Emergence Of Non-vaccine Serotypes Research Articles

Emerging pneumococcal serotypes in Iraq: scope for improved vaccine development.

Pneumococcal disease is a global public health concern as it affects the young, aged and the immunocompromised. The development of pneumococcal vaccines and their incorporation in the immunization programs has helped to reduce the global burden of disease. However, serotype replacement and the emergence of non-vaccine serotypes as well as the persistence of a few vaccine serotypes underscores the need for development of new and effective vaccines against such pneumococcal serotypes. In the Middle East, places of religious mass gatherings are a hotspot for disease transmission in addition to the global risk factors. Therefore, the periodic surveillance of pneumococcal serotypes circulating in the region to determine the effectiveness of existing prevention strategies and develop improved vaccines is warranted. Currently, there is a lack of serotype prevalence data for Iraq due to inadequate surveillance in the region. Thus, this review aims to determine the pneumococcal serotypes circulating in Iraq which may help in the development and introduction of improved pneumococcal vaccines in the country.

The metabolic, virulence and antimicrobial resistance profiles of colonising Streptococcus pneumoniae shift after PCV13 introduction in urban Malawi

Streptococcus pneumoniae causes substantial mortality among children under 5-years-old worldwide. Polysaccharide conjugate vaccines (PCVs) are highly effective at reducing vaccine serotype disease, but emergence of non-vaccine serotypes and persistent nasopharyngeal carriage threaten this success. We investigated the hypothesis that following vaccine, adapted pneumococcal genotypes emerge with the potential for vaccine escape. We genome sequenced 2804 penumococcal isolates, collected 4-8 years after introduction of PCV13 in Blantyre, Malawi. We developed a pipeline to cluster the pneumococcal population based on metabolic core genes into “Metabolic genotypes” (MTs). We show that S. pneumoniae population genetics are characterised by emergence of MTs with distinct virulence and antimicrobial resistance (AMR) profiles. Preliminary in vitro and murine experiments revealed that representative isolates from emerging MTs differed in growth, haemolytic, epithelial infection, and murine colonisation characteristics. Our results suggest that in the context of PCV13 introduction, pneumococcal population dynamics had shifted, a phenomenon that could further undermine vaccine control and promote spread of AMR.

Recent progress in pneumococcal protein vaccines.

Pneumococcal infections continue to pose a significant global health concern, necessitating the development of effective vaccines. Despite the progress shown by pneumococcal polysaccharide and conjugate vaccines, their limited coverage and the emergence of non-vaccine serotypes have highlighted the need for alternative approaches. Protein-based pneumococcal vaccines, targeting conserved surface proteins of Streptococcus pneumoniae, have emerged as a promising strategy. In this review, we provide an overview of the advancements made in the development of pneumococcal protein vaccines. We discuss the key protein vaccine candidates, highlight their vaccination results in animal studies, and explore the challenges and future directions in protein-based pneumococcal vaccine.

Multi epitope vaccine candidate design against Streptococcus pneumonia

Streptococcus pneumonia, the causative agent of sepsis, meningitis and pneumonia, is held responsible for causing invasive diseases predominantly in children along with adults from both developing and developed countries. The available vaccines coverage in the context of different serotypes is limited and emergence of non-vaccine serotypes could further emerge as a threat in future. Advanced immunoinformatics tools have been used for developing a multi epitope subunit vaccine. In the current study we have subjected these four surface antigenic proteins Ply, PsaA, PspA and PspK to construct vaccine designs. We have predicted different B-cell and T-cell epitopes by using NetCTL 1.2, IEDB (Immune Epitope Databases) and ABCpred. An adjuvant (griselimycin) has been added to the vaccine construct sequence in order to improve its immunogenicity. The vaccine construct has been evaluated for its antigenicity, allergenicity, toxicity and different physio-chemical properties. The bioinformatic tools have been used for prediction, refinement and validation of the 3 D structure. Further, the vaccine structure has been docked with a toll-like receptor (TLR-4) by ClusPro 2.0. In conclusion, the proposed multi-epitope vaccine designs could potentially activate both humoral and cellular immune responses and has a potential to be a vaccine candidate against S.pneumoniae, and requires experimental validation for ensuring immunogenicity and safety profile. Communicated by Ramaswamy H. Sarma

Prevention of pneumococcal diseases: the challenge remains

Streptococcus pneumoniae (pneumococcus) is a leading cause of pneumonia that kills almost a million children worldwide annually, mostly in African and Asian countries.1 By 2015, 129 countries have introduced pneumococcal conjugate vaccines (PCVs) that have substantially reduced child morbidity and mortality.2 However, post-vaccine surveillance has shown the emergence of diseases caused by non-vaccine serotypes as well as serotype replacement in nasopharyngeal colonisation.3 Although an impact of vaccination on invasive pneumococcal disease has been observed in young children (particularly those younger than 2 years, even after many years of pneumococcal conjugate vaccine implementation) the emergence of non-vaccine serotypes with antibiotic resistance has become a new global threat to the control and prevention of pneumococcal diseases.

High prevalence of multiple serotypes of pneumococci in patients with pneumonia and their associated risk factors

BackgroundMultiple serotypes of pneumococci have epidemiological and clinical implications, such as the emergence of non-vaccine serotypes and the acquisition of antimicrobial resistance. Prevalence of multiple serotypes of pneumococci in adults...

Diverse Mechanisms of Protective Anti-Pneumococcal Antibodies.

The gram-positive bacterium Streptococcus pneumoniae is a leading cause of pneumonia, otitis media, septicemia, and meningitis in children and adults. Current prevention and treatment efforts are primarily pneumococcal conjugate vaccines that target the bacterial capsule polysaccharide, as well as antibiotics for pathogen clearance. While these methods have been enormously effective at disease prevention and treatment, there has been an emergence of non-vaccine serotypes, termed serotype replacement, and increasing antibiotic resistance among these serotypes. To combat S. pneumoniae, the immune system must deploy an arsenal of antimicrobial functions. However, S. pneumoniae has evolved a repertoire of evasion techniques and is able to modulate the host immune system. Antibodies are a key component of pneumococcal immunity, targeting both the capsule polysaccharide and protein antigens on the surface of the bacterium. These antibodies have been shown to play a variety of roles including increasing opsonophagocytic activity, enzymatic and toxin neutralization, reducing bacterial adherence, and altering bacterial gene expression. In this review, we describe targets of anti-pneumococcal antibodies and describe antibody functions and effectiveness against S. pneumoniae.

Antimicrobial Susceptibility Pattern and Serotype Distribution of Streptococcus pneumoniae Isolates From a Hospital-Based Study in Chandigarh, North India.

Streptococcus pneumoniae (pneumococcus) causes significant infection-related morbidity and mortality worldwide. The genome plasticity of pneumococcus is an essential factor in antibiotic resistance, serotype switching, and the emergence of nonvaccine serotypes. Information regarding the serotype distribution as well as antimicrobial susceptibility in pneumococcus clinical isolates responsible for various infections in Northern India is limited. Here, we have explored the antibiotic resistance and serotype pattern associated with S. pneumoniae infections from both invasive and noninvasive sites of patients of all ages, visiting out-patient department of a tertiary care hospital (PGIMER, Chandigarh, India). This study was carried out on 68 S. pneumoniae isolates and the isolates exhibited the highest resistance (76.5%) to cotrimaxozole followed by resistance toward tetracycline (36.8%) and erythromycin (23.5%). All isolates showed vancomycin susceptibility and 86.8% of isolates showed sensitivity to chloramphenicol. Multidrug resistance was found in 32% (n=22) of the S. pneumoniae isolates showing resistance toward three different antibiotics. Serotype 19F was found to be the most prevalent serotype (39%) followed by serotypes 6A/B/C (19%) and 1 (12%). These data shed light on the latest trends in antibiotic susceptibility and prevalent serotype patterns of hospital-based S. pneumoniae isolates. This information can be helpful in designing future disease-preventive strategies.

Phylogeography and resistome of pneumococcal meningitis in West Africa before and after vaccine introduction.

Despite contributing to the large disease burden in West Africa, little is known about the genomic epidemiology of Streptococcus pneumoniae which cause meningitis among children under 5 years old in the region. We analysed whole-genome sequencing data from 185 S. pneumoniae isolates recovered from suspected paediatric meningitis cases as part of the World Health Organization (WHO) invasive bacterial diseases surveillance from 2010 to 2016. The phylogeny was reconstructed, accessory genome similarity was computed and antimicrobial-resistance patterns were inferred from the genome data and compared to phenotypic resistance from disc diffusion. We studied the changes in the distribution of serotypes pre- and post-pneumococcal conjugate vaccine (PCV) introduction in the Central and Western sub-regions separately. The overall distribution of non-vaccine, PCV7 (4, 6B, 9V, 14, 18C, 19F and 23F) and additional PCV13 serotypes (1, 3, 5, 6A, 19A and 7F) did not change significantly before and after PCV introduction in the Central region (Fisher's test P value 0.27) despite an increase in the proportion of non-vaccine serotypes to 40 % (n=6) in the post-PCV introduction period compared to 21.9 % (n=14). In the Western sub-region, PCV13 serotypes were more dominant among isolates from The Gambia following the introduction of PCV7, 81 % (n=17), compared to the pre-PCV period in neighbouring Senegal, 51 % (n=27). The phylogeny illustrated the diversity of strains associated with paediatric meningitis in West Africa and highlighted the existence of phylogeographical clustering, with isolates from the same sub-region clustering and sharing similar accessory genome content. Antibiotic-resistance genotypes known to confer resistance to penicillin, chloramphenicol, co-trimoxazole and tetracycline were detected across all sub-regions. However, there was no discernible trend linking the presence of resistance genotypes with the vaccine introduction period or whether the strain was a vaccine or non-vaccine serotype. Resistance genotypes appeared to be conserved within selected sub-clades of the phylogenetic tree, suggesting clonal inheritance. Our data underscore the need for continued surveillance on the emergence of non-vaccine serotypes as well as chloramphenicol and penicillin resistance, as these antibiotics are likely still being used for empirical treatment in low-resource settings. This article contains data hosted by Microreact.

1515. Nationwide trends of invasive pneumococcal disease in Spain for the period 2009-2019

BackgroundIntroduction of pneumococcal conjugate vaccines (PCV) is an effective measure to control the invasive pneumococcal disease (IPD) although the emergence of non-vaccine serotypes is of great concern worldwide.MethodsThis study includes national data from IPD cases affecting pediatric and adult population for the period (2009-2019). Data contain 25341 laboratory-confirmed clinical isolates of Streptococcus pneumoniae causing IPD in Spain.ResultsThe overall reduction of IPD cases by serotypes included in PCV13 was 88% for children and 67% in adults with a constant increase of IPD cases by serotype 8 in adults since 2015. In children, serotypes 24F (12%), 8 (10%) and 3 (9%) were the most frequent in 2019 whereas in adults, serotypes 3 and 8 accounted for 37% of IPD cases. IPD cases in adults by additional serotypes covered by the 23-valent polysaccharide vaccine (PPV23) have risen constantly within the years, increasing from 19% in 2009 to 52% in 2019. IPD cases by Non-vaccine types in adults (not covered by PCV13 or PPV23) show a moderate increase from 14% in 2009 to 24% in 2019.ConclusionEmerging serotypes are observed in Spain with the rise of serotype 24F in children and 8 in adults as a worrisome event.Disclosures Jose Yuste, n/a, GSK (Consultant)MSD (Consultant, Research Grant or Support)Pfizer (Consultant)

Evaluating post-vaccine expansion patterns of pneumococcal serotypes

BackgroundStreptococcus pneumoniae remains a leading cause of morbidity and mortality. Pneumococcal conjugate vaccines (PCVs) are effective but target only a fraction of the more than 90 pneumococcal serotypes. As a result, the introduction of PCVs has been followed by the emergence of non-vaccine serotypes. With higher-valency PCVs currently under development, there is a need to understand and predict patterns of serotype replacement to anticipate future changes. MethodsIn this study, we fit a hierarchical Bayesian regression model to evaluate patterns of change in serotype prevalence post-PCV introduction in Israel from 2009 to 2016. ResultsWe found that the assumption that non-vaccine serotypes increase by the same proportion overestimates changes in serotype prevalence in Jewish and Bedouin children. Furthermore, pre-vaccine prevalence was positively associated with increases in prevalence over the study period. From our analyses, serotypes 12F, 8, 16F, 33F, 9N, 7B, 10A, 22F, 24F, and 17F were estimated to have gained the most cases of invasive pneumococcal disease through serotype replacement in the Jewish population. However, this model also failed to quantify some additional cases gained, suggesting that changes in carriage in children alone may be insufficient to explain serotype replacement in disease. ConclusionsUnderstanding of serotype replacement is important as higher-valency vaccines are introduced.

Nationwide Trends of Invasive Pneumococcal Disease in Spain From 2009 Through 2019 in Children and Adults During the Pneumococcal Conjugate Vaccine Era.

Introduction of pneumococcal conjugate vaccines (PCVs) has reduced the disease caused by vaccine serotypes in children, providing herd protection to adults. However, the emergence of nonvaccine serotypes is of great concern worldwide. This study includes national laboratory data from invasive pneumococcal disease (IPD) cases that affected pediatric and adult populations during 2009-2019. The impact of implementing different vaccine strategies for immunocompetent adults by comparing Spanish regions that used the 13-valent PCV (PCV13) vs regions that used the 23-valent pneumococcal polysaccharide vaccine (PPV23) was also analyzed for 2017-2019. The overall reductions in IPD cases by PCV13 serotypes in children and adults were 88% and 59%, respectively, during 2009-2019, with a constant increase in serotype 8 in adults since 2015. IPD cases by additional serotypes covered by PPV23 increased from 20% in 2009 to 52% in 2019. In children, serotype 24F was the most frequent in 2019, whereas serotypes 3 and 8 accounted for 36% of IPD cases in adults. Introduction of PCV13 or PPV23 in the adult calendar of certain Spanish regions reduced the IPD cases by PCV13 serotypes by up to 25% and 11%, respectively, showing a decrease of serotype 3 when PCV13 was used. Use of PCV13 in children has affected the epidemiology, reducing the burden of IPD in children but also in adults by herd protection; however, the increase in serotype 8 in adults is worrisome. Vaccination with PCV13 in adults seems to control IPD cases by PCV13 serotypes including serotype 3.

Persistent and Emerging Pneumococcal Carriage Serotypes in a Rural Gambian Community After 10 Years of Pneumococcal Conjugate Vaccine Pressure.

The continuing impact of pneumococcal conjugate vaccines (PCVs) in regions with high pneumococcal transmission is threatened by the persistence of vaccine serotypes (VTs) and the emergence of nonvaccine serotypes (NVTs). In 2016, we conducted a cross-sectional carriage survey (CSS5) in a community where PCV7 was first introduced in 2006 during a cluster-randomized trial conducted before nationwide introduction of PCV7 (2009) and PCV13 (2011). We estimated prevalence of PCV13 VT and NVT by age and compared these with earlier surveys before (CSS0), during (CSS1-3), and after the trial but before PCV13 (CSS4). Genomic analysis was conducted for the nontypeable pneumococci. Prevalence of PCV13 VT carriage decreased during the 10 years between CSS0 and CSS5 across all age groups (67.6% to 13.5%, P < .001; 59.8% to 14.4%, P < .001; 43.1% to 17.9%, P < .001; and 24.0% to 5.1%, P < .001, in <2, 2-4, 5-14, and ≥15 years, respectively). However, there was no difference between CSS4 and CSS5 in children ≥2 years and adults (children <2 years, no data). The prevalence of PCV13 NVT increased between CSS0 and CSS5 for children <2 years but decreased in older children and adults. In CSS5, serotypes 3, 6A, and 19F were the most common VT and nontypeable isolates were the most common NVT. Among nontypeable isolates, 73.0% lost the ability to express a capsule. Of these, 70.8% were from a VT background. The decrease in PCV13 VT that has occurred since the introduction of PCV13 appears to have plateaued. Significant carriage of these serotypes remains in all age groups.

Emerging concepts in the pathogenesis of the Streptococcus pneumoniae: From nasopharyngeal colonizer to intracellular pathogen.

Streptococcus pneumoniae (the pneumococcus) is a human respiratory tract pathogen and a major cause of morbidity and mortality globally. Although the pneumococcus is a commensal bacterium that colonizes the nasopharynx, it also causes lethal diseases such as meningitis, sepsis, and pneumonia, especially in immunocompromised patients, in the elderly, and in young children. Due to the acquisition of antibiotic resistance and the emergence of nonvaccine serotypes, the pneumococcus has been classified as one of the priority pathogens for which new antibacterials are urgently required by the World Health Organization, 2017. Understanding molecular mechanisms behind the pathogenesis of pneumococcal infections and bacterial interactions within the host is crucial to developing novel therapeutics. Previously considered to be an extracellular pathogen, it is becoming evident that pneumococci may also occasionally establish intracellular niches within the body to escape immune surveillance and spread within the host. Intracellular survival within host cells also enables pneumococci to resist many antibiotics. Within the host cell, the bacteria exist in unique vacuoles, thereby avoiding degradation by the acidic lysosomes, and modulate the expression of its virulence genes to adapt to the intracellular environment. To invade and survive intracellularly, the pneumococcus utilizes a combination of virulence factors such as pneumolysin (PLY), pneumococcal surface protein A (PspA), pneumococcal adhesion and virulence protein B (PavB), the pilus‐1 adhesin RrgA, pyruvate oxidase (SpxB), and metalloprotease (ZmpB). In this review, we discuss recent findings showing the intracellular persistence of Streptococcus pneumoniae and its underlying mechanisms.

Emergence of serotype 19A Streptococcus pneumoniae after PCV10 associated with a ST320 in adult population, in Porto Alegre, Brazil.

Use of pneumococcal conjugate vaccines has caused emergence of non-vaccine serotypes. No Brazilian data specifically about serotype 19A are available. We aimed to evaluate the frequency of occurrence, susceptibility profile and molecular epidemiology of serotype 19A before and after vaccine introduction in Brazil. Pneumococcal identification was performed by the conventional method. Strain serotype was determined by multiplex polymerase chain reaction (PCR) and/or Quellung reaction. Resistance was determined by Etest® and PCR was performed to determine the presence of macrolide resistance genes, ermB and/or mefA. Pneumococci were typed by Multilocus Sequence Typing. Thirty-eight serotype 19A Streptococcus pneumoniae were recovered, mostly from invasive diseases. Prevalence of serotype 19A increased following vaccination (from 3.5% before vaccination to 8.1% after, p = 0.04196). Non-susceptibility increased to most antimicrobials after vaccine introduction and was associated with clonal complex (CC)320. MLST showed nine different STs, which were grouped in one main CC: CC320 (63.9%). During the post-vaccination era, the frequency of this serotype increased significantly from 1.2% in 2011 to 18.5% in 2014 (p = 0.00001), with a concomitant decrease in the genetic variability: ST320 consistently predominated after vaccine-introduction (61.1%). Overall, our results showed a post-PCV10 increase in the frequency of serotype 19A. This was accompanied by a selection of CC320 and antimicrobial resistance.

Genome-wide analysis of Streptococcus pneumoniae serogroup 19 in the decade after the introduction of pneumococcal conjugate vaccines in Australia

The decline in invasive pneumococcal disease (IPD), following the introduction of the 7-valent pneumococcal conjugate vaccination (PCV-7), was tempered by emergence of non-vaccine serotypes, particularly 19A. In Australia, three years after PCV-7 was replaced by PCV-13, containing 19A and 19F antigens, serogroup 19 was still a prominent cause of IPD in children under five. In this study we examined the evolution of serogroup 19 before and after introduction of paediatric vaccines in New South Wales (NSW), Australia. Genomes of 124 serogroup 19 IPD isolates collected before (2004) and after introduction of PCV-7 (2008) and PCV-13 (2014), from children under five in NSW, were analysed. Eleven core genome sequence clusters (cgSC) and 35 multilocus sequence types (ST) were identified. The majority (78/124) of the isolates belonged to four cgSCs: cgSC7 (ST199), cgSC11 (ST320), cgSC8 (ST63) and cgSC9 (ST2345). ST63 and ST2345 were exclusively serotype 19A and accounted for its predominantly intermediate penicillin resistance; these two clusters first appeared in 2008 and largely disappeared after introduction of PCV-13. Serogroup 19 was responsible for the highest proportion of vaccine failures in NSW. Relatively low immunogenicity of serogroup 19 antigens and Australia’s three-dose vaccine schedule could affect the population dynamics of this serogroup.

Draft Genome Sequence of a Highly Resistant Streptococcus pneumoniae Serotype 15A Strain Isolated from Blood.

ABSTRACTAfter the introduction of the pneumococcal conjugate vaccine in Malaysia in recent years, the emergence of nonvaccine serotypes is of concern, particularly the antibiotic-resistant strains, with an increase specifically in serotype 15A. Here, we report the draft genome sequence of Streptococcus pneumoniae strain SS40_16, isolated from the blood sample of a 19-month-old female in 2016. SS40_16 is a multidrug-resistant strain with resistance to penicillin (MIC, ≥2 µg/ml), tetracycline, and trimethoprim-sulfamethoxazole. The strain belongs to serotype 15A and sequence type 1591 (ST1591).

Redistribution of Streptococcus pneumoniae Serotypes After Nationwide 13-valent Pneumococcal Conjugate Vaccine Program in Children in Northern Taiwan.

After the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) against Streptococcus pneumoniae, public health officials in Taiwan monitored a decline in circulating vaccine serotypes and the emergence of nonvaccine serotypes in children with invasive pneumococcal disease. A gradually expanded PCV13 national immunization program was launched in 2013 in Taiwan. Here, we evaluate the changes in the distribution of pneumococcal serotypes and antimicrobial nonsusceptibility in children during the evolution of vaccination policy. S. pneumoniae isolates from children with pneumococcal disease were collected and serotyped from 2010 to 2015 in northern Taiwan. PCVs were administered at the recipients' expense between 2010 and 2012, and then PCV13 was partially reimbursed by the government beginning in 2013. The distribution and diversity of serotypes were analyzed along with their antimicrobial susceptibilities. Among a total of 498 isolates, the proportion of invasive pneumococcal disease isolates declined (47.1%-10.6%) during the study period, and serotype diversity increased after 2011. Between 2010 and 2012, the dominant serotypes were 19A, 19F, 3, 6B and 14, and serotype 19A rose from 44.1% to 57.5%. Serotypes 19A, 15A, 19F and 15B were more prevalent from 2013 to 2015, and serotype 19A decreased from 42.1% to 4.5%. Serotypes 19F and 15A became the most commonly detected serotypes in 2015. Overall, PCV13 additional serotypes were reduced by 80% (P < 0.0001) but nonvaccine serotypes increased from 8.8% to 51.5% (P < 0.0001). The step-by-step PCV13 national immunization program is effective against pneumococcal disease in Taiwanese children, mainly by reducing PCV13 additional serotypes.

Noninvasive Pneumococcal Pneumonia in Adults in Portugal (2012–2015): Resilience of Vaccine Serotypes and Emergence of Non-vaccine Serotypes

BackgroundThe 13-valent pneumococcal conjugate vaccine (PCV13) is available in Portugal through the private sector for children since 2010. In 2015 it was included in the national immunization program for children. With the aim of evaluating a possible herd effect, we monitored the serotypes and antimicrobial resistance of isolates (2012–2015) causing noninvasive pneumococcal pneumonia (NIPP) in adults (≥18 yrs).Methods1435 adult NIPP isolates were recovered, serotyped by the Quellung reaction and tested for susceptibility to antimicrobials by disk diffusion or Etest.ResultsThere were 50 different serotypes among the 1435 isolates. The most common were serotypes 3 (14%), 11A (8%), 19F (6%), 23A (5%), 6C (5%), 19A (4%), 23B (4%) and 9N (4%). Non-typable isolates accounted for 4% of the collection. The overall proportion of PCV13 serotypes declined from 44% in 2010 to 30% in 2015 (P < 0.001) although it remained relatively stable in 2012–2015. Several serotypes exhibited strong fluctuations in 2007–2015, suggesting that adult NIPP was under the influence of both vaccine-related and non-vaccine-related pressures. PCV7 serotypes (12% in 2012–2015) and the serotypes exclusively found in the 23-valent polysaccharide vaccine (26% in 2012–2015) did not change significantly in 2007–2015, while non-vaccine types increased in proportion (from 27% in 2010 to 42% in 2015, P < 0.001). Penicillin non-susceptibility and erythromycin resistance was found in 18% and 22% of the isolates recovered in 2012–2015, with no significant changes seen since 2007.ConclusionWhile a significant fraction of NIPP is still caused by vaccine serotypes, the availability of PCV13 in the national immunization program for children from 2015 onwards may further reduce their importance in NIPP, questioning the need for adult vaccination.Disclosures M. Ramirez, Pfizer: Speaker’s Bureau, Speaker honorarium; GSK: Consultant, Consulting fee; J. Melo-Cristino, Pfizer: Grant Investigator, Independent Contractor and Speaker’s Bureau, Grant recipient, Research grant and Speaker honorarium; GSK: Grant Investigator and Speaker’s Bureau, Grant recipient and Speaker honorarium; Bial: Speaker’s Bureau, Speaker honorarium; Novartis: Speaker’s Bureau, Speaker honorarium

The Changing Epidemiology of Invasive Pneumococcal Disease Among the Indigenous and Non-indigenous Population of Northwestern Ontario, Canada, from 2006 Through 2015 and Emergence of Non-vaccine Serotypes

BackgroundRates of invasive pneumococcal disease (IPD) among indigenous populations remain substantially higher than their non-indigenous counterparts. The goal of this study was to analyze the epidemiology and demographic features of IPD in northwestern Ontario (NWO) among the indigenous and non-indigenous population in the context of recent changes in the provincial pneumococcal vaccination programs.MethodsTwo databases were used to identify cases of IPD in NWO: Thunder Bay Regional Health Sciences Centre and the Thunder Bay District Health Unit. Adult patients with a diagnosis of IPD at the TBRHSC from January 1, 2006 to December 31, 2015 had their medical charts retrospectively reviewed; TBDHU data contained only serotype, age, and gender data.ResultsTable 1.Number of IPD cases and case fatality rate by indigenous status at the TBRHSC, 2006–2015# of cases# of deathsyearindigenousnon-indigenoustotalindigenousnon-indigenoustotal2006371000020070880112008511160112009820282022010517220222011622281122012381101120131012221342014101121000201531316022total531291824111553 of 182 (29.0%) of patients were indigenous. 35 of 53 (66.0%) of indigenous patients were immunocompromised, whereas 38 of 129 (29.5%) of non-indigenous patients were immunocompromised and the difference was statistically significant (P < 0.001, by chi square test). 35 of 73 (48.0%) of immunocompromised patients were indigenous.Table 2.Serotype distribution of Streptococcus pneumoniae causing IPD in northwestern Ontario, Canada, 2006–2015 (includes both TBRHSC + TBDHU data).yearPCV7PCV13PCV23non-vaccine serotypesunknown serotypestotal200600002626200710211216200822541427200931293164320100784123120112101249372012021184252013032128342014129382320151076923total10388435118285The proportion of non-vaccine serotypes has increased, on average, by 16% per year (P = 0.024, 95% CI: 1.02, 1.32).ConclusionHigh rates of IPD were found to occur among immunocompromised indigenous adults in NWO. Our findings identify a vulnerable cohort of the population that would benefit from pneumococcal vaccination coverage. The proportion of non-vaccine serotypes causing IPD has increased during the 10-year observation period.Disclosures M. Ulanova, Pfizer: Grant Investigator, Grant recipient