Streptococcus pneumoniae colonization after introduction of 13-valent pneumococcal conjugate vaccine for US adults 65 years of age and older, 2015–2016

Background

Vaccination of children with 13-valent pneumococcal conjugate vaccine (PCV13) led to declines in vaccine-type pneumococcal nasopharyngeal carriage among adults through indirect effects. In August 2014, PCV13 immunization of all U.S. adults ≥65?years of age was recommended. This study sought to define prevalence and serotype distribution of pneumococcal carriage among adults ≥65?years of age and to describe risk factors for colonization soon after introduction of PCV13 in adults.

Colonization with 19F and other pneumococcal conjugate vaccine serotypes in children in St. Louis,Missouri, USA

BackgroundThe epidemiology of nasopharyngeal (NP) pneumococcal carriage varies with geography and has changed in response to pneumococcal conjugate vaccine (PCV): a low prevalence (3% or less of colonizing isolates) of colonization by vaccine-type (VT) pneumococcal serotypes after PCV introduction has been reported. The primary goal of this study was to determine the VT serotype prevalence of NP pneumococcal colonization of children residing in the St. Louis, MO, USA metropolitan area following introduction of the 13-valent PCV in 2010. The secondary goal of this study was to identify characteristics associated with NP pneumococcal carriage of any serotype.MethodsBetween July 2013 and April 2016, we enrolled 397 healthy children, aged 0–17 years, who required sedation for procedures or minor surgeries at St. Louis Children’s Hospital. NP swabs were collected after sedation or anesthesia and cultured for pneumococcus. Vaccine records were obtained from primary care providers or from state immunization databases. Parents/guardians completed a questionnaire to provide demographics, past medical history and household characteristics.ResultsOf the 88 pneumococcal isolates recovered from 84 colonized subjects (21.2% of all enrolled subjects; 95% CI 17.2–25.2%), 16 were VT. Eleven isolates were serotype 19F (12.5%), four (4.5%) were 6A and one (1.1%) was 19A. Prevalence of VT among colonizing isolates was thus 18.2% (CI 10.1–26.1%) in our cohort, despite complete PCV vaccination in 87% of colonized children. Factors associated with pneumococcal colonization by any serotype included younger age and daycare attendance.ConclusionChildren in St. Louis exhibit a higher prevalence of VT serotypes among pneumococcal carriage isolates than has been reported in other areas in the US, demonstrating the necessity of ongoing surveillance of local epidemiology and providing evidence that serotype 19F can remain prevalent in a pediatric population despite high vaccine uptake.     

Impact of the Hajj on pneumococcal carriage and the effect of various pneumococcal vaccines

BackgroundThe Islamic Hajj pilgrimage is the largest annual mass gathering in the world. The overcrowding of people promotes the acquisition, spread and transmission of respiratory pathogens, including Streptococcus pneumoniae.MethodsWe conducted a methodological review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The objective was to summarize the available data regarding the prevalence of pneumococcal carriage among Hajj pilgrims and about carriage acquisition and circulation of S. pneumoniae among pilgrims before and after participating in the Hajj according to their vaccination status.ResultsEight articles met eligibility criteria for pneumococcal carriage and impact of pneumococcal vaccination on carriage. Seven of them showed a significant increase in nasopharyngeal carriage of pneumococci following the pilgrimage, with acquisition rates ranging from 18 to 36%. Serotypes 3, 19F and 34 are the most common. A significant increase in antibiotic resistant strains was observed following participation in the Hajj. A lower prevalence was found in pilgrims treated with antibiotics, those who used a hand sanitizer, or those who washed their hands more frequently than usual. An increased carriage of pneumococcal serotypes included in pneumococcal vaccines (10-valent pneumococcal conjugate vaccine (PCV10), 13-valent pneumococcal conjugate vaccine (PCV13), 23-valent pneumococcal polysaccharide vaccine (PPV23)) was observed following participation in the Hajj. To date, no study has shown a significant reduction in pneumococcal carriage among pilgrims after vaccination with PPV23 or PCV. In fact, no significant difference was currently observed in the prevalence ratio of pneumococcal carriage between vaccinated and unvaccinated pilgrims.ConclusionThe studies analyzed in this review showed an increased carriage of pneumococcus in post-Hajj pilgrims compared to pre-Hajj pilgrims, including vaccine serotypes. Further studies are needed to investigate the possible relationships between carriage, disease and vaccine in pilgrims.     

Pneumococcal carriage among adults aged 50 years and older with co-morbidities attending medical practices in Rome,Italy

BackgroundData on Streptococcus pneumoniae carriage in adults with co-morbidities are limited. In this study we estimated the pneumococcal carriage among adults with co-morbidities and evaluated socio-demographic and clinical risk factors. The potential coverage of the current pneumococcal vaccines recommended for adults (PCV13 and PPV23) was also investigated.MethodsA cross-sectional study on S. pneumoniae carriage among unvaccinated adults ≥50 years with co-morbidities, presenting with or without acute respiratory symptoms at general practitioners in Rome, Italy, between October 2015 and July 2016 was conducted. Pneumococcal carriage was investigated by both cultural and molecular methods. Socio-demographic variables and co-morbidities were evaluated by logistic models as possible risk factors for pneumococcal carriage.ResultsOut of 248 patients (median age: 73 yrs; IQR: 65–79), 12 (4.8%) and 83 (33.5%) individuals were found colonized using cultural or molecular methods, respectively. Potential risk factors for pneumococcal colonization as ascertained by molecular methods were: low level of education (adjusted OR = 3.71, 95% CI: 1.62–9.40), winter months (December-March vs other months, adjusted OR = 2.56, 95% CI: 1.29–5.14), and presence of chronic lung diseases (adjusted OR = 2.18, 95% CI: 1.15–4.16). The combination of serotype-specific multiplex RT-PCR and conventional PCR allowed to identify 22 serotypes/group of serotypes, of which the most common were: 24F/24A/24B, 12F/12A/12B/44/46, 6A/6B, 14, 15B/15C, and 22F/22A. Prevalence of pneumococcal carriage due to PCV13 serotypes and non-PCV13 serotypes was 23.6% and 67.3%, respectively. Prevalence of colonization due to PPV23 serotypes was estimated to be 54.6%.ConclusionsA high prevalence of S. pneumoniae carriage was observed among adults with co-morbidities, especially among individuals affected by chronic lung diseases. These results support vaccine strategies based on the sequential administration of PCV13 and PPV23 to control potentially invasive pneumococcal strains in adults, especially in subjects with co-morbidities.     

Cost-effectiveness of an in-development adult-formulated pneumococcal vaccine in older US adults

IntroductionCDC pneumococcal vaccination recommendations for older adults now include either 15- or 20-valent pneumococcal conjugate vaccine (PCV15/PCV20). However, an in-development 21-valent vaccine (PCV21), formulated based on adult pneumococcal disease epidemiology, could substantially increase coverage of disease-causing pneumococcal serotypes, particularly in Black older adults, who are at greater risk. The potential public health impact and cost-effectiveness of PCV21 compared to currently recommended vaccines in older adults is unclear.MethodsA Markov decision model compared current pneumococcal vaccination recommendations to PCV21 use in Black and non-Black 65-year-old cohorts. CDC Active Bacterial Core surveillance data informed population and serotype-specific pneumococcal disease risk. Vaccine effectiveness was estimated using Delphi panel estimates and clinical trial data, with variation in sensitivity analyses. Potential indirect effects on adult disease from PCV15 childhood vaccination were examined. All model parameters were varied individually and collectively in sensitivity analyses. Scenarios with decreased PCV21 effectiveness and potential COVID-19 pandemic effects were also examined.ResultsIn the Black cohort, the PCV21 strategy cost $88,478 per quality adjusted life-year (QALY) gained without and $97,952/QALY with childhood PCV15 indirect effects. PCV21 in the non-Black cohort cost $127,436/QALY gained without and $141,358/QALY with childhood PCV15 effects. Current recommendation strategies were economically unfavorable, regardless of population or indirect childhood vaccination effects. Results favoring PCV21 use were robust in sensitivity analyses and alternative scenarios.ConclusionAn in-development PCV21 vaccine would likely be economically and clinically favorable compared to currently recommended pneumococcal vaccines in older adults. While PCV21 was more favorable in Black cohort analyses, results for both Black and non-Black populations were economically reasonable, highlighting the potential importance of adult-specific pneumococcal vaccine formulations and, pending further investigation, potentially justifying a future general population recommendation for PCV21 use in older adults.     

Perceptions of influenza and pneumococcal vaccine uptake by older persons in Australia

BackgroundInfluenza and pneumococcal vaccinations reduce adverse health outcomes in older adults. The Australian National Immunisation Program (NIP) provides free seasonal influenza and pneumococcal vaccinations for adults ≥65 y. Guidelines recommend all adults ≥65 y receive one dose of 23-valent pneumococcal polysaccharide vaccine (23vPPV) regardless of their risk of invasive pneumococcal disease. However, the reported rate of vaccination against pneumococcal disease is much lower than seasonal influenza. Identifying and understanding the perspective of older people on vaccination is important to informing effective promotional strategies for this age group.MethodsUsing a purposive and snowball recruitment strategy, 36 participants aged between 65 and 84 years of age were recruited in south-east Queensland and northern New South Wales. Face-to-face qualitative interviews conducted between July 2017 and January 2018 were recorded, transcribed and thematically analysed.ResultsIn this sample, the uptake of the influenza vaccine (n = 28, 78%) was greater than for the pneumococcal vaccine (n = 14, 39%). Five key themes identified were health practitioner influence; anti-vaccination influence; social responsibility; work-based vaccination; and perceptions of age. The influences on uptake were complex and multi-faceted.ConclusionsFindings provide new insights, in particular, the role of social responsibility, the long-term impact of workplace vaccinations, and how older people do not necessarily consider themselves old.     

Indirect effects of childhood pneumococcal vaccination on pneumococcal carriage among adults and older children in Australian Aboriginal communities

Nasopharyngeal carriage of Streptococcus pneumoniae in unimmunised adults and older children in three remote Australian Aboriginal communities was compared in 2002 and 2004. Universal childhood pneumococcal vaccination with a catch-up program was introduced in late 2001. Carriage prevalence across all age groups of pneumococcal serotypes included in the 7-valent vaccine was 10% in both 2002 and 2004 (12 and 30 months after introduction of vaccination). This carriage prevalence was lower than anticipated. It is likely that indirect effects of childhood vaccination occurred before the 2002 survey. To further assess indirect effects on carriage of childhood pneumococcal vaccination, data prior to 2002 are required. Between 12 and 30 months following introduction of conjugate pneumococcal vaccination, indirect effects on carriage were unchanged.     

Reduced nontypeable Haemophilus influenzae lower airway infection in children with chronic endobronchial suppuration vaccinated with the 10-valent pneumococcal H. influenzae protein D conjugate vaccine

BackgroundNontypeable Haemophilus influenzae (NTHi), the most common bacterial lower airway infection in children with protracted bacterial bronchitis, is associated with progression to bronchiectasis. We determined whether vaccination with 10-valent pneumococcal NTHi protein-D conjugate vaccine (PHiD-CV) reduced NTHi lower airway infection compared to children not PHiD-CV-vaccinated. Our unique childhood vaccination schedule and prospective 9-year bronchoalveolar lavage (BAL) collection provided an exclusive opportunity to examine this hypothesis.MethodsPaired BAL fluids and nasopharyngeal (NP) swabs were collected from 543 children (2007–2016) undergoing bronchoscopy for chronic cough. Children who received a primary course of ≥2 doses of one pneumococcal conjugate vaccine (PCV) and <2 doses of another PCV were included in each vaccine group. Logistic regression determined associations between NTHi lower airway infection (≥10⁴ colony-forming units/mL BAL) and age, sex, Indigenous status, antibiotic exposure, and PHiD-CV vaccination.ResultsOf 262 PCV7-vaccinated, 53 PHiD-CV-vaccinated and 166 PCV13-vaccinated children (62 had mixed schedules, <2 PCV doses or missing vaccination data), NTHi lower airway infection was detected in 89 (34%), 9 (17%) and 47 (28%), respectively. On multivariate regression, significant independent factors associated with reduced NTHi lower airway infection were PHiD-CV vaccination (OR_adjusted = 0.42, 95%CI 0.19–0.93), macrolide use (OR_adjusted = 0.57, 95%CI 0.35–0.93) and increasing age (OR_adjusted = 0.88, 95%CI 0.80–0.96). PHiD-CV vaccination had no impact on NTHi NP carriage.ConclusionsPHiD-CV-vaccinated children were significantly less likely to have NTHi lower airway infection than children not PHiD-CV-vaccinated. PHiD-CV is likely an effective intervention for reducing NTHi endobronchial infection in children at risk of chronic suppurative lung diseases.     

Effectiveness of the 23-valent pneumococcal polysaccharide vaccine against community-acquired pneumonia in older individuals after the introduction of childhood 13-valent pneumococcal conjugate vaccine: A multicenter hospital-based case-control study in Japan

BackgroundIn the era of childhood pneumococcal conjugate vaccine (PCV) immunization, especially 13-valent pneumococcal conjugate vaccine (PCV13) immunization, serotype replacement of Streptococcus pneumoniae and herd immunity in adults have been reported worldwide. Therefore, continuous evaluation of the effectiveness of the pneumococcal vaccine in adults is crucial because vaccine effectiveness may change owing to these factors. The purpose of this study was to evaluate the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against all-cause pneumonia and pneumococcal pneumonia in older individuals with community-acquired pneumonia (CAP) after the introduction of childhood PCV13 in Japan, a topic that has remained largely unexplored.MethodsWe evaluated pneumococcal vaccine effectiveness in this multicenter, matched case-control study conducted in hospitals and clinics. Cases included patients (aged ≥ 65 years) newly diagnosed with CAP between October 2016 and September 2019. A maximum of five non-pneumonia control patients matched for sex, school grade, date of outpatient visit, and medical institution were selected for each case. Conditional logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of pneumococcal vaccines for the occurrence of all-cause CAP and pneumococcal CAP.ResultsThe analysis included 740 individuals (142 patients and 598 controls). The median age of participants was 75 years (men: 54%). The adjusted OR for pneumococcal vaccination against all-cause CAP was 1.31 (95% CI: 0.84–2.06), while that for PPSV23 vaccination in the previous 5 years was 1.33 (95% CI: 0.85–2.09). The adjusted OR for PPSV23 vaccination in the previous 5 years against pneumococcal CAP was 0.93 (95% CI: 0.35–2.50).ConclusionsThis study was unable to demonstrate the effectiveness of PPSV23 against all-cause and pneumococcal pneumonia after the introduction of childhood PCV13 in Japan. Nonetheless, additional studies are needed to validate these results.     

Safety,tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine,followed by sequential PPSV23 vaccination in healthy adults aged ≥50 years: A randomized phase III trial (PNEU-PATH)

BackgroundStreptococcus pneumoniae causes pneumococcal disease, and older adults are at an increased risk. Sequential vaccination of 13-valent pneumococcal conjugate vaccine (PCV13) followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for broad protection against pneumococcal disease in some countries.MethodsThis phase III trial evaluated the safety, tolerability, and immunogenicity of sequential administration of either V114 (a 15-valent PCV containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F) or PCV13, followed 12 months later by PPSV23, in healthy adults aged ≥50 years (NCT03480763). A total of 652 participants were randomized 1:1 to receive either V114 or PCV13, followed by PPSV23.ResultsThe most common solicited adverse events (AEs) following PCV vaccination included injection-site pain and fatigue. Higher proportions of participants with these events were observed in the V114 group following PCV; however, these differences were not clinically significant. Following PPSV23 vaccination, the most common solicited AEs were injection-site pain and injection-site swelling; the proportions of participants with these events were comparable between both groups. Incidence of serious AEs was low in both groups following PCV and PPSV23, and none were related to study vaccines. No deaths occurred during the study. Serum opsonophagocytic activity geometric mean titers and immunoglobulin G geometric mean concentrations were comparable between both groups for all 15 serotypes in V114 following PPSV23. Immune responses elicited by V114 persisted for at least 12 months. Immune responses at 30 days and 12 months post-vaccination with PCV were comparable between both groups for the 13 shared serotypes and higher in the V114 group for the V114-unique serotypes (22F and 33F).ConclusionAdministration of V114 followed by PPSV23 was well tolerated and induced comparable antibody levels to PCV13 followed by PPSV23 in healthy adults aged ≥50 years.     

Vaccine preferences and acceptance of older adults

BackgroundExpanding vaccination programs for the older population might be important as older adults are becoming a larger proportion of the general population. The aim of this study is to determine the relative importance of vaccine and disease specific characteristics and acceptance for Dutch older adults, including pneumococcal disease, herpes zoster, pertussis vaccination, and influenza vaccination.MethodsA discrete choice experiment was conducted to generate choice data that was analyzed using a mixed multinomial logit statistical model.ResultsImportant factors that were associated with vaccination acceptance in older adults are high mortality risk of the infectious disease, high susceptibility of getting the infectious disease, and high vaccine effectiveness. Age, influenza vaccination in 2013 and self-perceived health score were identified as personal factors that affect vaccine preference. Potential vaccination rates of older adults were estimated at 68.1% for pneumococcal vaccination, 58.1% for herpes zoster vaccination, 53.9% for pertussis vaccination and 54.3% for influenza vaccination. For persons aged 50–65, potential vaccination rates were estimated at 58.1% for pneumococcal vaccination, 49.5% for herpes zoster vaccination, 43.9% for pertussis vaccination and 42.2% for influenza vaccination. For persons aged 65 and older, these were respectively 76.2%, 67.5%, 57.5% and 65.5%.DiscussionOur results suggest that older adults are most likely to accept pneumococcal vaccination of the four vaccines. Information provision accompanied with the implementation of a new vaccine has to be tailored for the individual and the vaccine it concerns. Special attention is needed to ensure high uptake among persons aged 50–65 years.     

Carriage of Streptococcus pneumoniae in asymptomatic,community-dwelling elderly in the Netherlands

Colonization of the upper respiratory tract by Streptococcus pneumoniae is considered prerequisite for pneumococcal disease. Despite high rates of pneumococcal disease in elderly, pneumococcal carriage rates are usually below 5% when detected by the conventional culture method.We assessed pneumococcal carriage in 330 asymptomatic community-dwelling elderly aged 65 years and older. While pneumococci were cultured from 25 (8%) individuals, 65 (20%) elderly were positive for the pneumococcus-specific lytA gene when tested by quantitative-PCR, increasing the overall number of carriers to 75 (22%). Significantly more oropharyngeal samples were pneumococci-positive (18% versus 10%, p < 0.001) when tested by the molecular method as compared to nasopharyngeal samples.Our findings indicate that pneumococcal carriage in elderly is higher than previously reported with up to 1 in 5 asymptomatic community-dwelling elderly positive for pneumococcal carriage, when detected by qPCR. The detection of pneumococci by conventional culture alone, greatly underestimates S. pneumoniae colonization in elderly.     

Vaccination anti-pneumococcique : place et indications dans la prévention des infections communautaires des voies respiratoires inférieures

Objective – The authors had for aim to evaluate the effectiveness and clinical indications of the anti pneumococcal vaccine.Methods – Seventy one articles were selected after a computerized research including the most recent studies on immunogenicity, all the prospective double blind randomized trials, and retrospective studies (case-control and indirect cohort studies). The evaluation concerned exclusively non conjugated vaccine.Results – The immune response was significant among vaccinated patients including elderly ones; antibody response was reduced or absent among immuno-compromised patients. Only one study among 11 randomized trials concerned the 23-valent vaccine. According to the results of these trials and of 2 meta-analysés, efficacy in preventing pneumococcal bacteremia and pneumococcal pneumonia is clearly established in young adults (with a response rate reaching around 80% for vaccine serotypes). Clinical studies in older adults, adults with risk factors, or immuno-compromised adults are inconclusive, usually because the number of patients was too small. Retrospective case-control and indirect cohort studies confirmed the clinical efficiency of pneumococcal vaccination. They showed that pneumococcal vaccination was efficient in 50–80% of the patients to prevent invasive pneumococcal diseases, including in older patients and those with associated diseases, particularly with COPD or cardiovascular diseases. Efficiency was not demonstrated in immuno-compromised patients. The vaccine proved safe with a good tolerance. Vaccination is recommended by the WHO and various advisory national committees in North America and Europe for elderly patients and those with associated diseases.     

Clinical effectiveness of 13-valent and 23-valent pneumococcal vaccination in middle-aged and older adults: The EPIVAC cohort study, 2015–2016

BackgroundClinical benefits using the 23-valent pneumococcal polysaccharide vaccine (PPsV23) or the 13-valent pneumococcal conjugate vaccine (PCV13) in adults are controversial. This study investigated clinical effectiveness for both PPsV23 and PCV13 in preventing pneumonia among middle-aged and older adults.MethodsPopulation-based cohort study involving 2,025,730 persons ≥50 years in Catalonia, Spain, who were prospectively followed between 01/01/2015 and 31/12/2016. Primary outcomes were hospitalisation from pneumococcal or all-cause pneumonia and main explanatory variable was PCV13/PPsV23 vaccination status. Multivariable Cox regression models were used to estimate vaccination effectiveness adjusted for age and baseline-risk conditions.ResultsCohort members were followed for 3,897,151 person-years (17,496 PCV13 vaccinated and 1,551,502 PPsV23 vaccinated), observing 3259 pneumococcal pneumonias (63 in PCV13 vaccinated, 2243 in PPsV23 vaccinated) and 24,079 all-cause pneumonias (566 in PCV13 vaccinated, 17,508 in PPsV23 vaccinated). Global incidence rates (per 100,000 person-years) were 83.6 for pneumococcal pneumonia (360.1 in PCV13 vaccinated, 144.6 in PPsV23 vaccinated) and 617.9 for all-cause pneumonia (3235.0 in PCV13 vaccinated, 1128.5 in PPsV23 vaccinated). In the multivariable analyses, the PCV13 appeared significantly associated with an increased risk of pneumococcal pneumonia (hazard ratio [HR]: 1.52; 95% confidence interval [CI]: 1.17–1.97; p = 0.002) and all-cause pneumonia (HR: 1.76; 95% CI: 1.61–1.92; p < 0.001) whereas the PPsV23 did not alter the risk of pneumococcal pneumonia (HR: 1.08; 95% CI: 0.98–1.19; p = 0.132) and slightly increased the risk of all-cause pneumonia (HR: 1.17; 95% CI: 1.13–1.21; p < 0.001). In stratified analyses focused on specific target population subgroups (i.e., elderly people, at-risk and high-risk individuals), protective effects of vaccination did not emerge either.ConclusionData does not support clinical benefits from pneumococcal vaccination (nor PCV13 neither PPsV23) against pneumonia among Catalonian adults in the current era of universal PCV’s childhood immunisation.     

The short-term impact of each primary dose of pneumococcal conjugate vaccine on nasopharyngeal carriage: Systematic review and meta-analyses of randomised controlled trials

BackgroundEarly onset of persistent otitis media is a priority issue for Australian Indigenous populations. The objective is to determine the direct and short-term impact of one, two and three doses of any pneumococcal conjugate vaccine (PCV) formulation on nasopharyngeal (NP) carriage of Streptococcus pneumoniae (Spn) and non-typeable Haemophilus influenzae (NTHi), the otopathogens targeted by current PCVs.MethodsWe searched MEDLINE (PubMed) and CENTRAL (Cochrane Library) to 29 September 2015. We also scanned reference lists of recent reviews and contacted authors. We included randomised controlled trials (RCTs) with a PCV schedule commencing ≤3 months of age that reported controlled non-cumulative group-specific prevalence data for carriage of Spn or NTHi at age < 12 months. We performed a standard risk of bias assessment. We estimated the pooled relative risk (RR) and 95% confidence interval (95%CI) for each vaccine dose on NP carriage by meta-analysis.ResultsWe included 16 RCTs involving 14,776 participants. The PCVs were conjugated to diphtheria toxin CRM₁₉₇, diphtheria toxoid, tetanus toxoid or NTHi protein D and varied in valency (4–13). Controls were non-PCVs, placebo or no vaccine. The earliest carriage outcome was from 2 to 9 months of age. Compared to controls, there were no significant differences between one or two doses of PCV on vaccine-type (VT) pneumococcal carriage at ∼4 and ∼6 months respectively. However, VT carriage was significantly lower at ∼7 months RR 0.67 95%CI 0.56–0.81 from 9 studies and 7613 infants and non-vaccine type (NVT) carriage was higher RR 1.23 95%CI 1.09–1.40 from 8 studies and 5861 infants. No impact on overall pneumococcal or NTHi carriage was found.ConclusionsThe primary PCV schedule had no significant short-term impact on overall pneumococcal or NTHi NP carriage and a limited impact on VT pneumococcal carriage before the third dose.     

Prevalence and characteristics of children with otitis media with effusion in Vietnam

PurposeOtitis media with effusion (OME) commonly occurs and persists in young children. It can cause hearing impairment and damage to the tympanic membrane without treatment. We aimed to determine the prevalence and association of Streptococcus pneumoniae in the nasopharynx of healthy children before the introduction of a pneumococcal conjugate vaccine.MethodsIn October 2016, nasopharyngeal swabs collection and otoscope examinations by an otolaryngologist were conducted in children aged less than 24 months in Nha Trang, Vietnam. OME was diagnosed as the presence of middle ear fluid using a digital otoscope equipped with a pneumatic otoscope. Quantitative PCR targeting pneumococci-specific lytA (the major autolysis gene) and bacterial culture were performed to detect S. pneumoniae. The point prevalence of OME in the study area was estimated. The association between OME and S. pneumoniae in the nasopharynx was evaluated using a multivariable logistic regression model.ResultsAmong the 274 children who underwent bilateral ear examinations and nasopharyngeal swab collections, 47 had OME (17.2%, 95% confidence interval [CI] 12.9–22.1%) and 96 were colonized with S. pneumoniae (35.0%, 29.4–41.0%). OME and nasopharyngeal S. pneumoniae carriage were positively associated in children aged less than 12  months (adjusted odds ratio [aOR] 3.83, 1.40–10.51). Day-care attendance and living in a rural area were independently associated with OME (aOR 5.87, 2.31–14.91, and aOR 3.77, 1.58–8.99, respectively).ConclusionsThe nasopharyngeal pneumococcal carriage was associated with OME among children aged  <12 months. A further study after introducing a pneumococcal conjugate vaccine (PCV) is required to better understand the effect of PCV and S. pneumoniae carriage on OME in young children.     

Using the impact of pneumococcal vaccines on nasopharyngeal carriage to aid licensing and vaccine implementation; A Pneumocarr meeting report March 27–28, 2012, Geneva

An international consultation was convened in March 2012 to provide feedback on the Case for Carriage, a summary statement by the Pneumococcal Carriage Consortium (PneumoCarr) proposing nasopharyngeal (NP) colonization as a supplementary or alternative endpoint in vaccine licensure. PneumoCarr members provided information to vaccine manufacturers, regulators and the WHO on the evidence for NP carriage as a precursor to pneumococcal disease, standardization of laboratory methods for the detection of multiple serotype carriage, definition and estimation of pneumococcal vaccine efficacy against carriage (VE-col), and the direct and indirect impact of vaccination on carriage. Manufacturers and regulators had the opportunity to respond to the information compiled by PneumoCarr and share their perspectives. VE-col as a licensure endpoint may be more useful for the next generation pneumococcal vaccine products, particularly those for which the immunological correlate of protection is not established, whereas it may be less needed for pneumococcal conjugate vaccines which have an established licensure pathway. The consultation supported the importance of NP carriage data as a critical element linking vaccine impact on the individual direct risk of disease to the population-level impact: indirect effects such as herd protection and serotype replacement. The indirect effects of vaccination, however, are not currently established as part of the licensure process and to include them would be a paradigm shift for regulatory agencies who currently consider this information in the post-licensure setting. More discussion and consensus-building is needed around the rationale and optimal mechanism to include carriage data in the licensure pathway for new pneumococcal vaccines. The WHO and national advisory groups on immunization policy may have an important role in considering the evidence for the indirect benefit of vaccination as informed by its impact on NP carriage.     

Intradermal administration of the pneumococcal conjugate vaccine in mice results in lower antibody responses as compared to intramuscular administration

IntroductionSeveral studies have shown that intradermal vaccination leads to improved immune responses. In addition, lowering vaccine doses will reduce costs and therefore potentially increase coverage. To determine whether intradermal delivery enhances the antibody responses against the 13-valent pneumococcal conjugate vaccine (PCV13), we compared intradermally and intramuscularly vaccinated mice.MethodsMice were immunized with PCV13, either intradermally or intramuscularly and CFU-counts in the nasal tissue were determined three or seven days after intranasal colonization with a serotype 4 clinical strain. Antibody concentrations against all thirteen polysaccharides were measured in blood and mucosal samples using a fluorescent-bead-based multiplex immunoassay.ResultsAntibody levels in both serum and mucosal samples were higher in the intramuscularly vaccinated group as compared to the intradermally vaccinated group. No protection against S. pneumoniae intranasal colonization was observed for either vaccination route.ConclusionsIntradermal vaccination was inferior to intramuscular immunization in inducing serotype-specific antibodies.     

Carriage of Haemophilus influenzae is associated with pneumococcal vaccination in Italian children

BackgroundThe pneumococcal population changes observed after the implementation of children immunization with pneumococcal conjugative vaccines (PCV) might have affected the composition of the microbial flora inhabiting the same ecological niche of Streptococcus pneumoniae. The aim of this study was to investigate the effect of PCV immunization, (PCV7 or PCV13), on S. pneumoniae and Haemophilus influenzae colonization in young children in Italy.MethodsNasopharyngeal swabs were obtained from 301 children under 6 years of age (vaccinated or unvaccinated with PCV) during the period January–April 2012. Presence of S. pneumoniae and H. influenzae was investigated using conventional cultural methods. S. pneumoniae isolates were serotyped by the Quellung reaction; capsular type of H. influenzae isolates was determined by PCR. The pattern of associations between the two species and potential risk factors were investigated by a Structural Equation Modelling (SEM) analysis.ResultsThe prevalence of carriage was 31.56% and 43.18% for S. pneumoniae and H. influenzae, respectively. The majority of S. pneumoniae isolates belonged to non vaccine serotypes (non PCV13-types 81.1%) while H. influenzae isolates were all non-typeable. SEM analysis revealed a synergistic association between S. pneumoniae and H. influenzae colonization (rho: 0.27; 95%CI: 0.09–0.46; p = 0.004). In addition, children vaccinated with PCV, either with PCV7 (coef 0.43; 95%CI: 0.07–0.79; p = 0.021) or with PCV13 (coef: 0.45; 95%CI: 0.08–0.82; p = 0.018), were more likely to be colonized by H. influenzae.ConclusionsPneumococcal vaccination increased H. influenzae nasopharyngeal carriage in children. This result highlights that an indirect effect of PCV vaccination can be perturbation of the nasopharyngeal flora. In the era of higher-valent pneumococcal vaccines, surveillance of carriage is crucial to monitor alterations in the bacterial ecosystem, thus preventing possible clinical problems.