scholarly journals Divergent serotype replacement trends and increasing diversity in pneumococcal disease in high income settings reduce the benefit of expanding vaccine valency

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Alessandra Løchen ◽  
Nicholas J. Croucher ◽  
Roy M. Anderson

Abstract Streptococcus pneumoniae is a significant cause of otitis media, pneumonia, and meningitis. Only seven of the approximately 100 serotypes were initially included in the pneumococcal polysaccharide conjugate vaccine (PCV) in 2000 before it was expanded in subsequent years. Although the invasive pneumococcal disease (IPD) incidence due to vaccine serotypes (VT) has declined, partial replacement by non-vaccine serotypes (NVT) was observed following widespread vaccine uptake. We conducted a trend analysis assembling the available evidence for PCV impact on European, North American and Australian national IPD. Significant effectiveness against VT IPD in infants was observed, although the impact on national IPD incidence varied internationally due to serotype replacement. Currently, NVT serotypes 8, 9N, 15A and 23B are increasing in the countries assessed, although a variety of other NVTs are affecting each country and age group. Despite these common emerging serotypes, there has not been a dominant IPD serotype post-vaccination as there was pre-vaccination (serotype 14) or post-PCV7 (serotype 19A), suggesting that future vaccines with additional serotypes will be less effective at targeting and reducing IPD in global populations than previous PCVs. The rise of diverse NVTs in all settings’ top-ranked IPD-causing serotypes emphasizes the urgent need for surveillance data on serotype distribution and serotype-specific invasiveness post-vaccination to facilitate decision making concerning both expanding current vaccination programmes and increasing vaccine valency.

2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
L Savrasova ◽  
I Zeltina ◽  
A Villerusha ◽  
S Balasegaram

Abstract Background In 2009 in Latvia, invasive pneumococcal disease (IPD) became notifiable for physicians and in 2010 vaccination of infants with PCV7 commenced. In 2012 PCV10 vaccination was introduced. The objectives of our study were to evaluate trend of incidence and trend serotype distribution of IPD in Latvia and to investigate factors associated with death from IPD. Methods Laboratory confirmed IPD cases are passively notified to the Centre for Disease Prevention and Control of Latvia by laboratories and clinicians. We calculated incidence by age, sex, case fatality and trend in serotypes. Results From 2012 to 2018, 466 cases of IPD were reported, mean annual incidence 3.4/100,000. The notified incidence remained stable from 2012-2014 (2.7), peaked in 2015 (4.4) and fell to 3.9 in 2018. The highest mean annual IPD incidence was in infants (4.8) and in elderly (6). The highest mean annual incidence was reported in males (4.5) in comparison to females (2.4) (IR-1.8 95%CI 1.6-2.4). Case fatality was 19% (87/466) and 23% (37/162) in cases aged > =65 years. 90% (421/466) of isolates were serotyped. The proportion of PCV10 vaccine serotypes fell from 50% (20/40) in 2012 to 19% (14/74) in 2018 (chi2 test for trend =0.000). Since year 2017, PPV23nonPCV13 and Non-vaccine serotypes become more common. We detected PCV13 serotype (RR 2.04 95%CI 1.37-3.02), S.pneumoniae serotype 3 (RR 1. 91 95% CI 1.25-2.93) significantly associated with IPD death. Conclusions Surveillance data indicate evidence of serotype replacement. Surveillance evaluation should asses the representativeness of notification. Furthermore S. pneumoniae carriage study may be useful to characterise serotype circulation. Serotype 3 and age demonstrate independent and significant association with fatal IPD outcome. Key messages IPD surveillance data analysis indicated evidence of serotype replacement with PPV23nonPCV13, NonVaccine serotypes. Serotype 19A becomes more common with significant increasing trend. Serotype 3 and age independently and significantly associated with fatal IPD outcome. S.pneumoniae carriage study would be very useful providing more evidence of characterizing serotypes circulation.


2016 ◽  
Vol 21 (27) ◽  
Author(s):  
Martine Sabbe ◽  
Nicolas Berger ◽  
Adriaan Blommaert ◽  
Benson Ogunjimi ◽  
Tine Grammens ◽  
...  

In 2006, Belgium was the first country in the European Union to recommend rotavirus vaccination in the routine infant vaccination schedule and rapidly achieved high vaccine uptake (86–89% in 2007). We used regional and national data sources up to 7 years post-vaccination to study the impact of vaccination on laboratory-confirmed rotavirus cases and rotavirus-related hospitalisations and deaths. We showed that (i) from 2007 until 2013, vaccination coverage remained at 79–88% for a complete course, (ii) in children 0–2 years, rotavirus cases decreased by 79% (95% confidence intervals (CI): 68–­89%) in 2008–2014 compared to the pre-vaccination period (1999–­2006) and by 50% (95% CI: 14–82%) in the age group ≥ 10 years, (iii) hospitalisations for rotavirus gastroenteritis decreased by 87% (95% CI: 84–90%) in 2008–­2012 compared to the pre-vaccination period (2002–­2006), (iv) median age of rotavirus cases increased from 12 months to 17 months and (v) the rotavirus seasonal peak was reduced and delayed in all post-vaccination years. The substantial decline in rotavirus gastroenteritis requiring hospitalisations and in rotavirus activity following introduction of rotavirus vaccination is sustained over time and more pronounced in the target age group, but with evidence of herd immunity.


2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S954-S955
Author(s):  
Jason J LeBlanc ◽  
May ElSherif ◽  
Amanda L S Lang ◽  
Hayley D Gillis ◽  
Lingyun Ye ◽  
...  

Abstract Background Streptococcus pneumoniae can colonizes the human nasopharynx, and can cause life-threatening infections like community-acquired pneumonia (CAP) and invasive pneumococcal diseases (IPD). In Canada, the 13-valent conjugate vaccine (PCV13) was introduced in childhood immunization since 2010, with hopes that it would not only protect the vaccinated, but also confer indirect protection to adults through herd immunity. Given data on S. pneumoniae nasopharyngeal (NP) carriage in adults is scarce, this study reports on S. pneumoniae-positivity and serotype distribution in adult carriage from years 2010 to 2017. Methods Active surveillance was performed in adults hospitalized with for CAP or IPD from December 2010 to 2017. For assessment of S. pneumoniae carriage, NP swabs were tested using lytA and cpsA real-time PCR. S. pneumoniae-positive NPs were subjected to serotyping using conventional and real-time multiplex PCRs. Results Overall, 6472 NP swabs were tested, and Spn was identified in 366 (5.7%). Of the 366 S. pneumoniae-positive NP swabs, a serotype was assigned in 355 (97.0%). From years 2010 to 2017, the proportion of S. pneumoniae-positive NP swabs declined from 8.9% to 4.3%. This was also reflected in the proportion of serotypeable results attributed to PCV13 serotypes, which also declined from 76.9% to 42.2%. The decline was primarily attributed to PCV13 serotypes 7F and 19A. PCV13 serotype 3 remained predominant throughout the study, as did non-PCV13 serotypes like 22F, 33F, and 11A. On the other hand, a proportional rise over time was noted for non-vaccine serotypes (from 15.4% to 31.1%). This was primarily attributed to serotypes 23A, 15A, and 35B. Conclusion Monitoring serotype trends is important to assess the impact of pneumococcal vaccines. While herd immunity from PCV13 childhood immunization was anticipated, few studies have assessed its impact on adult carriage. This study described Spn serotype distribution in adults over years 2010 to 2017, demonstrating not only a reduction of PCV13 serotypes over time, but a proportional rise in non-vaccine serotypes. These emerging serotypes may represent the emergence of serotype replacement. Ongoing serotype surveillance will be needed to compare S. pneumoniae carriage to serotypes associated with pneumococcal CAP and IPD. Disclosures All authors: No reported disclosures.


2019 ◽  
Author(s):  
Caroline Colijn ◽  
Jukka Corander ◽  
Nicholas J. Croucher

AbstractStreptococcus pneumoniae (the pneumococcus) is a common nasopharyngeal commensal capable of infecting normally sterile anatomical sites, resulting in invasive pneumococcal disease (IPD). Effective vaccines preventing IPD exist, but each of the antigens they contain typically induces protective immunity against only one of the approximately 100 pneumococcal serotypes, which are differentiated by immunogenically-distinct polysaccharide capsules. Serotypes vary in their propensity to cause IPD, quantified as their invasiveness. Vaccines are designed to include serotypes commonly isolated from IPD, but the immunity they induce is sufficiently strong to also eliminate vaccine serotypes from carriage. This enables their replacement by non-vaccine serotypes in the nasopharynx. The emergence of invasive non-vaccine serotypes has undermined some vaccination programmes’ benefits. Recent advances in genomics and modeling have enabled forecasting of which non-vaccine serotypes will be successful post-vaccination. Here, we demonstrate that vaccines optimised using this framework can minimise IPD and antibiotic-resistant disease more effectively than existing formulations in the model, through mitigating the consequences of serotype replacement. The simulations also demonstrate that tailoring vaccines to the pre-vaccine bacterial population is likely to have a substantial impact on reducing IPD, highlighting the importance of epidemiological data, genomics and ecological models as tools for vaccine design and evaluation.


2021 ◽  
Vol 9 (7) ◽  
pp. 1428
Author(s):  
Catarina Silva-Costa ◽  
Joana Gomes-Silva ◽  
Lúcia Prados ◽  
Mário Ramirez ◽  
José Melo-Cristino ◽  
...  

The introduction of pneumococcal conjugate vaccines PCV7 and PCV13 led to decreases in incidence of pediatric invasive pneumococcal disease (pIPD) and changes in serotype distribution. We evaluated the consequences of higher vaccine uptake after the introduction of PCV13 in the National Immunization Plan (NIP) in 2015. Besides culture and conventional serotyping, the use of molecular methods to detect and serotype pneumococci in both pleural and cerebrospinal fluid samples contributed to 30% of all pIPD (n = 232) in 2015–2018. The most frequently detected serotypes were: 3 (n = 59, 26%), 10A (n = 17, 8%), 8 (n = 16, 7%) and 19A (n = 10, 4%). PCV13 serotypes still accounted for 46% of pIPD cases. Serotypes not included in any currently available conjugate vaccine (NVT) are becoming important causes of pIPD, with the increases in serotypes 8 and 33F being of particular concern given the importance of serotype 8 in adult IPD and the antimicrobial resistance of serotype 33F isolates. This study highlights the importance of using molecular methods in pIPD surveillance since these allowed a better case ascertainment and the identification of serotype 3 as the leading cause of pIPD. Even in a situation of vaccine uptake >95% for 3 years, PCV13 serotypes remain important causes of pIPD.


2020 ◽  
Author(s):  
Maile T. Phillips ◽  
Joshua L. Warren ◽  
Noga Givon-Lavi ◽  
Adrienn Tothpal ◽  
Gili Regev-Yochay ◽  
...  

ABSTRACTStreptococcus 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. In this study, we evaluated patterns of change in serotype prevalence post-PCV introduction in Israel. We 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. Understanding of serotype replacement is important as higher-valency vaccines are introduced.


2018 ◽  
Vol 14 (01) ◽  
pp. 013-015
Author(s):  
Elena Bozzola ◽  
Andrzej Krzysztofiak ◽  
Annausa Pantosti ◽  
Laura Lancella ◽  
Paola Bernaschi ◽  
...  

AbstractDiseases caused by Streptococcus pneumoniae are mostly preventable infections by current immunization programs. The objective of this study was to evaluate the impact of the introduction of the heptavalent and the 13-valent pneumococcal conjugate vaccines (PCV7 and PCV13) on the burden of pneumococcal disease and on the serotype distribution of S. pneumoniae causing invasive pneumococcal diseases (IPDs) in the pediatric age over a 5-year study (from January 2008 till December 2012). We observed a decrease in IPD rate in children after PCV13 introduction despite increases in nonvaccine serotype (NVS) rates in 2011. Nevertheless, from 2012, an increase in IPD rates due to non-PCV13 serotypes was observed.


2020 ◽  
Vol 30 (Supplement_5) ◽  
Author(s):  
C Chiavenna ◽  
A Presanis ◽  
A Charlett ◽  
S Ladhani ◽  
D De Angelis

Abstract Background Increased incidence of invasive pneumococcal disease (IPD) attributable to non-vaccine serotypes (NVT) has been reported in several countries following introduction of PCV7 and PCV13 vaccines, concurrently with a reduction in vaccine-type IPD. Such serotype replacement has, importantly, emerged in England, offsetting the benefit of PCV introduction. We scrutinise most recent findings to assess if the estimated increase in NVT disease might result from surveillance artefacts. Methods Using IPD surveillance for 2000-2018, we estimate the impact of PCV7 and PCV13 introduction on age-serotype-specific incidence rates through a synthetic control regression model, building counterfactuals by combining age-specific incidences reported for pathogens unaffected by PCVs. Results Following the introduction of PCV7 and PCV13 (pre-2006 vs post-2011), total IPD incidence declined by 57% and by 76% in children younger than 5. PCV7-IPD decreased by 93% in all age groups, whereas PCV13-IPD declined by 68% since PCV13 was introduced. Importantly, NVT-IPD increased by 43% after PCV7, with non-significant statistical increases in most age groups. Conclusions Through appropriate statistical modelling, we disentangled the impact of vaccine and improved surveillance on the changes in IPD incidence rates. By controlling for the confounding effects of improved surveillance, we are able to estimate a lower serotype replacement. Key messages Pneumococcal vaccine has been beneficial despite serotype replacement. Adequate statistical methods are needed to disentangle the two phenomena.


2021 ◽  
Vol 9 (5) ◽  
pp. 1078
Author(s):  
Oluwaseun Rume-Abiola Oyewole ◽  
Phung Lang ◽  
Werner C. Albrich ◽  
Kerstin Wissel ◽  
Stephen L. Leib ◽  
...  

Pneumococcal conjugate vaccines (PCVs) have lowered the incidence of invasive pneumococcal disease (IPD) worldwide. However, the influence of regional vaccine uptake differences on the changing epidemiology of IPD remains unclear. We aimed to examine the overall impact of both seven- and 13-valent PCVs (PCV7 and PCV13) on IPD in Switzerland. Three-year periods from 2005–2010 and 2011–2019 were considered, respectively, as (early and late) PCV7 eras and (early, mid and late) PCV13 eras. Vaccine coverage was estimated from a nationwide survey according to east (German-speaking) and west (French/Italian-speaking) regions for each period. Reported incidence rate ratios (IRRs) were compared between successive periods and regions using nationwide IPD surveillance data. Overall IPD incidence across all ages was only 16% lower in the late PCV13 era compared to the early PCV7 era (IRR 0.83, 95% CI 0.79–0.88), due to increasing incidence of non-PCV-type IPD (2.59, 2.37–2.83) in all age groups, except children <5 years. PCV uptake rates in swiss children were slightly higher in the west than the east (p < 0.001), and were accompanied by lower IPD incidences across all age groups in the former region. Post-PCV13, non-PCV serotypes 8, 22F and 9N were the major cause of IPD in adults ≥65 years. Increased PCV coverage in both areas of Switzerland resulted in a decrease in vaccine-type and overall IPD incidence across all age groups, in a regionally dependent manner. However, the rising incidence of non-vaccine-type IPD, exclusive to older adults, may undermine indirect beneficial effects.


2021 ◽  
Vol 9 (4) ◽  
pp. 742 ◽  
Author(s):  
Maria Deloria Knoll ◽  
Julia Bennett ◽  
Maria Garcia Quesada ◽  
Eunice Kagucia ◽  
Meagan Peterson ◽  
...  

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.


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