Pneumococcal carriage in children in Ulaanbaatar,Mongolia before and one year after the introduction of the 13-valent pneumococcal conjugate vaccine

BackgroundNasopharyngeal carriage of Streptococcus pneumoniae precedes disease, is the source of pneumococcal community spread, and the mechanism for herd protection provided by pneumococcal conjugate vaccines (PCVs). There are few PCV impact studies in low- and middle-income countries, particularly in Asia. In 2016, Mongolia introduced the 13-valent PCV (PCV13) in a phased manner using a 2 + 1 schedule, with catch-up. We aimed to assess the impact of PCV13 introduction on nasopharyngeal pneumococcal carriage and density in children in Mongolia.MethodsWe conducted two cross-sectional carriage surveys (pre- and one year post-PCV) at community health clinics in two districts of the capital city, Ulaanbaatar in both May-July 2015 and 2017. The study analysis included 961 children too young to be vaccinated (5–8 weeks old) and 989 children eligible for vaccination (12–23 months old). Pneumococci were detected by quantitative real-time PCR and molecular serotyping performed using DNA microarray.FindingsOne year post-PCV introduction, PCV13 serotype carriage reduced by 52% in 12–23 month olds (adjusted prevalence ratio [aPR] 0.48 [95% confidence interval [CI] 0.39–0.59]), with evidence of non-PCV13 serotype replacement (aPR 1.55 [95% CI 1.30–1.85]), compared with the pre-PCV period. In 5–8 week olds, PCV13 serotype carriage reduced by 51% (aPR 0.49 [95% CI 0.33–0.73]) with no significant change in non-PCV13 serotype carriage (aPR 1.10 [95% CI 0.83–1.46]). An increase was observed in both PCV13 and non-PCV13 pneumococcal density post-PCV introduction. Antimicrobial resistance (AMR) genes were common, with 82.3% of samples containing at least one of the 10 AMR genes assessed.ConclusionThis study demonstrates substantive PCV13 impact on pneumococcal carriage one year post-vaccine introduction in Mongolia. The reductions in PCV13 serotype carriage are likely to result in reductions in pneumococcal disease including indirect effects. Increases in non-PCV13 serotypes require further monitoring.     

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.     

Lack of effectiveness of 13-valent pneumococcal conjugate vaccination against pneumococcal carriage density in Papua New Guinean infants

BackgroundPapua New Guinea (PNG) introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in 2014, with administration at 1, 2, and 3 months of age. PCV13 has reduced or eliminated carriage of vaccine types in populations with low pneumococcal carriage prevalence, carriage density and serotype diversity. This study investigated PCV13 impact on serotype-specific pneumococcal carriage prevalence, density, and serotype diversity in PNG infants, who have some of the highest reported rates of pneumococcal carriage and disease in the world.MethodsNasopharyngeal swabs were collected at 1, 4 and 9 months of age from PCV13-vaccinated infants (n = 57) and age-/season-matched, unvaccinated infants (at approximately 1 month, n = 53; 4 months, n = 57; 9 months, n = 52). Serotype-specific pneumococcal carriage density and antimicrobial resistance genes were identified by qPCR and microarray.ResultsPneumococci were present in 89% of swabs, with 60 different serotypes and four non-encapsulated variants detected. Multiple serotype carriage was common (47% of swabs). Vaccine type carriage prevalence was similar between PCV13-vaccinated and unvaccinated infants at 4 and 9 months of age. The prevalence of non-vaccine type carriage was also similar between cohorts, with non-vaccine types present in three-quarters of samples (from both vaccinated and unvaccinated infants) by 4 months of age. The median pneumococcal carriage density was high and similar at each age group (~7.0 log₁₀ genome equivalents/mL). PCV13 had no effect on overall pneumococcal carriage density, vaccine type density, non-vaccine type density, or the prevalence of antimicrobial resistance genes.ConclusionPNG infants experience dense and diverse pneumococcal colonisation with concurrent serotypes from 1 month of age. PCV13 had no impact on pneumococcal carriage density, even for vaccine serotypes. The low prevalence of vaccine serotypes, high pneumococcal carriage density and abundance of non-vaccine serotypes likely contribute to the lack of PCV13 impact on carriage in PNG infants. Indirect effects of the infant PCV programs are likely to be limited in PNG. Alternative vaccines with broader coverage should be considered.     

Impaired serotype-specific immune function following pneumococcal vaccination in infants with prior carriage

The impact of prior nasopharyngeal carriage on serotype-specific IgG responses following immunization with pneumococcal conjugate vaccines (PCV) has recently been described. This report extends these findings to describe the attenuation of functional immune responses following 23-valent pneumococcal polysaccharide vaccination (PPS). We report the attenuation of immune responses following booster with the 23-valent pneumococcal polysaccharide vaccination (PPS) in infants with prior nasopharyngeal carriage of Streptococcus pneumoniae. Fijian infants who were part of a phase II randomized, controlled trial of reduced dose PCV7 schedules were the basis of this study. Pneumococcal carriage was determined at 6, 9 and 12 months of age, prior to PPS immunization. Serum samples collected at 18 weeks (post-PCV7), 12 months (pre-PPS), 12.5 months and 17 months (post-PPS) of age were assessed for serotype-specific IgG and opsonophagocytic responses.     

PneuMum: Impact from a randomised controlled trial of maternal 23-valent pneumococcal polysaccharide vaccination on middle ear disease amongst Indigenous infants,Northern Territory,Australia

BackgroundWe assessed maternal 23-valent pneumococcal polysaccharide (23vPPV) vaccine efficacy (VE) against middle ear disease and pneumococcal carriage amongst Australian Indigenous infants.MethodsIn an open label, allocation concealed, outcome-assessor blinded, community stratified, randomised controlled trial, healthy pregnant Indigenous women aged 17–39 years in the Northern Territory of Australia received the 23vPPV (1:1:1) at: 30–36 weeks gestation, birth, or were unvaccinated (ClinicalTrials.gov NCT00714064). Co-primary outcomes were the point prevalences of infant middle ear disease and 23vPPV-type carriage at age 7 months.ResultsThe consent rate was 50% (313/632). Among 227 eligible participants randomised, retention rates were 86% (66/77) controls; 89% (67/75) pregnancy vaccinees; 88% (66/75) birth vaccinees. At infant age 7 months, ear disease prevalence was: 71% (47/66) controls, 63% (42/67) pregnancy vaccinees, 76% (50/66) birth vaccinees; and 23vPPV-type carriage was: 26% (17/66) controls, 18% (12/67) pregnancy vaccinees, 18% (12/66) birth vaccinees. For pregnancy vaccinees, VE was 12% (95% CI −12% to 31%) against infant ear disease and 30% (95% CI −34% to 64%) against 23vPPV-type carriage. In a post-hoc analysis, VE against infant ear disease concurrent with carriage of 23vPPV or related types was 51% (95% CI −2% to 76%). There were no serious adverse effects following receipt of the 23vPPV in pregnancy or at birth.ConclusionsIn a high risk population, our study was unable to demonstrate efficacy of 23vPPV in pregnancy against the co-primary outcomes of either all-cause infant ear disease or 23vPPV-type nasopharyngeal carriage at age 7 months. Efficacy against ear disease concurrent with carriage of vaccine-related serotypes (a more specific outcome) suggests 23vPPV in pregnancy may complement childhood pneumococcal vaccination programs.     

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.     

Pneumococcal carriage in vaccine-eligible children and unvaccinated infants in Lao PDR two years following the introduction of the 13-valent pneumococcal conjugate vaccine

Pneumococcal carriage is a prerequisite for disease, and underpins herd protection provided by pneumococcal conjugate vaccines (PCVs). There are few data on the impact of PCVs in lower income settings, particularly in Asia. In 2013, the Lao People's Democratic Republic (Lao PDR) introduced 13-valent PCV (PCV13) as a 3?+?0 schedule (doses at 6, 10 and 14?weeks of age) with limited catch-up vaccination. We conducted two cross-sectional carriage surveys (pre- and two years post-PCV) to assess the impact of PCV13 on nasopharyngeal pneumococcal carriage in 5–8?week old infants (n?=?1000) and 12–23?month old children (n?=?1010). Pneumococci were detected by quantitative real-time PCR, and molecular serotyping was performed using DNA microarray. Post PCV13, there was a 23% relative reduction in PCV13-type carriage in children aged 12–23?months (adjusted prevalence ratio [aPR] 0.77 [0.61–0.96]), and no significant change in non-PCV13 serotype carriage (aPR 1.11 [0.89–1.38]). In infants too young to be vaccinated, there was no significant change in carriage of PCV13 serotypes (aPR 0.74 [0.43–1.27]) or non-PCV13 serotypes (aPR 1.29 [0.85–1.96]), although trends were suggestive of indirect effects. Over 70% of pneumococcal-positive samples contained at least one antimicrobial resistance gene, which were more common in PCV13 serotypes (p?<?0.001). In 12–23?month old children, pneumococcal density of both PCV13 serotypes and non-PCV13 serotypes was higher in PCV13-vaccinated compared with undervaccinated children (p?=?0.004 and p?<?0.001, respectively). This study provides evidence of PCV13 impact on carriage in a population without prior PCV7 utilisation, and provides important data from a lower-middle income setting in Asia. The reductions in PCV13 serotype carriage in vaccine-eligible children are likely to result in reductions in pneumococcal transmission and disease in Lao PDR.     

Uptake of pneumococcal conjugate vaccine among children in the 1998-2002 United States birth cohorts

BACKGROUND: Routine childhood immunization with pneumococcal conjugate vaccines (PCV7s) began in 2000 in the United States. Despite vaccine shortages, reductions in invasive pneumococcal disease occurred rapidly during 2000-2002. Age-appropriate PCV7 coverage was estimated and characteristics associated with undervaccination were identified for children in the 1998-2002 birth cohorts. METHODS: Data were analyzed for 85,135 children aged 19-35 months in the 2001-2004 National Immunization Surveys. To obtain PCV7 coverage estimates by birth cohorts, a pooled analysis was conducted by combining individual survey years that sampled children with appropriate birth dates. Logistic regression models were used to identify factors associated with age-appropriate vaccination. RESULTS: The proportion of children receiving the primary 3-dose PCV7 series by age 12 months increased from 45.5% (+/-0.6) among children born in 2000 to 62.1% (+/-0.7) among those born in 2002. By age 24 months, an estimated 30.7% (+/-0.6), 38.0% (+/-0.6), and 49.0% (+/-1.1) of children born in 2000, 2001 and 2002, respectively, had received all four PCV7 doses; however, only 15.0% (+/-0.4), 16.1% (+/-0.4) and 24.4% (+/-0.6) of children were age-appropriately immunized. Among children born in 1998 and 1999, 10.1% +/-0.5) and 37.6% (+/-0.7), respectively, received one or more catch-up doses during their second year of life. Lower age-appropriate PCV7 coverage was independently associated with black race, Hispanic ethnicity, receiving vaccinations from public health providers, and low household income. CONCLUSIONS: The dramatic reductions in pneumococcal-related diseases from direct and indirect vaccine effects occurred when few children had received the recommended complete vaccine schedule, and there were substantial racial and socioeconomic disparities in coverage.     

Using pneumococcal carriage studies to monitor vaccine impact in low- and middle-income countries

Pneumococcal disease is a leading cause of childhood mortality, globally. The pneumococcal conjugate vaccine (PCV) has been introduced to many countries worldwide. However there are few studies evaluating PCV impacts in low- and middle-income countries (LMIC) because measuring the impact of PCV on pneumococcal disease in LMICs is challenging. We review the role of pneumococcal carriage studies for the evaluation of PCVs in LMICs and discuss optimal methods for conducting these studies. Fifteen carriage studies from 13 LMICs quantified the effects of PCV on carriage, and identified replacement carriage serotypes in the post-PCV era. Ten studies reported on the indirect effects of PCV on carriage. Results can be used to inform cost-effectiveness evaluations, guide policy decisions on dosing and product, and monitor equity in program implementation. Critically, we highlight gaps in our understanding of serotype replacement disease in LMICs and identify priorities for research to address this gap.     

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.

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.     

Associations between ethnicity,social contact,and pneumococcal carriage three years post-PCV10 in Fiji

BackgroundPneumococcal carriage is a prerequisite for pneumococcal disease. Little is known about whether social contact frequency and intensity are associated with pneumococcal carriage. In Fiji, indigenous iTaukei have higher prevalence of pneumococcal carriage compared with Fijians of Indian Descent (FID). We hypothesised that contact differences may contribute to ethnic differences in pneumococcal carriage prevalence and density.MethodsIn 2015, young infants (5–8 weeks), toddlers (12–23 months), children (2–6 years), and caregivers from Suva and surrounding areas, participated in a cross-sectional survey (n = 2014), three years post pneumococcal conjugate vaccine introduction. Demographic and contact data, and nasopharyngeal swabs were collected. Pneumococci were detected, and quantified using quantitative real-time PCR, with molecular serotyping by microarray. Associations between ethnicity, contact, and pneumococcal carriage and density were estimated using multivariable generalised estimating equation regression models.ResultsiTaukei participants had larger household sizes, higher pneumococcal carriage rates, more contacts, and more frequent contacts of longer duration, compared with FID. The odds of vaccine-type carriage increased by 28% (95% CI 8–53%) P < 0.01 in association with physical contact with 7–14 year old children. iTaukei ethnicity was associated with vaccine-type carriage (aOR) 1.73; 95% CI 1.06–2.82, P = 0.03) and non-vaccine type carriage (aOR 5.98; 95% CI 4.47–8.00, P < 0.01). Ethnicity and contact were not associated with pneumococcal density.ConclusionsiTaukei had greater frequency and intensity of contact compared with FID. Physical contact was associated with pneumococcal carriage. Observed differences in pneumococcal nasopharyngeal carriage prevalence between iTaukei and FID were not explained by differences in social contact patterns by ethnicity.     

Outbreak of invasive pneumococcal disease--Alaska, 2003-2004

In Alaska, statewide laboratory-based surveillance revealed an increase in invasive pneumococcal disease (IPD) in a rural region during 2003-2004. This report summarizes the outbreak, regional trends in serotype-specific pneumococcal carriage, and an assessment of use of standing orders for vaccination. The results of this analysis underscore the preventability of IPD and the importance of vaccination.     

Nasopharyngeal microbial interactions in the era of pneumococcal conjugate vaccination

The nasopharynx of children is often colonised by microorganisms such as Streptococcus pneumoniae (the pneumococcus) that can cause infections including pneumonia and otitis media. In this complex environment, bacteria and viruses may impact each other through antagonistic as well as synergistic interactions. Vaccination may alter colonisation dynamics, evidenced by the rise in non-vaccine serotypes following pneumococcal conjugate vaccination. Discovery of an inverse relationship between S. pneumoniae and Staphylococcus aureus carriage generated concern that pneumococcal vaccination could increase S. aureus carriage and disease. Here we review data on co-colonisation of pathogens in the nasopharynx, focusing on S. pneumoniae and the impact of pneumococcal vaccination. Thus far, pneumococcal vaccination has not had a sustained impact on S. aureus carriage but it is associated with an increase in non-typeable Haemophilus influenzae in acute otitis media aetiology. Advances in bacterial and viral detection methodologies have facilitated research in nasopharyngeal microbiology and will aid investigation of potential vaccine-induced changes, particularly when baseline studies can be conducted prior to pneumococcal vaccine introduction.     

The influence of competition and vaccination on the coexistence of two pneumococcal serotypes

Streptococcus pneumoniae (pneumococcus) is one of the most important bacterial pathogens and a leading cause of mucosal infections (e.g. otitis media) and various forms of serious diseases (e.g. pneumonia, meningitis, bacteraemia) in developing and developed countries. Based on the polysaccharide capsule, there are at least 90 different pneumococcal serotypes, which may compete with each other to colonize the nasopharynx. Newly developed protein-polysaccharide conjugated vaccines have been shown to provide protection against disease caused by the serotypes included in the vaccine, and also against colonization (carriage). It is feared that yet uncommon, but nonetheless pathogenic serotypes which have been suppressed by competition, may become more prevalent in carriage and disease after large-scale use of conjugate vaccines. In this paper, we use transmission models of pneumococcal carriage to study how competition and vaccination influence the coexistence of two serotypes. According to our results, direct (physical) competition between two pneumococcal serotypes only influences colonization if the duration of naturally acquired immunity is short. By contrast, indirect (antibody-mediated) competition is of influence only if naturally acquired immunity is long lasting. Vaccination reduces the prevalence of the target serotype--an effect that is enforced by the presence of directly competing bacteria. The emergence of a non-target serotype after vaccination is only observed if bacteria compete directly. These results emphasize the importance of studying whether bacteria compete directly or indirectly and for how long people are protected in order to assess the long-term effects of sero-competition.     

Impact of pneumococcal conjugate vaccines on nasopharyngeal carriage and invasive disease among unvaccinated people: Review of evidence on indirect effects

Background

Invasive disease due to Streptococcus pneumoniae remains an important worldwide cause of morbidity and mortality, particularly in young children and the elderly. The development and use of pneumococcal conjugate vaccines (PCVs) have had a dramatic impact on rates of vaccine-type invasive pneumococcal disease (IPD) not only in the pediatric population targeted for vaccination but in non-vaccinated age-groups as well. This indirect effect is directly mediated by a reduction of vaccine-type nasopharyngeal carriage and thus transmission by vaccinated children. Current PCV licensing procedures do not take into consideration nasopharyngeal carriage impact, and thus the indirect effect. This review summarizes the evidence for the indirect effect of PCV on vaccine-type disease and its correlation with changes in carriage among unvaccinated populations, to assess the basis for inclusion of carriage in the PCV licensing process.

Methods

Randomized controlled trials, surveillance and other observational studies published between 1994 and 2013 were systematically identified from global, regional and review databases and conference abstracts. We included as primary evidence, studies in non-vaccinated groups addressing changes in both vaccine-type IPD and carriage between pre- and post-PCV introduction periods; studies missing one of these four components were included as supporting rather than primary evidence.

Results

We identified studies from 14 countries, nearly all developed countries. Vaccine-type IPD and carriage in non-targeted populations consistently decreased after PCV introduction, with the magnitude of decrease growing over time. Where IPD and carriage were observed in the same population, VT-decreases occurred contemporaneously. These relationships held true across age-groups and between indigenous and non-indigenous populations in the US and Australia.

Conclusions

Indirect PCV impact on VT-IPD and VT-carriage has been significant. Impact on carriage should be considered for inclusion in the PCV licensure process as a predictor of indirect effects.     

Polysaccharide-based pneumococcal vaccines in the prevention of acute otitis media

New pneumococcal vaccines, consisting of 7-11 capsular polysaccharides coupled to protein carriers, are able to induce functionally active humoral and mucosal antibody responses. They also reduce mucosal carriage of pneumococci in the vaccinees. Preliminary results from efficacy trials suggest that about one-third of pneumococcal otitis could be prevented by using the seven-valent pneumococcal conjugate vaccine. If these efficacy estimates are true throughout childhood, up to 1.2 million episodes of acute otitis are preventable annually in the US. The true impact of the vaccine on otitis burden is dependent not only on the efficacy as demonstrated in the efficacy trials but also on the impact of the vaccine on the mucosal carriage of bacteria and on the herd immunity induced by vaccinations. Ongoing follow-up studies will reveal whether these factors increase or decrease the efficiency of the proposed vaccination programme.     

Antimicrobial susceptibility and clonality of Streptococcus pneumoniae isolates recovered from invasive disease cases during a period with changes in pneumococcal childhood vaccination,Norway, 2004–2016

Changes in pneumococcal antimicrobial resistance (AMR) have been reported following use of pneumococcal conjugate vaccines (PCVs) in childhood vaccination programmes. We describe AMR trends and clonality in Norway during 2004–2016; we studied 10,239 invasive pneumococcal disease (IPD) isolates in terms of serotypes, antimicrobial susceptibility, and for a systematically collected subset of 2473 isolates, multilocus sequence types (ST). The IPD cases were notified to the Norwegian Surveillance System for Communicable Diseases and pneumococcal isolates were collected through the National Reference Laboratory for Pneumococci. The cases are sourced from the entire Norwegian population. We supplemented the IPD isolates with isolates from carriage studies in children attending day-care, performed in 2006 (before mass childhood vaccination with PCV7), 2008 (2 years after PCV7 introduction), 2013 (2 years after the transition to PCV13), and 2015. IPD cases were 0–102 years old; median 64 years. Carriage study participants were typically aged 1–5 years. Overall, AMR was low; a maximum of 7% of IPD isolates were resistant, depending on the antimicrobial. Erythromycin and trimethoprim/sulfamethoxazole resistant IPD (ERY-R and SXT-R, respectively) decreased in the PCV7 period (2006–2010). In the PCV13 period (2011–2016) however, we saw an indication of increased non-susceptibility among IPD isolates. This increase was mainly due to non-vaccine serotypes 15A-ST63 (multidrug resistant), 24F-ST162 (SXT-R), 23B-ST2372 (penicillin non-susceptible and SXT-R) and 33F (ERY-R and clindamycin resistant). Resistant or non-susceptible IPD isolates were often clones introduced into Norway during the study period. The exception was ERY-R isolates; initially, these largely consisted of an established serotype 14-ST9 clone, which disappeared after introducing PCV7. The carriage study results mostly resembled the changes seen in IPD with a maximum of 9% of the participants per study carrying resistant pneumococci. As actual PCVs are not fully limiting AMR, higher-valency vaccines and prudent use of antimicrobials are still needed to temper pneumococcal AMR.     

What do we know about 7vPCV coverage in Aboriginal and Torres Strait Islander children? A 2007 update

In 2001, a publicly funded 7 valent pneumococcal conjugate vaccine (7vPCV) program commenced for Aboriginal and Torres Strait Islander children aged less than 2 years. This study updates early estimates of 7vPCV coverage in Aboriginal and Torres Strait Islander children using Australian Childhood Immunisation Register data between 31 December 2004 and 30 September 2007. We chose four 3-month birth cohorts of children and assessed their immunisation status at 12 months of age for pneumococcal conjugate vaccine and for 'fully immunised'. After the introduction of universal childhood conjugate pneumococcal vaccination in 2005, 7vPCV coverage increased substantially among Aboriginal and Torres Strait Islander children nationally, and in all jurisdictions but remained lower than among non-Indigenous children. The results re-emphasise the greater impact of universal, compared with targeted, programs on vaccine coverage among Indigenous children.     

Unaltered pneumococcal carriage prevalence due to expansion of non-vaccine types of low invasive potential 8 years after vaccine introduction in Stockholm,Sweden

ObjectiveTo evaluate the carriage prevalence, serotype distribution, and antibiotic resistance for pneumococcal carriage isolates collected 4–8 years after introduction of pneumococcal conjugate vaccines (PCVs) in Stockholm, Sweden, and to identify risk factors for carriage and calculate the invasive disease potential for emerging serotypes.MethodsNasopharyngeal aspirates were collected from 3024 children aged 0–<5 years at regular visits at 23 Child Health Centers in Stockholm County in 2011–2015, and from 787 parents in 2014–2015. The invasive disease potential was calculated for serotypes using invasive disease isolates from 824 patients of all ages identified in the Stockholm County during the same time period as the carriage isolates.ResultsA total carriage prevalence of 30% did not change during the study period. Non-vaccine types (NVT) dominated (94% by 2015) and the most common serotypes in descending order were 11A, 23B, 35F and 21. Risk factors for carriage were: age ⩾3 months–<3 years, having siblings, attending day-care and having travelled abroad the last 3 months. Antibiotic resistance remained low. The invasive disease potential was high for NVT 8, 9N, 12F, and 22F, while low for a majority of emerging NVTs in carriage.ConclusionThe carriage prevalence remained the same 4–8 years after vaccine introduction, but serotype replacement became almost complete. A majority of emerging NVTs in carriage showed a low invasive disease potential. Carriage studies are an important complement to invasive disease surveillance to understand the full effect of PCV vaccine programs.