Introduction Of Pneumococcal Vaccine Research Articles

Serotypes and Antimicrobial Susceptibility of <i>Streptococcus pneumoniae</i> Isolated from Cases of IPD in Tokyo after Introduction of Pneumococcal Vaccines (2013-2022)

Serotypes and Antimicrobial Susceptibility of <i>Streptococcus pneumoniae</i> Isolated from Cases of IPD in Tokyo after Introduction of Pneumococcal Vaccines (2013-2022)

How common is otogenic meningitis? A retrospective study in southern Sweden over 18years.

Bacterial meningitis is a rare, but life-threatening disease, which sometimes occurs as a complication to acute otitis media (AOM). The proportion of meningitis cases originating from AOM is not clear. The aim of this study was to investigate the proportion of meningitis cases caused by AOM, to compare risk factors, bacteriology and outcome between otogenic and non-otogenic meningitis, and to analyse the incidence of bacterial meningitis after the introduction of conjugate pneumococcal vaccines (PCV). The medical charts of all patients admitted to hospitals in southern Sweden with bacterial meningitis between 2000 and 2017 were retrieved. Based on otoscopy and/or imaging, the proportion of otogenic meningitis cases was calculated, as were annual incidences. A total of 216 patients were identified, 25 of whom died. The proportion of otogenic meningitis was 31% but varied from 6% among teenagers to 40% among adults. Before PCV, 23% of all meningitis cases were children < 2years, compared to 1% post-PCV. The average incidence in the adult population, on the other hand, increased post-PCV, though there were large annual variations. S. pneumoniae was the most commonly identified pathogen in everyone but teenagers, in whom N. meningitidis was predominant. AOM is an important cause of meningitis in children and adults. Though bacterial meningitis almost disappeared in children < 2years after the introduction of PCV, the incidence of pneumococcal meningitis in adults seems to have increased.

Serotype replacement and an increase in non-encapsulated isolates among community-acquired infections of Streptococcus pneumoniae during post-vaccine era in Japan

ObjectivesIt is feared that the serotype replacement of Streptococcus pneumoniae occurred by the introduction of pneumococcal vaccines as periodical inoculation leads to reduced efficacy of the approved vaccines and altered antimicrobial susceptibility. MethodsWe determined serotypes of 351 S. pneumoniae isolates collected at a commercial clinical laboratory in Hokkaido prefecture, Japan, from December 2018 to February 2019 by using the polymerase chain reaction procedure of the US Centers for Disease Control and Prevention. Antimicrobial susceptibility and resistance gene profiles were also examined. ResultsVaccine coverage rates were 7.9% for 13-valent conjugate vaccine, and 32.5% for 23-valent polysaccharide vaccine, respectively. Non-typable strains were 19.7%. cpsA-positive isolates (group I), and null capsule clade (NCC)1, NCC2 and NCC3 (group II) comprised 31.3%, 28.4%, 32.8%, and 7.5% of the 69 non-typable strains, respectively. No penicillin-resistant/intermediate isolates were found; however, serotypes 35B and 15A/F showed low susceptibility to β-lactams. Only five strains (1.4%) were levofloxacin-resistant, and all were from the older persons, and three strains were serotype 35B. ConclusionThe progression of serotype replacement in non-invasive pneumococcal infections has occurred during the post-vaccine era in Japan, and non-encapsulated isolates, such as NCC, have increased. Antimicrobial susceptibility is not worsened.

Nasopharyngeal competition dynamics are likely to be altered following vaccine introduction: bacteriocin prevalence and diversity among Icelandic and Kenyan pneumococci.

Bacteriocins are antimicrobial peptides produced by bacteria to inhibit other bacteria in the surrounding environment. Streptococcus pneumoniae is a leading cause of disease worldwide and colonises the healthy human nasopharynx, where it competes for space and nutrients. Pneumococcal conjugate vaccines have reduced the incidence of disease, but they also restructure the bacterial population, and this restructuring likely alters the nasopharyngeal competition dynamics. Here, the distribution of bacteriocins was examined in over 5000 carriage and disease-causing pneumococci from Iceland and Kenya, recovered before and after the introduction of pneumococcal vaccination. Overall, up to eleven different bacteriocin gene clusters were identified per pneumococcus. Significant differences in the prevalence of bacteriocins were observed before and after vaccine introduction, and among carriage and disease-causing pneumococci, which were largely explained by the bacterial population structure. Genetically similar pneumococci generally harboured the same bacteriocins although sometimes different repertoires of bacteriocins were observed, which suggested that horizontal transfer of bacteriocin clusters had occurred. These findings demonstrated that vaccine-mediated changes in the pneumococcal population altered the prevalence and distribution of bacteriocins. The consequences of this for pneumococcal colonisation and disease remain to be determined.

Herd immunity in older adults from a middle-income country: A time-series trend analysis of community-acquired pneumonia mortality 2003-2017.

Community-acquired pneumonia is responsible for substantial mortality, and pneumococcus is commonly accepted as a major cause of pneumonia, regardless of laboratory confirmation. Child immunization programs have reported success in decreasing pneumonia mortality: directly in young children and indirectly (herd immunity) in unvaccinated adult populations in some countries. We assess changes in mortality trends for all-cause pneumonia in older adults associated with the introduction of pneumococcal vaccination for children in Peru. This is a secondary analysis on administrative data collected periodically by the Peruvian Ministry of Health. An observational retrospective time series analysis was conducted using longitudinal population-based data from death certificates in Peru between 2003 and 2017. The time series includes 6 years before and 9 years after the introduction of the pneumococcal-conjugated vaccines in the national child immunization program in 2009. Monthly frequencies and annual rates for all-cause pneumonia deaths in children under 5 years of age and adults over 65 years of age are presented. Linear and quadratic trends are analyzed. Deaths among older adults accounted for 75.6% of all-cause pneumonia mortality in Peru, with 94.4% of these reporting "pneumonia due to unspecified organism" as the underlying cause of death. Comparing pre- and post-child immunization program periods, annual average mortality rates from unspecified pneumonia decreased by 22.7% in young children but increased by 19.6% in older adults. A linear trend model supports this overall tendency, but a quadratic curve explains the data better. Pneumococcal-conjugated vaccines are developed using serotypes prevalent in selected countries from less common (invasive) pneumococcal disease and expected to prevent mortality worldwide from widespread (noninvasive) pneumonia. Our results do not support the presence of herd immunity from pneumococcal vaccination of children for community-acquired pneumonia in the increasingly ageing population of Peru. This should direct future research and could influence public health policy.

Update of the consensus document on the aetiology, diagnosis and treatment of acute otitis media and sinusitis

Update of the consensus on acute otitis media (AOM) (2012) and sinusitis (2013) following the introduction of pneumococcal vaccines in the immunization schedule, and related changes, such as epidemiological variation, colonization by of nonvaccine serotypes and emerging antimicrobial resistances. A majority of studies show that the introduction of the pneumococcal 13-valent conjugate vaccine has been followed by a reduction in the nasopharyngeal carriage of pneumococcus, with an increase in the proportion of drug-resistant nonvaccine serotypes. The diagnosis of AOM is still clinical, although more stringent criteria are proposed, which are based on the visualization of abnormalities in the tympanic membrane and the findings of pneumatic otoscopy performed by trained clinicians. The routine diagnosis of sinusitis is also clinical, and the use of imaging is restricted to the assessment of complications. Analgesia with acetaminophen or ibuprofen is the cornerstone of AOM management; watchful waiting or delayed antibiotic prescription may be suitable strategies in select patients. The first-line antibiotic drug in children with AOM and sinusitis and moderate to severe disease is still high-dose amoxicillin, or amoxicillin-clavulanic acid in select cases. Short-course regimens lasting 5–7 days are recommended for patients with uncomplicated disease, no risk factors and a mild presentation. In allergic patients, the selection of the antibiotic agent must be individualized based on severity and whether or not the allergy is IgE-mediated. In recurrent AOM, the choice between watchful waiting, antibiotic prophylaxis or surgery must be individualized based on the clinical characteristics of the patient.

Actualización del documento de consenso sobre etiología, diagnóstico y tratamiento de la otitis media aguda y sinusitis

Update of the consensus on acute otitis media (AOM) (2012) and sinusitis (2013) following the introduction of pneumococcal vaccines in the immunization schedule, and related changes, such as epidemiological variation, colonization by of nonvaccine serotypes and emerging antimicrobial resistances. A majority of studies show that the introduction of the pneumococcal 13-valent conjugate vaccine has been followed by a reduction in the nasopharyngeal carriage of pneumococcus, with an increase in the proportion of drug-resistant nonvaccine serotypes. The diagnosis of AOM is still clinical, although more stringent criteria are proposed, which are based on the visualization of abnormalities in the tympanic membrane and the findings of pneumatic otoscopy performed by trained clinicians. The routine diagnosis of sinusitis is also clinical, and the use of imaging is restricted to the assessment of complications. Analgesia with acetaminophen or ibuprofen is the cornerstone of AOM management; watchful waiting or delayed antibiotic prescription may be suitable strategies in select patients. The first-line antibiotic drug in children with AOM and sinusitis and moderate to severe disease is still high-dose amoxicillin, or amoxicillin-clavulanic acid in select cases. Short-course regimens lasting 5–7 days are recommended for patients with uncomplicated disease, no risk factors and a mild presentation. In allergic patients, the selection of the antibiotic agent must be individualized based on severity and whether or not the allergy is IgE-mediated. In recurrent AOM, the choice between watchful waiting, antibiotic prophylaxis or surgery must be individualized based on the clinical characteristics of the patient.

In praise of Prais-Winsten: An evaluation of methods used to account for autocorrelation in interrupted time series.

Interrupted time series are increasingly being used to assess the population impact of public health interventions. These data are usually correlated over time (auto correlated) and this must be accounted for in the analysis. Typically, this is done using either the Prais-Winsten method, the Newey-West method, or autoregressive-moving-average (ARMA) modeling. In this paper, we illustrate these methods via a study of pneumococcal vaccine introduction and explore their performance under 20 simulated autocorrelation scenarios with sample sizes ranging between 20 and 300. We show that in terms of mean square error, the Prais-Winsten and ARMA methods perform best, while in terms of coverage the Prais-Winsten method generally performs better than other methods. All three methods are unbiased. As well as having good statistical properties, the Prais-Winsten method is attractive because it is decision-free and produces a single measure of autocorrelation that can be compared between studies and used to guide sample size calculations. We would therefore encourage analysts to consider using this simple method to analyze interrupted time series.

Invasive Pneumococcal Diseases in Korean Adults After the Introduction of Pneumococcal Vaccine into the National Immunization Program.

Although Streptococcus pneumoniae has been one of the most common bacterial causes of disease in humans, its impact has been blunted by the broad use of vaccines. Since 2018, the incidence of invasive pneumococcal disease in Korea decreased with effective pneumococcal vaccines but is on the rise again recently. In this paper I will review the epidemiology, risk factors, and antibiotic resistance of invasive pneumococcal disease after the introduction of the pneumococcal vaccine in Korean adults.

Pneumococcal concentration and serotype distribution in preschool children with radiologically confirmed pneumonia compared to healthy controls prior to introduction of pneumococcal vaccination in Zanzibar: an observational study

The World Health Organization recommends pneumococcal vaccination (PCV) in the first year of life. We investigated pneumococcal serotypes in children with clinical or radiologically confirmed pneumonia and healthy controls prior to PCV13 vaccine introduction in Zanzibar. Children (n = 677) with non-severe acute febrile illness aged 2-59months presenting to a health centre in Zanzibar, Tanzania April-July 2011 were included. Nasopharyngeal swabs collected at enrolment were analysed by real-time PCR to detect and quantify pneumococcal serotypes in patients (n = 648) and in healthy asymptomatic community controls (n = 161). Children with clinical signs of pneumonia according to the Integrated Management of Childhood illness guidelines ("IMCI pneumonia") were subjected to a chest-X-ray. Consolidation on chest X-ray was considered "radiological pneumonia". Pneumococcal DNA was detected in the nasopharynx of 562/809 (69%) children (70% in patients and 64% in healthy controls), with no significant difference in proportions between patients with or without presence of fever, malnutrition, IMCI pneumonia or radiological pneumonia. The mean pneumococcal concentration was similar in children with and without radiological pneumonia (Ct value 26.3 versus 27.0, respectively, p = 0.3115). At least one serotype could be determined in 423 (75%) participants positive for pneumococci of which 33% had multiple serotypes detected. A total of 23 different serotypes were identified. One serotype (19F) was more common in children with fever (86/648, 13%) than in healthy controls (12/161, 7%), (p = 0.043). Logistic regression adjusting for age and gender showed that serotype 9A/V [aOR = 10.9 (CI 2.0-60.0, p = 0.006)] and 14 [aOR = 3.9 (CI 1.4-11.0, p = 0.012)] were associated with radiological pneumonia. The serotypes included in the PCV13 vaccine were found in 376 (89%) of the 423 serotype positive participants. The PCV13 vaccine introduced in 2012 targets a great majority of the identified serotypes. Infections with multiple serotypes are common. PCR-determined concentrations of pneumococci in nasopharynx were not associated with radiologically confirmed pneumonia. Trial registrationClinicaltrials.gov (NCT01094431).

Minilungs from Human Embryonic Stem Cells to Study the Interaction of Streptococcus pneumoniae with the Respiratory Tract.

ABSTRACTThe new generation of organoids derived from human pluripotent stem cells holds a promising strategy for modeling host-bacteria interaction studies. Organoids recapitulate the composition, diversity of cell types, and, to some extent, the functional features of the native organ. We generated lung bud organoids derived from human embryonic stem cells to study the interaction of Streptococcus pneumoniae (pneumococcus) with the alveolar epithelium. Invasive pneumococcal disease is an important health problem that may occur as a result of the spread of pneumococcus from the lower respiratory tract to sterile sites. We show here an efficient experimental approach to model the main events of the pneumococcal infection that occur in the human lung, exploring bacterial adherence to the epithelium and internalization and triggering an innate response that includes the interaction with surfactant and the expression of representative cytokines and chemokines. Thus, this model, based on human minilungs, can be used to study pneumococcal virulence factors and the pathogenesis of different serotypes, and it will allow therapeutic interventions in a reliable human context.IMPORTANCE Streptococcus pneumoniae is responsible for high morbidity and mortalities rates worldwide, affecting mainly children and adults older than 65 years. Pneumococcus is also the most common etiologic agent of bacterial pneumonia and nonepidemic meningitis, and it is a frequent cause of bacterial sepsis. Although the introduction of pneumococcal vaccines has decreased the burden of pneumococcal disease, the rise of antibiotic-resistant strains and nonvaccine types by serotype replacement is worrisome. To study the biology of pneumococcus and to establish a reliable human model for pneumococcal pathogenesis, we generated human minilungs from embryonic stem cells. The results show that these organoids can be used to model some events occurring during the interaction of pneumococcus with the lung, such as adherence, internalization, and the initial alveolar innate response. This model also represents a great alternative for studying virulence factors involved in pneumonia, drug screening, and other therapeutic interventions.

Clinical Presentations and Outcomes of Children in Canada With Recurrent Invasive Pneumococcal Disease From the IMPACT Surveillance Network.

Invasive pneumococcal disease due to Streptococcus pneumoniae can cause mortality and severe morbidity due to sepsis, meningitis and pneumonia, particularly in young children and the elderly. Recurrent invasive pneumococcal disease is rare yet serious sequelae of invasive pneumococcal disease that is associated with the immunocompromised and leads to a high mortality rate. This retrospective study reviewed recurrent invasive pneumococcal disease cases from the Canadian Immunization Monitoring Program, ACTive (IMPACT) between 1991 and 2019, an active network for surveillance of vaccine-preventable diseases and adverse events following immunization for children ages 0-16 years. Data were collected from 12 pediatric tertiary care hospitals across all 3 eras of public pneumococcal conjugate vaccine implementation in Canada. The survival rate within our cohort of 180 recurrent invasive pneumococcal disease cases was 98.3%. A decrease of 26.4% in recurrent invasive pneumococcal disease due to vaccine serotypes was observed with pneumococcal vaccine introduction. There was also a 69.0% increase in the rate of vaccination in children with preexisting medical conditions compared with their healthy peers. The decrease in recurrent invasive pneumococcal disease due to vaccine-covered serotypes has been offset by an increase of non-vaccine serotypes in this sample of Canadian children.

Carriage of Streptococcus pneumoniae in children under five years of age prior to pneumococcal vaccine introduction in Southeast Asia: A systematic review and meta-analysis (2001-2019).

A number of pneumococcal carriage studies in children have been conducted in recent years. However, summary data of carriage prevalence and serotype distribution from South East Asia Region (SEAR) are limited. This may lead to the misconception that Streptococcus pneumoniae vaccine-types are uncommon in the region. Systematic reviews of pneumococcal carriage and the distribution of serotypes are critically important for evidence-based decision-making. We aimed to summarize published data on the serotype prevalence of S. pneumoniae carried in the nasopharynx of children under 5 years of age in SEAR. We performed a systematic review and meta-analysis for relevant studies on S. pneumoniae carriage conducted prior to PCV program implementation from online journal databases published between January 2001 to December 2019. The pooled prevalence of S. pneumoniae in healthy children under 5 years of age in SEAR was 36.0% (95% CI 34.2%-37.8%), and ranged from 68.0% (95% CI: 61.9%-74.0%) in Cambodia to 7.6% (95% CI: 5.7%-9.6%) in Malaysia. Serotypes 6A/B, 23F and 19F were the most common serotypes in children <5 years, accounting for 12.9% (95% CI: 9.4%-16.3%), 9.3% (95% CI: 5.9%-12.8%) and 10.1% (95% CI: 6.6%-13.5%) of isolates, respectively. Vaccine policy makers should take these results into account when making decisions on pneumococcal conjugate vaccine programs implementation. Given the paucity of data, collection of more extensive and updated information of S. pneumoniae serotype epidemiology in children under five years in SEAR is also very important for future studies.

The impact of 10-valent pneumococcal vaccine introduction on invasive disease in Fiji

SummaryBackgroundIn 2012, Fiji introduced the 10-valent pneumococcal conjugate vaccine (PCV10). We assessed the impact of PCV10 on invasive pneumococcal disease (IPD), probable bacterial or pneumococcal meningitis (PBPM), meningitis and sepsis 3-5 years post-introduction.MethodsLaboratory-confirmed IPD and PBPM cases were extracted from national laboratory records. ICD-10-AM coded all-cause meningitis and sepsis cases were extracted from national hospitalisation records. Incidence rate ratios were used to compare outcomes pre/post-PCV10, stratified by age groups: 1-23m, 2-4y, 5-9y, 10-19y, 20-54y, ≥55y. To account for different detection and serotyping methods in the pre-and post-PCV10 period, a Bayesian inference model estimated serotype-specific changes in IPD, using pneumococcal carriage and surveillance data.FindingsThere were 423 IPD, 1,029 PBPM, 1,391 all-cause meningitis and 7,611 all-cause sepsis cases. Five years post-PCV10 introduction, IPD declined by 60% (95%CI: 37%, 76%) in children 1-23m months old, and in age groups 2-4y, 5-9y, 10-19y although confidence intervals spanned zero. PBPM declined by 36% (95%CI: 21%, 48%) among children 1-23 months old, and in all other age groups, although some confidence intervals spanned zero. Among children <5y of age, PCV10-type IPD declined by 83% (95%CI; 70%, 90%) and with no evidence of change in non-PCV10-type IPD (9%, 95%CI; -69, 43%). There was no change in all-cause meningitis or sepsis. Post-PCV10, the most common serotypes in vaccine age-eligible and non-age eligible people were serotypes 8 and 23B, and 3 and 7F, respectively.InterpretationsOur study demonstrates the effectiveness of PCV10 against IPD in a country in the Asia-Pacific of which there is a paucity of data.FundingThis study was support by the Department of Foreign Affairs and Trade of the Australian Government and Fiji Health Sector Support Program (FHSSP). FHSSP is implemented by Abt JTA on behalf of the Australian Government.

Comparative Genomic Analysis of Streptococcus pneumoniae Strains: Penicillin Non-susceptible Multi-drug-Resistant Serotype 19A Isolates.

Streptococcus pneumoniae can cause several diseases including otitis media, sinusitis, pneumonia, sepsis and meningitis. The introduction of pneumococcal vaccines has changed the molecular epidemiological and antibiotic resistance profiles of related diseases. Analysis of molecular patterns and genome sequences of clinical strains may facilitate the identification of novel drug resistance mechanism. Three multidrug resistance 19A isolates were verified, serotyped and the complete genomes were sequenced combining the Pacific Biosciences and the Illumina Miseq platform. Genomic annotation revealed that similar central networks were found in the clinical isolates, and Mauve alignments indicated high similarity between different strains. The pan-genome analysis showed the shared and unique cluster in the strains. Mobile elements were predicted in the isolates including prophages and CRISPER systems, which may participate in the virulence and antibiotic resistance of the strains. The presence of 31 virulence factor genes was predicted from other pathogens for PRSP 19339 and 19343, while 30 for PRSP 19087. Meanwhile, 33 genes antibiotic resistance genes were predicted including antibiotic resistance genes, antibiotic-target genes and antibiotic biosynthesis genes. Further analysis of the antibiotic resistance genes revealed new mutations in the isolates. By comparative genomic analysis, we contributed to the understanding of resistance mechanism of the clinical isolates with other serotype strains, which could facilitate the concrete drug resistance mechanism study.

Influence of pneumococcal conjugate vaccine 13 on upper respiratory tract microbial biodiversity in infants

Abstract. Kozhakhmetov S, Aitenov Y, Ramazanova B, Koloskova Y, Burkutbayeva T, Yeraliyeva L, Mustafina K, Beglarova G, Yergazina M, Kushugulova A. 2021. Influence of pneumococcal conjugate vaccine 13 on upper respiratory tract microbial biodiversity in infants. Biodiversitas 22: 5055-5060. Pneumococcal disease and its associated mortality are burdens on the healthcare system. The intensive introduction of pneumococcal vaccines has provided robust control and infection management worldwide. The Pneumococcal Conjugate Vaccine (PCV) has been successfully employed in the national programs of many countries. However, no studies have yet analyzed the effect of pneumococcal vaccines on Central Asian populations. We investigated the effect of the pneumococcal vaccine on the nasopharyngeal microbiome of infants under the age of two years. Samples were collected from healthy patients as part of routine hospital check-ups, then subjected to high-throughput sequencing of the V1–V3 region of 16S rRNA for bioinformatics analysis. The obtained data were combined with the results of a previously published study (with matching criteria) to increase statistical power. No significant differences were found in vaccination status, sex or age. Nevertheless, the results demonstrated structural changes in the microbiome of the upper respiratory tract under the influence of the PCV13 vaccine. The results of beta-diversity unweighted UniFrac distance measuring showed that the experimental groups differed in their qualitative (taxonomic) structure (p &lt; 0.1). In the vaccinated group, the abundance of several symbiotic taxa was significantly decreased, including Streptococcus pneumonia.

Surveillance of pediatric parapneumonic effusion/empyema in New Zealand.

The incidence of childhood empyema has been increasing in some developed countries despite the introduction of pneumococcal vaccination. This study aimed to document the incidence, bacterial pathogens, and morbidity/mortality of parapneumonic effusion/empyema in New Zealand. A prospective study of 102 children <15 years of age requiring hospitalization with parapneumonic effusion/empyema between May 1, 2014 and May 31, 2016 notified via the New Zealand Paediatric Surveillance Unit. Parapneumonic effusion/empyema was defined as pneumonia and pleural effusion persisting ≥7 days, and/or any pneumonia, and pleural effusion necessitating drainage. Notifying pediatricians completed standardized questionnaires. Annual pediatric parapneumonic effusion/empyema incidence was 5.6/100,000 (95% confidence interval [CI]: 4.7-6.9). Most children (80%) required surgical intervention and 31% required intensive care. A causative organism was identified in 71/102 (70%) cases. Although Staphylococcus aureus (25%) and Streptococcus pneumoniae (25%) infection rates were equal, prolonged hospitalization and intensive care admission were more common in children with S. aureus PPE/E. Māori and Pasifika children were over-represented at 2.2 and 3.5 times, their representation in the New Zealand pediatric population. Pneumococcal vaccination was incomplete, with only 61% fully immunized and 30% unimmunized. Haemophilus influenzae type b vaccine uptake was near complete at 89/94 (95%), with influenza immunization only 3/78 (4%). New Zealand has a high incidence of pediatric complicated parapneumonic effusion/empyema with significant morbidity. S. aureus was a significant cause of severe empyema in New Zealand, particularly for Māori and Pasifika children. Improvements in vaccine coverage are needed along with strategies to reduce S. aureus disease morbidity.

Comparative genomics of invasive Streptococcus pneumoniae CC320/271 serotype 19F/19A before the introduction of pneumococcal vaccine in India.

The emergence of multi drug resistant clone CC320 serotype19F/19A and their capsular (cps) antigenic variants due to selective pressures such as vaccine had been reported worldwide. Hence, it is important to identify the prevalent clones, sequence types and cps variants of serotype 19F/19A in India, where PCV13 has been recently introduced. Multi-locus sequence typing (MLST) was performed for all (n = 21) invasive S. pneumoniae isolates of serotype 19A (n = 5) and 19F (n = 16) collected between the years 2012 and 2018 from children less than 5years. The genome characterization by whole genome sequencing for the Sequence types (STs) 320 and 271(n = 7) were performed and compared with another six Indian WGSs of similar STs available from the GPS platform. The predominant STs in the serotype 19F/19A study isolates were of CC320: ST 320, 236 and 271, associated with PMEN clone Taiwan19F-14. The WGSs of CC320 study isolates showed high genomic similarity to the Taiwan19F-14 clone, and the penicillin binding protein (PBP) amino acid sequence similarity was 100% for PBP1A, 93% for PBP 2B and 2X. Whilst PBP comparison with other global MDR ST320 strains revealed that the ST320 clones in India are of low-level penicillin resistance. The presence of a few ST320/19A/19F invasive isolates with high similarity to the Taiwan clone suggests slow and gradual expansion of Taiwan19F-14 associated CC320 clones in India. Since serotype 19F/19A is covered by PCV13 vaccine, the expansion of 19F/19A cones with non-PCV13 vaccine serotype in India should be monitored.

Estimating the power to detect a change caused by a vaccine from time series data

When evaluating the effects of vaccination programs, it is common to estimate changes in rates of disease before and after vaccine introduction. There are a number of related approaches that attempt to adjust for trends unrelated to the vaccine and to detect changes that coincide with introduction. However, characteristics of the data can influence the ability to estimate such a change. These include, but are not limited to, the number of years of available data prior to vaccine introduction, the expected strength of the effect of the intervention, the strength of underlying secular trends, and the amount of unexplained variability in the data. Sources of unexplained variability include model misspecification, epidemics due to unidentified pathogens, and changes in ascertainment or coding practice among others. In this study, we present a simple simulation framework for estimating the power to detect a decline and the precision of these estimates. We use real-world data from a pre-vaccine period to generate simulated time series where the vaccine effect is specified a priori. We present an interactive web-based tool to implement this approach. We also demonstrate the use of this approach using observed data on pneumonia hospitalization from the states in Brazil from a period prior to introduction of pneumococcal vaccines to generate the simulated time series. We relate the power of the hypothesis tests to the number of cases per year and the amount of unexplained variability in the data and demonstrate how fewer years of data influence the results.

Molecular epidemiological characterization in mucoid-type Streptococcus pneumoniae isolates obtained from invasive pneumococcal disease patients in Japan

IntroductionStreptococcus pneumoniae with a mucoid-type capsule is associated with invasive pneumococcal diseases (IPDs). Despite the introduction of pneumococcal vaccines, IPDs caused by mucoid-type isolates are still prevalent. The present study aimed to characterize mucoid-type S. pneumoniae isolated from IPD patients throughout Japan in 2017 (post-vaccination era). MethodsA total of 225 mucoid-type isolates were collected. The serotype, antimicrobial susceptibility, and multilocus sequence type of these isolates were determined. ResultsThe prevalence of IPDs caused by mucoid-type isolates was high in adults, especially in the elderly (≥65 years of age), and prognosis in these patients was significantly poor. Of the mucoid-type isolates, the predominant serotype was serotype 3 (84.4%), and the remaining were serotypes 37 (15.1%) and 8 (0.4%). Antimicrobial susceptibility showed that most mucoid isolates exhibited the penicillin-intermediate resistant S. pneumoniae genotype (gPISP). However, the serotype 3 isolate exhibited the penicillin-resistant S. pneumoniae genotype (gPRSP). This gPRSP isolate was classified into ST166, which is related to serotypes 9 V and 11 strains. Sequence analysis of the capsule-coding regions and its flanking regions indicated that recombination occurred upstream and downstream of the capsule-coding region, suggesting that gPRSP (serotype 9 V/ST166) obtaining the type-3 capsule gene cluster resulted in the emergence of gPRSP (serotype 3/ST166). ConclusionsOur findings indicated that IPDs caused by mucoid-type S. pneumoniae are still a serious concern and mucoid-type S. pneumoniae with novel phenotype could emerge via capsular switching in response to environmental changes such as introduction of vaccines and improper use of antimicrobial agents.