5%), 23F (13.1%), 6A (9.2%), 6B (6.2%) and 19A (5.2%) were most common. The proportion of serotypes included in the 10- and 13-valent vaccines was 44.9% and 61.7%, respectively, with no significant differences by HIV status or age group. Overall 36.9% (n = 268) of children were colonized with a PCV10 serotype and 49.7% (n = 361) with a PCV13 serotype. Pneumococcal carriage was common, with little variation by geographic region, age, or HIV status. PCV10 was introduced in April 2013; ongoing carriage studies will examine the benefits of PCV10 among HIV-infected and–uninfected children.

The Impact of the 13-Valent Pneumococcal Conjugate Vaccine on Pneumococcal Carriage in the Community Acquired Pneumonia Immunization Trial in Adults (CAPiTA) Study.

The impact of pneumococcal conjugate vaccination on the prevalence of nasopharyngeal carriage with pneumococci and other bacteria in adults is unknown. The direct effects of the 13-valent pneumococcal conjugate vaccine (PCV13) in community dwelling older adults was investigated as part of the randomized controlled Community Acquired Pneumonia immunization Trial in Adults (CAPiTA). We determined the carriage of Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis before and 6, 12, and 24 months after vaccination using polymerase chain reaction (PCR)-based methods and conventional cultures of nasopharyngeal and oropharyngeal swab samples in 1006 PCV13 recipients and 1005 controls. Serotyping of the 13 vaccine-type (VT) pneumococci was performed by PCR targeting capsular synthesis genes and Quellung reaction of isolates. Before randomization and based on PCR, 339 of 1891 subjects had nasopharyngeal carriage with any pneumococci (17.9%), and 114 of 1891 (6.0%) carried VT pneumococci. At 6 months after vaccination, VT pneumococcal carriage was significantly lower in PCV13 recipients than in the placebo group (relative risk, 0.53; 95% confidence interval, .35-.80; P = .04). There was no difference between the groups at 12 and 24 months after vaccination. Carriage of non-VT pneumococci, S. aureus, H. influenzae, and M. catarrhalis did not change between groups. In community-dwelling adults aged ≥65 years, a single dose of PCV13 seems to elicit a small and temporary reduction in VT carriage 6 months after vaccination. Neither replacement by non-VT serotypes nor impact on other nasopharyngeal bacteria was observed.

Nasopharyngeal Carriage of Streptococcus pneumoniae and Related Risk Factors in Children Attending Day Care Centers

Nasopharyngeal Carriage of Streptococcus pneumoniae and Related Risk Factors in Children Attending Day Care Centers

The prevalence of carriage of Streptococcus pneumoniae among organized groups in Barnaul with assessment of antibiotic resistance and disinfectant resistance

The prevalence of carriage of Streptococcus pneumoniae among organized groups in Barnaul with assessment of antibiotic resistance and disinfectant resistance

Prevalence and serotype distribution of nasopharyngeal carriage of Streptococcus pneumoniae in China: a meta-analysis

BackgroundTo explore the overall prevalence and serotype distribution of nasopharyngeal carriage of Streptococcus pneumoniae(S. pneumoniae) among healthy children.MethodsA search for pneumococcal nasopharyngeal carriage studies including children published up to July 31th, 2016 was conducted to describe carriage in China. The review also describes antibiotic resistance in and serotypes of S. pneumoniae and assesses the impact of vaccination on carriage in this region. Summary measures for overall prevalence, antibiotic resistance, and serotype distributions extracted from the analyzed data were determined with 95% confidence intervals (CIs) using random-effects models. Heterogeneity was assessed using I2 test statistics.ResultsThirty-seven studies were included in this review, and the majority of studies (64.9%) were located in the pre-introduction period of 7-valent pneumococcal conjugate vaccine (PCV7) in China. The pooled prevalence of S. pneumoniae nasopharyngeal carriage was 21.4% (95% CI: 18.3–24.4%). Carriage was highest in children attending kindergartens [24.5%, (19.7–29.3%)] and decreased with increasing age. Before the introduction of PCV7 into China, the prevalence of S. pneumoniae nasopharyngeal carriage was 25.8% (20.7–30.9%), the pooled carriage of S. pneumoniae sharply dropped into the 14.1% (11.3–16.9%) by PCV7 vaccination period (P < 0.001). Before the pneumococcal conjugate vaccine (PCV) was introduced in China, the penicillin resistance rate in S. pneumoniae isolated from healthy children was 31.9% (21.2–42.6%); however, this rate sharply decreased after the introduction of PCV7 in China [21.6%, (7.4–35.9%)], and the difference between the rates during these two time periods was statistically significant (P value <0.05). Serotypes 19F, 6A and 23F were the most commonly isolated. Meta-analysis of data from young children showed a pooled rate estimate of 46.6% (38.8–54.4%) for PCV7 vaccine coverage and 66.2% (58.6–73.8%) for PCV13 vaccine coverage.ConclusionsThe prevalence of nasopharyngeal carriage among children was high in China. PCV7 immunization was found to be associated with reduction of nasopharyngeal colonization of S. pneumoniae. Conjugate vaccination coverage was slightly affected by the introduction of PCV7 into China because of low vaccination rate. The government should implement timely adjusted conjugate vaccination strategies based on our findings.

Measurement of pneumococcal IgG antibody, carriage and infection with Streptococcus pneumoniae in children under five years of age with acute respiratory infection in Niger.

Pneumonia is the major cause of mortality in children under five years. A total of 751 children aged 1-59 months admitted for acute respiratory infection were included in this study. Pneumococcal serum IgG antibody was determined by ELISA. Carriage of Streptococcus pneumoniae was determined by molecular analyses of nasopharyngeal swabbings, and the rapid urinary diagnostic test Binax NOW®Sp was used for detection of pneumococcal antigen in urine. A total of 224 (29.8%) children had vaccination record books, and among them, 186 (83%) were vaccinated with the 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV-23), 7 (3%) were vaccinated with the 13-Valent Pneumococcal Conjugate Vaccine (PCV-13), and 31 (14%) had not been vaccinated. IgG levels against pneumococcal polysaccharide were ≥1.3μg/mL in most of the children (99.4%). The carriage rate of S. pneumoniae was 39%, and the Binax NOW®Sp test was positive in 26% of children. There was no significant variation between the means of IgG concentrations against pneumococcal polysaccharides as related to vaccination status, age and nasopharyngeal carriage of S. pneumoniae. However, there was a weak positive correlation between age and level of IgG (r=0.08; p=0.021), and there was a significant variation (p=0.038) of the IgG level according to presence of S. pneumoniae antigen in urine. The presence of S. pneumoniae antigen in urine is significantly (p≤0.01) higher in children with nasopharyngeal carriage of S. pneumoniae (40%) than non-carriers (20%). This study shows that S. pneumoniae has high circulation in children under the age of five years either through infection or carriage.

Nasopharyngeal Carriage and Antimicrobial Susceptibility Patterns of Streptococcus pneumoniae among Children under Five in Southwest Ethiopia.

Nasopharyngeal carriage of Streptococcus pneumoniae is found to play an important role in the development and transmission of pneumococcal diseases. In this study, we assessed the nasopharyngeal carriage, antimicrobial susceptibility patterns and associated risk factors of S. pneumoniae among children under five. A total of 361 children under five attending the outpatient department of Shanan Gibe Hospital in Jimma, Southwest Ethiopia were enrolled from June to September 2014. Nasopharyngeal specimens were collected using sterile plastic applicator rayon tipped swab and inoculated on tryptone soy agar supplemented with 5% sheep blood and 5 µg/mL gentamycin. Antimicrobial susceptibility testing was performed using the modified disk diffusion method. The overall prevalence of S. pneumoniae carriage was 43.8% (158/361) among children under five. Resistance to tetracycline, cotrimoxazole, penicillin, chloramphenicol and erythromycin was observed in 53.2% (84/158), 43.7% (69/158), 36.1% (57/158), 13.3% (21/158) and 8.9% (14/158) of isolates respectively. Multidrug resistance was seen in 17.7% (28/158) of isolates. In multivariate logistic regression analysis, children living with sibling(s) < 5 years old (adjusted odds ratio (AOR) = 1.798; 95% confidence interval (CI), 1.169–2.766) and malnutrition (AOR = 2.065; 95% CI, 1.239–3.443) were significantly associated with S. pneumoniae carriage. A high nasopharyngeal carriage of S. pneumoniae was observed among children under five in Southwest Ethiopia. There should be a strategy to prevent S. pneumoniae nasopharyngeal colonization and identify the appropriate antibiotic to the individual child.

Efficacy of a novel, protein-based pneumococcal vaccine against nasopharyngeal carriage of Streptococcus pneumoniae in infants: A phase 2, randomized, controlled, observer-blind study

BackgroundConserved pneumococcal proteins are potential candidates for inclusion in vaccines against pneumococcal diseases. In the first part of a two-part study, an investigational vaccine (PHiD-CV/dPly/PhtD-30) containing 10 pneumococcal serotype-specific polysaccharide conjugates (10VT) combined with pneumolysin toxoid and pneumococcal histidine triad protein D (30μg each) was well tolerated by Gambian children. Part two, presented here, assessed the efficacy of two PHiD-CV/dPly/PhtD formulations against pneumococcal nasopharyngeal carriage (NPC) prevalence in infants. MethodsIn this phase 2, randomized, controlled, observer-blind trial, healthy infants aged 8–10weeks, recruited from a peri-urban health center, were randomized (1:1:1:1:1:1) into six groups. Four groups received PHiD-CV/dPly/PhtD (10 or 30μg of each protein), PHiD-CV, or 13-valent pneumococcal conjugate vaccine at ages 2–3–4months (3+0 infant schedule) and two groups PHiD-CV/dPly/PhtD-30 or PHiD-CV at 2–4–9months (2+1 infant schedule). The primary objective was impact on non-10VT NPC at ages 5–9–12months. Secondary objectives included confirmatory analysis of protein dose superiority and safety/reactogenicity. Impact on pneumococcal NPC acquisition, bacterial load, and ply and phtD gene sequencing were explored. Results1200 infants were enrolled between June 2011 and May 2012. Prevalences of pneumococcal (60–67%) and non-10VT (55–61%) NPC were high at baseline. Across all post-vaccination time points, efficacy of PHiD-CV/dPly/PhtD-10 and PHiD-CV/dPly/PhtD-30 against non-10VT NPC (3+0 schedule) was 1.1% (95% CI −21.5, 19.5) and 2.1% (−20.3, 20.3), respectively; efficacy of PHiD-CV/dPly/PhtD-30 (2+1 schedule) was 0.5% (−22.1, 18.9) versus PHiD-CV. No differences were observed in pneumococcal NPC acquisition, clearance, or bacterial load. Both protein-based vaccines elicited immune responses to pneumococcal proteins. ConclusionsIn this high carriage prevalence setting, inclusion of pneumococcal proteins in the PHiD-CV/dPly/PhtD investigational vaccine had no impact on pneumococcal NPC in infants, regardless of protein dose or schedule. Future evaluations will assess its impact against pneumococcal disease endpoints.Funding: PATH, GlaxoSmithKline Biologicals SA. ClinicalTrials.gov identifier NCT01262872.

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.

Effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae among children in São Paulo, Brazil

In March 2010, Brazil introduced the 10-valent pneumococcal conjugate vaccine (PCV10) in the routine infant immunization program using a 4-dose schedule and catch-up for children <23months. We investigated PCV10 effect on nasopharyngeal carriage with vaccine-type Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) among children in São Paulo city. Cross-sectional surveys were conducted in 2010 (baseline) and 2013 (post-PCV10). Healthy PCV-naïve children aged 12–23months were recruited from primary health centers during immunization campaigns. Nasopharyngeal swabs were collected and tested for Hi; for Spn, all baseline and a stratified random sample of 400 post-PCV10 swabs were tested. We compared vaccine-type Spn and NTHi carriage prevalence pre-/post-PCV10, and used logistic regression to estimate PCV10 effectiveness (1-adjusted odds ratio×100%). Overall 501 children were included in the baseline and 1167 in the post-PCV10 survey (including 400 tested for Spn). Spn was detected in 40.3% of children at baseline and 48.8% post-PCV10; PCV10 serotypes were found in 19.8% and 1.8% respectively, representing a decline of 90.9% (p<0.0001). Carriage of vaccine-related serotypes increased (10.8–21.0%, p<0.0001), driven primarily by a rise in serotype 6C (1.8–11.2%, p<0.0001); carriage of serotypes 6A and 19A did not significantly change. PCV10 effectiveness (4 doses) against vaccine-type carriage was 97.3% (95% confidence interval 88.7–99.3). NTHi prevalence increased from 26.0% (130/501) to 43.6% (509/1167, p<0.0001); PCV10 vaccination seemed significantly associated with NTHi carriage, even after adjusting for other known risk factors. Carriage with PCV10 serotypes among toddlers declined dramatically following PCV10 introduction in São Paulo, Brazil. No protection of PCV10 against NTHi was observed. Our findings contribute to a growing body of evidence of PCV10 impact on vaccine-type carriage and highlight the importance of PCV10 as a tool to reduce the burden of pneumococcal disease in Brazil and globally.

Aboriginal and non-Aboriginal children in Western Australia carry different serotypes of pneumococci with different antimicrobial susceptibility profiles.

BackgroundCarriage of Streptococcus pneumoniae is considered a precursor to pneumococcal diseases including pneumonia. As part of the Kalgoorlie Otitis Media Research Project, we characterised pneumococci isolated from the nasopharynx of Western Australian Aboriginal and non-Aboriginal children.MethodsBetween 1999 and 2005, 100 Aboriginal and 180 non-Aboriginal children were followed from birth to two years, with nasopharyngeal aspirates collected at ages 1–3 and 6–8 weeks, then at 4, 6, 12, 18 and 24 months. Introduction of 7-valent pneumococcal conjugate vaccine (7vPCV) in 2001 enabled evaluation of its impact on carriage in study participants according to vaccines doses received. Pneumococcal serotyping was performed by Quellung and antimicrobial susceptibility by disk diffusion and Etest®. Molecular epidemiology of pneumococcal isolates was investigated by pulse-field gel electrophoresis and multilocus sequence typing.ResultsOverall, the prevalence of 7vPCV serotypes was similar for Aboriginal and non-Aboriginal children (19 % vs. 16 %), but the prevalence of non-vaccine serotypes was higher in Aboriginal children (22 % vs. 7 %). A multi-resistant 6B clone (ST90) was found only in non-Aboriginal children. Aboriginal children who received three doses of 7vPCV had lower odds of carrying 7vPCV serotypes (odds ratio [OR] 0.19, 95 % CI 0.08–0.44) and higher odds of carrying non-vaccine serotypes (OR 2.37, 95 % CI 1.13–4.99) than unvaccinated Aboriginal children; this finding was not observed in non-Aboriginal children.ConclusionsThis unique study shows important differences in pneumococcal serotypes, genotypes, and antimicrobial susceptibility between Aboriginal and non-Aboriginal children living in the same geographic area before widespread 7vPCV use, and highlights the need for ongoing post-vaccination surveillance in outback Australia.Electronic supplementary materialThe online version of this article (doi:10.1186/s41479-016-0015-9) contains supplementary material, which is available to authorized users.

Limited impact of neonatal or early infant schedules of 7-valent pneumococcal conjugate vaccination on nasopharyngeal carriage of Streptococcus pneumoniae in Papua New Guinean children: A randomized controlled trial

Streptococcus pneumoniae is a leading cause of pneumonia, the most common cause of childhood death. Papua New Guinean children experience high rates of nasopharyngeal pneumococcal colonization within weeks of birth, predisposing them to pneumococcal disease. In a trial to determine the safety and immunogenicity of early infant vaccination with 7-valent pneumococcal conjugate vaccine (7vPCV), we investigated the impact of early schedules on pneumococcal carriage.Infants were randomized at birth to receive 7vPCV in a 0–1–2-month (n=101) or a 1–2–3-month (n=105) schedule or no 7vPCV (n=106). All children received 23-valent pneumococcal polysaccharide vaccine at age 9months. We cultured nasopharyngeal swabs (NPS) collected at ages 1, 2, 3, 4weeks and 3, 9, 18months, and middle ear discharge if present. Pneumococcal serotypes were identified by the Quellung reaction.A total of 1761 NPS were cultured. The prevalence of pneumococcal carriage was 22% at 1week of age, rising to 80% by age 3months and remained >70% thereafter, with high-density carriage in 42% of pneumococcus-positive samples. We identified 63 different serotypes; 43% of isolates from controls were 13vPCV serotypes. There were no significant differences in 7vPCV serotype carriage between 7vPCV recipients and controls at any age (22% vs. 31% at 9months, p=0.2). At age 9months the prevalence of non-7vPCV carriage was 17% higher in 7vPCV recipients (48%) than in controls (25%, p=0.02). More non-7vPCV serotypes were isolated from ear discharge in 16 7vPCV recipients than from 4 controls (48% vs. 25%, p=0.13).The limited impact of neonatal or accelerated infant 7vPCV schedules on vaccine serotype carriage is probably due to the early onset of dense carriage of a broad range of pneumococcal serotypes. While serotype-independent pneumococcal vaccines are needed in high-risk populations, the underlying environmental factors and sources of infection must be investigated.http://clinicaltrials.gov/ct2/show/NCT00219401.

The impact of a pneumococcal conjugate vaccination program on the nasopharyngeal carriage, serotype distribution and antimicrobial resistance of Streptococcus pneumoniae among healthy children in Turkey

BackgroundThe 7-valent conjugate pneumococcal vaccine (PCV7) was introduced by the Turkey National Immunization Program in 2008 and replaced by the PCV13 in 2011. We assessed the impact of PCV vaccination on the nasopharyngeal (NP) carriage, serotype distribution and antimicrobial resistance of Streptococcus pneumoniae (SP) among healthy Turkish children. MethodsA prospective surveillance study was performed between September 2011 and September 2013 in Istanbul, Turkey. NP swabs, demographic data, and vaccination statuses were obtained from 2165 healthy children aged 0–18years. Pneumococcal carriage was defined by a positive culture; serotyping was performed via multiplex conventional PCR, and the antibiotic susceptibilities of the isolates were determined based on the minimum inhibitory concentration (MIC) values of the Clinical Laboratory Standards Institute (CLSI). ResultsThe prevalence of pneumococcal carriage was 6.4%. The carriage rates were 8%, 7%, and 5% in the following age groups: 0–24months, 25–60months, and >60months, respectively. The carriage rate was significantly higher in the 0–24month age group than in the >60months age group (p=0.03). Sixty percent of the children were not vaccinated with any PCV; 4%, 2%, and 4% received at least 1, 2 or 3 doses and 30% children received the full schedule (4 doses) of either PCV7 or PCV13. Among the isolated S. pneumoniae strains, 45% were of the non-vaccine type (NVT) and 55% were of the vaccine type (VT). The children who received at least a single PCV dose had significantly lower odds of colonization via VT serotypes than the non-vaccinated children [odds ratio: 0.61 (95% confidence interval=0.41–0.91), p=0.01]. The percentages of the serotypes covered by PCV7 and PCV13 were 51% and 56%, respectively. The most frequently isolated serotypes were 6A/B/C (n=22, 16.5%), 19F (n=18, 13.5%), 23F (n=15, 11.2%), serotype 9V/A (n=10, 7.5%), 12F (n=5, 4.5%), 15A/F (n=7, 4.5%) and 22 A/F (n=6, 4.5%). Using the meningitis criteria and the MIC, 62% of the isolates were resistant to penicillin and 13% were non-sensitive to ceftriaxone. Erythromycin and clindamycin resistance were 43% and 31%, respectively. ConclusionWe shown that following nation-wide PCV vaccination, S. pneumoniae NP carriage was decreased.

Associations between nasopharyngeal carriage of Group B Streptococcus and other respiratory pathogens during early infancy.

BackgroundIn West Africa, the carriage of Group B Streptococcus (GBS), among infants is poorly characterised. We investigated co-carriage of GBS with other respiratory pathogens in the infants’ nasopharynx in The Gambia.MethodsWe assessed the carriage, serotypes and antibiotic susceptibility of Beta-haemolytic Streptococci (BHS) groups A-G; along with the carriage of Streptococcus pneumoniae; Haemophilus influenzae; Staphylococcus aureus and Moraxella catarrhalis in 1200 two-month old infants.ResultsThe BHS prevalence was 20.0 % and GBS dominated (13.8 %), particularly serotypes V and II; serotype V being negatively associated with H. Influenzae carriage (OR 0.41 [95 % CI: 0.18–0.93], p = 0.033). Although co-colonization of GBS and other BHS was not seen, colonization with GBS was positively associated with S. aureus (OR 1.89 [95 % CI: 1.33–2.69], P < 0.001) and negatively associated with S. pneumoniae (OR 0.47 [95 % CI: 0.33–0.67], p < 0.001) and M. catarrhalis (OR 0.61 [95 % CI: 0.40–0.92], p = 0.017). ≥ 89 % of GBS isolates were susceptible to most antibiotics tested, except for tetracycline resistance, which was 89 %.ConclusionThis study provides baseline data on the carriage of GBS in two month old infants from West Africa. The dominant serotypes of GBS in this setting are serotypes V and II. This may be important for future GBS vaccine development for the West African sub-region.

General health, otitis media, nasopharyngeal carriage and middle ear microbiology in Northern Territory Aboriginal children vaccinated during consecutive periods of 10-valent or 13-valent pneumococcal conjugate vaccines

ObjectivesThis study aims to monitor the prevalence of suppurative otitis media in remote Indigenous communities after introduction of 13-valent pneumococcal conjugate vaccine (PCV13) in October 2011. We previously reported a decline in suppurative OM following replacement of PCV7 by 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10) in October 2009. MethodsWe continued regular surveillance in remote Indigenous communities between February 2010 and August 2013. This analysis reports the general health, otitis media (OM), nasopharyngeal (NP) carriage and middle ear microbiology in children less than 36 months of age who received a primary course of at least two doses of PHiD-CV10 or PCV13, and not more than one dose of another pneumococcal vaccine. ResultsMean ages of 511 PHiD-CV10- and 140 PCV13-vaccinated children were 19 and 13 months, respectively. Most children received 3-dose non-mixed PCV schedules. At the time of assessment, general health was poor and prevalence of risk factors was high in both groups: overall, around 14% of children had scabies, 20% had impetigo, 59% had runny nose and 39% had cough. Average household size was 8 persons, and 60% of the mothers smoked. Bilaterally normal middle ears were detected in 10% and 7%, respectively. OM with effusion (OME), almost all bilateral, was diagnosed in 52% and 50%, any suppurative OM (acute OM or any tympanic membrane perforation [TMP]) in 37% and 41%, and TMP in 14% and 12%, respectively. Children in the PCV13 group had significantly less NP carriage of combined Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi) (62% versus 51%) but significantly more polymicrobial (Spn and NTHi) middle ear cultures (12% versus 43%), and significantly less Staphylococcus aureus-positive middle ears (40% versus 7%). Although NP carriage of pneumococcal serotype 19A was low in the PCV13 group, serotypes 19F and 23F persist. ConclusionsThe general health, particularly ear health, of little children in remote Australian Indigenous communities remains in crisis. In particular, transition to PCV13 did not show substantial further improvement in ear health. Possible vaccine-related differences in microbiology, including potential beneficial effects of PHiD-CV10 on NTHi infection, need to be further evaluated in randomised trials.